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12,600 | 26,000,050 | Overall the studies failed to show a remarkable advantage in RR in the combination group compared to historical control subjects receiving AIs alone | Inhibition of aberrantly activated pathways cross-talking with hormone receptor ( HR ) improves response to endocrine therapy in patients with HR-positive advanced breast cancer .
We performed a Pubmed data base systematic review to ascertain the existence of a better clinical response when combining endocrine therapy with targeted agents in the neoadjuvant setting . | BACKGROUND Some oestrogen-receptor ( ER ) positive breast cancers express epidermal growth factor receptor ( EGFR ) , but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known . METHODS In a double-blind , placebo-controlled r and omised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer , 27 women were r and omly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib ( 250 mg given orally once a day ) and the aromatase inhibitor anastrozole ( 1 mg given orally once a day ) , and 29 women to gefitinib ( 250 mg given orally once a day ) and placebo of identical appearance to anastrozole given orally once a day , all given for 4 - 6 weeks before surgery . Primary outcome was inhibition of tumour-cell proliferation , as measured by Ki67 antigen labelling index . Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845 , reduction in ER phosphorylation at Ser 118 , tumour size , and toxic effects . Analyses were by intention to treat . FINDINGS Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone ( mean % reduction 98.0 [ 95 % CI 96.1 - 98.9 ] vs 92.4 [ 85.1 - 96.1 ] ; difference between groups 5.6 % [ 5.1 - 6.0 ] , p=0.0054 ) . Tumour size was reduced by 30 - 99 % ( partial response ) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib , as assessed by ultrasonography . Reduction in phosphorylation of ER at Ser 118 was similar for both groups . Treatment was well tolerated and much the same for both groups . INTERPRETATION Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy Endocrine therapy in patients with breast cancer can be limited by the problem of resistance . Pre clinical studies suggest that complete blockade of the estrogen receptor ( ER ) combined with inhibition of the epidermal growth factor receptor can overcome endocrine resistance . We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer . After a baseline tumor core biopsy , patients were r and omized to receive anastrozole and fulvestrant or anastrozole , fulvestrant , and gefitinib ( AFG ) for 3 weeks . After a second biopsy at 3 weeks , all patients received AFG for 4 months and surgery was done if the tumor was operable . The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers . The study closed after 15 patients were enrolled because of slow accrual . Median patient age was 67 years and median clinical tumor size was 7 cm . Four patients had metastatic disease present . Three patients withdrew before response was assessed . In the remaining 12 patients , there were two complete clinical responses ( 17 % ) , three partial responses ( 25 % ) , five had stable disease ( 41 % ) , and two ( 17 % ) had progressive disease . Most common adverse events were rash in four patients , diarrhea in four , joint symptoms in three , and abnormal liver function tests in three . There were no grade 4 toxicities and all toxicities were reversible . At 3 weeks , cell proliferation as measured by Ki-67 was significantly reduced in the AFG group ( P value = 0.01 ) , with a parallel reduction in the expression of the Cyclin D1 ( P value = 0.02 ) . RNA microarray data showed a corresponding decrease in the expression of cell cycle genes . These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors PURPOSE This study was design ed to determine the effect of adding docetaxel ( T ) to preoperative doxorubicin and cyclophosphamide ( AC ) on breast cancer response rates and disease-free survival ( DFS ) and overall survival ( OS ) . PATIENTS AND METHODS Women with operable breast cancer ( N = 2,411 ) were r and omly assigned to receive preoperative AC followed by surgery , AC followed by T and surgery , or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy . Median time on study for 2,404 patients with follow-up was 77.9 months . RESULTS Addition of T to AC did not significantly impact DFS or OS . There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events ( P = .0034 ) . Preoperative T , but not postoperative T , significantly improved DFS in patients who had a clinical partial response after AC ( hazard ratio [ HR ] = 0.71 ; 95 % CI , 0.55 to 0.91 ; P = .007 ) . Pathologic complete response , which was doubled by addition of preoperative T , was a significant predictor of OS regardless of treatment ( HR = 0.33 ; 95 % CI , 0.23 to 0.47 ; P < .0001 ) . Pathologic nodal status after chemotherapy was a significant predictor of OS ( P < .0001 ) . CONCLUSION The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS , slightly improved DFS , and decreased the incidence of local recurrences . The sample size of this study was not sufficient to yield significance for the moderate DFS improvement . Concurrent use of tamoxifen may have limited the impact of adding INTRODUCTION Tumor content or expression of vascular endothelial growth factor ( VEGF ) is associated with impaired efficacy of antiestrogen adjuvant therapy . We design ed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab ( anti-VEGF ) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor-positive breast cancer . PATIENTS AND METHODS Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer . Patients were followed for toxicity at 3-week intervals , and tumor assessment ( a physical examination and ultrasound ) was performed at 6-week intervals . Positron emission tomography ( PET ) scans were performed before therapy and 6 weeks after the initiation of therapy . RESULTS Twenty-five evaluable patients were treated . The regimen was well-tolerated , except in 2 patients who were taken off the study for difficulties controlling their hypertension . An objective clinical response occurred in 17 of 25 patients ( 68 % ) , including 16 % complete responses ( CRs ) and 52 % partial responses . The 4 patients with clinical CRs manifested pathologic CRs in their breasts ( 16 % ) , although 1 patient had residual tumor cells in her axillary nodes . Eight of 25 patients ( 32 % ) attained stage 0 or 1 status . The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks ( P < .0036 ) . CONCLUSION Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and result ed in impressive clinical and pathologic responses . The Translational Breast Cancer Research Consortium has an ongoing r and omized phase II trial of this regimen in this patient population Background : The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response ( pathCR ) and assess Ki-67 expression as an early predictor of response . Patients and methods : This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer ( clinical stage ⩾T2 , N0–1 ) , from three sequential cohorts ( cohort A of 40 , cohort B of 40 and cohort C of 40 patients , respectively ) based on different duration of the neoadjuvant letrozole . Biological markers such as ER , progesterone receptor , HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery . Results : A total of 89 patients ( 75.4 % ) achieved an objective response with 44 ( 37.3 % ) clinical CRs and 45 ( 38.1 % ) partial responses . The clinical CRs were significantly observed in cohort C ( 23 out of 40 patients , 57.5 % ) and B ( 16 out of 38 patients , 42.1 % ) compared with cohort A ( 5 out of 40 patients , 12.5 % ) ( P-value for trend < 0.001 ) . Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts . The pathCR rate was significantly more frequent in cohort C ( 7 out of 40 patients , 17.5 % ) than in cohort A ( 1 out of 40 patients , 2.5 % ) and B ( 2 out of 40 patients , 5.0 % ) ( P-value for trend < 0.04 ) . Conclusion : One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure PURPOSE To assess patient and tumor characteristics associated with a complete pathologic response ( pCR ) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Three hundred seventy-two LABC patients received treatment in two prospect i ve neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy . Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy . Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics . Median follow-up was 58 months ( range , 8 to 99 months ) . RESULTS The initial nodal status , age , and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR ( P>.05 ) . Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative ( P<.01 ) , and anaplastic ( P = .01 ) but of smaller size ( P<.01 ) than those of patients with less than a pCR . Upon multivariate analysis , the effects of ER status and nuclear grade were independent of initial tumor size . Sixteen percent of the patients in this study ( n = 60 ) had a pathologic complete primary tumor response . Twelve percent of patients ( n = 43 ) had no microscopic evidence of invasive cancer in their breast and axillary specimens . A pathologic complete primary tumor response was predictive of a complete axillary lymph node response ( P<.01 ) . The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR ( 89 % and 87 % , respectively ) than in the group who had less than a pCR ( 64 % and 58 % , respectively ; P<.01 ) . CONCLUSION Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery . Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate . However , a pCR does not entirely eliminate recurrence . Further efforts should focus on elucidating the molecular mechanisms associated with this response A panel of international breast cancer experts formulated a declaration of consensus regarding many key issues in the use of primary systemic therapy ( PST ) either in clinical routine or research practice . The attainment of pathological complete response ( pCR ) , defined as no residual invasive tumor in the surgical specimens both in breast and in axillary nodes , is one of the main goals of PST , and pCR can be used as the primary objective in prospect i ve clinical trials . However , pCR is not a reliable endpoint with all treatment approaches , and alternatives such as Ki67 index of the residual invasive disease or after 2 weeks of PST are also potential endpoints . PST has several advantages : breast conservation and the unique opportunity to obtain information on the interaction between treatment and tumor biology . Changes in tumor biology after PST are an early phenomenon ; so , an additional core biopsy performed after 14 days from treatment start should be considered in clinical trials PURPOSE Within breast tissue , aromatase expression and activity is increased by prostagl and in E2 , providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor . To evaluate the effect of these drugs on aromatase and other biomarkers , a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed . METHODS Postmenopausal women with estrogen receptor ( ER ) and /or progesterone ( PR ) positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily , followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily . Core biopsies were collected pretreatment , after 8 weeks of exemestane , and at definitive breast cancer surgery . A tissue microarray was constructed and immunohistochemistry ( IHC ) for aromatase , ER , PR , HER-2 , Ki-67 , and COX-2 was performed . RESULTS Twenty-two women were enrolled . Celecoxib was discontinued in 4 ( 18 % ) women for toxicity ( all grade 1 and 2 ) and 2 ( 9 % ) developed serious cardiac events occurring at 1 and 4 months after completing treatment . By US , there were 8 (36%)-partial responses and 12 (55%)-stable disease . There were no pathological complete responses ( pCR ) . There were statistically significant decreases in ER ( P = .003 ) , PR ( P = .002 ) , Ki-67 ( P < .001 ) , and COX-2 ( P = .004 ) expression . No significant differences in aromatase or HER-2 expression were observed ( P = .13 and P = .39 , respectively ) . CONCLUSION The addition of celecoxib to exemestane was tolerated by the majority of women and anti-tumor response was observed . Additional studies , including gene expression , are required to more fully underst and the basis for the decreased expression of ER , PR , Ki-67 , and COX-2 Sequential doxorubicin/paclitaxel ( AT ) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer ( ECTO I trial ) . The aim of the current study ( ECTO II ) is to assess the complete pathological response ( pCR ) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens , with or without capecitabine ( X ) . Patients with operable , invasive breast cancer > 2.0 cm in diameter , were r and omized to AT→CMF , AT→CMX or AC→TX regimens in two parallel , r and omized , open-label , phase II trials ( within a single study ) in patients with estrogen receptor negative ( ER− ) and estrogen receptor positive ( ER+ ) diseases , respectively . Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors . Achievement of pCR was more common in ER− than ER+ women ( 45.3 vs. 10.4 % ) . Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT→CMX . Overall response rates ( ORR ) ranged from 88 to 97 % , and this translated into high rates of breast-conserving surgery ( 67 % of ER− patients and 72 % of ER+ patients ) . All three regimens were well tolerated . Febrile neutropenia and gastrointestinal effects were the most common grade ≥3 adverse events . As expected , the ECTO II study showed higher pCR rates in patients with ER− disease . Substituting capecitabine for fluorouracil ( ± methotrexate ) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors . Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy OBJECTIVES To evaluate the efficacy and safety of combing aromatase inhibitor ( AI ) and cyclooxygenase-2 ( COX-2 ) inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer . METHODS Eighty-two patients were r and omly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice daily ( group A , n=30 ) , exemestane 25 mg daily ( group B , n=24 ) and letrozole 2.5 mg daily ( group C , n=28 ) . RESULTS All groups showed clinical responses ( 58.6 % for group A , 54.5 % for group B and 62.0 % for group C ) and decrease in tumor area ( 61.8 % for group A , 58.1 % for group B and 55.7 % for group C ) . 3 out of 5 patients with complete clinical response were observed from group A and 2 out of 69 patients operated with pathologic complete response were observed in group C. The mean microscopic tumor size was 2.53 cm for group A , 3.05 cm for group B and 2.10 cm for group C. The differences were only statistically significant when group C was compared with group B ( P=0.025 ) . The toxicity profiles among groups were satisfactory . CONCLUSION AI is effective in treating breast cancer and may be safely used preoperatively . The addition of COX-2 inhibitor may provide additional benefit PURPOSE Increased epidermal growth factor receptor ( EGFR ) expression may promote breast cancer resistance to endocrine therapy . We have therefore investigated whether neoadjuvant gefitinib , an EGFR inhibitor , might overcome biologic and clinical resistance to neoadjuvant anastrozole in a phase II placebo-controlled trial . PATIENTS AND METHODS Postmenopausal women with stage I to IIIB hormone receptor-positive early breast cancer received anastrozole 1 mg daily for 16 weeks and were r and omly assigned at a ratio of 2:5:5 to receive , in addition , gefitinib 250 mg/d orally for 16 weeks : placebo 1 tablet/d orally for 2 weeks and then gefitinib for 14 weeks or placebo for 16 weeks . The primary end point was biologic change in proliferation as measured by Ki67 at 2 and 16 weeks ; the main secondary end point was overall objective response ( OR ) . RESULTS Two hundred six women were r and omly assigned . Mean changes in Ki67 with anastrozole and gefitinib versus anastrozole alone were -77.4 % and -83.6 % , respectively , between baseline and 16 weeks ( geometric mean ratio = 1.37 ; 95 % CI , 0.79 to 2.39 ; P = .26 ) , -80.1 % and -71.3 % between baseline and 2 weeks ( geometric mean ratio = 0.70 ; 95 % CI , 0.39 to 1.25 ; P = .22 ) and -19.3 % and -43 % ( geometric mean ratio = 1.42 ; 95 % CI , 0.86 to 2.35 ; P = .16 ) between 2 and 16 weeks . ORs in the combination and anastrozole alone groups were 48 % and 61 % ( estimated difference = -13.1 % ; 95 % CI , -27.3 % to 1.2 % ) , respectively , with a nonsignificant trend against the combination ( P = .08 ) and 48 % versus 72 % ( estimated difference = -24.1 % ; 95 % CI , -45.3 % to -2.9 % ) in the progesterone-receptor-positive subgroup , which was significant ( P = .03 ) and consistent with Ki67 changes . Common treatment-related adverse events included diarrhea , rash , alopecia , dry skin , and nausea . There was no evidence of a pharmacokinetic interaction . CONCLUSION Addition of gefitinib to neoadjuvant anastrozole had no additional clinical or biologic effect , failing to support our original hypothesis PURPOSE To evaluate the efficacy and safety of combing aromatase inhibitor ( AI ) and signal transduction inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer . PATIENTS AND METHODS Postmenopausal women with hormone-sensitive breast cancer were given three months of letrozole 2.5 mg daily and imatinib 400 mg twice daily preoperatively . End-points of this study included clinical and pathologic responses , toxicities , and change in [(18)F]fluorodeoxyglucose ( FDG ) uptake in tumor . Expression of c-Kit was also evaluated in breast cancer tissue by immunostaining . RESULTS Thirteen patients , aged 52 - -78 , were accrued . Five patients ( 38.5 % ) experienced grade 3 toxicity including neutropenia , skin rash , dermatitis , hypokalemia , shortness of breath , acute coronary syndrome , and acute chronic gastritis . Three patients were withdrawn after two months of treatment due to hematoma in tumor and toxicity . Of the ten evaluable patients , nine patients ( 90 % ) achieved clinical partial response and one patient ( 10 % ) had stable disease . One patient ( 10 % ) achieved pathologic complete response . Average relative changes of FDG uptake was -69.5 % among responders . Eight out of 13 tissue sample s were tested for c-Kit expression and the expression was detected in all . CONCLUSIONS In this pilot study , the dramatic response to this neoadjuvant combination treatment warrants further clinical trials . Further investigation on the involvement of c-Kit pathway in the treatment response is also suggested . However , dosage reduction of imatinib may be required to avoid its potential toxicity The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy ( PCT ) is unclear . We review ed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT . The incidence of pathological complete remission ( pCR ) and outcome were assessed with respect to the degree of estrogen ( ER ) and progesterone receptor ( PgR ) expression ( ER and PgR absent , vs. ER or PgR 0–49 % , vs. ER and PgR ≥50 % of the cells positive ) . A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors ( 17.7 % ) versus patients with tumors expressing high ER and PgR ( 0 % ) ( OR 14.4 P < 0.001 ) . Despite the higher incidence of pCR , a statistically significant worse disease-free survival ( DFS ) , and overall survival ( OS ) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR ( HR 6.4 , 95 % CI 3.5–11.6 , for DFS ; HR 3.6 95 % CI 2.4–5.6 for OS ) . Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors . Studies on tailored preoperative therapies are needed PURPOSE Cross-talk between the estrogen receptor ( ER ) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin ( mTOR ) pathways is a mechanism of resistance to endocrine therapy , and blockade of both pathways enhances antitumor activity in pre clinical models . This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor , everolimus ( RAD001 ) . PATIENTS AND METHODS Two hundred seventy postmenopausal women with operable ER-positive breast cancer were r and omly assigned to receive 4 months of neoadjuvant treatment with letrozole ( 2.5 mg/day ) and either everolimus ( 10 mg/day ) or placebo . The primary end point was clinical response by palpation . M and atory biopsies were obtained at baseline and after 2 weeks of treatment ( ie , day 15 ) . Sample s were assessed for PI3 K mutation status ( PIK3CA ) and for pharmacodynamic changes of Ki67 , phospho-S6 , cyclin D1 , and progesterone receptor ( PgR ) by immunohistochemistry . RESULTS Response rate by clinical palpation in the everolimus arm was higher than that with letrozole alone ( ie , placebo ; 68.1 % v 59.1 % ) , which was statistically significant at the preplanned , one-sided , alpha = 0.1 level ( P = .062 ) . Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms , and dramatic downregulation of phospho-S6 occurred only in the everolimus arm . An antiproliferative response , as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15 , occurred in 52 ( 57 % ) of 91 patients in the everolimus arm and in 25 ( 30 % ) of 82 patients in the placebo arm ( P < .01 ) . The safety profile was consistent with historical results of everolimus monotherapy ; grade s 3 to 4 adverse events occurred in 22.6 % of patients who received everolimus and in 3.8 % of patients who received placebo . CONCLUSION Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer Primary chemotherapy in localised breast cancer may prevent tumour spread during surgical treatment and reduce proliferation of micrometastases . A r and omised clinical trial , in 196 premenopausal and postmenopausal patients with operable ( T2 - 3 , N0 - 1b ) breast cancer , was started in November 1983 at the Institut Curie to compare neoadjuvant and adjuvant regimens of chemotherapy with radiotherapy with or without surgery . The patients have been followed up for 35 - 70 months ( median 54 ) . A neoadjuvant group received two monthly cycles of intravenous doxorubicin/cyclophosphamide/5-fluorouracil before locoregional therapy and four cycles subsequently . Six monthly cycles following locoregional therapy were administered to the adjuvant group . Because of inclusion of postmenopausal and /or node-negative patients , compliance was less than optimal in 39 patients who were analysed separately according to actual dose received . Tumour response , evaluated after two cycles of neoadjuvant chemotherapy , was significantly associated with dose ( P = 0.003 ) . Survival showed a slight non-significant advantage for the neoadjuvant group . Survival plotted by actual dose was also similar . Neoadjuvant chemotherapy was safe and at least as effective as the adjuvant regimen . Patients have been accrued to a subsequent larger trial of chemotherapy as first-line treatment In order to explore the effect of neoadjuvant chemotherapy ( NACT ) on clinical mid-course and pathological complete response ( pCR ) at surgery in different biological breast cancer subtypes . The GeparTrio study included 2,072 patients with operable or locally advanced breast cancer . After two cycles with docetaxel , doxorubicin and cyclophosphamide ( TAC ) patients were r and omized according to their clinical response . Clinical and biological factors were assessed for predicting clinical ly mid-course response and pCR at surgery . The overall pCR rate , defined as no invasive residuals in breast and axilla , was 20.5 % . The highest pCR rate of 57 % was observed in patients below 40 years of age with triple negative or grade 3 tumors . Independent factors for mid-course response and pCR were : young age , non-T4 tumors , high grade , and hormone receptor status , the strongest single predictive factor . Within the biological subtypes , grading was an independent factor to predict pCR for luminal tumors , clinical tumor stage for the HER2 like tumors and age for the triple negative ones . Grading gave independent information for mid-course response within the triple negative group . No factor predicted mid-course response within the other groups . Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from NACT BACKGROUND Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin ( mTOR ) intracellular signaling pathway . In early studies , the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity . METHODS In this phase 3 , r and omized trial , we compared everolimus and exemestane versus exemestane and placebo ( r and omly assigned in a 2:1 ratio ) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease ( or both ) . The primary end point was progression-free survival . Secondary end points included survival , response rate , and safety . A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed . RESULTS Baseline characteristics were well balanced between the two study groups . The median age was 62 years , 56 % had visceral involvement , and 84 % had hormone-sensitive disease . Previous therapy included letrozole or anastrozole ( 100 % ) , tamoxifen ( 48 % ) , fulvestrant ( 16 % ) , and chemotherapy ( 68 % ) . The most common grade 3 or 4 adverse events were stomatitis ( 8 % in the everolimus-plus-exemestane group vs. 1 % in the placebo-plus-exemestane group ) , anemia ( 6 % vs. < 1 % ) , dyspnea ( 4 % vs. 1 % ) , hyperglycemia ( 4 % vs. < 1 % ) , fatigue ( 4 % vs. 1 % ) , and pneumonitis ( 3 % vs. 0 % ) . At the interim analysis , median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane , according to assessment s by local investigators ( hazard ratio for progression or death , 0.43 ; 95 % confidence interval [ CI ] , 0.35 to 0.54 ; P<0.001 ) . Median progression-free survival was 10.6 months and 4.1 months , respectively , according to central assessment ( hazard ratio , 0.36 ; 95 % CI , 0.27 to 0.47 ; P<0.001 ) . CONCLUSIONS Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors . ( Funded by Novartis ; BOLERO-2 Clinical Trials.gov number , NCT00863655 . ) AIM To describe surgical outcomes in patients with HER2-positive locally advanced ( LABC ) or inflammatory breast cancer ( IBC ) participating in the NeOAdjuvant Herceptin ( NOAH ) study ( IS RCT N86043495 ) . PATIENTS AND METHODS A total of 235 patients with HER2-positive disease were r and omized to neoadjuvant trastuzumab plus chemotherapy ( doxorubicin plus paclitaxel , followed by paclitaxel , followed by cyclophosphamide , methotrexate and fluorouracil ) or neoadjuvant chemotherapy alone . Of these patients , 228 received their allocated treatment ( 115 received trastuzumab plus chemotherapy and 113 received chemotherapy alone ) and were potentially eligible for surgery . Mastectomy was required for all patients with IBC and was recommended for all patients with LABC . However , breast-conserving therapy could be considered for patients with peripheral neoplasms measuring ≤ 4 cm in diameter at diagnosis , with a favorable ratio of tumor to breast volume , or at the patient 's request if there had been a good response to treatment . RESULTS As previously reported , the addition of trastuzumab to neoadjuvant chemotherapy improved the overall , complete and pathological complete response to therapy and significantly improved event-free survival ( the primary endpoint of the study ) . Trastuzumab also enabled more patients to have breast conserving surgery ( BCS ) ( 23 % versus 13 % respectively ) without an apparent detrimental effect on local disease control ( no patient treated with trastuzumab plus chemotherapy had experienced a local recurrence after BCS at the time of analysis ) . CONCLUSIONS Although this was not an aim of the trial , neoadjuvant trastuzumab given concurrently with chemotherapy enabled 23 % of patients with HER2-positive LABC/IBC to avoid mastectomy ( including a small number of patients with IBC ) The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery . Between 1983 and May 1994 , 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy . We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates . After a median follow-up of 60 months the multivariate model revealed lymph node status ( p=0.002 ) as highly significant with regard to local recurrence free survival . We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status : both patient groups with or without irradiation had similar locoregional recurrence rates of 3 % . In a subgroup of patients who were lymph node negative , receptor positive , and received adjuvant tamoxifen therapy , the local recurrence rates were as low as 2 % in both groups . Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery ( T1 , N0 , positive hormone receptor , adjuvant tamoxifen ) without increasing risk of locoregional recurrence . These data have to be confirmed in a prospect ively r and omized fashion BACKGROUND A r and omized , double-blind , multicenter study was conducted to compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal women with ER and /or PgR positive primary untreated breast cancer . PATIENTS AND METHODS Three hundred thirty-seven postmenopausal women with ER and /or PgR positive primary untreated breast cancer were r and omly assigned once daily treatment with either letrozole 2.5 mg or tamoxifen 20 mg for four months . At baseline none of the patients were considered to be c and i date s for breast-conserving surgery ( BCS ) and 14 % of the patients were considered inoperable . The primary endpoint was to compare overall objective response ( CR + PR ) determined by clinical palpation . Secondary endpoints included overall objective response on ultrasound and mammography and the number of patients who qualified for BCS . RESULTS Overall objective response rate ( clinical palpation ) was statistically significantly superior in the letrozole group , 55 % compared to tamoxifen , 36 % ( P < 0.001 ) . Secondary endpoints of ultrasound response , 35 % vs. 25 % ( P = 0.042 ) , mammographic response , 34 % vs. 16 % ( P < 0.001 ) , and BCS , 45 % vs. 35 % ( P = 0.022 ) between the letrozole and tamoxifen groups , respectively , showed letrozole to be significantly superior . Both treatments were well tolerated . CONCLUSIONS This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and /or PgR positive primary untreated breast cancer and is at least as well tolerated PURPOSE The Immediate Preoperative Anastrozole , Tamoxifen , or Combined With Tamoxifen ( IMPACT ) trial was design ed to test the hypothesis that the clinical and /or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor ( ER ) -positive , invasive , nonmetastatic breast cancer might predict for outcome in the Arimidex , Tamoxifen Alone or in Combination ( ATAC ) adjuvant therapy trial . PATIENTS AND METHODS Postmenopausal women with ER-positive , invasive , nonmetastatic , and operable or locally advanced potentially operable breast cancer were r and omly assigned to neoadjuvant tamoxifen ( 20 mg daily ) , anastrozole ( 1 mg daily ) , or a combination of tamoxifen and anastrozole for 3 months . The tumor objective response ( OR ) was assessed by both caliper and ultrasound . Comparisons were also made of clinical response with ultrasound response , actual and feasible surgery with feasible surgery at baseline , OR in human epidermal growth factor receptor 2 (HER2)-positive cancers , and tolerability . RESULTS There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen , anastrozole , or the combination . In patients who were assessed as requiring mastectomy at baseline ( n = 124 ) , 44 % of patients received breast-conserving surgery ( BCS ) after anastrozole compared with 31 % of patients after tamoxifen ( P = .23 ) ; this difference became significant for patients who were deemed feasible for BCS by their surgeon ( 46 % v 22 % , respectively ; P = .03 ) . The OR for patients with HER2-positive cancer ( n = 34 ) was 58 % for anastrozole compared with 22 % for tamoxifen ( P = .18 ) . All treatments were well tolerated . CONCLUSION Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women , but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled BACKGROUND Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer . We aim ed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting . METHODS In this phase 3 , r and omised , double-blind , parallel-group , multicentre study , we enrolled premenopausal women with oestrogen receptor (ER)-positive , HER2-negative , operable breast cancer with WHO performance status of 2 or lower . Patients were r and omly assigned ( 1:1 ) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery . Patients were r and omised sequentially , stratified by centre , with r and omisation codes . All study personnel were masked to study treatment . The primary endpoint was best overall tumour response ( complete response or partial response ) , assessed by callipers , during the 24-week neoadjuvant treatment period for the intention-to-treat population . The primary endpoint was analysed for non-inferiority ( with non-inferiority defined as the lower limit of the 95 % CI for the difference in overall response rates between groups being 10 % or less ) ; in the event of non-inferiority , we assessed the superiority of the anastrozole group versus the tamoxifen group . We included all patients who received study medication at least once in the safety analysis set . We report the primary analysis ; treatment will also continue in the adjuvant setting for 5 years . This trial is registered with Clinical Trials.gov , number NCT00605267 . FINDINGS Between Oct 2 , 2007 , and May 29 , 2009 , 204 patients were enrolled . 197 patients were r and omly assigned to anastrozole ( n=98 ) or tamoxifen ( n=99 ) , and 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery ( 95 in the anastrazole group , 90 in the tamoxifen group ) . More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment ( anastrozole 70·4 % [ 69 of 98 patients ] vs tamoxifen 50·5 % [ 50 of 99 patients ] ; estimated difference between groups 19·9 % , 95 % CI 6·5 - 33·3 ; p=0·004 ) . Two patients in the anastrozole group had treatment-related grade 3 adverse events ( arthralgia and syncope ) and so did one patient in the tamoxifen group ( depression ) . One serious adverse event was reported in the anastrozole group ( benign neoplasm , not related to treatment ) , compared with none in the tamoxifen group . INTERPRETATION Given its favourable risk-benefit profile , the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer . FUNDING AstraZeneca PURPOSE We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)- amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor ( ER ) when expressed . In this clinical trial , we sought to translate these findings to patients using targeted therapy without chemotherapy . PATIENTS AND METHOD Women with stages II to III HER2-positive breast cancers were eligible . They received trastuzumab once per week ( 4 mg/kg loading , then 2 mg/kg ) and lapatinib 1000 mg once per day for 12 weeks . Women with ER-positive tumors also received letrozole ( plus a luteinizing hormone-releasing hormone [ LHRH ] agonist if premenopausal ) . Pathologic response was assessed by ER status . Biopsies were obtained at baseline , weeks 2 and 8 , and time of surgery . RESULTS Sixty-six patients were enrolled , and 64 were eligible and evaluable for response . Median tumor size was 6 cm ( range , 1.5 to 30 cm ) . Adverse events were mainly grade s 1 to 2 ( GI , 63 % ; skin , 46 % ) . Grade 3 metabolic , GI , and liver ( 18 % ; 12 patients ) and grade 4 liver toxicities ( one patient ) were also observed . Overall , in-breast pathologic complete response ( pCR ; ypT0-is ) was 27 % ( ER positive , 21 % ; ER negative , 36 % ) . The rate of low-volume residual disease ( ypT1a-b ) was 22 % ( ER positive , 33 % ; ER negative , 4 % ) . CONCLUSION In patients with locally advanced HER2-positive breast cancer , our approach of targeted therapy only result ed in a high pCR rate without chemotherapy . Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy , and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study PURPOSE The exact definition of pathologic complete response ( pCR ) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain . METHODS Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven r and omized trials were analyzed . RESULTS Disease-free survival ( DFS ) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes ( n = 955 ) compared with patients with residual ductal carcinoma in situ only ( n = 309 ) , no invasive residuals in breast but involved nodes ( n = 186 ) , only focal-invasive disease in the breast ( n = 478 ) , and gross invasive residual disease ( n = 4,449 ; P < .001 ) . Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals ( 0.446 ) and increased monotonously when in situ residuals ( 0.523 ) , no invasive breast residuals but involved nodes ( 0.623 ) , and focal-invasive disease ( 0.727 ) were included in the definition . pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 ( HER2 ) -negative ( P = .005 ) , HER2-positive/nonluminal ( P < .001 ) , and triple-negative ( P < .001 ) tumors but not in luminal A ( P = .39 ) or luminal B/HER2-positive ( P = .45 ) breast cancer . pCR in HER2-positive ( nonluminal ) and triple-negative tumors was associated with excellent prognosis . CONCLUSION pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes . Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR . pCR is a suitable surrogate end point for patients with luminal B/HER2-negative , HER2-positive ( nonluminal ) , and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors Background . Few women with locally advanced breast cancer remain disease‐free , even for 2 years . Response to induction chemotherapy may be associated with longer disease‐free and overall survival rates . The role of breast conservation in selected patients with response to induction chemotherapy was evaluated The Pre‐Operative “ Arimidex ” Compared to Tamoxifen ( PROACT ) study was a r and omized , multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large , operable ( T2/3 , N0‐2 , M0 ) , or potentially operable ( T4b , N0‐2 , M0 ) breast cancer . The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated PURPOSE To evaluate whether preoperative neoadjuvant chemotherapy in patients with primary operable breast cancer results in better overall survival ( OS ) and relapse-free survival rates and whether preoperative chemotherapy permits more breast-conserving surgery procedures than postoperative chemotherapy . PATIENTS AND METHODS Six hundred ninety-eight breast cancer patients ( T1c , T2 , T3 , T4b , N0 to 1 , and M0 ) were enrolled onto a r and omized phase III trial that compared four cycles of fluorouracil , epirubicin , and cyclophosphamide administered preoperatively versus the same regimen administered postoperatively ( the first cycle administered within 36 hours after surgery ) . Patients were followed up for OS , progression-free survival ( PFS ) , and locoregional recurrence ( LRR ) . RESULTS At a median follow-up of 56 months , there was no significant difference in terms of OS ( hazards ratio , 1.16 ; P = .38 ) , PFS ( hazards ratio , 1.15 ; P = .27 ) , and time to LRR ( hazards ratio , 1.13 ; P = .61 ) . Fifty-seven patients ( 23 % ) were downstaged by the preoperative chemotherapy , whereas 14 patients ( 18 % ) underwent mastectomy and not the planned breast-conserving therapy . CONCLUSION The use of preoperative chemotherapy yields similar results in terms of PFS , OS , and locoregional control compared with conventional postoperative chemotherapy . In addition , preoperative chemotherapy enables more patients to be treated with breast-conserving surgery . Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy , future trials should involve quality -of-life studies to investigate whether patients will benefit from this treatment modality PURPOSE To determine whether preoperative doxorubicin and cyclophosphamide ( AC ) permits more lumpectomies to be performed and decreases the incidence of positive nodes in women with primary breast cancer . PATIENTS AND METHODS Women ( n = 1,523 ) were r and omized to National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-18 ; 759 eligible patients received postoperative AC and 747 , preoperative AC . The clinical size of breast and axillary tumors was determined before each of four cycles of AC and before surgery . Tumor response to preoperative therapy was clinical ly complete ( cCR ) , partial ( cPR ) , stable ( cSD ) , or progressive disease ( cPD ) . Tissue from patients with a cCR was evaluated for a pathologic complete response ( pCR ) . RESULTS Breast tumor size was reduced in 80 % of patients after preoperative therapy ; 36 % had a cCR . Tumor size and clinical nodal status were independent predictors of cCR . Twenty-six percent of women with a cCR had a pCR . Clinical nodal response occurred in 89 % of node-positive patients : 73 % had a cCR and 44 % of those had a pCR . There was a 37 % increase in the incidence of pathologically negative nodes . Before r and omization , lumpectomy was proposed for 86 % of women with tumors < or = 2 cm , 70 % with tumors 2.1 to 5.0 cm , and 3 % with tumors > or = 5.1 cm . Clinical tumor size and nodal status influenced the physician 's decision . Overall , 12 % more lumpectomies were performed in the preoperative group ; in women with tumors > or = 5.1 cm , there was a 175 % increase . CONCLUSION Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes . The greatest increase in lumpectomy after preoperative therapy occurred in women with tumors > or = 5 cm , since women with tumors less than 5 cm were already lumpectomy c and i date s. Preoperative therapy should be considered for the initial management of breast tumors judged too large for lumpectomy This study reports the value of the tumor markers estrogen receptor ( ER ) , progesterone receptor ( PR ) , and human epidermal growth factor receptor 2 ( HER2 ) in predicting the response of breast cancer to neoadjuvant chemotherapy . A community cancer center prospect ively maintained breast cancer data base containing over 8,000 patient records was used . Since 1989 , 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR . Estrogen receptor and /or PR positive patients were considered hormone receptor ( HR ) positive . Human epidermal growth factor receptor 2 status was available on 368 patients . Total , breast , and nodal pathologic complete response ( pCR ) rates , recurrence , and overall survival were assessed . Total and breast pCR rates were higher in HR negative ( HR- ) patients ( 26 % and 32 % , respectively ) than in HR positive ( HR+ ) patients ( 4 % and 7 % , respectively ; p < 0.001 ) . Compared to HR+ patients , HR- patients had higher recurrence rates ( 38 % versus 22 % ; p < 0.001 ) , a shorter time to recurrence ( 1.28 versus 2.14 years ; p < 0.001 ) , and decreased overall survival ( 67 % versus 81 % ; p < 0.001 ) . Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab ( NAT ) demonstrated higher total pCR ( 34 % versus 13 % ; p = 0.008 ) , breast pCR ( 37 % versus 17 % ; p = 0.02 ) , and nodal pCR rates ( 47 % versus 23 % ; p = 0.05 ) compared to HER2 + patients not treated with NAT . Furthermore , HER2 + patients who received NAT had lower recurrence rates ( 5 % versus 42 % ; p < 0.001 ) and increased overall survival ( 97 % versus 68 % ; p < 0.001 ) . In conclusion , breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy . Although HR- patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response , they have worse outcomes in terms of recurrence and survival . Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy , but significantly better overall outcome . For both HR- and HR+ , addition of NAT for HER2 + tumors results in both a superior response and outcome |
12,601 | 18,677,161 | Conclusion Pharmacologic , biobehavioral and exercise strategies for secondary prevention of CAD significantly increase HRV . | Background Heart rate variability ( HRV ) is reported as a surrogate index for clinical outcome in trials of secondary prevention strategies for coronary artery disease ( CAD ) , but a st and ardized guide for interpreting HRV change is not established .
Design We evaluated HRV change in trials with CAD patients who received conventional medications ( β-blockers , calcium channel blockers , angiotensin converting enzyme inhibitors ) , biobehavioral treatment ( psychotropics , biofeedback , relaxation ) or exercise training . | Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implication s. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure , and second whether there were any differences between st and ard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol . In this double-blind r and omized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily , metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period . Thirty-five healthy normal subjects were also studied . Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components ( the alpha angle ) during controlled respiration . High-frequency power was used as a measure of vagal modulation . Satisfactory recordings for analysis were obtained in 31 patients with heart failure . The results showed that at baseline baroreceptor gain ( alphaHF ) was significantly depressed in patients with heart failure compared with the normal control group ( 4.95+/-0 . 55 versus 11.73+/-1.32 ms/mmHg , P<0.0001 ) . After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine ( P=0.03 ) or st and ing ( P=0.009 ) , and this was associated with a significant increase in R-R HF power ( P=0 . 008 ) . There were no significant changes after treatment with celiprolol or placebo . We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure . The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure CONTEXT Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality , but the effects of behavioral interventions on psychosocial and medical end points remain uncertain . OBJECTIVE To determine the effect of 2 behavioral programs , aerobic exercise training and stress management training , with routine medical care on psychosocial functioning and markers of cardiovascular risk . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 134 patients ( 92 male and 42 female ; aged 40 - 84 years ) with stable ischemic heart disease ( IHD ) and exercise-induced myocardial ischemia . Conducted from January 1999 to February 2003 . INTERVENTIONS Routine medical care ( usual care ) ; usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks ; usual care plus weekly 1.5-hour stress management training for 16 weeks . MAIN OUTCOME MEASURES Self-reported measures of general distress ( General Health Question naire [ GHQ ] ) and depression ( Beck Depression Inventory [ BDI ] ) ; left ventricular ejection fraction ( LVEF ) and wall motion abnormalities ( WMA ) ; flow-mediated dilation ; and cardiac autonomic control ( heart rate variability during deep breathing and baroreflex sensitivity ) . RESULTS Patients in the exercise and stress management groups had lower mean ( SE ) BDI scores ( exercise : 8.2 [ 0.6 ] ; stress management : 8.2 [ 0.6 ] ) vs usual care ( 10.1 [ 0.6 ] ; P = .02 ) ; reduced distress by GHQ scores ( exercise : 56.3 [ 0.9 ] ; stress management : 56.8 [ 0.9 ] ) vs usual care ( 53.6 [ 0.9 ] ; P = .02 ) ; and smaller reductions in LVEF during mental stress testing ( exercise : -0.54 % [ 0.44 % ] ; stress management : -0.34 % [ 0.45 % ] ) vs usual care ( -1.69 % [ 0.46 % ] ; P = .03 ) . Exercise and stress management were associated with lower mean ( SE ) WMA rating scores ( exercise : 0.20 [ 0.07 ] ; stress management : 0.10 [ 0.07 ] ) in a subset of patients with significant stress-induced WMA at baseline vs usual care ( 0.36 [ 0.07 ] ; P = .02 ) . Patients in the exercise and stress management groups had greater mean ( SE ) improvements in flow-mediated dilation ( exercise : mean [ SD ] , 5.6 % [ 0.45 % ] ; stress management : 5.2 % [ 0.47 % ] ) vs usual care patients ( 4.1 % [ 0.48 % ] ; P = .03 ) . In a subgroup , those receiving stress management showed improved mean ( SE ) baroreflex sensitivity ( 8.2 [ 0.8 ] ms/mm Hg ) vs usual care ( 5.1 [ 0.9 ] ms/mm Hg ; P = .02 ) and significant increases in heart rate variability ( 193.7 [ 19.6 ] ms ) vs usual care ( 132.1 [ 21.5 ] ms ; P = .04 ) . CONCLUSION For patients with stable IHD , exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone AIMS Reduced heart rate variability is associated with an unfavourable prognosis in patients with ischaemic heart disease . Whether physical training can modify this risk factor is not definitely proven . Our hypothesis was that training might increase both physical capacity and heart rate variability in elderly patients recovering from an acute coronary event , i.e. acute myocardial infa rct ion ( n=38 ) or an episode of unstable angina ( n=27 ) . METHODS AND RESULTS 24 h ambulatory ECG recordings were obtained from 65 patients r and omized to either a 3 months supervised outpatient group training programme 50 min three times a week ( n=29 ) or to a control group ( n=36 ) . The two groups were well balanced as regards demographic data and pharmacological treatment at the time of r and omization . Body mass index and pharmacological therapy remained unchanged during the study . Heart rate variability was analysed in the time and frequency domains . At the 3 month follow-up , exercise tolerance had increased from 103 to 120 W in the training group ( P<0.001 ) , and from 102 to 106 W in the control group ( ns ) . The time-domain heart rate variability measures SDNN ( st and ard deviation of all filtered RR intervals over the analysed time period ) and SDANN ( st and ard deviation of the means of all filtered RR intervals for all 5 min epochs of the analysed time period ) increased significantly during the daytime in the training group ( P<0.01 and P<0.05 , respectively ) , but not in the control group . A significant improvement in night-time heart rate variability was observed among controls . There was a statistically significant correlation ( P<0.05 ) between changes in 24 h overall power ( frequency domain measure ) and changes in maximal exercise capacity in the training group . CONCLUSION A regular aerobic group training programme after an acute coronary event can significantly improve exercise capacity and modify heart rate variability in a prognostically favourable direction in elderly low-to-intermediate risk patients , recovering from an acute coronary event BACKGROUND AND PURPOSE Cardiac autonomic dysfunction is associated with risk of restenosis and cardiovascular mortality in patients after percutaneous transluminal coronary angioplasty ( PTCA ) . Analysis of heart rate variability ( HRV ) is an important , widely used method for assessing cardiac autonomic regulation . The purpose of this study was to investigate the effect of exercise training on HRV in subjects after PTCA . SUBJECTS AND METHODS A total of 84 subjects who had undergone PTCA were recruited for this study . The subjects ( age [mean+/-SD]=57.0+/-9.3 years ) were r and omly assigned to either an exercise group to undergo an 8-week outpatient exercise program or a control group to undergo usual care . Heart rate variability was measured for 5 minutes in the supine resting position at baseline and at the end of 8 weeks . RESULTS The parasympathetically modulated HRV of the subjects in the exercise group increased significantly compared with the HRV of subjects in the control group . The effects of training on HRV were independent of angioplasty type ( balloon or stent ) and were unrelated to whether the subjects had received previous PTCA . DISCUSSION AND CONCLUSION Exercise training can increase parasympathetic modulation of cardiac function in people after they have undergone successful PTCA . Our results suggest that analysis of HRV can be extended to assess the effect of exercise training on cardiac autonomic dysfunction in people after coronary angioplasty To investigate the effects of carteolol , which is a nonselective beta-adrenergic agent with intrinsic sympathomimetic activity , on silent myocardial ischemia , exercise-induced myocardial ischemia , indexes of heart rate variability , and pain-modulating system , 20 patients ( mean 60 + /- 9 years ) with chronic stable angina underwent exercise treadmill testing and 24-hour ambulatory electrocardiographic monitoring during 2 weeks of carteolol administration ( 15 mg/day ) in a double-blind , placebo-controlled design . Plasma levels of beta-endorphin and bradykinin and electrical pain stimulation to the skin were measured at rest and peak exercise . Indexes of heart rate variability of both time-domain and frequency-domain analysis were derived from 24-hour ambulatory electrocardiographic monitoring . Carteolol decreased maximal heart rate responses to daily activities during ambulatory monitoring and significantly reduced the median frequency and duration of silent myocardial ischemic episodes ( from 1.0 to 0.0 events/24 hr and from 16 to 0 min/24 hr , respectively ) . Carteolol significantly decreased the rate-pressure product at rest and during exercise with improving maximal ST segment depression , suggesting amelioration of exercise-induced myocardial ischemia . Carteolol did not significantly affect plasma levels of beta-endorphin and bradykinin or pain threshold . It significantly decreased some indexes ( st and ard deviation of all normal sinus R-R intervals in the entire 24-hour recording and st and ard deviation of the mean of all 5-minute segments of normal R-R intervals of a 24-hour recording ) of heart rate variability . These results suggest that carteolol may reduce total myocardial ischemic burden by the reduction of cardiac oxygen dem and during daily activities and exercise stress , while not affecting plasma levels of beta-endorphin , bradykinin , and pain threshold . Because carteolol tended to decrease indexes of heart rate variability , significant caution might be necessary in prescribing the beta-blocking agents with intrinsic sympathomimetic activity like carteolol to patients with potential serious arrhythmia Background It is unclear how much of the reduction in cardiac mortality in coronary heart disease ( CHD ) patients with exercise training is the result of direct effects on the heart and coronary vasculature , or to indirect effects , via primary risk factors . Objective The aim of this article was to quantify the cardiac mortality benefits of exercise-based rehabilitation attributable to risk factor reductions versus the direct effects on the heart and vasculature . Methods The IMPACT coronary heart disease model was used to examine the reduction in cardiac mortality attributable to changes in risk factors from a meta- analysis of cardiac rehabilitation r and omized , controlled trials . Patients were receiving rehabilitation following an acute myocardial infa rct ion , angina pectoris or revascularization . Outcomes considered were primary risk factors ( total cholesterol , systolic blood pressure and smoking behaviour ) and cardiac mortality . Results Nineteen exercise-only cardiac rehabilitation trials ( including 2984 patients ) were identified . Across these trials , exercise training reduced pooled cardiac mortality by 28 % ( relative risk , 0.72 , 95 % confidence interval 0.55–0.95 ) , with 30 fewer deaths than in the control group . Applying the CHD model , approximately 17 ( 58 % ) of these 30 fewer deaths were attributable to reductions in major cardiovascular risk factors : 7.1 deaths ( minimum estimate 6.2 , maximum estimate 9.5 ) attributable to an 18 % reduction in smoking prevalence ; 5.9 deaths ( minimum −0.6 , maximum 12.6 ) to a 0.11 mmol/l reduction in cholesterol , and 4.4 deaths ( −1.0 minimum , 6.7 maximum ) to a 2.0 mmHg reduction in systolic blood pressure . Conclusions Approximately half of the 28 % reduction in cardiac mortality achieved with exercise-based cardiac rehabilitation may be attributed to reductions in major risk factors , particularly smoking . Eur J Cardiovasc Prev Rehabil 13:369–374 © 2006 The European Society of To investigate the effects of physical training on neurovegetative profile of patients with previous anterior myocardial infa rct ion ( MI ) , we studied 38 patients out of the EAMI study at 4 to 6 weeks after anterior MI ( test 1 ) , who were then assigned r and omly to a training group ( n = 22 ) or to a control group ( n = 16 ) and studied again 6 months later ( test 2 ) . Neurovegetative function was assessed by analyzing the heart rate variability ( HRV ) of 24 h , from ambulatory ECG recording , both in time domain , as st and ard deviation of sinus rhythm RR intervals ( sdRR ) and percentage of differences greater than 50 ms for successive sinus rhythm R-R intervals ( pNN50 ) , and in frequency domain , as low frequency ( LF ) and high frequency ( HF ) components of RR variability power spectrum . At test 1 , HRV was almost in normal range or slightly decreased in few subjects . HRV increased on average at test 2 : sdRR augmented significantly ( p less than 0.05 ) without significant differences between training group and control group ; mean LF/HF ratio increased slightly ( p less than 0.05 ) at test 2 . This might suggest a shift of neurovegetative balance toward a sympathetic rule , but the difference is too small and the patient population limited to reach firm conclusions . Analysis of 24-h dynamics of HRV in single patients showed different patterns and different adaptations during the time course of 6 months after anterior MI BACKGROUND Patients with coronary heart disease ( CHD ) who experience depressed mood or psychological stress exhibit decreased vagal control of heart rate ( HR ) , as assessed by spectral analysis of HR variability ( HRV ) . Myocardial infa rct ion and sudden cardiac death are independently associated with depression and stress , as well as impaired vagal HR control . This study examined whether a behavioral neurocardiac intervention to reduce stress or depression can augment cardiovagal modulation in CHD patients . We hypothesized that ( 1 ) cognitive-behavioral training with HRV biofeedback would augment vagal recovery from acute stress , and ( 2 ) vagal regulation of HR would be inversely associated with stress and depression after treatment . METHODS This r and omized controlled trial enrolled 46 CHD patients from 3 clinics of CHD risk reduction in Toronto and Vancouver , Canada . Subjects were r and omized to five 1.5-hour sessions of HRV biofeedback or an active control condition . Outcome was assessed by absolute and normalized high-frequency spectral components ( 0.15 - 0.50 Hz ) of HRV , and by the Perceived Stress Scale and Centre for Epidemiologic Studies in Depression scale . RESULTS Both groups reduced symptoms on the Perceived Stress Scale ( P = .001 ) and Centre for Epidemiologic Studies in Depression scale ( P = .004 ) . Hierarchical linear regression determined that improved psychological adjustment was significantly associated with the high-frequency index of vagal HR modulation only in the HRV biofeedback group . Adjusted R 2 was as follows : HRV biofeedback group , 0.86 for stress ( P = .02 ) and 0.81 for depression ( P = .03 ) ; versus the active control group , 0.04 ( P = .57 ) and 0.13 ( P = .95 ) , respectively . CONCLUSION A novel behavioral neurocardiac intervention , HRV biofeedback , can augment vagal HR regulation while facilitating psychological adjustment to CHD Twenty-five patients ( aged 62 + /- 2 years ) with stable , moderate to severe ischemic congestive heart failure ( CHF ) ( New York Heart Association class II/III : 15/10 ; ejection fraction 21.6 + /- 2 % ; and peak oxygen uptake 13.6 + /- 0.7 ml/kg/min ) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF . Sympathovagal balance was assessed by : ( 1 ) heart rate variability in the time domain , assessed by the SD of RR intervals ; ( 2 ) heart rate variability in the frequency domain , assessed by low- ( 0.03 to 0.14 Hz ) and high- ( 0.18 to 0.40 Hz ) frequency components of heart rate variability by autoregressive power spectral analysis ; ( 3 ) 24-hour , daytime and nighttime heart rate ; ( 4 ) submaximal heart rate during upright bicycle exercise , with respiratory gas analysis to obtain peak oxygen uptake ; and ( 5 ) radiolabeled norepinephrine spillover . These methods did not correlate , with the exception of day and nighttime heart rate ( r = 0.74 ; p < 0.001 ) and the expected inverse correlation between low and high frequency ( r = -0.92 ; p < 0.001 ) . No method correlated significantly with peak oxygen uptake , exercise tolerance or ejection fraction . After 8 weeks of physical training at home , all methods showed improvement in autonomic balance : increases in SD of RR intervals ( + 21 % ; p < 0.02 ) and high frequency ( + 41 % ; p < 0.007 ) , and decreases in low frequency ( -19 % ; p < 0.002 ) , low-/high-frequency ratio ( -48 % ; p < 0.03 ) , norepinephrine spillover ( -28.9 % ; p < 0.03 ) , 24-hour heart rate ( -2.7 % ; p < 0.005 ) and submaximal heart rate ( -10.8 % ; p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The effect of quinapril or metoprolol on heart rate variability ( HRV ) indexes was studied in patients who had recovered from acute myocardial infa rct ion . Patients with stable coronary artery disease and normal volunteers were used as controls . Sixty patients with uncomplicated myocardial infa rct ion ( aged 32 to 74 years [ mean 56.7 ] ) were r and omized to quinapril ( n = 25 ) , metoprolol ( n = 25 ) , and placebo ( n = 10 ) . HRV was assessed 5 days ( baseline ) and 35 days after the onset of acute myocardial infa rct ion . After the baseline studies , the post-myocardial infa rct ion patients were treated with metoprolol ( 50 to 100 mg/day ) , quinapril ( 5 to 10 mg/day ) , or placebo . Twenty patients with stable coronary artery disease and 20 healthy volunteers , age- and sex-matched to myocardial infa rct ion patients , were used as controls . Compared with placebo , quinapril and metoprolol increased HRV indexes significantly 35 days after the onset of myocardial infa rct ion . HRV indexes were not statistically different between the 2 treatment groups . At baseline and after therapy , HRV was similar in patients with anterior or inferior wall myocardial infa rct ion . HRV 35 days after the onset of myocardial infa rct ion was not different from HRV in patients with stable coronary artery disease , but was decreased when compared with that in normal volunteers . Data suggest that quinapril has the same beneficial effect on HRV indexes as metoprolol in patients who have recovered from uncomplicated acute myocardial infa rct ion Analysis of heart rate variability ( HRV ) can identify patients at risk of sudden cardiac death after myocardial infa rct ion . The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity , exercise capacity , and cardiac output ( CO ) after coronary artery bypass grafting ( CABG ) . Twenty-eight patients were r and omly divided into the training group or the control group and performed exercise tests at 1 week , 3 weeks , 3 months , 6 months and 1 year after CABG . The HRV was measured , and the high-frequency component of HRV was used as an index of parasympathetic nerve activity ( PNA ) ; the plasma norepinephrine concentration ( NE ) was used as an index of sympathetic nervous activity . Cardiac output was also measured . In the training group , peak VO2 , peak CO and PNA during exercise had improved at 3 weeks , but there was no improvement in these indices in the control group . NE decreased 1 week after CABG in both groups . These results indicate that physical training soon after CABG improves not only the exercise capacity , but also PNA Congestive heart failure ( CHF ) is characterized by sympathetic activation and parasympathetic withdrawal , and the magnitude of sympathoneural activation is associated with adverse outcome . Angiotensin-converting enzyme inhibitor therapy has been shown to reduce mortality and improve prognosis in patients with CHF , but whether this therapy improves cardiac autonomic control is not well known . This double-blind , placebo-controlled , crossover study examines the effects of enalapril on autonomic control in 12 patients with mild to moderate CHF by heart rate variability analysis . Compared with placebo , enalapril increased the SD of all normal RR intervals ( SDNN ) from 39 + /- 13 to 48 + /- 15 ms ( p < 0.01 ) , the SD of the average RR intervals for all 5-minute segments from 33 + /- 12 to 42 + /- 15 ms ( p < 0.01 ) , and the mean of the SDs of all RR intervals for all 5-minute segments ( SDNN index ) from 19 + /- 5 to 23 + /- 6 ms ( p < 0.01 ) . The root-mean-square successive differences and the percent differences between adjacent RR intervals > 50 ms were also increased from 17 + /- 8 to 21 + /- 8 ms ( p < 0.01 ) and from 1.1 + /- 2.1 to 2.8 + /- 2.9 % ( p < 0.05 ) . In addition , total , low-frequency , and high-frequency power were increased from 560 + /- 349 to 786 + /- 504 ms2/Hz ( p < 0.01 ) , from 125 + /- 107 to 179 + /- 135 ms2/Hz ( p < 0.01 ) , and from 46 + /- 32 to 94 + /- 78 ms2/Hz ( p < 0.01 ) , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS Because decreased heart rate variability measured after an acute myocardial infa rct ion ( AMI ) has been demonstrated to predict subsequent mortality and sudden death , and an efficacy analysis of the Danish Verapamil Infa rct ion Trial II ( DAVIT II ) demonstrated that long-term postinfa rct ion treatment with verapamil significantly reduced sudden death , the aim of the present sub study was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain , measured in two 5-minute segments during the day and night . Thirty-eight patients were examined by Holter monitoring , at 1 week , that is , before r and omization , and at 1 month after infa rct ion ; 22 of the patients were examined 12–16 months after infa rct ion as well . In both treatment groups ( verapamil and placebo ) no significant alteration of heart rate variability during the daytime was demonstrated from before to after 1 and 12–16 months of treatment . In accord with the known reduction of overall heart rate by verapamil , a significant increase of mean NN interval from before to after 1 ( P = 0.0004 ) and 12–16 months ( P = 0.004 ) of treatment was seen in the verapamil , but not in the placebo , group at night . Parameters generally interpreted as an index of parasympathetic modulation , that is , RMSSD , pNN50 , and high-frequency power , increased significantly at 1 month ( P = 0.04 , P = 0.03 , NS , respectively ) and 12–16 months ( P = 0.03 , P = 0.04 , P < 0.05 ) after AMI in the verapamil , but not in the placebo , group . In conclusion , the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfa rct ion period Background Many secondary abnormalities in chronic heart failure ( CHF ) may reflect physical deconditioning . There has been no prospect i ve , controlled study of the effects of physical training on hemodynamics and autonomic function in CHIF . Methods and Results In a controlled crossover trial of 8 weeks of exercise training , 17 men with stable moderate to severe CHF ( age , 61.8±1.5 years ; left ventricular ejection fraction , 19.6±2.3 % ) , increased exercise tolerance ( 13.9±1.0 to 16.5±1.0 minutes , p<0.001 ) , and peak oxygen uptake ( 13.2±0.9 to 15.6±1.0 mI/kg/min , p<0.01 ) significantly compared with controls . Training increased cardiac output at submaximal ( 5.9 - 6.7 1/min , p<0.05 ) and peak exercise ( 6.3 - 7.1 /min , p<0.05 ) , with a significant reduction in systemic vascular resistance . Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production ( −10.5 % , p<0.05 ) . Sympathovagal balance was altered by physical training when assessed by three methods : 1 ) RR variability ( + 19.2 % , p<0.05 ) ; 2 ) autoregressive power spectral analysis of the resting ECG divided into low-frequency ( −21.2 % , p<0.01 ) and high-frequency ( + 51.3 % , p<0.05 ) components ; and 3 ) whole-body radiolabeled norepinephrine spillover ( −16 % , p<0.05 ) . These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training . Conclusions Carefully selected patients with moderate to severe CHF can achieve significant , worthwhile improvements with exercise training . Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF , including abnormalities in autonomic balance OBJECTIVES This study assessed the effects of beta-blockade on heart rate variability in patients with coronary artery disease and determined whether the effects of metoprolol in a controlled-release formulation and atenolol differ with regard to electrocardiographic measures of cardiac autonomic control . BACKGROUND Low heart rate variability is common in coronary artery disease and is associated with increased mortality . Beta-adrenergic blocking drugs may increase heart rate variability in healthy subjects , but there is limited knowledge of whether they are able to modify heart rate variability in patients with uncomplicated coronary artery disease . METHODS In a r and omly allocated , double-blind crossover study with three 2-week treatment periods , 200 mg of controlled-release metoprolol once a day , 100 mg of atenolol once a day or placebo once a day were administered in 18 male patients with stable coronary artery disease . The 24-h heart rate variability was measured in both the time and frequency domains . RESULTS Beta-blockade induced a significant increase in heart rate variability , but no significant differences were found between atenolol and metoprolol . The average 24-h high frequency power increased by 64 % after atenolol and by 62 % after metoprolol . The root-mean-square successive difference of normal RR intervals increased by 70 % after atenolol and by 62 % after metoprolol , and the st and ard deviations of RR intervals increased by 20 % and 16 % , respectively . Beta-blockade had no significant effects on the amplitude of the circadian rhythm of heart rate variability , although both metoprolol and atenolol blunted the abrupt decrease of high frequency power after arousal . CONCLUSIONS Beta-blockade by metoprolol and atenolol enhance the heart rate variability in patients with coronary artery disease . This may contribute to the protective effects of beta-blockade in ischemic heart disease BACKGROUND The aim of this study was to verify the changes in the autonomic balance by means of heart rate variability assessment in patients with myocardial infa rct ion referred for cardiac rehabilitation . METHODS We studied 122 patients ( 79 males , 43 females , mean age 56 + /- 5 years ) , with a first uncomplicated myocardial infa rct ion ( anterior 48 , thrombolysis 72 ) , Killip class 1 , preserved left ventricular function ( ejection fraction 49 + /- 6 % ) . All patients were free of inducible residual ischemia . Four weeks after myocardial infa rct ion , patients were r and omized into two groups ; Group 1 ( n = 58 ) referred for an 8 week cardiac rehabilitation program ( scheduled : 24 sessions ) ; Group 2 ( n = 64 ) : normal daily physical activity . During a 24-hour Holter ECG monitoring the following parameters were calculated in pharmacological wash-out at r and omization ( T0 ) and at the end of cardiac rehabilitation/control period ( T1 ) : mean value of RR intervals ( RR ) , its st and ard deviation ( SDNN ) , pNN50 , rMSSD in the time domain ; low frequency ( LF ) and high frequency ( HF ) value and the LF/HF ratio in the frequency domain . T1-T0 changes in percent values ( delta % ) were considered and compared between the two groups . RESULTS Thirty-one patients were excluded from the study either for insufficient adhesion to the cardiac rehabilitation program ( < 13 sessions , 22 patients ) or recurrent ischemia ( 3 Group 1 patients and 3 Group 2 patients ) and non-assessable 24-hour Holter ECG monitoring ( 3 patients ) . Thirty-one Group 1 patients and 60 Group 2 patients completed the study with a first and a second 24-hour Holter ECG monitoring performed at 30 + /- 3 days and 60 + /- 4 days respectively . At the same time an ergospirometric test was performed to evaluate cardiopulmonary function by means of exercise time , maximum oxygen consumption , anaerobic threshold , exercise time at the anaerobic threshold , and maximum oxygen consumption at the anaerobic threshold . Twenty-eight Group 1 patients and 44 Group 2 patients completed the study with a first and a second ergospirometric test . Baseline heart rate variability parameters were comparable in the two groups . During the observation period only in Group 1 patients heart rate variability parameters changed significantly : RR ( Group 1 = + 18.3 + /- 21.3 ; Group 2 = + 4.2 + /- 5.2 , p = 0.000 ) , pNN50 ( Group 1 = 45.0 + /- 38.9 ; Group 2 = + 24.2 + /- 34.7 , p = 0.011 ) , HF ( Group 1 = + 81.6 + /- 124 ; Group 2 = -28.7 + /- 75.4 , p = 0.014 ) and LF/HF ratio ( Group 1 = -26.0 + /- 16.1 ; Group 2 = -4.9 + /- 6.1 , p = 0.062 ) . There were no significant differences in SDNN , rMSSD and LF . A linear correlation between delta LF/HF ratio and baseline LF/HF ratio values was found in Group 1 ( r = 0.489 , p = 0.006 ) , whereas no correlation was found between this parameter and age , ejection fraction , creatine phosphokinase , and infa rct localization . Group 1 patients had a significant improvement in exercise tolerance compared to Group 2 patients . CONCLUSIONS A cardiac rehabilitation program positively modifies the sympatho-vagal balance in patients with uncomplicated myocardial infa rct ion , increasing the parasympathetic tone and exercise tolerance BACKGROUND Resistance exercise training was applied to patients with chronic heart failure ( CHF ) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance , aerobic power ( VO(2peak ) ) , heart rate variability ( HRV ) , and forearm blood flow ( FBF ) that are all putative factors in the syndrome . METHODS AND RESULTS Thirty-nine CHF patients ( New York Heart Association Functional Class=2.3+/-0.5 ; left ventricular ejection fraction 28%+/-7 % ; age 65+/-11 years ; 33:6 male : female ) underwent 2 identical series of tests , 1 week apart , for strength and endurance of the knee and elbow extensors and flexors , VO(2peak ) , HRV , FBF at rest , and FBF activated by forearm exercise or limb ischemia . Patients were then r and omized to 3 months of resistance training ( EX , n=19 ) , consisting of mainly isokinetic ( hydraulic ) ergometry , interspersed with rest intervals , or continuance with usual care ( CON , n=20 ) , after which they underwent repeat endpoint testing . Combining all 4 movement patterns , strength increased for EX by 21+/-30 % ( mean+/-SD , P<.01 ) after training , whereas endurance improved 21+/-21 % ( P<.01 ) . Corresponding data for CON remained almost unchanged ( strength P<.005 , endurance P<.003 EX versus CON ) . VO(2peak ) improved in EX by 11+/-15 % ( P<.01 ) , whereas it decreased by 10+/-18 % ( P<.05 ) in CON ( P<.001 EX versus CON ) . The ratio of low-frequency to high-frequency spectral power fell after resistance training in EX by 44+/-53 % ( P<.01 ) , but was unchanged in CON ( P<.05 EX versus CON ) . FBF increased at rest by 20+/-32 % ( P<.01 ) , and when stimulated by submaximal exercise ( 24+/-32 % , P<.01 ) or limb ischemia ( 26+/-45 % , P<.01 ) in EX , but not in CON ( P<.01 EX versus CON ) . CONCLUSIONS Moderate-intensity resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance , VO(2peak ) , FBF , and HRV OBJECTIVES To determine if cardiorespiratory biofeedback increases heart rate variability ( HRV ) in patients with documented coronary artery disease ( CAD ) . BACKGROUND Diminished HRV has been associated with increased cardiac morbidity and mortality . Evidence suggests that various lifestyle changes and pharmacologic therapies can improve HRV . The objective of this study was to determine if biofeedback increases HRV in patients with CAD . METHODS Patients with established CAD ( n = 63 ; mean age , 67 years ) were r and omly assigned to conventional therapy or to 6 biofeedback sessions consisting of abdominal breath training , heart and respiratory physiologic feedback , and daily breathing practice . HRV was measured by the st and ard deviation of normal-to-normal QRS complexes ( SDNN ) at week 1 ( pretreatment ) , week 6 ( after treatment ) , and week 18 ( follow-up ) . RESULTS Baseline characteristics were similar for the treatment and control groups . The SDNN for the biofeedback and control groups did not differ at baseline or at week 6 but were significantly different at week 18 . The biofeedback group showed a significant increase in SDNN from baseline to week 6 ( P < .001 ) and to week 18 ( P = .003 ) . The control subjects had no change from baseline to week 6 ( P = .214 ) and week 18 ( P = .27 ) . CONCLUSIONS Biofeedback increases HRV in patients with CAD and therefore may be an integral tool for improving cardiac morbidity and mortality rates BACKGROUND Experimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity ( BRS ) may contribute to postinfa rct ion risk stratification . There are clinical data to support this concept for heart-rate variability . The main objective of the ATRAMI study was to provide prospect i ve data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infa rct ion in whom left-ventricular ejection fraction ( LVEF ) and ventricular arrhythmias were known . METHODS This multicentre international prospect i ve study enrolled 1284 patients with a recent ( < 28 days ) myocardial infa rct ion . 24 h Holter recording was done to quantify heart-rate variability ( measured as st and ard deviation of normal to normal RR intervals [ SDNN ] ) and ventricular arrhythmias . BRS was calculated from measurement of the rate-pressure response to intravenous phenylephrine . FINDINGS During 21 ( SD 8) months of follow-up , the primary endpoint , cardiac mortality , included 44 cardiac deaths and five non-fatal cardiac arrests . Low values of either heart-rate variability ( SDNN < 70 ms ) or BRS ( < 3.0 ms per mm Hg ) carried a significant multivariate risk of cardiac mortality ( 3.2 [ 95 % CI 1.42 - 7.36 ] and 2.8 [ 1.24 - 6.16 ] , respectively ) . The association of low SDNN and BRS further increased risk ; the 2-year mortality was 17 % when both were below the cut-offs and 2 % ( p<0.0001 ) when both were well preserved ( SDNN > 105 ms , BRS > 6.1 ms per mm Hg ) . The association of low SDNN or BRS with LVEF below 35 % carried a relative risk of 6.7 ( 3.1 - 14.6 ) or 8.7 ( 4.3 - 17.6 ) , respectively , compared with patients with LVEF above 35 % and less compromised SDNN ( > or = 70 ms ) and BRS ( > or = 3 ms per mm Hg ) . INTERPRETATION ATRAMI provides clinical evidence that after myocardial infa rct ion the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability & NA ; We examined the effects of & bgr;-blockers on the associations between heart rate and number of premature ventricular beats ( PVBs ) and on heart rate variability and myocardial ischemia in patients with coronary heart disease . After 2 weeks of run-in placebo treatment , 18 patients with coronary artery disease were r and omized to a 7-day treatment with either propranolol ( 40 mg ) three times a day or placebo . During run-in and after 7 days of treatment , patients underwent 24-hour Holter monitoring and exercise tests . We analyzed the 24-hour Holter recordings with customized software that computes the correlation between heart rate and occurrence of PVBs . We also computed spectral measures of heart rate variability on the same recordings . Propranolol caused a significant decrease in the log-transformed total number of PVBs recorded over 24 hours and during the day . The number of PVBs was much lower during the night than during the day both after placebo and after propranolol . There were no differences between the two treatments . During the day , there was a positive correlation between heart rate and the number of PVBs in all 18 patients . The mean correlation coefficients between heart rate and number of PVBs increased significantly after propranolol treatment both during the 24-hour monitoring ( p < 0.05 ) and during the day ( p < 0.05 ) . The night-recorded correlation coefficients between heart rate and number of PVBs were not significantly different in the placebo versus propranolol group . Propranolol significantly increased the total power during the day . Placebo caused a significant decrease in the low-frequency b and ( LF ) and a significant increase in the high-frequency b and ( HF ) during the night compared with the day . During the day , propranolol significantly reduced LF power and increased HF power , with respect to placebo . After propranolol treatment , the values of LF and HF power during the day were comparable to those recorded at night . The LF/HF ratio decreased significantly after propranolol treatment with respect to placebo in the day and became similar to that recorded during sleep . Propranolol significantly reduced heart rate and systolic blood pressure at rest and at peak exercise and reduced signs of myocardial ischemia . Propranolol administration reduces PVBs in patients with coronary artery disease and severe ventricular arrhythmias possibly through an improvement of cardiac autonomic regulation and through anti-ischemic effects , antiarrhythmic effects , or both This study evaluated the effects of propranolol on recovery of heart rate variability ( HRV ) after acute myocardial infa rct ion and its relation to outcome in the Beta-blocker Heart Attack Trial ( BHAT ) . Beta blockers improve mortality after acute myocardial infa rct ion , but through an unknown mechanism . Depressed HRV , a measure of autonomic tone , predicts mortality after acute myocardial infa rct ion . Whether beta blockers influence recovery of HRV after acute myocardial infa rct ion , and thereby improve outcome , is unknown . We compared 24-hour HRV parameters at 1 week after acute myocardial infa rct ion and after 6 weeks of treatment with propanolol ( n = 88 ) or placebo ( n = 96 ) . The relation between 25-month outcome ( death/acute myocardial infa rct ion/congestive heart failure ) , propranolol treatment , and HRV was further analyzed . After 6 weeks , high-frequency ( HF ) power ( log-normalized ) , an index of vagal tone , increased more in propranolol-treated patients ( 4.28 + /- 0.1 to 5.17 + /- 0.09 ms(2 ) ) than in placebo-treated patients ( 4.26 + /- 0.09 to 4.77 + /- 0.1 ms(2 ) , p < 0.05 ) . Sympathovagal balance measured by the low-frequency ( LF ) to HF ratio increased in placebo-treated patients ( 3.55 + /- 0.24 to 3.86 + /- 0.24 ) but decreased in those treated with propranolol ( 3.76 + /- 0.29 to 3.17 + /- 0.23 , p < 0.01 ) . Other frequency-domain parameters increased over time but were not affected by propranolol . Propranolol blunted the morning increase in the LF/HF ratio . Recovery of HF , the strongest HRV predictor of outcome , and propranolol therapy independently predicted outcome . In summary , after acute myocardial infa rct ion , propranolol therapy improves recovery of parasympathetic tone , which correlates with improved outcome , and decreases morning sympathetic predominance . These findings may eluci date the mechanisms by which beta blockers decrease mortality and reduce the early morning risk of sudden death after acute myocardial infa rct ion AIM Autonomic impairment is related to the incidence of sudden death in chronic heart failure ( CHF ) . Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease , and to investigate the value of add-on beta-blockade . METHODS AND RESULTS Measures of autonomic function ( plasma norepinephrine , heart rate [ HR ] variability , autonomic function testing ) , and exercise capacity , were compared between 24 patients with mild CHF , and 24 healthy controls . In this mechanistic study , we assessed the effect of 26 weeks metoprolol treatment in a double-blind , r and omized , placebo-controlled design . All patients received metoprolol sustained release ( 200 mg ; n=12 ) or placebo ( n=12 ) . Assessment s were made at baseline and after 10 and 26 weeks ' treatment . At baseline , norepinephrine levels were elevated , while HR variability parameters were decreased in patients vs. controls ( both P<0.05 ) . Autonomic function testing showed only small differences , although significant alterations were observed with deep breathing and head up tilting ( both P<0.05 ) . After 26 weeks ' , metoprolol did not affect exercise capacity or norepinephrine concentrations . In contrast , HR variability was markedly improved in metoprolol-treated patients vs. placebo-treated patients ( P<0.05 ) . In particular , a shift toward normal in the sympathovagal balance was observed ( P<0.05 ) . Autonomic function testing showed only small , and generally non-significant trends after metoprolol . CONCLUSIONS Marked autonomic abnormalities are already present in mild CHF , which may be ( partially ) reversed by metoprolol . These observations support the reported reduction of sudden death by beta-blockade in patients with CHF Signs of sympathetic hyperactivity and low parasympathetic activity have been found during the acute and recovery phases of myocardial infa rct ion and have been associated with an increased risk of cardiac mortality . Beneficial effects of physical training have been recently reported in post-myocardial infa rct ion patients . We tested the hypothesis that physical training would be effective in improving the autonomic balance by study ing 22 patients with a first and recent myocardial infa rct ion who were r and omly assigned to enter or not enter a 4-week in-hospital physical training program . Spectral indices of heart rate variability were analyzed at rest and during 70 degrees head-up tilt before and after the index training , not training period . As expected , physical training induced a significant increase in exercise duration ( 13.7 + /- 0.8 vs 17.1 + /- 0.1 min , p less than 0.001 ) and in the anaerobic threshold ( 9.5 + /- 0.7 vs 12.0 + /- 1.0 min , p less than 0.02 ) in trained patients , while no changes were observed in the untrained group . At entry , in both groups , spectral profile of heart rate variability was characterized by a predominant LF component and a smaller HF component with no further modification after head-up tilt . After 4 weeks , in resting conditions , no significant changes in spectral components were observed in both trained and untrained patients . After physical training , head-up tilt produced significant modifications in spectral profile with an increase in the LF component ( 84 + /- 3 vs 69 + /- 5 nu , p less than 0.01 ) and a decrease in the HF component ( 7 + /- 1 vs 19 + /- 4 nu , p less than 0.05 ) in trained patients , while no changes were observed in the untrained patients . Our data suggest that in postmyocardial infa rct ion patients , 4 weeks of physical training may induce an improvement in the autonomic balance with a restoration toward normal in the reflex activity of the system BACKGROUND Brain serotonin is known to possess sympathoinhibitory properties . The aim of this clinical physiologic study was to determine whether sertraline , a selective serotonin reuptake inhibitor , facilitates the rate of recovery of cardiac autonomic function after an acute myocardial infa rct ion ( MI ) in patients with depression . METHODS AND RESULTS Thirty-eight post-MI depressed patients were r and omized to receive either sertraline 50 mg per day or placebo for 6 months . Depression was defined as a score > 15 on the st and ardized Inventory to Diagnose Depression question naire taken at prehospital discharge and again within 2 weeks of the acute infa rct . Eleven stable post-MI nondepressed patients served as a nonr and omized reference group during follow-up . Twenty-seven patients completed the r and omization . All 3 groups were followed up closely in a multidisciplinary post-MI clinic where they underwent serial testing for both time and frequency domain heart rate variability ( HRV ) indices at baseline ( 1 - 2 weeks after MI ) and at 6 , 10 , 14 , 18 , and 22 weeks . The rate of recovery of HRV was determined by use of a growth curve model based on repeated- measures analysis of variance . There was a linear rate of increase in the SD of 24-hour N-N intervals ( SDNN ) in the sertraline-treated group that paralleled that of the nondepressed reference group . This contrasted with a modest but significant decline in SDNN in the placebo group from 2 to 22 weeks ( t = 2.10 , P < .05 ) . However , the short-term power spectral indices , while trending toward a more rapid rate of recovery in the treated group , did not reach statistical significance compared with the placebo group . CONCLUSION In depressed patients who have survived the acute phase of an MI sertraline facilitates the rate of recovery of SDNN , a recognized predictor of clinical outcome A depressed heart rate variability ( HRV ) is a powerful predictor of poor outcome in myocardial infa rct ion patients . The beneficial effect of specific interventions on its recovery has been reported , but data concerning calcium antagonists are scarce . We evaluated the effect of a phenylalkylamine derivative , verapamil , and a dihydropyridine derivative , felodipine , on time- and frequency-domain measurements of HRV by 24-hour Holter monitoring in 60 patients with acute myocardial infa rct ion ( AMI ) . After a first Holter recording ( 65 + /- 8 hours from the onset of symptoms ) , patients were r and omly assigned to continue st and ard treatment or to also receive verapamil retard ( 120 mg 3 times daily ) or felodipine extended-release ( 10 mg/day ) . Holter recording was repeated after 7 days . After verapamil , mean RR interval increased from 823 + /- 92 to 907 + /- 95 ms and the SD of all normal RR ( NN ) intervals ( SDNN ) from 99 + /- 24 to 120 + /- 30 ms ( p < 0.01 ) ; the root mean square successive difference ( r-MSSD ) and the percent of differences between adjacent NN intervals > 50 ms ( pNN50 ) also increased ( p < 0.01 ) . After felodipine , only SDNN increased ( p < 0.01 ) . Regarding frequency-domain measurements , after receiving verapamil , very low frequency , low- and high-frequency powers increased ( p < 0.01 ) , whereas the low- to high-frequency ratio decreased ( p < 0.01 ) . After receiving felodipine , very low-frequency power increased ( p < 0.01 ) , whereas low- and high-frequency powers and the low- to high-frequency ratio remained unchanged . This study demonstrates that verapamil , but not felodipine , improves HRV in the early phase after AMI The effect of physical training on the circadian pattern of heart rate variability ( recorded over 24 h in relation to both time and frequency ) was assessed in 12 chronic heart failure patients r and omized , in a cross-over design , to 8 weeks training or detraining , and compared with 12 age-matched normals . Training improved heart rate variability indices : all R-R interval 5 min st and ard deviations increased by 17.6 % , the root mean square of the differences of successive R-R intervals by 34.9 % , the percentage difference between adjacent normal R-R intervals > 50 ms by 112.5 % , total power by 58.3 % , high frequency by 128.5 % and low frequency by 65.0 % . Compared with controls , circadian variations in autonomic parameters were maintained in chronic heart failure . Training-induced changes were observed at different time intervals throughout the day : the highest values were at 0100 h-0700 h ( detraining : low frequency 361 + /- 83 ms2 , high frequency 126 + /- 47 ms2 ; training : low frequency 535 + /- 202 ms2 , high frequency 227 + /- 115 ms2 , P < 0.01 ) and the lowest at 1300 h-1900 h ( detraining : low frequency 91 + /- 23 ms2 , high frequency 39 + /- 14 ms2 ; training : low frequency 154 + /- 42 ms2 , high frequency 133 + /- 67 ms2 , P < 0.05 ) . In chronic heart failure , training maintains and improves circadian variations in heart rate variability measures OBJECTIVES This study sought to determine whether a moderate intensity supervised exercise training program , performed immediately after an uncomplicated acute myocardial infa rct ion , improves recovery in cardiac autonomic function compared with st and ard advice about activity at home . BACKGROUND Exercise training has beneficial effects on cardiac autonomic function and may improve prognosis after acute myocardial infa rct ion . METHODS Thirty-nine male and 10 female patients , mean ( + /-SE ) age 57 + /- 1 years , with an uncomplicated acute myocardial infa rct ion were r and omized to either a 6-week moderate intensity supervised hospital-based exercise training program ( exercise group ) or to an unsupervised low intensity home walking program ( control group ) . Outcome measures included changes in baroreflex sensitivity ( phenylephrine bolus method ) and heart rate variability ( 24-h Holter monitoring ) and the endurance time at 85 % of peak oxygen consumption . RESULTS At baseline , there were no significant differences in left ventricular ejection fraction ( 57 + /- 2 % vs. 53 + /- 2 % ) , frequency of anterior infa rct ion ( 27 % vs. 18 % ) and peak creatine kinase ( 1,256 + /- 170 vs. 2,599 + /- 295 IU ) between the exercise and control groups . Baroreflex sensitivity ( 10.5 + /- 1.0 vs. 8.4 + /- 1.2 ms/mm Hg ) and time domain measures of heart rate variability were also similar . After completion of the program , the exercise group exercised for a median of 15 min ( interquartile range 12 to 25 ) at a workload of 104 + /- 7 W compared with 7 min ( interquartile range 3.5 to 12 ) at a workload of 89 + /- 8 W in the control group ( p < 0.01 ) . There were significant ( p < 0.001 ) improvements in baroreflex sensitivity and heart rate variability for the 49 patients combined but no differences between the exercise and control groups . Baroreflex sensitivity improved by 3.4 + /- 1.0 and 1.7 + /- 1.0 ms/mm Hg and the st and ard deviation of 24-h RR intervals by 36 + /- 6 and 40 + /- 10 ms , respectively ( p > 0.1 ) . CONCLUSIONS A hospital-based exercise training program increased endurance capacity but did not improve recovery of cardiovascular antonomic function after uncomplicated acute myocardial infa rct ion BACKGROUND Beneficial effects of physical training on exercise tolerance , autonomic and skeletal muscle function and limb blood flow have been demonstrated in chronic heart failure . Because this rehabilitation is expensive , may involve risk , and has unknown effects on prognosis , the possibility of predicting benefit on the basis of individual patient data is intriguing . The most suitable exercise training programme has not yet been established . METHODS AND RESULTS We review ed the progress of 134 stable heart failure patients studied in r and omized controlled trials of physical training . A significant training effect ( + 13 % peak oxygen consumption , + 17 % exercise duration ) was associated with improved autonomic indices ( resting catecholamines and hormones , heart rate variability ) , without significant side-effects . No ventilatory , haemodynamic , autonomic or clinical factor at baseline was a predictor of outcome . Similar beneficial effects were observed in both male and female patients . The improvement in oxygen consumption after 16 weeks training was higher than after 6 weeks ( + 2.6 + /- 3.0 vs + 0.3 + /- 3.1 ml.kg.min-1 , P < 0.05 ) . The combination of cycle ergometer with calisthenic exercises was more beneficial than cycle ergometer alone ( + 2.7 + /- 4.2 vs 1.2 + /- 2.0 ml.kg.min-1 , P < 0.01 ) . The presence of nonsustained ventricular tachycardia did not preclude a training effect . Patients older than 70 years were able to train , although less effectively than the younger ones . No difference in exercise gain was observed whether the patients trained in the hospital or at home . CONCLUSION The positive effects of physical rehabilitation in chronic stable heart failure patients are confirmed . No baseline patient factor was significantly correlated with outcome . A tailored , moderate , home-based , combined cycle ergometer , plus calisthenic exercise training seems safe and beneficial in a large cohort of heart failure patients , with similar benefits in a variety of conditions and different hospital setting This study investigated the effects of aerobic exercise training on the early phase of the recovery process following acute myocardial infa rct ion ( AMI ) in terms of the autonomic nervous system , cardiac function and exercise capacity . Twenty-eight patients in the first week after the onset of AMI were assigned r and omly to either a training group or a control group . The training group performed aerobic exercise for 2 weeks . Cardiopulmonary exercise testing was performed 3 times during the 3 months after the onset . Heart rate variability , plasma norepinephrine ( NE ) levels , and cardiac index ( CI ) during exercise were measured . In the training group , plasma NE level and deltaCI ( peak CI-rest CI ) were significantly improved from 1 to 3 weeks after the onset , and the high frequency of heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset . In the control group , the plasma NE level and the deltaCI during the 1 - 3 weeks post-AMI , the high frequency of heart rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset . These results indicate that sympathetic nervous activity improves soon after the onset of AMI , in conjunction with improvement in cardiac function , and that this improvement is not affected by exercise training . In contrast , the recovery of parasympathetic nervous activity requires a longer period , along with the recovery of exercise capacity , which is facilitated by even short-term aerobic exercise training BACKGROUND Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability ( HRV ) toward parasympathetic dominance in patients after acute myocardial infa rct ion ( MI ) . However , its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown . We aim ed to investigate the effects of 8 weeks of supervised , high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population . METHODS AND RESULTS Twenty-five men with an acute MI and a low ejection fraction were r and omly assigned to enter or not to enter a training program in a regional rehabilitation center . HRV was evaluated before and after 1 and 2 months of training and at 12 months . Maximal exercise testing with respiratory gas exchange was performed at baseline and after training . Resting heart rate decreased ( P < . 01 ) and the percentage of R-R intervals differing > 50 ms from the preceding one ( pNN50 ) increased ( P < .05 ) after training . The st and ard deviation of R-R intervals ( SDRR ) tended to increase , but frequency-domain indexes remained unchanged . There was a significant decrease in SDRR ( P < .05 ) and high-frequency power ( P < .01 ) at 12 months in untrained patients . Exercise time increased by 38 % and maximal oxygen uptake increased by 29 % in the training group ( P < . 01 ) . CONCLUSIONS Despite beneficial effects on clinical variables , exercise training did not markedly alter HRV indexes . A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction In order to assess additional anti-ischaemic effects of amlodipine ( AML ) on coronary artery disease ( CAD ) treated with beta-blockers , 32 patients with CAD , verified on angiograms , and stable angina were r and omized to receive 5 mg/day of AML or placebo , increasing to 10 mg/day after 2 weeks . Baseline recording of 24-h ambulatory ECG and blood pressure , echocardiography and bicycle exercise test was repeated after treatment for 2 weeks and for 6 weeks . Reduction of ambulatory ischaemia was not significantly greater with AML than with placebo . In exercise tests the time to 0.1 mV ST segment depression and the total exercise time remained unaltered . Blood pressure was reduced by 10 mg AML . The total variability and the very low frequency component of heart rate were reduced after both doses . The clinical significance of the possible unfavourable change in autonomic modulation of the heart in CAD patients is not known |
12,602 | 12,540,794 | In conclusion , chemoembolization improves survival of patients with unresectable HCC and may become the st and ard treatment .
Treatment with tamoxifen does not modify the survival of patients with advanced disease | There is no st and ard treatment for patients with unresectable hepatocellular carcinoma ( HCC ) .
Survival benefits derived from medical interventions are controversial .
The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival . | BACKGROUND AND AIMS There is currently no proven chemotherapy regimen for hepatocellular carcinoma ( HCC ) . The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors . However , the clinical effects of chemotherapy are extremely poor . Therefore , in the present study , we conducted a prospect i ve r and omized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC . METHODS From 1994 to 1999 , a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospect ively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors . Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment . Another 20 patients were given conservative management only . The remaining eight patients withdrew from the study . RESULTS In the group treated only with enteric-coated tegafur/uracil , the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9 % , respectively . In the control group , the median survival time and 1 year survival rate were 6.20 months and 5.5 % , respectively . By both univariate analysis and multivariate analysis using Cox 's proportional hazards model , treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis . CONCLUSIONS Although the prognosis of most patients with stage IV-A HCC is poor , administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC We conducted a prospect i ve r and omized trial to evaluate the efficacy of Lipiodol in intrahepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma ( HCC ) . A total of 38 patients with unresectable HCCs and underlying cirrhosis were entered in this trial , and 36 of them were evaluable . Every 4 weeks , 17 patients received 70 mg of 4′-epidoxorubicin ( epirubicin ) alone ( group A ) , whereas 19 patients received a Lipiodol emulsion containing the same dose of epirubicin ( group B ) through the hepatic artery . A tumor response ( CR+PR ) was observed in 12 % of group A patients and in 42 % of group B patients . The group B patients showed a significantly higher response rate than the group A patients . There was a tendency for an increased duration of survival ( P=0.09 ) in the group B patients . These results suggested that the infusion of the Lipiodol emulsion with epirubicin was more effective than epirubicin alone for the treatment of these patients with HCC Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are associated with aggressive clinical course and unresponsiveness to tamoxifen . To evaluate the impact on survival and on tumour growth of megestrol ( progestin drug acting at post-receptorial level ) we enrolled 45 patients with HCC characterized by variant liver oestrogen receptors in a prospect i ve , r and omized study with megestrol vs. placebo . Presence of variant oestrogen receptors was determined by RT/PCR . 24 patients were r and omized to no treatment and 21 to therapy with megestrol 160 mg day–1 . Results were analysed by Kaplan-Meier and Cox methods . Survival of hepatocellular carcinoma characterized by variant oestrogen receptors was extremely poor ( median survival 7 months ) ; megestrol significantly improved survival ( 18 months ) ( P = 0.0090 ) . Tumour growth at one year was significantly slowed down in megestrol-treated patients ( P = 0.0212 ) . Bilirubin levels , presence of portal thrombosis , HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival ; at multivariate analysis , only megestrol therapy ( P = 0.0003 ) , presence of HBV infection ( P = 0.0009 ) and presence of portal vein thrombosis ( P = 0.0051 ) were factors independently related with survival . ( 1 ) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant estrogen receptors and ( 2 ) is also able to favourably influence the course of disease , more than doubling median survival . © 2001 Cancer Research One hundred ninety‐two patients with unresectable primary liver cancer studied by members of the Eastern Cooperative Oncology Group ( ECOG ) were evaluable in a prospect ively r and omized clinical trial . Patient discriminants such as performance status were carefully evaluated to assess their influence on prognosis and to evaluate the importance of patient status on response and survival . Patients who were totally bedridden or with signs of overt liver failure were not entered on study . The median survival time for all evaluable previously untreated patients was 17 weeks ( 19 weeks for North American and European , and 10 weeks for South African black patients ) . Among the South African patients , however , there was a significantly larger proportion with an initially poor performance status . Prognostic variables ( performance status , jaundice , and reduced appetite ) dominate any differences among the treatments studied . Among North American and European patients on intravenous ( IV ) 5‐fluorouracil ( 5‐FU ) + Methyl‐CCNU ( MeCCNU ) + Adriamycin ( ADM , doxorubicin ) , the 19 % response rate is offset by 63 % with severe toxicity and a median survival time of only 17 weeks , making this treatment unacceptable clinical ly . The median survival time of North American and European patients treated with IV 5‐FU + MeCCNU was 28 weeks in contrast to a median survival time of 12 weeks with ADM ( P ≤ 0.01 ) . EST 2273 was the ECOG study of patients with primary liver cancer . The results of the first part of the trial were published in 1978 . This report up date s those findings and reports the results of patients entered subsequently on the second part of that study after it was amended in 1979 . With more than 300 evaluable patients in EST 2273 , this duet of studies is the largest ever conducted in patients with primary liver cancer , and draws a new baseline from which to measure the disease and its response to treatment A r and omized controlled trial of tamoxifen ( 60 mg/die ) versus placebo was performed in patients with cirrhosis and advanced inoperable hepatocellular carcinoma . Twenty-two patients were matched and coupled for sex , age , Child-Pugh class and tumour mass and then r and omized to tamoxifen or placebo . Median survival was 74 weeks in the tamoxifen group ( range 27 to 144 weeks ) and 52 weeks in the placebo group ( range 4 to 112 weeks ) . The survival of patients treated with tamoxifen improved significantly compared to the controls ( Logrank-test , p = 0.04 ) . These findings suggest that the effect of the antiestrogen tamoxifen is both statistically and clinical ly significant in increasing survival in patients with advanced hepatocellular carcinoma OBJECTIVES : A prospect i ve r and omized study was performed to test the hypothesis that tamoxifen might improve the survival of patients with advanced hepatocellular carcinoma ( HCC ) and to correlate the response of treatment with the expression of hormone receptors . METHODS : One hundred nineteen patients with advanced and otherwise untreatable HCC were included in a placebo-controlled , single-blind trial . The patients were r and omized to tamoxifen group ( 61 patients ) and control group ( 58 patients ) and were prescribed with a daily dose of 30 mg of tamoxifen and placebo , respectively . Immunohistochemical tests for estrogen and progesterone receptors were performed on the tumor tissues obtained from 66 patients . All patients were closely monitored and the survival outcome of the two groups of patients was compared and stratified according to the hormonal receptor status . RESULTS : There was no difference in the 1-month mortality rates ( 32.8 % vs 43.1 % , p = 0.246 ) and the median survival ( 44 days vs 41 days , p = 0.703 ) between the tamoxifen group and the control group . Furthermore , the expression of hormone receptors in the tumors did not affect the survival outcome of the patients treated with tamoxifen . None of the patients who survived longer than 3 months had tumor that had partial response to tamoxifen treatment on follow-up imaging study . CONCLUSIONS : Tamoxifen has no efficacy in the treatment of patients with advanced HCC and response to treatment was not affected by the expression of hormone receptors Lipiodol injected into the hepatic artery is selectively retained in hepatomas so has been used as a vehicle for cytotoxic drugs . This study compared treatment with 5-epidoxorubicin emulsified in lipiodol and infused into the hepatic artery with symptomatic treatment alone in a r and omised trial . Of 136 patients with hepatoma 78 ( 57 % ) were not eligible , eight ( 6 % ) refused to take part , and 50 entered the trial ( chemotherapy : n = 25 , symptomatic treatment : n = 25 ) . The two groups had similar prognostic indices . Seven of 25 patients allocated to chemotherapy were unable to receive it . The slight survival disadvantage associated with chemotherapy was not significant ( median survival 48 days compared with 51 days , log rank chi 2 = 0.07 , p > 0.05 ) . Patients given chemotherapy spent significantly longer in hospital , however ( median three days compared with one , p = 0.0008 ) . Changes in symptoms and indices of tumour growth did not differ significantly between the two groups . It is concluded that infusion of 5-epidoxorubicin emulsified in lipiodol for hepatoma increased morbidity but did not affect survival . In addition , most patients were unsuitable for this treatment because of advanced disease . The patients in the trial had a short median survival time so the conclusions may not be valid for other patients with hepatoma Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were r and omly allocated to two groups : group I included 20 patients who were treated with 10 mg bid . tamoxifen and group II with 16 non-treated patients . The two groups were homogeneous according to clinical and analytical data . Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group ( p = 0.01 ) . Cumulative survival at the end of the first year was 48.5 % in the treated patients and 9.1 % in controls . Median survival was 261 days in the treated group vs. 172 in the non-treated group ( p < 0.05 ) . Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls , but not significantly so . Tamoxifen was well tolerated and no marked side effects were observed . In this series , tamoxifen improved survival in patients with advanced hepatocellular carcinoma BACKGROUND / AIMS Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma , but its efficacy is still debated . The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma . METHODS Seventy-three patients with unresectable hepatocellular carcinoma , but without severe liver disease or portal vein occlusion , were r and omly assigned to receive either repeated lipiodol chemoembolization ( lipiodol , cisplatin ( 2 mg/kg ) , lecithin , and gelatin sponge injected into the hepatic artery ) plus tamoxifen ( 40 mg ) or tamoxifen alone . The main end-point was survival . RESULTS The 37 patients in the lipiodol chemoembolization group received 104 courses ( median 3 per patient ) . By 1 September 1996 , 58 patients had died : 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group . There was no difference in survival between the two groups ( p=0.77 ) . The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 ( 95 % confidence interval 0.55 to 1.56 ) . At 1 year , survival was 51 % and 55 % , respectively . An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group ( 24 versus 5.5 % , respectively , p=0.046 ) . Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51 % of the patients assigned to this treatment . CONCLUSION In our r and omized study , lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen A r and omized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma . These patients represented 41 % of patients with hepatocellular carcinoma seen during the inclusion period . In the remaining 59 % , 9 % had resectable tumours and 50 % had unresectable tumours with contraindication for chemoembolization . Patients received either repeated chemoembolization with gelfoam powder and doxorubicin ( group 1 ) or symptomatic treatment ( group 2 ) . There was no difference in age , prevalence of cirrhosis or staging according to Okuda between the two groups of patients . A complete tumour response ( assessed by arteriography , ultrasonography and serum alphafetoprotein ) was observed in four patients , and a partial response in three other patients from group 1 . Actuarial survival rates were 33 and 24 % in group 1 and 52 and 31 % in group 2 at 6 and 12 months , respectively ( differences were not significant -- logrank test ) . With the treatment used in our study , chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma . There were , however , some complete or partial responses . The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients . Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma This r and omized , controlled trial assessed the efficacy of transarterial Lipiodol ( Lipiodol Ultrafluide , Laboratoire Guerbet , Aulnay-Sous-Bois , France ) chemoembolization in patients with unresectable hepatocellular carcinoma . From March 1996 to October 1997 , 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and r and omly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery ( chemoembolization group , 40 patients ) or symptomatic treatment ( control group , 40 patients ) . One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis . Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease . Survival was the main end point . The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 ( range , 1 - 15 ) courses per patient . Chemoembolization result ed in a marked tumor response , and the actuarial survival was significantly better in the chemoembolization group ( 1 year , 57 % ; 2 years , 31 % ; 3 years , 26 % ) than in the control group ( 1 year , 32 % ; 2 years , 11 % ; 3 years , 3 % ; P = .002 ) . When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model , the survival benefit of chemoembolization remained significant ( relative risk of death , 0.49 ; 95 % CI , 0.29 - 0.81 ; P = .006 ) . Although death from liver failure was more frequent in patients who received chemoembolization , the liver functions of the survivors were not significantly different . In conclusion , in Asian patients with unresectable hepatocellular carcinoma , transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment PURPOSE The aim of the study was to evaluate the efficacy of anti and rogen therapy on overall survival and response in unresectable hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial . According to a two-by-two factorial design , patients were r and omly assigned to receive one of the following treatments : pure anti and rogen plus placebo ( A+P group , 60 patients ) ; luteinizing hormone-releasing hormone ( LHRH ) agonist plus placebo ( LHRH+P group , 62 patients ) ; pure anti and rogen plus LHRH agonist ( A+LHRH group , 62 patients ) ; or placebo plus placebo ( P+P group , 60 patients ) . Pure anti and rogen consisted of An and ron ( Roussel-Uclaf Laboratory , Romainville , France ) administered orally ( 300 mg daily for 1 month , then 150 mg daily ) . LHRH consisted of goseriline acetate ( 3.6 mg ) or triptoreline ( 3.75 mg ) administered monthly by subcutaneous injection . Treatment was given until death . Response was evaluated every 8 weeks according to World Health Organization ( WHO ) criteria . RESULTS Six patients were considered ineligible . One patient had a complete response ( A+P arm ) and three had a partial response ( two in the LHRH+P arm and one in the A+LHRH arm ) . An overall log-rank test did not demonstrate any significant difference in survival among the four arms . Taking the factorial design into account , comparison of survival showed no significant difference between An and ron-containing regimens and others , or between LHRH-containing regimens and others . No serious side effects occurred for any regimen . CONCLUSION This controlled study shows clearly the lack of efficacy of and rogen treatment in unresectable HCC Summary A r and omized , controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization ( L-TAE ) in the presence versus the absence of Adriamycin ( ADR ) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989 . In all , 125 Japanese hospitals participated in this study and 289 patients were entered in the trial . The patients were r and omly allocated into group A ( L-TAE ) or group B ( L-TAE+ADR ) by telephone registration . There was no significant difference in background factors between group A and group B. Additional treatment , including repeated TAE or hepatic resection , was given to 189 patients . Among the four endpoints analyzed , the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups . The 3-year survival values for groups A and B were 33.6 % and 34.9 % , respectively ; the difference was not significant . The serum alpha-fetoprotein level , however , decreased to a significantly greater extent in the group that received ADR than in the group that did not ( P<0.05 ) . This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma Summary A r and omized clinical trial comparing L-TAE with Farmorubicin ( FARM ) and L-TAE with Adriamycin ( ADR ) in the treatment of hepatocellular carcinoma was conducted from October 1989 through December 1990 . In all , 192 hospitals participated in this study and 117 patients were entered . The patients were r and omly allocated to group A ( L-TAE+FARM ) or group B ( L-TAE+ADR ) . There was no significant intergroup difference in background factors . Additional treatment consisting of repeated TAE or surgery was given to 66 patients . Four factors were analyzed in this study : the percentage of reduction in tumor size , the change in the AFP level , lipiodol accumulation , and survival . None of these factors differed significantly between the two groups . The final evaluation of this study will be based on differences in survival after a long-term follow-up . Toxic effects manifested less frequently in group A than in group B , and the decrease in the platelet count in the peripheral blood was significantly lower in group A than in group B. These results suggest that FARM exerts a more favorable effect than does ADR in the treatment of hepatocellular carcinoma The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon ( IFN-α ) and all-trans-retinoic acid ( tRA ) . Fifty patients with incurable malignancies received IFN-α administered subcutaneously three times weekly , and tRA administered by mouth at bedtime . Doses were escalated between patient groups , starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-α . Major , dose-limiting toxicities were attributable to either the tRA ( rash , chelitis ) or IFN ( constitutional symptoms ) , and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2 , or 6 million units of IFN-α . The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-α was well-tolerated , with no grade 3 or 4 toxicities attributable to therapy . One patient at the third dose level ( 75 mg/m2 of tRA and 3 million units of IFN-α ) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology . We conclude that tRA and IFN-α may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects . The recommended doses of IFN-α and tRA for Phase II trials are 3 million units of IFN-α and 172.5 mg/m2 of tRA Summary A total of 135 patients with hepatocellular carcinoma ( HCC ) were treated by intra-arterial injection of an Adriamycin/mitomycin C oil ( lipiodol ) suspension ( ADMOS ) alone or of ADMOS pluscis-diamminedichloroplatinum ( CDDP ) . In all , 59 patients were treated with ADMOS alone and 76 were treated with ADMOS plus CDDP . A reduction of more than 25 % in the tumor size was obtained in 13 of 38 ( 34 % ) evaluable patients in the former group and in 39 of 76 ( 51 % ) evaluable patients in the latter group . Serum alpha-fetoprotein ( AFP ) levels decreased by more than 50 % in 10 of 17 ( 59 % ) and 23 of 33 ( 70 % ) patients in the respective groups whose pretreatment AFP level was estimated to be over 200 ng/ml . Overall , the 1-year survival value was 68 % and the 2-year value was 41 % as determined by the Kaplan-Meier method . No statistically significant difference in survival was observed between the two groups . The initial tumor response correlated with the survival value . No severe complication was encountered except for one case of liver abscess formation . No serious change in the laboratory data was observed following treatment with these regimens . Although the tumor response was significantly better in patients treated with ADMOS combined with CDDP injection than in those treated with ADMOS alone ( P<0.05 ) , no significant difference in survival was found between the two groups PURPOSE To evaluate the effectiveness of radio-frequency ( RF ) ablation and percutaneous microwave coagulation ( PMC ) for treatment of hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Seventy-two patients with 94 HCC nodules were r and omly assigned to RF ablation and PMC groups . Thirty-six patients with 48 nodules were treated with RF ablation , and 36 patients with 46 nodules were treated with PMC . Therapeutic effect , residual foci of untreated disease , and complications of RF ablation and PMC were prospect ively evaluated with statistical analyses . RESULTS The number of treatment sessions per nodule was significantly lower in the RF ablation group than in the PMC group ( 1.1 vs 2.4 ; P < .001 ) . Complete therapeutic effect was achieved in 46 ( 96 % ) of 48 nodules treated with RF ablation and in 41 ( 89 % ) of 46 nodules treated with PMC ( P = .26 ) . Major complications occurred in one patient treated with RF ablation and in four patients treated with PMC ( P = .36 ) . During follow-up ( range , 6 - 27 months ) , residual foci of untreated disease were seen in four of 48 nodules treated with RF ablation and in eight of 46 nodules treated with PMC . No significant difference in rates of residual foci of untreated disease was noted ( P = .20 , log-rank test ) . CONCLUSION RF ablation and PMC thus far have had equivalent therapeutic effects , complication rates , and rates of residual foci of untreated disease . However , RF tumor ablation can be achieved with fewer sessions This r and omized , controlled trial assessed the effect of transarterial embolization ( TAE ) ( without associated chemotherapy ) on the survival of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Eighty consecutive patients were r and omized to treatment with embolization ( Group A , n = 40 ) , or to symptomatic treatment ( Group B , n = 40 ) , there being no differences between both groups regarding the degree of liver function impairment and tumor stage . Eighty‐two percent of the patients presented a self‐limited postembolization syndrome , without treatment‐related mortality . Fifty‐five percent of the treated cases exhibited a partial response , which result ed in a lower probability of tumor progression during follow‐up ( 57 % vs. 77 % at 1 year ; P < .005 ) . However , after a median follow‐up of 24 months ( 30 deaths in each group ) , there are no differences in survival ( Group A : 49 % and 13 % ; Group B : 50 % and 27 % , at 2 and 4 years , respectively ; P = .72 ) . The absence of differences was maintained even when dividing patients according to Child‐Pugh 's grade , Okuda stage , or performance status test ( PST ) . Furthermore , there were no differences in the probability of complications or in the need of hospital admissions . In conclusion , TAE has a marked antitumoral effect associated to a slower growth of the tumor , but it does not improve the survival of patients with nonsurgical HCC To assess whether ultrasound‐guided percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small hepatocellular carcinoma ( HCC ) , 60 patients with one to four HCCs smaller than 3 cm were entered onto a r and omized controlled trial . Thirty‐one and 29 patients , respectively , were treated by percutaneous acetic acid injection using 50 % acetic acid or by percutaneous ethanol injection using absolute ethanol . There were no significant differences in age , sex ratio , Child‐Pugh class , size of tumors , or number of tumors between the two groups . When there was no evidence of viable HCC from biopsy , plain and helical dynamic computed tomography , or angiography , the treatment was considered successful and was discontinued . All original tumors were treated successfully by either therapy . However , 8 % of 38 tumors treated with percutaneous acetic acid injection and 37 % of 35 tumors treated with percutaneous ethanol injection developed a local recurrence ( P < .001 ) during the follow‐up periods of 29 ± 8 months and 23 ± 10 months , respectively . The 1‐ and 2‐year survival rates were 100 % and 92 % in percutaneous acetic acid injection and 83 % and 63 % in percutaneous ethanol injection ( P = .0017 ) . A multivariate analysis of prognostic factors revealed that treatment was an independent predictor of survival . The risk ratio of percutaneous acetic acid injection versus percutaneous ethanol injection was 0.120 ( range , 0.027‐0.528;P = .0050 ) . In conclusion , percutaneous acetic acid injection is superior to percutaneous ethanol injection in the treatment of small HCC In a prospect i ve trial of 75 Chinese patients with histologically proven inoperable hepatocellular carcinoma ( HCC ) , 25 patients were r and omised to receive doxorubicin 60 - 75 mg m-2 intravenously once every 3 weeks , 25 to receive recombinant alpha 2 interferon ( rIFN ) ( Roferon ) 9 - 18 x 10(6 ) IU m-2 intramuscularly ( i.m . ) daily and 25 to receive rIFN 25 - 50 x 10(6 ) IU m-2 i.m . three times weekly . Patients were switched to the other drug if : ( a ) there was progressive disease after 12 weeks , ( b ) unacceptable toxicity developed and ( c ) they had received a total of 500 mg m-2 of doxorubicin . Six patients had switching over of therapy , three on doxorubicin and three on rIFN . In the remaining 69 patients on single drug therapy , the median survival rate of patients on doxorubicin and rIFN was 4.8 and 8.3 weeks respectively ( P = ns . ) . rIFN induced tumour regression of 25 - 50 % in 12 % of patients and of over 50 % in 10 % of patients . When compared with doxorubicin , rIFN was associated with more tumour regression ( P = 0.00199 ) and less progressive tumours ( P = 0.00017 ) . It caused less prolonged and less severe marrow suppression ( P = 0.01217 ) , and had significantly less fatal complications than doxorubicin ( P = 0.01383 ) . Doxorubicin caused fatal complications due to cardiotoxicity and neutropenia in 25 % of patients . rIFN was associated with fatal complications due to dementia and renal failure in 3.8 % of patients . In the treatment of inoperable HCC , rIFN is superior to doxorubicin in causing more tumour regression , less serious marrow suppression and less fatal complications UNLABELLED Portal vein thrombosis is a poor prognostic factor in patients with hepatocellular carcinoma ( HCC ) and a contraindication for chemoembolization . Intra-arterial injection of 131I-iodized oil which does not modify arterial flow , is feasible in this condition . The aim of this prospect i ve r and omized controlled trial was to compare the efficacy of treatment with radiolabeled oil ( treated group ) versus medical support ( control group ) in patients with stage I or II HCC ( classification of Okuda ) with portal vein thrombosis . METHODS Twenty-seven HCC patients ( 26 males , 1 female ) , aged 53 - 79 yr , with portal vein thrombosis were r and omly assigned to Lipiocis group ( n = 14 ) or Control group ( n = 13 ) . Additional injections of radiolabeled oil were given 2 , 5 , 8 and 12 mo after initial therapy . Medical support treatment consisted of : tamoxifen ( n = 5 ) , 5 FU intravenously ( n = 1 ) , NSAIDs or corticosteroids ( n = 5 ) . Efficacy was evaluated according to survival rate ( Kaplan-Meier method ; log rank test ) , AFP serum values ( measured at 2 , 5 , 8 and 12 mo ) and angiography . RESULTS The two groups were comparable ( Child 's classification , Okuda 's classification , liver function tests , location of the thrombus ) . Tolerance was excellent in the Treated group . The actuarial survival curves were significantly different ( p < 0.01 ) between the two groups , the survival rates ( Cl 95 % ) at 3 , 6 and 9 mo being 71 % ( 48%-95 % ) , 48 % ( 12%-55 % ) , 7 % ( 1%-31 % ) for the Treated group ; and 10 % ( 1%-33 % ) , 0 % and 0 % for the Control group . CONCLUSION Intra-arterial hepatic injection of 131I-labeled iodized oil is a safe and effective palliative treatment of HCC with portal vein thrombosis Chemotherapy is not effective for hepatocellular carcinoma ( HCC ) . HMG-CoA redutase inhibitors have cytostatic activity for cancer cells , but their clinical usefulness is unknown . To investigate whether pravastatin , a potent HMG-CoA reductase inhibitor , prolongs survival in patients with advanced HCC , this r and omized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital . 91 consecutive patients < 71 years old ( mean age 62 ) with unresectable HCC were enroled in this study . 8 patients were withdrawn because of progressive liver dysfunction ; 83 patients were r and omized to st and ard treatment with or without pravastatin . All patients underwent transcatheter arterial embolization ( TAE ) followed by oral 5-FU 200 mg–1d for 2 months . Patients were then r and omly assigned to control ( n = 42 ) and pravastatin ( n = 41 ) groups . Pravastatin was administered at a daily dose of 40 mg . The effect of pravastatin on tumour growth was assessed by ultrasonography . Primary endpoint was death due to progression of HCC . The duration of pravastatin administration was 16.5 ± 9.8 months ( mean ± SD ) . No patients in either group were lost to follow-up . Median survival was 18 months in the pravastatin group versus 9 months in controls ( P = 0.006 ) . The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival . Pravastatin prolonged the survival of patients with advanced HCC , suggesting its value for adjuvant treatment . © 2001 Cancer Research In a prospect i ve clinical trial , 39 patients with advanced hepatocellular carcinoma were r and omized to receive either Adriamycin ( 20 patients ) or a combination of 5‐fluorouracil , methotrexate , cyclophosphamide , and vincristine ( 19 patients ) . Five patients receiving Adriamycin and none receiving quadruple chemotherapy responded ( P < 0.05 in favor of Adriamycin ) . A further 25 patients were treated with Adriamycin , making a total of 45 . The overall objective response rate was 24 % ( 11 patients ) , with 3 complete remissions and 8 partial remissions . The median survival for Adriamycin‐treated patients ( 13.0 weeks for the first 20 patients and 14.4 weeks for all patients ) was longer than those treated by quadruple chemotherapy ( 6.5 weeks ) . The difference , however , was not significant by the Wilcoxan test as modified by Gehan . Patients with positive HbsAg had a significantly higher chance of having a response , while serum alpha‐fetoprotein levels did not correlate with response A previously reported Phase I/II multimodality program for non-resectable hepatocellular cancer began with external beam-radiation and chemotherapy , followed by administration of 131I antiferritin-specific radioimmunoglobulin and led to a 48 % remission ( 7 % complete remission and 41 % partial remission ) . Survival and response depended on alpha fetoprotein status . AFP+ patients had a median survival of 5 months ; AFP- patients had a median survival of 10.5 months . No acute effects occurred relative to treatment with radiolabeled antibody . A r and omized prospect i ve study was design ed to compare full dose chemotherapy consisting of 60 mg/m2 , doxorubicin and 500 mg/m2 of 5-fluorouracil administered every 3 weeks , to 131I antiferritin administration every 8 weeks and allowed for crossover treatment if tumor progression occurred . Overall , radiolabeled antibody administration and full dose chemotherapy led to equivalent partial remission rates ( 22 - 30 % vs 23 - 25 % ) and survival rates compared to chemotherapy ( 6 month median ; AFP+ 5 months ; AFP- 10 months ) . The most important new observations were the response in AFP- patients who , following chemotherapy failure , achieved remission using 131I radiolabeled antibody ( 7/11 ) and a subset of patients ( 7 % ) who were treated with radiolabeled antibody and converted from non-resectable to resectable status followed by surgical excision Background —St and ard treatment of inoperable hepatocellular carcinoma has not been established . Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours . Aims —To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue , octreotide . Methods —Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis , cirrhosis , and hepatocellular carcinoma . Fifty eight patients with advanced hepatocellular carcinoma were r and omised to receive either subcutaneous octreotide 250 μg twice daily , or no treatment . Groups were comparable with respect to age , sex , Okuda classification , presence of cirrhosis , and liver biochemistry and virology . Results —Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma . Treated patients had an increased median survival ( 13 months versus four months , p=0.002 , log rank test ) and an increased cumulative survival rate at six and 12 months ( 75 % versus 37 % , and 56 % versus 13 % respectively ) . Octreotide administration significantly reduced α fetoprotein levels at six months . When a multivariable Cox ’s proportional hazards model was fitted , variables associated with increased survival were : treatment administration , absence of cirrhosis , increased serum albumin , and small tumours . Treated patients clearly had a lower hazard ( 0.383 ) in the multivariate analysis . Conclusions —Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma This article reports a prospect i ve r and omized controlled study to investigate the effect of sex hormone therapy combined with intra-arterial chemotherapy for hepatocellular carcinoma ( HCC ) . Thirty patients with unresectable HCC were r and omly divided into two groups . A catheter was inserted into the hepatic artery of all patients . The first group ( group A ) was administered 60 mg/m2 of cisplatin ( CDDP ) on day 15 and 13 mg/m2 of Adriamycin ( ADM ) on day 1 and 8 post-operatively via the hepatic artery cannula ; in addition , a daily dose of 150 mg 5-fluorouracil ( 5-FU ) was administered orally . Tamoxifen ( TAM ) 25 mg/m2 daily and medroxyprogesterone acetate ( MPA ) 400 mg/m2 daily were also administered orally . TAM and MPA administration were alternated every 4 weeks . For the second group ( group B ) the same protocol of anti-cancer drugs administration , without the hormonal agents , was given . At least three courses of the treatments were carried out . Twelve patients in group A and 14 in group B were evaluated . Partial response of the hepatic tumor to the treatments was observed in 33.3 % of group A patients and 21.4 % of group B patients , a difference that was not statistically significant . The 1-year survival rate was 44.5 % in group A and 33.0 % in group B. The performance status of 25 % of the patients in group A was significantly improved compared with 14.3 % in group B ( p < 0.05 ) . TAM- and MPA-combined chemotherapy may not prolong the survival of patients with HCC , although it improves their quality of life Background . Arterially administered iodized oil ( Lipiodol ) is selectively retained by hepatocellular carcinomas ( HCCs ) , and has been used as a vehicle for delivery of therapeutic agents to these tumors . This study compared the efficacy of Lipiodol‐targeted epirubicin chemotherapy with Lipiodol‐131I radiotherapy AIM To conduct a r and omized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization ( TACE ) in the treatment of large hepatocellular carcinoma ( HCC ) . METHODS From January 1993 to June 1998 , 473 patients with unresectable hepatocellular carcinoma were divided into two groups : 216 patients in group A received more than 20 mL iodized oil during the first TACE treatment ; 257 patients in group B received 5 - 15 mL iodized oil in the same way . The Child 's classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment . During the TACE procedure the catheters were inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography . The anticancer drugs mixed with iodized oil ( Lipiodol ) were Epirubicin and Mitomycin . In group A , 112 cases received 20 - 29 mL Lipiodol in the first procedure , 85 cases 30 - 39 mL , 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B , 119 cases received 5 - 10 mL Lipiodol,138 cases received 11 - 15 mL and the average dose was 11.8 mL. RESULTS High-dose Lipiodol chemoembolization had tolerable side effects and a little hurt to the liver function in the patients with Child 's A or ICG-R15<20 . But the patients with child 's B or ICG-R15>20 had higher risk of liver failure after high-dose TACE . More type I and type II in CT scan after 4 weeks of TACE were seen in the patients of group A than those in the patients of group B ( P<0.01 ) . The resection rate and complete tumor necrosis rate of group A were higher than those of group B ( P<0.05 ) . The 1-,2- , 3-year survival rates of group A patients with Child 's A were 79.2 , 51.8 and 34.9 , respectively , better than those of group A ( P<0.001 ) . CONCLUSION High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor . High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose . For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20 % , oily chemoembolization with 20 - 40 mL Lipiodol is recommended Background . This r and omized controlled study was objective ly design ed to evaluate the utility cisplatin ( 50 mg ) in transcatheter arterial embolization ( TAE ) for treatment of hepatocellular carcinoma ( HCC ) To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma , 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were r and omized to receive recombinant interferon-alpha 2a ( 50 x 10(6 ) IU/m2 ) intramuscularly three times a week ( n = 35 ) or no antitumor therapy ( n = 36 ) . The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy ( p = 0.0471 ) ; median lengths of survival were 14.5 and 7.5 wk , respectively . Objective tumor regression greater than 50 % was observed in 31.4 % ( 11 of 35 ) of patients receiving interferon-alpha . Interferon-alpha induced tumor regression greater than 50 % in 11 ( 31.4 % ) patients . Compared with the group receiving no antitumor therapy , the interferon-alpha therapy group had more tumor regression ( p < 0.0001 ) and less tumor progression ( p = 0.001 ) . This high-dose interferon-alpha therapy was relatively well tolerated ; only 34.3 % of patients required reduction of dosage by one third or one half because of persistent fatigue . Two patients with diabetes mellitus ( one also had tabes dorsalis ) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy . We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma , both in prolonging survival and in inducing tumor regression BACKGROUND There is no st and ard treatment for unresectable hepatocellular carcinoma . Arterial embolisation is widely used , but evidence of survival benefits is lacking . METHODS We did a r and omised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment , of Child-Pugh class A or B and Okuda stage I or II , to assess the survival benefits of regularly repeated arterial embolisation ( gelatin sponge ) or chemoembolisation ( gelatin sponge plus doxorubicin ) compared with conservative treatment . 903 patients were assessed , and 112 ( 12 % ) patients were finally included in the study . The primary endpoint was survival . Analyses were by intention to treat . FINDINGS The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment ( hazard ratio of death 0.47 [ 95 % CI 0.25 - 0.91 ] , p=0.025 ) . 25 of 37 patients assigned embolisation , 21 of 40 assigned chemoembolisation , and 25 of 35 assigned conservative treatment died . Survival probabilities at 1 year and 2 years were 75 % and 50 % for embolisation ; 82 % and 63 % for chemoembolisation , and 63 % and 27 % for control ( chemoembolisation vs control p=0.009 ) . Chemoembolisation induced objective responses sustained for at least 6 months in 35 % (14)of cases , and was associated with a significantly lower rate of portal-vein invasion than conservative treatment . Treatment allocation was the only variable independently related to survival ( odds ratio 0.45 [ 95 % CI 0.25 - 0.81 ] , p=0.02 ) . INTERPRETATION Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma The classifications of hepatocellular carcinoma ( HCC ) currently used are based on prognostic factors obtained from studies performed years ago when most tumors were diagnosed at advanced stages and the survival rates were substantially poor . Recent investigations have review ed the survival of early tumors properly selected to receive radical therapies and the natural outcome of nonsurgical HCC patients . These data enable a new staging system to be proposed , the Barcelona Clinic Liver Cancer ( BCLC ) staging classification , that comprises four stages that select the best c and i date s for the best therapies currently available . Early stage ( A ) includes patients with asymptomatic early tumors suitable for radical therapies -- resection , transplantation or percutaneous treatments . Intermediate stage ( B ) comprises patients with asymptomatic multinodular HCC . Advanced stage ( C ) includes patients with symptomatic tumors and /or an invasive tumoral pattern ( vascular invasion/extrahepatic spread ) . Stage B and C patients may receive palliative treatments/new agents in the setting of phase II investigations or r and omized controlled trials . End-stage disease ( D ) contain patients with extremely grim prognosis ( Okuda stage III or PST 3 - 4 ) that should merely receive symptomatic treatment The Cooperative Study Group conducted a study to assess the therapeutic effects of chemoembolization in patients with advanced hepatocellular carcinoma ( HCC ) using either epirubicin hydrochloride ( FARM ) or doxorubicin hydrochloride ( ADR ) . A total of 77 patients were enrolled in this study and r and omized into 2 groups : 39 patients were treated with a FARM solution as the material for Lipiodol-transcatheter arterial embolization ( TAE ; FARM group ) , and 38 patients were treated with an ADR solution as the material for L-TAE ( ADR group ) . For the FARM group , the 1-year survival rate was 69.9 % and the 2-year survival rate was 44.5 % . For the ADR group , the corresponding survival rates were 74.7 % and 44.0 % . The differences among the above figures were not statistically significant . As side effects , fever , nausea , and generalized fatigue occurred at almost the same frequencies in the two groups . Changes detected in the liver function and the peripheral blood cell count in both groups were not severe . There was no significant difference between the toxic effects observed in the two groups . In conclusion , there was no significant difference in therapeutic efficacy between the FARM and ADR groups Sixty-one of 76 patients entered on a prospect i ve r and omized trial of neocarzinostatin ( NCZ ) versus m-AMSA or doxorubicin were eligible for analysis . Among these 61 patients at least one episode of severe toxicity was documented in 39 % of patients on NCZ and 58 % on m-AMSA . Fifty-one of the 61 patients were previously untreated with chemotherapy . Among these 51 patients objective response was documented in two of 25 patients treated with NCZ , none of 17 treated with m-AMSA , and one of nine treated with doxorubicin . Among previously untreated North American and European ( NA/E ) patients the median survival times were : NCZ 11 weeks and m-AMSA 12 weeks . The data on South African ( SA ) patients with similar entrance criteria entered on earlier Eastern Cooperative Oncology Group trials were analyzed with that from the r and omized trial and show that for SA patients the median survival times were : NCZ , 11 weeks ( 31 patients ) ; m-AMSA , 13 weeks ( 33 patients ) ; and doxorubicin , 15 weeks ( 29 patients ) A prospect i ve r and omized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose 5'-deoxy-5-fluorouridine ( 5'-DFUR ) as an adjuvant chemotherapy , following transcatheter arterial embolization ( TAE ) in 40 patients with hepatocellular carcinoma ( HCC ) . Forty eligible patients were r and omized into two groups : 20 with TAE plus 5'-DFUR ( 400 mg/day ) and 20 with TAE alone . A good necrosis rate or decrease in size of more than 70 % of the original tumor mass was attained in 14 by the TAE plus 5'-DFUR arm , and in 12 by the TAE arm at 3 months after the first TAE . Although all five patients with HCC and 70 - 99 % necrosis rate after the first TAE in the TAE alone arm showed a less than 70 % necrosis rate at 12 months , four of the seven patients with a 70 - 99 % necrosis in the TAE plus 5'-DFUR arm retained a necrosis of more than 70 % at 12 months after the first TAE . The appearance rate of ascites and /or encephalopathy in patients with chemotherapy was not different from that of patients with TAE alone . One-year survival rates in the TAE plus 5'-DFUR arm and the TAE alone arm were 75.0 % and 85.0 % , 2-year rates were 64.2 % and 66.2 % , and 3-year rates were 64.6 % and 49.7 % , respectively . There was no significant difference in the survival curves . In conclusion , adjuvant therapy with 5'-DFUR was well tolerated without significant side effects , and it might maintain a good necrosis state of HCC after TAE . In order to confirm a beneficial effect of the chemotherapy on the survival period , a study using more patients and longer observation periods will be required We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for patients with hepatocellular carcinoma ( HCC ) . Eighty‐five consequent , previously untreated HCC patients with inoperable disease , were r and omized to receive the luteinizing hormone‐releasing hormone (LR‐RH)‐analogue triptorelin and the antiestrogen tamoxifen ( 33 patients ) or triptorelin plus the anti and rogen flutamide ( 23 patients ) , or only placebo ( 29 patients ) in a double blind fashion . All groups were comparable as to age , sex , tumor extension , underlying cirrhosis and biochemical parameters . The tamoxifen ( TMX ) group had a significantly longer survival ( 282 days ) compared with flutamide ( 112 days ) and with placebo ( 127 days ) groups ( P = 0.0238 , log rank test ) . The upper quartile of patients in the TMX group lived 384 days or longer , and most of them ( 57.1 % ) were women ( P < 0.0005 ) , in contrast to the upper quartile of the placebo ( 170 days , 16.7 % women ) and the flutamide group ( 134 days , 33.3 % women ) . The calculated tumor volume doubling time ( TVDT ) was significantly higher in the TMX group ( 296 days ) than in the other two groups ( 99 and 101 days for placebo and flutamide groups , respectively , P = 0.023 ) . In a Cox proportional hazards model , the TMX treatment , along with the baseline Okuda 's HCC stage , the hepatitis B surface antigen , the portal vein diameter , the carcino embryonic antigen ( CEA ) and a self‐ assessment score of quality of life , were covariates predicting survival . Although the degree of serum sex hormone suppression was not a significant predictor of survival , the interaction of female sex and TMX treatment , it was ( P = 0.0052 ) . We conclude that TMX treatment significantly prolongs survival and the TVDT in unresectable HCC . The effect is most pronounced in female patients and is unrelated to sex hormone suppression Intra-arterial injection of radioactive Lipiodol has shown promising results in patients with hepatocellular carcinoma ( HCC ) and portal obstruction . The aim of this prospect i ve , r and omized trial was to compare the efficacy and tolerance of 131I-labeled Lipiodol and chemoembolization for the treatment of patients with HCC . From September 1990 to September 1993 , 142 patients ( 135 men , 7 women ; age : 65 + /- 6.6 years ) were r and omly assigned to treatment groups and given either intra-arterial injections of 131I-labeled Lipiodol ( 60 mCi ; 2.2 GBq ) ( n = 73 ) or chemoembolization ( 70 mg cisplatin ) ( n = 69 ) . Subsequent injections were given at 2 , 5 , 8 , 12 , and 18 months . Tumor response was assessed on the basis of tumor size and serum alpha-fetoprotein levels . Patient tolerance was assessed clinical ly and angiographically . Survival rate was the main end-point . A total of 129 patients ( 65 in the 131I-labeled Lipiodol group and 64 in the chemoembolization group ) were available for analysis ; 13 were excluded , mainly because of portal vein thrombosis . The two groups were comparable . Actuarial survival curves were not significantly different between the two groups . Overall survival rates at 6 months , 1 , 2 , 3 , and 4 years were 69 % , 38 % , 22 % , 14 % , and 10 % , and 66 % , 42 % , 22 % , 3 % , and 0 % in the 131I-labeled Lipiodol and chemoembolization groups , respectively . Reduction in tumor size was similar for the two groups , with complete response in 1 and 0 patients and partial response in 15 and 16 patients in the 131I-labeled Lipiodol and chemoembolization groups , respectively . Tolerance was significantly better in the 131I-labeled Lipiodol group both clinical ly ( 3 severe side effects vs. 29 in the chemoembolization group ; P < .001 ) and angiographically ( 1 arterial thrombosis vs. 10 in the chemoembolization group ; P < .01 ) . In terms of patient survival and tumor response , radioactive 131I-labeled Lipiodol and chemoembolization were equally effective in the treatment of HCC , but tolerance to 131I-labeled Lipiodol was significantly better A r and omized , controlled clinical trial was conducted to compare the use of epirubicin ( EPI ) and doxorubicin ( DOX ) in Lipiodol ( Laboratoire Guerbet , Roissy-Charles-de-Gaulle Cedex , France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma . One hundred ninety-two hospitals participated , and 415 patients were enrolled in the study during the period between October 1989 and December 1990 . The patients were r and omly allocated to group A ( EPI ) or group B ( DOX ) by a central ized telephone registration . The actual doses of EPI and DOX were 72 mg/body and 48 mg/body , respectively . The 1- , 2- , and 3-year survival rates were , respectively , 69 % , 44 % , and 33 % for group A and 73 % , 54 % , and 37 % for group B. There were no statistically significant differences ( P = .2296 , log-rank test ) . When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors ( the pretreatment tumor size , the pretreatment serum alpha-fetoprotein level , tumor encroachment , and Child 's classification ) , the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup ( P = .0182 ) . However , there was no significant difference between the high-risk subgroups ( P = .4606 ) . The change in the serum alpha-fetoprotein level , the extent of Lipiodol accumulation in the tumor , and the extent of tumor reduction after the treatment did not show any significant differences between the groups . The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization . In conclusion , there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma One hundred and sixty‐eight patients with unresectable primary liver cancer were prospect ively studied by members of the Eastern Cooperative Oncology Group . These patients were r and omized to receive treatment with oral 5‐Fluorouracil ( 5‐Fu ) , oral 5‐Fu plus Streptozotocin , oral 5‐Fu plus MethylCCNU or Adriamycin . The single agent treatments ( oral 5‐Fu and Adriamycin ) were associated with less gastrointestinal toxicity than were the oral 5‐Fu treatment combinations . A total of 15 partial responses were reported . Adriamycin appears to be the most active agent and responsible for 9 of the 15 responses . No response was seen in any of the 48 patients r and omized to oral 5‐Fu alone . The survival associated with oral 5‐Fu alone was significantly shorter than the survival time associated with the remaining 3 treatment programs among both North American and South African patients . A multivariate model of survival was formulated . Covariates of prognostic significance were treatment , initial performance status and sex . South African black patients had a shorter survival time than North American black patients . Excluding oral 5‐Fu from consideration , prognostic variables appeared to dominate any differences between the remaining treatments under study . Cancer 42:2149–2156 , 1978 A prospect i ve r and omized trial was conducted to evaluate the efficacy of long-term oral administration of low-dose tegafur combined with uracil as an adjuvant chemotherapy , following transcatheter arterial embolization ( TAE ) in 40 patients with hepatocellular carcinoma ( HCC ) . Forty eligible patients were r and omized into two groups : 20 with TAE plus LIFT ( a compound of tegafur 200 mg and uracil 448 mg per day ) and 20 with TAE alone . A good necrosis rate or decrease in size of more than 70 % of the original tumor mass was attained in 10 by TAE plus UFT arm and in 12 by TAE arm alone . As for the “ responded ” patients , there was no significant difference in the time from tumor response to tumor regrowth between the two groups . The appearance rate of ascites and /or encephalopathy in patients with chemotherapy was slightly higher than that in control patients . The median survival time was 22.7 months for TAE plus UFT arm and 28.2 months for TAE arm alone . There was no significant difference in the cumulative survival curves . In conclusion , these results indicated no substantial benefit for this chemotherapy regimen , as an adjuvant therapy for patients with HCC during repeated TAE The aim of this r and omized controlled trial was to assess the efficacy of interferon alfa-2b ( IFN ) for the treatment of advanced hepatocellular carcinoma ( HCC ) . Fifty-eight patients with HCC who were not suitable for resection , transplantation , ethanol injection , or arterial embolization were stratified according to their Okuda stage and r and omized to receive IFN ( 3 x 10(6 ) , 3 times a week , for 1 year ) ( n = 30 ) or symptomatic treatment ( n = 28 ) . Both groups were identical in terms of age , sex , performance status , presence of constitutional syndrome , Child-Pugh class , Okuda stage , multinodularity , portal thrombosis , and extrahepatic spread . Adhesion to IFN treatment was adequate in 27 patients , with a mean duration of treatment of 8 + /- 3 months . However , IFN treatment was associated with side effects in 23 patients , leading to treatment discontinuation in 13 patients . Two of the 30 patients ( 6.6 % ) presented a partial response with greater than 50 % size reduction and normalization of alpha-fetoprotein levels . The survival at 1 and 2 years according to intention to treat was not different between the 2 groups ( 58 % and 38 % vs. 36 % and 12 % , respectively , Breslow P = . 19 , log rank P = .14 ) and the absence of difference was maintained when dividing patients according to their Okuda stage . The probability of presenting tumor progression ( P = .17 ) , or deterioration of Child-Pugh class ( P = .37 ) , performance status ( P = . 07 ) , or Okuda stage ( P = .44 ) was not modified by IFN treatment . These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis PURPOSE To compare the efficacy of transcatheter arterial chemoembolization ( TACE ) combined with percutaneous ethanol injection ( PEI ) versus repeated TACE in the treatment of large hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Fifty-three patients with cirrhosis and a large HCC ( main tumor , 3.1 - 8.0 cm in diameter with no more than two daughter nodules ) were enrolled in a prospect i ve , r and omized study . Twenty-six patients underwent a single TACE session followed by PEI ( TACE-PEI group ) , whereas 27 patients underwent two to five TACE sessions ( TACE group ) . Both groups of patients were similar with regard to liver function . Follow-up ranged from 8 to 39 months . RESULTS Complete therapeutic responses were higher ( P < .05 ) and tumor recurrences during follow-up were lower ( P < .05 ) in the TACE-PEI group than in the TACE group . Patients in the TACE-PEI group survived longer than those in the TACE group , although the difference was not significant ( P > .1 ) . The rates of survival without recurrence were better in the TACE-PEI group than in the TACE group ( P < .05 ) . CONCLUSION Use of a single TACE session combined with PEI is more effective than repeated TACE in the treatment of large HCC THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard We analyzed 56 of 75 previously untreated patients with hepatocellular carcinoma who entered on a prospect ively r and omized trial of acivicin versus 4'deoxydoxorubicin ( esorubicin ) . At least one episode of severe toxicity was documented in 23 % of the patients on acivicin and 45 % of those on 4'deoxydoxorubicin . Two patients responded to 4'deoxydoxorubicin . One response was partial , lasting 58 weeks , and one was complete , lasting more than 4 years . The 90 % confidence interval for response is 1–20 % . In view of a 45 % rate of severe or worse toxicity with 4'deoxydoxorubicin , this drug can not be recommended as treatment . There were no responses on acivicin To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma , we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter , double-blind , placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival . The patients were r and omized to receive tamoxifen , 40 mg/day ( group 1 ) , or placebo ( group 2 ) . Both groups were similar in age , sex , etiology of cirrhosis , biochemical , hematologic and hormonal parameters , morphology of the tumor ( nodular vs multinodular or massive ) , Child-Pugh 's score , and Okuda 's stage . The 1-year survival rate was similar in both groups ( 30 % in group 1 vs 37.8 % in group 2 ; p = 0.31 ) . Tamoxifen treatment was well tolerated by the patients . We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma This study was undertaken to investigate the response rate , time to treatment failure and survival time of patients with hepatocellular cancer ( HCC ) treated with beta-interferon or menogaril . Sixty-nine patients with histologically confirmed , advanced , measurable hepatocellular carcinoma were r and omized to receive beta-interferon or menogaril . Eligibility criteria included an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 , 1 , 2 , or 3 , as well as adequate kidney and liver function and hematologic reserve . The number of patients with lethal , life-threatening , and severe toxicities on beta-interferon were 1 , 3 , and 12 and on menogaril 2 , 5 , and 10 , respectively . No objective responses were documented among the 61 patients who had HCC , histologically review ed and confirmed . The time to treatment failure was 6.7 weeks on beta-interferon and 8.6 weeks on menogaril . The median survival time was 11.1 weeks on beta-interferon and 23.1 weeks on menogaril ( South African patients 10.1 weeks ) . The difference is not significant . Poor prognostic factors were jaundice , age , and associated hepatitis . After controlling for other covariates , beta-interferon appears to increase the relative risk of dying by 2.7 . This trial reconfirms the importance , previously reported by ECOG of jaundice and age in the prognosis of patients with HCC . It shows that further trials with neither beta-interferon nor menogaril are warranted Following reports that specific estrogen receptors could be detected in sample s of hepatocellular carcinoma tissue , a prospect i ve r and omized controlled trial was undertaken in 59 patients , half of whom received doxorubicin ( 60 mg/m2 at 3-week intervals ) and half doxorubicin and tamoxifen ( 10 mg twice per day ) . Response occurred in three ( 11 % ) of those patients receiving doxorubicin alone and in four ( 16 % ) of those given both drugs . This difference was not statistically significant nor was the difference in survival when compared by life-table analysis . One patient treated with both drugs achieved complete remission for 30 months which was maintained ( on tamoxifen alone ) for 18 months before death from a non-tumor-related condition . Tamoxifen may have a role in maintenance of doxorubicin-induced remissions To assess whether the effectiveness of a combination of transcatheter arterial chemoembolization ( TACE ) and percutaneous ethanol injection ( PEI ) is superior to PEI alone in the treatment of patients with small hepatocellular carcinoma ( HCC ) , a r and omized controlled study was performed In the Asia‐Pacific region and elsewhere , almost 85 % of patients with hepatocellular carcinoma ( HCC ) are inoperable at diagnosis and have a dismal prognosis . Tamoxifen ( TMX ) is believed to inhibit HCC positive for estrogen receptor ( ER ) , but most HCCs are ER negative . Results of previous phase 3 trials in inoperable HCC have been conflicting and inconclusive . At higher doses , however , TMX inhibits HCC through ER‐independent mechanisms . A multicenter r and omized controlled trial was performed to assess the role of high‐dose TMX versus placebo ( P ) in the treatment of patients with inoperable HCC with respect to survival and quality of life ( QoL ) . A total of 329 patients from 10 centers in 9 countries in the Asia‐Pacific region enrolled in a double‐blind r and omized controlled trial of TMX 120 mg/d ( TMX120 ) against P as a control arm with an intermediate dosage of TMX 60 mg/d ( TMX60 ) to assess possible dose response . An independent data monitoring committee review ed all aspects of the trial . QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ‐C30 question naire . Three‐month survival rates for the P , TMX60 , and TMX120 groups were 44 % , 41 % , and 35 % , respectively , with a statistically significant trend difference in survival across the 3 treatment regimens ( P = .011 ) . There was a significantly higher risk of death in the TMX120 group compared with the P group ( hazard ratio , 1.39 ; 95 % confidence interval , 1.07‐1.81 ) . Adverse drug reactions were reported in 3 % ( 9 patients ) , and 8 patients were lost to follow‐up . In conclusion , TMX does not prolong survival in patients with inoperable HCC and has an increasingly negative impact with increasing dose . No appreciable advantage to QoL with TMX was observed Hepatocellular carcinoma ( HCC ) is one of the most common cancers worldwide . The prognosis of HCC is poor and current therapies are largely ineffective . Genetic abnormalities are commonly seen in HCC tumors particularly with inactivation of the p53 tumor suppressor . Gene therapy with E1B-deleted ( dl1520 ) adenovirus could be of therapeutic value as it offers the potential of tumor growth control in patients with p53 mutation . Ten patients with posthepatitis cirrhosis and histologically proven HCC were enrolled into an open label , r and omized prospect i ve study . R and omization was to receive either percutaneous ethanol injection ( control group ) or dl1520 . Toxicity and complications in the ethanol group were pain and fever , whereas in the gene therapy group complications were minimal . Grade I – II toxicity fever , stable performance status , and no significant rise in liver enzymes were observed in patients treated with dl1520 . Analysis of patients ' response to treatment in the gene therapy group showed one patient with a partial response and four patients with progressive disease . In the ethanol-treated group two patients had stable disease and three patients showed disease progression . In conclusion , this study showed that the adenovirus was well tolerated , but did not seem to offer significant tumor control . Although only a small number of patients were treated here it appears that more effective vectors are needed to achieve a useful clinical impact BACKGROUND / AIM Inoperable hepatocellular carcinoma is common in Asia and is usually treated with repeated transarterial chemoembolization . Gunji et al. showed better survival and fewer complications with autologous blood clot as compared with gelfoam used for embolization . Our aim was to compare the effect of blood clot versus gelfoam . METHODS We conducted a prospect i ve r and omized trial in 100 patients with inoperable hepatocellular carcinoma , and compared the side effects and cumulative survival in the two groups . Cox 's proportional hazard model was used to study the prognostic factors . RESULTS The diameter of the main tumor was 7.9+/-4.6 cm . Our study did not show additional beneficial effects of blood clot . The proportion of side effects was similar and the common ones included fever , pain and vomiting . Though the hepatic artery remained patent for a longer period with blood clot ( p=0.061 ) , there was no difference in survival ( p=0.129 for Okuda I disease and p=0.388 for Okuda II disease ) . Subgroup analysis showed longer survival in patients with vascular occlusion ( p=0.034 for Okuda I and p=0.029 for Okuda II disease ) . The independent factors of survival were sex , Child 's class , Okuda stage , tumor type and presence of metastases . CONCLUSION This study showed no additional benefits of blood clot in patients with inoperable hepatocellular carcinoma , in Okuda I and II disease . The longer survival in patients with vascular occlusion suggested that the damage to normal liver tissue by planned periodic transarterial chemoembolization may outweigh its benefit in later sessions of repeated TACE in certain patients A r and omized controlled trial of hepatic arterial embolization was conducted in 63 consecutive patients who had unresectable but still embolizable hepatocellular carcinoma . Patients were r and omized into three groups . Patients in group 1 received multiple hepatic arterial embolizations ; patients in group 2 were given hepatic arterial embolization once , followed by monthly chemotherapy with high doses of 5-fluorouracil ; and patients in group 3 received only monthly chemotherapy with high doses of 5-fluorouracil . Complete response was achieved in only 1 patient who received multiple hepatic arterial embolizations . Partial responses were observed in 13 patients ( 61.9 % ) in group 1 , 10 patients ( 47.6 % ) in group 2 , and 2 patients ( 9.5 % ) in group 3 . The survival rates of patients in group 1 at the end of the ninth , 12th , 15th , 18th , and 21st months were 53.2 % , 42.2 % , 42.2 % , 42.2 % , and 42.2 % , respectively , which were not significantly different from those of patients in group 2 but were better than the survival rates of patients in group 3 . The results suggest that hepatic arterial embolization is an effective palliative treatment that prolongs survival of patients with unresectable hepatocellular carcinoma 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 This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics To assess the efficacy and safety of Adriamycin ( Adria Laboratories , Columbus , OH ) in inoperable hepatocellular carcinoma ( HCC ) , 60 patients were r and omized to receive Adriamycin 60 to 75 mg/m2 at 3‐week intervals and 46 patients to receive no antitumor therapy . The median survival rate of the Adriamycin group was 10.6 weeks ; that of the group receiving no antitumor therapy was 7.5 weeks ( P = 0.036 ) . Adriamycin induced tumor regression of 25 % to 50 % in 5 % of patients and of over 50 % in only 3.3 % of patients . It caused fatal complications ( septicemia and cardiotoxicity ) in 25 % of patients . The severity of neutropenia leading to septicemia for a particular dose was unpredictable . Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin . We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC Between October , 1986 , and March , 1990 , 20 consecutive untreated and noncirrhotic patients with measurable and histologically and /or cytologically confirmed unresectable primary liver cancer were r and omly assigned to intravenous ( 10 patients ) or intra-arterial ( 10 patients ) therapy . Patients were treated every 4 weeks with a combination chemotherapy regimen containing 4′ epidoxorubicin and 5-fluorouracil . A 3-min bolus injection of 4′ epidoxorubicin was followed by 5-fluorouracil given in a 90-min infusion . The dose of 4′ epidoxorubicin was escalated : the starting dose was 40 mg/m2 , the second dose was 50 mg/m2 , and thereafter 60 mg/m2 during subsequent cycles . The dose of 5-fluorouracil was always 800 mg/m2 . Objective response rates ( 20 % ) were similar in both treatments ; two patients had partial responses in the intra-arterially treated group and one complete and one partial response were recorded in the intravenously treated group . The median survival time was 15.2 months for the patients treated intra-arterially and 13.8 months for the patients treated intravenously . Toxicity was mainly mild in both groups with less hematopoietic toxicity in the I.A.-treated group . 4′ epidoxorubicin combined with 5-fluorouracil given intra-arterially is not superior to the intravenous therapy , but it may diminish systemic toxicity Following a pilot study of VP‐16.213 ( 180 mg/m2 on 3 consecutive days at 2 weekly intervals ) in the treatment of patients with hepatocellular carcinoma , the efficacy of the drug was compared with that of adriamycin in another 35 patients in a r and omized crossover trial . Each drug gave a similar response rate ( 18 and 28 % , respectively ) but the duration of response was significantly longer in those receiving Adriamycin . Some patients who had not responded to treatment with Adriamycin had worthwhile remission with VP 16 Forty-seven patients with hepatocellular cancer were treated in a r and omised trial comparing adriamycin + VM 26 + 5-Fluorouracil ( 5-FU ) to mAMSA + VM 26 + 5-FU . Thirteen patients had a partial response to treatment ( 28 % ) and another 6 ( 13 % ) showed disease stabilisation . There were no significant differences in the response rates between the two treatment regimens . Patients who responded to treatment showed significant prolongation of survival ( 48 weeks ) when compared to non-responders ( 5 weeks ) |
12,603 | 24,768,666 | Findings indicate that ED visits in combination with ED-initiated tobacco cessation interventions are correlated with higher cessation rates than those reported in the National Health Interview Survey . | STUDY OBJECTIVE Cigarette smoking remains the leading cause of preventable death in the United States , and tobacco use rates are known to be higher among emergency department ( ED ) patients than in the general population .
Despite recommendations from the Society for Academic Emergency Medicine and the American College of Emergency Physicians , many emergency clinicians remain uncertain about the benefits of providing ED-based smoking cessation interventions .
To address this gap in knowledge , we performed a systematic review of cessation interventions initiated in the adult or pediatric ED setting . | Objectives : Emergency department ( ED ) patients show high smoking rates . The effects of ED-initiated tobacco control ( ETC ) on 7-day abstinence at 12 months were investigated . Methods : A r and omised controlled intention-to-treat trial ( trials registry no. : IS RCT N41527831 ) was conducted with 1044 patients in an urban ED . ETC consisted of on-site counselling plus up to four telephone booster sessions . Controls received usual care . Analysis was by logistic regression . Results : In all , 630 ( 60.7 % ) participants were males , the median age was 30 years ( range 18–81 ) and the median smoking intensity was 15 ( range 1–60 ) cigarettes per day . Overall , 580 study participants ( 55.6 % ) were unmotivated , 331 ( 31.7 % ) were ambivalent and 133 ( 12.7 % ) were motivated smokers . ETC ( median time 30 ( range 1–99 ) min ) was administered to 472 ( 91.7 % out of 515 ) r and omised study participants . At follow-up , 685 study participants ( 65.6 % of 1044 ) could be contacted . In the ETC group , 73 out of 515 ( 14.2 % ) in the ETC group were abstinent , whereas 60 out of 529 ( 11.3 % ) controls were abstinent ( OR adjusted for age and gender = 1.31 ( 95 % CI 0.91 to 1.89 , p = 0.15 ) . Stratified for motivation to change behaviour , the adjusted ORs for ETC versus usual care were OR = 1.00 ( 95 % CI 0.57 to 1.76 ) in unmotivated smokers , respectively OR = 1.37 ( 95 % CI 0.73 to 2.58 ) in ambivalent smokers and OR = 2.19 ( 95 % CI 0.98 to 4.89 ) in motivated smokers , p for trend = 0.29 . Conclusions : ETC , in the form of on-site counselling with up to four telephone booster sessions , showed no overall effect on tobacco abstinence after 12 months . A non-significant trend for a better performance of ETC in more motivated smokers was observed Background Emergency departments ( EDs ) have strong potential to initiate tobacco interventions with economically disadvantaged population s. Purpose We piloted three ED-initiated tobacco interventions and derived parameter estimates for future trials . Methods The study enrolled adult patients being treated in an urban ED who were daily smokers . Exclusion criteria included severe illness or pain , isolation ( for contagion ) , altered mental status , an insurmountable language barrier , temporary residence , and lack of telephone access . Subjects in the Bedside + Booster group received motivational counseling by a trained counselor at the bedside , up to three telephone sessions post-visit , and a self-help guide . Subjects in the Faxed Referral group had their personal contact information faxed to the hospital ’s tobacco dependence clinic , whereupon they received identical treatment as the Bedside + Booster group , but all sessions occurred over the telephone ( i.e. , no bedside counseling ) . The St and ard Referral group received the self-help guide and a referral to the hospital ’s tobacco dependence clinic . We used a 2:2:1 r and omization schedule to maximize our experience with the motivational interventions . Outcomes were assessed at 1 and 3 months . Results We enrolled 90 subjects . Of the 36 subjects assigned to the Bedside + Booster condition , 31 ( 87 % ) completed bedside counseling and at least one booster session , while 22 ( 61 % ) completed the maximum four sessions . Of the 37 subjects assigned to the Faxed Referral group , 28 ( 76 % ) completed at least one telephone session , while 19 ( 51 % ) completed the maximum four sessions . Quit attempts over the 3 months ranged from 18 % ( St and ard Referral ) to 57 % ( Faxed Referral ) . Seven-day abstinence was attained by 8 % ( Bedside + Booster ) , 14 % ( Faxed Referral ) , and 6 % ( St and ard Referral ) at 3 months . Conclusions Motivational cessation counseling can be feasibly initiated during the ED encounter with minimal medical staff involvement . Adequately powered trials are needed to study ED-initiated interventions that include post-visit follow-up Introduction Motivational interviewing techniques have been minimally research ed as a function of a teenage smoking intervention . The present study examined the efficacy of a theory-based motivational tobacco intervention ( MTI ) . Methods A r and omized two-group design was used to compare 6-month post-baseline quit and reduction rates among teenagers who received the MTI with those who received brief advice or care as usual . Participants were smokers aged 14 to 19 years ( N = 75 ) who presented for treatment in a university-affiliated hospital emergency department ( ED ) . Motivational interviewing techniques were used by trained providers to facilitate individual change ; stage-based take-home material s also were provided . Results Similar to past clinic-based studies of motivational interviewing with teenage smokers , our study found negative results in terms of intervention efficacy for cessation . Six-month follow-up cessation rates were nonsignificant — two teenagers quit smoking . Among teenagers who were available at follow-up , a medium effect size ( Cohen 's h = .38 ) was found for reduction and a large effect size ( Cohen 's h = .69 ) was found for percentage reduction , although these results also were not statistically significant . Conclusion Although the major findings of this study were not significant , the reductions in tobacco use suggest that motivational interviewing may be a clinical ly relevant counseling model for use in teenage smoking interventions . However , many questions remain , and the current literature lacks studies on trials with significant outcomes using motivational interviewing in smoking cessation . Additionally , more research is needed to examine the suitability of the ED for MTI-type interventions OBJECTIVE To assess the effect of physician counseling and referral on smoking cessation rates and attendance at a smoking cessation program . METHODS This was a prospect i ve , r and omized clinical trial set in a suburban , community teaching hospital emergency department ( ED ) . During study hours , dedicated research associates enrolled consecutive , stable , oriented patients who were smokers . Eligible , consenting patients were r and omized to one of two intervention groups . The control group received a two-page " Stop Smoking " pamphlet from the American Heart Association ( AHA ) . Patients in the intervention group were given the AHA pamphlet along with pharmacologic information and st and ardized counseling by the attending emergency physician , including written and oral referral to a smoking cessation program . The primary outcome measures were telephone contact/attendance at the smoking cessation program by the intervention group and the rate of smoking cessation in both study groups at three months post-ED visit . Categorical data were analyzed by chi-square and Fisher 's exact tests . Rank data were analyzed by Mann-Whitney tests and continuous data by t-tests . All tests were two-tailed with alpha set at 0.05 . RESULTS One hundred fifty-two patients were enrolled ; 78 were r and omized to the intervention group . Nearly 70 % of patients ( 103 ) were available for telephone follow-up . The study groups were statistically similar with regard to baseline demographic characteristics and the prevalence of moderate or severe nicotine addiction . None of the patients ( 0 % ) in the intervention group contacted or attended the smoking cessation program during the study period ( 95 % CI = 0 - 4 % ) . The percentages of patients who stopped smoking after three months were similar in the two groups [ 10.4 % ( 5/48 ) control vs 10.9 % ( 6/55 ) intervention ; p = 1 ] . CONCLUSION The authors found no difference in the smoking cessation rates between ED patients who received written material and those who were counseled by emergency physicians . Referral of patients who smoked to a cessation program was unsuccessful BACKGROUND Many people rely on EDs for routine health care . Often , however , screening and counseling for health risks are not provided . OBJECTIVE To determine prevalence rates of chronic disease and injury risk factors and access to routine health care in a r and om sample of ED patients in 3 cities . METHODS A prospect i ve survey was conducted at 3 hospital EDs in Akron , OH , Boston , MA , and Denver , CO . A modified version of the national Behavioral Risk Factor Surveillance Survey was administered by trained research ers to a convenience sample of non-critically ill patients during r and omly selected shifts . RESULTS Of 1,143 eligible patients , 923 ( 81 % ) agreed to participate . Their mean age was 39 ( range = 17 - 96 ) years . Most were female ( 58 % ) , white ( 60 % ) , and unmarried ( 68 % ) . Thirty-eight percent had no access to primary care . Injury-prone behaviors were prevalent : 53 % of the respondents did not wear seat belts regularly ; 15 % had no working smoke detector ; 3 % kept loaded , unlocked h and guns in their homes ; 11 % had attempted suicide ; 23 % had a positive CAGE screen for alcoholism ; 3 % had operated a motor vehicle in the preceding month while alcohol-intoxicated ; and 11 % had ridden in an automobile with an intoxicated driver . Cancer and chronic disease risks were also common : 48 % smoked ; 16 % had not received a blood pressure check in the preceding year ; and 4 % reported unsafe sexual practice s. Among women aged > 50 years , 42 % had not received a Pap test in the prior 2 years and 14 % had never had mammography . Many prevalence rates and access to care varied among the 3 sites . However , for most risk factors , prevalence rates did not differ in patients with and without access to primary health care . CONCLUSIONS ED patients have high rates of injury and chronic disease risks , and many have no other source of routine health care . Research is needed to determine whether ED-based programs , design ed to reduce injury and chronic disease risks , are feasible and cost-effective OBJECTIVE To define the prevalence of smokers and nicotine-addicted patients in a suburban , community ED . METHODS This was a prospect i ve survey of consecutive ED patients seen in a suburban ED with an annual patient census of 48,000 . Medically stable patients aged 18 years or older were eligible for inclusion . Patients were excluded if they had predominantly psychiatric complaints or were critically ill . Patients were queried about their smoking habits by a closed- question survey , which included the previously vali date d Fagerstrom Test for Nicotine Dependence . The study was conducted during a six-week period , only at times when there were dedicated research associates available to ensure consecutive patient entry . Continuous variables were analyzed by Student 's t-tests . Clinical variables were analyzed by chi-square tests . All tests were two-tailed with alpha at 0.05 . RESULTS 1,515 patients comprised the study group . The mean age ( + /-SD ) was 45.6 ( + /-18.9 ) years ; 52 % were female , 25 % were nonwhite , and 47 % were college graduates . There were 317 ( 21 % ) smokers . Patients having private physicians were less likely to smoke ( 18 % vs 29 % , p = 0.001 ) . Of all smokers , 46 % were moderately to severely nicotine-dependent , 69 % wanted to quit , and 30 % expressed an interest in joining a smoking cessation program . CONCLUSION A substantial percentage of ED patients smoke , many of them are nicotine-addicted , and the majority would like to quit . R and omized , controlled trials are needed to determine whether interventions by physicians in the ED can have an impact on the smoking habits of these patients This study examines the efficacy of a smoking cessation intervention on abstinence rates and motivation to quit smoking . Participants were adult smokers ( N = 543 ) who presented to the emergency department with chest pain and who were admitted to an observation unit for 24-hour observation to rule out myocardial infa rct ion . Participants were r and omly assigned to either usual care or a tailored intervention employing motivational interviewing and telephone follow-up . All individuals choosing to quit were offered nicotine patch therapy . Follow-up assessment s were conducted at 1 , 3 and 6 months . Abstinence ( 7-day point prevalence ) rates were significantly greater among participants receiving the tailored intervention compared with those given usual care ( OR = 1.62 , 95 % CI [ 1.05 - 2.50 ] ) . The largest difference occurred at 1 month : 16.8 % of usual care and 27.3 % of the tailored intervention group were abstinent , with differences decreasing over time . One-third of participants who were quit at month 6 were late quitters whose initial abstinence began after the 1-month follow up . In addition to treatment assignment , psychosocial variables including motivation to quit , confidence , reduced temptation to smoke in response to negative affect , and the perception that their chest pain was related to their smoking , were significant predictors of cessation . Tailored interventions are effective in promoting initial quit attempts for emergency chest pain patients admitted to an observation unit . Additional intervention may be needed to assist late quitters and to prevent relapse The prevalence of adult tobacco users who utilize the emergency department as patients or parents is disproportionately higher than the national average rates of tobacco use . Thus , it is advised that the emergency department be utilized as a venue for providing tobacco cessation counseling to adult tobacco users . Using a r and omized control trial design , this pilot study evaluated the effect of a brief tobacco cessation intervention for tobacco using parents of children brought to a pediatric emergency department . Participants received either usual care or a brief tobacco cessation intervention based on the first 2 of the 5A 's of the Clinical Practice Guidelines and fax referral to the Quitline . The primary outcome was self-reported repeated point prevalence of tobacco use at 6 weeks and 3 months following the intervention . Secondary aims included number of quit attempts , increases in readiness to quit , comparisons of participants who were successfully retained , and contact rates by Quitline counselors . At 3-month follow-up , compared to the Usual Care Control group , intervention participants were more likely to have made at least one quit attempt ( 59 % vs. 34 % ; p<.01 ) , be seriously thinking about quitting ( 68 % vs. 37 % ; p<.001 ) , and have higher Ladder scores ( 6.2 vs. 5.3 ; p<.05 ) . Study personnel were able to contact 68 % and 52 % , respectively , of participants at 6-week and 3-month follow-up . Quitline counselors were unable to reach 54 % of participants . Our results reveal increased intentions to quit and trends toward quitting , however we experienced difficulties with participant retention . Suggestions for improvements in point prevalence and retention are given Context The best way to estimate deaths from smoking is to observe people over many decades , as done in a 50-year study of male British physicians . No such study exists for women . Content A 25-year study of residents of rural Norway included 24505 women . Of these women , 2333 women died at age 40 to 70 years ( 9.4 % of never smokers and 18.7 % of continuing smokers ) , mostly from cardiovascular disease and cancer . Continuing heavy smokers survived 1.4 fewer years than never smokers . Mortality rates in smokers and nonsmokers were lower in women than in men . Caution s Participants were white and lived in rural areas . Implication s Active smoking has a large effect on women 's longevity in middle age . The Editors An early report on smoking and longevity appeared more than 60 years ago ( 1 ) , and it suggested a clear survival advantage of nonsmokers over heavy smokers in midlife . More than a half century later , another report presented precise survival curves for men by smoking habits ( 2 ) . In the time between these reports , the historic dimension of the health consequences of smoking was increasingly realized ( 3 - 9 ) . The World Health Organization now recognizes tobacco use as the major preventable cause of adult death , and about 5 million deaths worldwide each year ( 8.8 % of all deaths annually ) are attributed to smoking ( 10 ) . More than half of smoking-attributable deaths worldwide ( 56 % ) occur in people younger than 70 years of age and account for 13 % of deaths in people 30 to 69 years of age ( 9 ) . On a global scale , the death toll from tobacco use is increasing ( 9 , 11 ) , and accurately quantifying and updating the number of premature deaths due to smoking is an important task . Estimated numbers of deaths caused by smoking on a national , international , or global level have been calculated by combining relative risks for smokers versus nonsmokers for different causes of death from the second large prospect i ve American Cancer Society Cancer Prevention Study ( CPS-II ) ( 12 , 13 ) with direct or indirect ( via lung cancer mortality rates ) estimates of smoking histories and national mortality statistics ( 6 , 9 , 14 - 17 ) . However , estimating the number of smoking-attributable deaths that occur in a population in a given year depends on the maturity of the smoking epidemic and will predict the lifetime mortality experience of smoking men and women only under certain conditions ( 18 ) . To predict individual risks precisely , follow-up studies of individuals through their lifetime are needed . Such studies are rare and have not always estimated direct long-term risk for death . Among studies of survival and smoking ( 1 , 19 , 20 ) , the British doctors ' study ( 2 , 21 ) has provided the longest follow-up ( 50 years ) and has allowed for direct and precise calculation of survival of men through middle age and beyond . Using data from nearly 50000 Norwegian adults who were born in the second quarter of the 20th century and were followed in the last quarter , we studied smoking , death in middle age ( 40 to 70 years of age ) , and causes of death in both women and men . Methods Study Sample Between 1974 and 1978 , all men and women 35 to 49 years of age who were residing in the 3 rural Norwegian counties of Oppl and , Sogn og Fjordane , and Finnmark were invited to a cardiovascular health screening examination . Excluding 783 men and 215 women who were temporarily absent from their residence , 91.4 % of the men and 94.2 % of the women gave a self-report of their past and current smoking habits and were screened for cardiovascular risk factors ( 22 , 23 ) . Thus , our report is based on mortality follow-up between 40 and 70 years of age ( middle age ) of 24505 women and 25034 men ( who were born between 1925 and 1941 ) . Approximately 92 % of the respondents attended a second survey and 65 % attended a third survey about 5 years and 10 years after the first examination , respectively . We grouped participants into never smokers ( no report of smoking at any examination ) ; former smokers ; or continuing smokers of 1 to 9 cigarettes , 10 to 19 cigarettes , or 20 or more cigarettes per day ( heavy smokers ) . As a supplementary analysis to facilitate comparison with the 40-year follow-up of the British doctors ' study ( 2 ) , we also studied men who reported smoking 25 or more cigarettes daily . We classified persons as continuing smokers on the basis of the information from the last of up to 3 examinations . On the basis of information given about time since smoking cessation and changes among the 3 examinations , we separated the former smokers into 3 groups on the basis of their age when they stopped smoking ( < 40 years , 40 to 49 years , or 50 to 59 years ) . Mortality Follow-up We performed mortality follow-up by record linkage using the Norwegian 11-digit birth number ( date of birth plus a 5-digit identifier ) , which is unique to each person residing in Norway , to obtain the date and underlying cause of death kept by Statistics Norway . Loss to follow-up was due only to emigration , and we censored 93 men and 99 women ( 0.4 % ) on their registered date of taking residence abroad . Our report is based on mortality follow-up through the year 2000 . We classified the 7013 deaths in middle age into 7 groups on the basis of the underlying cause of death coded at Statistics Norway by using the 8th , 9th , or 10th revisions of the International Classification of Diseases ( ICD ) and European shortlist categories ( 24 ) . The groups were deaths due to 1 ) lung cancer ( 151 deaths in women and 316 deaths in men ) ; 2 ) other types of smoking-related cancer , including cancer of the lip , oral cavity , pharynx , larynx , esophagus , stomach , liver , pancreas , cervix uteri , kidney , bladder , and acute myelogenous leukemia ( 262 deaths in women and 386 deaths in men ) ; 3 ) other types of cancer ( 796 deaths in women and 648 deaths in men ) ; 4 ) cardiovascular disease , including sudden death ( 624 deaths in women and 2252 deaths in men ) ; 5 ) other medical causes ( 358 deaths in women and 505 deaths in men ) ; 6 ) alcohol abuse and chronic liver disease ( 20 deaths in women and 115 deaths in men ) ; and 7 ) accidents and violence ( 122 deaths in women and 458 deaths in men ) . Types of smoking-related cancer were those reported to be associated with smoking in the 2004 U.S. Surgeon General report ( 25 ) . Statistical Analysis We estimated KaplanMeier survival curves from 40 to 70 years of age separately for men and women , and for the various smoking categories , using age as the time scale . We performed computations with the survfit function of S-PLUS , version 6.1 ( Insightful Corp. , Seattle , Washington ) . The limited number of individuals who were recruited before 40 years of age led to unstable survival estimates . For this reason , we calibrated all survival analyses to start at 100 % at age 40 years . We estimated mortality hazard ( rate ) ratios comparing the persons in various smoking categories with never smokers by using the Cox proportional hazards model with age as the time scale and calculated with and without adjustment for potential confounding . The confounders were the following variables , which were all registered at the first examination : marital status ( not married or married ) , duration of education ( 0 to 9 years , 10 years , 11 to 12 years , or 13 years ) , county of residence , and physical activity in leisure time ( sedentary , moderate , intermediate , or intensive ) . We also used the Cox model to estimate womenmen mortality hazard ratios overall and with the different cause-of-death groups as outcomes . We performed these analyses for never smokers and for continuing smokers with additional adjustment for age when smokers began smoking and for number of cigarettes smoked per day . We performed tests for difference in regression coefficients between men and women and between smokers and nonsmokers ( interaction tests ) , with the variance estimated as the sum of each coefficient 's variance . We calculated adjusted survival first by predicting survival probabilities for each individual from the Cox model with confounders and then by averaging over all individuals in the sample ( 26 , 27 ) . We did this separately for women and men . We computed the average number of years of life lost between 40 and 70 years of age by summing person-time lost over the survival curves . To compute cause-specific mortality probabilities for the interval of 40 to 70 years of age , we analyzed the different cause-of-death groups in a competing risk framework . Again , we performed the computations separately for men and women and for the different smoking categories . Let Pxj be the probability of death of cause j between 40 and 70 years of age for a person in smoking group x. This probability can be estimated from the following formula : where Sx(t ) is the KaplanMeier estimate of all-cause survival in smoking group x and xj ( t ) is the NelsonAalen estimator of cumulative cause-specific hazard , which is computed by using cause j as the outcome and treating all other causes as censoring ( 28 ) . Note that the probabilities Pxj sum to Px , the all-cause probability of dying between 40 and 70 years of age for a person in smoking group x. The NelsonAalen estimator is used rather than the KaplanMeier , since cause-specific KaplanMeier estimates do not correctly account for deaths from other causes . We estimated the probability of dying between 40 and 70 years of age as a function of age when smoking began . We calculated these probabilities separately for men and women and for the 3 smoking categories ( 1 to 9 cigarettes per day , 10 to 19 cigarettes per day , and 20 cigarettes per day ) . We obtained the estimates by fitting a Cox model with a P-spline function ( pspline function of S-PLUS ) ( 29 ) to show the effect of age when smoking began . The P-spline allows for a flexible effect estimation , avoiding the need to assume a prespecified functional relationship between exposure and outcome , such as linear or polynomial ( 30 ) . We then estimated the predicted survival from 40 to 70 years of age by using the S-PLUS survfit OBJECTIVES The objective was to determine the efficacy of an emergency department (ED)-based smoking cessation intervention . METHODS This study was a r and omized trial conducted from January 2006 to September 2007 at an urban ED that treats 90,000 adults per year . Discharged adults who smoked at least 10 cigarettes per day were r and omized to 1 ) usual care , receiving a smoking cessation brochure ; or 2 ) enhanced care , receiving the brochure , a motivational interview ( MI ) , nicotine patches , and a phone call at 3 days . Interventions were performed by a peer educator trained in tobacco treatment . Blinded follow-up was performed at 3 months . RESULTS A total of 338 subjects were enrolled , mean ( ±SD ) age was 40.2 ( ±12.0 ) years , 51.8 % were female , and 56.5 % were either self-pay or Medicaid . Demographic and clinical variables were comparable between groups . Enhanced and usual care arms showed similar cessation rates at 3 months ( 14.7 % vs. 13.2 % , respectively ) . The proportion of subjects making a quit attempt ( 69.2 % vs. 66.5 % ) and decrease in daily cigarette use ( five vs. one ; all p > 0.05 ) were also similar . In logistic modeling , factors associated with quitting included any tobacco-related International Classification of Diseases , ninth revision ( ICD-9 ) , code for the ED visit ( odds ratio [OR]= 3.42 , 95 % confidence interval [ CI ] = 1.61 to 7.26 ) or subject belief that the ED visit was tobacco-related ( OR = 2.47 , 95 % CI = 1.17 to 5.21 ) . Conversely , subjects who reported having a preexisting tobacco-related illness were less likely to quit ( OR = 0.22 , 95 % CI = 0.10 to 0.50 ) . CONCLUSIONS The primary endpoint was negative , reflecting a higher-than-expected quit rate in the control group . Subjects whose ED visit was tobacco-related , based either on physician diagnosis or subject perception , were more than twice as likely to quit . These data suggest that even low-intensity screening and referral may prompt substantial numbers of ED smokers to quit or attempt to quit Objectives : To assess the acceptability to parents and staff of providing a brief tobacco cessation intervention incorporating the first 2 A 's of the Clinical Practice Guideline on Treating Tobacco Use and Dependence ( Ask and Advise ) + fax referral to a state tobacco quitline from the emergency department ( ED ) of a large children 's hospital . Methods : Data were collected from a written survey of ( 1 ) parental smokers accompanying their children to a pediatric ED who consented and were r and omized to participate in a tobacco cessation intervention and ( 2 ) medical doctors ( MDs ) or nurse practitioners ( NPs ) caring for their child . Acceptability of the intervention was measured on a 5-point Likert scale ranging from " strongly agree " to " strongly disagree . " Results : Of the 1643 parental subjects that were screened to participate in this study , 557 ( 33.9 % ) were smokers , 240 of whom were enrolled in the intervention group and a total of 215 ( 90 % ) completed the survey . A total of 230 ( 100 % ) of the MDs/NPs approached completed the survey . Of the 215 parental subjects in the intervention group , 212 ( 98.6 % ) and 208 ( 96.7 % ) agreed that the intervention provided them with " useful information " and " easy to underst and " advice , respectively . Most parental subjects agreed that the advice given was sufficient and met their needs ( n = 208 , 96.7 % ) and that the study length was " just right " ( n = 206 , 95.8 % ) . On a rating scale of 1 to 10 , the mean ( SD ) rating of the study was 9.1 ( 1.3 ) . Of the MDs/NPs participating in this survey , 224 ( 97.4 % ) and 206 ( 89.6 % ) agreed that the " ED is a good place to screen parents for tobacco use " and that the " ED is a good place to give advice about tobacco cessation , " respectively . In addition , 202 ( 87.8 % ) and 196 ( 85.2 % ) reported that they felt comfortable giving tobacco cessation advice to parents or referring parents to the national quitline , respectively . Only 7 ( 3 % ) felt that the study interfered with patient care . Conclusions : An ED tobacco cessation intervention using the 2 A 's + Quitline referral had excellent acceptability in this study of parents and staff of pediatric patients . The use of the pediatric ED as a venue to providing tobacco cessation counseling to a population with a high prevalence of parental smokers warrants further consideration |
12,604 | 20,810,980 | These data confirm the value of certain urinary polyphenols as biomarkers of intake . | BACKGROUND To identify associations between polyphenol intake and health and disease outcomes in cohort studies , it is important to identify biomarkers of intake for the various compounds commonly consumed as part of the diet .
OBJECTIVE The objective of this systematic review was to assess the usefulness of polyphenol metabolites excreted in urine as biomarkers of polyphenol intake in humans . | The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents . The hypothesis was tested that , in healthy humans , p.o . administration of resveratrol is safe and results in measurable plasma levels of resveratrol . A phase I study of oral resveratrol ( single doses of 0.5 , 1 , 2.5 , or 5 g ) was conducted in 10 healthy volunteers per dose level . Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-t and em mass spectrometry and quantitated by high-performance liquid chromatography-UV . Consumption of resveratrol did not cause serious adverse events . Resveratrol and six metabolites were recovered from plasma and urine . Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL ( 2.4 μmol/L , mean ± SD ; n = 10 ) , which occurred 1.5 h post-dose . Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher . The area under the plasma concentration curve ( AUC ) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol . Urinary excretion of resveratrol and its metabolites was rapid , with 77 % of all urinary agent-derived species excreted within 4 h after the lowest dose . Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy . However , the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52 Despite extensive research , the cardiovascular effects of coffee consumption in humans remain controversial . Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine ( tHcy ) concentration in humans . The study consisted of a multiple-dose clinical supplementation trial and a single-dose study . In the long-term trial , 43 healthy nonsmoking men optionally consumed daily either no coffee , 3 cups ( 450 mL ) , or 6 cups ( 900 mL ) of filtered coffee for 3 weeks , while in the short-term study 35 subjects consumed a single dose of 0 , 1 ( 150 mL ) , or 2 cups ( 300 mL ) of coffee . Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid . The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5 % of the amount ingested daily . Plasma tHcy concentrations increased nonsignificantly , but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes . In conclusion , the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men . The effect of coffee consumption on tHcy concentrations needs further investigation Subjects of this study consisted of 333 women ( aged 45 - 75 years ) drawn from a large United Kingdom prospect i ve study of diet and cancer , the European Prospect i ve Investigation of Cancer and Nutrition-Norfolk study . Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply (13)C-labeled st and ards , seven phytoestrogens ( daidzein , genistein , glycitein , O-desmethylangolensin , equol , enterodiol , and enterolactone ) were measured in 114 spot urines and 97 available serum sample s from women who later developed breast cancer . Results were compared with those from 219 urines and 187 serum sample s from healthy controls matched by age and date of recruitment . Dietary levels were low , but even so , mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels . Phytoestrogen concentrations in spot urine ( adjusted for urinary creatinine ) correlated strongly with that in serum , with Pearson correlation coefficients > 0.8 . There were significant relationships ( P < 0.02 ) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes . Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake ( r = 0.13 - 0.29 ) . Exposure to all isoflavones was associated with increased breast cancer risk , significantly so for equol and daidzein . For a doubling of levels , odds ratios increased by 20 - 45 % [ log(2 ) odds ratio = 1.34 ( 1.06 - 1.70 ; P = 0.013 ) for urine equol , 1.46 ( 1.05 - 2.02 ; P = 0.024 ) for serum equol , and 1.22 ( 1.01 - 1.48 ; P = 0.044 ) for serum daidzein ] . These estimates of risk are similar to those established for estrogens and and rogens in postmenopausal breast cancer but need confirmation in larger studies Soya isoflavones , genistein and daidzein , are the focus of numerous studies investigating their potential effects on health and results remain controversial . Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies . This study aim ed at assessing : ( 1 ) the isoflavone content of sixty-nine European soya-derivative products sold on the French market ; ( 2 ) the bioavailability of isoflavones comparing supplement with food . Twelve healthy volunteers were recruited in a r and omized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese , both containing different patterns of isoflavone conjugates and different daidzein : genistein ratios . A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters , which were then normalized to mg of each isoflavone ingested . Results showed that the normalized Cmax of daidzein ( P = 0.002 ) and similarly the normalized AUC0 -- > infinity and Cmax of genistein ( P = 0.002 ) from soya-based capsules were higher than that from soya-based cheese . In conclusion , this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products . Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability , this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese . Although the supplement is more bioavailable , the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy Green tea has been shown to exhibit cancer-preventive activities in pre clinical studies . Its principal active components include epigallocatechin gallate ( EGCG ) , epigallocatechin ( EGC ) , epicatechin ( EC ) , and epicatechin gallate , of which EGCG is the most abundant and possesses the most potent antioxidative activity . We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E ( decaffeinated green tea catechin mixture ) . Twenty healthy subjects ( five subjects/dose level ) were r and omly assigned to one of the dose levels ( 200 , 400 , 600 , and 800 mg based on EGCG content ) . All subjects were r and omly crossed-over to receive the two catechin formulations at the same dose level . Blood and urine sample s were collected for up to 24 h after oral administration of the study medication . Tea catechin concentrations in plasma and urine sample s were determined using high-performance liquid chromatography with the coulometric electrode array detection system . After EGCG versus Polyphenon E administration , the mean area under the plasma concentration-time curves ( AUC ) of unchanged EGCG were 22.5 versus 21.9 , 35.4 versus 52.2 , 101.9 versus 79.7 , and 167.1 versus 161.4 min x microg/ml at the 200- , 400- , 600- , and 800-mg dose levels , respectively . EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration . High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine sample s after Polyphenon E administration . There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications . The AUC and maximum plasma concentration ( Cmax ) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose . The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses . We conclude that the two catechin formulations result ed in similar plasma EGCG levels . EGC and EC were present in the body after the Polyphenon E administration ; however , they were present predominantly in conjugated forms . The systemic availability of EGCG increased at higher doses , possibly due to saturable presystemic elimination of orally administered green tea polyphenols Dietary estrogens , such as lignans , are similar in structure to endogenous sex steroid hormones and may act in vivo to alter hormone metabolism and subsequent cancer risk . The objective of this study was to examine the effect of dietary intake of a lignan-rich plant food ( flaxseed ) on urinary lignan excretion in postmenopausal women . This r and omized , cross-over trial consisted of three 7-week feeding periods during which 31 healthy postmenopausal women , ages 52 - 82 years , consumed their habitual diets plus 0 , 5 , or 10 grams of ground flaxseed per day . Urine sample s collected for 2 consecutive days during the last week of each feeding period were analyzed for lignan content ( enterodiol , enterolactone , and matairesinol ) by isotope dilution gas chromatography/mass spectrometry . Compared with the 0-gram flaxseed diet , consumption of 5 or 10 grams of flaxseed significantly increased excretion of enterodiol by 1,009 and 2,867 nmol/day , respectively ; significantly increased excretion of enterolactone by 21,242 and 52,826 nmol/day , respectively ; and significantly increased excretion of total lignans ( enterodiol + enterolactone + matairesinol ) by 24,333 and 60,640 nmol/day , respectively . Excretion of matairesinol was not significantly altered by flaxseed consumption . Consumption of flax , a significant source of dietary estrogens , in addition to their habitual diets increased excretion of enterodiol and enterolactone , but not matairesinol , in a dose-dependent manner in this group of postmenopausal women . Urinary excretion of lignan metabolites is a dose-dependent biomarker of flaxseed intake within the context of a habitual diet Estimation of dietary intake of polyphenols is difficult , due to limited availability of food composition data and bias inherent to dietary assessment methods . The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake . Fifty-three participants of the SU.VI.MAX study ( a r and omised primary -prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases ) collected a 24 h urine and a spot urine sample and filled a dietary record during a 2 d period . Thirteen polyphenols and metabolites , chlorogenic acid , caffeic acid , m-coumaric acid , gallic acid , 4-O-methylgallic acid , quercetin , isorhamnetin , kaempferol , hesperetin , naringenin , phloretin , enterolactone and enterodiol , were measured using HPLC-electrospray ionisation-MS-MS . In spot sample s apple consumption was positively correlated to phloretin , grapefruit consumption to naringenin , orange to hesperetin , citrus fruit consumption to both naringenin and hesperetin , with r coefficients ranging from 0.31 to 0.57 ( P < 0.05 ) . The combination of fruits and /or fruit juices was positively correlated to gallic acid and 4-O-methylgallic acid , isorhamnetin , kaempferol , hesperetin , naringenin and phloretin ( r 0.24 - 0.44 , P < 0.05 ) . Coffee consumption was positively correlated to caffeic and chlorogenic acids ( r 0.29 and 0.63 , P < 0.05 respectively ) . Black tea and wine consumption were positively correlated with gallic and 4-O-methylgallic acids ( r 0.37 - 0.54 , P < 0.001 ) . The present results suggest that several polyphenols measured in a spot urine sample can be used as biomarkers of polyphenol-rich food intake We investigated the effects of consuming an isoflavone aglycone-enriched soya milk containing viable bifidobacteria on urinary isoflavone excretion and percentage recovery . Sixteen postmenopausal women were r and omly divided into two groups to consume either fermented or non-fermented soya milk . Each group participated in a double-blind , crossover study with three 14 d supplementation periods , separated by a 14 d washout . Subjects ingested three daily dosages of isoflavone via the soya milk and collected four 24 h pooled urine specimens per supplementation period . Soya milks were prepared with soya protein isolate and soya germ , followed by fermentation with bifidobacteria . Isoflavone levels were quantified using HPLC . Non-fermented soya milks at 20 , 40 and 80 mg isoflavone/200 ml contained 10 % , 9 % and 7 % aglycone , respectively , with their fermented counterparts containing 69 % , 57 % and 36 % aglycone ( P<0.001 ) . A trend to a greater percentage urinary recovery of daidzein and glycitein was observed among women consuming fermented soya milk at a dosage of 40 mg isoflavone ( P=0.13 ) . A distinct linear dose response for the fermented soya milk group ( R2=0.9993 ) compared with the non-fermented group ( R2=0.8865 ) suggested less interindividual variation in isoflavone absorption . However , total urinary isoflavone excretion was similar for both groups ( P>0.05 ) , with urinary isoflavone recovery at approximately 31 % . Increasing the isoflavone dosage correlated positively with its urinary excretion , but urinary percentage recovery of isoflavone was inversely related to dosage level . Hence , a modest dosage ranging from 20 to 30 mg/d may provide the most bioavailable source of isoflavone , regardless of whether it is via an aglycone-rich fermented soya milk or a glucoside-rich soya milk The objective of this investigation was to examine the pharmacokinetics of isoflavone concentrations over a 24-h period among healthy adults consuming either soy foods or soy isoflavone tablets at different doses . This r and omized , cross-over trial was conducted with 12 generally healthy adults . The three phases of the intervention included isoflavone tablets at ( 1 ) 144 mg/day or ( 2 ) 288 mg/day and ( 3 ) soy foods design ed to provide a calculated 96 mg isoflavones/day ( doses in aglycone equivalents ) . Doses were spread out over three meals per day . After 6 days on each study phase , plasma isoflavone concentrations were determined on the seventh day at 0 , 4 , 8 , 10 , 12 and 24 h. Average levels of total isoflavone concentrations at 8 , 10 and 12 h were > 4 micromol/L for the soy food phase and for the higher dose tablet phase . Genistein concentrations were higher overall in the soy food vs. both the lower and the higher dose supplement phases of the study ( P<.05 ) . When comparing plasma concentrations for the two doses of tablets , saturation appeared more evident for genistein than for daidzein at the higher dose level . In conclusion , we observed important differences in the pharmacokinetics of genistein and daidzein contrasting the sources and doses of isoflavones when administered three times daily , including a possible advantage for increasing serum concentrations of isoflavones from consuming soy foods relative to isoflavone supplements We evaluated the levels of (-)-epicatechin ( EC ) and its metabolites in plasma and urine after intake of chocolate or cocoa by male volunteers . EC metabolites were analyzed by HPLC and LC/MS after glucuronidase and /or sulfatase treatment . The maximum levels of total EC metabolites in plasma were reached 2 hours after either chocolate or cocoa intake . Sulfate , glucuronide , and sulfoglucuronide ( mixture of sulfate and glucuronide ) conjugates of nonmethylated EC were the main metabolites present in plasma rather than methylated forms . Urinary excretion of total EC metabolites within 24 hours after chocolate or cocoa intake was 29.8 ± 5.3 % and 25.3 ± 8.1 % of total EC intake . EC in chocolate and cocoa was partly absorbed and was found to be present as a component of various conjugates in plasma , and these were rapidly excreted in urine 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 Flavonoids , which are found in certain plant foods , are thought to lower cancer risk through their antioxidant , antiestrogenic and antiproliferative properties . We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung , colorectal , breast , pancreatic and upper aerodigestive cancer among women in a large prospect i ve cohort study . Study participants were 34,708 postmenopausal women in the Iowa Women 's Health Study who completed a food frequency question naire and were followed for cancer occurrence from 1986 through 2004 . Flavonoid intake was estimated from 3 data bases developed by the USDA Nutrient Data Laboratory ( NDL ) . Hazard ratios ( HR ) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories . Interactions between smoking history and flavonoid intake were also examined . After multivariable adjustment , lung cancer incidence was inversely associated with intakes of flavanones ( HR = 0.68 ; 95 % CI : 0.53 - 0.86 , all results highest vs. lowest quintile ) and proanthocyanidins ( HR = 0.75 ; 95 % CI : 0.57 - 0.97 ) . Among current and past smokers , those with intakes in the highest quintile for flavanones ( HR = 0.66 ; 95 % CI : 0.50 - 0.86 ) , and proanthocyanidins ( HR = 0.66 ; 95 % CI ; 0.49 - 0.89 ) had significantly lower lung cancer incidence than those in the lowest quintile . Similar associations were not seen in never smokers . Isoflavone intake was inversely associated with overall cancer incidence ( HR = 0.93 , 95 % CI : 0.86 - 1.00 ) . This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk , especially among current and past smokers |
12,605 | 18,444,984 | Our meta- analysis showed that the viral response was greater in patients with chronic kidney disease who received antiviral therapy than controls .
No difference in the drop-out rate between study and control patients occurred in the subgroup of dialysis patients on IFN monotherapy .
These results support IFN-based therapy for hepatitis C in patients on maintenance dialysis | Hepatitis C virus ( HCV ) infection remains frequent in patients with chronic kidney disease and the detrimental role of HCV on survival is well-established in this population .
Several authors have reported on efficacy and safety of antiviral therapy for hepatitis C in this polulation but there is no clear consensus on management . | Chronic non-A , non-B hepatitis occurs in 50 % of Saudi patients with end-stage renal failure and requires long-term hemodialysis since it is a contraindication to renal transplantation . Thirteen patients with biochemical and histological documented chronic non-A , non-B hepatitis ( 11 with HCV antibodies ) entered a double-blind placebo controlled cross-over study , in which Roferon A 3 MU or placebo were administered subcutaneously 3 times weekly after hemodialysis for 6 months . The mean ALT fell significantly from pretreatment levels of 74.7 ( 95 % confidence interval ( CI ) 54.7 , 92.5 ) ( 13 patients in the 6-month run-in period ) and 66.8 ( CI 47.7 , 85.8 ) ( 7 patients in the run-in period + 6 patients in the placebo period ) ( difference NS ) to 37.6 ( CI 21.0 , 54.2 ) during interferon treatment ( P < 0.005 ) . In 10/13 patients ( 77 % ) ALT levels became normal . In the 6-month follow-up period immediately after therapy , the mean ALT was 45.2 ( CI 28.0 , 62.0 ) . Although this change was not significant ( P = 0.49 ) , only 7 of these 10 patients sustained biochemical remission in the 6-month follow-up period . The corresponding total Histological Activity Index improved from 8.9 ( CI 7.5 , 10.3 ) , 8.9 ( CI 7.2 , 10.7 ) ( difference NS ) to 6.2 ( CI 3.9 , 8.5 ) ( P < 0.05 ; P = 0.052 , respectively ) . Intralobular inflammation and periportal inflammation showed the most significant changes . Five of 13 ( 39 % ) and 2/13 patients ( 15 % ) had complete resolution of piecemeal necrosis and intralobular inflammation , respectively . Toxic effects of interferon were mild , early and self-limiting . ( ABSTRACT TRUNCATED AT 250 WORDS R and omized clinical trials ( RCTs ) provide the most reliable therapeutic information available . Unfortunately , there are no systemic listing of RCTs . We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966 - 1982 . For the former search we used subject headings ( 1 ) liver disease or ( 2 ) biliary tract disease and subheadings ( 1 ) drug therapy , ( 2 ) surgery , ( 3 ) radiotherapy , or ( 4 ) therapy , and check tags ( 1 ) comparative study or ( 2 ) clinical research . For the manual search , the contents of 34 arbitrarily selected , gastroenterologic , hepatologic , surgical , or general journals were perused . The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160 . One hundred fifty-four RCTs were identified by both methods . The manual search identified 208 RCTs and an additional 34 were found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals , an efficiency rate of 51 % . We estimate that 330 hepatobiliary RCTs had been published during this 17-year period . Sixty percent of the RCTs found by MEDLARS used the key word " r and omized , " " double blind , " or " controlled " in the title , compared to 36 % in those found by the manual search . In order to retrieve RCTs , it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as " controlled , " " r and omized , " and " double blind , " that papers be so catalogued and indexed , and that search ers be instructed in appropriate search strategies BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences Mortality rates among hemodialysis patients vary greatly across regions . Representative data bases containing extensive profiles of patient characteristics and outcomes are lacking . The Dialysis Outcomes and Practice Patterns Study ( DOPPS ) is a prospect i ve , observational study of representative sample s of hemodialysis patients in France , Germany , Italy , Japan , Spain , the United Kingdom , and the United States ( US ) that captures extensive data relating to patient characteristics , prescriptions , laboratory values , practice patterns , and outcomes . This report describes the case-mix features and mortality among 16,720 patients followed up to 5 yr . The crude 1-yr mortality rates were 6.6 % in Japan , 15.6 % in Europe , and 21.7 % in the US . After adjusting for age , gender , race , and 25 comorbid conditions , the relative risk ( RR ) of mortality was 2.84 ( P < 0.0001 ) for Europe compared with Japan ( reference group ) and was 3.78 ( P < 0.0001 ) for the US compared with Japan . The adjusted RR of mortality for the US versus Europe was 1.33 ( P < 0.0001 ) . For most comorbid diseases , prevalence was highest in the US , where the mean age ( 60.5 + /- 15.5 yr ) was also highest . Older age and comorbidities were associated with increased risk of death ( except for hypertension , which carried a multivariate RR of mortality of 0.74 [ P < 0.0001 ] ) . Variability in demographic and comorbid conditions ( as identified by dialysis facilities ) explains only part of the differences in mortality between dialysis centers , both for comparisons made across continents and within the US . Adjustments for the observed variability will allow study of association between practice patterns and outcomes BACKGROUND AND AIM Hepatitis C virus ( HCV ) is prevalent in hemodialysis ( HD ) patients . These patients experience more side-effects with antiviral treatment . The aim of the present study was to evaluate the efficacy and tolerability of pegylated interferon ( PEG-IFN ) alpha-2a in chronic hemodialysis patients with chronic hepatitis C. METHODS Twenty-five patients were included into the study . All of the patients were interferon naive , anti-HCV antibodies positive and polymerase chain reaction HCV-RNA positive . Twelve of the patients received PEG-IFN alpha-2a at a dose of 135 microg weekly for 48 weeks ( Group 1 ) . The remaining 13 patients who received no specific treatment were used as controls ( Group 2 ) . The patients were prospect ively followed up for a period of 18 months . Biochemical and virological responses were evaluated at the end of the study period ( end-of-treatment response ) and 6 months after the completion of therapy ( sustained response ) . RESULTS Virological end-of-treatment response was observed in 10 patients ( 83.4 % ) in Group 1 and one patient ( 7.7 % ) in Group 2 ( P < 0.001 ) . Sustained virological response was observed in nine patients ( 75 % ) in Group 1 and one patient ( 7.7 % ) in Group 2 ( P < 0.001 ) . Alanine aminotransferase ( ALT ) levels were initially increased in seven patients in Group 1 and normalized in five of these patients at the end of the treatment and sustained biochemical response was 71.4 % . In contrast , ALT levels in Group 2 were initially high in five patients and normalized in two of them ( 40 % ) at the end of the 48 weeks . Even if most of the patients experienced several side-effects ( anemia 75 % , fatigue 58.3 % , thrombocytopenia 33.3 % and leukopenia 33.3 % ) , they did not impose the discontinuation of the treatment . CONCLUSION The present study showed that PEG-IFN alpha-2a for 48 weeks is efficacious and well tolerated in hemodialysis patients with HCV BACKGROUND Hepatitis C virus ( HCV ) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease , particularly following renal transplantation . METHODS In order to assess the efficacy and tolerance of interferon ( IFN ) in the treatment of chronic hepatitis C in haemodialysis ( HD ) patients and their clinical course following renal transplantation , a multicentre , r and omized , open-label study was conducted to compare IFN therapy vs a control group . RESULTS Nineteen HCV RNA-positive patients received 3 x 10(6 ) U of IFN s.c . , three times a week ( post-HD ) , and 17 HCV RNA-positive patients were assigned to the control group . Tolerance to IFN therapy was good in nine patients , while treatment was discontinued in the other 10 due to the occurrence of side effects . HCV RNA was negative at the end of treatment in 14 out of 19 patients ( 74 % ) receiving IFN and in one patient ( 5 % ) in the control group . Six out of the 14 patients who initially responded to IFN therapy had a virological relapse ( 43 % ) . Eight patients ( 42 % ) remained HCV RNA-negative , three of them until the day that renal transplantation ( RT ) was performed ( 7 , 12 and 27 months , respectively ) , as did five patients on HD during the follow-up ( 27+/-5 months ) . Eight out of the nine patients ( 89 % ) who completed therapy were HCV RNA-negative at the end of treatment , and seven of them ( 78 % ) remained HCV RNA-negative during the follow-up on dialysis ( 21+/-8 months ) . Mean transaminase ( ALT ) values were significantly decreased following IFN therapy , while no changes were observed during the follow-up period in the control group . Fifteen patients ( 10 in the treatment group and five in the control group ) underwent RT . Three patients in the treatment group were HCV RNA-negative at RT , and one of them had a virological relapse 20 months after RT , while the other two remained HCV RNA-negative at 3 months and 24 months after RT , respectively . In contrast to the control group , transaminase ( ALT ) remained within normal limits in all patients in the treatment group . Finally , during the post-RT follow-up , the transaminase mean values were significantly lower in treated patients vs patients in the control group ( P<0.05 ) . CONCLUSIONS It is concluded that the biochemical and virological response to IFN therapy is good in HD patients . In addition , IFN therapy appears to exert a beneficial effect on the course of liver disease following RT , regardless of the virological response . Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects , these disappeared following discontinuation of therapy . Therefore , IFN therapy is advisable for HCV-infected dialysis patients who are c and i date s for RT Twenty‐eight prospect i ve r and omized controlled clinical trials evaluating the use of total parenteral nutrition ( TPN ) in cancer patients were identified through a search of major indexing sources . The data were pooled across studies to increase the ability to detect therapeutic effects . The impact of publication bias and the quality of reporting each trial were used to critically assess the conclusions drawn from the pooled analysis . The authors conclude that TPN may be useful when used preoperatively in patients with gastrointestinal tract cancer . It appears to be beneficial in reducing major surgical complications ( pooled P = 0.01 ) and operative mortality ( pooled P = 0.02 ) . No statistically significant benefit from TPN could be demonstrated in survival , treatment tolerance , treatment toxicity , or tumor response in patients receiving chemotherapy or radiotherapy . An increase in the risk of developing an infection in chemotherapy patients given TPN ( pooled P > 0.0001 ) underscores the importance of demonstrating significant benefits in r and omized trials before TPN is used routinely in these patients In this prospect i ve controlled study , the pharmacokinetic profiles of alpha-interferon 2b ( alphaIFN-2b ) were determined by the enzyme-linked immunosorbent assay method in hepatitis C virus-positive ( HCV+ ) dialysis and nonuremic patients , after a single subcutaneous injection of 3 million units . Ten HCV+/RNA+ patients ( group A ) with a normal renal function ( mean serum creatinine : 1.03 + /- 0.26 [ SD ] mg/dl ) and 10 HCV+/RNA+ patients undergoing chronic hemodialysis ( group B ) were included . The pharmacokinetic profiles of alphaIFN were determined after the very first subcutaneous injection of the drug . Plasma alphaIFN concentrations were determined before the injection and then 1 , 2 , 3 , 4 , 6 , 8 , 12 , 16 , 20 , 24 , 28 , 32 , and 36 h after the injection . They were assessed by means of an enzyme-linked immunosorbent assay test . Patients from both groups had a similar body surface area . It was found that in group B : ( 1 ) the mean maximum ( SD ) serum alphaIFN concentration ( Cmax ) was significantly higher ( 52 + /- 12 pg/ml ) than in group A ( 39 + /- 12 pg/ml ; P = 0.03 ) ; ( 2 ) the time at which Cmax occurred ( Tmax ) was significantly higher ( 10 + /- 3 h ) than in group A ( 7.5 + /- 2 h ; P = 0.05 ) ; ( 3 ) the observed area under the plasma alphaIFN concentration-time curve was about twice as much , i.e. , 936 + /- 212 pg x h/ml , as that for group A ( 485 + /- 184 pg x h/ml ; P < 0.0001 ) ; and ( 4 ) the alphaIFN half-life was significantly longer ( 9.6 + /- 2.9 h ) than in group A ( 5.3 + /- 1.3 h ) . As early as 24 h after the alphaIFN injection was given , the drug was no longer detectable in nonuremic patients ' sera , whereas it could be detected up to the next injection in all of the dialysis patients ' sera . When trough levels of alphaIFN were measured just before the 10th injection , they were always below the threshold level in the 10 patients from group A , i.e. , 4.1 pg/ml , whereas in group B they were measurable for four of nine patients ( P = 0.05 ) and ranged between 5.8 and 36.1 pg/ml . Severe neurologic side effects were observed only in group B , i.e. , in three patients . Hemoglobin levels did significantly decrease but only in group B patients , and this was significantly correlated with the Cmax ( r = 0.67 ; P = 0.03 ) . This is the first controlled study to demonstrate that the clearance of alphaIFN is about twice as low in dialysis patients as in nonuremic patients . These results might be of relevance when deciding the optimal alphaIFN therapy scheme for HCV+ patients , either with normal renal function or undergoing chronic hemodialysis BACKGROUND / AIMS We undertook a pilot study to investigate the efficacy and safety of peginterferon alfa-2a ( 40 kDa ) plus ribavirin in haemodialysed chronic HCV patients awaiting renal transplant . METHODS Patients received peginterferon alfa-2a 135 microg/week plus ribavirin 200 mg/day for 24 or 48 weeks ( genotype non-1 and 1 , respectively ) . The dose of ribavirin was tailored according to plasma concentrations and to haemoglobin levels . Outcomes in treated patients were compared with those of a matched untreated control group . RESULTS Thirty-five patients received treatment , while 35 served as untreated controls . Thirty patients completed treatment ; patients were withdrawn due to transplantation ( n=2 ) , severe anaemia ( n=1 ) , dermatitis ( n=1 ) and non-response ( n=1 ) result ing in a drop-out rate of 14 % . Overall , 34/35 treated patients were HCV RNA negative at week 4 and had undetectable RNA at the end of treatment , compared with none of the untreated controls ( ETR 97 % vs 0 % ; p<0.001 ) . Moreover , all achieved sustained virological response after 24 weeks of treatment-free follow-up versus no control patients ( SVR 97 % vs 0 % ; p<0.001 ) . CONCLUSIONS In this study , we have shown for the first time in a large cohort of patients that HCV- patients on haemodialysis can be treated successfully with peginterferon alfa-2a ( 40 kDa ) plus ribavirin BACKGROUND St and ard treatment of chronic hepatitis C virus ( HCV ) infection based on interferon is not an option in renal transplant recipients due to the high risk of acute allograft rejection . OBJECTIVES To assess efficacy and tolerability of combined treatment with ribavirin and amantadine regarding viral clearance , normalization of liver enzymes , and improvement of HCV-related hepatopathy and graft nephropathy in HCV-RNA-positive renal transplant patients . STUDY DESIGN Prospect i ve r and omized controlled study comparing ribavirin , 1000 mg daily ( n=7 ) , versus ribavirin , 1000 mg , in combination with amantadine , 200 mg daily ( n=8 ) , for 12 months , versus no therapy ( controls , n=26 ) . Results were evaluated by intention-to-treat analysis . RESULTS No relevant differences among treatment groups were found regarding liver enzymes , HCV viremia , liver histology and renal parameters . However , antiviral treatment was limited by anemia , result ing in premature withdrawal from therapy and requiring substitution with recombinant erythropoietin in most patients . The best predictor for tolerability of active treatment was a creatinine clearance rate>50 ml/min . CONCLUSIONS Addition of amantadine to ribavirin seems not to be superior to ribavirin monotherapy in renal transplant patients with chronic replicating HCV infection . However , this may be explained in part by the poor tolerability of both ribavirin and amantadine in patients with impaired renal function , result ing in drop-outs and subtherapeutic drug dosage BACKGROUND A prospect i ve multicentre study was initiated in HCV-infected haemodialysis patients to assess the tolerance and efficacy of alpha-2b interferon . METHODS We had planned to include 120 patients with HCV RNA detectable by polymerase chain reaction ( PCR ) ( Amplicor Roche ) and histologically documented chronic hepatitis . The dose of alpha-interferon was 3 million units ( MU ) three times weekly ( TTW ) , to be reduced to 1.5 MU TTW in case of side-effects . Tolerance was evaluated monthly ; virological efficacy was evaluated by PCR . A liver biopsy was performed at month 18 ( M18 ) . RESULTS ( a ) TOLERANCE After 37 patients had been included , the study was discontinued by the promoting institution because of severe side-effects requiring that treatment be stopped in 19 patients . The side-effects were : cardiac ( 4 ) neuropsychiatric ( 2 ) , digestive ( 3 ) , acute necrosis of the graft ( 1 ) , severe asthenia ( 9 ) , minor side-effects were observed in 22 patients . A complete 12-month course was completed in 12 patients for the 3 MU TTW dose and in six patients for the 1.5 MU TTW reduced dose . Normal ALT level ( OR , 0.16 ; CI 95 % , 0.03 - 0.89 ) at inclusion was associated with interruption of treatment ( univariate analysis ) . ( b ) EFFICACY Sustained virological response was observed in only seven ( 18.9 % ) , of the 18 patients who completed the treatment ( 38 % ) . Increased ALT at inclusion ( OR , 1.04 ; CI 95 % , 1.01 - 1.09 ) and cumulated doses of interferon ( OR , 1.01 ; CI 95 % , 1.004 - 1.026 ) were jointly associated with a sustained response , while positive PCR at M2 was strongly predictive of treatment failure . CONCLUSION Tolerance of interferon is poor in haemodialysis patients . Sustained response is fairly high in patients who have 12 months of treatment and seems to be based on the immune status of the patients ( ALT ) and the cumulative doses of interferon Background . Hepatitis C virus ( HCV ) infection is common in kidney transplantation and is known to affect long-term patient and graft survival , as is time in renal-replacement therapy ( RRT ) . The aim of this study was to investigate HCV in relation to time in RRT and its impact on outcome after transplantation . Methods . A follow-up cohort study using Kaplan-Meier analysis and Cox proportional hazards model was performed in 545 kidney and 26 kidney-pancreas transplant recipients receiving transplants between 1989 and 1997 , with last follow-up on December 31 , 2002 . HCV status at transplantation and time in RRT were analyzed . Results . Time in RRT was significantly longer ( P<0.0001 ) , and previous transplantations were more common ( P=0.04 ) in the HCV-positive group . HCV significantly reduced patient ( P=0.0012 ) and graft survival ( P=0.0003 ) after transplantation . Adjustment for age , sex , diabetes , previous transplantations , type of transplant , and time in RRT result ed in a relative risk ( RR ) for death of 2.23 , 1.92 , and 1.07 for HCV , diabetes , and age , respectively . The RR for graft loss was 1.96 and 1.03 for HCV and age . Sex , previous transplants , and time in RRT did not affect HCV as an independent risk factor for patient or graft survival . The leading cause of death was cardiovascular disease in both groups . Conclusions . HCV was , in our series , more important than time in RRT for patient death and graft loss posttransplant . Successful pretransplant antiviral therapy could be more beneficial for HCV-infected patients rather than early transplantation for long-term outcome , but this needs to be studied prospect ively In view of the high rate of chronicity of acute hepatitis C and the low efficacy of interferon ( IFN ) treatment in advanced liver disease , it may be beneficial to treat patients during the acute phase of the infection . Here we assessed the effects of variable-dose IFNalpha-2b treatment in haemodialysis patients with acute hepatitis C virus ( HCV ) infection , and identified factors that may predict response to this therapy . The study population included 67 patients , but 14 were excluded due to side-effects or because they were lost to follow-up . Seventeen patients who received no specific treatment were used as controls ( Group 1 ) . Sixteen and 20 patients received low-(3 MU ) and high-dose ( 6 - 10 MU ) IFNalpha-2b three times weekly for 3 months ( Groups 2 and 3 , respectively ) . Virological end-of-treatment response ( ETR ) was observed in 1 ( 5.6 % ) , 13 ( 56.5 % ) , and 17 ( 65.4 % ) patients in Groups 1 , 2 , and 3 , respectively , and virological sustained response ( SR ) was observed in 1 ( 5.6 % ) , 6 ( 26.1 % ) , and 13 ( 50 % ) patients in the three groups . The rates of virological ETR and SR in the treated groups were significantly higher than those of the control group ( P < 0.01 for all comparisons ) . In multivariate logistic regression analysis , single str and ed confirmational polymorphysm ( SSCP ) b and number ( P=0.02 ) was the only factor that was significantly associated with virological SR . In conclusion , IFN-alpha treatment initiated during the acute phase of HCV infection is associated with a higher rate of virological ETR and SR . This study suggested that quasispecies heterogeneity has predictive value with regard to virological SR BACKGROUND Long-term renal transplant ( RT ) recipient mortality and graft loss increase significantly in hepatitis C virus positive ( HCV-[+]ve ) patients . Treatment with alpha-interferon in this population is associated with a high rate of acute rejection . The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+ ) RT patients ( group A ) matched to 32 HCV-(+ ) RT patients ( group B ) who did not receive ribavirin . METHODS Ribavirin was started at a daily dose of 1,000 mg and then adapted to hemoglobin level . The study was scheduled for 1 year . RESULTS Ribavirin monotherapy was associated with a decrease in liver enzymes and serum creatinine levels . When proteinuria was present , this decreased or disappeared . There were no significant changes in HCV viremia . There was a significant progression in liver fibrosis with no improvement in inflammation scores . Hemoglobin levels fall dramatically , despite an important support by recombinant erythropoeitin ( median , 20,000 IU/wk ) . In 3 cases , ribavirin therapy had to be stopped . In the control group , after 1 year of follow-up , there was a significant increase in serum alanine aminotransferase and creatinine values . Proteinuria decreased in only 2 of 12 patients ( P = 0.03 as compared with group A ) . CONCLUSION One year of ribavirin monotherapy seems to have , at best , no beneficial effect on liver histology , although it improves liver enzyme levels . Despite its efficiency to dramatically decrease proteinuria , its impact on renal function remains unknown Background : α-Interferon-2a ( IFNα ) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus ( HCV ) infection . In dialyzed patients , such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect . Protocol : Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospect i ve open study of treatment with IFNα . We used , as did others , doses of 3 million units ( MU ) , three times a week , but for a longer period of treatment of 12 months . Follow-up was continued for 6 months after the end of IFNα in order to document any sustained biochemical , virological and histological responses . Results : Aminotransferase levels returned to the normal range within 1–2 months of treatment in all patients in whom they had been elevated at baseline . At 1 month of treatment , serum HCV-RNA was not detected in 5 ( 41 % ) patients and in 9 ( 75 % ) at 12 months . A sustained virological response was documented in 4 ( 33 % ) patients 6 months after the end of treatment . Relapse occurred in 5 patients within 2 months after IFNα withdrawal . HCV genotype was not predictive of any sustained response . At inclusion , using the histologic Metavir scoring system , half of the patients had low- grade cytolytic activity and none had cirrhosis . After IFNα , liver biopsy specimens were available from 9 patients and showed histologic improvement in 3 . IFNα tolerance was poor , inducing a 5 % mean weight loss and the acute rejection of two nonfunctioning kidney grafts . Conclusion : This study documents that administration of IFNα at 3 MU three times a week , for 12 months , in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75 % of the patients . A sustained response was maintained in one third of these patients after cessation of IFNα , and was predicted by the early serum clearance of the virus within the first 2 months of treatment . We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods . These encouraging results call for larger studies in uremic patients , using IFNα alone or in association with new antiviral drugs Chronic hepatitis C is a common cause of viral liver disease in kidney transplant ( KT ) recipients . To assess the efficacy and safety of therapy with interferon alpha we conducted a prospect i ve study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b ( IFNa ) 3 million units three times weekly ( scheduled ) for 6 months ( group A ) . 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period ( group B ) . All the patients in both groups had had stable renal function for at least one year . All patients in both groups had a positive HCV viremia at the beginning of the study . Patients of group A were treated for 142 + /- 34.8 days ( range 65 - 168 ) ; elevated serum aminotransferase ( ALT ) levels decreased rapidly and significantly from 100.3 + /- 48.9 to 37.7 + /- 13.9 IU/L ( P = 0.001 ) ; 10 patients ( 77 % ) were " responders , " whereas the others experienced a decrease in ALT values but without reaching the normal ranges . With a mean follow-up of twelve months after discontinuation of IFNa therapy , 8 responders -- i.e . , 80%--relapsed within 1 - 20 weeks . Only 4 patients had no detectable HCV viremia at the end of the IFNa ; two of them already have abnormal values of ALT . Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment . Side effects of IFNa ( fatigue , anorexia , weight loss ) were frequent , and 3 patients decided to drop out of the treatment . The hematological tolerance was good although there was a significant decrease in hemoglobin ( 11.9 + /- 1.7 vs. 13.4 + /- 1.7 g/dl ; P = 0.0044 ) . In group B , serum ALT levels did not significantly decrease ( 84.2 + /- 47.6 vs. 105.2 + /- 68.8 IU/L ) . At the end of the study period serum ALT levels were significantly lower in group A than in group B ( 37.7 + /- 13.9 vs. 84.2 + /- 47.6 IU/L , P = 0.013 ) . The major concern in group A was the occurrence of 5 renal failures . Kidney transplant biopsies showed edema , no significant tubulitis , scarcely scattered interstitial inflammatory cellular infiltration , and mesangial thickening . Four patients received methylprednisolone pulses but renal function improved in only two cases . We were not able to discover predictive factors of renal failure . We conclude that IFNa therapy is effective in controlling disease activity -- i.e . , reducing amino-transferase levels in KT patients with chronic hepatitis C , although relapse and detection of HCV RNA after the cessation of treatment were observed , respectively , in 80 % and 100 % of patients . ( ABSTRACT TRUNCATED AT 400 WORDS The prevalence of hepatitis C virus ( HCV ) infection is high in patients who are on chronic hemodialysis , but the role of HCV infection and HCV-related liver disease in the mortality of these patients has not been shown . Therefore , we conducted a prospect i ve cohort study of 1470 patients who were on chronic hemodialysis ( 17 to 89 yr old ) from 16 dialysis centers in Japan . Among them , 276 patients ( 18.8 % ) were positive for anti-HCV antibodies and 1194 patients were negative . The patients were followed for 6 yr from 1993 to 1999 . Only one case , a patient from the anti-HCV-antibody-positive group , was lost to the follow-up during this period . The mortality was higher in the anti-HCV-antibody-positive group ( 91 of 276 patients died ) than in the anti-HCV-antibody-negative group ( 277 of 1193 died ) ( 33.0 % versus 23.2 % , P < 0.01 ) . A Cox proportional hazard examination showed that positivity for anti-HCV antibodies was one of the risk factors for death with an adjusted relative risk of 1.57 ( 95 % confidence interval , 1.23 to 2.00 ) . As a cause of death , hepatocellular carcinoma and liver cirrhosis were significantly more frequent in the anti-HCV-antibody-positive patients than in the anti-HCV-antibody-negative patients ( 5.5 % versus 0.0 % , P < 0.001 ; 8.8 % versus 0.4 % , P < 0.001 , respectively ) . These findings show that the mortality is increased in anti-HCV-antibody-positive patients who are on chronic hemodialysis . Hepatocellular carcinoma and liver cirrhosis are factors that may influence the mortality The impact of hepatitis B ( HBV ) and C ( HCV ) on patient survival after kidney transplantation is controversial . The aims of this study were ( 1 ) to assess the independent prognostic values of HBsAg and anti-HCV in a large renal transplant population , ( 2 ) to compare infected patients with noninfected patients matched for factors possibly associated with graft and patient survival , and ( 3 ) to assess the prognostic value of biopsy-proven cirrhosis . Eight hundred thirty-four transplanted patients were included : 128 with positive HBsAg ( group I ) , 216 with positive anti-HCV ( group II ) , and 490 without serological markers of HBV and HCV ( group III ) . Fifteen percent and 29 % of patients were HBsAg-positive and anti-HCV-positive , respectively . Ten-year survivals of group I ( 55 + /- 6 % ) and group II ( 65 + /- 5 % ) were significantly lower than survival of group III ( 80 + /- 3 % , P < .001 ) . At 10 years , among overall patients with HCV screening ( n = 834 ) , four variables had independent prognostic values in patient survival : age at transplantation ( P < .0001 ) , year of transplantation ( P = .02 ) , biopsy-proven cirrhosis ( P = .03 ) , and presence of HCV antibodies ( P = .02 ) . In the case control study , comparison of infected patients with their matched control patients showed that age at transplantation ( P < .05 ) , HBsAg ( P = .005 ) , and anti-HCV ( P = .005 ) were independent prognostic factors . HCV , biopsy-proven cirrhosis , and age are independent prognostic factors of 10-year survival in patients with kidney grafts . The case-control study showed that anti-HCV and HBsAg were independently associated with patient and graft survivals . In infected patients , a routine liver histological analysis would improve selection of patients for renal transplantation Background . The effect of hepatitis C virus ( HCV ) infection on patients undergoing kidney transplantation ( KTx ) is uncertain . This study aim ed to evaluate the outcomes of our HCV+/end-stage renal disease ( ESRD ) patient population based on the therapeutic option including KTx or continuation in dialysis . Methods . KTx performed at Virginia Commonwealth University Hospital between January 2000 and December 2004 were tracked prospect ively . Forty-three out of a total of 394 KTx patients included in the analysis were HCV+ . A group of 52 contemporaneous HCV+/ESRD patients listed , but never transplanted , was also analyzed . HCV-negative transplanted patients were used as the control group . Results . Patient survival posttransplantation was 81.4 % and 68.5 % at 1 and 3 years in the HCV+ group , and 97.1 % and 92.9 % at 1 and 3 years in the HCV- group , respectively ( P=0.001 ) . Graft survival was 81.2 % and 64.1 % at 1 and 3 years in the HCV+ group , and 93.2 % and 84.1 % at 1 and 3 years posttransplantation in the HCV- group ( P=0.01 ) . Univariate analysis identified Knodell score as a predictor of mortality in HCV+ patients ( P=0.04 ) . Cox proportional hazards multivariate analysis identified deceased donor ( P=0.02 ) , previous kidney transplant ( P=0.007 ) , pretransplant diabetes ( P=0.05 ) , and Knodell Score ( P=0.012 ) as predictors of patient mortality . Patient survival was superior in HCV+ patients undergoing KTx versus remaining on dialysis . Conclusions . Patients with ESRD/HCV+ benefit from KTx without achieving the excellent survival of HCV-/ESRD patients . Liver biopsy is a useful tool to identify advanced liver disease at pretransplantation time Hepatitis C virus infection has been identified as the major cause of parenterally transmitted hepatitis [ 1 ] . Chronic hepatitis C is a major problem in patients on maintenance hemodialysis awaiting kidney transplantation [ 21 . Whereas uremia seems to predispose to chronic viral carrier status with little inflammatory activity in the liver , the change in immune status after kidney transplantation modified by immunosuppressive drugs causes acceleration of inflammatory liver disease often leading to death from liver failure [ 3 ] . For the first time an effective therapy became available with the advent of interferon treatment for chronic hepatitis virus infection . A bulk of evidence has accumulated during the last decade showing that this therapy is of benefit in nonuremic patients with chronic hepatitis C [ 4 , 5 ] . However , little information has been presented so far on chronically hepatitis C virus-infected uremic patients treated with interferon . Therefore , we conducted a study of interferon treatment in patients on maintenance dialysis with regard to its efficacy in suppressing viremia and tolerability of side effects . We report the result of an open multicenter trial of interferon treatment in patients on maintenance hemodialysis suffering from chronic hepatitis C virus infection . The trial was conducted by the Austrian Association of Nephrology In spite of the availability of hepatitis B vaccine , acute hepatitis B continues to be a worldwide problem for which no specific therapy is available . We investigated the safety and the effectiveness of recombinant interferon-alpha2b ( rIFN-alpha2b ) in the treatment of acute hepatitis B by determining overall severity and duration of symptoms , time required to clear viral antigens and hepatitis B virus ( HBV ) DNA , and titre of antibodies to hepatitis B surface antigen ( HBsAb ) , 24 weeks after the onset of therapy . One hundred patients were r and omly assigned to treatment with either 3 million units ( MU ) ( n = 34 ) or 10 MU ( n = 33 ) rIFN-alpha2b or to placebo ( n = 33 ) , three times weekly for 3 weeks . Follow-up was for 24 weeks . A significantly shorter duration of the symptoms and signs of acute hepatitis was observed in patients who received 3 MU rIFN-alpha2b compared with those who received 10 MU rIFN-alpha2b or placebo . Twenty-one weeks post-therapy , patients treated with 10 MU rIFN-alpha2b showed a significantly higher geometric mean HBsAb titre than those treated with placebo ( 85.1 vs 35.5 IU l-1 , P < 0.05 ) . rIFN-alpha2b administration was well tolerated even in jaundiced patients . No serious side-effects were observed necessitating reduction in dose or discontinuation of the drug . The effect of rIFN-alpha2b on transition of HBV infection to chronicity could not be evaluated in this trial because such an unfavourable course was not seen in any of the treated or the control patients . In conclusion , rIFN-alpha2b was safe in acute hepatitis B , and at low dose was found to ameliorate symptoms and to shorten significantly the duration of illness Patients who are anti-HCV positive before renal transplantation ( Tx ) have a significantly increased risk of posttransplant liver disease . We conducted a prospect i ve , controlled study to evaluate the posttransplant outcome of renal graft c and i date s with HCV-associated chronic hepatitis ( n = 30 ) . Patients were r and omly assigned to either of two groups . All patients on enrollment underwent liver biopsy , which showed mild-to-moderate hepatitis activity ( mean 4.1 , range 2–6 ) . Half the patients received interferon-alpha ( IFN-a ) administered at a dosage of 3 million units three times weekly for 1 year . Liver biopsy was repeated for treated patients at the end of IFN-a treatment . Of these , 11 patients received renal transplant ( group A ) . The other half did not receive IFN-a and to date 10 patients have been transplanted ( group B ) . Renal transplant recipients were prospect ively followed for a period of 12 months and a follow-up liver biopsy was also done at the end of this period ( end of study ) . Biochemical and virological responses were evaluated and the histologic activity index ( HAI ) scoring according to Knodell was assessed . The mean pretreatment serum HCV RNA level was 1.14 ± 0.84 and 1.0 ± 0.89 mEq/ml for groups A and B , respectively ( bDNA assay sensitivity threshold is < 0.2 mEq/ml ) . HCV RNA became undetectable in 4 patients of group A. At the end of study period the mean quantitative HCV RNA titers were 1.43 ± 4.07 and 15.18 ± 11.08 mEq/ml in groups A and B , respectively ( p < 0.0001 ) . In group A , the mean HAI score decreased from 4.27 ± 1.19 to 1.64 ± 0.67 after IFN-a treatment ( p < 0.0001 ) . This score was maintained till the end of the study period with a mean of 1.82 ± 0.6 . Mean HAI score of group B on enrollment was 3.9 ± 1.2 and at the end of study increased to 5.5 ± 1.35 ( p = 0.01 ) . There was statistically significant difference ( p value less than 0.0001 ) between the HAI scores at the end of the study period between the two groups . These results demonstrate that interferon therapy while on dialysis is associated with less viremia and decreased progression of chronic liver disease in renal transplant patients with hepatitis |
12,606 | 25,860,273 | RESULTS Self efficacy perception , work motivation , a lower age and a better socioeconomic status were identified as worker-related return to work facilitators .
Among work environment facilitators , good communication practice s , supervisor support , a good assessment and modification of work load , adjustment of expectations , a good relationship between employers and employees and positive work experiences were identified .
Treatment may improve return to work using a multidisciplinary approach , reducing stress and identifying psychosocial determinants of mental problems rather than symptoms and providing a timely health care . | BACKGROUND There is growing interest in the treatment and return-to-work of workers with labor related mental illnesses .
AIM To perform a systematic review of practice s and interventions that improve return to work . | Introduction Return to work ( RTW ) of employees on sick leave for common mental disorders may require a multidisciplinary approach . This article aims to assess time to RTW after a psychiatric consultation providing treatment advice to the occupational physician ( OP ) for employees on sick leave for common mental disorders in the occupational health ( OH ) setting , compared to care as usual ( CAU ) . Methods Cluster r and omized clinical trial evaluating patients of 12 OPs receiving consultation by a psychiatrist , compared to CAU delivered by 12 OPs in the control group . 60 patients suffering from common mental disorders and ≥ six weeks sicklisted were included . Follow up three and six months after inclusion . Primary outcome measure was time to RTW . Intention- to-treat multilevel analysis and a survival analysis were performed to evaluate time to RTW in both groups . Results In CAU , referral was the main intervention . Both groups improved in terms of symptom severity and quality of life , but time to RTW was significantly shorter in the psychiatric consultation group . At three months follow up , 58 % of the psychiatric consultation group had full RTW versus 44 % of the control group , a significant finding ( P = 0.0093 ) . Survival analysis showed 68 days earlier RTW after intervention in the psychiatric consultation group ( P = 0.078 ) compared to CAU . Conclusion Psychiatric consultation for employees on sick leave in the OH setting improves time to RTW in patients with common mental disorders as compared to CAU . In further research , focus should be on early intervention in patients with common mental disorders on short sick leave duration . Psychiatric consultation might be particularly promising for improvement of RTW in those patients . Trial registration number IS RCT N : Background In the present study the effect of a workplace-oriented intervention for persons on long-term sick leave for clinical burnout , aim ed at facilitating return to work ( RTW ) by job-person match through patient-supervisor communication , was evaluated . We hypothesised that the intervention group would show a more successful RTW than a control group . Methods In a prospect i ve controlled study , subjects were identified by the regional social insurance office 2 - 6 months after the first day on sick leave . The intervention group ( n = 74 ) was compared to a control group who had declined participation , being matched by length of sick leave ( n = 74 ) . The RTW was followed up , using sick-listing register data , until 1.5 years after the time of intervention . Results There was a linear increase of RTW in the intervention group during the 1.5-year follow-up period , and 89 % of subjects had returned to work to some extent at the end of the follow-up period . The increase in RTW in the control group came to a halt after six months , and only 73 % had returned to work to some extent at the end of the 1.5-year follow-up . Conclusions We conclude that the present study demonstrated an improvement of long-term RTW after a workplace-oriented intervention for patients on long-term sick leave due to burnout . Trial registration Current Controlled Trials NCT01039168 Background Stress-related disorders are widespread and responsible for high societal costs e.g. sick leave payment and reduced productivity . The aim of this study was to evaluate the effect of an intervention program on return to work or labour market . Methods In a controlled interventional study design we compared 72 emotionally distressed patients , who received support during 2006 , with 89 control individuals who had also been sick listed for emotional distress . Intervention was provided by trained psychologists and social workers who were in continuous dialog with the patients , providing counselling e.g. on decisions concerning resumption of work , support to families , participation in meetings with the workplace . Basically , the controls and the intervention group share the same access to welfare benefits . The main outcome was time to return to labour market ( TTR ) . Results The baseline characteristics were similar in the two groups . There were no differences in the rate of resuming work between the two groups . About 80 % in both groups had returned to the labour market after one year . Conclusion An intervention program with psychological stress management and case management did not improve work capability compared to usual care . Work resumption as a single outcome probably is an insensitive parameter of intervention management quality , and should be supplemented by other data on different aspects of treatment BACKGROUND Sickness absence due to mental health problems ( MHPs ) is increasing in several European countries . However , little is known about return to work ( RTW ) for employees with MHPs . This prospect i ve study aim ed to identify predictors for RTW in employees sick-listed with MHPs . METHODS Employees were recruited when applying for sickness benefit due to MHPs from the Municipality of Copenhagen ( n = 644 ) . Information about age , gender , occupation , self-reported RTW expectancy , self-reported reason for absence and prior absence with MHPs was retrieved from application forms for sickness benefit . Each participant was followed-up in the National Register for Social Transfer Payments for a maximum period of 52 weeks to estimate time to RTW . Hazard ratios for RTW with 95 % confidence intervals were calculated using Cox proportional regression analyses . RESULTS Employees sick-listed with self-reported stress/burnout returned to work faster than those with self-reported depression ( HR = 0.76 ) , and other MHPs ( HR = 0.56 ) . A positive RTW expectancy of the sick-listed person ( HR = 1.27 ) and no prior absence with MHPs ( HR = 1.29 ) were associated with a shorter time to RTW . CONCLUSION Sickness absence due to self-reported stress/burnout , a positive RTW expectancy and no prior absence with MHPs predicted a shorter time to RTW among Danish employees sick listed with MHPs . Findings could help social insurance officers and other rehabilitation professionals to identify groups at high risk for prolonged absence Background In recent years an increasing number of patients have been referred to the medical sector with stress symptoms . Moreover , these conditions imply increased sickness absence . This indicates a need for treatment programmes in general medical practice . The aim of this study was to test the effect of a multidisciplinary stress treatment programme on the return to work ( RTW ) rate in persons with work-related stress and establish predictive factors for this outcome . Methods During a two-year period 63 out of 73 referrals to the Stress Clinic ( a section of a Clinic of Occupational Medicine ) completed a stress treatment programme consisted of the following:1 ) Identification of relevant stressors . 2 . Changing the coping strategies of the participants . 3 . Evaluating/changes in participant workload and tasks . 4 . Relaxation techniques . 5 . Physical exercise . 6 . Psychiatric evaluation when indicated by depression test score . On average each patient attended six one-hour sessions over the course of four months . A group of 34 employees referred to the Clinic of Occupational Medicine by their general practitioners served as a control group . Each participant had a one-hour consultation at baseline and after four months . A specialist in occupational medicine carried out all sessions . Return To Work ( RTW ) , defined as having a job and not being on sick leave at the census , was used as outcome measure four months after baseline , and after one and two years . Results The level of sick leave in the stress treatment group dropped from 52 % to 16 % during the first four months of follow-up and remained stable . In the control group , the reduction in sick leave was significantly smaller , ranging from 48 % at baseline to 27 % after four months and 24 % after one year . No statistically significant difference between the two groups was observed after one and two years . Age below 50 years and being a manager increased the odds ratio for RTW after one and two years , while gender and depression had no predictive value . Conclusions The stress treatment programme showed a significant effect on the return to work rate . The stress treatment programme seems feasible for general practitioners . Trial Registration IS RCT Background The aim of the present study was to conduct subgroup-analyses in a prospect i ve cohort of workers on long-term sickness absence to investigate whether associations between perceived work attitude , self-efficacy and perceived social support and time to RTW differ across different health conditions . Methods The study was based on a sample of 926 workers on sickness absence ( 6–12 weeks ) . The participants filled out a baseline question naire and were subsequently followed until the tenth month after listing sick . Perceived work attitude was measured with a Dutch language version of the Work Involvement Scale . Perceived social support was measured with a self-constructed st and ardized scale reflecting a person ’s perception of social support regarding RTW . Self-efficacy was measured with the st and ardised Dutch version of the General self-efficacy scale , assessing the subjects ’ expectations of their general capacities . The sample was divided into three subgroups : musculoskeletal health conditions , other physical health conditions and mental health conditions . Anova analyses and Cox proportional hazards regression analyses were used to identify differences in association between the three factors and the time to RTW between different subgroups . Results The associations between the perceived work attitude , self-efficacy and perceived social support and the time to RTW vary across different health condition subgroups , not only with regard to the strength of the association but also for the type of factor . In the multivariate model , hazard ratios ( HRs ) of 1.33 ( 95 % CI 1.01–1.75 ) in the musculoskeletal subgroup , and 1.26 ( 95 % CI 0.89–1.78 ) in the other physical subgroup were found in perceived work attitude . With regard to perceived social support HRs of 1.39 ( 95 % CI 1.12–1.99 ) respectively 1.51 ( 1.05–2.17 ) in the same subgroups were found . Only self-efficacy remained in the multivariate model in all subgroups with HRs of 1.49 ( 95 % CI 1.12–1.99 ) in the musculoskeletal subgroup , 1.53 ( 95 % CI 1.07–2.18 ) in the other physical subgroup and 1.60 ( 1.07–2.40 ) in the mental subgroup . Conclusions The results of this study show that perceived work attitude , self-efficacy and perceived social support are relevant predictors with regard to the time to RTW in all types of health conditions , but that important differences are observed in type of factor and strengths of the relationships between physical and mental health conditions The aim of this study was to compare the effectiveness of two individual-level psychotherapy interventions : ( a ) treatment as usual consisting of cognitive-behavioral therapy ( CBT ) and ( b ) work-focused CBT ( W-CBT ) that integrated work aspects early into the treatment . Both interventions were carried out by psychotherapists with employees on sick leave because of common mental disorders ( depression , anxiety , or adjustment disorder ) . In a quasi-experimental design , 12-month follow-up data of 168 employees were collected . The CBT group consisted of 79 clients , the W-CBT group of 89 . Outcome measures were duration until return to work ( RTW ) , mental health problems , and costs to the employer . We found significant effects on duration until RTW in favor of the W-CBT group : full RTW occurred 65 days earlier . Partial RTW occurred 12 days earlier . A significant decrease in mental health problems was equally present in both conditions . The average financial advantage for the employer of an employee in the W-CBT group was estimated at $ 5,275 U.S. dollars compared with the CBT group . These results show that through focusing more and earlier on work-related aspects and RTW , functional recovery in work can be substantially speeded up within a regular psychotherapeutic setting . This result was achieved without negative side effects on psychological complaints over the course of 1 year . Integrating work-related aspects into CBT is , therefore , a fruitful approach with benefits for employees and employers alike OBJECTIVE The aim of this study was to explore what characterizes patients receiving clinical interventions vs combined clinical and work-related interventions in a cohort of sick-listed subjects with musculoskeletal or mental disorders . Factors associated with return-to-work were also analysed . DESIGN A prospect i ve cohort study . METHODS A total of 699 newly sick-listed patients responded to a question naire on sociodemographics , measures of health , functioning , work ability , self-efficacy , social support , work conditions , and expectations . The 3-month follow-up question naire included patients ' self-reported measures of return-to-work , work ability and type of interventions . The most frequent International Classification of Diseases-10 diagnoses for patients ' musculoskeletal disorders were dorsopathies ( M50 - 54 ) and soft tissue disorders ( M70 - 79 ) , and for patients with mental disorders , depression ( F32 - 39 ) and stress reactions ( F43 ) . RESULTS Patients with mental disorders who received combined interventions returned to work to a higher degree than those who received only clinical intervention . The prevalence of work-related interventions was higher for those who were younger and more highly educated . For patients with musculoskeletal disorders better health , work ability and positive expectations of return-to-work were associated with return-to-work . However , combined interventions did not affect return-to-work in this group . CONCLUSION Receiving combined interventions increased the probability of return-to-work for patients with mental disorders , but not for patients with musculoskeletal disorders . Better health , positive expectations of return-to-work and better work ability were associated with return-to-work for patients with musculoskeletal disorders Objectives To describe gender differences in work modifications and changed job characteristics during return-to-work after sickness absence . Methods A 13 month prospect i ve cohort study was performed among 119 employees ( 54 women and 65 men ) who had reported sick for more than 1 month due to mental or musculoskeletal disorders . Men and women were of comparable ages and educational levels , worked in similar sectors , at corresponding functional levels , and were experiencing the same types of health disorders . They were interviewed bi-monthly . Work modifications and job characteristics were assessed at return-to-work . Job characteristics were also assessed upon the employee ’s inclusion in the study . Results Work modifications occurred in 77.4 % of the return-to-work attempts ( no gender differences ) ; reduced working hours , reduced work pace , or task reassignments were most frequent . Compared to men , reduced hours and pace were more often used for women between 12 and 20 weeks of absence ( P > 0.001 and 0.01 < P < 0.001 respectively ) and reduced hours also during the whole period ( 0.01 < P < 0.001 ) . Applying reduced hours related to type of disorder in men and applying different time-schedules in women . Upon return to work both women and men reported increased job autonomy and emotional dem and s ( P < 0.001 ) ; women reported more job satisfaction ( P < 0.001 ) . Conclusions Work modifications were widely applied during the return-to-work process and predominantly aim ed at reduction of pressure at work . Women had a few more work modifications . The marginal gender differences may be due to male and female respondents having similar characteristics . Upon return to work some job characteristics improved This article describes ( i ) gender differences in initial return to work ( RTW ) and lasting return to work ( LRTW ) ; ( ii ) health characteristics that predicted the observed gender differences in LRTW ; and ( iii ) associations between health characteristics and (L)RTW in men and women separately . A 13-month prospect i ve cohort study was performed with 119 employees ( 54 women and 65 men ) who had reported sick for more than 1 month because of mental or musculoskeletal complaints . These employees were interviewed bimonthly about their work status and health . The health characteristics included were self-rated health , the reason for reporting sick , the presence of at least one long-term disease , early improvement in health and a change in diagnosis . Cox regression analyses on the time to (L)RTW were performed . No gender differences were found regarding RTW . Women , however , did report a longer time to LRTW than men . This was predicted by their reason for reporting sick , the presence of at least one long-term disease , lack of early improvement in health and change in diagnosis . Women who experienced no early improvement and /or whose diagnosis changed during their sickness absence had lower chances of attaining a LRTW than other women . Men who were absent owing to mental complaints were less likely to RTW than men with musculoskeletal complaints . Men who had at least one long-term disease were also less likely to RTW than men who had no long-term diseases . The findings showed a delayed LRTW for women when compared with men , as predicted by health characteristics . The health characteristics , however , that predicted LRTW in women differed from those that predicted LRTW in men . Clearly , the findings support a gender-specific approach to sickness absence guidance . The results also suggest that women are misdiagnosed more often than men . This requires further investigation . Die vorliegende Studie beschreibt : ( i ) Geschlechtsunterschiede beim Wiedereinstieg in den Beruf ( return to work , RTW ) und dem dauerhaften Wiedereinstieg in den Beruf ( lasting return to work , LRTW ) ; ( ii ) Gesundheitsmerkmale , die die beobachteten Geschlechtsunterschiede beim LRTW vorhersah ; und ( iii ) Verbindungen zwischen Gesundheitsmerkmalen und (L)RTW bei Männern und Frauen getrennt . Eine 13-monatige prospektive Kohortenstudie wurde mit 119 Mitarbeitern ( 54 Frauen und 65 Männern ) durchgeführt , die sich aufgrund psychischer Symptome oder Beschwerden der Skelettmuskulatur für länger als einen Monat krank gemeldet hatten . Diese Mitarbeiter wurden jeden zweiten Monat zu ihrem Arbeitsstatus und ihrer Gesundheit befragt . Die eingeschlossenen Gesundheitsmerkmale beinhalteten : selbst beurteilte Gesundheit , Grund für die Krankmeldung , Vorliegen mindestens einer Langzeiterkrankung , frühzeitige Verbesserung der Gesundheit und Änderung der Diagnose . Cox-Regressionsanalysen wurden zur Dauer bis zum (L)RTW durchgeführt . Bezüglich des RTW wurden keine Geschlechtsunterschiede festgestellt . Allerdings kam es bei Frauen zu einer längeren Dauer bis zum LRTW als bei Männern . Dies wurde von dem Grund für ihre Krankmeldung , dem Vorliegen mindestens einer Langzeiterkrankung , dem Ausbleiben einer frühzeitigen Verbesserung der Gesundheit und der Änderung der Diagnose vorhergesagt . Bei Frauen , bei denen es nicht zu einer frühzeitigen Verbesserung kam und/oder deren Diagnose sich während ihrer krankheitsbedingten Abwesenheit änderte , waren die Chancen geringer , einen LRTW zu erzielen , als bei and eren Frauen . Bei Männern , die aufgrund von psychischen Symptomen fehlten , waren die Chancen geringer , einen RTW zu erzielen , als bei Männern mit Beschwerden der Skelettmuskulatur . Bei Männern , die mindestens eine Langzeiterkrankung aufwiesen , waren auch die Chancen geringer , einen RTW zu erzielen , als bei Männern ohne Langzeiterkrankung . Die Ergebnisse zeigten einen verzögerten LRTW für Frauen i m Vergleich zu Männern , wie aus den Gesundheitsmerkmalen zu schließen war . Die Gesundheitsmerkmale , die LRTW bei Frauen prognostizierten , unterschieden sich von jenen , die LRTW bei Männern prognostizierten . Die Ergebnisse sprechen eindeutig für ein geschlechtsspezifisches Vorgehen bei krankheitsbedingtem Fehlen . Die Ergebnisse deuten ebenfalls an , dass bei Frauen häufiger Fehldiagnosen gestellt werden als bei Männern . Dies bedarf weiterer Untersuchungen . Este estudio describe : ( i ) las diferencias según el sexo en relación con la reincorporación inicial al trabajo ( RAT ) y la reincorporación duradera al trabajo ( RDAT ) ; ( ii ) las características de salud que predijeron las diferencias según el sexo observadas en relación con la RDAT ; y ( iii ) las correlaciones entre las características del estado de salud y la RAT y la RDAT en varones y en mujeres , de manera independiente . Se realizó un estudio prospect ivo de cohorte de 13 meses de duración en el que participaron 119 empleados ( 954 mujeres y 65 varones ) que faltaron al trabajo durante más de 1 mes por trastornos psicológicos o musculoesqueléticos . Se entrevistó a estos empleados cada dos meses para indagar sobre la situación laboral y de salud de cada uno de ellos . Las características del estado de salud utilizadas fueron : valoración personal del estado de salud , afectación de la salud causante de la ausencia al trabajo , presencia de al menos una enfermedad crónica , mejoría rápida de la salud , y cambio de diagnóstico . Se realizaron análisis de Cox en el caso de la RDAT . No se hallaron diferencias según al sexo en relación con la RAT . Sin embargo , el tiempo de RDAT fue mayor en las mujeres que en los varones . Esto se predijo a partir de las razones expuestas para faltar al trabajo por motivos de enfermedad , la presencia de al menos una enfermedad crónica , la ausencia de una recuperación temprana , y el cambio del diagnóstico . Las mujeres que no experimentaron una mejoría temprana o cambio del diagnóstico , o ambas , durante su ausencia al trabajo por enfermedad tuvieron menos oportunidades de lograr una RDAT que el resto de las mujeres . Los varones ausentes al trabajo por motivos de trastornos psicológicos fueron menos propensos a la RAT que aquellos cuya ausencia al trabajo se debió a trastornos musculoesqueléticos . Los varones que presentaban al menos una enfermedad crónica fueron también menos propensos a la RAT que aquellos que no presentaban enfermedades crónicas . Los result ados mostraron un retardo en la RDAT en las mujeres en comparación con los varones , según se predijo a partir de las características del estado de salud . Las características del estado de salud que predijeron la RDAT en las mujeres fueron diferentes de las que predijeron la RDAT en los varones . Los result ados respaldan claramente la existencia de diferencias relacionadas con el sexo en cuanto a la ausencia al trabajo por motivos de enfermedad , e indican además que las mujeres son más propensas que los varones a recibir diagnósticos erróneos . Este tema requiere una investigación más minuciosa . Cette étude décrit : ( i ) les différences entre les sexes en ce qui concerne le retour initial au travail ( RIT ) et le retour durable au travail ( RDT ) ; ( ii ) les caractéristiques de santé qui prédisent les différences observées entre les sexes au niveau du RDT ; et ( iii ) les associations entre les caractéristiques de santé et le RIT/RDT chez les hommes et les femmes séparément . Une étude de cohorte prospect i ve sur 13 mois a été effectuée auprès de 119 employés ( 54 femmes et 65 hommes ) qui avaient été en absence maladie pendant plus d'un mois en raison de problèmes mentaux ou musculo-squelettiques . Ces employés ont été interrogés deux fois par mois sur leur état de travail et de santé . Les caractéristiques de santé incluses étaient les suivantes : autoévaluation de santé , raison du congé maladie , présence d'au moins une maladie de long terme , amélioration précoce de la santé et changement de diagnostic . Des analyses par régression de Cox ont été effectuées sur le délai jusqu'au RIT/RDT . Aucune différence entre les sexes n'a été détectée en ce qui concerne le RIT . Par contre , les femmes affichent un délai jusqu'au RDT plus long que les hommes . Cette situation était prédite par les raisons avancées pour le congé maladie , la présence d'au moins une maladie de long terme , le manque d'amélioration précoce de la santé et les changements de diagnostic . Les femmes qui ne connaissent pas d'amélioration précoce de la santé et/ou do nt le diagnostic change durant le congé maladie présentent une plus faible chance de parvenir au RDT que les autres femmes . Les hommes absents pour raisons de problèmes mentaux sont moins susceptibles d'atteindre le RIT que les hommes souffrant de problèmes musculo-squelettiques . Les hommes souffrant d'au moins une maladie de long terme sont également moins susceptibles d'atteindre le RIT que les hommes ne présentant pas de maladies de long terme . Les résultats indiquent un RDT plus tardif des femmes par rapport aux hommes , comme prédit par les caractéristiques de santé . Les caractéristiques de santé prédictives du RDT chez les femmes diffèrent des caractéristiques prédictives du RDT chez les hommes . Les résultats indiquent clairement qu'une approche spécifique selon le sexe est requise en matière de recomm and ations concernant l'absentéisme pour maladie . Les résultats suggèrent également que les femmes font plus souvent l'objet que les hommes de diagnostics erronés . Ce point nécessitera des recherches complémentaires This article assessed depressive symptoms associated with work-related psychosocial risk factors according to gender in Chile , using the dem and -control model ( Karasek ) and effort-reward imbalance ( Siegrist ) . A cross-sectional study was conducted in a r and om sample of 3,010 workers ( 35 % female and 65 % male ) from the country . Data analysis determined prevalence and associations through various statistical techniques ( χ2 , logistic regression ) . Exposure to psychosocial risk factors at work and prevalence of depressive symptoms were higher in women than men ( 15 % vs. 5 % ) . The adjusted analysis highlighted that female workers exposed to Isostrain ( OR = 2.34 ; 95%CI : 1.42 - 3.85 ) and low rewards ( OR = 2.13 ; 95%CI : 1.41 - 3.21 ) and male workers exposed to psychological dem and s ( OR = 3.04 ; 95%CI : 1.94 - 4.76 ) and effort-reward imbalance ( OR = 2.19 ; 95%CI : 1.39 - 3.46 ) had increased risk of depressive symptoms . Exposure to work-related psychosocial risk factors was associated with depressive symptoms in Chilean workers . Effective prevention in key aspects of work organization is thus needed |
12,607 | 29,996,879 | Conclusion The pooled prevalence of anemia among children was high , indicating that it had been continuing to be a public health problem . | Background Anemia is one of the global public health problems affecting more than one-third of the world population .
It has been strongly associated with limited psychomotor development ; and poor growth and performance in cognitive , social , and emotional function in children .
Despite published data revealed that anemia is a public health problem among children in Ethiopia , there is no a pooled national estimate on the prevalence and associated risk factors of anemia . | Background Anemia is a major health problem worldwide . Because of health and socioeconomic problems , the prevalence of anemia is higher in developing countries . Children and pregnant women are the most vulnerable groups to anemia . The aim of the present study was to determine the magnitude of anemia among school children . Methods A cross-sectional household survey was conducted in January 2011 on 423 children , aged 6–14 years , selected through systematic r and om sampling method . Sociodemographic and anthropometric data were collected using a pre-tested question naire . Capillary blood was taken from the fingertip of each child and hemoglobin was measured using HaemoCue digital photometer . All the necessary safety measures were taken during blood collection . Anthropometric indicators were measured using WHO ’s guideline . Data analysis was made using SPSS Version 16.0 for Windows . The association between predictors and outcome variables were measured by a stepwise logistic regression model . Ethical permission was obtained ; consent of the parents/guardian was taken and confidentiality was maintained . Result A total of 404 children were studied . The mean age was 10.21(SD ± 1.89 ) years . The proportion of females was 217(53.7 % ) . The mean hemoglobin level for both sexes was 11.59(SD ± 1.97 g/dl ) . The current prevalence of anemia was 152(37.6 % ) , out of which , 73(18.1 % ) had mild while 79(19.6 % ) of them had moderate anemia . The prevalence of anemia among the age group of 6–11 years was 118(40.5 % ) while the prevalence among the group of 12–14 years old children was 34(30.1 % ) . Among the selected variables in the logistic regression analysis , low family income [ OR = 4.925 , 95 % CI(1.063,22.820 ) ] , mothers ’ education [ OR = 4.621 , 95 % CI(1.383,15.439 ) ] , intake of plant food [ OR = 3.847 , 95 % CI(2.068 , 7.157 ) ] and intake of animal food [ OR = 2.37 , 95 % CI(1.040,5.402 ) ] were significantly and independently associated with anemia . Conclusion Anemia is a moderate public health problem in the study area . Family income , educational status of parents and inadequate plant and animal food intake are the predictors of anemia . Improving the economic status of the family , women education and health education about balanced animal and plant food consumption are recommended strategies to reduce the burden of anemia Background Causes of child undernutrition are diverse and change in space and time . Investigating current determinants of undernutrition remains vital to design an effective intervention strategy . The study assessed prevalence of undernutrition and its associated factors among children living in Addis Ababa , Ethiopia . Methods A community based cross-sectional study was conducted in 459 school age children and their parents or caregivers living in Lideta sub-city , Addis Ababa , Ethiopia . Participants were selected using a multi-stage simple r and om sampling technique . Height and weight of children was measured and their parents or care givers were interviewed for factors associated with undernutrition . Results About 31 % ( n = 141 ) of the children were undernourished ( 19.6 % stunted , 15.9 % underweight ) . Being male , higher birth order ( > 2 ) , larger family size ( 6–8 ) , low meal frequency ( ≤3 times ) in a day prior to the survey and mud floor house were significantly associated with undernutrition . Similarly , the risk of underweight increased significantly with an increase in age , birth order , family size and also the absence of h and washing facilities . The odds of undernutrition was lower in children born to 20–30 years old mothers compared to those born to mothers younger than 20 years . Conclusions Undernutrition is prevalent among school age children living in Lideta sub city , Addis Ababa . Policy makers should consider school age children in their nutrition policy documents and implement screening program and intervention strategy Background The interaction between malaria and under-nutrition is not well eluci date d in Ethiopia . The objective of this study was to assess the magnitude of under-nutrition and its correlation with malaria among under-five children in south-west Ethiopia . Methods This cross-sectional study was undertaken during March – February , 2009 as part of the baseline assessment of a cluster r and omized trial around Gilgel Gibe Hydroelectric dam , south-west Ethiopia . A total of 2410 under-five children were included for anthropometric measurement and blood investigation for the diagnosis of malaria and anemia . The nutritional status of children was determined using the International Reference Population defined by the U.S National Center for Health Statistics ( NCHS ) . Blood film was used to identify malaria parasite and haemoglobin concentration was determined by Hemo Cue analyzer ( HemoCue Hb 301 , Sweden ) . Results Significant proportion ( 40.4 % ) of under-five children were stunted ( height-for-age<−2SD ) . The prevalence of under-weight was 34.2 % . One third and one tenth of the children had anemia and malaria parasite respectively . Older children were more likely to have under-nutrition . There was no association between malaria and under-nutrition . Children who had malaria parasite were 1.5 times more likely to become anaemic compare to children who had no malaria parasite , [ OR = 1.5 , ( 95 % CI : 1.1–2.0 ) ] . Conclusion In this study , there is no association between malaria and under-nutrition . Children who have malaria are more likely to be anaemic . Malaria prevention and control program should consider nutrition interventions particularly anemia Background Anemia during childhood impairs physical growth , cognitive development and school performance . Identifying the causes of anemia in specific context s can help efforts to prevent negative consequences of anemia among children . The objective of this study was to assess prevalence and identify correlates of anemia among school children in Eastern Ethiopia . Methods A cross sectional study was conducted from January 2012 to February 2012 in Kersa , Eastern Ethiopia . The study included r and omly selected primary school students . Hemoglobin concentration was measured using a Hemocue haemoglobinometer . A child was identified as anemic if the hemoglobin concentration was < 11.5 g/dl for children ( 5–11 yrs ) and < 12 g/dl for child older than 12 years age . Poisson regression model with robust variance was used to calculate prevalence ratios . Result The overall prevalence of anemia was 27.1 % ( 95 % CI : 24.98 , 29.14 ) : 13.8 % had mild , 10.8 % moderate , and 2.3 % severe anemia . Children with in the age group of 5 - 9 years ( APR , 1.083 ; 95 % CI , 1.044- 1.124 ) were at higher risk for anemia . Paternal education ( Illiterate , 1.109 ; 1.044 - 1.178 ) was positively associated with anemia . Children who had irregular legume consumption ( APR , 1.069 ; 95 % CI , 1.022 -1.118 ) were at higher risk for anemia . Conclusion About a quarter of school children suffer from anemia and their educational potential is likely to be affected especially for those with moderate and severe anemia . Child age , irregular legume consumption , and low paternal schooling were associated with anemia . Intervention programmes aim ed to reduce anemia among school children are crucial to ensure proper growth and development of children Background Child malnutrition during the first 1,000 days , commencing at conception , can have lifetime consequences . This study assesses the prevalence of anemia and undernutrition among children aged 6–23 months in midl and and lowl and agroecological zones of rural Ethiopia . Methods Cross-sectional data examining sociodemographic , anthropometry , hemoglobin levels , and meal frequency indicators were collected from 216 children aged 6–23 months and their mothers r and omly selected from eight rural kebele ( villages ) . Results Of 216 children , 53.7 % were anemic , and 39.8 % , 26.9 % , and 11.6 % were stunted , underweight , and wasted , respectively . The prevalence of anemia was higher in the lowl and agroecological zone ( 59.5 % ) than the midl and ( 47.6 % ) . Among those children who were stunted , underweight , and wasted , 63.5 % , 66.7 % , and 68.0 % were anemic , respectively . Child anemia was significantly associated with the child not achieving minimum meal frequency , sickness during the last 2 weeks before the survey , stunting and low body mass index , and with maternal hemoglobin and h and washing behavior . The prevalence of stunting was higher in the lowl and agroecological zone ( 42.3 % ) than the midl and ( 36.2 % ) . The predictors of stunting were age and sex of the child , not achieving MMF , maternal body mass index , and age . As maternal height increases , the length for age of the children increases ( P=0.003 ) . Conclusion The overall prevalence of anemia and undernutrition among children aged 6–23 months in these study areas is very high . The prevalence was higher in the lowl and agro-ecological zone . Health information strategies focusing on both maternal and children nutrition could be sensible approaches to minimize stunting and anemia Introduction . The aim of this study was to determine the prevalence of anemia and determinant factors among children aged 6–59 months living in Kilte Awulaelo Woreda , eastern zone . Method . A community based cross-sectional study was conducted during February 2013 among 6 tabias of Kilte Awulaelo Woreda , northern Ethiopia . A total of 568 children were selected by systematic r and om sampling method . Anthropometric data and blood sample were collected . Bivariate and multivariate logistic regression analyses were performed to identify factors related to anemia . Result . The mean hemoglobin level was 11.48 g/dl and about 37.3 % of children were anemic . Children who were aged 6–23 months [ AOR = 1.89 : 95 % CI ( 1.3 , 2.8 ) ] , underweight [ AOR = 2.05 : 95 % CI ( 1.3 , 3.3 ) ] , having MUAC less than 12 cm [ AOR = 3.35 : 95 % CI ( 2.1 , 5.3 ) ] , and from households with annual income below 10,000 Ethiopian birr [ AOR = 4.86 : 95 % CI ( 3.2 , 7.3 ) ] were more likely to become anemic . Conclusion . The prevalence of anemia among the children is found to be high . It was associated with annual household income , age , and nutritional status of the child . So , improving family income and increasing awareness of the mother/caregiver were important intervention Background . Globally , about 47.4 % of children under five are suffering from anemia . In Ethiopia , 60.9 % of children under two years are suffering from anemia . Anemia during infancy and young childhood period is associated with poor health and impaired cognitive development , leading to reduced academic achievement and earnings potential in their adulthood life . However , there is scarcity of information showing the magnitude of iron deficiency anemia among young children in Ethiopia . Therefore , this study aim ed at assessing prevalence and associated factors of iron deficiency anemia among children under two ( 6–23 months ) . Methods . Institution based cross-sectional study was carried out from March to May , 2014 , at Tsitsika Health Center in Wag-Himra Zone , Northeast Ethiopia . Systematic r and om sampling technique was employed . Automated hemoglobin machine was used to determine the hemoglobin level . Socioeconomic and demographic data were collected by using a pretested and structured question naire . Binary logistic regression analysis was used to identify associated factors and odds ratio with 95 % CI was computed to assess the strength of association . Results . Total of 347 children participated in this study . The overall prevalence of anemia was 66.6 % . In multivariate logistic regression analysis , male sex ( AOR = 3.1 ( 95 % CI : 1.60–5.81 ) ) , 9–11 months of age ( AOR = 9.6 ( 95 % CI : 3.61–25.47 ) ) , poor dietary diversity ( AOR = 3.2 ( 95 % CI : 1.35–7.38 ) ) , stunting ( AOR = 2.7 ( 95 % CI : 1.20–6.05 ) ) , diarrhea ( AOR = 4.9 ( 1.63–14.59 ) ) , no formal education ( AOR = 2.6 ( 95 % CI : 1.26–5.27 ) ) , early initiation of complementary food ( AOR = 11.1 ( 95 % CI : 4.08–30.31 ) ) , and lowest wealth quintile ( AOR = 3.0 ( 95 % CI : 1.01–8.88 ) ) were significantly associated with anemia . Conclusion . The overall prevalence of anemia among children who aged 6–23 months has sever public health importance in the study area . Integrated efforts need to be prioritized to improve health as well as appropriate infant and young child feeding practice among children under OBJECTIVE To estimate the prevalence of chronic health and nutritional conditions of schoolchildren in Ethiopia . METHODS Cross-sectional survey in schools in each region r and omly selected in proportion to size , then a r and om sample of 50 - 68 children in grade s 3 and 4 in each school . Children were examined for signs of micronutrient deficiencies and chronic infections ; weighed and measured ; provided a faecal sample to diagnose intestinal parasitic infections ; and were interviewed about their recent diet and hygiene practice s. RESULTS A total of 7572 children were studied in 142 schools in all 11 regions of Ethiopia . Nearly 17 % of children were orphans . The prevalence of stunting was 22.3 % and 23.1 % of children were thin for age , but these may be underestimates as there was evidence that age may have been estimated based on stature when children enroll in school . Just under 10 % of children were anaemic when altitude was accounted for . The overall prevalence of trachoma was 13 % and children who washed their face before school were at lower risk of trachoma than children who had not . Children who reported that they had eaten fruits or vegetables the day before also had a lower risk of xerophthalmia than children who had not . Only 30 % of children were infected with intestinal worms . CONCLUSIONS Trachoma is a problem but anaemia and intestinal worms are relatively uncommon in Ethiopian schoolchildren . These data provide a basis for developing a school health policy and programmes BACKGROUND The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear . METHODS We assessed the hormonal and hematologic responses to testosterone administration in a clinical trial in which older men with mobility limitation were r and omized to either placebo or testosterone gel daily for 6 months . RESULTS The 7%-10 % increase in hemoglobin and hematocrit , respectively , with testosterone administration was associated with significantly increased erythropoietin ( EPO ) levels and decreased ferritin and hepcidin levels at 1 and 3 months . At 6 months , EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration , but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline , suggesting a new set point . Consistent with increased iron utilization , soluble transferrin receptor ( sTR ) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men . Hormonal and hematologic responses were similar in anemic participants . The majority of testosterone-treated anemic participants increased their hemoglobin into normal range . CONCLUSIONS Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations . We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis Background : Anemia is an indicator of both poor nutrition and health . In low-income countries like Ethiopia , the prevalence of anemia remains high due to several determinant factors . There is a lack of regular surveillance system to determine the magnitude of anemia among school age children . The aim of this study was to determine the burden and determinant factors of anemia among school children . Material s and Methods : A comparative cross-sectional study was conducted from March 2014 to May 2014 among elementary school children in Northwest Ethiopia . Multi stage and simple r and om sampling techniques were used to select the schools and the study subjects . St and ard question naire was employed to assess the socioeconomic status of study participants . Intestinal parasitosis infections and hemoglobin level were determined by formula ether concentration technique and automated hematology analyzer , respectively . Descriptive statistics were used to determine the burden of anemia . Stepwise logistic regression was used to identify the determinants of anemia . Results : Among 2,372 elementary school children , the prevalence of anemia was 7.6 % ( 95 % CI : 7 % - 9 % ) . The mean hemoglobin level was 11.6 g/dl ranging from 10 g/dl to 13g/dl . The magnitude of hookworm infection was 530 ( 22.3 % ) . In multivariate analysis anemia was found associated with residence , source of water , availability of latrine , maternal education , family size and hookworm infection . Conclusion : Anemia still remains as a major public health problem among the school children in the study area . Residence , source of water , availability of latrine , maternal education , family size and hookworm infection are also the major determinant factors for the high prevalence of anemia . Therefore , health education , iron supplement and deworming should be given to school age children OBJECTIVE To identify the prevalence and factors associated with anemia in children attending Municipal Early Childhood Education Day Care Center ( Centros Municipais de Educação Infantil [ CMEI ] ) nurseries in Colombo-PR . METHODS Analytical , cross-sectional study with a representative sample of 334 children obtained by stratified cluster sampling , with r and om selection of 26 nurseries . Data collection was conducted through interviews with parents , assessment of iron intake by direct food weighing , and hemoglobin measurement using the finger-stick test . Bivariate association tests were performed followed by multiple logistic regression adjustment . RESULTS The prevalence of anemia was 34.7 % . Factors associated with anemia were : maternal age younger than 28 years old ( p=0.03 ) , male children ( p=0.02 ) , children younger than 24 months ( p=0.01 ) , and children who did not consume iron food sources ( meat+beans+dark green leafy vegetables ) ( p=0.02 ) . There was no association between anemia and iron food intake in CMEI . However , iron intake was well below the recommended levels according to the National Education Development Fund resolution , higher prevalence of anemia was observed in children whose intake of iron , heme iron , and nonheme iron was below the median . CONCLUSIONS In terms of public health , the prevalence of anemia is characterized as a moderate problem in the studied population and demonstrates the need for coordination of interdisciplinary actions for its reduction in CMEI nurseries Abstract Research on associated risk factors for intestinal parasitic infections and malnutrition in various geographic regions is needed for the development of appropriate control strategies . The aim of this study was to determine the risk factors associated with intestinal parasitic infections , anaemia , and malnutrition in school children , living in urban and rural areas of northern Ethiopia . Six hundred school children , aged 6–15 years , were r and omly selected in a cross-sectional survey from 12 primary schools . Sociodemographic and anthropometric data were collected . Faecal sample s were examined using direct , concentration , and the Kato – Katz methods . Urine specimens were analysed for Schistosoma haematobium ova . Haemoglobin was measured using a HemoCue spectrometer . The overall prevalence of intestinal parasitosis was 72 % ( 95 % confidence interval ( CI ) : 66–76 % ) . The prevalence of anaemia , stunting , and thinness were 11 % ( 95 % CI : 8–13 % ) , 35 % ( 95 % CI : 31–38 % ) , and 34 % ( 95 % CI : 30–38 % ) , respectively . Poor personal hygiene habits were generally associated with anaemia and nutritional deficiency ( low body mass index ) . Multivariate logistic regression models related Schistosoma mansoni infection with boys . Boys were also more likely to be malnourished . Hookworm infection was associated with anaemia and unhygienic finger nails . Access to clean water and latrines , with some hygiene and sanitation communication activities , could improve health of children in Ethiopia . The use of smartphone technology in demographic data collection proved to be successful . The potential advantage offered by this technology for parasitological field surveys merits further investigation OBJECTIVE : We aim ed to compare affect and behavior of 3 groups of nonanemic 4-year-old children : children with iron-deficiency anemia ( IDA ) in infancy whose anemia was not corrected before 24 months ( chronic IDA ) ( n = 27 ) ; children with IDA in infancy whose anemia was corrected before 24 months ( corrected IDA ) ( n = 70 ) ; and children who were nonanemic in infancy and at 24 months ( n = 64 ) . METHOD : Mother and child dyads were invited to a local clinic room . Children 's social referencing , wariness , frustration-tolerance behavior , and affect were observed during a set of situations encountered in the laboratory , including free play , stranger approach , novel toy , and delay of gratification . The whole procedure was videotaped . The children 's affective and behavioral displays were coded by using a time-sampling ( 5-second segments ) code scheme . Iron status of children was determined on the basis of hemoglobin concentration measured with the cyanomethemoglobin method in blood sample s obtained by fingerstick in infancy and at the ages of 24 months and 4 years . RESULTS : Children who had chronic IDA in infancy displayed less positive affect , less frustration tolerance , more passive behavior , and more physical self-soothing in the stranger approach and delay of gratification . In contrast , the behavior and affect of children whose anemia was corrected before the age of 24 months were comparable to those of children who were nonanemic throughout infancy . CONCLUSION : The results point to the potential benefits of preventing iron deficiency in infancy and treating it before it becomes chronic or severe |
12,608 | 30,285,081 | Conclusions and Relevance We failed to find a significant association between PFS and HRQoL in cancer clinical trials .
These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer . | Importance Progression-free survival ( PFS ) has become a commonly used outcome to assess the efficacy of new cancer drugs .
However , it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit .
Objective To evaluate the association between PFS and health-related quality of life ( HRQoL ) in oncology through a systematic review and quantitative analysis of published r and omized clinical trials . | BACKGROUND In the CALYPSO trial , carboplatin-pegylated liposomal doxorubicin ( CD ) demonstrated superior therapeutic index versus carboplatin-paclitaxel ( CP ) in patients with recurrent ovarian cancer . This paper reports the health-related quality of life ( HRQoL ) findings . MATERIAL S AND METHODS HRQoL was measured with the EORTC QoL-QC30 question naire and OV28 ovarian cancer module . Mean change scores from baseline in HRQoL subscales ( five functional scales and global health status ) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months . RESULTS Compliance was 90 % at baseline and 76 % , 64 % , 57 % at 3 , 6 , and 9 months , respectively . Baseline HRQoL showed already impaired global scores ( mean 62/100 ) and considerable symptom burden ( 90 % of patients reporting nonzero scores ) . Global QoL and abdominal symptom scores improved over time in both arms ; at 6 months , 36 % of patients met criteria for improved symptoms . Treatment with CD result ed in less peripheral neuropathy ( 9.8 versus 24.2 ) , fewer other chemotherapy side-effects ( 9.5 versus 16.2 ) , and less impact on body image ( 3.8 versus 10.4 ) versus CP ( all P<0.02 ) at 6 months . CONCLUSIONS These patient-reported outcomes confirm the overall lower toxicity of CD versus CP . The improved disease-related outcomes achieved with CD were not at the expense of Summary Background In the UK , chemotherapy is the st and ard treatment for inoperable , locally advanced , non-metastatic pancreatic cancer . Chemoradiotherapy is also an acceptable treatment option , for which gemcitabine , fluorouracil , or capecitabine can be used as concurrent chemotherapy agents . We aim ed to assess the activity , safety , and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer . Methods In this open-label , r and omised , two-arm , phase 2 trial , patients aged 18 years or older with histologically proven , locally advanced pancreatic cancer ( with a tumour diameter of 7 cm or less ) were recruited from 28 UK centres between Dec 24 , 2009 and Oct 25 , 2011 . After 12 weeks of induction gemcitabine and capecitabine chemotherapy ( three cycles of gemcitabine [ 1000 mg/m2 on days 1 , 8 , 15 of a 28-day cycle ] and capecitabine [ 830 mg/m2 twice daily on days 1–21 of a 28-day cycle ] ) , patients with stable or responding disease , tumour diameter of 6 cm or less , and WHO performance status 0–1 were r and omly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine ( 300 mg/m2 once per week ) or capecitabine ( 830 mg/m2 twice daily , Monday to Friday only ) , both in combination with radiation ( 50·4 Gy in 28 fractions ) . R and omisation ( 1:1 ) was done via a central computerised system and used stratified minimisation . The primary endpoint was 9-month progression-free survival , analysed by intention to treat including only those patients with valid CT assessment s. This trial is registered with IS RCT N , number 96169987 . Findings 114 patients were registered and 74 were r and omly allocated ( 38 to the gemcitabine group and 36 to the capecitabine group ) . After 9 months , 22 of 35 assessable patients ( 62·9 % , 80 % CI 50·6–73·9 ) in the capecitabine group and 18 of 35 assessable patients ( 51·4 % , 39·4–63·4 ) in the gemcitabine group had not progressed . Median overall survival was 15·2 months ( 95 % CI 13·9–19·2 ) in the capecitabine group and 13·4 months ( 95 % CI 11·0–15·7 ) in the gemcitabine group ( adjusted hazard ratio [ HR ] 0·39 , 95 % CI 0·18–0·81 ; p=0·012 ) . 12-month overall survival was 79·2 % ( 95 % CI 61·1–89·5 ) in the capecitabine group and 64·2 ( 95 % CI 46·4–77·5 ) in the gemcitabine group . Median progression-free survival was 12·0 months ( 95 % CI 10·2–14·6 ) in the capecitabine group and 10·4 months ( 95 % CI 8·9–12·5 ) in the gemcitabine group ( adjusted HR 0·60 , 95 % CI 0·32–1·12 ; p=0·11 ) . Eight patients in the capecitabine group had an objective response at 26 weeks , as did seven in the gemcitabine group . More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects ( seven [ 18 % ] vs none , p=0·008 ) and non-haematological toxic effects ( ten [ 26 % ] vs four [ 12 % ] , p=0·12 ) during chemoradiation treatment ; the most frequent events were leucopenia , neutropenia , and fatigue . Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy . Of the 34 patients in the capecitabine group who received chemoradiotherapy , 25 ( 74 % ) received the full protocol dose of radiotherapy , compared with 26 ( 68 % ) of 38 patients in the gemcitabine group . Quality -of-life scores were not significantly different between the treatment groups . Interpretation Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer . However , these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small . Funding Cancer Research UK PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P < .01 ) leading to early discontinuation ( 15 % v 6 % ; P < .001 ) occurred more frequently in the CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP BACKGROUND GOG 240 was a practice -changing r and omised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival , and the proportion of patients achieving an overall objective response , compared with chemotherapy alone . In this study , we aim ed to analyse patient-reported outcomes in GOG 240 . METHODS Eligible adult participants ( aged ≥18 years ) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0 - 1 . Participants were r and omly assigned by web-based permuted block r and omisation ( block size 4 ) in a 1:1:1:1 ratio to the four treatment groups : cisplatin ( 50 mg/m(2 ) intravenously on day 1 or 2 of the treatment cycle ) and paclitaxel ( 135 mg/m(2 ) intravenously over 24 h or 175 mg/m(2 ) intravenously over 3 h on day 1 ) , with or without bevacizumab ( 15 mg/kg intravenously on day 1 or 2 ) , or paclitaxel ( 175 mg/m(2 ) over 3 h on day 1 ) and topotecan ( 0·75 mg/m(2 ) for 30 min on days 1 - 3 ) with or without bevacizumab ( 15 mg/kg intravenously on day 1 ) . Treatment assignment was concealed at r and omisation ( everyone was masked to treatment assignment , achieved by the use of a computer encrypted numbering system at the National Cancer Institute ) and became open-label when each patient was registered to the trial . Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity , whichever occurred first . The co primary endpoints of the trial were overall survival and safety ; the primary quality -of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index ( FACT-Cx TOI ) . For our analysis of patient-reported outcomes , participants were assessed before treatment cycles 1 , 2 , and 5 , and at 6 and 9 months after the start of cycle 1 , with the FACT-Cx TOI , items from the FACT-GOG-Neurotoxicity subscale , and a worst pain item from the Brief Pain Inventory . All patients who completed baseline quality -of-life assessment s and at least one further follow-up assessment were evaluable for quality -of-life outcomes . This study is registered with Clinical Trials.gov , number NCT00803062 . FINDINGS Between April 6 , 2009 , and Jan 3 , 2012 , a total of 452 patients were enrolled in the trial , of whom 390 completed baseline quality -of-life assessment and at least one further assessment and were therefore evaluable for quality -of-life outcomes . In these patients , patient-reported outcome completion declined from 426 ( 94 % ) of 452 ( at baseline ) to 193 ( 63 % ) of 307 ( 9 months post-cycle 1 ) , but completion rates did not differ significantly between treatment regimens ( p=0·78 ) . The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not ( p=0·27 ) . Compared with patients who received chemotherapy alone , patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1·2 points lower ( 98·75 % CI -4·1 to 1·7 ; p=0·30 ) . INTERPRETATION Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life . Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit . FUNDING National Institutes of Health The purpose of our study was to compare progression-free survival and quality of life ( QOL ) after cisplatin – gemcitabine ( CG ) or epirubicin – gemcitabine ( EG ) in chemotherapy-naive patients with unresectable non-small-cell lung cancer . Patients ( n=240 ) were r and omised to receive gemcitabine 1125 mg m−2 ( days 1 and 8) plus either cisplatin 80 mg m−2 ( day 2 ) or epirubicin 100 mg m−2 ( day 1 ) every 3 weeks for a maximum of five cycles . Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status ⩽2 . QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 question naires . There were no significant differences in median progression-free survival ( CG 26 weeks , EG 23 weeks ) , median overall survival ( CG 43 weeks , EG 36 weeks ) , or tumour response rates ( CG 46 % , EG 36 % ) . Toxicity was mainly haematologic . In the EG arm granulocytopenia occurred more frequently , leading to more febrile neutropenia . Also , elevation of serum transaminases , mucositis , fever , and decline in LVEF were more common in the EG arm . In the CG arm , more patients experienced elevated serum creatinine levels , sensory neuropathy , nausea , and vomiting . Global QOL was not different in both arms . Progression-free survival , overall survival , response rate , and QOL were not different between both arms ; however , overall toxicity was more severe in the EG arm PURPOSE To analyze quality of life ( QOL ) in a r and omized , placebo-controlled phase III trial concluding that the addition of concurrent and maintenance bevacizumab ( Arm 3 ) to carboplatin and paclitaxel prolongs progression-free survival in front-line treatment of advanced ovarian cancer compared to chemotherapy alone ( Arm 1 ) or chemotherapy with bevacizumab in cycles 2 - 6 only ( Arm 2 ) . PATIENTS AND METHODS The Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary ( FACT-O TOI ) was used to assess QOL before cycles 1 , 4 , 7 , 13 , and 21 ; and 6months after completing study therapy . Differences in QOL scores were assessed using a linear mixed model , adjusting for baseline score , and age . The significance level was set at 0.0167 to account for multiple comparisons . RESULTS 1693 patients were queried . Arm 2 ( p<0.001 ) and Arm 3 ( p<0.001 ) reported lower QOL scores than those in Arm 1 . The treatment differences were observed mainly at cycle 4 , when the patients receiving bevacizumab ( Arm 2 and Arm 3 ) reported 2.72 points ( 98.3 % CI : 0.88 - 4.57 ; effect size=0.18 ) and 2.96 points ( 98.3 % CI : 1.13 - 4.78 ; effect size=0.20 ) lower QOL respectively , than those in Arm 1 . The difference in QOL scores between Arm 1 and Arm 3 remained statistically significant up to cycle 7 . The percentage of patients who reported abdominal discomfort dropped over time , without significant differences among study arms . CONCLUSION The small QOL difference observed during chemotherapy did not persist during maintenance bevacizumab BACKGROUND The purpose of this study was to compare quality of life and overall toxicity in patients with advanced non-small-cell lung cancer ( NSCLC ) treated with vinorelbine-gemcitabine ( VG ) or carboplatin-paclitaxel ( Taxol ) ( CP ) . PATIENTS AND METHODS A total of 165 previously untreated patients were r and omized to the two regimens . Quality of life was assessed by the Lung Cancer Symptom Scale ( LCSS ) . Overall toxicity and secondary efficacy end points were evaluated by st and ard WHO criteria . RESULTS There was no significant difference in overall quality of life between the two treatments . Neutropenia , thrombocytopenia , peripheral neuropathy , and alopecia , were more common in the CP arm , whereas constipation was more frequent in the VG arm . Response rates were 14.6 % in the VG arm and 16.9 % in the CP arm . Median survival times were 7.8 and 8.6 months , and 1 year survival rates were 38.4 % and 31.9 % , respectively . CONCLUSIONS Patients treated with VG experienced lower toxicity , but overall quality of life was similar in both arms . Efficacy seemed comparable between VG and CP . Our study shows that VG is a viable alternative to platinum-based chemotherapy in patients with advanced NSCLC PURPOSE To prospect ively assess the impact of treatment with cisplatin alone or in combination with topotecan ( CT ) on quality of life ( QOL ) in patients with advanced or recurrent cervical cancer , and to explore the prognostic value of baseline QOL scores . PATIENTS AND METHODS Patients entered on Gynecologic Oncology Group ( GOG ) Protocol 179 were expected to complete QOL assessment s at four time points using Functional Assessment of Cancer Therapy-General ( FACT-G ) , Cervix subscale ( Cx subscale ) , FACT/GOG-Neurotoxicity subscale ( NTX subscale ) , Brief Pain Inventory ( BPI ) , and UNISCALE ( UNI ) . Adjusting for patient age , baseline scores , and effects of time , we longitudinally examined treatment effect on QOL during and after chemotherapy . RESULTS Among patients r and omly allocated to receive cisplatin ( n = 146 ) or CT ( n = 147 ) , there were no statistically significant differences in QOL up to 9 months after r and omization despite more hematologic toxicity in the combination arm . QOL assessment s were completed at rates of 98 % , 85 % , 68 % , and 59 % , respectively , for the four time points , with similar rates and reasons for nonparticipation between regimens . Baseline FACT-G ( P = .0016 ) and BPI ( P = .0001 ) scores were significantly associated with patient age ; older patients had better QOL and less pain . Baseline UNI was positively correlated with FACT-G ( r = 0.66 ; P < .001 ) and Cx subscale ( r = 0.29 ; P < .001 ) , and negatively related to BPI ( r = -0.41 ; P < .0001 ) . Baseline FACT-Cx ( FACT-G + Cx subscale ) was associated with survival . CONCLUSION Despite increased toxicity , CT did not significantly reduce patient QOL when compared with cisplatin alone . Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer BACKGROUND St and ard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination . The Gynecologic Oncology Group conducted a r and omized , phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer . METHODS We r and omly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 ( intravenous-therapy group ) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 ( intraperitoneal-therapy group ) . Treatment was given every three weeks for six cycles . Quality of life was assessed . RESULTS Of 429 patients who underwent r and omization , 415 were eligible . Grade 3 and 4 pain , fatigue , and hematologic , gastrointestinal , metabolic , and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group ( P < or = 0.001 ) . Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy , but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months , respectively ( P=0.05 by the log-rank test ) . The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months , respectively ( P=0.03 by the log-rank test ) . Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment . CONCLUSIONS As compared with intravenous paclitaxel plus cisplatin , intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer OBJECTIVE Trabectedin in combination with PLD improves progression-free survival ( PFS ) and overall response rate ( ORR ) in comparison to PLD alone in patients with relapsed ovarian cancer ( J Clin Oncol ; 2010 28:3107 - 14 ) . Here we report the impact of the treatment combination on patient-reported functional status and symptoms . METHODS Patient-reported outcome ( PRO ) question naires , EORTC-QLQ C30 , OV28 , and EQ-5D were completed by patients at screening and on Day 1 of every other treatment cycle starting with Cycle 1 , and at the end-of-treatment visit . RESULTS Of the 672 patients r and omized in this study , 663 treated patients completed at least one of the baseline question naires . Median cycles of treatment was 6 ( 131 days ) for the combination arm and 5 ( 143 days ) for the monotherapy arm . Longitudinal data analyses showed no significant differences between the treatment arms for any of the pre-specified scales . Similar analyses of other scales , including Health Index scores and Health State on the Visual Analog Scale , support these findings . Start of subsequent therapy was significantly delayed in the combination arm compared with the monotherapy arm ( p=0.0032 ) . CONCLUSIONS The addition of trabectedin to PLD led to little or no decrement in patient-reported functional status and symptoms in patients with relapsed ovarian cancer , as compared to treatment with PLD alone . The combination led to manageable and non-cumulative overall toxicity with a fewer PLD-associated adverse events , and a significant improvement in PFS and ORR compared to single agent Introduction There is an increasing number of new oncology drugs being studied , approved and put into clinical practice based on improvement in progression-free survival , when no overall survival benefits exist . In oncology , the association between progression-free survival and health-related quality of life is currently unknown , despite its importance for patients with cancer , and the unverified assumption that longer progression-free survival indicates improved health-related quality of life . Thus far , only 1 study has investigated this association , providing insufficient evidence and inconclusive results . The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology . Methods and analysis Using the OVID platform in MEDLINE , Embase and Cochrane data bases , we will conduct a systematic review of r and omised controlled human trials addressing oncology issues published starting in 2000 . A team of review ers will , in pairs , independently screen and abstract data using st and ardised , pilot-tested forms . We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life , along with total related error estimates , and a 95 % CI around incremental area . To describe the progression-free survival to health-related quality of life association , we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival . To estimate the association , we will use a weighted simple regression approach , comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR , in the absence of overall survival benefit . Discussion Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically important in interpreting results of oncology trials . Systematic evidence produced from our study will contribute to improvement of patient care and practice of evidence -based medicine in oncology BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer PURPOSE This phase III study ( V-15 - 32 ) compared gefitinib ( 250 mg/d ) with docetaxel ( 60 mg/m(2 ) ) in patients ( N = 489 ) with advanced/metastatic non-small-cell lung cancer ( NSCLC ) who had failed one or two chemotherapy regimens . METHODS The primary objective was to compare overall survival to demonstrate noninferiority for gefitinib relative to docetaxel . An unadjusted Cox regression model was used for the primary analysis . RESULTS Noninferiority in overall survival was not achieved ( hazard ratio [ HR ] , 1.12 ; 95.24 % CI , 0.89 to 1.40 ) according to the predefined criterion ( upper CI limit for HR < or= 1.25 ) ; however , no significant difference in overall survival ( P = .330 ) was apparent between treatments . Post study , 36 % of gefitinib-treated patients received subsequent docetaxel , and 53 % of docetaxel-treated patients received subsequent gefitinib . Gefitinib significantly improved objective response rate and quality of life versus docetaxel ; progression-free survival , disease control rates , and symptom improvement were similar for the two treatments . Grade s 3 to 4 adverse events occurred in 40.6 % ( gefitinib ) and 81.6 % ( docetaxel ) of patients . Incidence of interstitial lung disease was 5.7 % ( gefitinib ) and 2.9 % ( docetaxel ) . Four deaths occurred due to adverse events in the gefitinib arm ( three deaths as a result of interstitial lung disease , judged to be treatment related ; one as a result of pneumonia , not treatment related ) , and none occurred in the docetaxel arm . CONCLUSION Noninferiority in overall survival between gefitinib and docetaxel was not demonstrated according to predefined criteria ; however , there was no statistically significant difference in overall survival . Secondary end points showed similar or superior efficacy for gefitinib compared with docetaxel . Gefitinib remains an effective treatment option for previously treated Japanese patients with NSCLC OBJECTIVES A phase II clinical trial compared docetaxel in combination with carboplatin to sequential single agent docetaxel followed by carboplatin for treatment of recurrent platinum-sensitive ovarian , peritoneal , or tubal cancer . This manuscript reports prospect ively collected health-related quality of life ( HRQL ) . METHODS Participants were r and omized to either weekly docetaxel 30 mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks ( cDC ) or docetaxel 30 mg/m(2)/days 1 and 8 , repeated every 3 weeks for 6 cycles followed by carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression ( sDC ) . The primary HRQL endpoint was the trial outcome index ( TOI ) score of the Functional Assessment of Cancer Therapy-Ovarian ( FACT-O ) instrument , and was assessed as an intent-to-treat analysis . The secondary HRQL endpoints included the FACT-O total score , the FACT-General , and several domain scores of the FACT-O instrument ( physical well-being ( PWB ) , social/family well-being ( SWB ) , emotional well-being ( EWB ) , functional well-being ( FWB ) , and the ovarian cancer specific ( OCS ) module ) . The FACT-O was administered at r and omization , prior to each of 6 cycles of treatment , and at study endpoint . RESULTS One hundred forty-eight participants were r and omized to each group . Sequential docetaxel followed by carboplatin ( sDC ) was associated with significant improvements in the FACT-O TOI ( p=0.013 ) , FACT-O total score ( p=0.033 ) , and OCS ( p=0.029 ) compared to the combination docetaxel and carboplatin group ( cDC ) . CONCLUSIONS Sequential single agent docetaxel followed by carboplatin is associated with improved HRQL when compared to cDC . The improved progression-free survival observed with cDC should be weighed against lower quality of life during treatment BACKGROUND Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma . This double-blind , multicenter , r and omized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance ( MPR-R ) with melphalan-prednisone-lenalidomide ( MPR ) or melphalan-prednisone ( MP ) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma . METHODS We r and omly assigned patients who were ineligible for transplantation to receive MPR-R ( nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [ 152 patients ] ) or to receive MPR ( 153 patients ) or MP ( 154 patients ) without maintenance therapy . The primary end point was progression-free survival . RESULTS The median follow-up period was 30 months . The median progression-free survival was significantly longer with MPR-R ( 31 months ) than with MPR ( 14 months ; hazard ratio , 0.49 ; P<0.001 ) or MP ( 13 months ; hazard ratio , 0.40 ; P<0.001 ) . Response rates were superior with MPR-R and MPR ( 77 % and 68 % , respectively , vs. 50 % with MP ; P<0.001 and P=0.002 , respectively , for the comparison with MP ) . The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age ( P=0.001 for treatment-by-age interaction ) . After induction therapy , a l and mark analysis showed a 66 % reduction in the rate of progression with MPR-R ( hazard ratio for the comparison with MPR , 0.34 ; P<0.001 ) that was age-independent . During induction therapy , the most frequent adverse events were hematologic ; grade 4 neutropenia was reported in 35 % , 32 % , and 8 % of the patients in the MPR-R , MPR , and MP groups , respectively . The 3-year rate of second primary tumors was 7 % with MPR-R , 7 % with MPR , and 3 % with MP . CONCLUSIONS MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation , with the greatest benefit observed in patients 65 to 75 years of age . ( Funded by Celgene ; MM-015 Clinical Trials.gov number , NCT00405756 . ) PURPOSE Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies . Pre clinical and early clinical evidence has supported targeting the epidermal growth factor receptor ( EGFR ) signaling pathway in patients with pancreas cancer . This trial was conducted to evaluate the contribution of an EGFR-targeted agent to st and ard gemcitabine therapy . Cetuximab is a monoclonal antibody against the lig and -binding domain of the receptor . PATIENTS AND METHODS Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were r and omly assigned to receive gemcitabine alone or gemcitabine plus cetuximab . The primary end point was overall survival . Secondary end points included progression-free survival , time to treatment failure , objective response , and toxicity . RESULTS A total of 745 eligible patients were accrued . No significant difference was seen between the two arms of the study with respect to the median survival time ( 6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm ; hazard ratio = 1.06 ; 95 % CI , 0.91 to 1.23 ; P = .23 , one-sided ) . Objective responses and progression-free survival were similar in both arms of the study . Although time to treatment failure was longer in patients on gemcitabine plus cetuximab ( P = .006 ) , the difference in length of treatment was only 2 weeks longer in the combination arm . Among patients who were studied for tumoral EGFR expression , 90 % were positive , with no treatment benefit detected in this patient subset . CONCLUSION In patients with advanced pancreas cancer , the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone . Alternate targets other than EGFR should be evaluated for new drug development OBJECTIVES The Gynecologic Oncology Group ( GOG ) compared methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) with topotecan and cisplatin ( TC ) or cisplatin alone ( C ) in advanced cervical cancer . The primary endpoint was overall survival ( OS ) , with response rate , progression-free survival ( PFS ) , and quality of life ( QOL ) as secondary objectives . METHODS Eligible patients were r and omly allocated to receive either cisplatin 50 mg/m2 q 3 weeks ( C ) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1 - 3 q 3 weeks ( TC ) or methotrexate 30 mg/m2 days 1 , 15 , and 22 , vinblastine 3 mg/m2 days 2 , 15 , and 22 , doxorubicin 30 mg/m2 day 2 , and cisplatin 70 mg/m2 day 2 q 4 weeks ( MVAC ) . QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix ( FACT-Cx ) , Neurotoxicity Subscale ( FACT/GOG-NTX subscale ) , and Brief Pain Inventory ( BPI ) . RESULTS One hundred eighty-six patients ( C = 60 ; TC = 63 ; MVAC = 63 ) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm . MVAC produced a 22 % overall response rate ( 95 % CI : 0.13 to 0.34 ) and median PFS and OS of 4.4 months and 9.4 months , respectively . Compared with C and TC , there was more hematologic toxicity with MVAC . There were no appreciable differences in QOL scores after controlling for baseline scores . CONCLUSIONS MVAC 's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule . Nevertheless , QOL , as measured by these instruments , was not substantially impaired by this regimen Gefitinib was compared with pemetrexed as second‐line therapy in a clinical ly selected population previously treated with platinum‐based chemotherapy Purpose Lapatinib is a small molecule , dual tyrosine kinase inhibitor of epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor type 2 ( HER2 ) . Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab . Up date d efficacy and initial biomarker results from this trial are reported . Methods Women with HER2-positive , locally advanced or metastatic breast cancer previously treated with anthracycline- , taxane- , and trastuzumab-containing regimens were r and omized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule . The primary endpoint was time to progression ( TTP ) as determined by an independent review panel . Relationship between progression-free survival ( PFS ) and tumor HER2 expression and serum levels of HER2 extracellular domain ( ECD ) were assessed . Results 399 women were r and omized . The addition of lapatinib prolonged TTP with a hazard ratio ( HR ) of 0.57 ( 95 % CI , 0.43–0.77 ; P < 0.001 ) and provided a trend toward improved overall survival ( HR : 0.78 , 95 % CI : 0.55–1.12 , P = 0.177 ) , and fewer cases with CNS involvement at first progression ( 4 vs. 13 , P = 0.045 ) . Baseline serum HER2 ECD did not predict for benefit from lapatinib . Conclusion The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive , advanced breast cancer progressing after treatment with anthracycline- , taxane- , and trastuzumab-based therapy . Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine BACKGROUND & AIMS The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure ( progression , death , stop of study treatment ) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut ( mainly pancreatic ) and midgut tumors . METHODS One hundred nine of 125 registered patients were r and omized starting in January 1995 , and 105 patients ( 51 monotherapy , 54 combination treatment ) were finally analyzed in March 2000 . Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging . Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not r and omized because of stable disease . RESULTS Partial tumor regression occurred in 2.9 % , 1.9 % , and 5.7 % and stabilization of tumor growth in 44.8 % , 27.6 % , and 15.2 % at 3 , 6 , and 12 months , respectively , with no significant differences between both treatment arms . In March 2000 , 9.5 % of patients were in treatment . Time to treatment failure and long-term survival did not differ significantly between the 2 groups , with a median survival of 32 and 54 months for the octreotide and the combination groups , respectively . Survival was longer in patients not r and omized because of stable disease ( median , 68 months ) and in those with low nuclear Ki-67 . A trend toward longer survival was shown for patients with slow spontaneous tumor growth before r and omization . Patients responding to treatment lived longer than unresponsive patients . CONCLUSIONS Combination treatment was not superior to monotherapy concerning progression-free and long-term survival . Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions BACKGROUND We evaluated the feasibility and tolerability of triple- versus double-drug chemotherapy in elderly patients with oesophagogastric cancer . METHODS Patients aged 65 years or older with locally advanced or metastatic oesophagogastric cancer were stratified and r and omised to infusional 5-FU , leucovorin and oxaliplatin without ( FLO ) or with docetaxel 50 mg/m(2 ) ( FLOT ) every 2 weeks . The study is registered at Clinical Trials.gov , identifier NCT00737373 . FINDINGS One hundred and forty three ( FLO , 71 ; FLOT , 72 ) patients with a median age of 70 years were enrolled . The triple combination was associated with more treatment-related National Cancer Institute Common Toxicity Criteria ( NCI-CTC ) grade 3/4 adverse events ( FLOT , 81.9 % ; FLO , 38.6 % ; P<.001 ) and more patients experiencing a ≥10-points deterioration of European Organization for Research and Treatment of Cancer Quality of Life ( EORTC QoL ) global health status scores ( FLOT , 47.5 % ; FLO 20.5 % ; p=.011 ) . The triple combination was associated with more alopecia ( P<.001 ) , neutropenia ( P<.001 ) , leukopenia ( P<.001 ) , diarrhoea ( P=.006 ) and nausea ( P=.029 ) . ) . No differences were observed in treatment duration and discontinuation due to toxicity , cumulative doses or toxic deaths between arms . The triple combination improved response rates and progression-free survival in the locally advanced subgroup and in the subgroup of patients aged between 65 and 70 years but not in the metastatic group or in patients aged 70 years and older . INTERPRETATION The triple-drug chemotherapy was feasible in elderly patients with oesophagogastric cancer . However , toxicity was significantly increased and QoL deteriorated in a relevant proportion of patients . FUNDING The study was partially funded by Sanofi-Aventis Support for prospect i ve registration of protocol s for systematic review s has been gathering momentum . The PRISMA statement , a guideline for reporting systematic review s and meta-analyses of studies that evaluate health-care interventions , advocates registration . Well-conducted systematic review s are accepted as the best- quality evidence to inform policy and practice , and the dramatic upward trend in the number of systematic review s published annually ( fi gure ) is set to continue . However , there is currently no single facility for identifying this type of research in advance of the appearance of the results of the review . There is concern about and evidence of publication and selective outcome -reporting biases associated with systematic review s. An open registry of review s captured at the protocol stage would facilitate good practice in systematic review s by providing transparency of the review process and outcomes . Discrepancies between the methods of the published review and those planned in the registered protocol could be more readily identifi ed . Registration might also encourage full publication of the review ’s fi ndings and transparency in changes to methods that could bias fi ndings . In both the prevention and revelation of potential bias , registration should improve quality and increase confi dence that policy or practice informed by the fi ndings of systematic review s are indeed drawing on best- quality evidence . A registry of protocol s of systematic review s could assist those planning new review s and updating existing ones . Easy access to information about ongoing review s should help to optimise the use of fi nite re sources by enabling funding and commissioning agencies to avoid unnecessary duplication and encourage collaboration . A comprehensive registry could also create opportunities for method ological and other research , both within and across disciplines . Existing access to systematic - review protocol s is limited to the outputs of individual organisations , such as the Cochrane and Campbell Collaborations and the Joanna Briggs Institute . The National Public Health Service for Wales is piloting an All Wales Systematic Review s Register , but , up to now , there has been no central ised comprehensive registry of systematic - review protocol s. We are developing an international facility to register the details of ongoing systematic review s in health and social care . Our registry is being established with the existing platform and infrastructure that supports the Data base of Abstract s of Review s of Eff ects ( DARE ) , the NHS Economic Evaluations Data base ( NHS EED ) and the Health Technology Assessment ( HTA ) data base produced by the Centre for Review s and Dissemination . The initial scope of the registry will be limited to systematic review s of the eff ectiveness of health interventions . However , the longterm aim is for the registry to include details of all ongoing systematic review s with a health-related outcome in the broadest sense . Ultimately , inclusion will encompass systematic review s of health-care interventions , and review s of the social determinants of health , of service delivery , and of risk factors and genetic associations . Our web-based registry will off er free public access , be electronically search able , and open to all prospect i ve registrants . Registration will require the provision of a minimum data set , the completeness of which will be checked automatically before registration . After acceptance , the registry ’s entry and protocol for the review , if available , will be loaded on the data base as a permanent entry and a unique identifi cation number issued . An audit trail for any amendments to the information will be available within the record . Links to result ing publications will be added . These provisions ensure that the registry will match the relevant criteria required of clinical trials registries OBJECTIVE To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin ( TC ) and TC combined with endostar in the treatment of advanced non-small cell lung cancer ( NSCLC ) . METHODS This is a prospect i ve , multicenter , r and omized , double-blind , placebo-controlled clinical study . A total of 126 cases of untreated advanced NSCLC were enrolled in this study . There were 63 patients in the TC control arm and TC combined endostar arm , respectively . All enrolled patients were continuously followed-up for disease progression and death . RESULTS The objective response rate ( ORR ) of TC combined with endostar arm was 39.3 % , and that of TC control arm was 23.0 % , P = 0.078 . The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3 % and 58.8 % , respectively , in 24 weeks ( P = 0.017 ) . The hazard ratio for the risk of disease progression was 0.35 ( 95%CI 0.13 to 0.90 , P = 0.030 ) . The median time to progression ( TTP ) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months ( P > 0.05 ) . The follow-up results showed that the median survival time ( mOS ) of the TC + Endostar arm was 17.6 months ; ( 95%CI 13.4 to 21.7 months ) , and the TC + placebo arm 15.8 months ( 95%CI 9.4 to 22.9 months ) ( P > 0.05 ) . The quality of life scores ( LCSS patient scale ) after treatment of the TC combined with endostar arm was improved , and that of the TC group was improved after completion of two cycles and three cycles of treatment . The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm ( P = 0.028 and ) , and TC arm ( P = 0.036 ) . It Indicated that TC combined with endostar treatment improved the patient 's quality of life in the early treatment . The difference of adverse and serious adverse event rates between the two groups was not significant ( P > 0.05 ) . CONCLUSIONS Compared with TC alone treatmrnt , TC combined with endostar treatment can reduce the risk of disease progression at early time ( 24 weeks ) , increase the ORR , and can be used as first-line treatment for advanced NSCLC . The TC combined with endostar treatment has good safety and tolerability , improves the quality of life , and not increases serious adverse effects and toxicity for patients with advanced NSCLC BACKGROUND In a double-blind , r and omised phase III trial of advanced renal cell carcinoma patients , pazopanib 800 mg QD ( n=290 ) versus placebo ( n=145 ) significantly prolonged progression-free survival ( hazard ratio (HR)=0.46 , 95 % confidence interval [ CI ] 0.34 - 0.62 , p-value<0.0001 ) , without important differences in health-related quality of life ( HRQoL ) . This post-hoc analysis evaluated time to HRQoL deterioration and whether tumour response/stabilisation was associated with HRQoL improvement . METHODS HRQoL was assessed using EORTC QLQ-C30 and EQ-5D . Effect of pazopanib on time to ⩾20 % decline from baseline in summary scores was estimated for all patients and by prior treatment . Analyses were conducted for different HRQoL deterioration thresholds . HRQoL changes were stratified by benefit and compared : complete response ( CR ) or partial response ( PR ) versus progressive disease ( PD ) ; CR/PR versus stable disease ( SD ) , and SD versus PD . RESULTS There was a trend for pazopanib patients to be less likely than placebo patients to experience ⩾20 % HRQoL deterioration in EORTC-QLQ-C-30 global health status/QOL scale ( HR=0.77 ; 95 % CI 0.57 - 1.03 , not significant ) . Results by prior treatment and different HRQoL deterioration thresholds were similar . Patients with CR/PR and SD experienced significantly less HRQoL deterioration than those with PD ( p<0.001 , p=0.0024 , respectively ) ; mean differences between patients with CR/PR and PD exceeded the pre-determined minimally important difference ( MID ) . Differences between patients with SD and PD did not exceed pre-determined MID . Results were generally consistent across treatment and EQ-5D summary scores . CONCLUSION Results support the favourable benefit-risk profile of pazopanib and suggest patients experiencing tumour response/stabilisation also may have better HRQoL compared to those without this response PURPOSE To compare fotemustine and dacarbazine ( DTIC ) in terms of overall response rate ( ORR ) as primary end-point and overall survival , duration of responses , time to progression , time to occurrence of brain metastases ( BM ) , and to assess safety and quality of life in patients with disseminated cutaneous melanoma . PATIENTS AND METHODS Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks ( two cycles ) . Nonprogressive patients received a maintenance treatment every 4 weeks ( fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days ) . RESULTS Two hundred twenty-nine patients were r and omly assigned to fotemustine or DTIC arms . The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population ( n=229 ; 15.2 % v 6.8 % ; P=.043 ) and in full analysis set ( n=221 ) ( 15.5 % v 7.2 % ; P=.053 ) . Similar median duration s of responses ( 5.8 months with fotemustine v 6.9 months with DTIC ) and time to progression ( 1.8 v 1.9 months , respectively ) were observed . In patients without BM at inclusion , the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC ( P=.059 ) . Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC ( P=.067 ) . The main toxicity was grade 3 to 4 neutropenia ( 51 % with fotemustine v 5 % with DTIC ) and thrombocytopenia ( 43 % v 6 % , respectively ) . No significant difference was noted for quality of life between arms . CONCLUSION ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma . A trend in favor of fotemustine in terms of overall survival and time to BM was evidence The last few years have seen an increase in the number of r and omized controlled trials ( RCTs ) of new agents in metastatic solid tumors using progression-free survival ( PFS ) as the primary end point . Some trials showing improvement in PFS , without a correspondingincreaseinoverallsurvival(OS),haveledtoapprovalofnew drugs and /or changes in st and ard of care . This suggests a growing belief in the oncology community that delaying progression in metastaticdiseaseisaworthy goal , evenifOSisnotimproved . Butisanew treatment that improves PFS really an advance for patients ? Or is it only lowering the bar to declare active some of our much-heralded new molecular targeted therapies ? We believe that as a community , this trend requires discussion and debate PURPOSE To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent . PATIENTS AND METHODS Patients were r and omized with equal probability to receive low- , intermediate- , or high-dose suramin ( total doses 3.192 , 5.320 , and 7.661 g/m(2 ) , respectively ) . Overall survival , time to progression , and response rate ( prostate-specific antigen [ PSA ] and objective ) for each treatment arm were compared . Relationships between plasma suramin concentrations and response , toxicity , and survival were also evaluated . RESULTS Three hundred ninety patients were r and omized . For the low- , intermediate- , and high-dose arms , the median survival time was 16 , 14 , and 13 months , respectively ( P = .49 ) . The objective response rate was 9 % , 7 % , and 15 % , respectively ( P = .10 ) . PSA response rates were 24 % , 28 % , and 34 % , respectively ( P = .082 ) . L and mark analyses of a 50 % decline in PSA at 20 weeks showed a significant correlation with survival . There was a dose-response relationship between dose and toxicity . After adjusting for treatment arm , the measured suramin concentration was not associated with clinical response , PSA response , survival , or toxicity . CONCLUSION Although high-dose suramin was associated with higher objective and PSA response rates , these were not statistically significant . Overall , no dose-response relationship was observed for survival or progression-free survival , but toxicity was increased with the higher dose . Patients treated with the low-dose level experienced modest toxicity , making it the preferred arm on this study . The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin , particularly high-dose suramin , as administered on this schedule BACKGROUND Dose-intensive chemotherapy has generated much interest in the treatment of patients with locally advanced breast cancer because it might offer a survival benefit . We aim ed to compare the effects of such an approach with those of st and ard chemotherapy on health-related quality of life ( HRQOL ) . METHODS 224 patients with locally advanced breast cancer were r and omly assigned to 75 mg/m(2 ) cyclophosphamide given orally on days 1 - 14 , and 60 mg/m(2 ) epirubicin and 500 mg/m(2 ) fluorouracil both given intravenously on days 1 and 8 , for six cycles every 28 days ( 6 months ' treatment ; st and ard treatment ) and 224 patients to 830 mg/m(2 ) cyclophosphamide and 120 mg/m(2 ) epirubicin both given intravenously on day 1 , and 5 microg/kg filgrastim per day given subcutaneously on days 2 - 13 , for six cycles every 14 days ( 3 months ' treatment ; dose-intensive treatment ) . HRQOL was assessed by use of the European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ( EORTC QLQ-C30 ) . Baseline assessment s were done before r and omisation ; then once a month for the first 3 months ; and at months 6 , 9 , 12 , 18 , 26 , 34 , 42 , 48 , and 54 . The primary endpoint was progression-free survival ; secondary endpoints were HRQOL , response , safety , overall response , and health economics . Analyses were by intention to treat . FINDINGS Previously reported data showed that groups did not differ in progression-free survival . Patients assigned shorter , intensified treatment had a significantly lower overall HRQOL score during the first 3 months than did those assigned st and ard treatment ( mean score at 3 months 41.8 [ SD 1.78 ] vs 49.6 [ 1.64 ] , p=0.0015 ) . However , scores returned to near baseline , with no difference between groups , at 12 months ( 62.6 [ 1.97 ] vs 65.6 [ 2.04 ] , p=0.3007 ) . Over the remaining 2 years , the groups showed few significant differences in HRQOL . INTERPRETATION Dose-intensive treatment only has a temporary effect on HRQOL , thus enabling more research on intensive treatment for patients with locally advanced breast cancer PURPOSE S0205 was a r and omized clinical trial that compared the therapeutic impact of gemcitabine versus gemcitabine plus cetuximab . Study results for patient-reported health-related quality of life ( HRQL ) outcomes are reported . PATIENTS AND METHODS Patients completed the Brief Pain Inventory and a measure of emotional well-being ( each measured on a 0 to 10 scale ) at baseline and at weeks 5 , 9 , 13 , and 17 postr and om assignment . Worst pain status was classified as palliated ( worst pain scores < 5 maintained for 2 consecutive cycles ) or not palliated ( remaining patients ) and tested with a chi(2 ) test . Change in emotional well-being and worst pain ( exploratory analysis ) were assessed over 17 weeks using generalized estimating equations with inverse probability of censoring weights . RESULTS Seven hundred twenty of 766 enrolled patients contributed baseline HRQL data . The two treatment arms did not differ statistically in the percentage of patients with successful worst pain palliation . Longitudinal analyses showed significantly improved emotional well-being for patients on both arms by weeks 13 and 17 ( P < .01 and P < .001 ) . An exploratory longitudinal analysis of worst pain showed significant decreases at all time points for both arms ( P < .01 and P < .001 ) . Significant treatment arm differences for either worst pain or emotional well-being were not observed at any of the assessment times . CONCLUSION We observed palliated pain and improved well-being for patients on this trial . However , these improvements were similar in both treatment arms , suggesting that the addition of cetuximab did not contribute to improvement in these HRQL outcomes Key Points Question Does the treatment effect size differ between overall survival and progression-free survival for PD-1 ( programmed cell death 1 ) inhibitors used in patients with advanced solid tumors , and are overall survival and progression-free survival correlated ? Findings This meta- analysis of 12 r and omized clinical trials found no significant correlation between overall survival and progression-free survival in terms of medians and gains in medians , but their hazard ratios were significantly correlated . The protective effects of treatment were greater for overall survival than for progression-free survival . Meaning Progression-free survival can not adequately capture the benefit of PD-1 inhibitors ; thus , overall survival should remain the gold st and ard end point for trials of PD-1 inhibitors PURPOSE To assess the differences in health-related quality of life ( HRQL ) of 4 cisplatin containing doublet chemotherapy combinations in women with advanced/recurrent cervical carcinoma . METHODS Patients were r and omized to three-week cycles of paclitaxel + cisplatin ( PC ) ; vinorelbine + C ( VC ) ; gemcitabine + C ( GC ) ; or topotecan + C ( TC ) . We report HRQL results from data available on 434 eligible patients enrolled into this 513 patient trial . HRQL was assessed with the Functional Assessment of Cancer Therapy-Cervix ( FACT-Cx ) the FACT/Gynecologic Oncology Group ( FACT/GOG ) four-item neurotoxicity scale , and the 0 - 10 " worst pain " item from the Brief Pain Inventory , at baseline ( pre-treatment ) , prior to beginning cycle 2 , prior to beginning cycle 5 , and at 9 months after enrollment . As reported by Monk et al. ( 2009 ) [ 13 ] VC , GC and TC were found not to be superior to PC with regard to progression-free survival or overall survival . RESULTS The trial was terminated early due to planned interim futility analysis , reducing power for HRQL analysis from 85 % to 55 % . Patients receiving VC , GC and TC doublets did not report significantly different HRQL , neuropathy , or pain from those who received the PC ( control ) doublet . Patients receiving PC tended to report worse neuropathy during treatment than patients who received other doublets ( especially GC and TC ) , but the differences were not statistically significant . CONCLUSION None of the 3 experimental doublets was different from PC in terms of HRQL during treatment . Long-term toxicity data are inconclusive . Except where patients may wish to reduce their risk of worsening pre-treatment neuropathy , PC remains the st and ard of care for this disease BACKGROUND This report describes quality of life ( QoL ) findings of a r and omized study comparing gefitinib with docetaxel in patients with advanced/metastatic pretreated non-small-cell lung cancer . PATIENTS AND METHODS This open-label , phase III study r and omized 490 Japanese patients to gefitinib ( 250 mg/day ) or docetaxel ( 60 mg/m(2)/3 weeks ) , with survival as the primary outcome . Preplanned QoL analyses included Functional Assessment of Cancer Therapy-Lung ( FACT-L ) , Trial Outcome Index ( TOI ) and Lung Cancer Subscale ( LCS ) improvement rates , and mean change from baseline . RESULTS Gefitinib showed statistically significant benefits over docetaxel in QoL improvement rates ( FACT-L 23 % versus 14 % , P = 0.023 ; TOI 21 % versus 9 % , P = 0.002 ) and mean change from baseline score [ mean treatment difference : FACT-L 3.72 points , 95 % confidence interval ( CI ) 0.55 - 6.89 , P = 0.022 ; TOI 4.31 points , 95 % CI 2.13 - 6.49 , P < 0.001 ] , although differences did not meet the clinical ly relevant six-point change . There were no significant differences between treatments in LCS improvement rates ( 23 % versus 20 % , P = 0.562 ) or mean change from baseline score ( 0.63 points , 95 % CI -0.07 to 1.34 , P = 0.077 ) . CONCLUSIONS Gefitinib improved aspects of QoL over docetaxel , with superior objective response rate and a more favorable tolerability profile and no statistically significant difference in overall survival ( although noninferiority was not statistically proven ) The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life . Patients ( n=459 ) with newly diagnosed multiple myeloma aged 65 years or over were r and omized 1:1:1 to nine 4-week cycles of lenalidomide , melphalan , and prednisone , followed by lenalidomide maintenance ; or lenalidomide , melphalan , and prednisone , or melphalan and prednisone , with no maintenance therapy . Patients completed health-related quality of life question naires at baseline , after every third treatment cycle , and at treatment end . Health-related quality of life improved in all treatment groups during induction therapy . Patients receiving lenalidomide maintenance had the most pronounced improvements , Global Health Status/ Quality of Life ( P<0.05 ) , Physical Functioning ( P<0.01 ) , and Side Effects of Treatment ( P<0.05 ) out of 6 pre-selected health-related quality of life domains . More patients receiving lenalidomide maintenance achieved minimal important differences ( P<0.05 for Physical Functioning ) . Therefore , lenalidomide , melphalan , and prednisone , followed by lenalidomide maintenance , improves health-related quality of life in patients with newly diagnosed multiple myeloma . ( Clinical trials.gov identifier NCT00405756 ) |
12,609 | 25,027,410 | The applicants challenged a government decision to offer Nevirapine in a few pilot sites when evidence showed Nevirapine significantly reduced HIV transmission rates and despite donor offers of a free supply . | Following the South African case , Treatment Action Campaign and Others v Minister of Health and Others , the use of ' pilot ’ studies to investigate interventions already proven efficacious , offered free of charge to government , but confined by the government to a small part of the population , may violate children ’s right to health , and the negative duty on governments not to prevent access to treatment .
Cluster r and omized trials involving children are increasingly popular , and are often used to reduce ' contamination ’ : the possibility that members of a cluster adopt behavior of other clusters . | Abstract Objective To compare the effect on prevalence of diarrhoea and mortality of household based treatment of drinking water with flocculant-disinfectant , sodium hypochlorite , and st and ard practice s in areas with turbid water source in Africa . Design Cluster r and omised controlled trial over 20 weeks . Setting Family compounds , each containing several houses , in rural western Kenya . Participants 6650 people in 605 family compounds . Intervention Water treatment : flocculant-disinfectant , sodium hypochlorite , and usual practice ( control ) . Main outcome measures Prevalence of diarrhoea and all cause mortality . Escherichia coli concentration , free residual chlorine concentration , and turbidity in household drinking water as surrogates for effectiveness of water treatment . Results In children < 2 years old , compared with those in the control compounds , the absolute difference in prevalence of diarrhoea was –25 % in the flocculant-disinfectant arm ( 95 % confidence interval –40 to –5 ) and –17 % in the sodium hypochlorite arm ( –34 to 4 ) . In all age groups compared with control , the absolute difference in prevalence was –19 % in the flocculant-disinfectant arm ( –34 to –2 ) and –26 % in the sodium hypochlorite arm ( –39 to –9 ) . There were significantly fewer deaths in the intervention compounds than in the control compounds ( relative risk of death 0.58 , P = 0.036 ) . Fourteen per cent of water sample s from control compounds had E coli concentrations < 1 CFU/100 ml compared with 82 % in flocculant-disinfectant and 78 % in sodium hypochlorite compounds . The mean turbidity of drinking water was 8 nephelometric turbidity units ( NTU ) in flocculant-disinfectant households , compared with 55 NTU in the two other compounds ( P < 0.001 ) . Conclusions In areas of turbid water , flocculant-disinfectant was associated with a significant reduction in diarrhoea among children < 2 years . This health benefit , combined with a significant reduction in turbidity , suggests that the flocculant-disinfectant is well suited to areas with highly contaminated and turbid water Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement Background Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement . However , there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality . This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya . Design A factorial , cluster r and omised trial is being implemented in 101 government primary schools on the coast of Kenya . The interventions are ( i ) intermittent screening and treatment of malaria in schools by public health workers and ( ii ) training workshops and support for teachers to promote explicit and systematic literacy instruction . Schools are r and omised to one of four groups : receiving either ( i ) the malaria intervention alone ; ( ii ) the literacy intervention alone ; ( iii ) both interventions combined ; or ( iv ) control group where neither intervention is implemented . Children from classes 1 and 5 are r and omly selected and followed up for 24 months . The primary outcomes are educational achievement and anaemia , the hypothesised mediating variables through which education is affected . Secondary outcomes include malaria parasitaemia , school attendance and school performance . A nested process evaluation , using semi-structured interviews , focus group discussion and a stakeholder analysis will investigate the community acceptability , feasibility and cost-effectiveness of the interventions . Discussion Across Africa , governments are committed to improve health and education of school-aged children , but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy . This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement . Reflection is made on the practical issues encountered in conducting research in schools in Africa . Trial Registration National Institutes of Health Abstract The cluster r and omized trial ( CRT ) is used increasingly in knowledge translation research , quality improvement research , community based intervention studies , public health research , and research in developing countries . However , cluster trials raise difficult ethical issues that challenge research ers , research ethics committees , regulators , and sponsors as they seek to fulfill responsibly their respective roles . Our project will provide a systematic analysis of the ethics of cluster trials . Here we have outlined a series of six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation:1.Who is a research subject?2.From whom , how , and when must informed consent be obtained?3.Does clinical equipoise apply to CRTs?4.How do we determine if the benefits outweigh the risks of CRTs?5.How ought vulnerable groups be protected in CRTs?6.Who are gatekeepers and what are their responsibilities ? Subsequent papers in this series will address each of these areas , clarifying the ethical issues at stake and , where possible , arguing for a preferred solution . Our hope is that these papers will serve as the basis for the creation of international ethical guidelines for the design and conduct of cluster r and omized trials A group-r and omized controlled trial of insecticide (permethrin)-treated bed nets ( ITNs ) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1 - 59 months of age . Child deaths were monitored over a two-year period by biannual household census in Asembo ( 1997 - 1998 ) and in Gem ( 1998 - 1999 ) . Overall , 1,722 deaths occurred in children 1 - 59 months followed for 35,932 child-years . Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1 - 59 months old . The protective efficacy ( PE ) ( 95 % confidence interval ) adjusted for age , study year , study site , and season was 16 % ( 6 - 25 % ) . Corresponding figures in 1 - 11- and 12 - 59-month-old children in control and ITN villages were 133.3 versus 102.3 , PE = 23 % ( 11 - 34 % ) and 31.1 versus 28.7 , PE = 7 % ( -6 - 19 % ) . The numbers of lives saved/1,000 child-years were 8 , 31 , and 2 for the groups 1 - 59 , 1 - 11 , and 12 - 59 months old , respectively . Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol ( every six months ) was 20 % ( 10 - 29 % ) , overall and 26 % ( 12 - 37 % ) and 14 % ( -1 - 26 % ) in 1 - 11- and 12 - 59-month-old children , respectively . ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission , but their efficacy is compromised if re-treatment is delayed beyond six months Background There are few reports of interventions to reduce the common but irrational use of antibiotics for acute non-bloody diarrhoea amongst hospitalised children in low-income setting s. We undertook a secondary analysis of data from an intervention comprising training of health workers , facilitation , supervision and face-to-face feedback , to assess whether it reduced inappropriate use of antibiotics in children with non-bloody diarrhoea and no co-morbidities requiring antibiotics , compared to a partial intervention comprising didactic training and written feedback only . This outcome was not a pre-specified end-point of the main trial . Methods Repeated cross-sectional survey data from a cluster-r and omised controlled trial of an intervention to improve management of common childhood illnesses in Kenya were used to describe the prevalence of inappropriate antibiotic use in a 7-day period in children aged 2 - 59 months with acute non-bloody diarrhoea . Logistic regression models with r and om effects for hospital were then used to identify patient and clinician level factors associated with inappropriate antibiotic use and to assess the effect of the intervention . Results 9 , 459 admission records of children were review ed for this outcome . Of these , 4 , 232 ( 44.7 % ) were diagnosed with diarrhoea , with 130 of these being bloody ( dysentery ) therefore requiring antibiotics . 1 , 160 children had non-bloody diarrhoea and no co-morbidities requiring antibiotics-these were the focus of the analysis . 750 ( 64.7 % ) of them received antibiotics inappropriately , 313 of these being in the intervention hospitals vs. 437 in the controls . The adjusted logistic regression model showed the baseline-adjusted odds of inappropriate antibiotic prescription to children admitted to the intervention hospitals was 0.30 times that in the control hospitals ( 95%CI 0.09 - 1.02 ) . Conclusion We found some evidence that the multi-faceted , sustained intervention described in this paper led to a reduction in the inappropriate use of antibiotics in treating children with non-bloody diarrhoea . Trial registration International St and ard R and omised Controlled Trial Number Register IS RCT A recent meta- analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation result ed in significantly greater hematological improvement in pregnant women . No such definitive beneficial effect was demonstrated in preschool children . We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [ hemoglobin ( Hb ) 50 - 109 g/L ] in children aged 2 - 59 mo living in a malaria-endemic area of western Kenya . The study was a cluster-r and omized trial using a factorial design ; participants were aware of the treatment assigned . All children ( n = 1049 ) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [ 3 - 6 mg/(kg.d ) ] , twice weekly supervised iron supplementation [ 6 - 12 mg/(kg.wk ) ] , daily unsupervised iron supplementation , or twice weekly unsupervised iron supplementation . In the supervised groups , Hb concentrations at 6 and 12 wk ( 6 wk postsupplementation ) were significantly higher in children given iron daily rather than twice weekly [ mean ( 95 % CI ) difference at 6-wk : 4.2 g/L ( 2.1 , 6.4 ) ; 12-wk : 4.4 g/L ( 1.8 , 7.0 ) ] . Among the unsupervised groups , Hb concentrations were not different at 6 wk [ mean ( 95 % CI ) difference : 0.86 g/L ( -1.4 , 3.1 ) ] , but significantly higher at 12 wk for those assigned daily iron [ mean ( 95 % CI ) difference : 3.4 g/L ( 0.79 , 6.0 ) , P = 0.02 ] . In this malarious area and after initial antimalarial treatment , 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children , regardless of whether adherence can be ensured OBJECTIVE To examine changes in energy intake along with markers of dietary quality ( animal- source energy and protein intakes ) among household members in the presence of supplementary school feeding in rural Kenya . DESIGN A 2-year , longitudinal , r and omized controlled feeding intervention study . SETTING Kyeni South Division , Embu District , Kenya . SUBJECTS A total of 182 schoolchildren and selected household members . RESULTS There was no evidence that schoolchildren who received supplementary snacks at school experienced reduced intakes at home or that intakes by other family members were increased at the expense of the schoolchild 's intake . CONCLUSIONS This analysis highlights a number of factors useful in planning for supplementary feeding interventions in rural Kenya and similar communities The Ottawa Ethics of Cluster Trials Consensus Group sets out 15 recommendations for the ethical design and conduct of cluster r and omized trials Summary Background Malaria is a major cause of morbidity and mortality in early childhood , yet its consequences for health and education during the school-age years remain poorly understood . We examined the effect of intermittent preventive treatment ( IPT ) in reducing anaemia and improving classroom attention and educational achievement in semi-immune schoolchildren in an area of high perennial transmission . Methods A stratified , cluster-r and omised , double-blind , placebo-controlled trial of IPT was done in 30 primary schools in western Kenya . Schools were r and omly assigned to treatment ( sulfadoxine-pyrimethamine in combination with amodiaquine or dual placebo ) by use of a computer-generated list . Children aged 5–18 years received three treatments at 4-month intervals ( IPT n=3535 , placebo n=3223 ) . The primary endpoint was the prevalence of anaemia , defined as a haemoglobin concentration below 110 g/L. This outcome was assessed through cross-sectional surveys 12 months post-intervention . Analysis was by both intention to treat , excluding children with missing data , and per protocol . This study is registered with Clinical Trials.gov , number NCT00142246 . Findings 2604 children in the IPT group and 2302 in the placebo group were included in the intention-to-treat analysis of the primary outcome ; the main reason for exclusion was loss to follow-up . Prevalence of anaemia at 12 months averaged 6·3 % in the IPT group and 12·6 % in the placebo group ( adjusted risk ratio 0·52 , 95 % CI 0·29–0·93 ; p=0·028 ) . Significant improvements were also seen in two of the class-based tests of sustained attention , with a mean increase in code transmission test score of 6·05 ( 95 % CI 2·83–9·27 ; p=0·0007 ) and counting sounds test score of 1·80 ( 0·19–3·41 ; p=0·03 ) , compared with controls . No effect was shown for inattentive or hyperactive-compulsive behaviours or on educational achievement . The per- protocol analysis yielded similar results . 23 serious adverse events were reported within 28 days of any treatment ( 19 in the IPT group and four in the placebo group ) ; the main side-effects were problems of balance , dizziness , feeling faint , nausea , and /or vomiting shortly after treatment . Interpretation IPT of malaria improves the health and cognitive ability of semi-immune schoolchildren . Effective malaria interventions could be a valuable addition to school health programmes . Funding Gates Malaria Partnership , the Norwegian Education Trust Fund and multidonor Education Development Programme Fund of the World Bank , DBL Centre for Health Research and Development , and the Wellcome Trust Philip Ayieko and colleagues report the outcomes of a cluster-r and omized trial carried out in eight Kenyan district hospitals evaluating the effects of a complex intervention involving improved training and supervision for clinicians . They found a higher performance of hospitals assigned to the complex intervention on a variety of process of care measures , as compared to those receiving the control intervention Cluster r and omized trials are increasingly used in research into health care and health services . Ethics of individual patient r and omized trials have been eluci date d in a number of different codes , but less attention has been given to the ethical issues raised by cluster r and omized trials . I assess the challenges raised by cluster r and omized controlled trials by considering three questions : What are the essential elements of ethical medical research , particularly experiments on people ? What are the features which distinguish cluster r and omized controlled trials from ordinary RCTs ? Do the distinctive features of cluster r and omized trials entail new ethical principles , or careful application of existing principles ? I conclude that cluster r and omized controlled trials raise new issues on the nature and practice of informed consent , because of the levels at which consent can be sought , and for which it can be sought . In addition , careful consideration of the principles relating to the quality of the scientific design and analysis , balance of risk and benefit , liberty to leave a trial , early stopping of a trial and the power to exclude people from potential benefits is required In a cluster r and omized trial , Beth Kangwana and colleagues find that provision of subsidized packs of the malaria therapy artemether-lumefantrine to shops more than doubled the proportion of children with fever who received drugs promptly OBJECTIVES There has been increased attention to access to water , sanitation and hygiene ( WASH ) at schools in developing countries , but a dearth of empirical studies on the impact . We conducted a cluster-r and omized trial of school-based WASH on pupil absence in Nyanza Province , Kenya , from 2007 to 2008 . METHODS Public primary schools nested in three geographical strata were r and omly assigned and allocated to one of three study arms [ water treatment and hygiene promotion ( WT & HP ) , additional sanitation improvement , or control ] to assess the effects on pupil absence at 2-year follow-up . RESULTS We found no overall effect of the intervention on absence . However , among schools in two of the geographical areas not affected by post-election violence , those that received WT and HP showed a 58 % reduction in the odds of absence for girls ( OR 0.42 , CI 0.21 - 0.85 ) . In the same strata , sanitation improvement in combination with WT and HP result ed in a comparable drop in absence , although results were marginally significant ( OR 0.47 , 0.21 - 1.05 ) . Boys were not impacted by the intervention . CONCLUSION School WASH improvements can improve school attendance for girls , and mechanisms for gendered impacts should be explored . Incomplete intervention compliance highlights the challenges of achieving consistent results across all setting Summary Background Health workers ' malaria case-management practice s often differ from national guidelines . We assessed whether text-message reminders sent to health workers ' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya . Methods From March 6 , 2009 , to May 31 , 2010 , we did a cluster-r and omised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya . With a computer-generated sequence , health facilities were r and omly allocated to either the intervention group , in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months , or the control group , in which health workers did not receive any text messages . Health workers were not masked to the intervention , although patients were unaware of whether they were in an intervention or control facility . The primary outcome was correct management with artemether-lumefantrine , defined as a dichotomous composite indicator of treatment , dispensing , and counselling tasks concordant with Kenyan national guidelines . The primary analysis was by intention to treat . The trial is registered with Current Controlled Trials , IS RCT N72328636 . Findings 119 health workers received the intervention . Case-management practice s were assessed for 2269 children who needed treatment ( 1157 in the intervention group and 1112 in the control group ) . Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points ( 95 % CI 7·6–40·0 ; p=0·004 ) immediately after intervention and by 24·5 percentage-points ( 8·1–41·0 ; p=0·003 ) 6 months later . Interpretation In re source -limited setting s , malaria control programmes should consider use of text messaging to improve health workers ' case-management practice s. Funding The Wellcome Trust Shortly after Kenya introduced artemether-lumefantrine ( AL ) for first-line treatment of uncomplicated malaria , we conducted a pre-post cluster r and omized controlled trial to assess the effect of providing malaria rapid diagnostic tests ( RDTs ) on recommended treatment ( patients with malaria prescribed AL ) and overtreatment ( patients without malaria prescribed AL ) in out patients > /= 5 years old . Sixty health facilities were r and omized to receive either RDTs plus training , guidelines , and supervision ( TGS ) or TGS alone . Of 1,540 patients included in the analysis , 7 % had uncomplicated malaria . The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points ( P = 0.04 ) , because diagnostic test use did not change ( -2%-points ) , but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing ( -36%-points ; P = 0.03 ) . Health workers generally adhered to RDT results when prescribing AL : 88 % of RDT-positive and 9 % of RDT-negative patients were treated with AL , respectively . Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs ( -12%-points , P = 0.30 ) . RDTs could potentially improve malaria case management , but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation BACKGROUND Although the efficacy of micronutrient powders [ MNPs ; eg , Sprinkles MNP ( Sprinkles Global Health Initiative ) ] in the reduction of anemia has been established , the effectiveness of these powders in real-world programs has seldom been assessed . OBJECTIVE In this study , we evaluated the effect of community-based marketing and distribution of Sprinkles MNP on childhood rates of anemia and iron and vitamin A deficiency . DESIGN In a cluster-r and omized trial in children aged 6 - 35 mo in Western Kenya , 60 villages were r and omly assigned to either intervention or control groups . Community vendors marketed and sold sachets of Sprinkles MNP in intervention villages . Biweekly household visits monitored the use of Sprinkles MNP . Hemoglobin , ferritin , retinol binding protein , malaria , and anthropometric measures were assessed at baseline ( n = 1063 ) and 12 mo of follow-up ( n = 862 ) . Data were analyzed by using an intention-to-treat analysis and generalized linear mixed models . RESULTS On average , 33 % of households in intervention villages purchased Sprinkles MNP ; the average weekly intake per child was 0.9 sachets ( ∼11.3 mg Fe and ∼328 μg vitamin A ) . Compared with control subjects , intervention children had greater improvements in hemoglobin concentrations ( increase of 0.9 compared with 0.6 g/dL , respectively ; P = 0.02 ) , iron deficiency ( decrease of 19.3 % compared with 5.3 % , respectively ; P = 0.001 ) , and vitamin A deficiency ( decrease of 7.5 % compared with an increase of 2.5 % , respectively ; P = 0.01 ) . Results adjusted for age , sex , socioeconomic status , and maternal education showed a significant association between the hemoglobin , iron , and vitamin A concentrations of children and the number of Sprinkles MNP sachets the children consumed . The prevalence of malaria , wasting , and stunting did not change significantly in either group . CONCLUSION Even with relatively low and infrequent use , Sprinkles MNP sales through community vendors were associated with decreased rates of anemia and iron and vitamin A deficiency in children in a re source -poor setting . This trial was registered at clinical trials.gov as NCT01088958 |
12,610 | 23,298,827 | CONCLUSION There is unequivocal evidence that sitting and UQMP are related in children and adolescents . | BACKGROUND Upper quadrant musculoskeletal pain ( UQMP ) is a common health problem in children and adolescents .
The upper quadrant refers to the occiput , cervical and upper thoracic spine including the clavicles and scapulae .
The current literature , which indicates that sitting , in terms of sedentary activities and sitting spinal posture , is a possible risk factor of UQMP , is controversial .
This systematic review is aim ed at ascertaining whether there is evidence for sitting as a risk factor for UQMP , and determining the different elements of sitting that are related to UQMP experienced by children and adolescents . | This study evaluated differences in sitting habits in the classroom between the project " Moving school " and a traditional school in 8-year-old children . Twenty-two children , since 1.5 years involved in the project were compared to 25 children in a traditional school . Making use of the Portable Ergonomic Observation ( PEO ) method , it was observed that children from a traditional school spend an average of 97 % of the lesson time sitting statically , from which one-third with the trunk bend over 45 degrees . In the " Moving school " this posture was replaced by dynamic sitting ( 53 % ) , st and ing ( 31 % ) and walking around ( 10 % ) , while trunk flexion over 45 degrees was nearly not observed . Children from the " Moving school " also showed significantly less neck and trunk rotation . Additionally , accelerometric data showed significantly more physical activity in lessons of the " Moving school " . Rates of self-reported back or neck pain did not differ significantly between both study groups . Results show that sitting habits are more favourable in a " Moving school " . Further research is needed to study the impact of implementing " Moving school " concepts in traditional schools on sitting habits OBJECTIVE To study the relation between neck pain and work related neck flexion , neck rotation , and sitting . METHODS A prospect i ve cohort study was performed with a follow up of 3 years among 1334 workers from 34 companies . Work related physical load was assessed by analysing objective ly measured exposure data ( video recordings ) of neck flexion , neck rotation , and sitting posture . Neck pain was assessed by a question naire . Adjustments were made for various physical factors that were related or not related to work , psychosocial factors , and individual characteristics . RESULTS A significant positive relation was found between the percentage of the working time in a sitting position and neck pain , implying an increased risk of neck pain for workers who were sitting for more than 95 % of the working time ( crude relative risk ( RR ) 2.01 , 95 % confidence interval ( 95 % CI ) 1.04 to 3.88 ; adjusted RR 2.34 , 95 % CI 1.05 to 5.21 ) . A trend for a positive relation between neck flexion and neck pain was found , suggesting an increased risk of neck pain for people working with the neck at a minimum of 20 ° of flexion for more than 70 % of the working time ( crude RR 2.01 , 95 % CI 0.98 to 4.11 ; adjusted RR 1.63 , 95 % CI 0.70 to 3.82 ) . No clear relation was found between neck rotation and neck pain . CONCLUSION Sitting at work for more than 95 % of the working time seems to be a risk factor for neck pain and there is a trend for a positive relation between neck flexion and neck pain . No clear relation was found between neck rotation and neck pain & NA ; Little is known about the epidemiology of widespread pain ( WSP ) in children and adolescents . This study aims to estimate the new‐onset and prognosis of WSP in schoolchildren and investigate factors predicting its development . A prospect i ve study was conducted among 1756 schoolchildren ( age 10–12 years ) in Southern Finl and . At baseline , information was collected on WSP , regional musculoskeletal pain symptoms , depressiveness , fatigue , sleep problems , physical activity and joint hypermobility . These children were contacted again 1 year and 4 years later to determine the outcome and the new‐onset of WSP . A total of 1282 children ( 73 % ) of the baseline study population were found at both follow‐ups . Of the children who had WSP at baseline , 31 % and 30 % reported persistence/recurrence of symptoms at 1‐ and 4‐year follow‐up , respectively . However , only 10 % of these children reported WSP at both 1 and 4 years . Of the children who were free of WSP at baseline , 18 % reported new‐onset WSP at 1‐year follow‐up and 3 % reported these symptoms at both follow‐up times . The independent baseline risk factors of WSP were older age ( OR 1.3 95 % CI 1.0–1.8 ) , female gender ( OR 1.4 , 1.1–1.9 ) , depressiveness ( OR 1.5 , 1.1–2.2 ) and regional back pain symptoms ( Neck pain : OR 1.7 , 1.1–2.4 ; Upper back pain : OR 2.1 , 1.1–4.1 ; Lower back pain : OR 3.0 , 1.6–5.7 ) . Both psychological factors and somatic pain symptoms predict future development of WSP in adolescents & NA ; The aim of this longitudinal study was to assess changes with age regarding prevalence of pain and perceived health in a student population , as well as change over time at grade level . Pain included frequency of headache , abdominal , and musculoskeletal pain and perceived health included problems sleeping and /or if they often felt tired , lonely , and sad . If gender , age ( grade level ) , stress , physically activity were related to pain and health complaints were tested with multivariate logistic regression analysis . The students ( n = 1908 ) came from r and omly selected schools throughout Sweden and attended grade s 3 , 6 and 9 ( ages 9 , 12 and 15 at the onset of the year ) in 2001 . Three years later , 67 % ( n = 1276 ) of the same students answered a question naire that was constructed for the purpose of the studies . The responses given by the same students showed that girls ’ complaints of pain and perceived health increased with age and boys decreased . Over half ( 56 % ) of the girls and two‐thirds ( 67 % ) of the boys reported no frequent complaints either year . At grade level most variables were rated the same as three years earlier by the same age group . Stress was significantly related to pain and health complaints for girls and the risk of complaints , as calculated with odds ratio , was most evident for students who were characterized as being physically inactive in 2001 and remained inactive three years later . Jointly , significant predictors , such as stress , being physically inactive , gender and grade level , explained 8–20 % of the frequent complaints Study Design . This is a 3-year prospect i ve study of juvenile low back pain ( LBP ) . Objectives . To investigate persistence and change in LBP . Summary of Background Data . Earlier episodes of LBP are a strong risk factor for LBP in adults , while the persistence of LBP through adolescence is not known . Methods . The material comprised all pupils in eighth and ninth grade s ( N = 105 , mean age 14.7 years ) , living within two geographic areas in Eastern Norway in January 1997 . The analyses included 88 adolescents at baseline , and 85 at follow-up . The question naire , which identified LBP as pain or ache in the low back during the preceding year , was answered at baseline in the classroom and at follow-up by post . Results . LBP was reported by 58 % at baseline and by 39 % at follow-up , and LBP provoked by manual work by 40 % at baseline and 26 % at follow-up . Thirty-one percent reported LBP at both occasions . LBP more than 7 days was reported by 32 % at baseline , by 26 % at follow-up , and by 18 % at both occasions . Twenty-two percent of those reporting LBP at baseline rejected ever LBP at follow-up . Baseline reports of LBP predicted corresponding reports of LBP at follow-up : Odds ratio was 4.7 ( 95 % confidence interval 1.7–12.7 ) for LBP generally , 9.1 ( 3.0–27.2 ) for LBP more than 7 days , 9.2 ( 2.9–28.8 ) for LBP provoked by manual work , and 3.8 ( 1.3–11.3 ) for LBP provoked by sitting at school . Conclusion . The findings indicate a persistent , but changeable , trend in LBP from midadolescence until late adolescence . The consistency and the high rates of reports of LBP provoked by manual work and sitting imply needs for more research on the persistence of LBP , and on relevant interventions during school age BACKGROUND School workstations are often inappropriate in not offering an optimal sitting posture . The aim of this study was to investigate the effects of individually adjustable saddle-type chairs with wheels and desks with comfort curve and arm support on schoolchildren 's working postures compared to conventional workstations . METHODS Ninety-seven participants aged 12 - 16 years were followed for 1 year , 47 at an intervention school and 50 at a control school . Anthropometrics and workstation dimensions were measured and working postures analyzed for a part of each group ( n = 21 , both groups ) by means of video recording at baseline , before new workstations were introduced , and during follow-up . RESULTS There was a significant increase in upright back ( p= .012 ) and neck ( p= .019 ) postures in the intervention group compared to controls during follow-up . The saddle-type chairs allowed significantly greater trunk-thigh angles ( p < .001 ) among participants than conventional chairs . CONCLUSIONS In schoolchildren , using individually adjustable saddle-type chairs and desks with comfort curve , a better match between workstations and anthropometric dimensions and improved working postures are obtained than using conventional workstations Study Design . A longitudinal study . Objectives . To estimate the prevalence and incidence of neck and shoulder pain in young adults and to identify the associated and predictive factors of neck and shoulder pain based on 7-year follow-up . Summary of Background Data . Several work-related , psychosocial , and sociodemographic factors have been verified as being related to neck and shoulder pain in adult population s , but far fewer longitudinal studies concerning the topic have been carried out in young population s. Methods . A r and om sample of 826 high school students was investigated when they were 15 to 18 years old and again at 22 to 25 years of age . Altogether , 394 ( 48 % ) patients participated in both surveys . The outcome variable was weekly neck and shoulder pain during the past 6 months in adulthood , and the explanatory variables included some sociodemographic factors , leisure time activities , self-assessed physical condition , psychosomatic stress symptoms , and symptoms of fatigue and sleep difficulties . Results . In 7 years , the prevalence of weekly neck and shoulder pain increased from 17 % to 28 % . Among those who were asymptomatic at baseline , 6-month incidence of occasional or weekly neck and shoulder pain was 59 % 7 years later . In an adjusted model , psychosomatic symptoms remained an associated factor for prevalent neck and shoulder pain 7 years later for both females and males . In females , neck and shoulder pain in adolescence was associated with prevalent neck and shoulder pain in adulthood , and sports loading dynamically in the upper extremities was an associated factor for a low prevalence of neck and shoulder pain 7 years later . In separate analyses of incident neck and shoulder pain , psychosomatic stress symptoms predicted neck and shoulder pain in adulthood . Conclusions . In young adults , the incidence of neck and shoulder pain is high , and the associated factors ofneck and shoulder pain are already multifactorial in a young population Prolonged sitting and psychosocial factors have been associated with musculoskeletal symptoms among adolescents . However , the impact of prolonged static sitting on musculoskeletal pain among South African high school students is uncertain . A prospect i ve observational study was performed to determine whether sitting postural alignment and psychosocial factors contribute to the development of upper quadrant musculoskeletal pain ( UQMP ) in grade ten high school students working on desktop computers . The sitting postural alignment , depression , anxiety and computer use of 104 asymptomatic students were measured at baseline . At three and six months post baseline , the prevalence of UQMP was determined . Twenty-seven students developed UQMP due to seated or computer-related activities . An extreme cervical angle ( < 34.75 degrees or > 43.95 degrees ; OR 2.8 ; 95 % CI : 1.1 - 7.3 ) and a combination of extreme cervical and thoracic angles ( < 63.1 degrees or > 71.1 degrees ; OR 2.2 ; 95 % CI : 1.1 - 5.6 ) were significant postural risk factors for the development of UQMP . Boys with any extreme angle were more likely to suffer pain compared with boys with all middle range angles ( OR 4.9 ; 95 % CI : 1.0 - 24.5 ) . No similar effect was found for girls . There was no strong relationship between depression , anxiety , computer exposure and UQMP among South African high school students |
12,611 | 17,670,446 | A greater number of drug related side-effects was observed , however , in the monoclonal group , including episodes of acute pulmonary edema and hypotension .
The increased rate of side-effects with monoclonal antibodies might suggest a superiority of polyclonal over monoclonal antibodies | Induction immunosuppression after heart transplantation is believed to reduce the risk of acute graft rejection .
While monoclonal and polyclonal antithymoglobulins are considered the optimal induction agents , controversy remains regarding their relative superiority .
This article presents a systematic review of the literature and a meta- analysis in order to assess the relative benefits and side-effects of monoclonal vs. polyclonal antithymoglobulins as induction immunosuppression agents . | Between August 1986 and December 1987 , 88 patients received either RATG or OKT3 for immunoprophylaxis before heart transplantation . By the end of the first month after transplantation , 25 % of the patients who received RATG had experienced a rejection episode compared with 43 % of those receiving OKT3 . This difference was persistent as many as 4 months after transplantation . While 50 % of the OKT3 patients had a second episode of rejection , only 35 % of the RATG patients did so . R and omization of these agents was complicated by severe cardiopulmonary side effects attributed to the first dose of OKT3 . Five hours after the first dose of OKT3 , a 25 % drop in mean arterial pressure , accompanied by significant hypoxia , was seen in a majority of patients . There was no difference in the incidence of infection between the two groups We compared an equine antithymocyte globulin (ATGAM)-based protocol with a Minnesota antilymphocyte globulin (MALG)-based protocol and a murine monoclonal CD-3 (OKT-)-based protocol in 3 groups of heart transplant ( HT ) recipients . Thirty-four recipients received a four-day course of ATGAM . Thirty HT recipients received a 14-day course of OKT3 . Fifteen HT recipients received MALG for an average of 10 days . The ATGAM group received cyclosporine beginning preoperatively , while the OKT3 and MALG groups received CyA beginning on post-transplant day 4 . All three groups received identical azathioprine and similar steroid therapy . The 3 groups were similar in age , donor/recipient HLA mismatches , and donor/recipient gender mismatches . The MALG and OKT3 groups had 20 % and 17 % females , respectively , while the ATG group had 41 % ( p < 0.05 ) . Average follow-up exceeded 14 months for each group . The ATGAM group received a higher dose of CyA during " induction " therapy than the OKT3 and MALG groups , and experienced a greater rise in post-transplant serum creatinine levels . We found no difference between the 3 groups in : preoperative creatinine levels , one-year post-transplant creatinine levels , number of patients who could be successfully " weaned " from steroids , or one-year survival . Other data are tabulated as episodes/patient : [ table : see text ] We conclude that ATG plus preoperative CyA is superior for rejection prophylaxis following heart transplantation when compared with either MALG plus postoperative CyA or OKT3 plus postoperative OKT3 is often used routinely for induction immunotherapy or selectively to avoid acute cyclosporine nephrotoxicity in heart transplant recipients at high risk for immediate postoperative kidney failure . It has not been shown in a r and omized trial to be useful in patients at low risk for early kidney failure . We r and omized 30 patients with a serum creatinine level of less than 1.4 mg/dl before heart transplantation to be treated with triple-drug immunotherapy with cyclosporine , which was started before surgery , ( group 1 ) or to be treated with OKT3 for 4 to 6 days after surgery with oral cyclosporine , which was started between days 2 and 4 , after renal function had stabilized ( group 2 ) . Follow-up for 6 months revealed no significant differences in the total number of rejection episodes , total number of infections , or in the serum creatinine level . Four patients in group 1 and five patients in group 2 have had no rejection . OKT3 showed a trend to delay time to first rejection ( p = 0.10 ) , as has been reported for the 14-day induction course of OKT3 . A short course of OKT3 induction in heart transplant recipients at low risk for immediate postoperative kidney failure prolongs the time to first rejection for most patients but does not appear to reduce the total incidence of rejection in the first 6 months after heart transplantation The aim of this study was to compare the efficacy and toxicity of prophylactic OKT3 and equine antithymo-cyte globulin when each drug was administered for a similar duration after heart transplantation . Forty-one patients ( 35 males , 6 females ; mean age 46±2 years ) were r and omized to receive either OKT3 for 10 days ( 20 patients ) commencing within 24–48 hr of transplantation or ATGAM for 8 days ( 21 patients ) commencing on the day of transplantation . All patients were maintained on triple-agent immunosuppression with prednisolone , azathioprine , and cyclosporine . The two groups were well matched with respect to age , sex distribution , pretransplant cardiac diagnosis , and donor heart ischemic time . Mean duration of follow-up was 14 months ( range 9–19 months ) : Actuarial survival at 12 months was 83±9 in the OKT3 group and 81±9 in the ATG group ( P = NS ) . Mean time to first cardiac rejection was 33±8 days in the OKT3 group compared with 27± 5 days in the ATG group ( P = NS ) . Linearized rejection rate did not differ between the two groups at any time point up to 12 months posttransplant . Viral infections were significantly more common in the OKT3 group : 1.6±0.3 vs. 0.8±0.2 infections per patient ( P<0.05 ) . Adverse reactions were more common in patients who received OKT3 prophylaxis and included three patients who developed acute respiratory distress , two of whom required assisted ventilation . In conclusion , prophylactic OKT3 and ATGAM result in comparable rejection rates and survival when administered for a similar duration after cardiac transplantation . OKT3 , however , is associated with increased morbidity due to a higher incidence of adverse reactions and of viral infections Thirty-nine heart transplant recipients were r and omized prospect ively to receive OKT3 or antilymphoblast globulin ( ALG ) for 7 days , having otherwise identical protocol s ( group 1 : OKT3 , n = 20 patients ; group 2 : ALG , n = 19 patients ) . No preoperative immunosuppression was given . The protocol consisted of methylprednisolone , 500 mg intraoperatively , followed by 1 mg/kg/day , intravenously or orally , tapering to 0.2 mg/kg/day at 1 month ; oral cyclosporine starting 3 to 5 days after transplantation ; selective use of azathioprine , 1 to 4 mg/kg/day ; and either OKT3 , 5 mg/day for 7 days , or ALG , 15 mg/kg/day for 7 days . Of the 39 patients in the study , 34 are alive 6 months to 2 years after transplantation . The actuarial survival at 2 years for the OKT3 and ALG groups was 92 % ( + /- 0.07 % ) and 83 % ( + /- 0.09 % ) , respectively ( not significant [ NS ] ) . The time to first rejection for group 1 was 5.6 weeks and for group 2 was 5.3 weeks ( NS ) . The mean number of rejections for group 1 and group 2 was 2.1 episodes per patient and 1.4 per patient , respectively ( NS ) . Three patients in each group were free of rejection at 6 months . The total number of infections at 6 months was 1.05 per patient in group 1 , 0.74 per patient in group 2 ( NS ) , with 35 % of patients receiving OKT3 and 52 % of patients receiving ALG actuarially free of infection by 6 months after surgery ( NS ) . During the first 24 hours after surgery , no significant differences were noted in mean blood pressure , central venous pressure , or Po2 between the groups . ( ABSTRACT TRUNCATED AT 250 WORDS To compare monoclonal anti-T3-receptor antibody ( OKT3 ) and horse antithymocyte globulin ( HATG ) immunoprophylaxis , 23 heart transplant recipients were r and omized to OKT3 ( N = 12 ) 5 mg IV x 14 days of HATG ( N = 11 ) 5 mg/kg IV x 10 days and followed up for 216 + /- 137 days receiving triple immunosuppression . Recipient groups were demographically and clinical ly similar . First rejection occurred later in OKT3 recipients vs HATG recipients ( 31.7 + /- 18.3 vs 15.1 + /- 2.3 days ; p less than 0.01 ) , but the first rejection necessitating intensified immunosuppression occurred at similar times ( 30.9 + /- 14.6 vs 21.9 + /- 10.2 days ; NS ) . Phenotypic characterization of peripheral blood lymphocytes by flow cytometry revealed that OKT3 and HATG recipients had similar decreases in total T lymphocytes and lymphocyte sub population s. During the follow-up period rejection rates in the OKT3- and in the HATG-treated patients were 3.4 + /- 2.7 and 5.9 + /- 4.7 , respectively ( NS ) . The number of rejection episodes per recipient treated with intensified immunosuppression was 1.4 + /- 1.2 in the OKT3- and 2.0 + /- 3.1 in the HATG-treated patients ( NS ) . Infection rates were 4.9 + /- 5.2 in the OKT3- and 2.7 + /- 1.7 in the HATG-treated patients ( NS ) . The number of infection episodes that necessitated intravenous antimicrobial therapy was 2.7 + /- 2.3 in the OKT3- and 1.6 + /- 1.3 in the HATG-treated recipients ( NS ) . The number and length of hospitalizations were similar in patients given OKT3-based or HATG-based immunoprophylaxis . We conclude that immunosuppressive prophylaxis with OKT3 vs HATG in heart transplant recipients is associated with a slightly lower incidence and severity of rejection and slightly higher infection rates The value of immunoprophylaxis with monoclonal anti-CD3 antibodies ( OKT3 ) was evaluated in 44 consecutive , nonr and omized heart transplant patients . The control group ( n = 22 ) was treated with polyclonal rabbit antithymocyte globulin ( RATG ) for 5 days . The study group ( n = 22 ) was treated with OKT3 for 14 days . All patients had identical perioperative immunosuppressive therapy and similar maintenance therapy , with cyclosporine , azathioprine , and low-dose prednisone ( starting prednisone : OKT3 group immediately , RATG group 3 weeks [ n = 11 ] or greater than 3 months [ n = 11 ] after transplantation ) . The mean histologic rejection grade ( Texas classification ) in the RATG and the OKT3 groups was 2.5 + /- 1.9 and 0.6 + /- 0.8 ( p less than 0.005 ) after 1 week and 4.3 + /- 1.6 and 2.0 + /- 1.5 ( p less than 0.001 ) after 2 weeks , but there was no difference in the first year . The linearized rejection rate ( rejections per 100 patient days ) was higher in the RATG group in the first 2 weeks ( 2.6 vs 0 , p less than 0.05 respectively , 7.8 vs 0.7 , p less than 0.001 ) and higher in the OKT3 group in the second month ( 1.4 vs 2.8 , p less than 0.01 ) . In the RATG group the rejection rate fell continuously , to 0.1 at the end of the first year , whereas in the OKT3 group it remained 0.4 ( NS ) . The cumulative first-year incidence was similar for persistent rejections ( RATG 0.38 + /- 0.29 vs OKT3 0.48 + /- 1.13 , NS ) and insignificantly higher for severe rejections in the OKT3 group ( RATG 0.21 + /- 0.32 vs OKT3 0.49 + /- 1.10 ) . Rejection-related mortality in the first year was 0 % ( RATG ) and 9 % ( OKT3 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Recent studies comparing the effects of induction therapy with polyclonal antilymphocyte globulins ( ALG ) or with monoclonal T-cell-specific antibodies are not unanimous . Therefore , 55 heart recipients were allocated to either 7-day courses of polyclonal ALG ( n = 28 ) or of monoclonal OKT3 ( n = 27 ) . Additionally , azathioprine and low dose steroids were given . There were no severe side effects after OKT3 ; the course of ALG , however , had to be discontinued in 20 patients because of extensive flares . No differences between the two groups were found in freedom from rejection or in the incidence of infection . The 1- and 2-year survival was 96 % in both groups . Although monoclonal and polyclonal induction therapies are equally effective for rejection prophylaxis , OKT3 may be preferred because of a lack of important side effects . However , the fact that a shorter course of ALG is equally effective may be in favour of ALG A r and omized trial of RATG ( polyclonal ) vs. OKT3 ( monoclonal ) antibody prophylaxis was carried out in 82 cardiac transplant recipients who , in addition , received baseline immunosuppression with cyclosporine , azathioprine and prednisone . One-year actuarial survival was comparable between groups ( 95 % and 98 % ) . The incidence of moderate or severe rejection within the first 30 days of transplant was over 7 times greater in patients receiving OKT3 vs. those receiving RATG . Patients receiving OKT3 were more likely to have repeated episodes of rejection and the mean time to rejection for patients receiving OKT3 was shorter ( 33 days ) than for RATG patients ( 67 days ) . At 120 days , 52 % of RATG patients were free of rejection while only 37 % of the OKT3 patients were rejection-free . There was no difference in the incidence of major or minor bacterial or viral infection between groups . Patients receiving OKT3 showed a less-prolonged depression of the CD3 and CD4 T cell subsets than did those receiving RATG . Significant hemodynamic side-effects were seen after the first dose of OKT3 and there was a 5 % incidence of aseptic meningitis associated with its use |
12,612 | 23,187,933 | p16 showed potential for treatment stratification between surgery and radiotherapy but needs further validation in independent studies .
Conclusions Despite years of research , very few tissue biomarkers retain predictive value in independent validation across therapy context .
Currently , none have conclusive ability to help treatment selection . | Background Tissue biomarkers could pivotally improve clinical outcome prediction following prostate cancer therapy .
Clinical ly , prostate cancer is managed by diverse treatment modalities whose individual influence on a biomarker ’s predictive ability is not well understood and poorly investigated in the literature .
Objective We conducted a systematic review to assess the predictive value of biomarkers in different treatment context s in prostate cancer . | A prospect i ve study on 16 patients with advanced ( stage III and IV ) prostate cancer was carried out . TNM stage , general clinical status , serum PSA level , the histological type and Gleason ’s grade of the tumor were registered . Total and rogen blockade or single-drug therapy ( flutamide ) was performed . On average , 4.81 months after the start of therapy rebiopsy , serum PSA determination and general clinical examination were performed . Histologic examination before and after treatment of HE-stained slides , as well as apop-tag reaction to show apoptotic cells , p53 , bcl2 , and Ki-67 immunostaining . Clinical improvement manifested by regression or lack of progression was observed in 10 patients . Increase of the apoptotic index and decrease of the mitotic index was detected in these cases . Serum PSA level decreased in all patients except in 3 fatal cases . The 6 clinical ly nonresponders who died after the second biopsy did not show an increased apoptotic or decreased mitotic index . Ki-67 positivity correlated well with the mitotic activity . Mutant p53 expression was higher in patients in whom anti and rogen therapy was ineffective . The bcl2 expression was a characteristic of the tumors of patients who later died . These results show that the degree of induction of apoptosis in prostate carcinoma by hormonal therapy varies from case to case . A given prostate cancer patient ’s response to therapy may be predicted by following apoptotic and mitotic activity , as well as Ki-67 and p53 expression in repeated biopsies Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer . Although effective surgical and radiation treatments exist for clinical ly localized prostate cancer , metastatic prostate cancer remains essentially incurable . Here we show , through gene expression profiling , that the polycomb group protein enhancer of zeste homolog 2 ( EZH2 ) is overexpressed in hormone-refractory , metastatic prostate cancer . Small interfering RNA ( siRNA ) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro . Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes . Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity . Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer ; in addition , clinical ly localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis . Thus , dysregulated expression of EZH2 may be involved in the progression of prostate cancer , as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression BACKGROUND Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic , and possibly surgical , outcome in several cancers . Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers , but few data exist on the association of extent of tumour hypoxia with treatment outcome . We aim ed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer , both in patients treated with radiotherapy and in those treated surgically . METHODS We applied a new , needle biopsy tissue microarray ( TMA ) technique to study diagnostic sample s from men with localised , previously untreated prostate cancer treated in two r and omised controlled trials of radiotherapy-dose escalation . Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome , in terms of biochemical control , and immunohistochemical staining of hypoxia inducible factor-1 alpha ( HIF-1 alpha ) , vascular endothelial growth factor ( VEGF ) , and osteopontin expression . The analysis was repeated on an independent series of men with localised , previously untreated prostate cancer treated by radical prostatectomy . The main outcome was time to biochemical ( ie , prostate-specific antigen [ PSA ] ) failure . FINDINGS Between Oct 12 , 1995 , and Feb 5 , 2002 , 308 patients were identified from two prospect i ve , r and omised trials at the Royal Marsden Hospital , London and Sutton , UK , for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients . Between June 6 , 1995 , and Nov 4 , 2005 , 329 patients were identified from the Aarhus University Hospital , Skejby , Denmark , for the prostatectomy cohort ; of these , 40 patients were excluded because the tumour was too small to sample ( 19 patients ) , because the paraffin block was too thin ( 19 patients ) , or because the blocks were missing ( two patients ) , leaving 289 patients for analysis . For patients treated with radiotherapy , increased staining for VEGF ( p=0.008 ) and HIF-1 alpha ( p=0.02 ) expression , but not increased osteopontin expression ( p=0.978 ) , were significant predictors of a shorter time to biochemical failure on multivariate analysis , independent of clinical tumour stage , Gleason score , serum PSA concentration , and dose of radiotherapy . For patients treated with surgery , increased staining for VEGF ( p<0.0001 ) and HIF-1 alpha ( p<0.0001 ) expression , and increased osteopontin expression ( p=0.0005 ) were each significantly associated with a shorter time to biochemical failure on multivariate analysis , independent of pathological tumour stage , Gleason score , serum PSA concentration , and margin status . INTERPRETATION To our knowledge , this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer . Increased expression of VEGF , HIF-1 alpha , and , for patients treated with surgery , osteopontin , identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer . We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies . A consecutive series of prostate biopsies of 279 men ( 72 % with clinical stage T1c and 23 % with T2 ) who subsequently underwent radical prostatectomy was prospect ively analysed for Gleason score , number and percentage of positive cores ( NPC , PPC ) , total percentage of biopsy tissue with tumour ( TPT ) , maximum tumour percentage per core ( MTP ) , and expression of Ki67 , Bcl‐2 and p53 . All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen . pT stage was independently predicted by PSA , seminal vesicle invasion by Ki67 LI , positive margins by PSA and MTP , large tumour diameter by PSA and PPC , and Gleason score by biopsy Gleason score , MTP , and Ki67 LI , respectively . Biopsy Gleason score , NPC ( 1 vs. > 1 ) , TPT ( < 7 vs. ≥7 % ) , and Ki67 LI ( < 10 vs. ≥10 % ) were significant predictors of biochemical recurrence after radical prostatectomy ( p < 0.01 , each ) . KI67 LI was the only independent prognostic factor in case of a low TPT ( < 7 % ) or low Gleason score ( < 7 ) , the hazard ratio being 6.76 and 6.44 , respectively . In summary , preoperative Gleason score , NPC , TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy , and Ki67 is an independent prognosticator in biopsies with low‐volume or low‐ grade prostate cancer . Analysis of Ki67 LI in these biopsies may help to better identify patients with clinical ly insignificant prostate cancer . © 2008 Wiley‐Liss , Purpose : We previously reported that protein kinase A type I ( PKARIα ) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy ( RT ) ± short-term and rogen deprivation ( STAD ) on Radiation Therapy Oncology Group ( RTOG ) protocol 86 - 10 . Here , we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKARIα overexpression . Experimental Design : There were 313 cases in the RTOG 92 - 02 study cohort with available tissue and suitable staining by immunohistochemistry . Median follow-up was 10.1 years . The intensity of PKARIα staining intensity was quantified manually and by image analysis . Multivariate analyses were done for overall mortality using Cox proportional hazards models and for local failure , biochemical failure , distant metastasis , and cause-specific mortality using Fine and Gray 's regression models . Results : The expression levels of PKARIα , determined by manual and image analysis , were strongly correlated ( P < 0.0001 ) . In the multivariate analyses , manual-quantified and image analysis –quantified PKARIα staining intensities were independent predictors of distant metastasis ( P < 0.01 ) , local failure ( P < 0.05 ) , and biochemical failure ( P ≤ 0.01 ) . Furthermore , the benefit of long-term AD over STAD was much less when PKARIα expression was high . Conclusions : PKARIα overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD + RT . In this series of contemporary high-risk patients , PKARIα overexpression was associated with diminished response to LTAD + RT relative to STAD + RT , suggesting that such patients would be ideal for a PKARIα knockdown strategy . ( Clin Cancer Res 2009;15(17):5478–84 PURPOSE Conventional pathological variables in prostate cancer may not provide optimal prediction of patient outcome . Pathological findings and p53 immunostaining were measured prospect ively in radical prostatectomy specimens to determine the incremental improvement in prediction of patient outcome over clinical findings . MATERIAL S AND METHODS From a previous prospect i ve study of 392 consecutive patients with prostate cancer who did not receive preoperative therapy and were treated with radical prostatectomy 25 had pathological stage pT3aN0M0 , 24 had pT3bN0M0 , 2 had pT2bN1M0 , 7 had pT3aN1M0 and 14 had pT3bN1 prostate cancer . These locally advanced stage cases comprise the current study population and further analysis was done with p53 immunostaining . All prostate specimens were totally embedded , serially sectioned and whole mounted . We examined pathological , clinical and laboratory findings as well as p53 immunostaining . RESULTS Median followup was 5.4 years ( range 0.5 to 6.4 ) . Univariate analysis revealed that pathological stage , 10 % or greater immunostaining for p53 , area and length of extraprostatic cancer extension , and cancer volume ( all p < /=0.03 ) were associated with biochemical ( prostate specific antigen ) or clinical failure . When all variables were considered in stepwise multivariate analysis none attained statistical significance after p53 status entered the model ( p < 0.01 , risk ratio 2.9 for 10 % or greater versus less than 10 % , 95 % confidence interval 1.4 - 6.2 ) . The concordance index analysis for the predictive ability of prostate specific antigen , stage , grade and ploidy ( c = 0.66 ) was inferior to the predictive ability of a statistical model also including p53 status ( c = 0.71 ) . CONCLUSIONS In cases of locally advanced stage cancer p53 immunoreactivity after radical prostatectomy improves outcome prediction . Addition of this variable to those routinely determined may identify a subset of patients who would benefit from more intensive postoperative surveillance and adjuvant therapy OBJECTIVES Locally advanced prostate cancer is frequently treated with radiotherapy and and rogen deprivation because of the greater rate of extracapsular disease and the concern that radical prostatectomy ( RP ) may not be curative in most cases . A case for surgery for locally advanced disease may be made on the basis of a lower rate of local recurrence compared with radiotherapy in our comparative data base , data suggesting a survival advantage with pelvic lymph node dissection in those with positive nodes , and the observation of improved survival in those with metastatic disease treated by RP compared with radiotherapy . We report on the feasibility of RP as a primary treatment modality for locally advanced disease . METHODS A total of 281 consecutive patients treated by RP between January 1998 and June 2004 were review ed . Locally advanced disease was defined as clinical Stage T2b or worse , prostate-specific antigen level greater than 15 ng/mL , and /or a Gleason score of 8 or greater . Data on the pathologic characteristics , operative complications , and follow-up were obtained from a prospect ively maintained institutional review board-approved data base . RESULTS Pathologic examination demonstrated organ-confined disease in 11.7 % , extracapsular extension in 56.9 % , seminal vesicle involvement in 23.1 % , and positive lymph nodes in 8.9 % . The overall complication rate was 9.7 % compared with 6.9 % for all patients undergoing RP . At a mean follow-up of 34 months ( range 1 to 78 ) , 198 ( 70.4 % ) of 281 patients had an undetectable prostate-specific antigen level at the last follow-up examination . CONCLUSIONS RP for locally advanced prostate cancer is feasible , with acute morbidity similar to RP for more localized disease . Furthermore , RP results in short-term biochemical recurrence-free survival similar to that of combined radiotherapy and and rogen ablation Summary The molecular mechanisms leading to and rogen-independent growth in prostate cancer ( PC ) are poorly understood . And rogen deprivation therapy ( ADT ) results physiologically in a decrease in proliferation and an increase in programmed cell death (PCD)/apoptosis . The aim of our study was to get more insight into these processes in prostatic carcinomas before and after ADT . For this purpose , immunohistologic staining for the and rogen receptor ( AR ) molecule , the Ki-67 antigen , the bcl-2 oncoprotein , the p53 protein and its physiologic effector , p21/WAF1 , was performed on archival material . PCD was visualized by enzymatic detection of DNA fragmentation . Specimens from 69 PC patients after ADT were studied in correlation to histopathology and prognosis . In 42 cases , corresponding tumour tissue from the untreated primary tumours could be analysed comparatively . Before ADT , histologic grade was associated with Ki-67 index ( P < 0.0001 , Spearman correlation ) and PCD rate ( P < 0.05 , Spearman correlation ) . Ki-67 index correlated with PCD rate ( P < 0.05 , Spearman correlation ) and p21/WAF1 expression ( P < 0.01 , Fisher ’s exact test ) . p21/WAF1 expression was the only statistically significant prognostic factor for shorter survival ( P < 0.002 , log-rank test ) . All p21/WAF1-positive cases showed high Ki-67 index and high histologic grade . After ADT , loss of AR expression was associated with high Ki-67 index , whereas histologic signs of regression correlated negatively with Ki-67 index ( P < 0.001 , Pearson χ2 test ) . p21/WAF1 expression increased significantly ( P < 0.02 , McNemar test ) and correlated with p53 accumulation ( P < 0.0001 , Pearson χ2 test ) . Most significant prognostic parameter after conventional ADT was high-rate p21/WAF1 expression ( > 50 % of tumour cells ; P < 0.00001 , log-rank test ) . This study demonstrates that p21/WAF1 overexpression before and after ADT characterizes a subgroup of advanced PC with paradoxically high proliferation rate and significantly worse clinical outcome . This finding might be clinical ly useful for planning therapy in these patients BACKGROUND COX-2 is overexpressed in some cancers , including prostate cancer ; however , little is known about the effect of COX-2 overexpression on outcome in radiation-treated patients with prostate cancer . We aim ed to study COX-2 overexpression and outcome in a well-defined cohort of men who received treatment with short-term and rogen deprivation ( STAD ) plus radiotherapy or long-term and rogen deprivation ( LTAD ) plus radiotherapy . METHODS Men with prostate cancer who had participated in the Radiation Therapy Oncology Group ( RTOG ) 92 - 02 trial and for whom sufficient diagnostic tissue was available for immunohistochemical staining and image analysis of COX-2 expression were enrolled in this study . Patients in the 92 - 02 trial had been r and omly assigned to treatment with STAD plus radiotherapy or LTAD plus radiotherapy . Multivariate analyses by Cox proportional hazards models were done to assess whether associations existed between COX-2 staining intensity and the RTOG 92 - 02 primary endpoints of biochemical failure ( assessed by the American Society for Therapeutic Radiology and Oncology [ ASTRO ] and Phoenix criteria ) , local failure , distant metastasis , cause-specific mortality , overall mortality , and any failure . FINDINGS 586 patients with sufficient diagnostic tissue for immunohistochemical staining and image analysis of COX-2 expression were included in this study . In the multivariate analyses , the intensity of COX-2 staining as a continuous covariate was an independent predictor of distant metastasis ( hazard ratio [ HR ] 1.181 [ 95 % CI 1.077 - 1.295 ] , p=0.0004 ) ; biochemical failure by two definitions ( ASTRO HR 1.073 [ 1.018 - 1.131 ] , p=0.008 ; Phoenix HR 1.073 [ 1.014 - 1.134 ] , p=0.014 ) ; and any failure ( HR 1.068 [ 1.015 - 1.124 ] , p=0.011 ) . The higher the expression of COX-2 , the greater the chance of failure . As a dichotomous covariate , COX-2 overexpression seemed to be most discriminating of outcome for those who received STAD compared with those who received LTAD . INTERPRETATION To our knowledge , this is the first study to establish an association of COX-2 expression with outcome in patients with prostate cancer who have had radiotherapy . Increasing COX-2 expression was significantly associated with biochemical failure , distant metastasis , and any failure . COX-2 inhibitors might improve patient response to radiotherapy in those treated with or without and rogen deprivation . Our findings suggest that LTAD might overcome the effects of COX-2 overexpression . Therefore , COX-2 expression might be useful in selecting patients who need LTAD Purpose : Neutral endopeptidase ( NEP ) is a cell-surface peptidase that inactivates neuropeptide growth factors implicated in prostate cancer progression . The clinical significance of decreased NEP expression observed in prostate cancer is unclear . We investigated whether decreased NEP expression in localized prostate cancers is associated with prostate-specific antigen ( PSA ) relapse after radical prostatectomy . Experimental Design : NEP expression patterns were examined by immunohistochemistry in 223 men , who underwent radical prostatectomy between 1990 and 2000 at the Veterans Administration Medical Center ( New York , NY ) with available representative tissues and adequate follow up . We also examined whether hypermethylation of the NEP promoter contributes to down-regulation of NEP protein expression in a subset of patients that showed decreased NEP expression ( n = 22 ) . Results : Three patterns of NEP expression were observed : ( a ) membranous expression similar to benign prostate epithelium ( n = 82 ; 37 % ) ; ( b ) complete loss of NEP expression in prostate cancer compared with adjacent benign prostate gl and s ( n = 105 ; 47 % ) ; and ( c ) heterogeneous NEP expression ( n = 36 ; 16 % ) . In a multivariate analysis , complete loss of NEP expression was associated with PSA relapse after controlling for grade , stage , pretreatment PSA , and race simultaneously ( hazard ratio , 1.99 ; 95 % confidence interval , 1.13–3.52 ; two-sided χ2 P = 0.017 ) . In addition , DNA hypermethylation of the NEP promoter was frequently ( 73 % ) identified in a subset of 22 of cases that showed decreased NEP expression . Conclusion : Our data suggest that decreased NEP expression might contribute to progression of localized prostate cancer after surgery . Data also suggest that methylation is an important mechanism of NEP protein silencing . Larger prospect i ve studies are required for confirmation PURPOSE We analyzed the potential prognostic significance of the immunohistochemical expression of and rogen and growth factor receptors determined in prostatectomy specimens of patients with prostate cancer . MATERIAL S AND METHODS A cohort of 211 patients with locally confined prostate cancer treated with radical prostatectomy with or without anti and rogen pretreatment between January 1 , 1990 and August 31 , 1996 was observed prospect ively . Prostatectomy sample s were processed immunohistochemically to visualize and rogen and growth factor receptors , of which immunoreaction intensity was scored relative to that of positive control tissue . Clinical postoperative data were processed using the Kaplan-Meier method , log rank test , and univariate and multivariate explorative Cox modeling to evaluate the contribution to overall and relapse-free survival . RESULTS There were statistical dependencies between the and rogen receptor and epidermal growth factor receptor staining indexes . Following data stratification according to the epidermal growth factor receptor staining index the prognosis associated with a low and rogen receptor staining index was worse than that with a higher and rogen receptor staining index . Cox regression analysis for relapse-free survival confirmed that the risk factors low and rogen receptor and increased epidermal growth factor receptor staining were associated with significantly increased relative risk . Univariate Kaplan-Meier analysis showed that patients with grade 3 carcinoma had a worse prognosis than those with better differentiated carcinoma , whereas anti and rogen pretreatment had no influence on overall survival or relapse-free survival . CONCLUSIONS Using a multivariate proportional hazards regression model for data on a cohort of 211 patients with 68 showing relapse/progress or death from disease a low intensity of and rogen receptor staining indicated a poor prognosis PURPOSE DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome . However , a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients . In this retrospective study , the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610 . The protocol treatment r and omization was RT alone versus RT plus short-course ( approximately 4 months ) neoadjuvant and concurrent total and rogen blockade ( RT+TAB ) . PATIENTS AND METHODS The study population consisted of 149 patients , of whom 74 received RT alone and 75 received RT+TAB . DNA content was determined by image analysis of Feulgen stained tissue sections ; 94 patients were diploid and 55 patients were nondiploid . Kaplan-Meier univariate survival , the cumulative incidence method , and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival . RESULTS DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses . In Kaplan-Meier analyses , 5-year overall survival was 70 % for those with diploid tumors and 42 % for nondiploid tumors . Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival . No correlation was observed between DNA ploidy and distant metastasis . The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage and rogen ablation ; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage and rogen ablation . CONCLUSIONS Nondiploidy was associated with shorter survival , which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB PURPOSE The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202 , which compared short-term and rogen deprivation ( STAD ) with radiation therapy ( RT ) to long-term and rogen deprivation + RT in men with locally advanced prostate cancer ( Pca ) . METHODS AND MATERIAL S Tumor tissue was sufficient for p53 analysis in 777 cases . p53 status was determined by immunohistochemistry . Abnormal p53 expression was defined as 20 % or more tumor cells with positive nuclei . Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes . RESULTS Abnormal p53 was detected in 168 of 777 ( 21.6 % ) cases , and was significantly associated with cause-specific mortality ( adjusted hazard ratio [ HR ] = 1.89 ; 95 % confidence interval ( CI ) 1.14 - 3.14 ; p = 0.014 ) and distant metastasis ( adjusted HR = 1.72 ; 95 % CI 1.13 - 2.62 ; p = 0.013 ) . When patients were divided into subgroups according to assigned treatment , only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality ( adjusted HR = 2.43 ; 95 % CI = 1.32 - 4.49 ; p = 0.0044 ) . When patients were divided into subgroups according to p53 status , only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality ( adjusted HR = 3.81 ; 95 % CI 1.40 - 10.37 ; p = 0.0087 ) . CONCLUSIONS Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term and rogen deprivation and radiotherapy . Long-term and rogen deprivation may significantly improve the cause-specific survival for those with abnormal p53 Purpose : Bcl-2 is antiapoptotic , and its overexpression has been associated with resistance to and rogen deprivation and poor outcome in some patients treated with radiotherapy . Bax is proapoptotic , regulating Bcl-2 through heterodimer formation . In a prior study , Bcl-2 and Bax were not related to outcome in locally advanced patients treated with radiotherapy or short-term and rogen deprivation + radiotherapy ( STAD+RT ) on another Radiation Therapy Oncology Group trial ( 86 - 10 ) . A follow-up investigation was carried out here in more contemporary high-risk men treated on Radiation Therapy Oncology Group 92 - 02 with STAD+RT or long-term AD+RT ( LTAD+RT ) . Experimental Design : Adequate tissue was available to be analyzed immunohistochemically in 502 patients for Bcl-2 and 343 patients for Bax . Univariate and multivariate analyses by Cox proportional hazards models were applied to end points of failure . Results : Bcl-2 was positive in 45.6 % cases , and Bax expression altered in 53.9 % cases . Abnormal Bcl-2 was not related to any of the failure end points tested . Altered Bax expression was significantly associated with any failure ( P = 0.023 ) and marginally with biochemical failure ( P = 0.085 ) . The combination of negative Bcl-2/normal Bax expression seemed more robust , being significantly related to reduced biochemical failure ( P = 0.036 ) and any failure ( P = 0.046 ) . The predictive value of negative Bcl-2/normal Bax was most pronounced in those who received STAD+RT , as opposed to LTAD+RT . Conclusions : Normal Bax expression was associated with significantly more favorable outcome . The combination of negative Bcl-2 and normal Bax was more consistently significant , particularly when STAD+RT was the treatment administered . These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed PURPOSE Deregulation of the retinoblastoma ( RB ) pathway is commonly found in virtually all known human tumors . p16 , the upstream regulator of RB , is among the most commonly affected member of this pathway . In the present study , we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202 . PATIENTS AND METHODS RTOG 9202 was a phase III r and omized study comparing long-term ( LT ) versus short-term ( ST ) and rogen-deprivation therapy ( AD ) . Of the 1,514 eligible cases , 612 patients had adequate tumor material for p16 analysis . Expression levels of p16 were determined by immunohistochemistry ( IHC ) . IHC staining was scored quantitatively using an image analysis system . RESULTS On multivariate analysis , intact p16 expression was significantly associated with decreased rate of distant metastases ( P = .0332 ) when both STAD and LTAD treatment arms were considered together . For patients with intact ( high levels of immunostaining ) p16 ( mean p16 index > 81.3 % ) , LTAD plus radiotherapy ( RT ) significantly improved prostate cancer survival ( PCS ) compared with STAD plus RT ( P = .0008 ) and reduced the frequency of distant metastasis ( P = .0069 ) compared with STAD plus RT . In contrast , for patients with tumors demonstrating p16 loss ( low levels of immunostaining , mean p16 index < or = 81.3 % ) , LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD ( P < .0001 ) primarily by decreasing the frequency of local progression ( P = .02 ) , as opposed to distant metastasis , which was the case in the high-p16 cohort . CONCLUSION Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients . p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD PURPOSE We determine the importance of clinical and pathological variables for predicting biochemical progression in patients after surgery for specimen confined prostate cancer . We developed a simple scoring algorithm for biochemical progression in node negative cases and tested the algorithm performance on an independent group . MATERIAL S AND METHODS Our study included 2,518 patients with pT2N0 or pT3N0 disease treated between 1990 and 1993 . Gleason score , preoperative prostate specific antigen ( PSA ) , margin status , extraprostatic extension , seminal vesicle involvement , DNA ploidy and adjuvant treatment were primary variables analyzed univariately . The Cox proportional hazards model was used on 2,000 r and omly selected patients to develop a multivariate scoring algorithm for the aforementioned factors to predict biochemical progression-free survival . The final model included Gleason score , preoperative PSA , margin status , seminal vesicle involvement and adjuvant treatment . The prognostic score derived from this model was vali date d by applying it to the remaining 518 patients . Harrell 's measure of concordance ( C ) was used to compare competing models . RESULTS For patients who did not receive adjuvant therapy the derived score based on the Cox model coefficient was Gleason + 1 ( PSA 4 to 10 ) , + 2 ( PSA 10.1 to 20 ) , + 3 ( PSA greater than 20 ) , + 2 ( positive seminal vesicle ) and + 2 ( positive margin ) . The score was reduced by 4 if adjuvant hormonal therapy was given and by 2 for only adjuvant radiotherapy . The 5-year progression-free survival was 94 % for scores less than 5 , 60 % for 10 and 32 % for greater than 12 ( C = 0 . 718 ) . Applying the score to the independent validation data set ( 518 ) result ed in 5-year progression-free survival of 96 % for scores less than 5 , 53 % for 10 and 30 % for greater than 12 ( C = 0.759 ) . CONCLUSIONS Progression-free survival determined by the model score group identified a wide range of risk levels for patients with specimen confined prostate cancer . This simple predictive model allows identification of patients at high risk for cancer progression with specimen confined disease who may be targeted for closer surveillance and adjuvant therapy , while those at lower risk may be simply observed The purpose s of this study were to evaluate if tumour vascularity by Chalkley counting ( TVC ) in prostate core biopsies can be a predictor of PSA recurrence after radical prostatectomy in prostate cancer and to estimate the concordance between the TVC in core biopsies and the subsequently examined prostatectomy specimen . All patients , with Gleason score ≤7 in core biopsy , clinical stage T1 or T2 who had a radical prostatectomy during 1990 – 1997 at Sahlgrenska University Hospital , were selected as a primary group . Patients with neoadjuvant hormonal therapy were excluded . The patients were divided into two groups , one with PSA recurrence and one group without PSA recurrence . 25 patients had PSA recurrence during the follow up period and 25 patients from non-recurrence group were r and omly selected . TVC was assessed from the prostate tissue by immunostaining against CD34 . TVC was statistically significant predictor of PSA relapse . The PSA-free survival rate was only 17 % in patients within the highest TVC quartile compared to 67 % in patients within the lowest TVC quartile PURPOSE The RI-alpha regulatory subunit of protein kinase A type 1 ( PKA ) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation . This report examined the association between PKA expression and the endpoints of biochemical failure ( BF ) , local failure ( LF ) , distant metastasis ( DM ) , cause-specific mortality ( CSM ) , and overall mortality in men treated with radiotherapy , with or without short-term and rogen deprivation in Radiation Therapy Oncology Group trial 86 - 10 . METHODS AND MATERIAL S Pretreatment archival diagnostic tissue sample s from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases . PKA intensity was scored manually and by image analysis . The Cox proportional hazards model for overall mortality and Fine and Gray 's regression models for CSM , DM , LF and BF were then applied to determine the relationship of PKA expression to the endpoints . RESULTS The pretreatment characteristics of the missing and determined PKA groups were not significantly different . On univariate analyses , a high PKA staining intensity was associated with BF ( image analysis , continuous variable , p = 0.022 ) , LF ( image analysis , dichotomized variable , p = 0.011 ) , CSM ( manual analysis , p = 0.037 ; image analysis , continuous , p = 0.014 ) , and DM ( manual analysis , p = 0.029 ) . On multivariate analyses , the relationships to BF ( image analysis , continuous , p = 0.03 ) , LF ( image analysis , dichotomized , p = 0.002 ) , and DM remained significant ( manual analysis , p = 0.018 ) . In terms of CSM , a trend toward an association was seen ( manual analysis , p = 0.08 ; image analysis , continuous , p = 0.09 ) . CONCLUSION PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy PURPOSE Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome . We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two r and omized controlled trials of radiotherapy dose escalation . METHODS AND MATERIAL S Between 1995 and 2001 , 308 patients with localized prostate cancer received neoadjuvant and rogen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials . The biopsy specimens in 201 cases were used to make a biopsy tissue microarray . We evaluated tumor expression of Bcl-2 , p53 , and MDM2 by immunohistochemistry with respect to outcome . RESULTS Median follow-up was 7 years , and 5-year freedom from biochemical failure ( FFBF ) was 70.4 % ( 95 % CI , 63.5 - 76.3 % ) . On univariate analysis , expression of Bcl-2 ( p < 0.001 ) and p53 ( p = 0.017 ) , but not MDM2 ( p = 0.224 ) , was significantly associated with FFBF . Expression of Bcl-2 remained significantly associated with FFBF ( p = 0.001 ) on multivariate analysis , independently of T stage , Gleason score , initial prostate-specific antigen level , and radiotherapy dose . Seven-year biochemical control was 61 % vs. 41 % ( p = 0.0122 ) for 74 Gy vs. 64 Gy , respectively , among patients with Bcl-2-positive tumors and 87 % vs. 81 % ( p = 0.423 ) for 74 Gy vs. 64 Gy , respectively , among patients with Bcl-2-negative tumors . There was no statistically significant interaction between dose and Bcl-2 expression . CONCLUSIONS Bcl-2 expression was a significant , independent determinant of biochemical control after neoadjuvant and rogen deprivation and radical radiotherapy for prostate cancer . These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients OBJECTIVE Our aim was to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the screening , diagnosis , and treatment of clinical ly localised cancer of the prostate ( PCa ) . METHODS The working panel performed a literature review of the new data emerging from 2007 to 2010 . The guidelines were up date d , and level of evidence and grade of recommendation were added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. RESULTS A full version is available at the EAU office or Web site ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . A systematic prostate biopsy under ultrasound guidance and local anaesthesia is the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy . PSA doubling time in <3 yr or a biopsy progression indicates the need for active intervention . In men with locally advanced PCa in whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) with equivalent oncologic efficacy . Active treatment is mostly recommended for patients with localised disease and a long life expectancy with radical prostatectomy ( RP ) shown to be superior to WW in a prospect i ve r and omised trial . Nerve-sparing RP represents the approach of choice in organ-confined disease ; neoadjuvant and rogen deprivation demonstrates no improvement of outcome variables . Radiation therapy should be performed with at least 74 Gy and 78 Gy in low-risk and intermediate/high-risk PCa , respectively . For locally advanced disease , adjuvant ADT for 3 yr results in superior disease-specific and overall survival rates and represents the treatment of choice . Follow-up after local therapy is largely based on PSA , and a disease-specific history with imaging is indicated only when symptoms occur . CONCLUSIONS The knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice Study Type – Prevalence ( prospect i ve cohort ) Level of Evidence |
12,613 | 27,271,789 | There is high- quality evidence that paracetamol has no effect on quality of life , function , global impression of recovery , and sleep quality for all included time periods .
There were also no significant differences between paracetamol and placebo for adverse events , patient adherence , or use of rescue medication .
For chronic LBP , there is very low- quality evidence ( based on a trial that has been retracted ) for no effect of paracetamol ( 1 g single intravenous dose ) on immediate pain reduction .
AUTHORS ' CONCLUSIONS We found that paracetamol does not produce better outcomes than placebo for people with acute LBP , and it is uncertain if it has any effect on chronic LBP | BACKGROUND Analgesic medication is the most frequently prescribed treatment for low back pain ( LBP ) , of which paracetamol ( acetaminophen ) is recommended as the first choice medication .
However , there is uncertainty about the efficacy of paracetamol for LBP .
OBJECTIVES To investigate the efficacy and safety of paracetamol for non-specific LBP . | Study Design . A prospect i ve , r and omized , single ( investigator ) blind , comparative efficacy trial was conducted . Objective . To compare the efficacy of continuous low-level heat wrap therapy ( 40 C , 8 hours/day ) with that of ibuprofen ( 1200 mg/day ) and acetaminophen ( 4000 mg/day ) in subjects with acute nonspecific low back pain . Summary of Background Data . The efficacy of topical heat methods , as compared with oral analgesic treatment of low back pain , has not been established . Methods . Subjects ( n = 371 ) were r and omly assigned to heat wrap ( n = 113 ) , acetaminophen ( n = 113 ) , or ibuprofen ( n = 106 ) for efficacy evaluation , or to oral placebo ( n = 20 ) or unheated back wrap ( n = 19 ) for blinding . Outcome measures included pain relief , muscle stiffness , lateral trunk flexibility , and disability . Efficacy was measured over two treatment days and two follow-up days . Results . Day 1 pain relief for the heat wrap ( mean , 2 ) was higher than for ibuprofen ( mean , 1.51;P = 0.0007 ) or acetaminophen ( mean , 1.32;P = 0.0001 ) . Extended mean pain relief ( Days 3 to 4 ) for the heat wrap ( mean , 2.61 ) also was higher than for ibuprofen ( mean , 1.68;P = 0.0001 ) or acetaminophen ( mean , 1.95;P = 0.0009 ) . Lateral trunk flexibility was improved with the heat wrap ( mean change , 4.28 cm ) during treatment ( P ≤ 0.009 vs acetaminophen [ mean change , 2.93 cm ] , P ≤ 0.001 vs ibuprofen [ mean change , 2.51 cm ] ) . The results were similar on Day 4 . Day 1 reduction in muscle stiffness with the heat wrap ( mean , 16.3 ) was greater than with acetaminophen ( mean , 10.5;P = 0.001 ) . Disability was reduced with the heat wrap ( mean , 4.9 ) , as compared with ibuprofen ( mean , 2.7;P = 0.01 ) and acetaminophen ( mean , 2.9;P = 0.0007 ) , on Day 4 . None of the adverse events were serious . The highest rate ( 10.4 % ) was reported in the ibuprofen group . Conclusion . Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain Acetaminophen , ibuprofen , and aspirin are the most commonly used drugs in the United States . Although the frequency of their use has been associated with hypertension , prospect i ve data examining the dose of these drugs and risk of hypertension are lacking . Furthermore , whether certain indications for analgesic use , particularly headache , mediate the association is unclear . We conducted 2 prospect i ve cohort studies among older women 51 to 77 years of age ( n=1903 ) from the Nurses ’ Health Study I and younger women 34 to 53 years of age ( n=3220 ) from the Nurses ’ Health Study II who completed detailed supplemental question naires pertaining to their analgesic use and who did not have hypertension at baseline . We analyzed incident hypertension according to categories of average daily dose of acetaminophen , nonsteroidal anti-inflammatory drugs , and aspirin . Information on indications for analgesic use as well as relevant confounders was also gathered prospect ively . Compared with women who did not use acetaminophen , the multivariable adjusted relative risk for those who took > 500 mg per day was 1.93 ( 1.30 to 2.88 ) among older women and 1.99 ( 1.39 to 2.85 ) among younger women . For nonsteroidal anti-inflammatory drugs , similar comparisons yielded multivariable relative risks of 1.78 ( 1.21 to 2.61 ) among older women and 1.60 ( 1.10 to 2.32 ) among younger women . These associations remained significant among women who did not report headache . Aspirin dose was not significantly associated with hypertension . Higher daily doses of acetaminophen and nonsteroidal anti-inflammatory drugs independently increase the risk of hypertension in women . Because acetaminophen and nonsteroidal anti-inflammatory drugs are commonly used , they may contribute to the high prevalence of hypertension in the United States Background — Although r and omized trials of cyclooxygenase-2 ( COX-2 ) inhibitors have shown increased cardiovascular risk , studies of nonselective , nonsteroidal antiinflammatory drugs ( NSAIDs ) and acetaminophen have been inconsistent . Methods and Results — We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events ( nonfatal myocardial infa rct ion , fatal coronary heart disease , nonfatal and fatal stroke ) in a prospect i ve cohort of 70 971 women , aged 44 to 69 years at baseline , free of known cardiovascular disease or cancer , who provided medication data biennially since 1990 . During 12 years of follow-up , we confirmed 2041 major cardiovascular events . Women who reported occasional ( 1 to 21 d/mo ) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events . However , after adjustment for cardiovascular risk factors , women who frequently ( ≥22 d/mo ) used NSAIDs had a relative risk ( RR ) for a cardiovascular event of 1.44 ( 95 % CI , 1.27 to 1.65 ) compared with nonusers , whereas those who frequently consumed acetaminophen had a RR of 1.35 ( 95 % CI , 1.14 to 1.59 ) . The elevated risk associated with frequent NSAID use was particularly evident among current smokers ( RR=1.82 ; 95 % CI , 1.38 to 2.42 ) and was absent among never smokers ( Pinteraction=0.02 ) . Moreover , we observed significant dose-response relations : Compared with nonusers , the RRs for a cardiovascular event among women who used ≥15 tablets per week were 1.86 ( 95 % CI , 1.27 to 2.73 ) for NSAIDs and 1.68 ( 95 % CI , 1.10 to 2.58 ) for acetaminophen . Conclusions — Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events , although more moderate use did not confer substantial risk Purpose Treatment of patients with chronic low back pain ( CLBP ) aims to reduce disability , improve functional capacity , and participation . Time contingent prescription of analgesics is a treatment modality in CLBP . The impact of analgesics on functional capacity is unknown . Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation , and self-reported disability in patients with CLBP . Methods Explorative R and omized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation . Included patients had low back pain lasting > 3 months , visual analogue scale worst pain ≥4.0 cm , and age > 18 years . Outcome measures before ( T0 ) and after treatment ( T1 ) : functional capacity , pain intensity , Rol and Morris Disability Question naire . T1 : global perceived pain relief . Patient characteristics and psychological question naires were assessed . Fifty patients were included in this study and were r and omly assigned to 2 weeks treatment or placebo . Treatment : acetaminophen/tramadol 325 mg/37.5 mg per capsule . Dose : maximum acetaminophen 1,950 mg and tramadol 225 mg per day ; treatment and placebo titrated identically . Compliance and side-effects were monitored . Treatment effects between groups over time were compared . Results One patient ( treatment group ) was lost to follow-up . Forty-nine patients remained in the study . Treatment effects in primary outcomes did not differ significantly between groups . A subgroup of 10 ( 42 % ) patients ( treatment group ) reported global pain relief ( responders ) who reduced self-reported disability ( p < 0.05 ) . Responders had significantly lower catastrophizing scores . Conclusion Overall treatment effects were small and non-significant . A subgroup , however , reported improved functioning as a result of treatment . Responders had lower catastrophizing scores Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in intracranial hemorrhage ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk factors who were undergoing noncardiac surgery ( 9 ) . However , these results contradict those of 2 much larger subsequently published trials , neither of which suggested that -blockers reduce cardiac risk in patients undergoing noncardiac surgery ( 10 , 11 ) . Further social detriment may occur when clinicians compromise the ability of others to conduct more definitive studies by placing undue confidence in the results of a truncated trial . Investigators ( including 2 contributors to this article ) who obtained funding for a trial of -blockers in noncardiac surgery with an enrollment target of 10000 patients ( 12 ) faced challenges in persuading clinicians that the question remained unanswered . Participant Consent and Respect for Participants Key prerequisites for informed consent include the participant 's decision-making capacity and voluntariness and whether he or she had received adequate information to decide that participation in the research was in alignment with his or her values and goals . However , informed consent is not a single event , but it is an ongoing collaboration between participants and investigators . When important changes occur during a trial , investigators should inform participants of the changes . One justification for stopping a trial early for benefit is to inform study participants of the preliminary results and offer them the superior treatment . According to this argument , uncertainty about the relative merits of alternative interventions ( equipoise ) has been lost and informed clinicians and patients will overwhelmingly choose the superior treatment ( 13 ) . However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial . Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results . Disclosing interim results to study participants may therefore prove misleading . Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial . These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity . Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) . Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . Continuing a 2-group trial gives participants at least a 50 % chance of receiving the experimental treatment , whereas if the trial is stopped early , the probability that participants will receive the treatment due to rapid dissemination is likely to be considerably less than 50 % . Independent Review Trials may have stopping rules that allow early termination because of genuine ( although misguided ) ethical concerns . However , investigators , trial sponsors , journals , and patients may all have additional motives for stopping trials early for apparent benefit . For example , truncated trials that report a large treatment effect tend to be published in the most prestigious medical journals ( 1 ) , which enhances the careers of the investigators and increases the likelihood that they will receive grants . Funding agencies have an interest in stopping trials early to minimize research costs . Pharmaceutical and for-profit sources that financially support trials are interested not only in controlling costs but also in the publicity and market share that result from reporting a trial stopped early for apparent benefit . Medical journals are interested in these trials because of publicity and citations , which result in increased journal impact factor , prestige , and advertising revenue . And patients and their advocates are motivated to stop a trial early when the experimental intervention is promising in order to hasten delivery of the intervention to clinical practice . All of these motives may affect investigators ' decisions and encourage an inappropriately early stop to a trial . These considerations m and ate that institutional review boards and data monitoring committees underst and the principles outlined in this article and insist on appropriate st and ards for stopping a trial early for apparent benefit to maintain the ethical integrity of clinical trials . OBJECTIVE To assess the long-term benefits of medication , needle acupuncture , and spinal manipulation as exclusive and st and ardized treatment regimens in patients with chronic ( > 13 weeks ) spinal pain syndromes . STUDY DESIGN Extended follow-up ( > 1 year ) of a r and omized clinical trial was conducted at the multidisciplinary spinal pain unit of Townsville 's General Hospital between February 1999 and October 2001 . PATIENTS AND METHODS Of the 115 patients originally r and omized , 69 had exclusively been treated with the r and omly allocated treatment during the 9-week treatment period ( results at 9 weeks were reported earlier ) . These patients were followed up and assessed again 1 year after inception into the study reapplying the same instruments ( ie , Oswestry Back Pain Index , Neck Disability Index , Short-Form-36 , and Visual Analogue Scales ) . Question naires were obtained from 62 patients reflecting a retention proportion of 90 % . The main analysis was restricted to 40 patients who had received exclusively the r and omly allocated treatment for the whole observation period since r and omization . RESULTS Comparisons of initial and extended follow-up question naires to assess absolute efficacy showed that only the application of spinal manipulation revealed broad-based long-term benefit : 5 of the 7 main outcome measures showed significant improvements compared with only 1 item in each of the acupuncture and the medication groups . CONCLUSIONS In patients with chronic spinal pain syndromes , spinal manipulation , if not contraindicated , may be the only treatment modality of the assessed regimens that provides broad and significant long-term benefit OBJECTIVE To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg ( tramadol/APAP ) combination tablets for treatment of chronic low back pain ( LBP ) . METHODS This 91 day , multicenter , outpatient , r and omized , double blind , placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months . Patients with at least moderate pain [ pain visual analog scale ( VAS ) with scores > or = 40/100 mm ] after washout were r and omized to tramadol/APAP or placebo . After a 10 day titration , patients received 1 or 2 tablets QID . Primary outcome measure was final pain VAS score . Secondary measures included pain relief , quality of life and physical functioning , efficacy failure , and overall medication assessment s. RESULTS In total , 336 intent-to-treat patients received tramadol/APAP ( n = 167 ) or placebo ( n = 169 ) . Mean baseline pain VAS score was 67.8 . Intent-to-treat analysis showed significantly better mean final pain VAS scores ( 47.4 vs 62.9 ; p < 0.001 ) and mean final pain relief scores ( 1.8 vs 0.7 ; p < 0.001 ) for tramadol/APAP than for placebo . Rol and Disability Question naire scores and physical-related subcategories of the McGill Pain Question naire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients . More patients rated tramadol/APAP as " very good " or " good " than placebo ( 63.6 vs 25.2 % ; p < 0.001 ) . Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9 % ( tramadol/APAP ) vs 54.7 % ( placebo ; p < 0.001 ) . The most common treatment related adverse events with tramadol/APAP were nausea ( 12.0 % ) , dizziness ( 10.8 % ) , and constipation ( 10.2 % ) . Average daily dose of tramadol/APAP was 4.2 tablets ( tramadol 158 mg/APAP 1369 mg ) . CONCLUSION Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction , in measures of physical functioning and quality of life , and in overall medication assessment s , with a tolerability profile comparable with other opioids used for the treatment of chronic LBP BACKGROUND Regular paracetamol is the recommended first-line analgesic for acute low-back pain ; however , no high- quality evidence supports this recommendation . We aim ed to assess the efficacy of paracetamol taken regularly or as-needed to improve time to recovery from pain , compared with placebo , in patients with low-back pain . METHODS We did a multicentre , double-dummy , r and omised , placebo controlled trial across 235 primary care centres in Sydney , Australia , from Nov 11 , 2009 , to March 5 , 2013 . We r and omly allocated patients with acute low-back pain in a 1:1:1 ratio to receive up to 4 weeks of regular doses of paracetamol ( three times per day ; equivalent to 3990 mg paracetamol per day ) , as-needed doses of paracetamol ( taken when needed for pain relief ; maximum 4000 mg paracetamol per day ) , or placebo . R and omisation was done according to a central ised r and omisation schedule prepared by a research er who was not involved in patient recruitment or data collection . Patients and staff at all sites were masked to treatment allocation . All participants received best- evidence advice and were followed up for 3 months . The primary outcome was time until recovery from low-back pain , with recovery defined as a pain score of 0 or 1 ( on a 0 - 10 pain scale ) sustained for 7 consecutive days . All data were analysed by intention to treat . This study is registered with the Australian and New Zeal and Clinical Trial Registry , number ACTN 12609000966291 . FINDINGS 550 participants were assigned to the regular group ( 550 analysed ) , 549 were assigned to the as-needed group ( 546 analysed ) , and 553 were assigned to the placebo group ( 547 analysed ) . Median time to recovery was 17 days ( 95 % CI 14 - 19 ) in the regular group , 17 days ( 15 - 20 ) in the as-needed group , and 16 days ( 14 - 20 ) in the placebo group ( regular vs placebo hazard ratio 0·99 , 95 % CI 0·87 - 1·14 ; as-needed vs placebo 1·05 , 0·92 - 1·19 ; regular vs as-needed 1·05 , 0·92 - 1·20 ) . We recorded no difference between treatment groups for time to recovery ( adjusted p=0·79 ) . Adherence to regular tablets ( median tablets consumed per participant per day of maximum 6 ; 4·0 [ IQR 1·6 - 5·7 ] in the regular group , 3·9 [ 1·5 - 5·6 ] in the as-needed group , and 4·0 [ 1·5 - 5·7 ] in the placebo group ) , and number of participants reporting adverse events ( 99 [ 18·5 % ] in the regular group , 99 [ 18·7 % ] in the as-needed group , and 98 [ 18·5 % ] in the placebo group ) were similar between groups . INTERPRETATION Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain , and question the universal endorsement of paracetamol in this patient group . FUNDING National Health and Medical Research Council of Australia and GlaxoSmithKline Australia We performed a r and omized double-blind controlled study in community medical practice comparing lysine acetylsalicylate ( LAS ) and paracetamol ( PAR ) . Both drugs were given at the same dose ( 1 g , thrice daily ) during two days ; from the third to the seventh day , the patients could freely take the same drug if necessary . The analgesic effect of drugs was measured by two means : an analog scale of pain during day 1 & 2 and the count of drugs units taken during days 3 to 7 . The side effects were reported . We included 473 patients ( 167 men , 306 women ) by means of a group of 54 general practitioners . 470 patients were stratified according to the site of pain : head ( n = 113 ) , joints ( n = 80 ) , back ( n = 193 ) , thorax ( n = 11 ) , teeth ( n = 48 ) , ENT ( n = 25 ) . The pain was either acute ( 73 % ) or chronic ( 27 % ) and scored an average + /- SD of 76 + /- 12 mm on an analog visual scale from 0 to 100 mm . Response was defined as a decrease of at least 50 % of the pain score . Before intake of active drugs , all patients were given placebo . Only 14 % responded . Under LAS or PAR , although the difference is not statistically significant , the number of responders was slightly higher with LAS than with PAR . Moreover , the study yields some interesting differences . During day 1 and day 2 , the patients of the LAS group had less pain than those of the PAR group . This difference became statistically significant at D2 H12 ( p < 0.05 ) . LAS was significantly more effective than PAR in patients with back pain ( p < 0.01 ) , and there was a trend in favor of LAS in dental and ENT pain , and for intense pain . PAR never yielded better response levels than LAS . Among the placebo-unresponsive patients , the amount of drug taken from day 3 to day 7 was significantly lower in the LAS group than in the PAR group ( p < 0.05 ) . The side effects were comparable in both groups . According to the investigators ' point of view both drugs were similarly well accepted by the patients ( 89.3 % in LAS group , 94 % in PAR group ) . The fact that LAS seems more effective than PAR in some kinds of pain is to bring near to the anti-inflammatory action of LAS and to its better bioavailability Introduction . This multiple-dose pharmacokinetic study has a r and omized , double-blind , placebo-controlled , parallel-group design with three dosing regimens . Healthy subjects received repeated doses of acetaminophen ( 4 then 6 g/d or 4 then 8 g/d ) or placebo . Methods . The disposition of acetaminophen and its metabolites and the tolerability of increased acetaminophen doses over 3 days of continuous consumption were characterized . Aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) activities measured throughout the study were consistent across the acetaminophen 4 , 6 , and 8 g/d dose levels and with placebo . Results . Serum aminotransferase activities did not exceed the upper limit of the reference range ( ULRR ) , except for one subject with an AST of 43 U/L ( ULRR , 42 U/L ) , which was not considered clinical ly significant . All doses were generally well tolerated . Conclusions . In a multiple-dose pharmacokinetics study of 4 , 6 , and 8 g/d of acetaminophen for 3 days , multiple aminotransferase determinations demonstrated no clinical ly important elevations at 1 , 1.5 , or 2 times the maximum recommended acetaminophen dose UNLABELLED This study evaluated the impact of treatment with Buprenorphine Transdermal System ( BTDS ) on the health-related quality of life for patients with moderate-to-severe chronic low back pain ( CLBP ) , and the correspondence between quality of life and pain . A multicenter , enriched , double-blind ( DB ) , placebo-controlled , r and omized trial evaluated BTDS 10 and 20 μg/hour for treatment of opioid-naïve patients with moderate-to-severe CLBP . The SF-36v2 survey , which measures 8 domains of quality of life , was administered at screening and following an open-label run-in period with BTDS and at weeks 4 , 8 , and 12 of the DB phase . Post hoc analyses compared SF-36v2 scores between BTDS and placebo groups during the DB phase . Condition burden was examined through comparisons with a U.S. general population sample . Correlations examined the correspondence between quality of life and pain measures . BTDS produced larger improvements than placebo at 12 weeks in all quality -of-life domains ( Ps < .05 ) . Treatment group differences in both physical and mental quality of life emerged by 4 weeks . Patients ' pretreatment quality of life was worse than that in the general population ( Ps < .05 ) ; only BTDS treatment eliminated deficits in pain , social functioning , and role limitations due to emotional health . Improvements in quality of life were moderately associated with pain reduction . These data suggest that moderate-to-severe CLBP patients receiving BTDS exhibited better quality of life than patients receiving placebo . PERSPECTIVE This post hoc analysis suggests that patients with moderate-to-severe CLBP treated with BTDS exhibit better health-related quality of life than those using placebo within 4 weeks of treatment , and were more likely to exhibit clinical ly meaningful improvements in quality of life following 12 weeks of treatment ABSTRACT Objective : This prospect i ve , r and omized , open-label , multicenter , community-based study was conducted to compare cyclobenzaprine 5 mg three times daily ( TID ) orally ( CYC5 ) given for 7 days as monotherapy or in combination with ibuprofen 400 mg TID ( CYC5/IBU400 ) or 800 mg TID ( CYC5/IBU800 ) in adults with acute neck or back pain with muscle spasm . Study design : Eligible patients were 18–65 years old , had cervical or thoracolumbar pain and spasm for ≤ 14 days , and , aside from the prescribed study medications , discontinued treatment with all analgesics , anti-inflammatory agents , and skeletal muscle relaxants during the study period . R and omization was 1:1:1 to the three treatment groups . Treatment outcome was assessed after 3 and 7 days of therapy using five patient-rated scales : spasm , pain , patient global impression of change ( PGIC ) , medication helpfulness , and Oswestry Disability Index ( ODI ) . Results : A total of 867 patients provided postbaseline data and were included in the intent-to-treat population ( CYC5 , n = 288 ; CYC5/IBU400 , n = 286 ; CYC5/IBU800 , n = 293 ) . All three treatment groups demonstrated significant improvements from baseline in PGIC , spasm , pain , ODI , and medication helpfulness ( p < 0.001 for all comparisons ) after 3 and 7 days of therapy . There were no significant differences in mean PGIC among groups after 3 days of therapy ( p = 0.65 for treatment effect ) or after 7 days of therapy ( primary endpoint ; p = 0.41 ) . A PGIC responder analysis of changes from baseline showed that 88 % and 93 % of patients reported at least mild improvement after 3 and 7 days of therapy , respectively . All three treatments were well tolerated , with no significant differences between treatments regarding the number of adverse events ( AEs ) reported or number of patients reporting AEs . The most common AEs in all groups were fatigue , somnolence , dizziness , sedation , and nausea . Limitations of this study include an unblinded design and possible introduction of bias into efficacy and safety results by use of a voluntary telephone reporting system . Conclusions : This r and omized , community-based clinical trial demonstrated that combination therapy with cyclobenzaprine 5 mg TID plus ibuprofen was not superior to cyclobenzaprine 5 mg TID alone in adult patients with acute neck and back pain with muscle spasm . All treatments were well tolerated BACKGROUND Tramadol and acetaminophen ( APAP ) have both shown efficacy in the treatment of lower back pain . The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios . OBJECTIVE This study assessed the long-term ( 3-month ) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain . METHODS Patients with at least moderate lower back pain ( pain visual analog [ PVA ] score > /=40 mm on a 100-mm scale ) were r and omized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days . Medication was titrated from 1 to 4 tablets/d by day 10 . The primary efficacy measure was PVA score at the final visit . Secondary measures included scores on the Pain Relief Rating Scale ( PRRS ) , Short-Form McGill Pain Question naire ( SF-MPQ ) , Rol and Disability Question naire ( RDQ ) , and 36-Item Short-Form Health Survey ( SF-36 ) ; the incidence of discontinuation due to insufficient pain relief ( Kaplan-Meier analysis ) ; and overall assessment s of medication by the patients and investigators . RESULTS Three hundred eighteen patients ( 161 tramadol/APAP , 157 placebo ) were included in the intent-to-treat population , defined as all patients who took > /=1 dose of study medication and had > /=1 postr and omization efficacy measurement . The mean age of the study population was 53.9 years , 63.2 % were female , 90.3 % were white , and the mean baseline PVA score was 70.0 mm . There were no significant differences between groups at baseline . Tramadol/APAP significantly improved final PVA scores ( P = 0.015 ) and final PRRS scores ( P < 0.001 ) compared with placebo . Tramadol/APAP also significantly improved RDQ scores ( P < /= 0.027 ) and scores on many subcategories of the SF-MPQ , including total score ( P = 0.021 ) . The tramadol/APAP group had significant improvements on the role-physical ( P = 0.005 ) , bodily pain ( P = 0.046 ) , role-emotional ( P = 0.001 ) , mental health ( P = 0.026 ) , reported health transition ( P = 0.038 ) , and mental component summary ( P = 0.008 ) subscales of the SF-36 . The cumulative incidence of discontinuation due to insufficient pain relief was 22.1 % for tramadol/APAP and 41.0 % for placebo ( P < 0.001 ) . Treatment-emergent adverse events in the tramadol/APAP group included nausea ( 13.0 % ) , somnolence ( 12.4 % ) , and constipation ( 11.2 % ) . CONCLUSIONS In this study , tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain Fifty-five patients suffering from refractory chronic back pain took part in a double-blind , multiple-dose , r and omised , cross-over study to compare the efficacy and tolerability of a fixed-dose capsule preparation containing 500 mg paracetamol ( CAS 103 - 90 - 2 ) and 30 mg codeine phosphate 1/2 H2O ( CAS 41444 - 62 - 6 ) ( talvosilen forte , test preparation ) with a reference capsule preparation containing 50 mg tramadol hydrochloride ( CAS 22204 - 88 - 2 ) , in a regimen of two capsules 8-hourly . There were two treatment periods of up to 7 days each . Cross-over took place , without washout , at the end of 7 days , or sooner if patients were unable to tolerate the first treatment . The test preparation was at least as efficacious as the reference in the treatment of back pain ( 81 % of patients experienced good or satisfactory pain relief ) . 81 % of patients tolerated the test well compared to only 69 % receiving the reference , as per protocol analysis . The results of this study suggest that the test product is at least as efficacious as tramadol in the treatment of patients with refractory chronic back pain , whilst being better tolerated In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted OBJECTIVE To compare the incidence of pain relief following injection of local anesthetic ( LA ) into lumbar discs that caused concordant pain during provocation testing . DESIGN Prospect i ve collected data review from two centers and compare with published results . OUTCOME MEASURES We compared subjective reported pain relief following provocative testing using the following protocol s at three separate facilities : 23 patients undergoing routine provocative discography using contrast alone ( PD ) ; 47 patients undergoing provocative discography performed using an equal combination of LA and contrast ( CPD ) ; 120 patients injected with LA following routine PD ( ADPD ) ; 33 patients undergoing st and -alone analgesic discography ( SAAD ) ; and 28 patients injected with LA through a catheter ( FAD ) placed during provocative discogaphy testing . RESULTS Pressure-controlled PD showed a positive response rate of 34 % per disc in patients with a clinical diagnosis of discogenic pain . None of the PD group without LA had pain relief and less than 10 % of the CPD group reported pain relief . Forty percent of the SAAD group with positive pain reproduction reported ≥50 % relief and 20 % reporting ≥80 % relief . Forty-six percent of the ADPD group reported ≥50 % relief and 30 % reporting ≥80 % relief . The FAD group had a greater 80 % patients reporting ≥50 % pain relief although fewer 26 % reporting more convincing ≥80 % relief . CONCLUSIONS If the criterion st and ard to confirm painful annular tears is concordant pain provocation and 80 % or greater pain relief following LA injected into lumbar discs , the SAAD , ADPD , and FAD protocol s show statistically similar 20 % to 30 % prevelance OBJECTIVE To evaluate the analgesic effectiveness/safety of the new oxycodone 7.5- and 10-mg/acetaminophen 325-mg ( Percocet ) formulations in patients with low back pain ( LBP ) suboptimally responsive to nonsteroidal anti-inflammatory drugs , muscle relaxants , tramadol , cyclo-oxygenase-2 inhibitors , and /or prn opioids . DESIGN Prospect i ve , open-label , nonr and omized , 4-week trial . SETTING Multicenter . PATIENTS Thirty-three men and women ( mean age : 52.2 years ) with LBP ( mean duration : 10.9 years ) . INTERVENTIONS All prior analgesics were discontinued , and oxycodone/acetaminophen was dosed three times a day ( TID ) , titrated to clinical ly meaningful pain relief . Initial oxycodone/acetaminophen dose : 2.5/325 mg TID ; maximum : 20/650 mg TID . OUTCOME MEASURES Effectiveness : Brief Pain Inventory ( BPI ) and Neuropathic Pain Scale 4 score ( sharp , hot , dull , and deep pain ) . Quality of life : BPI and North American Spine Society Lumbar Spine question naire . SAFETY Adverse events , physical/neurologic examinations , vital signs , and clinical laboratory tests . RESULTS In all , 28 of 33 patients ( 85 % ) completed the study ; discontinuations were for adverse events ( N=3 ) , patient choice ( N=1 ) , and lack of effectiveness ( N = 1 ) . The mean oxycodone/acetaminophen dose at the end of treatment was 8.2/325 mg TID . After 4 weeks , treatment significantly reduced BPI pain intensity and improved pain relief ( P < 0.0005 ) , improved Neuropathic Pain Scale 4 score ( P = 0.007 ) , reduced pain interference with quality of life ( P < 0.0004 ) , and reduced disability ( P < 0.0001 ) . Treatment was found to be safe and well tolerated . Adverse events were those most commonly expected from an opioid , and most were of mild-to-moderate intensity . CONCLUSIONS The primary purpose of this study was to preliminarily test the effectiveness of the new formulations of oxycodone/acetaminophen with reduced acetaminophen in the clinical practice setting . The results from this trial suggest that these formulations are effective in the treatment of moderate-to-severe chronic LBP . Most patients ( 67 % ) reported significant pain relief/tolerable side effects with a TID dosing frequency or less ( mean : 3.04 doses/day ) , suggesting chronic pain patients can experience meaningful pain relief with around-the-clock dosing of oxycodone/acetaminophen and minimal risk of hepatotoxicity . Further long-term , controlled studies of the efficacy/safety of the new formulations of oxycodone/acetaminophen in LBP are warranted to fully characterize efficacy in this patient population and corroborate the findings from our study Background : Chronic low back pain ( LBP ) is a growing health problem . Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) are used to treat this condition , but have not demonstrated efficacy beyond 2 weeks , and no studies have shown that NSAIDs produce durable improvements in disability . Methods : To evaluate the efficacy and durability of effect of etoricoxib for chronic LBP , a r and omized , double blind , placebo‐controlled trial was conducted at 46 centres . Three hundred and twenty‐five patients with chronic LBP requiring treatment with an NSAID or paracetamol were r and omized 1:1:1 to etoricoxib 60 mg ( n=109 ) , 90 mg ( n=106 ) , or placebo ( n=110 ) , daily for 3 months . Pre‐specified endpoints over 3 months included LBP intensity scale ( visual analog scale 0–100 mm ) time‐weighted average change from baseline , the Rol and –Morris Disability Question naire ( RMDQ ) , the LBP bothersomeness scale , patient and investigator global assessment s , and measures of quality of life . Results : Both etoricoxib groups experienced significant reductions in LBP intensity at 4 weeks versus placebo [ −15.15 mm and −13.03 mm for 60 and 90 mg , respectively , probability (p)<0.001 for each ] , which was maintained over 3 months . Treatment result ed in significant improvement from baseline compared to placebo in RMDQ scores ( etoricoxib 60 mg , −2.82 and 90 mg , −2.38 , p<0.001 for each ) over 12 weeks and most other efficacy endpoints . There were no significant differences between treatments in incidence of adverse events ( AEs ) or discontinuations due to AEs . Conclusion : Etoricoxib provided significant relief of symptoms and disability associated with chronic LBP detected at 1 week , confirmed at 4 weeks , and maintained over 3 months . Reductions in chronic LBP severity corresponded to improvements in physical functioning and quality of life . All treatments were generally well tolerated BACKGROUND Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs ; however , both types of medications are associated with side effects that can limit their usefulness in the outpatient setting . OBJECTIVE Two studies with identical protocol s assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib , a specific cyclooxygenase-2 inhibitor , in the treatment of acute pain after orthopedic surgery . METHODS These were multicenter , r and omized , placebo- and active-controlled , double-blind , parallel-group trials conducted between January and June 1998 . Both consisted of a single-dose assessment period ( SDAP ) and a multiple-dose assessment period ( MDAP ) . In the SDAP , patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg , hydrocodone 10 mg/acetaminophen 1000 mg , or placebo within 24 hours after the end of anesthesia , with pain assessment s conducted over the following 8-hour period . In the MDAP , extending from 8 hours after the first dose of study medication up to 5 days , patients who had received < or = 1 dose of rescue medication during the SDAP continued on study medication ( placebo recipients were rer and omized to active treatment ) , which could be taken up to 3 times a day as needed . RESULTS A total of 418 patients were enrolled in the 2 trials . During the SDAP , 141 patients received celecoxib , 136 received hydrocodone/acetaminophen , and 141 received placebo . During the MDAP , 185 patients received celecoxib and 181 received hydrocodone/acetaminophen . When the combined data were analyzed , mean pain intensity difference ( PID ) scores generally favored the active treatments over placebo from 1 to 6 hours ( with the exception of 1.5 hours ) after dosing ( P < or = 0.016 ) and favored celecoxib over the other treatments at 7 and 8 hours after dosing ( P < 0.001 ) . The active treatments demonstrated superior summed PID scores through 8 hours ( P < 0.001 ) , significantly shorter median times to onset of analgesia ( P < 0.05 ) , and significantly longer median times to first use of rescue medication ( P < 0.05 ) . During the MDAP , more hydrocodone/acetaminophen-treated patients ( 20 % ) than celecoxib-treated patients ( 12 % ) required rescue medication ( P < 0.05 ) , and the celecoxib group had significantly lower maximum pain intensity scores ( P < 0.001 , days 2 - 5 ) , required fewer doses of study medication ( P < or = 0.01 , days 3 - 5 ) , and had superior scores on a modified American Pain Society Patient Outcome Question naire ( P < or = 0.013 ) . In addition , a significantly lower proportion of celecoxib-treated patients experienced adverse events ( 43 % ) compared with hydrocodone/acetaminophen-treated patients ( 89 % ; P < 0.001 ) . CONCLUSIONS Over 8 hours , patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen . Over a 5-day period , oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day . Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain BACKGROUND Addition of nonopioid analgesic drugs reduces pain and opioid requirements in acute low back pain . In noncancer chronic low back pain ( CLBP ) , the efficacy of a combined regimen to reduce breakthrough pain has not been proven so far . OBJECTIVE Evaluation of the effects of intravenous ( i.v . ) nonopioid analgesic drugs on pain intensity and lumbar mobility in CLBP patients on chronic opioid therapy . DESIGN R and omised , placebo-controlled , double blinded , crossover study . SETTING Vienna General Hospital , Austria , from December 2002 to May 2004 . PATIENTS Thirty-six adults with CLBP on chronic opioid therapy . Inclusion criteria are as follows : American Society of Anesthesiologists ' physical status less than 3 , visual analogue scale ( VAS ) more than 4 and no known allergy to any of the used drugs . INTERVENTION After written informed consent and VAS assessment , any oral nonopioid analgesic drug ( NSAIDs , metamizol , paracetamol ) was replaced by placebo 10 days before the first test infusion as a washout period . Coanalgesics ( anticonvulsants , antidepressants ) were maintained . Each patient received r and omly four i.v . test infusions of diclofenac 75 mg ( and orphenadrine 30 mg ) , parecoxib 40 mg , paracetamol 1 g and isotonic saline . A washout time of 72 h was allowed between each infusion . MAIN OUTCOME MEASURES Primary outcome was as follows : VAS pain intensity ( 0 to 100 mm ) at inclusion , before and within 30 min after infusion . Secondary outcomes were as follows : Rol and -Morris question naire , McGill pain question naire and a test panel of physical functioning for spinal mobility , muscular endurance , balance and coordination . The differences in means of the above assessment s among the groups were analysed . RESULTS We found an improvement in VAS from the day of inclusion to the day of each appointment . We observed no improvement in pain intensity ( VAS ) or in any of the physical functioning tests immediately before versus after administration of the four i.v . drugs . Reductions in sensory , affective and cognitive dimensions of the McGill pain question naire were statistically significant in the diclofenac group . A trend of McGill pain question naire improvement existed in the other groups . CONCLUSION The present data show that the anticipation of an i.v . infusion of nonopioid analgesic drug improves VAS significantly , probably through expectation-related mechanisms . However , single dose i.v . infusions of nonopioid analgesic drugs fail to improve pain intensity and spinal mobility in CLBP patients on chronic opioid treatment , even immediately after the infusion |
12,614 | 23,415,822 | The tested web applications offered similar functionalities for recording food intake .
The systems studied provided some degree of personalization : users can access some systems via PCs or mobile phones and they can choose among various types of data input content for recording food intake .
Many functions , such as search in a food data base , reports , graphical presentation , listing of favorite foods , and overview of the user 's own meals , are optimized to simplify the recording process and save time .
Data sharing and reports are common features of the review ed systems .
However , none use the user 's recorded food history to make suggestions on new nutritional intake , during the food recording process . | BACKGROUND Increasing healthcare costs related to lifestyle-related chronic diseases require new solutions .
Research on self-management tools is exp and ing and many new tools are emerging .
Recording food intake is a key functionality in many of these tools .
Nutrition monitoring is a relevant method to gain an overview of factors influencing health .
However , keeping a food diary often constitutes a challenge for a patient , and developing a user-friendly and useful electronic food diary is not straightforward .
PURPOSE To gain insight into the existing approaches to recording food intake , and to analyze current functionalities and input methods . | Technology may improve self-monitoring adherence and dietary changes in weight loss treatment . Our study aim ed to investigate whether using a personal digital assistant ( PDA ) with dietary and exercise software , with and without a feedback message , compared to using a paper diary/record ( PR ) , results in greater weight loss and improved self-monitoring adherence . Healthy adults ( N = 210 ) with a mean BMI of 34.01 kg/m(2 ) were r and omized to one of three self-monitoring approaches : PR ( n = 72 ) , PDA with self-monitoring software ( n = 68 ) , or PDA with self-monitoring software and daily feedback messages ( PDA+FB , n = 70 ) . All participants received st and ard behavioral treatment . Self-monitoring adherence and change in body weight , waist circumference , and diet were assessed at 6 months ; retention was 91 % . All participants had a significant weight loss ( P < 0.01 ) but weight loss did not differ among groups . A higher proportion of PDA+FB participants ( 63 % ) achieved ≥ 5 % weight loss in comparison to the PR group ( 46 % ) ( P < 0.05 ) and PDA group ( 49 % ) ( P = 0.09 ) . Median percent self-monitoring adherence over the 6 months was higher in the PDA groups ( PDA 80 % ; PDA+FB 90 % ) than in the PR group ( 55 % ) ( P < 0.01 ) . Waist circumference decreased more in the PDA groups than the PR group ( P = 0.02 ) . Similarly , the PDA groups reduced energy and saturated fat intake more than the PR group ( P < 0.05 ) . Self-monitoring adherence was greater in the PDA groups with the greatest weight change observed in the PDA+FB group PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by cellular phone and Internet would improve blood pressure , weight control , and serum lipids of obese patients with hypertension during 8 weeks . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the family medicine outpatient department of tertiary care hospital located in an urban city of South Korea . Twenty-eight patients were assigned to an intervention group and 21 to a control group . The goal of intervention was to bring blood pressure , body weight , and serum lipids levels close to normal ranges . Patients in the intervention group were requested to record their blood pressure and body weight in a weekly web based diary through the Internet or by cellular phones . The research ers sent optimal recommendations as an intervention to each patient , by both cellular phone and Internet weekly . The intervention was applied for 8 weeks . RESULTS Systolic ( SBP ) and diastolic blood pressures ( DBP ) significantly decreased by 9.1 and 7.2 mmHg respectively at 8 weeks from the baseline in the intervention group ( p<0.05 ) . However , after 8 weeks from the baseline both SBP and DBP in the control group had not changed significantly . Yet , There were significant mean decreases in body weight and waist circumference by 1.6 kg ( p<0.05 ) and 2.8 cm ( p<0.05 ) in the intervention group , respectively . In the control group increases in body weight and waist circumference ( p<0.05 ) mean changes were also significant . High density lipoprotein cholesterol ( HDL-C ) significantly increased , with a mean change of 3.7 mg/dl at 8 weeks from baseline in the intervention group ( p<0.05 ) . The mean change of HDL-C in the control group was , however , not significant . CONCLUSION During 8 weeks using this web-based intervention by way of cellular phone and Internet SMS improved blood pressure , body weight , waist circumference , and HDL-C in patients with obese hypertension Background For most individuals , long-term maintenance of weight loss requires long-term , supportive intervention . Internet-based weight loss maintenance programs offer considerable potential for meeting this need . Careful design processes are required to maximize adherence and minimize attrition . Objective This paper describes the development , implementation and use of a Web-based intervention program design ed to help those who have recently lost weight sustain their weight loss over 1 year . Methods The weight loss maintenance website was developed over a 1-year period by an interdisciplinary team of public health research ers , behavior change intervention experts , applications developers , and interface design ers . Key interactive features of the final site include social support , self-monitoring , written guidelines for diet and physical activity , links to appropriate websites , supportive tools for behavior change , check-in accountability , tailored reinforcement messages , and problem solving and relapse prevention training . The weight loss maintenance program included a reminder system ( automated email and telephone messages ) that prompted participants to return to the website if they missed their check-in date . If there was no log-in response to the email and telephone automated prompts , a staff member called the participant . We tracked the proportion of participants with at least one log-in per month , and analyzed log-ins as a result of automated prompts . Results The mean age of the 348 participants enrolled in an ongoing r and omized trial and assigned to use the website was 56 years ; 63 % were female , and 38 % were African American . While weight loss data will not be available until mid-2008 , website use remained high during the first year with over 80 % of the participants still using the website during month 12 . During the first 52 weeks , participants averaged 35 weeks with at least one log-in . Email and telephone prompts appear to be very effective at helping participants sustain ongoing website use . Conclusions Developing interactive websites is expensive , complex , and time consuming . We found that extensive paper prototyping well in advance of programming and a versatile product manager who could work with project staff at all levels of detail were essential to keeping the development process efficient . Trial Registration clinical trials.gov OBJECTIVE To develop and evaluate a pictorial , web-based version of the NCI diet history question naire ( Web-PDHQ ) . DESIGN The Web-PDHQ and paper version of the DHQ ( Paper-DHQ ) were administered 4 weeks apart with 218 participants r and omised to order . Dietary data from the Web-PDHQ and Paper-DHQ were vali date d using a r and omly selected 4 d food record recording period ( including a weekend day ) and two r and omly selected 24 h dietary recalls during the 4 weeks intervening between these two diet history administrations . SETTING Research office in Reston , VA , USA . PARTICIPANTS Computer-literate men and women recruited through newspaper advertisements . RESULTS Mean correlation of energy and the twenty-five examined nutrients between the Web-PDHQ and Paper-DHQ was 0.71 and 0.51 , unadjusted and energy-adjusted by the residual method , respectively . Moderate mean correlations ( unadjusted 0.41 and 0.38 ; energy-adjusted 0.41 and 0.34 ) were obtained between both the Web-PDHQ and Paper-DHQ with the 4 d food record on energy and nutrients , but the correlations between the Web-PDHQ and Paper-DHQ with the 24 h recalls were modest ( unadjusted 0.31 and 0.29 ; energy-adjusted 0.37 and 0.26 ) . A subset of participants ( n 48 ) completing the Web-PDHQ at the initial visit performed a retest on the same question naire 1 week later to determine repeatability , and the unadjusted mean correlation was 0.82 . CONCLUSIONS These data indicate that the Web-PDHQ has comparable repeatability and validity to the Paper-DHQ but did not improve the relationship of the DHQ to other food intake measures ( e.g. food records , 24 h recall ) PURPOSE The present study evaluated whether an intervention using the SMS by personal cellular phone and internet would improve the levels of plasma glucose of obese type 2 diabetes at 3 , 6 , 9 , and 12 months . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the endocrinology outpatient department of tertiary care hospital located in an urban city of South Korea . Eighteen patients were r and omly assigned to an intervention group and 16 to a control group . The goal of the intervention was to decrease body weight and keep blood glucose concentrations close to the normal range . Patients were requested to record their blood glucose level in a weekly diary on the website by personal cellular phones or computer internet . The research er sent optimal recommendations to each patient , by both the cellular phone and the Internet weekly . The intervention was applied for 1 year . RESULTS Glycosylated hemoglobin ( HbA(1)c ) decreased 1.22 percentage points at 3 months , 1.09 percentage points at 6 months , 1.47 percentage points at 9 months , and 1.49 percentage points at 12 months compared with baseline in the intervention group ( all time points , p<0.05 ) . The percentage change in the control group was , however , not significant . Patients in the intervention group had a decrease of 2-h post-pr and ial test ( 2HPPT ) of 120.1mg/dl at 3 months , 58.9 mg/dl at 6 months , 62.0mg/dl at 9 months , and 102.9 mg/dl at 12 months compared with baseline ( all time points , p<0.05 ) . The mean change in the control group was , however , not significant . CONCLUSION This web-based intervention using SMS of personal cellular phone and Internet improved HbA(1)c and 2HPPT at 3 , 6 , 9 , and 12 months in patients with obese type 2 diabetes OBJECTIVE To determine the characteristics and behaviors associated with adherence to dietary protein interventions among participants with chronic renal disease in the Modification of Diet in Renal Disease ( MDRD ) Study . DESIGN Participants were categorized as consistent adherers or nonadherers on the basis of urinary urea nitrogen excretion and dietary protein intake data from self-reports . Psychosocial and behavioral factors were compared between groups . SUBJECTS Subgroups of consistently adherent and non-adherent participants in the MDRD Study . SETTING 15 clinical centers in the United States . INTERVENTION In the nutrition intervention program , participants were assigned r and omly to a usual- , low- , or very-low-protein diet group . Each eating pattern also specified a phosphorus goal . STATISTICAL ANALYSIS Analysis of variance . RESULT Psychosocial factors significantly related to adherence included participant knowledge , attitude , support , satisfaction , and self-perception of success . Behavioral strategies including participant self-monitoring of protein intake and the provision of feedback by the dietitian were also significantly related to adherence . APPLICATION Nutrition interventions for patients with renal disease should focus on psychosocial factors and behavioral approaches . Such approaches can be successfully incorporated into treatment programs and will assist the dietitian in promoting adherence to usual- , low- , and very-low-protein eating patterns Objective : To evaluate the capability of DietMatePro , a PDA-based dietary assessment program , to monitor dietary intake and to improve adherence to a dietary regimen . Design : R and omized controlled trial . Subjects . Overweight and obese ( Body Mass Index ( BMI ) 25–40 ) participants without dietary restrictions . Intervention : Participants ( n = 174 ) were r and omized to record usual dietary intake using either DietMatePro or a paper food diary for one week to compare concordance with 24-hr recall . At the week 1 visit , participants were individually counseled to follow the diet recommendations of the Ornish Prevention Diet for three weeks and continue monitoring food intake using the assigned method to estimate adherence to the intervention by monitoring condition . Outcome Measures : Spearman correlations between week 1 24-hr recall and the assigned recording method were compared to assess validity . Mean pre-post changes in intake measured by 24-hr recall were compared according to monitoring condition to measure adherence to the Ornish diet . Results : Correlations of energy and nutrient values reported on the food label ranged from 0.41 to 0.71 for the DietMatePro condition versus 0.63 to 0.83 for the paper-based diary . Diet adherence was higher among DietMatePro ( 43 % ) compared to the paper diary ( 28 % ) group ( p = 0.039 ) . Conclusions /Applications : DietMatePro does not appear to produce more valid data than paper-based approaches . DietMatePro may improve adherence to dietary regimens compared to paper-based methods |
12,615 | 24,606,458 | This meta- analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled .
CONCLUTIOS : Abiraterone significantly prolonged OS , RPFS and time to progression patients with mCRPC , regardless of prior chemotherapy or whether chemotherapy-naive , and no unexpected toxicity was evident .
Abiraterone can serve as a new st and ard therapy for mCRPC | INTRODUCTION Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy , progression eventually occurs .
Based on the exciting results of several r and omized controlled trials ( RCTs ) , it seems that patients with metastatic castration-resistant prostate cancer ( mCRPC ) might benefit more from treatment withabiraterone .
Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC . | BACKGROUND Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive and rogen-independent prostate cancer . We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic , hormone-independent prostate cancer . METHODS We r and omly assigned 770 men to one of two treatments , each given in 21-day cycles : 280 mg of estramustine three times daily on days 1 through 5 , 60 mg of docetaxel per square meter of body-surface area on day 2 , and 60 mg of dexamethasone in three divided doses before docetaxel , or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily . The primary end point was overall survival ; secondary end points were progression-free survival , objective response rates , and post-treatment declines of at least 50 percent in serum prostate-specific antigen ( PSA ) levels . RESULTS Of 674 eligible patients , 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone . In an intention-to-treat analysis , the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone ( 17.5 months vs. 15.6 months , P=0.02 by the log-rank test ) , and the corresponding hazard ratio for death was 0.80 ( 95 percent confidence interval , 0.67 to 0.97 ) . The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone ( P<0.001 by the log-rank test ) . PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients , respectively ( P<0.001 ) , and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease , respectively ( P=0.30 ) . Grade 3 or 4 neutropenic fevers ( P=0.01 ) , nausea and vomiting ( P<0.001 ) , and cardiovascular events ( P=0.001 ) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone . Pain relief was similar in both groups . CONCLUSIONS The improvement in median survival of nearly two months with docetaxel and estramustine , as compared with mitoxantrone and prednisone , provides support for this approach in men with metastatic , and rogen-independent prostate cancer This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence PURPOSE Abiraterone acetate is a prodrug of abiraterone , a selective inhibitor of CYP17 , the enzyme catalyst for two essential steps in and rogen bio synthesis . In castration-resistant prostate cancers ( CRPCs ) , extragonadal and rogen sources may sustain tumor growth despite a castrate environment . This phase I dose-escalation study of abiraterone acetate evaluated safety , pharmacokinetics , and effects on steroidogenesis and prostate-specific antigen ( PSA ) levels in men with CPRC with or without prior ketoconazole therapy . PATIENTS AND METHODS Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled . Nineteen patients ( 58 % ) had previously received ketoconazole for CRPC . Bone metastases were present in 70 % of patients , and visceral involvement was present in 18 % . Three patients ( 9 % ) had locally advanced disease without distant metastases . Fasted or fed cohorts received abiraterone acetate doses of 250 , 500 , 750 , or 1,000 mg daily . Single-dose pharmacokinetic analyses were performed before continuous daily dosing . RESULTS Adverse events were predominantly grade 1 or 2 . No dose-limiting toxicities were observed . Hypertension ( grade 3 , 12 % ) and hypokalemia ( grade 3 , 6 % ; grade 4 , 3 % ) were the most frequent serious toxicities and responded to medical management . Confirmed > or = 50 % PSA declines at week 12 were seen in 18 ( 55 % ) of 33 patients , including nine ( 47 % ) of 19 patients with prior ketoconazole therapy and nine ( 64 % ) of 14 patients without prior ketoconazole therapy . Substantial declines in circulating and rogens and increases in mineralocorticoids were seen with all doses . CONCLUSION Abiraterone acetate was well tolerated and demonstrated activity in CRPC , including in patients previously treated with ketoconazole . Continued clinical study is warranted PURPOSE It has been postulated that castration-resistant prostate cancer ( CRPC ) commonly remains hormone dependent . Abiraterone acetate is a potent , selective , and orally available inhibitor of CYP17 , the key enzyme in and rogen and estrogen bio synthesis . PATIENTS AND METHODS This was a phase I/II study of abiraterone acetate in castrate , chemotherapy-naive CRPC patients ( n = 54 ) with phase II expansion at 1,000 mg ( n = 42 ) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen ( PSA ) decline of > or = 50 % ( null hypothesis = 0.1 ; alternative hypothesis = 0.3 ; alpha = .05 ; beta = .14 ) . Computed tomography scans every 12 weeks and circulating tumor cell ( CTC ) enumeration were performed . Prospect i ve reversal of resistance at progression by adding dexamethasone 0.5 mg/d to suppress adrenocorticotropic hormone and upstream steroids was pursued . RESULTS A decline in PSA of > or = 50 % was observed in 28 ( 67 % ) of 42 phase II patients , and declines of > or = 90 % were observed in eight ( 19 % ) of 42 patients . Independent radiologic evaluation reported partial responses ( Response Evaluation Criteria in Solid Tumors ) in nine ( 37.5 % ) of 24 phase II patients with measurable disease . Decreases in CTC counts were also documented . The median time to PSA progression ( TTPP ) on abiraterone acetate alone for all phase II patients was 225 days ( 95 % CI , 162 to 287 days ) . Exploratory analyses were performed on all 54 phase I/II patients ; the addition of dexamethasone at disease progression reversed resistance in 33 % of patients regardless of prior treatment with dexamethasone , and pretreatment serum and rogen and estradiol levels were associated with a probability of > or = 50 % PSA decline and TTPP on abiraterone acetate and dexamethasone . CONCLUSION CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses , confirming that CRPC commonly remains hormone driven PURPOSE The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate , an oral , specific , irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer ( CRPC ) . PATIENTS AND METHODS In this multicenter , two-stage , phase II study , abiraterone acetate 1,000 mg was administered once daily continuously . The primary end point was achievement of a prostate-specific antigen ( PSA ) decline of > or = 50 % in at least seven of 35 patients . Per an attained phase II design , more than 35 patients could be enrolled if the primary end point was met . Secondary objectives included : PSA declines of > or = 30 % and > or = 90 % ; rate of RECIST ( Response Evaluation Criteria in Solid Tumors ) responses and duration on study ; time to PSA progression ; safety and tolerability ; and circulating tumor cell ( CTC ) enumeration . RESULTS Docetaxel-treated patients with CRPC ( N = 47 ) were enrolled . PSA declines of > or = 30 % , > or = 50 % and > or = 90 % were seen in 68 % ( 32 of 47 ) , 51 % ( 24 of 47 ) , and 15 % ( seven of 47 ) of patients , respectively . Partial responses ( by RECIST ) were reported in eight ( 27 % ) of 30 patients with measurable disease . Median time to PSA progression was 169 days ( 95 % CI , 113 to 281 days ) . The median number of weeks on study was 24 , and 12 ( 25.5 % ) of 47 patients remained on study > or = 48 weeks . CTCs were enumerated in 34 patients ; 27 ( 79 % ) of 34 patients had at least five CTCs at baseline . Eleven ( 41 % ) of 27 patients had a decline from at least five to less than 5 CTCs , and 18 ( 67 % ) of 27 had a > or = 30 % decline in CTCs after starting treatment with abiraterone acetate . Abiraterone acetate was well tolerated . CONCLUSION Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC . R and omized , phase III trials of abiraterone acetate are underway to define the future role of this agent PURPOSE Studies indicate that castration-resistant prostate cancer ( CRPC ) remains driven by lig and -dependent and rogen receptor ( AR ) signaling . To evaluate this , a trial of abiraterone acetate-a potent , selective , small-molecule inhibitor of cytochrome P ( CYP ) 17 , a key enzyme in and rogen synthesis -was pursued . PATIENTS AND METHODS Chemotherapy-naïve men ( n = 21 ) who had prostate cancer that was resistant to multiple hormonal therapies were treated in this phase I study of once-daily , continuous abiraterone acetate , which escalated through five doses ( 250 to 2,000 mg ) in three-patient cohorts . RESULTS Abiraterone acetate was well tolerated . The anticipated toxicities attributable to a syndrome of secondary mineralocorticoid excess-namely hypertension , hypokalemia , and lower-limb edema-were successfully managed with a mineralocorticoid receptor antagonist . Antitumor activity was observed at all doses ; however , because of a plateau in pharmacodynamic effect , 1,000 mg was selected for cohort expansion ( n = 9 ) . Abiraterone acetate administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone , downstream and rogenic steroids , and estradiol in all patients . Declines in prostate-specific antigen > or= 30 % , 50 % , and 90 % were observed in 14 ( 66 % ) , 12 ( 57 % ) , and 6 ( 29 % ) patients , respectively , and lasted between 69 to > or= 578 days . Radiologic regression , normalization of lactate dehydrogenase , and improved symptoms with a reduction in analgesic use were documented . CONCLUSION CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC . These data confirm that CRPC commonly remains dependent on lig and -activated AR signaling To test the hypothesis that maximal and rogen blockade improves the effectiveness of the treatment of prostatic cancer , we conducted a r and omized , double-blind trial in patients with disseminated , previously untreated prostate cancer ( stage D2 ) . All 603 men received leuprolide , an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins , in combination with either placebo or flutamide , a nonsteroidal anti and rogen that inhibits the binding of and rogens to the cell nucleus . As compared with the 300 patients receiving leuprolide and placebo , the 303 patients r and omly assigned to receive leuprolide and flutamide had a longer progression-free survival ( 16.5 vs. 13.9 months ; P = 0.039 ) and an increase in the median length of survival ( 35.6 vs. 28.3 months ; P = 0.035 ) . The differences between the treatments were particularly evident for men with minimal disease and good performance status ; however , further studies should be conducted in this subgroup . Symptomatic improvement was greatest during the first 12 weeks of the combined and rogen blockade , when leuprolide alone often produces a painful flare in the disease . We conclude that in patients with advanced prostate cancer , treatment with leuprolide and flutamide is superior to treatment with leuprolide alone PURPOSE Persistence of lig and -mediated and rogen receptor signaling has been documented in castration-resistant prostate cancers ( CRPCs ) . Abiraterone acetate ( AA ) is a potent and selective inhibitor of CYP17 , which is required for and rogen bio synthesis in the testes , adrenal gl and s , and prostate tissue . This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy . PATIENTS AND METHODS Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA ( 1,000 mg daily ) with prednisone ( 5 mg twice daily ) . Twenty-seven ( 47 % ) patients had received prior ketoconazole . The primary outcome was > or = 50 % prostate-specific antigen ( PSA ) decline , with objective response by Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria , and changes in Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) and circulating tumor cell ( CTC ) numbers . Safety was also evaluated . RESULTS A > or = 50 % decline in PSA was confirmed in 22 ( 36 % ) patients , including 14 ( 45 % ) of 31 ketoconazole-naïve and seven ( 26 % ) of 27 ketoconazole-pretreated patients . Partial responses were seen in four ( 18 % ) of 22 patients with RECIST-evaluable target lesions . Improved ECOG PS was seen in 28 % of patients . Median time to PSA progression was 169 days ( 95 % CI , 82 to 200 days ) . CTC conversions with treatment from > or = 5 to < 5 were noted in 10 ( 34 % ) of 29 patients . The majority of AA-related adverse events were grade 1 to 2 , and no AA-related grade 4 events were seen . CONCLUSION AA plus prednisone was well tolerated , with encouraging antitumor activity in heavily pretreated CRPC patients . The incidence of mineralocorticoid-related toxicities ( hypertension or hypokalemia ) was reduced by adding low-dose prednisone . The combination of AA plus prednisone is recommended for phase III investigations |
12,616 | 30,170,996 | Moderate level evidence favoured eccentric exercise over control for improving pain and function in mid-portion tendinopathy .
Moderate level evidence favoured eccentric exercise over concentric exercise for reducing pain .
There was moderate level evidence of no significant difference in pain or function between eccentric exercise and heavy slow resistance exercise .
There was low level evidence that eccentric exercise was not superior to stretching for pain or QoL. There was moderate level evidence that a combined exercise protocol was not superior to a lower dosage protocol for improving functional performance .
Eccentric exercise was not superior to splinting for pain ( moderate evidence ) or function ( low level evidence ) .
Summary We conditionally recommend exercise for improving pain and function in mid-portion Achilles tendinopathy .
The balance of evidence did not support recommendation of one type of exercise programme over another .
We conditionally recommend against the addition of a splint to an eccentric exercise protocol and we do not recommend the use of orthoses to improve pain and function in Achilles tendinopathy | Objectives To assess the efficacy of exercise , orthoses and splinting on function , pain and quality of life ( QoL ) for the management of mid-portion and insertional Achilles tendinopathy , and to compare different types , applications and modes of delivery within each intervention category . | Background —There is no disease specific , reliable , and valid clinical measure of Achilles tendinopathy . Objective —To develop and test a question naire based instrument that would serve as an index of severity of Achilles tendinopathy . Methods —Item generation , item reduction , item scaling , and pretesting were used to develop a question naire to assess the severity of Achilles tendinopathy . The final version consisted of eight questions that measured the domains of pain , function in daily living , and sporting activity . Results range from 0 to 100 , where 100 represents the perfect score . Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy ( n = 45 ) , presurgical patients with Achilles tendinopathy ( n = 14 ) , and two normal control population s ( total n = 87 ) . Results —The VISA-A question naire had good test-retest ( r = 0.93 ) , intrarater ( three tests , r = 0.90 ) , and interrater ( r = 0.90 ) reliability as well as good stability when compared one week apart ( r = 0.81 ) . The mean ( 95 % confidence interval ) VISA-A score in the non-surgical patients was 64 ( 59–69 ) , in presurgical patients 44 ( 28–60 ) , and in control subjects it exceeded 96 ( 94–99 ) . Thus the VISA-A score was higher in non-surgical than presurgical patients ( p = 0.02 ) and higher in control subjects than in both patient population s ( p<0.001 ) . Conclusions —The VISA-A question naire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects . The continuous numerical result of the VISA-A question naire has the potential to provide utility in both the clinical setting and research . The test is not design ed to be diagnostic . Further studies are needed to determine whether the VISA-A score predicts prognosis Background The common regime of eccentric exercise in use for Achilles tendinopathy is somewhat arduous and compliance issues can arise . This is the first study to investigate the effectiveness of a regime of fewer exercise sessions combined with photobiomodulation for the treatment of Achilles tendinopathy . Methods A double blind r and omized controlled trial and intention-to-treat analysis were performed . Eighty participants , 18–65 years with Achilles tendinopathy and symptoms for longer than 3 months , were included in the trial . Participants r and omized into one of four groups ; 1 ( Placebo + Ex Regime 1 ) or 2 ( Laser + Ex Regime 1 ) or 3 ( Placebo + Ex Regime 2 ) or 4 ( Laser + Ex Regime 2 ) . The primary outcome measure was the Victorian Institute of Sports Assessment -Achilles ( VISA-A ) question naire . Outcomes were collected at baseline , week 4 and week 12 . Results Sixteen participants were lost to follow-up at 12 weeks , 4 of which due to adverse reactions . As per intention to treat , missing data were imputed , 80 participants were included in the final analysis . For VISA-A at 12 weeks , group 4 achieved significant gains over the other 3 groups : group 1 ( 18.5 [ 9.1 , 27.9 ] ) , group 2 ( 10.4 [ 1.5 , 19.2 ] ) , group 3 ( 11.3 [ 3.0 , 19.6 ] ) . There was a moderate effect size in favour of exercise twice per week ( 7.2 [ −1.8 , 16.2 ] , ES .7 ) . Conclusions Twice-daily exercise sessions are not necessary as equivalent results can be obtained with two exercise sessions per week . The addition of photobiomodulation as adjunct to exercise can bring added benefit Objective The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic midportion Achilles tendinopathy . Design One-year follow-up of a r and omised controlled single blinded clinical trial . Setting Sports medicine department in a general hospital . Patients 58 patients ( 70 tendons ) were included . Interventions All patients completed a 12-week heavy load eccentric training programme . One group received a night splint in addition to eccentric exercises . Main outcome measurements Outcome scores were : Victorian Institute of Sport Assessment —Achilles ( VISAA ) score , subjective patient satisfaction and neovascularisation score measured with power Doppler ultrasonography ( PDU ) . Results For both groups the VISA-A score increased significantly ( from 50 to 76 ( p<0.01 ) in the eccentric group and from 49 to 78 ( p<0.01 ) in the night splint group ) . No significant differences in the VISA-A score were found between the groups from baseline to one year ( p = 0.32 ) . The presence of neovessels at baseline did not predict a change in the VISA-A score after one year in the whole group ( p = 0.71 ) . Conclusion Eccentric exercises with or without a night splint improved functional outcome at one year follow-up . At follow-up there was no significant difference in clinical outcome when a night splint was used in addition to an eccentric exercise programme . Between 3 months and one year follow-up , a continuing increase in the VISA-A score was found . Assessment of the neovascularisation score with PDU at baseline has no prognostic value on long-term clinical outcome AIM Prognosis and treatment of Achilles tendon pain ( achillodynia ) has been insufficiently studied . The purpose of the present study was to examine the long-term effect of eccentric exercises compared with stretching exercises on patients with achillodynia . METHODS Patients with achillodynia for at least 3 months were r and omly allocated to one of two exercise regimens . Exercise was performed daily for a 3-month period . Symptom severity was evaluated by tendon tenderness , ultrasonography , a question naire on pain and other symptoms , and a global assessment of improvement . Follow-up was performed at time points 3 , 6 , 9 , 12 weeks and 1 year . RESULTS Of 53 patients with achillodynia 45 patients were r and omized to either eccentric exercises or stretching exercises . Symptoms gradually improved during the 1-year follow-up period and were significantly better assessed by pain and symptoms after 3 weeks and all later visits . However , no significant differences could be observed between the two groups . Women and patients with symptoms from the distal part of the tendon had significantly less improvement . CONCLUSIONS Marked improvement in symptoms and findings could be gradually observed in both groups during the 1-year follow-up period . To that extent this is due to effect of both regimens or the spontaneous improvement is unsettled Aim To evaluate the effectiveness of customised foot orthoses in chronic mid-portion Achilles tendinopathy . Methods This was a participant-blinded , parallel-group r and omised controlled trial at a single centre ( La Trobe University , Melbourne , Australia ) . One hundred and forty participants aged 18–55 years with mid-portion Achilles tendinopathy were r and omised to receive eccentric calf muscle exercises with either customised foot orthoses ( intervention group ) or sham foot orthoses ( control group ) . Allocation to intervention was concealed . The Victorian Institute of Sports Assessment -Achilles ( VISA-A ) question naire was completed at baseline , then at 1 , 3 , 6 and 12 months , with 3 months being the primary end point . Differences between groups were analysed using intention to treat with analysis of covariance . Results After r and omisation into the customised foot orthoses group ( n=67 ) or sham foot orthoses group ( n=73 ) , there was 70.7 % follow-up of participants at 3 months . There were no significant differences between groups at any time point . At 3 months , the mean ( SD ) VISA-A score was 82.1 ( 16.3 ) and 79.2 ( 20.0 ) points for the customised and sham foot orthosis groups , respectively ( adjusted mean difference ( 95 % CI)=2.6 ( −2.9 to 8.0 ) , p=0.353 ) . There were no clinical ly meaningful differences between groups in any of the secondary outcome measures . Conclusions Customised foot orthoses , prescribed according to the protocol in this study , are no more effective than sham foot orthoses for reducing symptoms and improving function in people with mid-portion Achilles tendinopathy undergoing an eccentric calf muscle exercise programme . Trial Registration Number Australian New Zeal and Clinical Trials Registry : number ACTRN12609000829213 Achilles tendinopathy is common and treatment with eccentric exercises seems promising . We design ed a prospect i ve r and omized clinical trial to test the hypothesis that eccentric calf muscle exercises reduce pain and improve function in patients with Achilles tendinopathy . Forty-four patients were recruited from primary care ( mean age : 45 years ; 23 women ; 65 % active in sports ) and r and omized to three treatment groups for 12 weeks : eccentric exercises , a night splint or a combination of both treatments . Pain and function were evaluated at 6 , 12 , 26 and 52 weeks by the Foot and Ankle Outcome Score . At 6 weeks , the eccentric group reported a significant pain reduction ( 27 % compared with baseline , P = 0.007 ) which lasted for 1 year ( 42 % , P = 0.001 ) . The two groups treated with a night splint also reported significant but less pain reduction than the eccentric group . Differences between all the three groups were not significant . At 12 weeks , the eccentric group reported significantly less pain than the splint-only group ( P = 0.04 ) . More patients in the eccentric group than in the splint group returned to sport after 12 weeks . We conclude that eccentric exercises seem to reduce pain and improve function in patients with Achilles tendinopathy . Our results are in line with previous studies and strengthen the recommendation that patients should undergo an eccentric exercise program prior to considering other treatments such as surgery Background Achilles tendinopathy is a common condition that can cause marked pain and disability . Numerous non-surgical treatments have been proposed for the treatment of this condition , but many of these treatments have a poor or non-existent evidence base . The exception to this is eccentric calf muscle exercises , which have become a st and ard non-surgical intervention for Achilles tendinopathy . Foot orthoses have also been advocated as a treatment for Achilles tendinopathy , but the long-term efficacy of foot orthoses for this condition is unknown . This manuscript describes the design of a r and omised trial to evaluate the efficacy of customised foot orthoses to reduce pain and improve function in people with Achilles tendinopathy . Methods One hundred and forty community-dwelling men and women aged 18 to 55 years with Achilles tendinopathy ( who satisfy inclusion and exclusion criteria ) will be recruited . Participants will be r and omised , using a computer-generated r and om number sequence , to either a control group ( sham foot orthoses made from compressible ethylene vinyl acetate foam ) or an experimental group ( customised foot orthoses made from semi-rigid polypropylene ) . Both groups will be prescribed a calf muscle eccentric exercise program , however , the primary difference between the groups will be that the experimental group receive customised foot orthoses , while the control group receive sham foot orthoses . The participants will be instructed to perform eccentric exercises 2 times per day , 7 days per week , for 12 weeks . The primary outcome measure will be the total score of the Victorian Institute of Sport Assessment - Achilles ( VISA-A ) question naire . The secondary outcome measures will be participant perception of treatment effect , comfort of the foot orthoses , use of co- interventions , frequency and severity of adverse events , level of physical activity and health-related quality of life ( assessed using the Short-Form-36 question naire - Version two ) . Data will be collected at baseline , then at 1 , 3 , 6 and 12 months . Data will be analysed using the intention to treat principle . Discussion This study is the first r and omised trial to evaluate the long-term efficacy of customised foot orthoses for the treatment of Achilles tendinopathy . The study has been pragmatically design ed to ensure that the study findings are generalisable to clinical practice .Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12609000829213 In a previous uncontrolled pilot study we demonstrated very good clinical results with eccentric calf muscle training on patients with painful chronic Achilles tendinosis located at the 2–6 cm level in the tendon . In the present prospect i ve multicenter study ( Sundsvall and Umeå ) patients with painful chronic Achilles tendinosis at the 2–6 cm level in the tendon were r and omized to treatment with either an eccentric or a concentric training regimen for the calf muscles . The study included 44 patients , with 22 patients ( 12 men , 10 women ; mean age 48 years ) in each treatment group . The amount of pain during activity ( jogging or walking ) was recorded by the patients on a visual analogue scale , and patient satisfaction was assessed before and after treatment . The patients were instructed to perform their eccentric or concentric training regimen on a daily basis for 12 weeks . In both types of treatment regimen the patients were told to do their exercises despite experiencing pain or discomfort in the tendon during exercise . The results showed that after the eccentric training regimen 82 % of the patients ( 18/22 ) were satisfied and had resumed their previous activity level ( before injury ) , compared to 36 % of the patients ( 8/22 ) who were treated with the concentric training regimen . The results after treatment with eccentric training was significantly better ( P<0.002 ) than after concentric training . The good clinical results previously demonstrated in the pilot study with eccentric calf muscle training on patients with chronic Achilles tendinosis , were thus reproduced in this multicenter , showing superior results to treatment with concentric training Background Achilles tendinopathy is a common overuse injury , especially among athletes involved in activities that include running and jumping . Often an initial period of rest from the pain-provoking activity is recommended . Purpose To prospect ively evaluate if continued running and jumping during treatment with an Achilles tendon-loading strengthening program has an effect on the outcome . Study Design R and omized clinical control trial ; Level of evidence , 1 . Methods Thirty-eight patients with Achilles tendinopathy were r and omly allocated to 2 different treatment groups . The exercise training group ( n = 19 ) was allowed , with the use of a pain-monitoring model , to continue Achilles tendon-loading activity , such as running and jumping , whereas the active rest group ( n = 19 ) had to stop such activities during the first 6 weeks . All patients were rehabilitated according to an identical rehabilitation program . The primary outcome measures were the Swedish version of the Victorian Institute of Sports Assessment —Achilles question naire ( VISA-A-S ) and the pain level during tendon-loading activity . Results No significant differences in the rate of improvements were found between the groups . Both groups showed , however , significant ( P < .01 ) improvements , compared with baseline , on the primary outcome measure at all the evaluations . The exercise training group had a mean ( st and ard deviation ) VISA-A-S score of 57 ( 15.8 ) at baseline and 85 ( 12.7 ) at the 12-month follow-up ( P < .01 ) . The active rest group had a mean ( st and ard deviation ) VISA-A-S score of 57 ( 15.7 ) at baseline and 91 ( 8.2 ) at the 12-month follow-up ( P < .01 ) . Conclusions No negative effects could be demonstrated from continuing Achilles tendon-loading activity , such as running and jumping , with the use of a pain-monitoring model , during treatment . Our treatment protocol for patients with Achilles tendinopathy , which gradually increases the load on the Achilles tendon and calf muscle , demonstrated significant improvements . A training regimen of continued , pain-monitored , tendon-loading physical activity might therefore represent a valuable option for patients with Achilles tendinopathy Although eccentric exercise training has shown favorable results in chronic mid-portion Achilles tendinopathy , the optimum dosage remains unknown . A systematic review of the literature was performed in accordance with the PRISMA guidelines , in order to describe different exercise protocol s and to determine the most effective training parameters . An extensive search in MEDLINE , EMBASE , CINAHL , and CENTRAL revealed 14 r and omized and clinical controlled trials . Strong evidence was found for the Alfredson exercise protocol . In this 12-week protocol , exercises are performed 3 × 15 repetitions twice daily , both with a straight and bent knee . Exercises are performed at slow speed , and load is increased when exercises are without pain . Strong evidence was also found for gradual onset of exercises during the first week of the Alfredson program , but no uniformity of protocol s exists . Other exercise protocol s did achieve similar results , but many studies had some method ological shortcomings or lacked a detailed description of their training parameters . Because of the heterogeneity of study population s and outcome measures , and lack of reporting of training compliance data , a definitive conclusion regarding the most effective training parameters could not be made . Further research comparing the content of different exercise protocol s is warranted Background : Previous studies have shown that eccentric training has a positive effect on Achilles tendinopathy , but few r and omized controlled trials have compared it with other loading-based treatment regimens . Purpose : To evaluate the effectiveness of eccentric training ( ECC ) and heavy slow resistance training ( HSR ) among patients with midportion Achilles tendinopathy . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 58 patients with chronic ( > 3 months ) midportion Achilles tendinopathy were r and omized to ECC or HSR for 12 weeks . Function and symptoms ( Victorian Institute of Sports Assessment –Achilles ) , tendon pain during activity ( visual analog scale ) , tendon swelling , tendon neovascularization , and treatment satisfaction were assessed at 0 and 12 weeks and at the 52-week follow-up . Analyses were performed on an intention-to-treat basis . Results : Both groups showed significant ( P < .0001 ) improvements in Victorian Institute of Sports Assessment –Achilles and visual analog scale from 0 to 12 weeks , and these improvements were maintained at the 52-week follow-up . Concomitant with the clinical improvement , there was a significant reduction in tendon thickness and neovascularization . None of these robust clinical and structural improvements differed between the ECC and HSR groups . However , patient satisfaction tended to be greater after 12 weeks with HSR ( 100 % ) than with ECC ( 80 % ; P = .052 ) but not after 52 weeks ( HSR , 96 % ; ECC , 76 % ; P = .10 ) , and the mean training session compliance rate was 78 % in the ECC group and 92 % in the HSR group , with a significant difference between groups ( P < .005 ) . Conclusion : The results of this study show that both traditional ECC and HSR yield positive , equally good , lasting clinical results in patients with Achilles tendinopathy and that the latter tends to be associated with greater patient satisfaction after 12 weeks but not after 52 weeks STUDY DESIGN R and omized clinical trial . OBJECTIVES To compare the effectiveness of the Alfredson eccentric heel-drop protocol with a " do-as-tolerated " protocol for nonathletic individuals with midportion Achilles tendinopathy . BACKGROUND The Alfredson protocol recommends the completion of 180 eccentric heel drops a day . However , completing this large number of repetitions is time consuming and potentially uncomfortable . There is a need to investigate varying exercise dosages that minimize the discomfort yet retain the clinical benefits . METHODS Twenty-eight individuals from outpatient physiotherapy departments were r and omized to either the st and ard ( n = 15 ) or the do-as-tolerated ( n = 13 ) 6-week intervention protocol . Apart from repetition volume , all other aspects of management were st and ardized between groups . Tendinopathy clinical severity was assessed with the Victorian Institute of Sport Assessment -Achilles ( VISA-A ) question naire . Pain intensity was assessed using a visual analog scale ( VAS ) . Both were assessed at baseline , 3 weeks , and 6 weeks . Treatment satisfaction was assessed at week 6 . Adverse effects were also monitored . RESULTS There was a statistically significant within-group improvement in VISA-A score for both groups ( st and ard , P = .03 ; do as tolerated , P<.001 ) and VAS pain for the do-as-tolerated group ( P = .001 ) at week 6 , based on the intention-to-treat analysis . There was a statistically significant between-group difference in VISA-A scores at week 3 , based on both the intention-to-treat ( P = .004 ) and per- protocol analyses ( P = .007 ) , partly due to a within-group deterioration at week 3 in the st and ard group . There were no statistically significant between-group differences for VISA-A and VAS pain scores at week 6 , the completion of the intervention . There was no significant association between satisfaction and treatment groups at week 6 . No adverse effects were reported . CONCLUSION Performing a 6-week do-as-tolerated program of eccentric heel-drop exercises , compared to the recommended 180 repetitions per day , did not lead to lesser improvement for individuals with midportion Achilles tendinopathy , based on VISA-A and VAS scores OBJECTIVE To compare eccentric and static exercises as proposed by Stanish with eccentric exercises as proposed by Alfredson in the management of Achilles tendinopathy . METHODS Patients with midportion Achilles tendinopathy for at least 3 months were included in this trial . They were sequentially allocated to receive either Stanish 's exercise programme or Alfredson 's exercise programme . Outcome measures were pain and function using the VISA-A score . Patients were evaluated at baseline , at the end of treatment ( week 12 ) , and 6 months ( week 36 ) after the end of treatment . RESULTS 41 patients met the inclusion criteria . At the end of treatment , there was a rise in VISA-A score in both groups compared with baseline ( p < 0.05 , paired t-test ) . There were significant differences in the VISA-A score between the groups at the end of treatment and at the 6-month follow up ; Alfredson exercise programme group produced the largest effect ( p < 0.0005 , independent t-test ) . CONCLUSION An exercise programme based on Alfredson protocol was superior to Stanish model to reduce pain and improve function in patients with Achilles tendinopathy at the end of the treatment and at the follow-up . Further research is needed to confirm our results Background Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy . Although short-term studies show significant improvement , little is known of the long-term ( > 3 years ) results . Aim To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson 's heel-drop exercise programme . Study design Part of a 5-year follow-up of a previously conducted r and omised controlled trial . Methods 58 patients ( 70 tendons ) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson . At baseline and at 5-year follow-up , the vali date d Victorian Institute of Sports Assessment –Achilles ( VISA-A ) question naire score , pain status , alternative treatments received and ultrasonographic neovascularisation score were recorded . Results In 46 patients ( 58 tendons ) , the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years ( p<0.001 ) and from the 1-year to 5-year follow-up from 75.0 to 83.4 ( p<0.01 ) . 39.7 % of the patients were completely pain-free at follow-up and 48.3 % had received one or more alternative treatments . The sagittal tendon thickness decreased from 8.05 mm ( SD 2.1 ) at baseline to 7.50 mm ( SD 1.6 ) at the 5-year follow-up ( p=0.051 ) . Conclusion At 5-year follow-up , a significant increase of VISA-A score can be expected . After the 3-month Alfredson 's heel-drop exercise programme , almost half of the patients had received other therapies . Although improvement of symptoms can be expected at long term , mild pain may remain STUDY DESIGN Single-blind , r and omized , clinical trial . BACKGROUND The effect of eccentric training for mid-portion Achilles tendinopathy is well documented ; however , its effect on insertional Achilles tendinopathy is inconclusive . The primary purpose of this study was to investigate the effect of eccentric training on pain and function for individuals with insertional Achilles tendinopathy . METHODS All patients received a 12-week conventional strengthening protocol . Patients who were r and omly assigned to the experimental group received additional eccentric exercises . Patients completed the Short Form-36 Health and Bodily Pain Surveys , the Foot and Ankle Outcomes Question naire , and the Visual Analog Scale at initial evaluation , after 6 weeks of therapy , and at 12 weeks after therapy . RESULTS Thirty-six patients ( 20 control and 16 experimental ; average age 54 years ; 72 % women ) completed the study . Both groups experienced statistically significant decreases in pain and improvements in function . No statistically significant differences were noted between the groups for any of the outcome measures . CONCLUSION Conventional physical therapy consisting of gastrocnemius , soleus and hamstring stretches , ice massage on the Achilles tendon , and use of heel lifts and night splints with or without eccentric training is effective for treating insertional Achilles tendinopathy . LEVEL OF EVIDENCE Level 2 We prospect ively studied the effect of heavy-load eccentric calf muscle training in 15 recreational athletes ( 12 men and 3 women ; mean age , 44.3 7.0 years ) who had the diagnosis of chronic Achilles tendinosis ( degenerative changes ) with a long duration of symptoms despite conventional nonsurgical treatment . Calf muscle strength and the amount of pain during activity ( recorded on a visual analog scale ) were measured before onset of training and after 12 weeks of eccentric training . At week 0 , all patients had Achilles tendon pain not allowing running activity , and there was significantly lower eccentric and concentric calf muscle strength on the injured compared with the noninjured side . After the 12-week training period , all 15 patients were back at their preinjury levels with full running activity . There was a significant decrease in pain during activity , and the calf muscle strength on the injured side had increased significantly and did not differ significantly from that of the noninjured side . A comparison group of 15 recreational athletes with the same diagnosis and a long duration of symptoms had been treated conventionally , i.e. , rest , nonsteroidal antiinflammatory drugs , changes of shoes or orthoses , physical therapy , and in all cases also with ordinary training programs . In no case was the conventional treatment successful , and all patients were ultimately treated surgically . Our treatment model with heavy-load eccentric calf muscle training has a very good short-term effect on athletes in their early forties Purpose . To compare eccentric training and the combination of eccentric training with the AirHeel ™ Brace for the management of tendinopathy of the main body of the Achilles tendon . Methods . We recruited 116 subjects with unilateral tendinopathy of the main body of the Achilles tendon , who were r and omized in two groups . Group A performed a regimen of daily eccentric training associated with the AirHeel ™ Brace ( Donjoy Orthopedics , Vista , CA , USA ) . Group B performed the same eccentric training without the AirHeel ™ Brace . Tendon microcirculatory mapping was performed using combined Laser-Doppler and spectrophotometry . Pre- and post-operative FAOS score and VAS score were used to evaluate the patients . Results . The FAOS score and the VAS score showed significant improvements from pre-operative to post-operative values in both groups ( A 5.1 ± 2 vs. 2.9 ± 2.4 , 43 % reduction and B : 5.4 ± 2.1 vs. 3.6 ± 2.4 , 33 % reduction , both p = 0.0001 ) . There were no statistically significant differences in FAOS score and VAS score when comparing the two groups after the end of the intervention . In Group A , tendon oxygen saturation in the main body of the Achilles tendon showed significant increase from pre- to post-management values ( 68 ± 12 vs.74 ± 8 % , p = 0.003 ) . Post-capillary venous filling pressures showed significant reduction from pre- to post-intervention values . Conclusion . Eccentric training , associated or not with the AirHeel ™ Brace , produces the same effect in patients with tendinopathy of the main body of the Achilles tendon . The combination of eccentric training with the AirHeel ™ Brace can optimize tendon microcirculation , but these micro-circulator advantages do not translate into superior clinical performance when compared with eccentric training alone The purpose was to examine the reliability of measurement techniques and evaluate the effect of a treatment protocol including eccentric overload for patients with chronic pain from the Achilles tendon . Thirty-two patients with proximal achillodynia ( 44 involved Achilles tendons ) participated in tests for reliability measures . No significant differences and strong ( r=0.56 - 0.72 ) or very strong ( r=0.90 - 0.93 ) correlations were found between pre-tests , except for the documentation of pain at rest ( P<0.008 , r=0.45 ) . To evaluate the effect of a 12-week treatment protocol for patients with chronic proximal achillodynia ( pain longer than three months ) 40 patients ( 57 involved Achilles tendons ) with a mean age of 45 years ( range 19 - 77 ) were r and omised into an experiment group ( n=22 ) and a control group ( n=18 ) . Evaluations were performed after six weeks of treatment and after three and six months . The evaluations ( including the pre-tests ) , performed by a physical therapist unaware of the group the patients belonged to , consisted of a question naire , a range of motion test , a jumping test , a toe-raise test , a pain on palpation test and pain evaluation during jumping , toe-raises and at rest . A follow-up was also performed after one year . There were no significant differences between groups at any of the evaluations , except that the experiment group jumped significantly lower than the control group at the six-week evaluation . There was , however , an overall better result for the experiment group with significant improvements in plantar flexion , and reduction in pain on palpation , number of patients having pain during walking , having periods when asymptomatic and having swollen Achilles tendon . The controls did not show such changes . Furthermore , at the one-year follow-up there were significantly more patients in the experiment group , compared with the control group , that were satisfied with their present physical activity level , considered themselves fully recovered , and had no pain during or after physical activity . The measurement techniques and the treatment protocol with eccentric overload used in the present study can be recommended for patients with chronic pain from the Achilles tendon STUDY DESIGN A controlled , r and omized , prospect i ve study , OBJECTIVE To assess the changes in paratendon microcirculation after 12 weeks of daily painful eccentric training in individuals with chronic Achilles tendinopathy . BACKGROUND Changes in tendon and paratendon microcirculation are evident in insertional and midportion Achilles tendinopathy . Whether the paratendon is involved in eccentric training response is not known . METHODS Twenty patients with chronic Achilles tendinopathy were recruited for a prospect i ve , controlled trial using eccentric exercise . A laser Doppler system assessed capillary blood flow ( flow ) , tissue oxygen saturation ( SO2 ) , and postcapillary venous filling pressure ( rHb ) at 8 paratendon locations at depths of 2 and 8 mm . RESULTS Pain in the eccentric-training group was reduced by 48 % ( from a mean of 4.1 + /- 2.9 to 2.1 + /- 2.2 , P<.05 ) . Deep paratendon blood flow decreased at the midportion paratendon location ( P<.05 ) . Superficial blood flow at the medial distal midportion position ( by 31 % , P = .008 ) and the lateral proximal midportion location ( by 45 % , P = .016 ) were significantly decreased postintervention , No significant change of superficial or deep paratendon oxygenation was found after intervention as compared to baseline . Deep paratendon postcapillary venous filling pressures were significantly reduced following eccentric training ( P<.05 ) . CONCLUSION An eccentric-training program performed daily over 12 weeks reduced the increased paratendinous capillary blood flow in Achilles tendinopathy by as much as 45 % and decreased pain level based on a visual analog scale . Local paratendon oxygenation was preserved while paratendinous postcapillary venous filling pressures were reduced after 12 weeks of eccentric training , which appears to be beneficial from the perspective of microcirculation Aim : To assess whether the use of a night splint is of added benefit on functional outcome in treating chronic midportion Achilles tendinopathy . Methods : This was a single-blind , prospect i ve , single centre , r and omised controlled trial set in the Sports Medical Department , The Hague Medical Centre , The Netherl and s. Inclusion criteria were : age 18–70 years , active participation in sports , and tendon pain localised at 2–7 cm from distal insertion . Exclusion criteria were : insertional disorders , partial or complete ruptures , or systemic illness . 70 tendons were included and r and omised into one of two treatment groups : eccentric exercises with a night splint ( night splint group , n = 36 ) or eccentric exercises only ( eccentric group , n = 34 ) . Interventions : Both groups completed a 12-week heavy-load eccentric training programme . One group received a night splint in addition to eccentric exercises . At baseline and follow-up at 12 weeks , patient satisfaction , Victorian Institute of Sport Assessment –Achilles question naire ( VISA-A ) score and reported compliance were recorded by a single-blind trained research er who was blinded to the treatment . Results : After 12 weeks , patient satisfaction in the eccentric group was 63 % compared with 48 % in the night splint group . The VISA-A score significantly improved in both groups ; in the eccentric group from 50.1 to 68.8 ( p = 0.001 ) and in the night splint group from 49.4 to 67.0 ( p<0.001 ) . There was no significant difference between the two groups in VISA-A score ( p = 0.815 ) and patient satisfaction ( p = 0.261 ) . Conclusion : A night splint is not beneficial in addition to eccentric exercises in the treatment of chronic midportion Achilles tendinopathy The purpose of this prospect i ve cohort study was to identify dynamic gait-related risk factors for Achilles tendinopathy ( AT ) in a population of novice runners . Prior to a 10-week running program , force distribution patterns underneath the feet of 129 subjects were registered using a footscan pressure plate while the subjects jogged barefoot at a comfortable self-selected pace . Throughout the program 10 subjects sustained Achilles tendinopathy of which three reported bilateral complaints . Sixty-six subjects were excluded from the statistical analysis . Therefore the statistical analysis was performed on the remaining sample of 63 subjects . Logistic regression analysis revealed a significant decrease in the total posterior-anterior displacement of the Centre Of Force ( COF ) ( P=0.015 ) and a laterally directed force distribution underneath the forefoot at ' forefoot flat ' ( P=0.016 ) as intrinsic gait-related risk factors for Achilles tendinopathy in novice runners . These results suggest that , in contrast to the frequently described functional hyperpronation following a more inverted touchdown , a lateral foot roll-over following heel strike and diminished forward force transfer underneath the foot should be considered in the prevention of Achilles tendinopathy Background Few r and omized controlled trials compare different methods of management in chronic tendinopathy of the main body of tendo Achillis . Purpose To compare the effectiveness of 3 management strategies — group 1 , eccentric loading ; group 2 , repetitive low-energy shock-wave therapy ( SWT ) ; and group 3 , wait and see — in patients with chronic tendinopathy of the main body of tendo Achillis . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-five patients with a chronic recalcitrant ( > 6 months ) noninsertional Achilles tendinopathy were enrolled in a r and omized controlled study . All patients had received unsuccessful management for > 3 months , including at least ( 1 ) peritendinous local injections , ( 2 ) nonsteroidal anti-inflammatory drugs , and ( 3 ) physiotherapy . A computerized r and om-number generator was used to draw up an allocation schedule . Analysis was on intention-to-treat basis . Results At 4 months from baseline , the Victorian Institute of Sport Assessment (VISA)-A score increased in all groups , from 51 to 76 points in group 1 ( eccentric loading ) , from 50 to 70 points in group 2 ( repetitive low-energy SWT ) , and from 48 to 55 points in group 3 ( wait and see ) . Pain rating decreased in all groups , from 7 to 4 points in group 1 , from 7 to 4 points in group 2 , and from 8 to 6 points in group 3 . Fifteen of 25 patients in group 1 ( 60 % ) , 13 of 25 patients in group 2 ( 52 % ) , and 6 of 25 patients in Group 3 ( 24 % ) reported a Likert scale of 1 or 2 points ( “ completely recovered ” or “ much improved ” ) . For all outcome measures , groups 1 and 2 did not differ significantly . For all outcome measures , groups 1 and 2 showed significantly better results than group 3 . Conclusion At 4-month follow-up , eccentric loading and low-energy SWT showed comparable results . The wait- and -see strategy was ineffective for the management of chronic recalcitrant tendinopathy of the main body of the Achilles tendon Background and objectives Treatment of chronic running-related overuse injuries by orthopaedic shoe orthoses is very common but not evidence -based to date . Hypothesis Polyurethane foam orthoses adapted to a participant 's barefoot plantar pressure distribution are an effective treatment option for chronic overuse injuries in runners . Design Prospect i ve , r and omised , controlled clinical trial . Intervention 51 patients with running injuries were treated with custom-made , semirigid running shoe orthoses for 8 weeks . 48 served as a r and omised control group that continued regular training activity without any treatment . Main outcome measures Evaluation was made by the vali date d pain question naire Subjective Pain Experience Scale , the pain disability index and a comfort index in the orthoses group ( ICI ) . Results There were statistically significant differences between the orthoses and control groups at 8 weeks for the pain disability index ( mean difference 3.2 ; 95 % CI 0.9 to 5.5 ) and the Subjective Pain Experience Scale ( 6.6 ; 2.6 to 10.6 ) . The patients with orthoses reported a rising wearing comfort ( pre-treatment ICI 69/100 ; post-treatment ICI 83/100 ) that was most pronounced in the first 4 weeks ( ICI 80.4/100 ) . Conclusion Customised polyurethane running shoe orthoses are an effective conservative therapy strategy for chronic running injuries with high comfort and acceptance of injured runners STUDY DESIGN R and omized clinical trial . OBJECTIVES To test the hypothesis that whole-body vibration training results in greater improvements in symptoms and pain , structural changes , and muscle flexibility and strength of the triceps surae muscle-tendon unit than those achieved with eccentric training or with a wait- and -see approach . BACKGROUND The potential use of vibration training for the treatment of Achilles tendinopathy has not been explored . METHODS Fifty-eight patients ( mean age , 46.0 years ) with Achilles tendinopathy were r and omly assigned to a 12-week intervention using whole-body vibration training , eccentric training , or a wait- and -see approach . Pain , tendon structure and path , and muscle flexibility and strength were assessed at baseline and follow-up , and compared using mixed-factor analyses of variance . RESULTS Pain improvements at the midsection of the tendon were greater in the vibration- and eccentric-training groups than in the wait- and -see group ( mean difference from the vibration-training group , -18.0 ; 95 % confidence interval [ CI ] : -35.0 , -1.1 ; mean difference from the eccentric-training group , -27.0 ; 95 % CI : -50.9 , -3.1 ) . Improvements in pain at the musculotendinous junction were greater in the eccentric-training group than in the other groups ( mean difference from the vibration-training group , -31.4 ; 95 % CI : -60.7 , -2.0 ; mean difference from the wait- and -see group , -50.2 ; 95 % CI : -82.3 , -18.1 ) . Improvements in most participants were achieved in the vibration-training group , followed by the eccentric-training group . CONCLUSION Vibration training may be an alternative or a complementary treatment in patients who do not respond well to eccentric training , especially in those with insertional pain . LEVEL OF EVIDENCE Therapy , level 2b- |
12,617 | 30,348,069 | In general , results of this systematic review show promising advances in the treatment of prostate cancer patients with monoclonal antibodies against prostate-specific antigens with regard to PSA/disease response .
Conclusion Currently , the role of immunotherapy in the treatment of advanced prostate cancer still remains debated . | Introduction Treatment of metastatic castration-resistant prostate cancer with conventional therapies is still not successful .
Therefore , application of novel biological approaches such as immunotherapy , which appears to be more effective and less toxic , is necessary .
Monoclonal antibodies against cancer specific antigens are a kind of immunotherapy that have been approved for specific types of cancer and are being investigated for prostate cancer as well .
The aim of this review was to assess the effectiveness and safety of monoclonal antibodies for treatment of advanced prostate cancer . | BACKGROUND Pre clinical and preliminary clinical data indicate that ch14.18 , a monoclonal antibody against the tumor-associated disialoganglioside GD2 , has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or interleukin-2 . We conducted a study to determine whether adding ch14.18 , GM-CSF , and interleukin-2 to st and ard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma . METHODS Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were r and omly assigned , in a 1:1 ratio , to receive st and ard therapy ( six cycles of isotretinoin ) or immunotherapy ( six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2 ) . Event-free survival and overall survival were compared between the immunotherapy group and the st and ard-therapy group , on an intention-to-treat basis . RESULTS A total of 226 eligible patients were r and omly assigned to a treatment group . In the immunotherapy group , a total of 52 % of patients had pain of grade 3 , 4 , or 5 , and 23 % and 25 % of patients had capillary leak syndrome and hypersensitivity reactions , respectively . With 61 % of the number of expected events observed , the study met the criteria for early stopping owing to efficacy . The median duration of follow-up was 2.1 years . Immunotherapy was superior to st and ard therapy with regard to rates of event-free survival ( 66±5 % vs. 46±5 % at 2 years , P=0.01 ) and overall survival ( 86±4 % vs. 75±5 % at 2 years , P=0.02 without adjustment for interim analyses ) . CONCLUSIONS Immunotherapy with ch14.18 , GM-CSF , and interleukin-2 was associated with a significantly improved outcome as compared with st and ard therapy in patients with high-risk neuroblastoma . ( Funded by the National Institutes of Health and the Food and Drug Administration ; Clinical Trials.gov number , NCT00026312 . Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis . RNASEL at chromosome 1q25 encodes ribonuclease L , part of the interferon-mediated immune response to viral infection . We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospect i ve Physicians ' Health Study . Eleven single-nucleotide polymorphisms ( SNPs ) were selected using the web-based ' Tagger ' in the HapMap CEPH panel ( Utah residents of Northern and Western European Ancestry ) . Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage ( T(3)/T(4 ) , T(0)-T(4)/M(1 ) and lethal disease ) and high Gleason grade ( > /=7 ) prostate cancer . Further analyses were stratified by calendar year of diagnosis . Cox proportional hazards models examined the relationship between genotype and prostate cancer-specific survival . We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) and tumor necrosis factor-alpha receptor 2 using linear regression . Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [ AA versus GG ; odds ratio ( OR ) : 1.63 , 95 % confidence interval ( CI ) : 1.18 - 2.25 ) , and more specifically , high- grade tumors ( OR : 1.90 , 95 % CI : 1.25 - 2.89 ) . The same genotype was associated with increased CRP ( P = 0.02 ) and IL-6 ( P = 0.05 ) levels . Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era . There were no significant associations with survival . The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation . These novel findings warrant replication in future studies BACKGROUND This first-in-human phase I/IIA study was design ed to evaluate the safety and pharmacokinetics ( PKs ) of AGS-PSCA a fully human monoclonal antibody directed to prostate stem cell antigen ( PSCA ) in progressive castration-resistant prostate cancer . PATIENTS AND METHODS Twenty-nine patients were administered infusions of AGS-PSCA ( 1 - 40 mg/kg ) every 3 weeks for 12 weeks ; 18 final patients received a 40-mg/kg loading dose followed by 20-mg/kg repeat doses . Primary end points were safety and PK . Immunogenicity , antitumor activity and circulating tumor cells were also evaluated . RESULTS No drug-related serious adverse events were noted . Dose escalation stopped before reaching the maximum tolerated dose as target concentrations were achieved . Drug levels accumulated linearly with dose and the mean terminal half-life was 2 - 3 weeks across dose levels . The 40-mg/kg loading dose followed by repeated 20-mg/kg doses yielded serum drug concentrations above the projected minimum therapeutic threshold after two to three doses without excessive drug accumulation or toxicity . Significant antitumor effects were not seen . CONCLUSIONS A 40-mg/kg loading dose followed by 20-mg/kg infusions every 3 weeks is the recommended phase II dose of AGS-PSCA . PSCA is a promising drug target and studies in prostate and other relevant solid tumors are planned PURPOSE To determine the maximum tolerated dose ( MTD ) , toxicity , human anti-J591 response , pharmacokinetics ( PK ) , organ dosimetry , targeting , and biologic activity of (177)Lutetium-labeled anti-prostate-specific membrane antigen ( PSMA ) monoclonal antibody J591 ( (177)Lu-J591 ) in patients with and rogen-independent prostate cancer ( PC ) . PATIENTS AND METHODS Thirty-five patients with progressing and rogen-independent PC received (177)Lu-J591 . All patients underwent (177)Lu-J591 imaging , PK , and biodistribution determinations . Patients were eligible for up to three retreatments . RESULTS Thirty-five patients received (177)Lu-J591 , of whom 16 received up to three doses . Myelosuppression was dose limiting at 75 mCi/m(2 ) , and the 70-mCi/m(2 ) dose level was determined to be the single-dose MTD . Repeat dosing at 45 to 60 mCi/m(2 ) was associated with dose-limiting myelosuppression ; however , up to three doses of 30 mCi/m(2 ) could be safely administered . Nonhematologic toxicity was not dose limiting . Targeting of all known sites of bone and soft tissue metastases was seen in all 30 patients with positive bone , computed tomography , or magnetic resonance images . No patient developed a human anti-J591 antibody response to deimmunized J591 regardless of number of doses . Biologic activity was seen with four patients experiencing > or= 50 % declines in prostate-specific antigen ( PSA ) levels lasting from 3 + to 8 months . An additional 16 patients ( 46 % ) experienced PSA stabilization for a median of 60 days ( range , 1 to 21 + months ) . CONCLUSION The MTD of (177)Lu-J591 is 70 mCi/m(2 ) . Multiple doses of 30 mCi/m(2 ) are well tolerated . Acceptable toxicity , excellent targeting of known sites of PC metastases , and biologic activity in patients with and rogen-independent PC warrant further investigation PURPOSE To compare single-agent gemtuzumab ozogamicin ( GO ) with best supportive care ( BSC ) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy . PATIENTS AND METHODS In this trial , patients at least 61 years old were central ly r and omized ( 1:1 ) to receive either a single induction course of GO ( 6 mg/m(2 ) on day 1 and 3 mg/m(2 ) on day 8) or BSC . Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m(2 ) . R and omization was stratified by age , WHO performance score , CD33 expression status , and center . The primary end point was overall survival ( OS ) by intention-to-treat analysis . RESULTS A total of 237 patients were r and omly assigned ( 118 to GO and 119 to BSC ) . The median OS was 4.9 months ( 95 % CI , 4.2 to 6.8 months ) in the GO group and 3.6 months ( 95 % CI , 2.6 to 4.2 months ) in the BSC group ( hazard ratio , 0.69 ; 95 % CI , 0.53 to 0.90 ; P = .005 ) ; the 1-year OS rate was 24.3 % with GO and 9.7 % with BSC . The OS benefit with GO was consistent across most subgroups , and was especially apparent in patients with high CD33 expression status , in those with favorable/intermediate cytogenetic risk profile , and in women . Overall , complete remission ( CR [ complete remission ] + CRi [ CR with incomplete recovery of peripheral blood counts ] ) occurred in 30 of 111 ( 27 % ) GO recipients . The rates of serious adverse events ( AEs ) were similar in the two groups , and no excess mortality from AEs was observed with GO . CONCLUSION First-line monotherapy with low-dose GO , as compared with BSC , significantly improved OS in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy . No unexpected AEs were identified and toxicity was manageable BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . PURPOSE To determine the maximum-tolerated dose ( MTD ) , toxicity , human antihuman antibody ( HAHA ) response , pharmacokinetics , organ dosimetry , targeting , and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ( (90)Y-J591 ) in patients with and rogen-independent prostate cancer ( PC ) . PATIENTS AND METHODS Patients with and rogen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by (90)Y-J591 at five dose levels : 5 , 10 , 15 , 17.5 , and 20 mCi/m(2 ) . Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory . RESULTS Twenty-nine patients with and rogen-independent PC received (90)Y-J591 , four of whom were re-treated . Dose limiting toxicity ( DLT ) was seen at 20 mCi/m(2 ) , with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions . The 17.5-mCi/m(2 ) dose level was determined to be the MTD . No re-treated patients experienced DLT . Nonhematologic toxicity was not dose limiting . Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients . No HAHA response was seen . Antitumor activity was seen , with two patients experiencing 85 % and 70 % declines in prostate-specific antigen ( PSA ) levels lasting 8 and 8.6 months , respectively , before returning to baseline . Both patients had objective measurable disease responses . An additional six patients ( 21 % ) experienced PSA stabilization . CONCLUSION The recommended dose for (90)Y-J591 is 17.5 mCi/m(2 ) . Acceptable toxicity , excellent targeting of known sites of PC metastases , and biologic activity in patients with and rogen-independent PC warrant further investigation of (90)Y-J591 in the treatment of patients with PC Purpose AGS-1C4D4 is a human monoclonal antibody against prostate stem cell antigen ( PSCA ) , a cell-surface protein expressed by most prostate cancers . AGS-1C4D4 is produced in Chinese hamster ovary ( CHO ) cells and has an identical sequence to AGS-PSCA , an anti-PSCA antibody produced in mouse hybridoma cells that has completed Phase I testing . Pre clinical studies demonstrated comparability of AGS-1C4D4 to AGS-PSCA with respect to pharmacokinetics ( PK ) and tumor inhibition . However , because of differences in antibody-dependent cellular cytotoxicity between AGS-PSCA and AGS-1C4D4 , a limited Phase I trial using AGS-1C4D4 was performed evaluating safety and PK . Patients and methods Thirteen patients with metastatic castration-resistant prostate cancer were enrolled . AGS-1C4D4 was administered intravenously every 3 weeks for four planned doses at 6 , 12 , 24 , or 48 mg/kg . Primary endpoints were safety and PK . Secondary endpoints were immunogenicity and clinical activity . Disease assessment s were conducted every 12 weeks and included radiographic and PSA evaluations . Patients with stable disease could receive extended treatment beyond four infusions . Results Adverse events were primarily grade 1–2 , without any grade 3–4 drug-related toxicities or infusion reactions . Anti-AGS-1C4D4 antibodies were not detected . Similar to AGS-PSCA , serum AGS-1C4D4 concentrations declined biphasically and elimination was characterized by slow clearance ( CL ) and a long terminal half-life ( t1/2 ) . Median CL for the four dose levels ranged from 0.10 to 0.14 ml/h kg , and t1/2 ranged from 2.2 to 2.9 weeks . No PSA reductions ≥50 % were observed . Six patients ( 46 % ) had radiographically stable disease , lasting a median of 24 weeks . Conclusion AGS-1C4D4 was well-tolerated and demonstrated linear PK . Despite pre clinical differences in antibody-dependent cellular cytotoxicity , AGS-1C4D4 and AGS-PSCA have similar safety and PK profiles . The recommended Phase II dose is 48 mg/kg A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma . Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration . Of the 12 patients , 58 % had at least one site of disease imaged after administration of 111In-CYT-356 . The dose of 90Y ranged from 1.83 - 12 mCi/m2 . Both 111In and 90Y-CYT-356 were tolerated well , without significant nonhematological toxicity . Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5 - 12 mCi/m2 . Of the patients receiving < /=9 mCi/m2 , 55 % had grade 1 or 2 leukopenia and /or thrombocytopenia . Two of three patients treated with 12 mCi/m2 experienced grade 3 thrombocytopenia and leukopenia . One patient treated with 12 mCi/m2 had grade 4 neutropenia . The maximum tolerated dose of 90Y-CYT-356 was 9 mCi/m2 . Only one patient developed a human anti-mouse antibody 4 weeks after treatment . No patient attained a complete or partial response based on prostate-specific antigen and /or radiological criteria . Three patients had transient subjective improvement in the symptomatology of their disease . In addition , patients treated with 12 mCi/m2 of 90Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of 90Y-CYT-356 < /=9 mCi/m2 Data from epidemiologic and twin studies suggest an important role of genetic susceptibility in prostate cancer . Variants of the macrophage scavenger receptor 1 ( MSR1 ) gene have been linked to both hereditary and sporadic prostate cancer , although the evidence is inconclusive . Most studies have been conducted on Caucasians . The role of MSR1 in prostate cancer development among Asians , for whom rates of prostate cancer are low but rising rapidly , is unclear . To evaluate further the relationship between MSR1 variants and prostate cancer risk , we sequenced all the 11 MSR1 exons , exon-intron junctions , promoter regions , as well as 5 ' and 3 ' untranslated regions ( UTRs ) in 86 individuals from Shanghai , China . We identified a total of 21 sequence variants , including three novel variants that have not been reported previously . To balance genotyping cost and the capacity to capture sufficient genetic variation , we genotyped four haplotype-tagging variants ( P275A , INDEL7 , P346P and 3 ' UTR 70006 ) , which capture 85 % of the genetic variation in MSR1 in this population . These four variants , plus two other variants ( PRO3 and INDEL1 ) that have been linked to prostate cancer risk in the previous studies , were typed for all study subjects , which included 130 prostate cancer cases , 130 patients with benign prostatic hyperplasia and 150 controls r and omly selected from the population . Three of the six variants were associated with prostate cancer . Men with a P346P ( a novel variant ) G allele ( AG + GG ) had a significantly reduced risk of total prostate cancer [ odds ratio = 0.47 , 95 % confidence interval ( CI ) 0.23 - 0.96 ] , whereas those with a P275A G allele had a 37 % reduced risk of prostate cancer ( 95 % CI 0.39 - 1.02 ) , with more pronounced reduction in risk seen for localized cancer cases ( odds ratio = 0.25 , 95 % CI 0.12 - 0.52 ; P = 0.001 ) . In addition , men with the INDEL7 variant had a 67 % reduced risk of localized cancer ( 95 % CI 0.16 - 0.68 ) . Based on the four tagging variants , we inferred four major haplotypes that accounted for > 90 % of the haplotype variation in this population . The haplotype frequencies were significantly different between localized prostate cancer cases and controls , with a global P value of 0.004 , and the haplotype containing the minor alleles of the P275A and INDEL7 variants was associated with a significantly reduced risk of localized prostate cancer ( odds ratio = 0.28 , 95 % CI 0.13 - 0.59 ) , relative to the most common haplotype . These results , although modest and confined mainly to localized prostate cancer , suggest that MSR1 polymorphisms may play a role in prostate cancer etiology in Chinese men . The role of MSR1 warrants further investigation in larger studies and other population BACKGROUND Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck . We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . METHODS We r and omly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin ( at a dose of 100 mg per square meter of body-surface area on day 1 ) or carboplatin ( at an area under the curve of 5 mg per milliliter per minute , as a 1-hour intravenous infusion on day 1 ) plus fluorouracil ( at a dose of 1000 mg per square meter per day for 4 days ) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab ( at a dose of 400 mg per square meter initially , as a 2-hour intravenous infusion , then 250 mg per square meter , as a 1-hour intravenous infusion per week ) for a maximum of 6 cycles . Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects , whichever occurred first . RESULTS Adding cetuximab to platinum-based chemotherapy with fluorouracil ( platinum-fluorouracil ) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab ( hazard ratio for death , 0.80 ; 95 % confidence interval , 0.64 to 0.99 ; P=0.04 ) . The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months ( hazard ratio for progression , 0.54 ; P<0.001 ) and increased the response rate from 20 % to 36 % ( P<0.001 ) . The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia ( 19 % and 13 % , respectively ) , neutropenia ( 23 % and 22 % ) , and thrombocytopenia ( 11 % in both groups ) . Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group ( P=0.02 ) . Of 219 patients receiving cetuximab , 9 % had grade 3 skin reactions and 3 % had grade 3 or 4 infusion-related reactions . There were no cetuximab-related deaths . CONCLUSIONS As compared with platinum-based chemotherapy plus fluorouracil alone , cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00122460 . BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems |
12,618 | 21,631,843 | Results and conclusion Limited evidence was found to indicate that CBT , regardless of its content ( i.e. with or without hopeful elements ) , is effective at preventing the onset of clinical levels of depression in young people on a sustained basis . | Background The onset of depression during adolescence can adversely impact future functioning .
Cognitive-Behavioural Therapy ( CBT ) has been suggested to prevent depression in adolescence by providing an individual with the ability to interpret and the tools to deal with the impact of negative life events .
Objective Examine the best available evidence to determine the effectiveness of CBT to prevent the onset of depression in young people , and assess whether the incorporation of hopeful elements makes CBT more effective . | A controlled trial was conducted to evaluate a prevention program aim ed at reducing depressive and anxious symptoms in rural school children . Seventh- grade children with elevated depression were selected . Nine primary schools ( n = 90 ) were r and omly assigned to receive the program , and 9 control schools ( n = 99 ) received their usual health education classes . Children completed question naires on depression , anxiety , explanatory style , and social skills . Parents completed the Child Behavior Checklist ( T. M. Achenbach , 1991 ) . No intervention effects were found for depression . Intervention group children reported less anxiety than the control group after the program and at 6-month follow-up and more optimistic explanations at postintervention . Intervention group parents reported fewer child internalizing and externalizing symptoms at postintervention only OBJECTIVE To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program . METHOD Three hundred ninety-two students age 13 to 15 from two schools were r and omized to intervention ( RAP-Kiwi ) and placebo programs run by teachers . RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy . The placebo was similar but with cognitive components removed . Outcomes were self-rated depression scales , the Reynolds Adolescent Depression Scale ( RADS ) , and the Beck Depression Inventory II ( BDI-II ) . Follow-up was to 18 months . Analysis was done on an intent-to-treat basis . RESULTS Immediately after the intervention , depression scores were reduced significantly more by RAP-Kiwi than by placebo , with a mean difference in change from baseline between groups of 1.5 on BDI-II ( CI > 0.38 , p = .01 ) and 2.24 on RADS ( CI > 0.22 , p = .04 ) . Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3 % ( 95 % CI , 1 - 11 % , McNemar chi , p = .03 ) , with the " number needed to treat " for short-term benefit of 33 . Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II . Retention rates were 91 % at 6 months and 72 % at 18 months . CONCLUSIONS The RAP-Kiwi program is a potentially effective public health measure . Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted The authors investigated the effectiveness and specificity of the Penn Resiliency Program ( PRP ; J. E. Gillham , L. H. Jaycox , K. J. Reivich , M. E. P. Seligman , & T. Silver , 1990 ) , a cognitive-behavioral depression prevention program . Children ( N = 697 ) from 3 middle schools were r and omly assigned to PRP , Control ( CON ) , or the Penn Enhancement Program ( PEP ; K. J. Reivich , 1996 ; A. J. Shatté , 1997 ) , an alternate intervention that controls for nonspecific intervention ingredients . Children 's depressive symptoms were assessed through 3 years of follow-up . There was no intervention effect on average levels of depressive symptoms in the full sample . Findings varied by school . In 2 schools , PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP . In the 3rd school , PRP did not prevent depressive symptoms . The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs This paper describes the development and preliminary efficacy of a program design ed to prevent depressive symptoms in at-risk 10 - 13 year-olds , and relates the findings to the current underst and ing of childhood depression . The treatment targets depressive symptoms and related difficulties such as conduct problems , low academic achievement , low social competence , and poor peer relations , by proactively teaching cognitive techniques . Children were identified as ' at-risk ' based on depressive symptoms and their reports of parental conflict . Sixty-nine children participated in treatment groups and were compared to 73 children in control groups . Depressive symptoms were significantly reduced and classroom behavior was significantly improved in the treatment group as compared to controls at post-test . Six-month follow-up showed continued reduction in depressive symptoms , as well as significantly fewer externalizing conduct problems , as compared to controls . The reduction in symptoms was most pronounced in the children who were most at risk This study evaluated the Penn Resiliency Program 's effectiveness in preventing depression when delivered by therapists in a primary care setting . Two-hundred and seventy-one 11- and 12-year-olds , with elevated depressive symptoms , were r and omized to PRP or usual care . Over the 2-year follow-up , PRP improved explanatory style for positive events . PRP 's effects on depressive symptoms and explanatory style for negative events were moderated by sex , with girls benefiting more than boys . Stronger effects were seen in high-fidelity groups than low-fidelity groups . PRP did not significantly prevent depressive disorders but significantly prevented depression , anxiety , and adjustment disorders ( when combined ) among high-symptom participants . Findings are discussed in relation to previous PRP studies and research on the dissemination of psychological interventions BACKGROUND Depressive disorders in adolescents are a widespread and increasing problem . Prevention seems a promising and feasible approach . METHODS We design ed a cognitive-behavioral school-based universal primary prevention program and followed 347 eighth- grade students participating in a r and omized controlled trial for three months . RESULTS In line with our hypothesis , participants in the prevention program remained on a low level of depressive symptoms , having strong social networks . The control group showed increasing depressive symptoms and a reduced social network . Contrary to our expectations , students low in self-efficacy benefited more from the program than high self-efficient students . Social network did not mediate the relationship between participation in the prevention program and changes in depressive symptoms . CONCLUSIONS Our results show that the prevention program had favorable effects . Further research is needed to explore the impact of self-efficacy on the effects of prevention programs |
12,619 | 22,997,224 | There is no evidence that oseltamivir reduces the likelihood of hospitalization , pneumonia or the combined outcome of pneumonia , otitis media and sinusitis in the ITT population | BACKGROUND Oseltamivir is widely used for the treatment of influenza .
Previous systematic review s suggest that they reduce complications , but had significant method ologic limitations .
OBJECTIVE To assess the effect of oseltamivir on duration of symptoms , complications and hospitalizations in adults . | BACKGROUND The value of azithromycin for treatment of acute bronchitis is unknown , even though this drug is commonly prescribed . We have investigated this question in a r and omised , double-blind , controlled trial . METHODS Adults diagnosed with acute bronchitis , without evidence of underlying lung disease , were r and omly assigned azithromycin ( n=112 ) or vitamin C ( n=108 ) for 5 days ( total dose for each 1.5 g ) . All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer . The primary outcome was improvement in health-related quality of life at 7 days ; an important difference was defined as 0.5 or greater . Analysis was by intention to treat . FINDINGS The study was stopped by the data -monitoring and safety committee when 220 patients had been recruited . On day 7 , the adjusted difference in health-related quality of life was small and not significant ( difference 0.03 [ 95 % CI -0.20 to 0.26 ] , p=0.8 ) . 86 ( 89 % ) of 97 patients in the azithromycin group and 82 ( 89 % ) of 92 in the vitamin C group had returned to their usual activities by day 7 ( difference 0.5 % [ -10 % to 9 % ] , p>0.9 ) . There were no differences in the frequency of adverse effects ; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects , compared with none in the azithromycin group . Most patients ( 81 % ) reported benefit from the albuterol inhaler . INTERPRETATION Azithromycin is no better than low-dose vitamin C for acute bronchitis . Further studies are needed to identify the best treatment for this disorder BACKGROUND Influenza causes lower respiratory tract complications ( LRTCs ) , particularly bronchitis and pneumonia , in both otherwise healthy adults and those with underlying conditions . The aim of this study was to assess the effect of oseltamivir treatment on the incidence of LRTCs leading to antibiotic treatment and hospitalizations following influenza illness . METHODS We analyzed prospect ively collected data on LRTCs and antibiotic use from 3564 subjects ( age range , 13 - 97 years ) with influenzalike illness enrolled in 10 placebo-controlled , double-blind trials of oseltamivir treatment . RESULTS In adults and adolescents with a proven influenza illness , oseltamivir treatment reduced overall antibiotic use for any reason by 26.7 % ( 14.0 % vs 19.1 % with placebo ; P<.001 ) and the incidence of influenza-related LRTCs result ing in antibiotic therapy by 55 % ( 4.6 % vs 10.3 % with placebo ; P<.001 ) . In those subjects considered at increased risk of complications , 74 ( 18.5 % ) of 401 placebo recipients developed an LRTC leading to antibiotic use compared with 45 ( 12.2 % ) of 368 oseltamivir recipients ( 34.0 % reduction ; P = .02 ) . Hospitalization for any cause occurred in 18 ( 1.7 % ) of 1063 placebo recipients compared with 9 ( 0.7 % ) of 1350 oseltamivir-treated patients ( 59 % reduction ; P = .02 ) . In contrast , among subjects with an influenzalike illness but without a confirmed influenza infection , the incidence of LRTCs ( 6.7 % vs 5.3 % ) , overall antibiotic use ( 19.7 % vs 19.3 % ) , or hospitalizations ( 1.7 % vs 1.9 % ) was similar between placebo and oseltamivir recipients , respectively . CONCLUSION Oseltamivir treatment of influenza illness reduces LRTCs , antibiotic use , and hospitalization in both healthy and " at-risk " adults OBJECTIVE To evaluate the efficacy and safety of oseltamivir phosphate as treatment for naturally acquired influenza infection . METHODS This study was conducted as a double-blind , r and omized , placebo-controlled , multicenter trial during the influenza epidemic season from January to April 2001 at 7 centers in China . A total of 478 adults without other medical history , aged 18 to 65 years , were enrolled into the study . All subjects demonstrated febrile respiratory illness of no more than 36 hours ' duration with a temperature of 37.8 degrees C or more plus at least two of the following symptoms : coryza/nasal congestion , sore throat , cough , myalgia/muscles aches and pain , fatigue , headache or chills/sweats . Individuals were r and omized into either the oseltamivir phosphate or placebo group with identical-looking capsules . Either oral oseltamivir phosphate , 75 mg twice daily , or placebo was administered to the subjects for 5 days . RESULTS A total of 451 individuals were analyzed for efficacy as the intent-to-treat population ( ITT ) ( 216 oseltamivir and 235 placebo ) and 273 individuals were identified as influenza-infected through laboratory test , who were then defined as the intent-to-treat infected population ( ITTI ) ( 134 oseltamivir and 139 placebo ) . Four hundred and fifty nine individuals were included in the safety analysis . In the ITTI population , the cumulative alleviation proportion of oseltamivir group was significantly higher than that of the placebo group ( P = 0.0466 ) ) . The median duration of illness was 91.6 h [ 95 % confidence interval ( CI ) = 80.2 - 101.3 h ] in the oseltamivir group and 95 h ( 95 % CI = 84.5 - 105.3 h ) in the placebo group . The median area under the curve of decreased total score was significantly higher in the oseltamivir group than in the placebo group , 1382.9 and 1236.7 score-hours , respectively ( P = 0.0196 ) . For the ITT population , similar results were observed . Adverse events ( AE ) were similarly reported in both the oseltamivir group and the placebo group . The main adverse events following test drug were gastrointestinal symptoms , neurological symptoms and rashes . CONCLUSION Oseltamivir was effective and well tolerated as treatment of early naturally acquired influenza We conducted the placebo-controlled double-blind multicenter Phase III trial of newly developed selective oral neuraminidase inhibitor , oseltamivir phosphate ( Ro64 - 0796 ) , in order to evaluate the efficacy and safety , when Ro64 - 0796 was administered orally to both type A and type B influenzavirus infected patients . Patients were r and omly assigned to either Ro64 - 0796 75 mg twice daily group or matching placebo group for five days . A total of 316 patients ( Ro64 - 0796 group ; 154 and placebo group ; 162 ) were recruited , and intent-to-treat infected population , which was defined as the patients that study drug was administered one or more and laboratory-confirmed influenzavirus infection was demonstrated , were 122 and 130 , respectively . Ro64 - 0796 decreased significantly median viral titers after 72 hours ( p = 0.0009 . Analysis of covariance ) , indicating the rapid inhibition of virus replication , and duration of illness which was primary variable of efficacy , was reduced statistically significant by one day ( 23.3 hours ) ( p = 0.0216 , generalized Wilcoxon test ) . Ro64 - 0796 treatment also result ed in the reduction of the fever duration and severity of clinical symptoms . Concerning the safety evaluation , the main accompanied symptoms with Ro64 - 0796 application were gastrointestinal disorders such as bellyache , nausea and vomiting . Most of these events were mild and allowable for the clinical use . There was no abnormal change attributable to Ro64 - 0796 application in the clinical laboratory tests as well as the physiological tests . Our data suggests that Ro64 - 0796 is useful in treating the acute influenzavirus infection In this guideline , evidence is presented and specific recommendations are made about how clinicians can differentiate between bacterial and viral causes of acute bronchitis and about when the use of antibiotics in acute bronchitis is beneficial . The numbers in square brackets are cross-references to the numbered sections in the accompanying background paper , Principles of Appropriate Antibiotic Use for Treatment of Acute Bronchitis in Adults : Background , which is part 2 of this guideline ( see pages 521 - 529 ) . Acute Bronchitis Acute bronchitis is a clinical diagnosis , usually referring to an acute respiratory tract infection in which cough , with or without phlegm , is a predominant feature . The American College of Chest Physicians defines acute cough illness , in contrast to chronic or persistent cough , as lasting less than 3 weeks . As one might expect , there is frequent overlap in how clinicians assign each diagnosis . For example , some clinicians diagnose acute bronchitis only when productive cough is present ; others insist on the presence of purulent sputum [ 1.1 ] . Acute upper respiratory tract infection accounted for approximately 70 % of primary diagnoses in adults presenting for an ambulatory office visit with a chief symptom of cough . Asthma and pneumonia were the next most common diagnoses , assigned to 6 % and 5 % of patients , respectively . Previously undiagnosed asthma is a consideration in patients presenting with an acute cough illness . However , in the setting of acute cough ( < 2 to 3 weeks ' duration ) , the diagnosis of asthma is difficult to establish because of transient bronchial hyperresponsiveness ( and abnormal results on spirometry ) , which many patients with uncomplicated acute bronchitis will have . Since pneumonia is the third most common cause of acute cough illness and potentially the most serious , the primary diagnostic objective should be to exclude the presence of pneumonia [ 1.11.3 ] . Diagnosis An evidence - and quality -based review of four prospect i ve studies evaluating the accuracy of history and physical examination in diagnosing radiographic pneumonia concluded that absence of abnormalities in vital signs ( heart rate 100 beats/min , respiratory rate 24 breaths/min , or oral temperature 38 C ) and chest examination ( focal consolidationfor example , rales , egophony , and fremitus ) sufficiently reduces the likelihood of pneumonia to the point where further diagnostic testing is usually not necessary . Cough lasting longer than 3 weeks exceeds the case definition for acute bronchitis ; such patients should be considered to have persistent cough or chronic cough illness . Irwin and colleagues have developed a well-defined approach to the adult with persistent cough that begins with chest radiography ( 1 ) [ 1.3 , 1.4 ] . As in community-acquired pneumonia , microbiological studies of uncomplicated acute bronchitis identify a pathogen in the minority of cases , ranging from 16 % to 40 % . This variability is most likely due to the epidemic nature of agents that produce uncomplicated acute bronchitis and to limitations in viral and bacterial identification techniques . In epidemiologic studies , respiratory viruses , particularly influenza , appear to cause the majority of cases of uncomplicated acute bronchitis when an agent is sought by culture , antibody serology , or polymerase chain reaction . Specific viruses most frequently associated with acute bronchitis include those that produce primarily lower respiratory tract disease ( influenza B , influenza A , parainfluenza 3 , and respiratory syncytial virus ) , as well as viruses that more commonly produce upper respiratory tract symptoms ( corona virus , adenovirus , and rhinoviruses ) [ 2.1 ] . Unless bacterial superinfection is present ( defined as pneumonia with an infiltrate on chest radiography ) , antibiotic treatment does not affect the clinical course of viral respiratory infection . To date , only Bordetella pertussis , Mycoplasma pneumoniae , and Chlamydia pneumoniae ( TWAR ) have been established as nonviral causes of uncomplicated acute bronchitis in adults . As a group , these agents are associated with 5 % to 10 % of total cases of uncomplicated acute bronchitis in adults . No evidence indicates that Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis produce acute bronchitis in adults without underlying lung disease . Since Gram stain and culture of sputum do not reliably detect M. pneumoniae , C. pneumoniae , or B. pertussis , these tests are not recommended in the evaluation of patients with uncomplicated acute bronchitis [ 2.2 ] . Treatment On the basis of the microbiology of acute bronchitis , it should not be surprising that r and omized , placebo-controlled trials have failed to support a role for antibiotic treatment . By the mid-1990s , published review s of r and omized , placebo-controlled trials had concluded that routine antibiotic treatment of acute bronchitis does not have a consistent impact on duration or severity of illness or on potential complications , such as development of pneumonia . Consistent with these conclusions , the U.S. Food and Drug Administration removed uncomplicated acute bronchitis ( and secondary bacterial infections of acute bronchitis ) as an indication for r and omized , controlled trials of antimicrobial therapy in 1998 . Since then , three meta-analyses have been published ; all reported no impact of antibiotic treatment on illness duration , activity limitation , or work loss , and all concluded that routine antibiotic treatment of adults with acute bronchitis is not justified [ 3.0 , 3.1 ] . The one uncommon circumstance for which evidence supports antibiotic treatment of uncomplicated acute bronchitis is suspicion of pertussis . Selected studies have identified pertussis in up to 10 % to 20 % of patients with cough lasting longer than 2 to 3 weeks . Unfortunately , no clinical features allow clinicians to distinguish adults with persistent cough due to pertussis , primarily because pertussis in adults with previous immunity does not lead to the classic features of whooping cough seen in patients ( usually children ) with primary infection . Therefore , clinicians should limit suspicion and treatment of adult pertussis to patients with a high probability of exposure to pertussis : for example , during documented outbreaks . Antimicrobial therapy of suspected pertussis in adults is recommended primarily to decrease shedding of the pathogen and spread of disease , since antibiotic treatment does not appear to improve resolution of symptoms if it is initiated 7 to 10 days after the onset of illness . Because of the public health implication s , diagnostic testing in consultation with local public health officials is appropriate for surveillance purpose s [ 3.2 ] . Clinicians caring for patients with uncomplicated acute bronchitis should be encouraged to discuss the lack of benefit of antibiotic treatment for uncomplicated acute bronchitis and stop prescribing for this condition as a st and ard of practice . Patients frequently expect to receive antibiotics for uncomplicated acute bronchitis , but this expectation appears to derive from previous episodes of uncomplicated acute bronchitis that were treated with antibiotics . Mounting evidence indicates that patient satisfaction with the office encounter for uncomplicated acute bronchitis does not depend on receipt of an antibiotic but instead is related to the patient-centered quality of the encounter ( for example , believing that the provider spent enough time with them and explained the illness and treatment plan ) . Discussion should provide the patient with realistic expectations for the duration of cough ( typically 10 to 14 days ) , the side effects of antibiotics and subsequent risk for carriage of resistant bacteria , and the ineffectiveness of antibiotics [ 4.0 ] . Since the most common pathogen isolated in patients with uncomplicated acute bronchitis is influenza , discussion of the recent advances in influenza therapy is warranted . The new class of anti-influenza agents , the neuroaminidase inhibitors , are active against both influenza A and B , whereas the previously available drugs amantadine and rimantadine are active only against influenza A. For any of these antiviral agents to be effective , influenza must be diagnosed and treatment initiated within 48 hours of symptom onset . During documented influenza outbreaks , the positive predictive value of clinical diagnosis based on clinician judgment appears to be as accurate as available rapid diagnostic tests for influenza , which have reported sensitivities of 63 % to 81 % . Clinical diagnosis of influenza becomes much less accurate outside of outbreak periods . All of these drugs have a similar impact on the course of influenza illness : about 1 less day of illness and about one-half day sooner return to normal activities . Patients and physicians ( and payers ) will need to weigh the high cost of the newer drugs and the possibility of the emergence of viral resistance against the degree to which the duration of symptoms and illness is shortened [ 3.3 ] . Summary Evaluation of adults with an acute cough illness or a presumptive diagnosis of uncomplicated acute bronchitis should focus on ruling out pneumonia . In the healthy , nonelderly adult , pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds , and chest radiography is usually not indicated . In patients with cough lasting 3 weeks or longer , chest radiography is warranted in the absence of other known causes . Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended , regardless of duration of cough . In the unusual circumstance in which pertussis is suspected , a diagnostic test should be performed and antimicrobial therapy initiated . Patient satisfaction with care for acute bronchitis is most dependent on physicianpatient communication rather than on whether an antibiotic is prescribed . Recommendations Recommendation 1 . The evaluation of adults with an acute cough illness or a OBJECTIVE To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza in China . METHODS A r and omized , double-blinded , placebo controlled trial of oseltamivir was conducted in China . Individuals of 18 to 65 years were enrolled presenting within 36 hours of influenzal symptoms and elevated temperature of 37.8 or higher . They should have at least two of the following symptoms : nasal congestion , sore throat , cough , myalgia , fatigue , headache , chill and sweating ) during an influenza outbreak in the community . Individuals were r and omized either to oseltamivir group ( 75 mg twice daily for 5 days ) or placebo group . RESULTS A total of 478 individuals were recruited , 16(3.35 % ) failed to follow up or refused to continue the trial , 3 ( 0.6 % ) were excluded immediately before taking medication because they did not meet the entry criteria and 8 ( 1.7 % ) individuals were excluded in the blinding review meeting because of protocol violation . Altogether 451 individuals were analyzed for efficacy as intent-to-treat population ( ITT ) ( 216 oseltamivir , 235 placebo ) and 273 individuals were identified as influenza-infected through laboratory test ; they were defined as intent-to-treat infected population ( ITTI ) ( 134 oseltamivir , 139 placebo ) . For safety analysis , 459 individuals were included . In ITTI population , the cumulative alleviation proportion in oseltamivir group was significantly higher than that of placebo group ( P = 0.046 6 ) . The median duration of illness was 91.6 hours [ 95 % confident interval ( CI ) 80.2 - 101.3 hours ] in oseltamivir group and 95.0 hours ( 95 % CI 84.5 - 105.3 hours ) in placebo group . The median area under the curve ( AUC ) of decreased total score was significantly higher in oseltamivir group than in placebo group , being 1 382.9 and 1 236.7 score-hours respectively ( P = 0.019 6 ) . The median duration of fever and myalgia were 27.9 and 35.5 hours in oseltamivir group , being significantly shorter than that of 51.5 and 36.0 hours in placebo group ( P = 0.000 1 and 0.036 1 ) . The median AUC of decreased score for fever and nasal symptom was 337.9 and 108.5 in oseltamivir group , being significantly higher than that of 311.3 and 43.3 in placebo group ( P = 0.011 8 and 0.040 3 ) . The proportion of subjects reporting fever in oseltamivir group were significantly lower than that in placebo group at 36 , 60 , 72 , 96 , 120 and 132 hours after the initiation of treatment ( P = 0.049 , 0.001 , 0.001 , 0.007 , 0.007 and 0.030 ) . The amount of paracetamol taken , incidence of secondary complications and antibiotics usage associated with secondary complications were similar in the two groups ( P = 0.085 1 , 0.944 , 1.000 ) . For ITT population , similar results were seen . Adverse events reported were similar in oseltamivir and placebo group . The main adverse events were gastrointestinal symptoms , headache , vertigo , and rashes . CONCLUSION Oseltamivir was effective and well tolerated in the treatment of early naturally acquired influenza Background Influenza is a potentially life-threatening illness that affects approximately 10 % of the population annually , with result ing personal misery and societal disruption . Oseltamivir is a novel influenza treatment that has been extensively investigated . We describe a series of retrospective analyses investigating various measures of clinical efficacy across different population s of influenza-infected patients enrolled in studies of oseltamivir ( Tamiflu ® ) that were conducted within the clinical development programme . Methods Adolescents and adults ( 13–97 years , n = 4015 ) presenting within 36 hours of onset of influenza symptoms were r and omised to receive oseltamivir 75 mg or placebo twice daily for 5 days during local influenza outbreaks . Of these patients , 2413 had laboratory-confirmed influenza and are included in the analysis . Approximately 30 % ( n = 739 ) of patients were ‘ high risk ’ ; 20 % were healthy elderly subjects ( n = 488 ) and 10 % ( n = 251 ) were patients with chronic respiratory and /or cardiac conditions . The primary endpoint was time to alleviation of a seven-symptom cluster in influenza-infected patients . Supplementary analyses were conducted using a variety of illness definitions and symptom clusters to investigate the sensitivity of the assessment of overall efficacy to differing disease definitions and also to explore efficacy in important sub population s. Results A total of 2413 patients had confirmed influenza infection ( placebo : n = 1063 ; oseltamivir : n = 1350 ) . Across all population s , the time to alleviation of illness was reduced by 19 % ( median duration 100.6 hours [ 95 % CI 94.8–104.7 ] ) compared with placebo ( 124.5 hours [ 95 % CI 117.7–132.3 ] , p < 0.0001 ) . Oseltamivir recipients returned to normal health status , regained ability to perform usual activities and regained normal sleep patterns significantly faster than placebo recipients . The median duration of troublesome influenza symptoms was significantly reduced by oseltamivir treatment , e.g. fatigue by 29 % and myalgia by 26 % ( both p < 0.0001 ) . After 48 hours of treatment , 57 % more placebo than oseltamivir recipients remained febrile , despite greater use of acetaminophen by placebo recipients . In addition , the median duration of acute febrile illness was significantly shortened by oseltamivir treatment compared with placebo in patients with cardiac disease ( 44.0 hours vs 64.7 hours , p = 0.026 ) or chronic obstructive airways disease ( 37.9 hours vs 53.8 hours , p = 0.004 ) . Efficacy was similar among influenza A- and influenza B-infected patients . Oseltamivir was well tolerated , with transient gastrointestinal effects ( observed in one in seven oseltamivir-treated patients compared with one in 12 patients on placebo ) that only rarely result ed in study discontinuation . Conclusions Oral oseltamivir is a well tolerated and effective treatment for influenza in adolescents and adults , including the elderly and patients with chronic cardiac and /or respiratory disease OBJECTIVE To evaluate the efficacy and safety of oseltamivir in the treatment of suspected influenza patients . METHODS A r and omized , open , control and multiple center trial was conducted among 1176 individuals with suspected influenza . They were r and omized either to oseltamivir group ( oseltamivir 75 mg , twice daily for 5 days ) or control group who were given symptom relief medicine . RESULTS No difference was found between two groups in influenza symptoms of the patients ( P > 0.05 ) before the treatment . ( 1 ) Oseltamivir treatment significantly reduced the duration of fever about 25 hours post treatment . ( 2 ) The AUC score of other symptoms was decreased by 160.21 ( about 30.21 % ) , and the duration was shorten by 20 hours . ( 3 ) The ratio and duration of antibiotic use in oseltamivir group were less than that of control group ( P < 0.0001 and P < 0.05 ) . ( 4 ) The incident rate of second generation influenza in oseltamivir group was also less than that of control group ( P < 0.0001 ) . ( 5 ) Secondary complications such as bronchitis , sinusitis and pneumonia occurred 3.23 % in Oseltamivir group and 4.16 % in the control group ( chi(2 ) = 1.209 , P = 0.272 ) . ( 6 ) Digestive symptom such as light nausea were occur in patients who took oseltamivir , there was no difference of side effects rate between two groups ( 5.18 % and 4.16 % , chi(2 ) = 0.680 , P = 0.410 ) . ( 7 ) 75.68 % ( 28 ) were confirmed with positive result of virus test in 37 suspected influenza patients . CONCLUSION Our data suggests that Oseltamivir is effective and well tolerated in suspected influenza patients . It can reduces the duration and severity of influenza symptom and fever , decrease the incidence of suspected influenza in the contacted population , antibiotic using , and with light side-effect ABSTRACT Objective : To evaluate the efficacy and safety of oseltamivir treatment in a population at high risk for influenza . Research design and methods : This was a r and omized , open-label , controlled trial involving Chinese patients with chronic respiratory diseases ( chronic bronchitis , obstructive emphysema , bronchial asthma or bronchiectasis ) or chronic cardiac disease . Patients showing symptoms of influenza were r and omly assigned to receive oral oseltamivir 75 mg twice daily for 5 days ( oseltamivir group ) , or symptomatic treatment ( control group ) within 48 h after symptom onset . Main outcome measures : The main outcome measures were duration and severity of illness in influenza-infected patients . Other outcome measures included incidence of complications , antibiotic use , hospitalization and total medical cost . Results : Of the 118 recruited patients , 56 were identified as influenza-infected through laboratory tests ( oseltamivir , N = 27 ; control , N = 29 ) . Relative to symptomatic treatment , oseltamivir significantly reduced the duration of influenza symptoms by 36.8 % ( p = 0.0479 ) , and the severity by 43.1 % ( p = 0.0002 ) . In addition , oseltamivir significantly reduced the duration of fever by 45.2 % ( p = 0.0051 ) , and the time to return to baseline health status by 5 days ( p = 0.0011 ) . The incidence of complications ( 11 % vs. 45 % , p = 0.0053 ) and antibiotic use ( 37 % vs. 69 % , p = 0.0167 ) were also significantly lower in the oseltamivir group compared with the control group . The cost of treating influenza and its complications was comparable between the two groups ( p = 0.2462 ) . Conclusions : Oseltamivir is effective and well tolerated in high-risk patients with chronic respiratory or cardiac diseases . It can reduce the duration and severity of influenza symptoms and decrease the incidence of secondary complications and antibiotic use , without increasing the total medical cost |
12,620 | 24,504,370 | Stratification by location and T lymphocyte subset indicated that in the tumour centre , CD3 + , CD8 + and FoxP3 + infiltrates were not statistically significant prognostic markers for OS or CS .
In the tumour stroma , high CD8 + , but not CD3 + or FoxP3 + cell infiltrates indicated increased OS .
Furthermore , high CD3 + cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS ; and high CCR7 + infiltrate was also indicated increased OS .
Conclusion : Overall , high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC . | Background : The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer ( CRC ) has not been fully evaluated .
The primary objective of our meta- analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes . | Regulatory T cells ( T(reg ) ) inhibit the generation of host-versus-tumor immunity via suppression of tumor-specific effector T-cell responses and development of immune tolerance to neoplastic cells . The transcription factor forkhead box P3 ( FOXP3 ) is an intracellular key molecule for T(reg ) development and function and is considered to represent the most specific T(reg ) cell marker . The aim of this study was to analyze the frequency and prognostic impact of tumor-infiltrating FOXP3(+ ) T(reg ) in colorectal cancer ( CRC ) stratified by mismatch-repair ( MMR ) status . Using the tissue microarray technique , 1,420 tumor sample s were immunohistochemically stained for FOXP3 and stratified into 1,197 MMR-proficient and 223 MMR-deficient CRCs . Additionally , the 1,197 MMR-proficient CRCs were r and omized into 2 subgroups ( Test Groups 1 and 2 ; n = 613 and 584 , respectively ) . In both MMR-proficient CRC subgroups high frequency tumor-infiltrating FOXP3(+ ) T(reg ) was associated with early T stage ( p = 0.001 and < 0.001 ) , tumor location ( p = 0.01 and 0.045 ) and increased 5-year survival rate ( p = 0.004 and < 0.001 ) , whereas in MMR-deficient CRCs an association between FOXP3(+ ) T(reg ) and absence of lymph node involvement ( p = 0.023 ) , absence of vascular invasion ( p = 0.023 ) and improved 5-year survival rate ( p = 0.029 ) could be detected . In a multivariable analysis including age , gender , T stage , N stage , tumor grade , vascular invasion , and tumor border configuration , a high FOXP3(+ ) T(reg ) frequency was an independent prognostic factor in both MMR-proficient CRC subsets ( p = 0.019 and p = 0.007 ) , but not in the MMR-deficient CRCs ( p = 0.13 ) . Therefore , high frequency of tumor-infiltrating FOXP3(+ ) T(reg ) is associated with early T stage and independently predicts improved disease-specific survival in MMR-proficient CRC patients Breast carcinomas are often infiltrated by inflammatory cells , particularly macrophages and T lymphocytes , but the significance of these cells remains unclear . One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma . CD8(+ ) lymphocytes are a known crucial component of cell-mediated immunity . The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+ ) cytotoxic lymphocytes in breast cancer . Tumor-infiltrating CD8(+ ) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up . The number of CD8(+ ) T cells was counted in tumor nests ( intratumoral ) , in stroma adjacent to tumor cells , and in stroma distant to tumor cells , and their relationship with clinical outcome was determined . The total number of CD8(+ ) cells was positively correlated with tumor grade ( r(s ) = 0.20 ; P < .001 ) and inversely correlated with patient 's age at diagnosis , estrogen receptor-alpha ( ER-α ) , and progesterone receptor ( PgR ) expression ( Mann-Whitney U test , P < .001 ) . The total patient cohort was r and omly divided into two separate training and validation sets before performing univariate survival analysis . Total number and distant stromal CD8(+ ) lymphocytes were associated with better patient survival ( P = .041 and P < .001 , respectively ) in the training set . In multivariate analysis , total CD8(+ ) T-cell count was an independent prognostic factor in both training and validation sets . These results suggest that tumor-infiltrating CD8(+ ) T lymphocytes have antitumor activity as judged by their favorable effect on patients ' survival and could potentially be exploited in the treatment of breast cancer Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies , like GOLFIG chemoimmunotherapy ( gemcitabine , oxaliplatin , 5-fluorouracil/folinic acid , granulocyte macrophage colony-stimulating factor , and aldesleukine ) , that result ed a safe and very active regimen . Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs , increase of central memory T cells , and decrease of regulatory T cells ( Treg ) in the peripheral blood . We thus investigated a potential correlation between the Treg tumor infiltration at diagnosis and the clinical outcome in a current r and omized phase 3 trial aim ed to compare the GOLFIG regimen with the st and ard FOLFOX chemotherapy ( GOLFIG-2 ) . An immunohistochemistry study was carried out to quantify the infiltration of Treg/FoxP3 + T lymphocytes in tumor sample s of 57 patients enrolled in the GOLFIG-2 trial . Treg tumor infiltration scores were correlated with overall survival , treatment-relative survival , and progression-free survival ( PFS ) . Higher Treg tumor infiltration scores were associated with a better prognosis in the whole series ( Treg high score vs. low score : overall survival = mean 43.2 mo vs. 28.6 mo , P=0.0005 ) and a better outcome after treatment ( Treg high score vs. low score : PFS = mean 15.8 mo vs. 8.8 mo , P=0.0009 ; treatment-relative survival = mean 23.1 mo vs. 18.2 mo , P=0.004 ) . PFS was significantly longer in GOLFIG high versus all other subgroups ( mean 18.1 mo vs. 9.9 mo , P=0.01 ) . Our results suggest that a higher FoxP3 + T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours , but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification . In the present study , the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed . Intra-operative tumour tissue sample s from 584 patients undergoing elective surgery for colorectal cancer were included . None of the patients received pre- or post-operative adjuvant chemotherapy . Tissue blocks were cut from the periphery of the tumours and embedded in paraffin . All blocks included both tumour tissue and normal bowel tissue . Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope , which allowed semi-automated quantification of cells within a fixed area . Total white cells and individual counts of eosinophils , neutrophils , mast cells , lymphocytes , and plasma cells were evaluated in every tumour specimen . Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival . The median observation period was 61 ( 49 - 75 ) months . In a multivariate analysis including Dukes ' stage , gender , age , peri-operative blood transfusion , tumour location , and counts of specific inflammatory cells , only advanced Dukes ' stage ( p < 0.0001 ) , high age ( p=0.0003 ) , and tumour location in the rectum predicted poor survival , while high counts of eosinophils ( p=0.006 ) and mast cells ( p=0.02 ) predicted good survival . Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer . Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth Purpose : An efficient adaptive immunity is critical for a longer survival in cancer . We investigated the prognostic value of tumor infiltration by CD8 + T cells expressing the chemokine-receptor-7 ( Tccr7 ) and the correlation between tumor infiltration by Tccr7 and regulatory CD4+FoxP3 + T cells ( Treg ) in 76 metastatic colorectal cancer ( mCRC ) patients enrolled in a phase III trial . Experimental Design : Tccr7 and Treg cell infiltration in tumor sample s was quantified by immunohistochemistry . The correlation among Tccr7 , Treg tumor infiltration , and patients ' outcome was evaluated . Results : High Tccr7 tumor infiltration was predictive of prolonged OS [ high vs. low Tccr7 score : median 38 months ( 95 % CI : 24.5–51.4 ) vs. 20 months ( 95 % CI : 11.4–28.5 ) ; HR = 0.48 ( 95 % CI : 0.24–0.96 ) ; P = 0.03 ] and prolonged progression-free survival [ PFS ; high vs. low Tccr7 score : median 12 months ( 95 % CI : 7.7–16.2 ) vs. 7 months ( 95 % CI : 5.2–8.7 ) ; HR = 0.54 ( 95 % CI : 0.28–1.01 ) ; P = 0.01 ] after front-line chemotherapy . Regression analysis did not show correlation between Tccr7 and Treg infiltration levels . However , the cluster of patients showing concomitant high infiltration by both Tccr7 and Treg disclosed a favorable outcome [ double high vs. double low tumor infiltration score : median OS = 35 months ( 95 % CI : 20.8–49.1 ) vs. 17 months ( 95 % CI : 4.6–29.3 ) ; HR = 0.32 ( 95 % CI : 0.12–0.87 ) ; P = 0.02 and median PFS = 11 months ( 95 % CI : 9.4–12.5 ) vs. 5 months ( 95 % CI : 2.2–7.7 ) ; HR = 0.43 ( 95 % CI : 0.17–1.06 ) ; P = 0.01 ] . Conclusions : High Tccr7 tumor infiltration score is a favorable prognostic factor for mCRC . Our findings underline the relevance of microenvironment-related immunologic events for patient outcome . Clin Cancer Res ; 18(3 ) ; 850–7 . © 2011 AACR Purpose : Host immune response to tumor may be an important prognostic factor for colon cancer patients . However , little is known on prognostic significance of histopathologic lymphoid reaction to tumor , independent of the number of lymph nodes examined and tumoral molecular alterations , including microsatellite instability ( MSI ) and the CpG isl and methylator phenotype ( CIMP ) , both of which are associated with lymphocytic reaction and clinical outcome . Experimental Design : Using 843 colorectal cancer patients in two independent prospect i ve cohorts , we examined patient prognosis in relation to four components of lymphocytic reaction ( i.e. , Crohn's-like reaction , peritumoral reaction , intratumoral perigl and ular reaction , and tumor-infiltrating lymphocytes ) and overall lymphocytic score ( 0 - 12 ) . CIMP was determined using eight markers including CACNA1 G , CDKN2A ( p16 ) , CRABP1 , IGF2 , MLH1 , NEUROG1 , RUNX3 , and SOCS1 . Cox proportional hazard models computed hazard ratio for mortality , adjusted for covariates including tumor stage , body mass index , lymph node count , KRAS , BRAF , p53 , cyclooxygenase-2 ( PTGS2 ) , MSI , CIMP , and LINE-1 methylation . Results : Increasing overall lymphocytic reaction score including tumor-infiltrating lymphocytes was associated with a significant improvement in colorectal cancer – specific and overall survival ( log-rank P < 0.003 ) . These findings remained significant ( adjusted hazard ratio estimates , 0.49 - 0.71 ; Ptrend < 0.009 ) in multivariate models that adjusted for covariates , including body mass index , MSI , CIMP , LINE-1 hypomethylation , and cyclooxygenase-2 . The beneficial effect of tumoral lymphocytic reaction was consistent across strata of clinical , pathologic , and molecular characteristics . Conclusions : Lymphocytic reactions to tumor were associated with improved prognosis among colorectal cancer patients , independent of lymph node count and other clinical , pathologic , and molecular characteristics . ( Clin Cancer Res 2009;15(20):6412–20 PURPOSE To assess the prognostic significance of clinicopathological factors , especially histological parameters of new Jass classification , following sphincter-sparing total mesorectal excision ( TME ) for high-risk rectal cancer . MATERIAL AND METHODS Forty-five consecutive patients treated with curative intent in 1998 - 1999 due to rectal cancer in Dukes stage B and C were studied prospect ively . All of them underwent anterior resection with TME technique . Prognostic value was evaluated by the impact on five-year recurrence-free survival ( RFS ) in uni- and multivariate analysis . Only factors significant in univariate analysis entered the multivariate regression model . P value < 0.05 was stated as a significance limit . RESULTS Regarding traditional clinico-pathological factors patient age , tumor site , differentiation grade , mucinous histology and the extent of direct tumor penetration did not significantly affect survival rates . Only the lymph nodes status was associated with prognosis with statistical importance ( negative vs positive , RFS : 53.8 + /- 10.0 % vs 26.3 + /- 10.4 % , respectively ) . Considering the additional parameters of Jass classification the character of invasive margin of the tumor did not reveal the important predictive value although the lymphocytic tumor infiltration was significantly related to patient outcome ( presence vs absence , RFS : 63.6 + /- 15.2 % vs 37.5 + /- 8.7 % , respectively ) . In multivariate analysis the only one statistically important and independent predictive parameter was the lymph nodes status . CONCLUSIONS Lymph nodes metastases remain the most important prognostic factor after anterior resection with TME for Dukes B and C rectal cancer . From variables included into Jass classification the absence of lymphocytic infiltration of the tumor can be helpful to identify patients with enhanced risk of oncological relapse OBJECTIVE To evaluate the prognostic significance of tumor-infiltrating lymphocytes ( TILs ) in patients with colorectal cancer . DESIGN A retrospective review of prospect ively collected data . SETTING Tertiary care hospital . PATIENTS A total of 546 patients who underwent curative surgery for primary nonmetastatic colorectal cancers from May 1 , 2004 , through December 31 , 2007 . MAIN OUTCOME MEASURES The prognostic value of macroscopic ulceration , tumor border configuration , and TILs at the invasive margin was assessed . RESULTS The low TIL group was significantly correlated with a poorly differentiated status and perineural invasion . During the median 54-month follow-up period , the low TIL group had significantly lower 5-year overall survival and disease-free survival rates than the high TIL group of patients with stage III colorectal cancer ( P = .005 and P = .03 , respectively ) ; however , for patients with stage I and II cancers , the survival rates did not differ between the 2 groups . The 5-year overall survival and 5-year disease-free survival rates were significantly different between the high and low TIL groups of patients with rectal cancer ( P = .003 and P = .01 , respectively ) . The multivariate analysis confirmed that the TIL grade was significantly and independently associated with a worse prognosis for overall survival but not for disease-free survival . CONCLUSIONS An inflammatory cell reaction at the tumor invasive border is considered a useful predictor of survival after colorectal cancer surgery , particularly for patients with stage III disease or rectal cancer |
12,621 | 25,164,542 | Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant setting s. However , in the metastatic setting , similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy .
Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy , but no statistical differences were observed in cardiac toxicity .
Conclusions This systematic review provides a summary of all the data currently available , and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer | Background Dual anti-human epidermal growth factor receptor 2 ( HER2 ) therapies have been shown to improve outcomes of HER2-positive breast cancer patients .
We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies . | BACKGROUND Studies with pertuzumab , a novel anti-HER2 antibody , show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy . We investigated the combination of pertuzumab or trastuzumab , or both , with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting . METHODS In this multicentre , open-label , phase 2 study , treatment-naive women with HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) central ly and stratified by operable , locally advanced , and inflammatory breast cancer , and by hormone receptor expression to receive four neoadjuvant cycles of : trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) , escalating , if tolerated , to 100 mg/m(2 ) every 3 weeks ; group A ) or pertuzumab ( loading dose 840 mg , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) or pertuzumab and trastuzumab ( group C ) or pertuzumab plus docetaxel ( group D ) . The primary endpoint , examined in the intention-to-treat population , was pathological complete response in the breast . Neither patients nor investigators were masked to treatment . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Of 417 eligible patients , 107 were r and omly assigned to group A , 107 to group B , 107 to group C , and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate ( 49 of 107 patients ; 45·8 % [ 95 % CI 36·1 - 55·7 ] ) compared with those given trastuzumab plus docetaxel ( group A ; 31 of 107 ; 29·0 % [ 20·6 - 38·5 ] ; p=0·0141 ) . 23 of 96 ( 24·0 % [ 15·8 - 33·7 ] ) women given pertuzumab plus docetaxel ( group D ) had a pathological complete response , as did 18 of 107 ( 16·8 % [ 10·3 - 25·3 ] ) given pertuzumab and trastuzumab ( group C ) . The most common adverse events of grade 3 or higher were neutropenia ( 61 of 107 women in group A , 48 of 107 in group B , one of 108 in group C , and 52 of 94 in group D ) , febrile neutropenia ( eight , nine , none , and seven , respectively ) , and leucopenia ( 13 , five , none , and seven , respectively ) . The number of serious adverse events was similar in groups A , B , and D ( 15 - 20 serious adverse events per group in 10 - 17 % of patients ) but lower in group C ( four serious adverse events in 4 % of patients ) . INTERPRETATION Patients given pertuzumab and trastuzumab plus docetaxel ( group B ) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel , without substantial differences in tolerability . Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile . These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer . FUNDING F Hoffmann-La Roche BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined . Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Overexpression of human epidermal growth factor receptor-2 ( HER2 ) in metastatic breast cancer ( MBC ) is associated with poor prognosis . This single-arm open-label trial ( EGF109491 ; NCT00508274 ) was design ed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC . The primary endpoint was clinical benefit rate ( CBR ) . Secondary endpoints included progression-free survival ( PFS ) , time to response ( TTR ) , duration of response ( DoR ) , central nervous system ( CNS ) as first site of relapse , and safety . The results showed that there were 23 patients with partial responses and 7 patients with stable disease , result ing in a CBR of 57.7 % . The median PFS was 6.34 months ( 95 % confidence interval , 4.93–9.82 months ) . The median TTR and DoR were 4.07 months ( range , 0.03–14.78 months ) and 6.93 months ( range , 1.45–9.72 months ) , respectively . Thirteen ( 25.0 % ) patients had new lesions as disease progression . Among them , 2 ( 3.8 % ) patients had CNS disease reported as the first relapse . The most common toxicities were palmar-plantar erythrodysesthesia ( 59.6 % ) , diarrhea ( 48.1 % ) , rash ( 48.1 % ) , hyperbilirubinemia ( 34.6 % ) , and fatigue ( 30.8 % ) . Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample , baseline PIK3CA mutation status was not associated with CBR ( P = 0.639 ) or PFS ( P = 0.989 ) . These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC , irrespective of PIK3CA status BACKGROUND The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer . We argue that the two anti-HER2 agents given together would be better than single-agent therapy . METHODS In this parallel groups , r and omised , open-label , phase 3 study undertaken between Jan 5 , 2008 , and May 27 , 2010 , women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were r and omly assigned to oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( loading dose 4 mg/kg [ DOSAGE ERROR CORRECTED ] , subsequent doses 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab . Treatment allocation was by stratified , permuted blocks r and omisation , with four stratification factors . Anti-HER2 therapy alone was given for the first 6 weeks ; weekly paclitaxel ( 80 mg/m(2 ) ) was then added to the regimen for a further 12 weeks , before definitive surgery was undertaken . After surgery , patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks . The primary endpoint was the rate of pathological complete response ( pCR ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , NCT00553358 . FINDINGS 154 patients received lapatinib , 149 trastuzumab , and 152 the combination . pCR rate was significantly higher in the group given lapatinib and trastuzumab ( 78 of 152 patients [ 51·3 % ; 95 % CI 43·1 - 59·5 ] ) than in the group given trastuzumab alone ( 44 of 149 patients [ 29·5 % ; 22·4 - 37·5 ] ; difference 21·1 % , 9·1 - 34·2 , p=0·0001 ) . We recorded no significant difference in pCR between the lapatinib ( 38 of 154 patients [ 24·7 % , 18·1 - 32·3 ] ) and the trastuzumab ( difference -4·8 % , -17·6 to 8·2 , p=0·34 ) groups . No major cardiac dysfunctions occurred . Frequency of grade 3 diarrhoea was higher with lapatinib ( 36 patients [ 23·4 % ] ) and lapatinib plus trastuzumab ( 32 [ 21·1 % ] ) than with trastuzumab ( three [ 2·0 % ] ) . Similarly , grade 3 liver-enzyme alterations were more frequent with lapatinib ( 27 [ 17·5 % ] ) and lapatinib plus trastuzumab ( 15 [ 9·9 % ] ) than with trastuzumab ( 11 [ 7·4 % ] ) . INTERPRETATION Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting . FUNDING GlaxoSmithKline PURPOSE This is a noncomparative , r and omized , phase II trial of preoperative taxane-anthracycline in combination with trastuzumab , lapatinib , or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 ( HER2 ) -positive , stage II to IIIA operable breast cancer . The primary aim was to estimate the percentage of pathologic complete response ( pCR ; no invasive tumor in breast and axillary nodes ) . PATIENTS AND METHODS In the three arms , chemotherapy consisted of weekly paclitaxel ( 80 mg/m(2 ) ) for 12 weeks followed by fluorouracil , epirubicin , and cyclophosphamide for four courses every 3 weeks . The patients r and omly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly ; in arm B patients received lapatinib 1,500 mg orally ( PO ) daily ; and in arm C , patients received trastuzumab and lapatinib 1,000 mg PO daily . RESULTS A total of 121 patients were r and omly assigned . Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib . No episodes of congestive heart failure were observed . The rates of breast-conserving surgery were 66.7 % , 57.9 % , and 68.9 % in arms A , B and C , respectively . The pCR rates were 25 % ( 90 % CI , 13.1 % to 36.9 % ) in arm A , 26.3 % ( 90 % CI , 14.5 % to 38.1 % ) in arm B , and 46.7 % ( 90 % CI , 34.4 % to 58.9 % ) in arm C ( exploratory P = .019 ) . CONCLUSION The primary end point of the study was met , with a relative increase of 80 % in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib . These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer PURPOSE The antibody-drug conjugate trastuzumab-DM1 ( T-DM1 ) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent , DM1 , to human epidermal growth factor receptor 2 (HER2)-overexpressing cancer cells . Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks , with evidence of efficacy , in patients with HER2-positive metastatic breast cancer ( MBC ) who were previously treated with trastuzumab , we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population . PATIENTS AND METHODS This report describes a single-arm phase II study ( TDM4258 g ) that assessed efficacy and safety of intravenous T-DM1 ( 3.6 mg/kg every 3 weeks ) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy . RESULTS With a follow-up of ≥ 12 months among 112 treated patients , the objective response rate by independent assessment was 25.9 % ( 95 % CI , 18.4 % to 34.4 % ) . Median duration of response was not reached as a result of insufficient events ( lower limit of 95 % CI , 6.2 months ) , and median progression-free survival time was 4.6 months ( 95 % CI , 3.9 to 8.6 months ) . The response rates were higher among patients with confirmed HER2-positive tumors ( immunohistochemistry 3 + or fluorescent in situ hybridization positive ) by retrospective central testing ( n = 74 ) . Higher response rates were also observed in patients whose tumors expressed ≥ median HER2 levels by quantitative reverse transcriptase polymerase chain reaction for HER2 expression , compared with patients who had less than median HER2 levels . T-DM1 was well tolerated with no dose-limiting cardiotoxicity . Most adverse events ( AEs ) were grade 1 or 2 ; the most frequent grade ≥ 3 AEs were hypokalemia ( 8.9 % ) , thrombocytopenia ( 8.0 % ) , and fatigue ( 4.5 % ) . CONCLUSION T-DM1 has robust single-agent activity in patients with heavily pretreated , HER2-positive MBC and is well tolerated at the recommended phase II dose PURPOSE We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)- amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor ( ER ) when expressed . In this clinical trial , we sought to translate these findings to patients using targeted therapy without chemotherapy . PATIENTS AND METHOD Women with stages II to III HER2-positive breast cancers were eligible . They received trastuzumab once per week ( 4 mg/kg loading , then 2 mg/kg ) and lapatinib 1000 mg once per day for 12 weeks . Women with ER-positive tumors also received letrozole ( plus a luteinizing hormone-releasing hormone [ LHRH ] agonist if premenopausal ) . Pathologic response was assessed by ER status . Biopsies were obtained at baseline , weeks 2 and 8 , and time of surgery . RESULTS Sixty-six patients were enrolled , and 64 were eligible and evaluable for response . Median tumor size was 6 cm ( range , 1.5 to 30 cm ) . Adverse events were mainly grade s 1 to 2 ( GI , 63 % ; skin , 46 % ) . Grade 3 metabolic , GI , and liver ( 18 % ; 12 patients ) and grade 4 liver toxicities ( one patient ) were also observed . Overall , in-breast pathologic complete response ( pCR ; ypT0-is ) was 27 % ( ER positive , 21 % ; ER negative , 36 % ) . The rate of low-volume residual disease ( ypT1a-b ) was 22 % ( ER positive , 33 % ; ER negative , 4 % ) . CONCLUSION In patients with locally advanced HER2-positive breast cancer , our approach of targeted therapy only result ed in a high pCR rate without chemotherapy . Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy , and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) 506 Background : Extinction of HER2 signaling in HER2 driven BC may be curative . Alternative activation pathways ( HER1 , HER3 ) & mutated downstream signal transducers allow resistance to therapy . STUDY AIM molecularly characterize HER2 + BC before & after 2 wks anti-HER2 therapy ( AHT ) with T , L , or T+L & to correlate these with pCR to continuation of same AHT with neoadjuvant chemo ( FEC75 x 4 Q3W->Paclitaxel x 12W ) . pCR is absence of all invasive cancer in breast & lymph nodes . pCR-Breast used for molecular analysis . METHODS 100 consenting patients ( pts ) with stage II/III , HER2 + BC , normal cardiac function were r and omized to T , L or T+L. Before & after AHT , all pts had core needle biopsies for tissue microarray , stem cell analysis & reverse phase protein microarrays , measuring 60 different phosphoprotein/post-translationally modified protein signaling & gene expression analysis endpoints . RESULTS pCR in the ITT-E ( ITT-E : Pts who had surgery , ≥75 % compliant to chemo and took no prohibited meds . ) pts : 54 % , 45 % , 74 % for T , L , T+L arms . Analysis by response : 1 ) Responders ( R ) have altered HER2 downstream interconnections with PI3 K ( Spearman rho correlation [ rho ] 0.5 , p=0.12 ) vs the non-responders [ NR ] ( rho 0.9 , p=0.037 ) & HER3Y1289 correlated ( p<0.001 for all endpoints ) with EGFRy1173 , mTOR 2448 , & Beta Catenin 33 . 2 ) NR have a ) intact signaling with PI3 K ( rho 0.9 , p=0.037 ) ; b ) intact interactions with autophagy ( PI3 K - LC3B rho 0.83 , p=0.04 ) ; c ) intact stem cell - proliferation signaling ( Musashi - p70S6 Kinase T389 ( p=0.007 , rho 0.89 ) , CD44 - PTEN S380 ( p<0.001 , rho 0.92 ) were not significant in R. Analysis by AHT , prior to AHT R vs. NR : 1 ) TRZ MMP-14 , 2 ) LAP EGFRtyr1068 & Fox01/03T24/32 were statistically different . CONCLUSIONS Our study provides a unique in vivo snapshot of molecular changes in signaling pathways of microdissected tumor cells before & after anti-HER2 therapy . Molecular profiles suggest NR use autophagy & stem cell related pathways to evade therapy , while R have disruption of HER2-HER3 linkages & known downstream regulators of growth & transcription . These results provide insights into novel c and i date " drugable " targets |
12,622 | 22,364,529 | Conclusions Currently there is limited positive EMR impact in the physician office . | Background Increased investments are being made for electronic medical records ( EMRs ) in Canada .
There is a need to learn from earlier EMR studies on their impact on physician practice in office setting s. To address this need , we conducted a systematic review to examine the impact of EMRs in the physician office , factors that influenced their success , and the lessons learned . | BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in elderly patients . Despite this , the ' rule of halves ' particularly applies to this group . We conducted a r and omised controlled trial to evaluate different levels of feedback design ed to improve identification , treatment and control of elderly hypertensives . Fifty-two general practice s were r and omly allocated to either : Control ( n=19 ) , Audit only feedback ( n=16 ) or Audit plus Strategic feedback , prioritising patients by absolute risk ( n=17 ) . Feedback was based on electronic data , annually extracted from practice computer systems . Data were collected for 265,572 patients , 30,345 aged 65 - 79 . The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced . There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group . Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure OBJECTIVE To review all r and omized clinical trials addressing the efficacy of clinical information systems and to determine the clinical setting s , types of interventions , and effects studied . DATA SOURCES Extensive and systematic MEDLINE search es were conducted using a combination of medical subject headings ( MeSH ) and textword terms to collect trial reports . Manual search es of books and monographs as well as informal contacts were also used . STUDY SELECTION The eligibility criteria were ( 1 ) r and omized controlled clinical trial , ( 2 ) computerized information intervention in the study group , and ( 3 ) effect measured on the process or outcome of care . DATA EXTRACTION Two research assistants independently abstract ed from the selected reports the following structured information : trial sites , computerized interventions , effect variables , and outcomes . Three investigators evaluated the combined list of trial features for setting , intervention , and effect . The statistical analysis included an evaluation of agreement in developing classifications and an analysis of the ratio of positive trial outcomes . DATA SYNTHESIS Most information services were tested in outpatient care ( 82 % ) , particularly in primary care ( 66 % ) . The information intervention targeted the provider in 64 % of the trials . The effect was primarily measured for the process of care ( 76 % ) . Provider prompt/reminder , computer-assisted treatment planner , interactive patient education/therapy , and patient prompt/reminder were significantly successful interventions ( sign test , P < .05 ) . CONCLUSIONS R and omized clinical trials confirm that four generic information interventions are active ingredients of computer systems and can make a significant difference in family medicine ( physician and patient reminders , treatment planner , and patient education ) . To manage care and improve quality , primary care computer systems should incorporate these effective information services OBJECTIVE To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners ( GPs ) . RESEARCH DESIGN AND METHODS A r and omized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Data base . Among these , 150 GPs ( intervention group ) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor ( " high risk " ) , whereas the other 150 GPs ( control group ) received only the letter . The electronic reminder , integrated into a st and ard software system for the management of the daily clinical practice , was displayed when every participating GP opened the medical record of diabetic patients aged > or = 30 years . Only high-risk diabetic patients were included in the analysis . Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up . RESULTS We selected 15,343 high-risk diabetic patients , 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group . Overall , 1,672 patients ( 22.9 % ) of the control group and 1,886 ( 23.5 % ) patients of the intervention group received antiplatelet drugs at baseline ( P = N.S. ) . At the end of the follow-up , the number of treated patients was significantly increased in the intervention group ( odds ratio 1.99 , 95 % CI 1.79 - 2.22 ) versus the control group . The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases ( CVDs ) , compared with those with CVDs . CONCLUSIONS These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs The majority of general practitioners in the Netherl and s have replaced traditional paper-based patient records with computer-based records ; physicians enter patient data themselves in the computer during patient encounters ( 1 ) . The use of electronic patient records creates new opportunities to influence physician behavior through implementation of decision support systems ( 2 - 7 ) . In recent years , research ers have documented various computer-based decision support systems that have influenced physician behavior ( 8 - 17 ) . Other investigators , however , have reported that computer-based decision support has not affected patient care ( 18 ) . To resolve the issue , investigators have compared the results of studies that were conducted in different setting s , used different methods , and involved different population s ( 19 ) . Studies comparing different methods of providing computer-based decision support in r and omized trials are not available . In the Netherl and s , 3 % to 4 % of patient encounters with general practitioners in primary care result in the ordering of blood tests ( 20 ) . However , ordering of blood tests is not always appropriate ( 21 - 29 ) . Research ers argue that excessive ordering of tests causes physicians to pursue evaluation of false-positive results , which in turn leads to additional unnecessary diagnostic examinations ( 30 - 35 ) . Two methods have proven effective in reducing the number of tests ordered by Dutch general practitioners . The first method is based on restricting the number of tests that are listed on an order form . Zaat and colleagues ( 36 , 37 ) developed a restricted paper order form that replaced the existing form . The second method involves introduction of indication-oriented order forms that are based on clinical practice guidelines ( 38 - 40 ) . We hypothesized that an indication-oriented order form based on guidelines , which would provide an optimally restricted list of tests that are relevant for a specific indication , would be more effective in decreasing the number of tests ordered compared with an order form that provides an initially limited list of tests . We therefore conducted a r and omized trial to compare the effect of two versions of BloodLink , a computer-based clinical decision support system , on blood test ordering among Dutch general practitioners . Methods Participants In August and September 1995 , all 64 practice s ( 94 general practitioners ) in the region of Delft , the Netherl and s , were invited to participate in the study . Only practice s that had replaced their paper-based patient records with electronic records and were using the computer during patient encounters were eligible . A total of 46 practice s ( 62 general practitioners ) agreed to participate . R and omization To avoid contamination , we performed r and om allocation at the level of the practice ( 41 , 42 ) . The practice s were first stratified by type : solo practice s or group practice s ( two or more general practitioners in the same practice ) . Each practice was subsequently assigned by simple r and om allocation to use BloodLink-Restricted or BloodLink- Guideline for the full study period . A research er who was not involved in the study and was blinded to the identity of the practice s performed the r and omization by using a r and om-numbers table . After r and omization , 22 practice s involving 30 general practitioners were assigned to use BloodLink-Restricted and 24 practice s involving 32 general practitioners were assigned to use BloodLink- Guideline . Intervention We developed two versions of BloodLink , a computer-based decision support system . BloodLink-Restricted initially displays a reduced list of tests , whereas BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . Both versions of BloodLink are integrated with the computer-based patient record ( 43 ) . The option to use BloodLink was added to the screen that the general practitioner uses when entering data in the electronic patient record during patient encounters . The general practitioner can activate BloodLink to order blood tests as an alternative to using paper order forms . Because the total number of tests that can be ordered is too large to display on a computer screen , a set of tests is presented for selection . If the physician requires additional tests that are not currently displayed , he or she can type the first few letters of the names of the required tests , and the system will present all possible matches ( including those corresponding to possible typing errors of the general practitioner ) for selection . The number of tests that the general practitioners had at their disposal was the same both before and during the intervention ( 52 clinical chemistry tests and 46 microbiological tests ) . Options for specific instructions to the laboratory ( for example , urgent processing or fasting values ) are available . Once the physician has made his or her selection s , BloodLink prints a patient-specific test order form and instructions for the laboratory and up date s the patient record with the tests that have been ordered . The only difference between the two versions of BloodLink is the method used to present the initial set of tests to the general practitioner . BloodLink-Restricted is based on the idea of a restricted order form . It offers the general practitioner an initial set of 15 tests that have been shown to cover most of the clinical situations seen in primary care ( 36 ) . BloodLink-Restricted can be viewed as a general electronic order form that presents only 15 tests on the screen , together with a field labeled other tests that allows the physician to request any other blood test ( 43 ) . The 15 tests are alanine aminotransferase , aspartate aminotransferase , total bilirubin , cholesterol , creatinine , erythrocyte sedimentation rate , free thyroxine , -glutamyltransferase , glucose ( and fasting glucose ) , glycosylated hemoglobin , hemoglobin , mean corpuscular volume , PaulBunnell , potassium , and thyroid-stimulating hormone . At any time , the physician can customize tests for individual patients by adding or deleting tests . BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . By January 1996 , the Dutch College of General Practitioners had published 54 guidelines . Some guidelines focus on symptoms that are frequently seen in the primary care setting , such as acute diarrhea , acute sore throat , low back pain , alcohol abuse , fever in children , and sleeping disorders . Other guidelines focus on common diseases in primary care , such as diabetes , asthma , depression , dementia , and eczema . Finally , a set of guidelines covers preventive medicine . We review ed the most recent version of each guideline , available in January 1996 , and noted whether it contained a reference to a blood test ( 44 ) . We determined the clinical situation in which the test should be performed ( indication ) and the tests that should be performed in that situation ( advised tests ) . When general practitioners activate the system , BloodLink- Guideline first provides an overview of the available guidelines . The names of these guidelines are familiar to Dutch general practitioners . The general practitioner selects the appropriate guideline . A guideline may describe several different indications for requesting blood tests ; for example , the guideline for blood tests and liver disease mentions 10 different indications . After the indication has been identified , the system proposes the relevant tests . The general practitioner then decides whether to adhere to the protocol . At any time , the physician can customize tests for individual patients by adding or removing tests from the proposed list . Although new guidelines are published at regular intervals , the currently available guidelines cover only a limited set of indications for blood tests ( 44 ) . In the absence of national guidelines , local or regional guidelines may be used . The version of BloodLink- Guideline used during the clinical trial in the Delft region included three regional guidelines for anemia , AIDS , and clotting disorders , in addition to all national guidelines . Even with these additional guidelines , BloodLink- Guideline does not cover all possible indications for blood tests in primary care . To deal with these situations , the general practitioner can select the heading other indication and order any test . Protocol Before the study , the general practitioners were using two paper order forms : one for clinical chemistry and one for microbiology . After BloodLink was installed , one of the authors gave a brief orientation presentation to the participating practitioners . During a 3-month phase-in period , the general practitioners were allowed to use BloodLink in their practice s to become acquainted with the system . After this period , the general practitioners were asked whether they were willing to participate in the trial . The study period was March 1996 through February 1997 . Physicians always had the choice to use either the BloodLink software or the paper forms to order clinical chemistry and microbiology tests ; thus , paper order forms were still available during the entire intervention period . When the general practitioner ordered blood tests during a patient encounter , only one order form was generated regardless of whether the general practitioner used paper forms or BloodLink . The electronic patient record monitored use of BloodLink by the practitioners . To include the requests for blood tests that were made by using traditional paper forms , we retrieved from the regional laboratory all requests for blood tests . Outcomes We counted the number of order forms that the laboratory received from the general practitioners and the number of tests on each form . The main outcome measure was the average number of tests per order form ( including paper forms ) per practice ( summary variable ) . We defined the most frequently ordered tests as the tests that accounted for 80 % of the total number of tests ordered . For these tests , we Background In spite of succesful adoption of electronic patient records ( EPR ) by Norwegian GPs , what constitutes the actual benefits and effects of the use of EPRs in the perspective of the GPs and patients has not been fully characterized . We wanted to study primary care physicians ' use of electronic patient record ( EPR ) systems in terms of use of different EPR functions and the time spent on using the records , as well as the potential effects of EPR systems on the clinician-patient relationship . Methods A combined qualitative and quantitative study that uses data collected from focus groups , observations of primary care encounters and a question naire survey of a r and om sample of general practitioners to describe their use of EPR in primary care . Results The overall availability of individual patient records had improved , but the availability of the information within each EPR was not satisfactory . GPs ' use of EPRs were efficient and comprehensive , but have result ed in transfer of administrative work from secretaries to physicians . We found no indications of disturbance of the clinician-patient relationship by use of computers in this study . Conclusion Although GPs are generally satisfied with their EPRs systems , there are still unmet needs and functionality to be covered . It is urgent to find methods that can make a better representation of information in large patient records as well as prevent EPRs from contributing to increased administrative workload of physicians Design : Mailed survey to a stratified r and om sample of all medical practice s in Massachusetts in 2005 , with one physician per practice r and omly selected for survey . Measurements : EHR adoption rates . Results : The response rate was 71 % ( 1345/1884 ) . Overall , while 45 % of physicians were using an EHR , EHRs were present in only 23 % of practice s. In multivariate analysis , practice size was strongly correlated with EHR adoption ; 52 % of practice s with 7 or more physicians had an EHR , as compared with 14 % of solo practice s ( adjusted odds ratio , 3.66 ; 95 % confidence interval , 2.28–5.87 ) . Hospital-based practice s ( adjusted odds ratio , 2.44 ; 95 % confidence interval , 1.53–3.91 ) and practice s that teach medical students or residents ( adjusted odds ratio , 2.30 ; 95 % confidence interval , 1.60–3.31 ) were more likely to have an EHR . The most frequently cited barriers to adoption were start-up financial costs ( 84 % ) , ongoing financial costs ( 82 % ) , and loss of productivity ( 81 % ) . Conclusions : While almost half of physicians in Massachusetts are using an EHR , fewer than one in four practice s in Massachusetts have adopted EHRs . Adoption rates are lower in smaller practice s , those not affiliated with hospitals , and those that do not teach medical students or residents . Interventions to exp and EHR use must address both financial and non-financial barriers , especially among smaller practice s. J Am Med Inform Assoc . 2007;14:110–117 . DOI 10.1197/jamia . M2187 . by gest on Sptem er 5 , 2016 OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice PURPOSE Care of patients with diabetes requires management of complex clinical information , which may be improved by the use of an electronic medical record ( EMR ) ; however , the actual relationship between EMR usage and diabetes care quality in primary care setting s is not well understood . We assessed the relationship between EMR usage and diabetes care quality in a sample of family medicine practice s. METHODS We conducted cross-sectional analyses of baseline data from 50 practice s participating in a practice improvement study . Between April 2003 and December 2004 chart auditors review ed a r and om sample of medical records from patients with diabetes in each practice for adherence to guidelines for diabetes processes of care , treatment , and achievement of intermediate outcomes . Practice leaders provided medical record system information . We conducted multivariate analyses of the relationship between EMR usage and diabetes care adjusting for potential practice - and patient-level confounders and practice -level clustering . RESULTS Diabetes care quality in all practice s showed room for improvement ; however , after adjustment , patient care in the 37 practice s not using an EMR was more likely to meet guidelines for process ( odds ratio [ OR ] , 2.25 ; 95 % confidence interval [ CI ] , 1.42–3.57 ) treatment ( OR , 1.67 ; 95 % CI , 1.07–2.60 ) , and intermediate outcomes ( OR , 2.68 ; 95 % CI , 1.49–4.82 ) than in the 13 practice s using an EMR . CONCLUSIONS The use of an EMR in primary care practice s is insufficient for insuring high- quality diabetes care . Efforts to exp and EMR use should focus not only on improving technology but also on developing methods for implementing and integrating this technology into practice reality Abstract BACKGROUND : In New Zeal and , more than 5 % of people aged 50 years and older have undiagnosed diabetes ; most of them attend family practitioners ( FPs ) at least once a year . OBJECTIVES : To test the effectiveness of patients or computers as reminders to screen for diabetes in patients attending FPs . DESIGN : A r and omized-controlled trial compared screening rates in 4 intervention arms : patient reminders , computer reminders , both reminders , and usual care . The trial lasted 2 months . The patient reminder was a diabetes risk self- assessment sheet filled in by patients and given to the FP during the consultation . The computer reminder was an icon that flashed only for patients considered eligible for screening . PARTICIPANTS : One hundred and seven FPs . MEASUREMENTS : The primary outcome was whether each eligible patient , who attended during the trial , was or was not tested for blood glucose . Analysis was by intention to treat and allowed for clustering by FP . RESULTS : Patient reminders ( odds ratio [ OR ] 1.72 , 95 % confidence interval [ CI ] 1.21 , 2.43 ) , computer reminders ( OR 2.55 , 1.68 , 3.88 ) , and both reminders ( OR 1.69 , 1.11 , 2.59 ) were all effective compared with usual care . Computer reminders were more effective than patient reminders ( OR 1.49 , 1.07 , 2.07 ) . Patients were more likely to be screened if they visited the FP repeatedly , if patients were non-European , if they were “ regular ” patients of the practice , and if their FP had a higher screening rate prior to the study . CONCLUSIONS : Patient and computer reminders were effective methods to increase screening for diabetes . However , the effects were not additive BACKGROUND Preventive care is an important role for general practitioners , yet opportunities for prevention are often missed . METHOD We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice . All patients who attended were r and omised by the terminal digit of their record number . RESULTS The control uptake of opportunistic prevention was low ; ranging from 1.5 % ( tetanus immunisation ) to 27 % ( influenza immunisation ) . The reminders increased this by significant but small amounts for four out of 12 activities ( immunisation for tetanus and pneumococcus and recording of allergies and weight ) , insignificant increases for four ( mumps , measles and rubella immunisation , recording of smoking , and taking of cervical smears and of blood pressure ) , and insignificantly decreased influenza immunisation , and screening for diabetes and hyperlipidaemia . DISCUSSION Opportunistic electronic reminders have the potential to increase preventive care in general practice OBJECTIVES To describe the patterns of computer use during patient visits to family doctors and to determine whether doctors alter their pattern of computer use in consultations which have significant psychological content . DESIGN Observational , non-r and omised cluster trial with data being collected from videotaped consultations . SETTING Three inner-city Family Practice offices involved in physician training in Belfast , Northern Irel and . PARTICIPANTS Ten family doctors , who declared using computers during their consultations and consecutive consenting adult patients attending these doctors . RESULTS One hundred consultations were videotaped ( 59 % patient participation rate ) . The average consultation time was 9min 48s , and number of problems per consultation was 1.9 . Three broad styles of computer use were defined : ( 1 ) " end users " who only used the computer at the end of a consultation to summarise the consultation , ( 2 ) " continuous users " , who interacted with the computer throughout the consultation , and ( 3 ) " minimal users " , who only ever used the computer at the end of the consultation mostly to issue prescriptions . Of the 100 consultations videoed 37 % were of a psychological nature . Consultations with psychological content were on average longer ( 11min 47s vs. 8min 39s ) and the average percentage time doctors spent on the computer was about half that of non-psychological consultations ( 11 % vs. 23 % and p<0.001 ) . CONCLUSION The doctors were found to adopt one of three broad styles of computer use during their consultations . In consultations with observable significant psychological content doctors significantly reduce the proportion of time at the computer suggesting an ability to appropriately tailor their use of the computer during consultations |
12,623 | 20,882,273 | No significant differences between the two calcineurin inhibitors were found with regard to acute rejections causing haemodynamic instability , diabetes , renal dysfunction , infection , malignancy , or neurotoxicity .
Conclusion Tacrolimus seems to be superior to cyclosporine in heart transplant patients with regard to hypertension , hyperlipidaemia , gingival hyperplasia and hirsutism .
In addition , tacrolimus seems to be superior to microemulsion cyclosporine in heart transplant patients with regard to a number of outcomes , including death . | Purpose We conducted a systematic review of r and omized trials to compare the benefits and harms of tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation . | OBJECTIVE In this study , we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation ( HT ) . PATIENTS AND METHODS From August 2004 to July 2007 , 108 adult patients underwent primary HT . The main exclusion criteria were : donors > 60 years ; cold ischemia times > 6 hours ; recipients of multiorgan transplantation or a previous transplantation ; and panel-reactive antibodies > or = 25 % . The cyclosporine plus everolimus regimen ( group CE , n = 32 ) was suggested first ; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection , then patient was r and omly assigned to success cyclosporine plus mycophenolate mofetil ( MMF ; group CM , n = 24 ) or tacrolimus plus MMF ( group TM , n = 25 ) . All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies . RESULTS No 30-day mortality was noted in any group . The efficacy failure rates were 3 % , 25 % , and 16 % in groups CE , CM , and TM , respectively ( P = .04 between groups CE and CM ) . The 1-year survivals were 96.7 % + /- 18.1 % , 89.7 % + /- 29.8 % , and 81.0 % + /- 35.5 % for groups CE , CM , and TM , respectively ( P = .04 between groups CE and TM ) . The 3-year survival rates were 91.9 % + /- 28.3 % , 79.8 % + /- 46.0 % , and 81.0 % + /- 35.5 % in groups CE , CM , and TM , respectively . CONCLUSIONS The 3 immunosuppressive regimens offered good efficacy after HT . The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure ( compared with cyclosporine plus MMF : 3 % vs 25 % ) and better 1-year survival compared with tacrolimus plus MMF : 96.7 % vs 81.0 % Reduction of allograft rejections remains a primary goal for patients after orthotopic heart transplantation . In an open , multicentre , prospect ively r and omised , parallel group study , patients with primary orthotopic heart transplantation under oral immunosuppressive treatments with tacrolimus ( FK506 ) or cyclosporine ( s and immun ) were compared with respect to medical outcome data . As health-related quality -of-life ( HRQOL ) is also supposed to be an important outcome parameter , it was assessed as a secondary variable in these two patient groups . Patients ' self-rated generic HRQOL was assessed 6 weeks , 3 months , 6 months and 12 months after surgery with the SF-36 question naire , a generic HRQOL instrument . For 70 patients ( 46 under tacrolimus , 24 under cyclosporine ) , intent-to-treat analyses were carried out . The tacrolimus group showed improvements in the different HRQOL subscales of the SF-36 compared to the cyclosporine group . Especially the SF-36 subscales ' vitality ' and ' mental health ' showed statistically higher scores for the tacrolimus group . Aggregating psychological and cognitive subscales in the ' mental component score ' , patients treated with tacrolimus showed a statistically significant improvement compared to the cyclosporine group . The assessment of HRQOL variables in the evaluation of treatment effects proved to be an outcome parameter in this study . The results demonstrate the benefit of tacrolimus with respect to the HRQOL of patients , especially in the psychological dimension BACKGROUND Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation . To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia , we conducted a prospect i ve , r and omized , open-label , multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation . METHODS Eighty-five adult patients ( pts ) at six United States cardiac transplant centers , undergoing their first cardiac transplant procedure , were prospect ively r and omized to receive either TAC-based ( n = 39 ) or cyclosporine (CYA)-based ( n = 46 ) immunosuppression . All pts received a triple-drug protocol with 15 pts ( 18 % ) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction . Endomyocardial biopsies were performed at Weeks 1 , 2 , 3 , 4 , 6 , 8 , 10 , 12 , 24 , and 52 . The study duration was 12 months . RESULTS Patients were mostly male ( 87 % ) Caucasian ( 90 % ) with a mean age of 54 years and primary diagnoses of coronary artery disease ( 55 % ) and idiopathic dilated cardiomyopathy ( 41 % ) . There were no significant demographic differences between groups . Patient and allograft survival were not different in the two groups . The probability and overall incidence of each grade of rejection , whether treated or not , and the types of treatment required did not differ between the groups . At baseline and through 12 months of follow-up , chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3 , 6 , and 12 months ( 239 vs 205 mg/dL , 246 vs 191 mg/dL , 212 vs 186 mg/dL , respectively , p < 0.001 ) . Likewise , LDL-cholesterol , HDL-cholesterol and triglycerides were significantly higher in the CYA group . More CYA patients received therapy for hypercholesterolemia ( 71 % vs 41 % at 12 months , p = 0.01 ) . There were no significant differences in renal function , hyperglycemia , hypomagnesemia , or hyperkalemia during the first 12 months . More CYA patients developed new-onset hypertension requiring pharmacologic treatment ( 71 % vs 48 % , p = 0.05 ) . The incidence of infection was the same for the two groups ( 2.6 episodes/pt/12 month follow-up ) . CONCLUSION Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function , hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression UNLABELLED This study compares the pharmacokinetics of tacrolimus ( TAC ) and cyclosporine Neoral ( CsA ) in cardiac transplant recipients . METHODS Twenty-six de novo cardiac recipients were prospect ively and r and omly assigned to receive oral TAC- or CsA-based regimens after 5 to 6 days of rabbit antithymocyte globulin induction . Blood sample s were collected at 0 ( before the dose ) and 0.5 , 1 , 2 , 3 , 4 , 6 , 8 , 10 , as well as 12 hours after drug administration . The pharmacokinetics of the first dose ( PK-1 ) and at steady state ( PK-S , 1 month after transplantation ) were analyzed . RESULTS Comparing the AUC per milligram dose , there was no significant difference between PK-1 and PK-S among TAC ( 46.0 + /- 24.3 ng x h/mg x mL versus 69.0 + /- 43.9 ng x h/mg x mL , P = .15 by paired t-test ) , but a significant difference in CsA ( 25.2 + /- 11.4 ng x h/mg x mL versus 45.4 + /- 12.9 ng x h/mg x mL , P = .0005 by paired t-test ) . This means better TAC absorption in the early post-heart transplant period . Using a single-point blood level to predict AUC , TAC showed a significantly higher correlation than CsA at all corresponding sampling times . Besides , C12 in both PK-1 and PK-S of TAC displayed good correlations to the AUC ( r2 = .895 , P = .00 in PK-1 and r2 = .81 , P = .00 in PK-S ) . The TAC trough level was accurate enough to predict the AUC . CONCLUSION The pharmacokinetic profile of TAC is more reliable than that of CsA in the early post-heart transplant period . A high correlation of trough blood levels with AUC omits the requirement for a multiple sampling strategy to more accurately measure AUC as is needed with INTRODUCTION This study compared the efficacy and safety of a tacrolimus (TAC)-based with a cyclosporine (CsA)microemulsion-based immunosuppressive regimen in primary cardiac transplantation . METHODS Heart recipients were r and omly assigned to receive either TAC or CsA regimen after sequential induction with rabbit anti-thymoglobulin . Endomyocardial biopsies were performed at weeks 1 , 2 , 3 , and 4 and months 2 , 3 , and 6 . RESULTS Among 21 adult patients ( TAC , 11 ; CsA , 10 ) in this study , patient survival rates were 100 % in both groups at the end of 6 months . One patient ( 9 % ) in the TAC group experienced acute rejection ( ISHLT > or = 1B ) versus 6 patients ( 60 % ) in the CsA group ( P = .02 ) . The effects on hematology , biochemistry , cytomegalovirus infection , and hemodynamics were similar in both groups except for better lipid profiles in the TAC group . There were no significant differences in severe adverse events . CONCLUSION The TAC-based regimen had a lower risk of acute rejection compared with CsA in heart transplant recipients . The safety profiles were similar in both groups . Therefore , TAC is an alternative to CsA as a primary maintenance immunosuppressant in heart transplantation BACKGROUND To compare the efficacy and safety of tacrolimus and cyclosporine in heart transplantation , this single-center , prospect i ve , r and omized , open-label clinical trial was undertaken . METHODS Seventy-three adult patients were r and omly assigned at the time of transplantation to receive either tacrolimus ( n=43 ) or cyclosporine ( n=30 ) as the primary immunosuppressant . Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period ; all other patients received only oral tacrolimus . RESULTS With a mean follow-up of 27 months , patient survival rates ( tacrolimus 83 % , cyclosporine 81 % ) were similar . Fewer patients experienced acute rejection in the tacrolimus group ( 79 % ) than in the cyclosporine group ( 100 % ) , but the difference was not statistically significant . The number of infections and dialysis and insulin requirements were similar for the 2 treatment groups , but the proportion of patients requiring multidrug antihypertensive regimens was lower in the tacrolimus group ( 12.5 % vs 50.0 % at month 6 ; p=.025 ) . The interpatient variance in pharmacokinetic parameters in a subset of 10 patients was much higher after the first oral dose of tacrolimus than at steady-state ( eg , first-dose time at which maximal concentration is reached ( t(max ) ) : 3.5+/-2.5h , steady-state t(max ) : 2.0+/-0.7h ) , and patients treated with intravenous tacrolimus ( n=13 ) rather than oral tacrolimus ( n=30 ) reached target concentrations faster and with less interpatient variability ( eg , at day 0 : 9.72+/-10.9 ng/mL intravenously vs 3.31+/-8.1 orally ) . CONCLUSIONS Tacrolimus was associated with similar efficacy and safety profiles compared with cyclosporine . The higher interpatient variance in absorption associated with oral tacrolimus during the first few days after transplantation would suggest that intravenous tacrolimus should be used during the perioperative period The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established . Between November 2001 and June 2003 , 343 de novo cardiac transplant recipients were r and omized to receive steroids and either tacrolimus ( TAC ) + sirolimus ( SRL ) , TAC + mycophenolate mofetil ( MMF ) or cyclosporine ( CYA ) + MMF . Antilymphocyte induction therapy was allowed for up to 5 days . The primary endpoint of ≥3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months ( TAC/MMF 22.4 % , TAC/SRL 24.3 % , CYA/MMF 31.6 % , p = 0.271 ) and 1 year ( p = 0.056 ) , but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year ( 23.4 % vs. 36.8 % ; p = 0.029 ) . Differences in the incidence of any treated rejection were significant ( TAC/SRL = 35 % , TAC/MMF = 42 % , CYA/MMF = 59 % ; p < 0.001 ) , as were median levels of serum creatinine ( TAC/SRL = 1.5 mg/dL , TAC/MMF = 1.3 mg/dL , CYA/MMF = 1.5 mg/dL ; p = 0.032 ) and triglycerides ( TAC/SRL = 162 mg/dL , TAC/MMF = 126 mg/dL , CYA/MMF = 154 mg/dL ; p = 0.028 ) . The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing . These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients , including fewer ≥3A rejections or hemodynamic compromise rejections and an improved side‐effect profile BACKGROUND Previous multicenter , r and omized trials , lacking st and ardized post-transplant protocol s , have compared tacrolimus ( Tac ) and cyclosporine ( CyA , S and immune ) and demonstrated similar outcomes with some different adverse effects . The microemulsion form of CyA ( mCyA , Neoral ) has replaced S and immune CyA as the more widely utilized CyA formulation . This is the first 5-year follow-up study of a large , single-center trial ( n = 67 ) under a st and ardized post-transplant protocol comparing Tac and mCyA. METHODS Sixty-seven heart transplant patients were r and omized to Tac ( n = 33 ) or mCyA ( n = 34 ) , both in combination with corticosteroids and azathioprine without cytolytic induction . Five-year end-points included survival , Grade > or = 3A or treated rejection , angiographic cardiac allograft vasculopathy ( CAV ; any lesion > or = 30 % stenosis ) , renal dysfunction ( creatinine > or = 2.0 mg/dl ) , use of two or more anti-hypertensive medications , percent diabetic and lipid levels . RESULTS Five-year survival , freedom from Grade > or = 3A or any treated rejection and angiographic CAV , mean cholesterol level and percent diabetic were similar between the two groups . The Tac group had a significantly lower 5-year mean triglyceride level ( Tac 97 + /- 34 vs mCyA 175 + /- 103 mg/dl , p = 0.011 ) and average serum creatinine level ( Tac 1.2 + /- 0.5 mg/dl vs mCyA 1.5 + /- 0.4 mg/dl , p = 0.044 ) . There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group ( Tac 33 % vs mCyA 59 % , p = 0.065 ) . CONCLUSIONS Tac and mCyA appear to be comparable with regard to 5-year survival , freedom from rejection and CAV . However , compared with mCyA , Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications BACKGROUND Tacrolimus ( FK506 ) may represent a major advance in the management of allograft rejection after solid organ transplantation . In August 1994 a European heart transplantation pilot study was initiated to assess the efficacy and safety of tacrolimus when administered exclusively through an oral route . METHODS Eighty-two heart transplant recipients were r and omized to treatment ( 2:1 ratio ) with either tacrolimus- ( n=54 ) or cyclosporine-based therapy ( n=28 ) . RESULTS No significant differences were evident between the two treatment groups in either rejection or survival rates at 1 year . Kaplan-Meier estimates of the freedom from rejection were 26.3 % and 18.5 % , respectively , for the tacrolimus and cyclosporine treatment groups ( p=.444 ) . Survival rates were 79.6 % and 92.9 % ( p=.125 ) . At 3 of the 5 centers , patients received antithymocyte globulin during the immediate postoperative period and fared better than those who did not ( with acute rejection-free rates of 49.2 % and 26.7 % for tacrolimus and cyclosporine , respectively [ p=.080 ] , as opposed to 7.1 % and 8.3 % [ p=.965 ] ; patient survival rates of 84.6 % and 93.3 % [ p=.382 ] vs 75.0 % and 92.3 % [ p=.243 ] ) . The overall rates of infection , impaired renal function ( 31.5 % vs 21.4 % ) , and glucose intolerance ( 7.0 % vs 4.3 % ) did not differ significantly between the tacrolimus and cyclosporine treatment groups . Tacrolimus seemed to possess an advantage with regard to a reduced requirement for antihypertensive therapy ( 59.5 % vs 87.5 % , p=.025 ) . CONCLUSIONS Immunosuppression with oral tacrolimus provides a viable alternative to treatment with cyclosporine , particularly when administered in conjunction with antibody therapy . Further studies are warranted to optimize the administration of tacrolimus in this indication OBJECTIVES This study aim ed to compare changes in coronary endothelial function , systemic endothelin-1 ( ET-1 ) levels , and vascular remodeling in heart transplant recipients r and omized to cyclosporin A ( CyA ) or tacrolimus ( Tac ) immunosuppression . BACKGROUND Functional endothelial abnormalities and intimal thickening are sensitive measures of early cardiac allograft vasculopathy ( CAV ) . METHODS The r and omized , prospect i ve study was performed in two groups of 22 patients , maintained on Tac or CyA and mycophenolate mofetil immunosuppression , 1 and 12 months after heart transplantation . We investigated epicardial luminal diameter , coronary blood flow velocity , and ET-1 plasma levels at 1 and 12 months after transplantation . Structural coronary alterations were determined using intravascular ultrasound . RESULTS Epicardial vasomotor function at baseline and during follow-up was comparable between the groups . Deterioration of microvascular endothelial function during follow-up was significantly enhanced in the CyA versus Tac group ( p < 0.05 ) . Circulating ET-1 concentration increased in the CyA group but significantly decreased over time in the Tac group ( CyA + 17 % vs. Tac -25 % ; p < 0.05 ) . The time-dependent increase in mean intimal area was significantly enhanced in the CyA versus Tac group , whereas the vessel area significantly increased during follow-up in the Tac compared with the CyA group . CONCLUSIONS Epicardial endothelial function is comparable between CyA- and Tac-treated patients . Microvascular endothelial function deteriorates more in CyA-treated patients , a finding that correlates with enhanced ET-1 concentration and an increased intimal area during follow-up . The mean vessel area in the Tac group increased over time , indicating positive vascular remodeling . Tac is superior to CyA with respect to microvascular endothelial function , intimal thickening , and vascular remodeling BACKGROUND The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection . The original oil-based form of cyclosporine demonstrated unpredictable absorption result ing in an increased frequency of acute and chronic rejection in patients with poor bioavailability . The primary end . points of the present , prospect i ve , r and omized multicenter , double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine ( CsA-NL ) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with S and immune CsA-(SM ) in the study population . The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection , fewer International Society of Heart and Lung Transplantation grade > or = 3A rejections in female patients and fewer infections . Our report represents the final analysis of the results 24 months after transplantation . METHODS A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States , Canada , and Europe were enrolled in this double-blind , r and omized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM . Acute allograft rejection was diagnosed by endomyocardial biopsy and grade d according to the International Society of Heart and Lung Transplantation nomenclature . Kaplan-Meier analysis and Fisher 's exact test were used for comparisons between groups . RESULTS After 24 months , allograft and recipient survival were identical in both groups . There were fewer CsA-NL patients ( 6.9 % ) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group ( 17.7 % , P=0.002 ) . There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups ( 7 ; 3.7 % ) compared with the CsA-SM group ( 18 ; 9.4 % , P=0.037 ) . The average corticosteroid dose was lower in the CsA-NL group ( 0.37 mg/kg/day ) compared with the CsA-SM group ( 0.48 mg/kg/day , P=0.034 ) over the 24-month study period . Overall , there was no difference in blood pressure or creatinine between the two study groups . CONCLUSIONS The final results of this multi-center , r and omized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM . The use of CsA-NL did not predispose these patients to a higher risk of adverse events Background . The purpose of this prospect i ve , r and omized , open-label , phase II , multicenter study was to optimize the initial oral dose of tacrolimus . Methods . A total of 113 patients were r and omly assigned to initial low-dose ( 0.075 mg/kg/day , n=55 ) or high-dose ( 0.15 mg/kg/day , n=58 ) oral tacrolimus and followed for 3 months . Target whole-blood trough levels were 10 to 20 ng/mL. Prophylactic use of corticosteroids and azathioprine was identical in both groups , and antibody induction was m and atory . The primary endpoint was the time to and incidence of the initial oral tacrolimus dose adjustment because of toxicity or rejection , or withdrawal before initial dose change . Efficacy was assessed by the occurrence of biopsy-proven rejection ( International Society for Heart and Lung Transplantation grade ≥1B ) . Results . In the primary endpoint , no significant difference was observed between the low- and high-dose groups . After 3 months , there was no difference in freedom from initial oral tacrolimus dose change because of rejection , toxicity , or withdrawal ( 89.0 % vs. 87.6 % ; not significant [ NS ] ) . In both groups , dose adjustments were mainly required to achieve and maintain target blood levels ( 80.0 % vs. 82.8 % ; NS ) . Patient survival was 92.7 % and 98.3 % ( NS ) . There was no significant difference between groups regarding freedom from biopsy-proven acute rejection ( 57.1 % vs. 66.3 % ; NS ) . The overall safety profiles indicated a tendency toward better tolerability in the low-dose group . Conclusions . Although low-dose and high-dose tacrolimus had similar efficacy , low-dose tacrolimus was associated with a more favorable safety profile . Therefore we recommend starting tacrolimus therapy after antibody induction at 0.075 mg/kg and adjust dose according to whole-blood trough levels We compared efficacy and safety of tacrolimus (Tac)‐based vs. cyclosporine ( CyA ) microemulsion‐based immunosuppression in combination with azathioprine ( Aza ) and corticosteroids in heart transplant recipients . During antibody induction , patients were r and omized ( 1:1 ) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies , which underwent local and blinded central evaluation . The full analysis set comprised 157 patients per group . Patient/graft survival was 92.9 % for Tac and 89.8 % for CyA at 18 months . The primary end point , incidence of first biopsy proven acute rejection ( BPAR ) of grade ≥ 1B at month 6 , was 54.0 % for Tac vs. 66.4 % for CyA ( p = 0.029 ) according to central assessment . Also , incidence of first BPAR of grade ≥ 3A at month 6 was significantly lower for Tac vs. CyA ; 28.0 % vs. 42.0 % , respectively ( p = 0.013 ) . Significant differences ( p < 0.05 ) emerged between groups for these clinical ly relevant adverse events : new‐onset diabetes mellitus ( 20.3 % vs. 10.5 % ) ; post‐transplant arterial hypertension ( 65.6 % vs. 77.7 % ) ; and dyslipidemia ( 28.7 % vs. 40.1 % ) for Tac vs. CyA , respectively . Incidence and pattern of infections over 18 months were comparable between groups , as was renal function . Primary use of Tac during antibody induction result ed in superior prevention of acute rejection without an associated increase in infections BACKGROUND Tacrolimus ( FK506 ) has recently become available clinical ly as an alternative to cyclosporine-based immunosuppression . This study reports the middle-term results of a prospect i ve , r and omized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients . METHODS Twenty-five consecutive patients were r and omized at a 2:1 ratio into two groups , one of which received FK506 ( 15 patients ) , the other cyclosporine ( 10 patients ) . Both groups received similar concomitant immunosuppression . The patients were followed up for 12 months . The following outcome parameters were analyzed : survival , rejection and infection rate , lymphocyte subsets , new-onset diabetes , renal and hepatic function , hypertension , right-sided heart catheterization data , graft coronary artery disease , and neurologic side effects . RESULTS The mortality rate ( two patients ) in the FK506 group was 13 % versus 0 % in the cyclosporine group ( p = NS ) . The two deaths were the consequences of early infections and higher doses of FK506 . From the outset , the FK506 group presented a lower prevalence of acute rejection , a lower requirement for rejection treatments and a higher incidence of infections . Accordingly , we reduced overall immunosuppression for the last seven patients in the FK506 group ; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate . There was no difference between the two groups in diabetes incidence , renal and hepatic function , right-sided heart catheterization data , or coronary angiograms . Hypertension was less frequent and milder in the FK506 group . CONCLUSIONS This experience suggests that FK506 can be safely used in heart transplantation . It can decrease the frequency of rejection episodes . Low-dose administration allows a lower infection rate without an increase in rejection . With a protocol of delayed starting and low dosing , side effects such as renal toxicity , hypertension , and neurologic toxicity seem to be unlikely . Further studies are needed to establish the exact dosage and therapeutic levels of the drug BACKGROUND While Tacrolimus ( Tac ) and Cyclosporine ( Cya ) immunosuppression are used after cardiac transplantation ( tx ) , few studies have evaluated their use in pediatric patients . METHODS We r and omized 26 heart transplant recipients ( pts ) in a prospect i ve , open-label trial to Tac ( n = 14 ) or Cya ( n = 12 ) to compare their efficacy and side-effects . Mean age at tx was 4.2 years for Tac and 5.8 years for Cya . Mean follow-up was 26 months ( range : 11 - 39 months ) for Tac and 24 months for Cya ( range : 33 - 13 months ) . RESULTS Our data suggest that both regimens are efficacious in the pediatric population . Conversion from Cya to Tac was useful for dealing with persistent rejection , although this sample did not suggest lower incidence of acute cellular rejection in the Tac group . CONCLUSIONS Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes Background . The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil ( MMF ) is more efficacious in combination with tacrolimus ( TAC ) or cyclosporine ( CsA ) and to evaluate the impact of either drug on MMF dosage . Methods . Sixty patients ( TAC , n=30 ; CsA , n=30 ) undergoing heart transplantation were r and omized into a prospect i ve , open-label , controlled trial . Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids . Target blood trough levels of TAC , CsA , and mycophenolic acid ( MPA ) were in the range of 10 to 15 ng/mL , 100 to 300 ng/mL , and 1.5 to 4.0 & mgr;g/mL , respectively . Acute rejection episodes ( ARE ) ; survival data ; and adverse events with a special emphasis on infections , diabetes , hypertension , hypercholesterolemia , and the development of graft vessel disease ( GVD ) were recorded . Results . Baseline characteristics were well balanced . All patients were successfully withdrawn from corticosteroids within 6 months of transplant . Freedom from acute rejection was significantly higher ( P=0.0001 ) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group ( 0.03 vs. 0.15 ; P=0.00007 ) . Overall patient survival during follow-up was similar ( 93 % vs. 90 % ) . To achieve the targeted MPA blood levels , a significantly lower dose of MMF was required for TAC versus CsA patients . After a follow-up time of 2 years , the mean GVD score was 1.85±3.18 in the TAC-MMF group and 3.95±4.8 in the CsA-MMF group ( P=0.08 ) . Conclusions . At the selected doses and target levels for TAC and CsA used in this study , trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE . Furthermore , CsA patients need significantly more MMF to achieve similar MPA levels FK 506 was given for immunosuppression in 14 liver recipients . The drug was used in the first 10 cases because the recipients under conventional immunosuppression had rejection , nephrotoxicity , or both . This salvage therapy was successful in 7 of the 10 attempts . 2 of the 10 patients in the original salvage group as well as 4 new patients underwent fresh orthotopic liver transplantation under FK 506 plus low-dose steroids from the outset . None of these 6 patients had rejection although 1 with preexisting cor pulmonale and coronary atherosclerosis died of a myocardial infa rct ion . In addition , 2 of the 14 liver recipients were given cadaveric kidneys , either from the same donor or from a different donor , and a third was given a pancreas as well as a kidney from the liver donor . There were no rejections of the kidney and pancreas grafts , and serious side-effects were not encountered |
12,624 | 28,447,363 | Studies of other behavioural outcomes found evidence of increased avoidance behaviours when using st and ardised packs , reduced dem and for st and ardised packs and reduced craving .
Corroborative evidence for the latter finding came from studies assessing non-behavioural outcomes , which in general found greater warning salience when viewing st and ardised , than br and ed packs .
There was mixed evidence for quitting cognitions , whereas findings with youth generally pointed towards st and ardised packs being less likely to motivate smoking initiation than br and ed packs .
We found the most consistent evidence for appeal , with st and ardised packs rating lower than br and ed packs .
Tobacco in st and ardised packs was also generally perceived as worse-tasting and lower quality than tobacco in br and ed packs .
St and ardised packaging also appeared to reduce misperceptions that some cigarettes are less harmful than others , but only when dark colours were used for the uniform colour of the pack .
The available evidence suggests that st and ardised packaging may reduce smoking prevalence .
A reduction in smoking behaviour is supported by routinely collected data by the Australian government .
Data on the effects of st and ardised packaging on non-behavioural outcomes ( e.g. appeal ) are clearer and provide plausible mechanisms of effect consistent with the observed decline in prevalence .
We did not find any evidence suggesting st and ardised packaging may increase tobacco use | BACKGROUND Tobacco use is the largest single preventable cause of death and disease worldwide .
St and ardised tobacco packaging is an intervention intended to reduce the promotional appeal of packs and can be defined as packaging with a uniform colour ( and in some cases shape and size ) with no logos or br and ing , apart from health warnings and other government-m and ated information , and the br and name in a prescribed uniform font , colour and size .
Australia was the first country to implement st and ardised tobacco packaging between October and December 2012 , France implemented st and ardised tobacco packaging on 1 January 2017 and several other countries are implementing , or intending to implement , st and ardised tobacco packaging .
OBJECTIVES To assess the effect of st and ardised tobacco packaging on tobacco use uptake , cessation and reduction . | PURPOSE To examine the extent to which increasingly plainer packaging might increase recall of health warnings . DESIGN A 4 ( pack ID levels ) x 2 ( smoking status : smokers and non-smokers ) between-subjects design in which participants were r and omly assigned to view one package . SAMPLE Two hundred and twenty students from three universities in Nova Scotia , Canada , participated in the survey . MEASURES Participants were asked to recall the health warning on their package . ANALYSIS A sequential binary logistic regression test to examine whether plain packaging and /or smoking status affects health warning recall . RESULTS The odds of recalling the correct health warnings were significantly higher for the two plainest packages relative to the original package . The odds of recalling the correct health warning were also higher for non-smokers relative to smokers . CONCLUSIONS The results provide compelling evidence that health warnings on plain packages can be more easily recalled Objectives To compare adolescents ’ responses to three different styles of cigarette packaging : novelty ( br and ed packs design ed with a distinctive shape , opening style or bright colour ) , regular ( br and ed pack with no special design features ) and plain ( brown pack with a st and ard shape and opening and all br and ing removed , aside from br and name ) . Design Cross-sectional in-home survey . Setting UK . Participants R and om location quota sample of 1025 never smokers aged 11–16 years . Main outcome measures Susceptibility to smoking and composite measures of pack appraisal and pack receptivity derived from 11 survey items . Results Mean responses to the three pack types were negative for all survey items . However , ‘ novelty ’ packs were rated significantly less negatively than the ‘ regular ’ pack on most items , and the novelty and regular packs were rated less negatively than the ‘ plain ’ pack . For the novelty packs , logistic regressions , controlling for factors known to influence youth smoking , showed that susceptibility was associated with positive appraisal and also receptivity . For example , those receptive to the innovative Silk Cut Superslims pack were more than four times as likely to be susceptible to smoking than those not receptive to this pack ( AOR=4.42 , 95 % CI 2.50 to 7.81 , p<0.001 ) . For the regular pack , an association was found between positive appraisal and susceptibility but not with receptivity and susceptibility . There was no association with pack appraisal or receptivity for the plain pack . Conclusions Pack structure ( shape and opening style ) and colour are independently associated , not just with appreciation of and receptivity to the pack , but also with susceptibility to smoke . In other words , those who think most highly of novelty cigarette packaging are also the ones who indicate that they are most likely to go on to smoke . Plain packaging , in contrast , was found to directly reduce the appeal of smoking to adolescents Background This study sought to examine the impact of cigarette packaging on young women , including the impact of ‘ plain ’ packaging . Methods Participants were r and omised to view eight cigarette packs design ed according to one of four experimental conditions : fully-br and ed female br and s ; the same br and s without descriptors ( eg , ‘ slims ’ ) ; the same br and s without br and imagery or descriptors ( ie , ‘ plain ’ packs ) ; and fully br and ed non-female br and s as a control condition . Participants rated packs on perceived appeal , taste , tar , health risks and smoker ‘ traits ’ . Results Fully-br and ed female packs were rated as significantly more appealing than ‘ no descriptor ’ packs , ‘ plain ’ packs and non-female br and ed packs . Female br and ed packs were associated with a greater number of positive attributes including glamour , slimness and attractiveness , compared to br and s without descriptors and ‘ plain ’ packs . Women who viewed plain packs were less likely to believe that smoking helps people control their appetite — an important predictor of smoking among young women — compared to women who viewed br and ed female packs . Conclusions ‘ Plain ’ packaging — removing colours and design elements— and removing descriptors such as ‘ slims ’ from packs may reduce br and appeal and thereby susceptibility to smoking among young women INTRODUCTION Cigarette packaging is among the most prominent forms of tobacco marketing . This study examined the impact of cigarette pack design among young women in the United States . METHOD A national sample of 18- to 19-year-old females in the United States completed an online survey in February 2010 . Participants were r and omized to view eight cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , same packs without descriptors ( e.g. , " slims " ) , same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk and completed a behavioral pack selection task . RESULTS Fully br and ed female packs were rated significantly more appealing than the same packs without descriptors , " plain " packs , and non-female-br and ed packs . Female-br and ed packs were associated with a greater number of positive attributes including glamour , slimness , and attractiveness and were more likely to be perceived as less harmful . Approximately 40 % of smokers and nonsmokers requested a pack at the end of the study ; female-br and ed packs were 3 times more likely to be selected than plain packs . CONCLUSION Plain packaging and removing descriptors such as " slims " from cigarette packs may reduce smoking susceptibility among young women Objective To examine the effect of br and ing , as indicated by br and name , on evaluation of the cigarette smoking experience . Design Between-subjects and within-subjects experimental study . Participants were r and omly allocated to smoke a cigarette from a pack featuring a premium br and name and a cigarette from a pack featuring a value br and name . Within each condition , participants unknowingly smoked two identical cigarettes ( either two premium or two value cigarettes ) . Setting Australia , October 2014 , 2 years after tobacco plain packaging implementation . Participants 81 current cigarette smokers aged 19–39 years . From apparently premium and value br and -name packs , 40 smokers were allocated to smoke the same actual premium cigarettes and 41 were allocated to smoke the same actual value cigarettes . Primary outcome measures Experienced taste ( flavour , satisfaction , enjoyment , quality , liking , mouthfeel and aftertaste ) , harshness , dryness , staleness , harm/strength measures ( strength , tar , lightness , volume of smoke ) , draw effort and purchase intent . Results Cigarettes given a premium br and name were rated as having a better taste , were less harsh and less dry than identical cigarettes given a value br and name . This pattern was observed irrespective of whether the two packs actually contained premium or value cigarettes . These effects were specific : the br and name did not influence ratings of cigarette variant attributes ( strength , tar , volume of smoke , lightness and draw effort ) . Conclusions Despite the belief that br and names represent genuine differences between cigarette products , the results suggest that at least some of this perceived sensory difference is attributable to br and image Objective To investigate whether st and ardised cigarette packaging increases the time spent looking at health warnings , regardless of the format of those warnings . Study design A factorial ( two pack styles x three warning types ) within-subject experiment , with participants r and omised to different orders of conditions , completed at a university in London , UK . Methods Mock-ups of cigarette packets were presented to participants with their br and ed portion in either st and ardised ( plain ) or manufacturer- design ed ( br and ed ) format . Health warnings were present on all packets , representing all three types currently in use in the UK : black & white text , colour text , or colour images with accompanying text . Gaze position was recorded using a specialised eye tracker , providing the main outcome measure , which was the mean proportion of a five-second viewing period spent gazing at the warning-label region of the packet . Results An opportunity sample of 30 ( six male , mean age = 23 ) young adults met the following inclusion criteria : 1 ) not currently a smoker ; 2 ) < 100 lifetime cigarettes smoked ; 3 ) gaze position successfully tracked for > 50 % viewing time . These participants spent a greater proportion of the available time gazing at the warning-label region when the br and ed section of the pack was st and ardised ( following current Australian guidelines ) rather than containing the manufacturer 's preferred design ( mean difference in proportions = 0.078 , 95 % confidence interval 0.049 to 0.106 , p < 0.001 ) . There was no evidence that this effect varied based on the type of warning label ( black & white text vs. colour text vs. colour image & text ; interaction p = 0.295 ) . Conclusions During incidental viewing of cigarette packets , young adult never-smokers are likely to spend more time looking at health warnings if manufacturers are compelled to use st and ardised packaging , regardless of the warning design Objectives To investigate the impact of Australia 's plain tobacco packaging policy on two stated purpose s of the legislation — increasing the impact of health warnings and decreasing the promotional appeal of packaging — among adult smokers . Design Serial cross-sectional study with weekly telephone surveys ( April 2006–May 2013 ) . Interrupted time-series analyses using ARIMA modelling and linear regression models were used to investigate intervention effects . Participants 15 745 adult smokers ( aged 18 years and above ) in New South Wales ( NSW ) , Australia . R and om selection of participants involved recruiting households using r and om digit dialling and selecting the nth oldest smoker for interview . Intervention The introduction of the legislation on 1 October 2012 . Outcomes Salience of tobacco pack health warnings , cognitive and emotional responses to warnings , avoidance of warnings , perceptions regarding one 's cigarette pack . Results Adjusting for background trends , seasonality , antismoking advertising activity and cigarette costliness , results from ARIMA modelling showed that , 2–3 months after the introduction of the new packs , there was a significant increase in the absolute proportion of smokers having strong cognitive ( 9.8 % increase , p=0.005 ) , emotional ( 8.6 % increase , p=0.01 ) and avoidant ( 9.8 % increase , p=0.0005 ) responses to on-pack health warnings . Similarly , there was a significant increase in the proportion of smokers strongly disagreeing that the look of their cigarette pack is attractive ( 57.5 % increase , p<0.0001 ) , says something good about them ( 54.5 % increase , p<0.0001 ) , influences the br and they buy ( 40.6 % increase , p<0.0001 ) , makes their pack st and out ( 55.6 % increase , p<0.0001 ) , is fashionable ( 44.7 % increase , p<0.0001 ) and matches their style ( 48.1 % increase , p<0.0001 ) . Changes in these outcomes were maintained 6 months postintervention . Conclusions The introductory effects of the plain packaging legislation among adult smokers are consistent with the specific objectives of the legislation in regard to reducing promotional appeal and increasing effectiveness of health warnings Objectives This study aim ed to test the potential impact of plain packaging for cigarettes on br and appeal among highly socioeconomically disadvantaged smokers using the new design for cigarettes implemented in Australia , which combines plain packaging with larger health warning labels . Design A 2 × 2 factorial design trial embedded within a cross-sectional computer touchscreen survey . Data were collected between March and December 2012 . Setting Socially disadvantaged welfare aid recipients were recruited through a large Social and Community Service Organisation in New South Wales , Australia . Participants N=354 smokers . The majority of the sample had not completed high school ( 64 % ) , earned less than $ A300/week ( 55 % ) and received their income from Government payments ( 95 % ) . Interventions Participants were r and omised to one of the four different pack conditions determined by br and name : Winfield versus Benson & Hedges , and packaging type : br and ed versus plain . Participants were required to rate their assigned pack on measures of br and appeal and purchase intentions . Results Plain packaging was associated with significantly reduced smoker ratings of ‘ positive pack characteristics ’ ( p<0.001 ) , ‘ positive smoker characteristics ’ ( p=0.003 ) and ‘ positive taste characteristics ’ ( p=0.033 ) in the Winfield br and name condition only . Across the four pack conditions , no main differences were found for ‘ negative smoker characteristics ’ ( p=0.427 ) or ‘ negative harm characteristics ’ ( p=0.411 ) . In comparison to plain packaging , the presentation of br and ed packaging was associated with higher odds of smokers ’ purchase intentions ( OR=2.18 , 95 % CI 1.34 to 3.54 ; p=0.002 ) . Conclusions Plain packs stripped of br and ing elements , featuring larger health warning labels , were associated with reduced positive cigarette br and image and purchase intentions among highly socioeconomically disadvantaged smokers Background : Cigarette packaging is a key marketing strategy for promoting br and image . Plain packaging has been proposed to limit br and image , but tobacco companies would resist removal of br and ing design elements . Method : A 3 ( br and types ) × 4 ( degree of plain packaging ) between-subject experimental design was used , using an internet online method , to expose 813 adult Australian smokers to one r and omly selected cigarette pack , after which respondents completed ratings of the pack . Results : Compared with current cigarette packs with full br and ing , cigarette packs that displayed progressively fewer br and ing design elements were perceived increasingly unfavourably in terms of smokers ’ appraisal s of the packs , the smokers who might smoke such packs , and the inferred experience of smoking a cigarette from these packs . For example , cardboard brown packs with the number of enclosed cigarettes displayed on the front of the pack and featuring only the br and name in small st and ard font at the bottom of the pack face were rated as significantly less attractive and popular than original br and ed packs . Smokers of these plain packs were rated as significantly less trendy/stylish , less sociable/outgoing and less mature than smokers of the original pack . Compared with original packs , smokers inferred that cigarettes from these plain packs would be less rich in tobacco , less satisfying and of lower quality tobacco . Conclusion : Plain packaging policies that remove most br and design elements are likely to be most successful in removing cigarette br and image associations Background Tobacco use is responsible for 5.4 million deaths every year worldwide and is a leading cause of preventable death . The burden of these deaths is rapidly shifting to low and middle-income countries , such as Brazil . Brazil has prohibited most forms of tobacco advertising ; however , the cigarette pack remains a primary source of marketing . The current study examined how tobacco packaging influences br and appeal and perceptions of health risk among young women in Brazil . Methods A between-subjects experiment was conducted in which 640 Brazilian women aged 16–26 participated in an online survey . Participants were r and omized to view 10 cigarette packages according to one of three experimental conditions : st and ard br and ed packages , the same packs without br and imagery ( “ plain packaging ” ) , or the same packs without br and imagery or descriptors ( e.g. , flavors ) . Participants rated packages on perceived appeal , taste , health risk , smoothness , and smoker attributes . Finally , participants were shown a range of br and ed and plain packs from which they could select one as a free gift , which constituted a behavioral measure of appeal . Results Br and ed packs were rated as significantly more appealing , better tasting , and smoother on the throat than plain packs . Br and ed packs were also associated with a greater number of positive smoker attributes including style and sophistication , and were perceived as more likely to be smoked by females than the plain packs . Removing descriptors from the plain packs further decreased the ratings of appeal , taste and smoothness , and also reduced associations with positive attributes . In the pack offer , participants were three times more likely to select br and ed packs than plain packs . Conclusions Plain packaging and removal of descriptors may reduce the appeal of smoking for youth and young adults , and consequently reduce smoking susceptibility . Overall , the findings provide support for plain packaging regulations , such as those in Australia PURPOSE Cigarette packaging is the most prominent form of tobacco marketing remaining in countries such as the United Kingdom . The current study examined perceptions of cigarette packaging among female youth and the potential impact of " plain " cigarette packaging regulations . METHODS A national sample of 947 16- to 19-year-old female subjects in the United Kingdom completed an online survey . Participants were r and omized to view 10 cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , the same packs without descriptor words , the same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk , positive smoker image , and completed a behavioral pack selection task . RESULTS Plain packs were rated as the least appealing and worse tasting compared with all other conditions . Plain packs were also associated with fewer false beliefs about health risks compared with br and ed packs . Removing br and descriptors from packs significantly reduced measures of appeal and taste , particularly for br and s with flavor descriptors , such as cherry and vanilla . Plain packs were significantly less likely to be associated with positive images , such as glamour , sophistication , and slimness . Most importantly , respondents were significantly less likely to accept a pack of cigarettes when offered only plain versus br and ed packs ( p = .026 ) . CONCLUSIONS Marketing in the form of pack br and ing remains a potent tool for increasing the appeal of tobacco products to young women . The findings provide empirical support for plain cigarette packaging regulations in Australia to be implemented in 2012 Background Plain packaging requires tobacco products to be sold in packs with a st and ard shape , method of opening and colour , leaving the br and name in a st and ard font and location . We ran a r and omised controlled trial to investigate the impact of plain packaging on smoking behaviour and attitudes . Methods In a parallel group r and omised trial design , 128 daily smokers smoked cigarettes from their usual UK br and , or a plain Australian br and that was closely matched to their usual UK br and for 24 hours . Primary outcomes were number of cigarettes smoked and volume of smoke inhaled per cigarette . Secondary outcomes were self-reported ratings of motivation to quit , cigarette taste , experience of using the pack , experience of smoking , attributes of the pack , perceptions of the health warning , changes in smoking behaviour , and views on plain packaging . Results There was no evidence that pack type had an effect on either of the primary measures ( ps > 0.279 ) . However , smokers using plain cigarette packs rated the experience of using the pack more negatively ( −0.52 , 95 % CI −0.82 to −0.22 , p = 0.001 ) , rated the pack attributes more negatively ( −1.59 , 95 % CI −1.80 to −1.39 , p < 0.001 ) , and rated the health warning as more impactful ( + 0.51 , 95 % CI 0.24 to 0.78 , p < 0.001 ) . Conclusions Plain cigarette packs reduce ratings of the experience of using the cigarette pack , and ratings of the pack attributes , and increase the self-perceived impact of the health warning , but do not change smoking behaviour , at least in the short term . Trial registration Current Controlled Trials IS RCT N52982308 . Registered 27 June 2013 Objectives To measure young people 's perceptions of tobacco packaging according to two current pieces of legislation : The EU Tobacco Products Directive ( TPD ) and Irel and 's Public Health ( St and ardisation of Tobacco Products ) Act . Design Within-subject experimental cross-sectional survey of a representative sample of secondary school students . School-based pen and paper survey . Setting 27 secondary schools across Irel and , r and omly stratified for size , geographic location , gender , religious affiliation and school-level socioeconomic status . Data were collected between March and May 2014 . Participants 1378 fifth year secondary school students aged 16–17 in Irel and . Main outcome measures Young people 's perceptions of attractiveness , health risk and smoker characteristics of packs according to EU and Irish br and ing and packaging guidelines . Results Packs with more br and ing elements were thought to be healthier than st and ardised packs for Silk Cut ( χ2=158.58 , p<0.001 ) , Marlboro ( χ2=113.65 , p<0.001 ) , and Benson and Hedges ( χ2=137.95 , p<0.001 ) br and s. Generalized estimating equation binary regressions found that gender was a significant predictor of pack attractiveness for Silk Cut , with females being more likely to find the EU packs attractive ( β=−0.45 , p=0.007 ) . Gender was a significant predictor for females with regards to the perceived popularity of the Silk Cut br and ( β=−0.37 , p=0.03 ) . Conclusions The removal of br and identifiers , including colour , font and embossing , reduces the perceived appeal of cigarette packs for young people across all three tested br and s. Packs st and ardised according to Irish legislation are perceived as less attractive , less healthy and smoked by less popular people than packs which conform to the EU TPD 2014 guidelines OBJECTIVE To estimate differences in dem and for cigarette packages with different packaging and health warning label formats . METHODS Adult smokers ( n=404 ) in four states participated in experimental auctions . Participants bid on two of four experimental conditions , each involving a different health warning label format but with the same warning message : ( 1 ) text on 50 % of pack side ; ( 2 ) text on 50 % of the pack front and back ; ( 3 ) text with a graphic picture on 50 % of the pack front and back ; and ( 4 ) same as previous format , but without br and imagery . RESULTS Mean bids decreased across conditions ( 1 : $ 3.52 ; 2 : $ 3.43 ; 3 : $ 3.11 ; 4 : $ 2.93 ) . Bivariate and multivariate r and om effects models indicated that there was no statistically significant difference in dem and for packs with either of the two text only warnings ; however , dem and was significantly lower for both packs with prominent pictorial warnings , with the lowest dem and associated with the plain , unbr and ed pack . CONCLUSIONS Results suggest that prominent health warnings with graphic pictures will reduce dem and for cigarettes . Regulators should not only consider this type of warning label , but also plain packaging policies for tobacco products Background Previous research on the effects of plain packaging has largely relied on self-report measures . Here we describe the protocol of a r and omized controlled trial investigating the effect of the plain packaging of cigarettes on smoking behavior in a real-world setting . Methods / Design In a parallel group r and omization design , 128 daily cigarette smokers ( 50 % male , 50 % female ) will attend an initial screening session and be assigned plain or br and ed packs of cigarettes to smoke for a full day . Plain packs will be those currently used in Australia where plain packaging has been introduced , while br and ed packs will be those currently used in the United Kingdom . Our primary study outcomes will be smoking behavior ( self-reported number of cigarettes smoked and volume of smoke inhaled per cigarette as measured using a smoking topography device ) . Secondary outcomes measured pre- and post-intervention will be smoking urges , motivation to quit smoking , and perceived taste of the cigarettes . Secondary outcomes measured post-intervention only will be experience of smoking from the cigarette pack , overall experience of smoking , attributes of the cigarette pack , perceptions of the on-packet health warnings , behavior changes , views on plain packaging , and the rewarding value of smoking . Sex differences will be explored for all analyses . Discussion This study is novel in its approach to assessing the impact of plain packaging on actual smoking behavior . This research will help inform policymakers about the effectiveness of plain packaging as a tobacco control measure . Trial registration Current Controlled Trials IS RCT N52982308 ( registered 27 June 2013 ) Background Implementation of tobacco plain packaging ( PP ) with larger graphic health warnings ( GHWs ) in Australia had positive effects on responses reflecting the specific objectives of the PP policy and on follow-up quitting-related cognitions and behaviours . The aim of this study was to examine predictive relationships between these proximal and distal outcomes . Methods A nationally representative sample of Australian adult cigarette smokers completed a baseline survey and a 1-month follow-up survey within the first year of policy implementation ( n(weighted)=3125 ) . Logistic regression analyses tested whether baseline measures of cigarette appeal , GHW effectiveness , perceived harm and concern/enjoyment predicted each of seven follow-up measures of quitting-related cognitions and behaviours , adjusting for baseline levels of the outcome and covariates . Results In multivariable models , we found consistent evidence that several baseline measures of GHW effectiveness positively and significantly predicted the likelihood that smokers at follow-up reported thinking about quitting at least daily , intending to quit , having a firm date to quit , stubbing out cigarettes prematurely , stopping oneself from smoking and having attempted to quit . Two of the quitting-related outcomes were also predicted by feeling more smoking-related concern than enjoyment . A smaller number of the appeal variables were prospect ively associated with quitting-related outcomes , while believing that br and s do not differ in harmfulness did not positively predict any outcomes . Conclusions These findings provide an initial insight into the pathways through which PP with larger GHWs may lead to changes in smoking behaviour . Future research should examine whether the effects are conditional on individual demographic and smoking characteristics Objective This study examined the impact of pictorial cigarette-warning labels , warning-label message framing and plain cigarette packaging , on young adult smokers ’ motivation to quit . Methods Smokers aged 18–30 years ( n=740 ) from a consumer research panel were r and omised to one of four experimental conditions where they viewed online images of four cigarette packs with warnings about lung disease , cancer , stroke/heart disease and death , respectively . Packs differed across conditions by warning-message framing ( gain vs loss ) and packaging ( br and ed vs plain ) . Measures captured demographics , smoking behaviour , covariates and motivation to quit in response to cigarette packs . Results Pictorial warnings about lung disease and cancer generated the strongest motivation to quit across conditions . Adjusting for pretest motivation and covariates , a message framing by packaging interaction revealed gain-framed warnings on plain packs generated greater motivation to quit for lung disease , cancer and mortality warnings ( p<0.05 ) , compared with loss-framed warnings on plain packs . Conclusions Warnings combining pictorial depictions of smoking-related health risks with text-based messages about how quitting reduces risks , may achieve better outcomes among young adults , especially in countries considering or implementing plain packaging regulations INTRODUCTION We examined the potential impact of banning tobacco displays and m and ating plain packaging and cigarette advertisements at the point of sale ( POS ) on adult outcomes . METHODS A virtual convenience store was created with scenarios in which the tobacco product display was either fully visible ( status quo ) or enclosed behind a cabinet ( display ban ) , and cigarette packs and advertisements were either in full color ( status quo ) or black and white , text only ( plain ) . A national convenience sample of 1313 adult current smokers and recent quitters was r and omized to 1 of 4 conditions and given a shopping task to complete in the virtual store . Main outcomes were participants ' self-reported urge to smoke and tobacco purchase attempts in the virtual store . RESULTS Compared with recent quitters in the status quo conditions , recent quitters in the display ban condition had lower urges to smoke ( β=-4.82 , 95 % CI=-8.16 - -1.49 , p<0.01 ) . Compared with current smokers in the status quo conditions , smokers in the display ban conditions were less likely to attempt to purchase cigarettes in the virtual store ( OR=0.05 , 95 % CI=0.03 - 0.08 , P<0.01 ) . Smokers exposed to plain packs and ads were significantly less likely to attempt to purchase cigarettes ( OR=0.31 , 95 % CI=0.20 - 0.47 , P<0.01 ) than those exposed to color packs and ads . CONCLUSIONS Policies that ban the display of tobacco products or require plain packaging and advertising at the POS may help reduce adult smoking Plain cigarette packaging , which seeks to remove all br and imagery and st and ardize the shape and size of cigarette packs , represents a novel policy measure to reduce the appeal of cigarettes . Plain packaging has been studied primarily in high-income countries like Australia and the UK . It is unknown whether the effects of plain packaging may differ in low- and -middle income countries with a shorter history of tobacco regulation , such as Mexico . An experimental study was conducted in Mexico City to examine perceptions of br and ed and plain cigarette packaging among smoking and non-smoking Mexican adolescents ( n = 359 ) . Respondents were r and omly assigned to a br and ed or plain pack condition and rated 12 cigarette packages for appeal , taste , harm to health and smoker-image traits . As a behavioral measure of appeal , respondents were offered ( although not given ) four cigarette packs ( either br and ed or plain ) and asked to select one to keep . The findings indicated that br and ed packs were perceived to be more appealing ( β = 3.40 , p < 0.001 ) and to contain better tasting cigarettes ( β = 3.53 , p < 0.001 ) , but were not perceived as less harmful than plain packs . Participants rated people who smoke the br and ed packs as having relatively more positive smoker-image traits overall ( β = 2.10 , p < 0.001 ) , with particularly strong differences found among non-smokers for the traits ' glamorous ' , ' stylish ' , ' popular ' and ' sophisticated ' ( p < 0.001 ) . No statistically significant difference was found for the proportion of youth that accepted when offered br and ed compared with plain packs . These results suggest that plain packaging may reduce br and appeal among Mexican youth , consistent with findings in high-income countries Background Research demonstrates that tobacco packaging elements ( including health warning labels , descriptive characteristics , and corporate br and ing ) are associated with knowledge of health risks and product appeal with cigarettes . Yet , little research has assessed this with smokeless tobacco ( SLT ) packaging . This study evaluates the association between three SLT packaging elements with knowledge of health risks and perceptions of novelty and appeal . Additionally , we assess how effects of these messages may differ across age groups , including youth ( 14 - 17 years ) , young adults ( 18 - 25 years ) , and older adults ( 26 - 65 years ) . Methods 1000 participants were administered a web-based survey in 2010 and shown three sets of SLT packs in r and om order , varied by descriptor ( flavor descriptor vs. none ) , warning label format ( graphic vs. text ) , and corporate br and ing ( br and ed vs. plain packaging ) . Participants rated the packs compared with “ no difference ” on appeal , novelty , and risk perceptions associated with product use . Chi-square tests were used to test for significant differences in pack selection s. Multinomial regression was employed to evaluate the association between effects of packaging elements and participant age . Results More respondents selected the pack with the graphic warning label as the pack to make them consider the health risks associated with SLT use , attract their attention , and be least attractive to a smoker . The product with the text warning label was the product someone their age would want to be seen using and would appeal to peers . The SLT pack with the flavor descriptor was not associated with health risks associated with product use . The pack with corporate br and ing was selected as more appealing , to attract attention , and one they would want to be seen using ; the plain pack was less attractive to smokers . Youth and young adults were more likely to indicate that pack elements affected their perceptions of appeal and risk associated with SLT products . Conclusion These results suggest that SLT pack characteristics have a measurable effect on perceptions of health risk and product appeal . Future research should assess these findings in the context of harm reduction . Specifically , research is needed to determine whether pack elements on SLT products can effectively convey risk and harm Objective : To assess whether st and ardised packs of the form introduced in Australia are associated with a reduction in acute craving and /or an increase in motivation to stop , and to replicate previous findings on perceptions of packaging , perceptions of smokers using it and perceived effects on behaviour . Design : Following abstinence of at least 12 h , 98 regular and occasional smokers were r and omised to exposure to their own cigarette package , another br and ed package or a st and ardised package . Main Outcome Measures : Craving ( QSU-brief ) , motivation to stop , both at baseline and post-exposure . Ratings of 10 attributes concerning package design , perceived smoker characteristics and effects on behaviour , post-exposure only . Results : For craving , a mixed model ANCOVA showed a significant interaction of packaging and time of measurement ( F(2,94 ) = 8.77 , p < .001 , partial η2 = .16 ) . There was no significant main effect or interaction for motivation to stop smoking ( p = .9 ) . The st and ardised pack was perceived to be significantly less appealing and less motivating to buy cigarettes , smokers using them were perceived as less popular and cigarettes from them expected to taste worse . Conclusion : St and ardised cigarette packaging may reduce acute ( hedonic ) craving and is associated with more negative perceptions than br and ed packaging with less prominent health warnings BACKGROUND In the U.S. , limited evidence exists on the impact of colors and br and imagery used in cigarette pack design . PURPOSE This study examined the impact of pack design , product descriptors , and health warnings on risk perception and br and appeal . METHODS A cross-sectional mall-intercept study was conducted with 197 adult smokers and 200 nonsmokers in Buffalo NY from June to July 2009 ( data analysis from July 2009 to December 2010 ) . Participants were shown 12 sets of packs r and omly ; each set varied by a particular design feature ( color , descriptor ) or warning label style ( text versus graphic , size , attribution , message framing ) . Packs were rated on criteria including risk perceptions , quit motivation , and purchase interest . RESULTS Participants selected larger , pictorial , and loss-framed warning labels as more likely to attract attention , encourage thoughts about health risks , motivate quitting , and be most effective . Participants were more likely to select packs with lighter color shading and descriptors such as light , silver , and smooth as delivering less tar , smoother taste , and lower health risk , compared to darker-shaded or full-flavor packs . Additionally , participants were more likely to select the br and ed compared to plain white pack when asked which delivered the most tar , smoothest taste , was more attractive , appealed to youth aged < 18 years , and contained cigarettes of better quality . CONCLUSIONS The findings support larger , graphic health warnings that convey loss-framed messages as most effective in communicating health risks to U.S. adults . The results also indicate that color and product descriptors are associated with false beliefs about risks . Plain packaging may reduce many of the erroneous misperceptions of risk communicated through pack design features PURPOSE To examine the effect of plain packaging on adolescents ' perceptions of cigarette packs , attributes of smokers , and expectations of cigarette taste , and to identify the effect of increasing the size of pictorial health warnings on appraisal of plain packs . METHODS We used a 5 ( degree of plain packaging and graphic health warning)x 3 ( br and type ) between-subjects experimental design , using a Web-based methodology to expose adolescents to one r and omly selected cigarette pack , during which respondents completed ratings . RESULTS When br and elements such as color , br and ed fonts , and imagery were progressively removed from cigarette packs , adolescents perceived packs to be less appealing , rated attributes of a typical smoker of the pack less positively , and had more negative expectations of cigarette taste . Pack appeal was reduced even further when the size of the pictorial health warning on the most plain pack was increased from 30 % to 80 % of the pack face , with this effect apparent among susceptible nonsmokers , experimenters , and established smokers . CONCLUSIONS Removing as much br and information from cigarette packs as possible is likely to reduce positive cigarette br and image associations among adolescents . By additionally increasing the size of pictorial health warnings , positive pack perceptions of those who are at greater risk of becoming regular addicted adult smokers are most likely to be reduced |
12,625 | 26,931,557 | Conclusion There is no best practice method for the categorisation of asthma severity with cl aims data .
Rather , a combination of algorithms seems to be a pragmatic approach . | Abstract Introduction Asthma is one of the most common chronic diseases in Germany .
Substantial economic evaluation of asthma cost requires knowledge of asthma severity , which is in general not part of cl aims data .
Algorithms need to be defined to use this data source .
Aims and objectives The aim of this study was to systematic ally review the international literature to identify algorithms for the stratification of asthma patients according to disease severity based on available information in cl aims data . | Background : The use of administrative data bases to perform epidemiological studies in asthma has increased in recent years . The absence of clinical parameters to measure the level of asthma severity and control is a major limitation of data base studies . A study was undertaken to develop and vali date two data base indexes to measure the control and severity of asthma . Methods : Data base indexes of asthma severity and control were derived from definitions in the Canadian Asthma Consensus Guidelines based on dispensed prescriptions and on medical services recorded in two large administrative data bases from the Canadian province of Québec ( Régie de l’Assurance Maladie du Québec ( RAMQ ) and MED-ECHO ) over 12 months . The data base indexes of asthma severity and control were vali date d against the pulmonary function test results of 71 patients with asthma r and omly selected from two asthma clinics , and they were also applied to a cohort of patients with asthma followed up for 139 283 person-years selected from the RAMQ and MED-ECHO data bases between 1 January 1997 and 31 December 2004 . Results : According to the data base indexes , 49.3 % , 29.6 % and 21.1 % of patients recruited at the asthma clinics were found to have mild , moderate and severe asthma , respectively , while 53.5 % were found to have controlled asthma . The mean predicted value of the forced expiratory volume in 1 s ( FEV1 ) ranged from 89.8 % for mild asthma to 61.5 % for severe asthma ( p<0.001 ) , whereas the range from controlled to uncontrolled asthma was 89.5 % to 67.3 % ( p<0.001 ) . The ratio of the FEV1 to the forced vital capacity ( FEV1/FVC ratio ) measured in 56 patients ranged from 75.8 % for mild asthma to 61.8 % for severe asthma ( p = 0.030 ) , whereas the range from controlled to uncontrolled asthma was 75.3 % to 65.7 % ( p<0.001 ) . Conclusion : In the absence of clinical data , these data base indexes could be used in epidemiological studies to assess the severity and control of asthma BACKGROUND Isl and and mainl and Puerto Rican children have the highest rates of asthma and asthma morbidity of any ethnic group in the United States . OBJECTIVE We evaluated the effectiveness of a culturally adapted family asthma management intervention called CALMA ( an acronym of the Spanish for " Take Control , Empower Yourself and Achieve Management of Asthma " ) in reducing asthma morbidity in poor Puerto Rican children with asthma . METHODS Low-income children with persistent asthma were selected from a national health plan insurance cl aims data base by using a computerized algorithm . After baseline , families were r and omly assigned to either the intervention or a control group . RESULTS No significant differences between control and intervention group were found for the primary outcome of symptom-free days . However , children in the CALMA intervention group had 6.5 % more symptom-free nights , were 3 times more likely to have their asthma under control , and were less likely to visit the emergency department and be hospitalized as compared to the control group . Caregivers receiving CALMA were significantly less likely to feel helpless , frustrated , or upset because of their child 's asthma and more likely to feel confident to manage their child 's asthma . CONCLUSION A home-based asthma intervention program tailored to the cultural needs of low income Puerto Rican families is a promising intervention for reducing asthma morbidity Our objective was to vali date the Council of State and Territorial Epidemiologists ( CSTE ) definition of " probable " asthma and the Health Plan Employer Data and Information Set ( HEDIS ) definition of persistent asthma for diagnosis of pediatric asthma , and examine modifications that improve case recognition . CSTE and HEDIS criteria were applied to a cross-sectional study of 3,905 Medicaid children with physician-confirmed diagnosis of asthma/no asthma using a vali date d survey instrument based upon National Asthma Education and Prevention Program ( NAEPP ) Guidelines . Modified criteria were applied to another group of 1,458 non-Medicaid children from a managed care organization ( MCO ) . Of 1,852 Medicaid children with physician-confirmed asthma , 906 had persistent asthma . CSTE identified 61 % of children with " probable " asthma ; HEDIS identified 44 % of children with persistent asthma . Correct identification increased with greater disease severity . A modified CSTE increased sensitivity from 0.61 to 0.90 , while maintaining high specificity . Three new HEDIS algorithms increased sensitivity from 0.44 to > 0.84 , with specificity > 0.89 . When applied prospect ively to MCO children , these new algorithms demonstrated improved sensitivity . In conclusion , studies using current CSTE or HEDIS algorithms for case recognition underestimate asthma prevalence and overestimate asthma severity in children . Modified algorithms improve the identification of " probable " and persistent asthma OBJECTIVE To assess the practice -level effects of ( 1 ) a physician peer leader intervention and ( 2 ) peer leaders in combination with the introduction of asthma education nurses to facilitate care improvement . And , to compare findings with previously reported patient-level outcomes of trial enrollees . STUDY SETTING Data were included on children 5 - 17 years old with asthma in 40 primary care practice s , affiliated with managed health care plans enrolled in the Pediatric Asthma Care Patient Outcomes Research Team ( PORT ) r and omized trial . STUDY DESIGN Primary care practice s were r and omly assigned to one of two care improvement arms or to usual care . Automated cl aims data were analyzed for 12-month periods using a repeated cross-sectional design . The primary outcome was evidence of at least one controller medication dispensed among patients with persistent asthma . Secondary outcomes included controller dispensing among all identified asthmatics , evidence of chronic controller use , and the dispensing of oral steroids . Health service utilization outcomes included numbers of ambulatory visits and hospital-based events . PRINCIPAL FINDINGS The proportion of children with persistent asthma prescribed controllers increased in all study arms . No effect of the interventions on the proportion receiving controllers was detected ( peer leader intervention effect 0.01 , 95 percent confidence interval [ CI ] : -0.07 , 0.08 ; planned care intervention effect -0.03 , 95 percent CI : -0.09 , 0.02 ) . A statistical trend was seen toward an increased number of oral corticosteroid bursts dispensed in intervention practice s. Significant adjusted increases in ambulatory visits of 0.08 - 0.10 visits per child per year were seen in the first intervention year , but only a statistical trend in these outcomes persisted into the second year of follow-up . No differences in hospital-based events were detected . CONCLUSIONS This analysis showed a slight increase in ambulatory asthma visits as a result of asthma care improvement interventions , using automated data . The absence of detectable impact on medication use at the practice level differs from the positive intervention effect observed in patient self-reported data from trial enrollees . Analysis of automated data on nonenrollees adds information about practice -level impact of care improvement strategies . Benefits of practice -level interventions may accrue disproportionately to the subgroup of trial enrollees . The effect of such interventions may be less apparent at the level of practice s or health plans Objective . Although the Health Plan Employer Data Information Set ( HEDIS ) is a common method for evaluating the quality of asthma care , its accuracy in characterizing persistent asthma in children is unknown . The objective of this study was to compare the assessment of asthma severity ( persistent vs nonpersistent asthma ) using the HEDIS criteria versus clinical criteria using National Heart , Lung , and Blood Institute ( NHLBI ) guidelines . Methods . In a cross-sectional study , we analyzed baseline data from interviews with the parents of 896 children who had asthma and participated in a r and omized controlled trial . Patients had an active clinical diagnosis of asthma , were between 2 and 12 years of age , and had no other pulmonary diseases . Patients had persistent asthma by parent report according to the HEDIS criteria when , within the last year , they had 1 asthma inpatient admission or emergency department visit or 4 asthma medication dispensing events , or 4 outpatient asthma visits and at least 2 asthma medication dispensing events . Patients had persistent asthma by parent report according to the NHLBI criteria when , within the last 2 months , they had nighttime asthma symptoms > 2 nights/mo or daytime asthma symptoms > 2 days/wk . We calculated the sensitivity of each HEDIS criterion , separately and then combined , using the NHLBI criteria as a gold st and ard . Results . On the basis of HEDIS criteria , 656 ( 73 % ) patients had persistent asthma , compared with 338 ( 38 % ) using NHLBI criteria . Although the HEDIS criteria for persistent asthma were fairly sensitive ( 0.89 ) , they were not very specific ( 0.70 ) . For children without daily controller medications ( n = 346 ) , the sensitivity was even lower ( 0.45 ) , but the specificity was similar ( 0.68 ) . We found that the test characteristics were fairly consistent across different age group strata ( 2–4 , 5–9 , and 10–12 years of age ) . Conclusions . HEDIS criteria used to determine the quality of asthma care should be interpreted with caution . Although the criteria for persistent disease — used to determine which children require daily controller medications — are fairly sensitive , they are not very specific and include children who may not require such medications Introduction Asthma is associated with a substantial economic burden on the German Statutory Health Insurance . Aims and objectives To determine costs and re source utilization associated with asthma and to analyze the impact of disease severity on subgroups based on age and gender . Methods A cl aims data base analysis from the statutory health insurance perspective was conducted . Patients with an ICD-10-GM code of asthma were extracted from a 10 % sample of a large German sickness fund . Five controls for each asthma patient matched by age and gender were r and omly selected from the same data base . Costs and re source utilization were calculated for each individual in the asthma and control group . Incremental asthma-related costs were calculated as the mean cost difference . Based on prescribed asthma medication , patients were classified as intermittent or persistent . In addition , age groups of ≤5 , 6–18 , and > 18 years were analyzed separately and gender differences were investigated . Results Overall , 49,668 individuals were included in the asthma group . On average , total annual costs per patient were € 753 higher ( p = 0.000 ) compared to the control group ( € 2,168 vs. € 1,415 ) . Asthma patients had significantly higher ( p = 0.000 ) outpatient ( € 217 ) , inpatient ( € 176 ) , and pharmacy costs ( € 259 ) . Incremental asthma-related total costs were higher for patients with persistent asthma compared to patients with intermittent asthma ( € 1,091 vs. € 408 ) . Women aged > 18 years with persistent asthma had the highest difference in costs compared to their controls ( € 1,207 ; p < 0.0001 ) . Corresponding healthcare re source utilization was significantly higher in the asthma group ( p = 0.000 ) . Conclusions The treatment of asthma is associated with an increased level of healthcare re source utilization and significantly higher healthcare costs . Asthma imposes a substantial economic burden on sickness funds BACKGROUND The risk of invasive pneumococcal disease among persons with asthma is unknown . METHODS We conducted a nested case-control study to examine the association between asthma and invasive pneumococcal disease . The study population included persons 2 to 49 years of age who were enrolled in Tennessee 's Medicaid program ( TennCare ) for more than one year during the study period ( 1995 through 2002 ) and who resided in counties participating in a prospect i ve laboratory-based program of surveillance for invasive pneumococcal disease . For each subject with invasive pneumococcal disease , 10 age-matched controls without invasive pneumococcal disease were r and omly selected from the same population . TennCare files were queried to identify the presence of coexisting conditions that confer a high risk of pneumococcal disease . For the purpose of our study , asthma was defined by documentation of one or more inpatient or emergency-department diagnoses of asthma , two outpatient diagnoses , or the use of asthma-related medications . High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department , the use of rescue therapy or long-term use of oral corticosteroids , or the dispensing of three or more prescriptions for beta-agonists within the year before enrollment in the study . RESULTS A total of 635 persons with invasive pneumococcal disease and 6350 controls were identified , of whom 114 ( 18.0 percent ) and 516 ( 8.1 percent ) , respectively , had asthma . Persons with asthma had an increased risk of invasive pneumococcal disease ( adjusted odds ratio , 2.4 ; 95 percent confidence interval , 1.9 to 3.1 ) as compared with controls . Among those without coexisting conditions , the annual incidence of invasive pneumococcal disease was 4.2 episodes per 10,000 persons with high-risk asthma and 2.3 episodes per 10,000 persons with low-risk asthma , as compared with 1.2 episodes per 10,000 persons without asthma . CONCLUSIONS Asthma is an independent risk factor for invasive pneumococcal disease . The risk among persons with asthma was at least double that among controls BACKGROUND Prior studies suggest that allergist care improves asthma outcomes , but many of these studies have method ological shortcomings . OBJECTIVE We sought to compare patient-based and medical utilization outcomes in r and omly selected asthmatic patients cared for by allergists versus primary care providers . METHODS A r and om sample of 3568 patients enrolled in a staff model health maintenance organization who were given diagnoses of persistent asthma completed surveys . Of these participants , 1679 ( 47.1 % ) identified a primary care provider as their regular source of asthma care , 884 ( 24.8 % ) identified an allergist , 693 ( 19.4 % ) reported no regular source of asthma care , and 195 ( 5.5 % ) identified a pulmonologist . Vali date d quality of life , control , severity , patient satisfaction , and self-management knowledge tools and linked administrative data that captured medication use were compared between groups , adjusting for demographics and baseline hospital and corticosteroid use . RESULTS Compared with those followed by primary care providers , patients of allergists reported significantly higher ( P < .001 ) generic physical and asthma-specific quality of life , less asthma control problems , less severe symptoms , higher satisfaction with care , and greater self-management knowledge . Patients of allergists were less likely than patients of primary care providers to require an asthma hospitalization ( odds ratio , 0.45 ) or unscheduled visit ( odds ratio , 0.71 ) and to overuse beta-agonists ( odds ratio , 0.47 ) and were more likely to receive inhaled steroids ( odds ratio , 1.81 ) during their past year . CONCLUSIONS Allergist care is associated with a wide range of improved outcomes in asthmatic patients compared with care provided by primary care providers BACKGROUND Asthma control has been defined clinical ly by using vali date d tools , but an asthma control scale using administrative data has not been reported . OBJECTIVE We sought to vali date a beta-agonist asthma control scale derived from administrative data . METHODS Surveys that included vali date d asthma symptom and control tools were completed by a r and om sample of 2250 health maintenance organization members aged 18 to 56 years with persistent asthma . Linked computerized pharmacy data provided beta-agonist canister and oral corticosteroid dispensings . The proposed 4-level asthma control scale was based on the number of short-acting beta-agonist canisters dispensed in 12 months . Construct validity and predictive validity were assessed . RESULTS For construct validity , factor analysis showed significant loading of the beta-agonist scale on the symptom control factor , and the beta-agonist scale was significantly related to the vali date d asthma control and symptom scales ( r = 0.31 , P < .0001 ) . For predictive validity , each progressive level of the proposed beta-agonist control scale was associated with an increased risk of subsequent asthma hospitalizations or emergency department visits and oral corticosteroid use , independent of prior use . CONCLUSION A scale based on the number of beta-agonists dispensed in a 1-year period and derived from administrative data reflects asthma symptom control over that period of time . This scale can help identify patients who are at risk for future acute asthma health care use . CLINICAL IMPLICATION S This information can be used in population management and by clinicians to assess long-term asthma control and identify patients who need intervention to prevent future morbidity BACKGROUND Excessive use of short-acting β2-agonists ( SABA ) indicates impaired asthma control . OBJECTIVE To determine whether real-time outreach to excessive SABA users reduces SABA canister dispensings . METHODS After real-time determination of a seventh SABA canister dispensing in the prior 12 months by using informational pharmacy technology , 12 to 56 year old patients with physician-coded asthma and inhaled corticosteroid dispensing were block r and omized by prior asthma specialist care and medication step-care level into intervention ( n = 1001 ) and control groups ( n = 998 ) . Intervention included real-time letter notification to patients and an electronic message to their physician with management suggestions , including facilitated allergy referral for patients without prior asthma specialist care . The control group received this organization 's st and ard asthma care management without research contact . Frequency of the seventh SABA canister dispensing in the follow-up year was the primary outcome . RESULTS Compared with controls , intervention patients reached 7 SABA canister dispensings less frequently ( 50.7 % vs 57.1 % ; risk ratio 0.89 [ 95 % CI , 0.82 - 0.97 ] ; P = .007 ) and later ( hazard ratio 0.80 [ 95 % CI , 0.71 - 0.91 ; P < .001 ) . SABA canister dispensings ( mean ± SD ) were less in intervention ( 7.5 ± 4.9 canisters ) than controls ( 8.6 ± 5.3 canisters ) ( rate ratio 0.87 [ 95 % CI , 0.82 - 0.93 ] ; P < .001 ) . The intervention reduced the risk of ≥7 SABA canister dispensings in patients without specialist care compared with patients with specialist care in the prior 3 years ( P < .001 ) ( P = .04 for interaction by prior specialist care ) . Visits to allergists were more frequent for intervention patients ( 30.9 % ) than for control patients ( 16.8 % ) ( risk ratio 1.83 [ 95 % CI , 1.54 - 2.16 ] ; P < .001 ) . Asthma exacerbations were unaffected . CONCLUSIONS A novel administrative-based asthma outreach program improves markers of asthma impairment in patients without prior asthma specialist care and is adaptable to managed care organizations with electronic medical records |
12,626 | 27,425,572 | RESULTS Media literacy had the most support for universal prevention .
Most universal approaches showed significant modest effects on risk factors .
Dissonance-based was the best supported approach for selective prevention .
Cognitive-behavior therapy ( CBT ) , a healthy weight program , media literacy , and psychoeducation , were also effective for selective prevention and effects were maintained at follow-up .
CBT was supported for indicated prevention and effects were maintained at follow-up .
DISCUSSION The modest effects for universal prevention were likely due to floor effects . | OBJECTIVE This systematic review evaluated the efficacy of universal , selective , and indicated eating disorder prevention . | OBJECTIVE Because universal psychoeducational eating disorder prevention programs have had little success , we developed and evaluated two interventions for high-risk population s : a healthy weight control intervention and a dissonance-based intervention . METHOD Adolescent girls ( N = 148 ) with body image concerns were r and omized to one of these interventions or to a waitlist control group . Participants completed baseline , termination , and 1 , 3 , and 6-month follow-up surveys . RESULTS Participants in both interventions reported decreased thin-ideal internalization , negative affect , and bulimic symptoms at termination and follow-up relative to controls . However , no effects were observed for body dissatisfaction or dieting and effects diminished over time . DISCUSSION Results provide evidence that both interventions effectively reduce bulimic pathology and risk factors for eating disturbances A population -based , r and omized universal classroom intervention trial for the prevention of disruptive behavior ( i.e. , attention-deficit/hyperactivity problems , oppositional defiant problems , and conduct problems ) is described . Impact on developmental trajectories in young elementary schoolchildren was studied . Three trajectories were identified in children with high , intermediate , or low levels of problems on all 3 disruptive behaviors at baseline . The intervention had a positive impact on the development of all disruptive behavior problems in children with intermediate levels of these problems at baseline . Effect sizes of mean difference at outcome were medium or small . In children with the highest levels of disruptive behavior at baseline , a positive impact of the intervention was found for conduct problems BACKGROUND The high prevalence and incidence of obesity and eating disorders in US adolescent girls are serious health problems . Because of the shared risk factors for obesity and eating disorders , a targeted prevention of both conditions is a priority . OBJECTIVE We determined whether an adapted interpersonal psychotherapy prevention program is more efficacious for reducing excess weight gain and worsening disordered eating than health education in adolescent girls at high risk of obesity and eating disorders . DESIGN A parallel-group , r and omized controlled trial was conducted between September 2008 and January 2013 in a university-based laboratory and a federal research hospital . The study included 113 adolescent ( 12 - 17-y-old ) girls deemed at high risk of adult obesity and eating disorders because of a body mass index ( BMI ) between the 75th and 97th percentiles and reports of episodes of a loss of control over their eating . Girls were r and omly assigned to participate in an adapted interpersonal psychotherapy or a health-education group program for 12 weekly 90-min group sessions . Follow-up assessment s occurred immediately after group programs and at 6 and 12 mo . RESULTS Participation in both conditions was associated with decreases in expected BMI gain , age-adjusted BMI metrics , the percentage of fat by using dual-energy X-ray absorptiometry , symptoms of depression and anxiety , and the frequency of loss-of-control eating over 12 mo of follow-up ( Ps < 0.001 ) with no group difference . In follow-up analyses , interpersonal psychotherapy was more efficacious than health education at reducing objective binge eating at the 12-mo follow-up ( P < 0.05 ) . CONCLUSIONS The intervention with adolescent girls with loss-of-control eating is associated with lower age-adjusted BMI and percentage of adiposity as well as improved mood symptoms over 1 y. Interpersonal psychotherapy further reduced objective binge eating . Additional research is needed to eluci date the mechanisms by which physical and psychological improvements were observed . This trial was registered at clinical trials.gov as NCT00680979 OBJECTIVE Body dissatisfaction in females is common and a risk factor for the development of an eating disorder . This study tested whether body dissatisfaction could be improved using a brief conditioning intervention in which photographs of participants ' bodies were selectively paired with positive social stimuli ( smiling faces ) and photographs of other bodies were paired with neutral or negative social stimuli ( neutral and frowning faces ) . METHOD 39 women ( mean age = 22.46 ; 64.1 % Caucasian ) with high body dissatisfaction were r and omized to either the evaluative conditioning intervention ( n = 22 ) or to a delayed waitlist control condition ( n = 17 ) . Body dissatisfaction ( specifically , shape and weight concern ) , restraint , eating concern , and self-esteem were assessed at baseline , post treatment and again after four and 12 weeks . RESULTS Compared to women in the delayed waitlist control condition , women in the treatment condition demonstrated a significant decrease in shape and weight concern , and a significant increase in self-esteem . Similar trends were found for the control condition after they completed the intervention . Changes at post treatment related to body dissatisfaction were maintained at 12-week follow-up . CONCLUSIONS Repeatedly pairing photographs of an individual 's body with positive social feedback may lead to improved body image and self-esteem OBJECTIVE A group dissonance-based eating disorder prevention program , in which young women critique the thin ideal , reduces eating disorder risk factors and symptoms , but it can be difficult to identify school clinicians with the time and expertise to deliver the intervention . Thus , we developed a prototype Internet version of this program and evaluated it in a preliminary trial . METHOD Female college students with body dissatisfaction ( N = 107 ; M age = 21.6 years , SD = 6.6 ) were r and omized to the Internet intervention , group intervention , educational video condition , or educational brochure condition . RESULTS Internet and group participants showed greater pre-post reductions in eating disorder risk factors and symptoms than video controls ( M ds = 0.47 and 0.54 , respectively ) and brochure controls ( M ds = 0.75 and 0.72 , respectively ) , with many effects reaching significance . Effects did not differ significantly for Internet versus group participants ( M ds = -0.13 ) or for video versus brochure controls ( M d = 0.25 ) . Effect sizes for the Internet intervention were similar to those previously observed for group versions of this intervention . CONCLUSIONS Results suggest that this prototype Internet intervention is as efficacious as the group intervention , implying that there would be merit in completing this intervention and evaluating it in a fully powered trial 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 This study evaluated a targeted intervention design ed to alleviate body image and eating problems in adolescent girls that was delivered over the internet so as to increase access to the program . The program consisted of six , 90-minute weekly small group , synchronous on-line sessions and was facilitated by a therapist and manual . Participants were 73 girls ( mean age=14.4 years , SD=1.48 ) who self-identified as having body image or eating problems and were r and omly assigned to an intervention group ( n=36 ) ( assessed at baseline , post-intervention and at 2- and 6-months follow-up ) or a delayed treatment control group ( n=37 ) ( assessed at baseline and 6–7 weeks later ) . Clinical ly significant improvements in body dissatisfaction , disordered eating , and depression were observed at post-intervention and maintained at follow-up . Internet delivery was enthusiastically endorsed . The program offers a promising approach to improve body image and eating problems that also addresses geographic access problems Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity BACKGROUND Body image dissatisfaction during adolescence is common but not benign . School-based interventions have the potential for wide reach , but scalability of previous programmes is limited by a reliance on external facilitators . AIMS To assess the acceptability , feasibility and efficacy of a teacher-delivered body image intervention . METHOD A pilot clustered r and omised controlled trial in which 16 classes of adolescent girls were allocated to a 6-session body image programme ( n = 261 ) , or usual curriculum control ( n = 187 ) ( registration : IS RCT N42594993 ) . RESULTS Students in the intervention group had significantly improved body esteem and self-esteem and reduced thin-ideal internalisation . Effects for body esteem and thin-ideal internalisation were maintained for 3 months . There were no group differences for eating pathology , peer factors or depression . Acceptability , feasibility and efficacy varied between schools . CONCLUSIONS Teacher-delivered body image lessons have promise but further work is needed to increase efficacy and make interventions suitable across a range of schools OBJECTIVE Lifestyle interventions that promote physical activity and healthy dietary habits may reduce binge eating symptoms and be more feasible and sustainable among ethnic minority women , who are less likely to seek clinical treatment for eating disorders . The purpose of this study was to investigate ( 1 ) whether participating in a lifestyle intervention is a feasible way to decrease binge eating symptoms ( BES ) and ( 2 ) whether changes in BES differed by intervention ( physical activity vs. dietary habits ) and binge eating status at baseline ( binger eater vs. non-binge eater ) in African American and Hispanic women . METHOD Health Is Power ( HIP ) was a longitudinal r and omized controlled trial to promote physical activity and improve dietary habits . Women ( N = 180 ) who completed anthropometric measures and question naires assessing fruit and vegetable and dietary fat intake , BES and demographics at baseline and post-intervention six months later were included in the current study . RESULTS Over one-fourth ( 27.8 % ) of participants were categorized as binge-eaters . Repeated measures ANOVA demonstrated significant two- and three-way interactions . Decreases in BES over time were greater in binge eaters than in non-binge eaters ( F(1,164 ) = 33.253 , p < .001 ) , and women classified as binge eaters who participated in the physical activity intervention reported greater decreases in BES than non-binge eaters in the dietary habits intervention ( F(1,157 ) = 5.170 , p = .024 ) . DISCUSSION Findings suggest behavioral interventions to increase physical activity may lead to reductions in BES among ethnic minority women and ultimately reduce the prevalence of binge eating disorder and health disparities in this population OBJECTIVE This study examined the outcome of a body image and disordered eating intervention for midlife women . The intervention was specifically design ed to address risk factors that are pertinent in midlife . METHOD Participants were 61 women aged 30 to 60 years ( M = 43.92 , SD = 8.22 ) r and omly assigned to intervention ( n = 32 ) or ( delayed treatment ) control ( n = 29 ) groups . Following an 8-session facilitated group cognitive behavioral therapy-based intervention , outcomes from the Body Shape Question naire ; Eating Disorder Examination Question naire ; Body Image Avoidance Question naire ; Physical Appearance Comparison Scale ; Sociocultural Attitudes Towards Appearance Scale , Internalization subscale ; measures of appearance importance , cognitive re appraisal , and self-care ; Dutch Eating Behavior Question naire ; and Kessler Psychological Distress Scale were compared for statistical and clinical significance from baseline to posttest and 6-month follow-up . RESULTS Following the intent-to-treat principle , mixed-model analyses with a mixed within-between design demonstrated that the intervention group had large improvements that were statistically significantly different from the control group in body image , disordered eating , and risk factor variables and that were maintained at 6-month follow-up . Furthermore , the improvements were also of clinical importance . CONCLUSIONS This study provides support for the efficacy of an intervention to reduce body image and eating concerns in midlife women . Further research into interventions tailored for this population is warranted This two-group experimental study evaluated the effectiveness of a cognitive-behavioral body image intervention , adapted from an effective clinical intervention , with normal college females . Participants included non clinical , freshman college women who were assigned r and omly to either the experimental intervention or the control group ( brief educational session ) . Participants were assessed prior to the intervention and again 1 month later on dieting behavior , body image , fear of fat , and anxiety concerning physical appearance . Although it was hypothesized that each of these variables would be lower in the experimental group , none of these results , except for a trend for decreased dieting , were found . Overall these results of slightly reduced dieting behavior are consistent with other research targeting primary and secondary prevention . This intervention 's failure to impact body image and eating behaviors of college students illustrates the continuing challenge of eating disorders prevention CONTEXT Eating disorders , an important health problem among college-age women , may be preventable , given that modifiable risk factors for eating disorders have been identified and interventions have been evaluated to reduce these risk factors . OBJECTIVE To determine if an Internet-based psychosocial intervention can prevent the onset of eating disorders ( EDs ) in young women at risk for developing EDs . SETTING San Diego and the San Francisco Bay Area in California . PARTICIPANTS College-age women with high weight and shape concerns were recruited via campus e-mails , posters , and mass media . Six hundred thirty-seven eligible participants were identified , of whom 157 were excluded , for a total sample of 480 . Recruitment occurred between November 13 , 2000 , and October 10 , 2003 . Intervention A r and omized controlled trial of an 8-week , Internet-based cognitive-behavioral intervention ( Student Bodies ) that included a moderated online discussion group . Participants were studied for up to 3 years . MAIN OUTCOME MEASURES The main outcome measure was time to onset of a sub clinical or clinical ED . Secondary measures included change in scores on the Weight Concerns Scale , Global Eating Disorder Examination Question naire , and Eating Disorder Inventory drive for thinness and bulimia subscales and depressed mood . Moderators of outcome were examined . RESULTS There was a significant reduction in Weight Concerns Scale scores in the Student Bodies intervention group compared with the control group at postintervention ( P < .001 ) , 1 year ( P < .001 ) , and 2 years ( P < .001 ) . The slope for reducing Weight Concerns Scale score was significantly greater in the treatment compared with the control group ( P = .02 ) . Over the course of follow-up , 43 participants developed sub clinical or clinical EDs . While there was no overall significant difference in onset of EDs between the intervention and control groups , the intervention significantly reduced the onset of EDs in 2 subgroups identified through moderator analyses : ( 1 ) participants with an elevated body mass index ( BMI ) ( > or = 25 , calculated as weight in kilograms divided by height in meters squared ) at baseline and ( 2 ) at 1 site , participants with baseline compensatory behaviors ( eg , self-induced vomiting , laxative use , diuretic use , diet pill use , driven exercise ) . No intervention participant with an elevated baseline BMI developed an ED , while the rates of onset of ED in the comparable BMI control group ( based on survival analysis ) were 4.7 % at 1 year and 11.9 % at 2 years . In the subgroup with a BMI of 25 or higher , the cumulative survival incidence was significantly lower at 2 years for the intervention compared with the control group ( 95 % confidence interval , 0 % for intervention group ; 2.7 % to 21.1 % for control group ) . For the San Francisco Bay Area site sample with baseline compensatory behaviors , 4 % of participants in the intervention group developed EDs at 1 year and 14.4 % , by 2 years . Rates for the comparable control group were 16 % and 30.4 % , respectively . CONCLUSIONS Among college-age women with high weight and shape concerns , an 8-week , Internet-based cognitive-behavioral intervention can significantly reduce weight and shape concerns for up to 2 years and decrease risk for the onset of EDs , at least in some high-risk groups . To our knowledge , this is the first study to show that EDs can be prevented in high-risk groups Previous research has addressed the issues of behavior change and eating disorder prevention among adolescents and young women . The current study was design ed to evaluate : ( a ) whether an 8-week psychoeducational intervention can reduce maladaptive weight-management practice s in women ( University females , N=24 ) with sub- clinical levels of eating pathology ; and ( b ) whether its implementation reduces the risk of developing more severe eating pathology across time . Participants were r and omly assigned to an experimental ( EX ) group or a self-monitoring control ( SMC ) group . Statistically significant changes on measures of eating pathology , including the Eating Attitudes Test-26 [ Garner , D. M. , Olmsted , M. P. , Bohr , Y. , & Garfinkel , P. ( 1982 ) . The Eating Attitudes Test : psychometric features and clinical correlates . Psychological Medicine , 12 , 871 - 878 ] ; Forbidden Food Survey [ Ruggerio , L. , Williamson , D. A. , Davis , C. J. , Schlundt , D. G. , & Carey , M. P. ( 1988 ) . Forbidden Food Survey : Measure of bulimic 's anticipated emotional reactions to specific foods . Addictive Behaviors , 13 , 267 - 274 ] ; and Bulimia Test-Revised [ Thelen , M. H. , Farmer , J. , Wonderlich , S. , & Smith , M. ( 1991 ) . A revision of the bulimia test : The BULIT-R. Journal of Consulting and Clinical Psychology , 3(1 ) , 119 - 124 ] were observed , as were changes in body image , as measured by the Body Shape Question naire [ Cooper , P. J. , Taylor , M. J. , Cooper , Z. , & Fairburn , C. G. ( 1987 ) . The development and validation of the body shape question naire . International Journal of Eating Disorders , 6(4 ) , 485 - 494 ] . Additional significant between-group differences in eating behavior , as measured by daily meal records , were also seen . Participants in the EX group evidence d improvements in scores which were significantly different from those observed in the SMC group . Unfortunately , attrition limited the utility of follow up data This is the first long-term , controlled study evaluating the effectiveness of a prevention curriculum design ed to modify the eating attitudes and unhealthful weight regulation practice s of young adolescent girls . Nine hundred sixty-seven sixth and seventh- grade girls were r and omized to experimental healthy weight regulation curriculum or no-treatment control classes . A prevention intervention was developed around three principal components : ( 1 ) Instruction on the harmful effects of unhealthful weight regulation ; ( 2 ) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity ; ( 3 ) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting . The intervention failed to achieve the hoped-for impact . We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only , there was a small albeit statistically significant effect on body mass index . These findings question the wisdom of providing a curriculum directed at all young adolescents , most of whom are not at risk to develop an eating disorder . Rather than targeting the entire population , a healthy weight curriculum design ed to modify the eating attitudes and unhealthful weight regulation practice s of young adolescent girls might better focus on " at risk " students The aim of the current research was to evaluate Shapesville , a children 's picture book design ed to promote positive body image in young children . Participants were a convenience sample comprising 84 girls ( aged 5 - 9 years ) recruited from four private girls ' schools . Girls were r and omly allocated to be read either Shapesville or a control book . Individual measures of body image , stereotyping on the basis of weight and media internalisation , as well as knowledge of non-appearance topics , were obtained at pre- and post-intervention , as well as at 6-week follow-up . Relative to the control book , girls ' appearance satisfaction increased after reading Shapesville . In addition , stereotyping on the basis of weight and internalisation of media ideals was reduced . Finally , reading Shapesville also increased girls ' knowledge base of non-appearance topics , such as recognising their special talents and awareness of healthy eating , at post-intervention . These gains were somewhat reduced at follow-up , yet were largely still significantly greater than at pre-intervention . The present study demonstrates that Shapesville has the potential to be a successful prevention tool for use with young girls . Schools can incorporate Shapesville into their curriculum as early as school entry , in order to help prevent the early development of body dissatisfaction and disordered eating This study evaluated an Internet-delivered computer-assisted health education ( CAHE ) program design ed to improve body satisfaction and reduce weight/shape concerns -- concerns that have been shown to be risk factors for the development of eating disorders in young women . Participants were 60 women at a public university r and omly assigned to either an intervention or control condition . Intervention participants completed the CAHE program Student Bodies . Measures of body image and disordered eating attitudes were assessed at baseline , postintervention , and 3-month follow-up . At follow-up , intervention participants , compared with controls , reported a significant improvement in body image and a decrease in drive for thinness . This program provides evidence for the feasibility and effectiveness of providing health education by means of the Internet OBJECTIVE Successful prevention of eating disorders represents an important goal due to damaging long-term impacts on health and well-being , modest treatment outcomes , and low treatment seeking among individuals at risk . Mindfulness-based approaches have received early support in the treatment of eating disorders , but have not been evaluated as a prevention strategy . This study aim ed to assess the feasibility , acceptability , and efficacy of a novel mindfulness-based intervention for reducing the risk of eating disorders among adolescent females , under both optimal ( trained facilitator ) and task-shifted ( non-expert facilitator ) conditions . METHOD A school-based cluster r and omized controlled trial was conducted in which 19 classes of adolescent girls ( N = 347 ) were allocated to a three-session mindfulness-based intervention , dissonance-based intervention , or classes as usual control . A subset of classes ( N = 156 ) receiving expert facilitation were analyzed separately as a proxy for delivery under optimal conditions . RESULTS Task-shifted facilitation showed no significant intervention effects across outcomes . Under optimal facilitation , students receiving mindfulness demonstrated significant reductions in weight and shape concern , dietary restraint , thin-ideal internalization , eating disorder symptoms , and psychosocial impairment relative to control by 6-month follow-up . Students receiving dissonance showed significant reductions in socio-cultural pressures . There were no statistically significant differences between the two interventions . Moderate intervention acceptability was reported by both students and teaching staff . DISCUSSION Findings show promise for the application of mindfulness in the prevention of eating disorders ; however , further work is required to increase both impact and acceptability , and to enable successful outcomes when delivered by less expert providers BACKGROUND A r and omized controlled trial of three school-based programs and a no-intervention control group was conducted to evaluate their efficacy in reducing eating disorder and obesity risk factors . METHOD A total of 1316 grade 7 and 8 girls and boys ( mean age = 13.21 years ) across three Australian states were r and omly allocated to : Media Smart ; Life Smart ; the Helping , Encouraging , Listening and Protecting Peers ( HELPP ) initiative ; or control ( usual school class ) . Risk factors were measured at baseline , post-program ( 5 weeks later ) , and at the 6- and 12-month follow-ups . RESULTS Media Smart girls had half the rate of onset of clinical ly significant concerns about shape and weight than control girls at the 12-month follow-up . Media Smart and HELPP girls reported significantly lower weight and shape concern than Life Smart girls at the 12-month follow-up . Media Smart and control girls scored significantly lower than HELPP girls on eating concerns and perceived pressure at the 6-month follow-up . Media Smart and HELPP boys experienced significant benefit on media internalization compared with control boys and these were sustained at the 12-month follow-up in Media Smart boys . A group × time effect found that Media Smart participants reported more physical activity than control and HELPP participants at the 6-month follow-up , while a main effect for group found Media Smart participants reported less screen time than controls . CONCLUSIONS Media Smart was the only program to show benefit on both disordered eating and obesity risk factors . Whilst further investigations are indicated , this study suggests that this program is a promising approach to reducing risk factors for both problems OBJECTIVE This study compared the efficacy of a media literacy program and a self-esteem program design ed to reduce general and specific risk factors for eating disorders . METHOD Four classes of 86 grade 8 students ( 53 boys and 33 girls ) , mean age of 13 years , were r and omly assigned to either a control condition or one of the two intervention conditions . Assessment of general and specific risk factors was carried out at baseline , postintervention and 3-month follow-up . RESULTS At postintervention the media literacy group had lower mean scores on weight concern than the control group ( p = 0.007 ) but the self-esteem group did not . There were some differences on self-esteem measures at the 3-month follow-up . DISCUSSION Media literacy programs combined with an interactive , student-centered framework may potentially be a safe and effective way of reducing risk factors for eating disorders . The impact of teaching style needs to be further evaluated in prevention research OBJECTIVE As psychoeducational eating disorder prevention programs have not been shown to reduce bulimic pathology , we developed and evaluated a dissonance-based intervention for high-risk population s. METHOD Young women ( N = 87 ) with body image concerns were r and omized to this intervention , which involves verbal , written , and behavioral exercises requiring them to critique the thin-ideal , or to a healthy weight management control group . Participants completed a baseline , termination , and 4-week follow-up survey . RESULTS Participants in the dissonance intervention reported decreased thin-ideal internalization , body dissatisfaction , dieting , negative affect , and bulimic symptoms at termination and at 4-week follow-up . Unexpectedly , participants in the healthy weight management control group also reported some benefits . DISCUSSION Taken in conjunction with past findings , these preliminary results suggest that the dissonance intervention , and to a lesser extent the healthy weight management intervention , may reduce bulimic pathology and risk factors for eating disturbances This study explored the efficacy of a mindfulness-based intervention for problematic eating behavior . A non- clinical sample of 26 women with disordered eating behavior was r and omly assigned to an 8-week MBCT-based eating intervention or a waiting list control group . Data were collected at baseline and after 8 weeks . Compared to controls , participants in the mindfulness intervention showed significantly greater decreases in food cravings , dichotomous thinking , body image concern , emotional eating and external eating . These findings suggest that mindfulness practice can be an effective way to reduce factors that are associated with problematic eating behaviour Background A large proportion of university students show symptoms of common mental disorders , such as depression , anxiety , substance use disorders and eating disorders . Novel interventions are required that target underlying factors of multiple disorders . Aims To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aim ed at reducing symptoms of common mental disorders in university students . Method Students were recruited online ( n = 1047 , age : M = 21.8 , SD = 4.2 ) and categorised into being at high or low risk for mental disorders based on their personality traits . Participants were allocated to a cognitive-behavioural trait-focused ( n = 519 ) or a control intervention ( n = 528 ) using computerised simple r and omisation . Both interventions were fully automated and delivered online ( trial registration : IS RCT N14342225 ) . Participants were blinded and outcomes were self-assessed at baseline , at 6 weeks and at 12 weeks after registration . Primary outcomes were current depression and anxiety , assessed on the Patient Health Question naire ( PHQ9 ) and Generalised Anxiety Disorder Scale ( GAD7 ) . Secondary outcome measures focused on alcohol use , disordered eating , and other outcomes . Results Students at high risk were successfully identified using personality indicators and reported poorer mental health . A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up . Attrition was high across intervention groups , but comparable to other web-based interventions . Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 ( p<.001 , 95%CI [ 5.19 , 1.98 ] ) and anxiety scores by 2.87 ( p = .018 , 95%CI [ 1.31 , 4.43 ] ) in students at high risk . In high-risk students , between group effect sizes were 0.58 ( depression ) and 0.42 ( anxiety ) . In addition , self-esteem was improved . No changes were observed regarding the use of alcohol or disordered eating . Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention . Trial Registration ControlledTrials.com IS RCT BACKGROUND Women reporting initial eating disorder ( ED ) symptoms are at highest risk for the development of an eating disorder . Preventive interventions should , therefore , be specifically tailored for this subgroup . AIMS To adapt and evaluate the effects of the Internet-based prevention program " Student Bodies ™ " for women with symptoms of disordered eating and /or subthreshold eating disorder ( ED ) syndromes . METHOD 126 women , reporting subthreshold ED symptoms ( high weight and shape concerns and below threshold bingeing , purging , chronic dieting or several of these symptoms ) were r and omly assigned to a Student Bodies ™ + ( SB+ ) intervention or a wait-list control group and assessed at pre-intervention , post-intervention , and 6-month follow-up . " Student Bodies ™ " was adapted to be suitable for subthreshold EDs . Main outcome measures were attitudes and symptoms of disordered eating . Pre-follow-up data were analyzed by ANCOVAS with mixed effects . RESULTS At 6-month follow-up , compared to participants in the control group , participants in the intervention group showed significantly greater improvements on ED-related attitudes . Intervention participants also showed 67 % ( 95 % CI = 20 - 87 % ) greater reductions in combined rates of subjective and objective binges , and 86 % ( 95 % CI = 63 - 95 % ) greater reduction in purging episodes . Also , the rates of participants abstinent from all symptoms of disordered eating ( restrictive eating , binge eating and any compensatory behavior ) were significantly higher in the intervention group ( 45.1 % vs. 26.9 % ) . Post-hoc subgroup analyses revealed that for participants with binge eating the effect on EDE-Q scores was larger than in the pure restricting subgroup . CONCLUSION The adapted " SB+ " program represents an effective intervention for women with subthreshold EDs of the binge eating subtype Adolescent girls with body dissatisfaction ( N = 481 , SD = 1.4 ) were r and omized to a dissonance-based thin-ideal internalization reduction program , healthy weight control program , expressive writing control condition , or assessment -only control condition . Dissonance participants showed significantly greater decreases in thin-ideal internalization , body dissatisfaction , negative affect , eating disorder symptoms , and psychosocial impairment and lower risk for eating pathology onset through 2- to 3-year follow-up than did assessment -only controls . Dissonance participants showed greater decreases in thin-ideal internalization , body dissatisfaction , and psychosocial impairment than did expressive writing controls . Healthy weight participants showed greater decreases in thin-ideal internalization , body dissatisfaction , negative affect , eating disorder symptoms , and psychosocial impairment ; less increases in weight ; and lower risk for eating pathology and obesity onset through 2- to 3-year follow-up than did assessment -only controls . Healthy weight participants showed greater decreases in thin-ideal internalization and weight than did expressive writing controls . Dissonance participants showed a 60 % reduction in risk for eating pathology onset , and healthy weight participants showed a 61 % reduction in risk for eating pathology onset and a 55 % reduction in risk for obesity onset relative to assessment -only controls through 3-year follow-up , implying that the effects are clinical ly important and enduring The purpose of this study was to assess the impact of a multidisciplinary intervention program on the attitudes and symptoms associated with bulimia nervosa ( BN ) . The Bulimia Test ( BULIT ) and subscales from the Eating Disorder Inventory-2 ( EDI-2 ) associated with BN were administered to 373 females to determine eligibility for participation in the study . In order to qualify for the study , participants had to be female , not be anorexic , and meet one of four criteria indicating that they had some of the symptoms of BN . Following the screening , 12 females were r and omly assigned to a control group ( C , n=6 ) or an intervention group ( I , n=6 ) . The I group then participated in an 8-week multidisciplinary intervention program consisting of small group discussion s , movement improvisation , and relaxation techniques . Dependent variables consisted of scores from st and ardized instruments for anxiety , self-esteem , and BN . A multivariate analysis of variance ( MANOVA ) on the difference score from post- to pretest was calculated for state and trait anxiety . That analysis indicated that compared to the C group , which showed no reduction in anxiety , the I group had a significant reduction in anxiety following the intervention program . No significant differences were found between groups for self-esteem or symptoms of BN . Conclusions were that anxiety levels were lowered in the I group ; however , attitudes or behaviors associated with BN were not affected by the intervention Research supports the efficacy of both cognitive dissonance ( CD ) and healthy weight ( HW ) eating disorders prevention , and indicates that CD can be delivered by peer-facilitators , which facilitates dissemination . This study investigated if peer-facilitators can deliver HW when it is modified for their use and extended follow-up of peer-facilitated CD as compared to previous trials . Based on pilot data , we modified HW ( MHW ) to facilitate peer delivery , elaborate benefits of the healthy-ideal , and place greater emphasis on consuming nutrient dense foods . Female sorority members ( N=106 ) were r and omized to either two 2-h sessions of CD or MHW . Participants completed assessment pre- and post-intervention , and at 8-week , 8-month , and 14-month follow-up . Consistent with hypotheses , CD decreased negative affect , thin-ideal internalization , and bulimic pathology to a greater degree post-intervention . Both CD and MHW reduced negative affect , internalization , body dissatisfaction , dietary restraint , and bulimic pathology at 14 months OBJECTIVE Although several eating disorder prevention programs reduce eating disorder risk factors and symptoms for female high school and college students , few efficacious prevention programs exist for female middle school students , despite the fact that body image and eating disturbances often emerge then . Two pilot trials evaluated a new dissonance-based eating disorder prevention program for middle school girls with body image concerns . METHOD Female middle school students with body dissatisfaction from two sites [ Study 1 : N = 81 , M age = 12.1 , st and ard deviation ( SD ) = 0.9 ; Study 2 : N = 52 , M age = 12.5 , SD = 0.8 ] were r and omized to a dissonance intervention ( MS Body Project ) or educational brochure control ; Study 2 included a 3-month follow-up . RESULTS Intervention participants showed significant post-test reductions in only one of the six variables with both Studies 1 and 2 ( i.e. , pressure to be thin and negative affect , respectively ) , though post-test effect sizes suggested medium reductions in eating disorder risk factors and symptoms ( Study 1 : M d = .40 ; Study 2 : M d = .65 ) ; reductions at 3-month follow-up in Study 2 were not evident ( M d = .19 ) . CONCLUSIONS Results suggest that this new middle school version of the Body Project is producing medium magnitude reductions in eating disorder risk factors at post-test but that effects are showing limited persistence . Continued refinement and evaluation of this intervention appears warranted to develop more effective prevention programs for this age group Because there have been few longitudinal investigations of integrative etiological theories of bulimia nervosa , this study prospect ively tested the dual-pathway model using r and om regression growth curve models and data from a 3-wave community sample of adolescent girls ( N = 231 ) . Initial pressure to be thin and thin-ideal internalization predicted subsequent growth in body dissatisfaction , initial body dissatisfaction predicted growth in dieting and negative affect , and initial dieting and negative affect predicted growth in bulimic symptoms . There was prospect i ve evidence for most of the hypothesized mediational effects . Results are consistent with the assertion that pressure to be thin , thin-ideal internalization , body dissatisfaction , dieting , and negative affect are risk factors for bulimic pathology and provide support for the dual-pathway model The aim of this study was to replicate and extend results of a previous trial that investigated the effectiveness of 2 peer-led eating disorders prevention interventions in reducing eating disorder risk factors in undergraduate women ( C. B. Becker , L. M. Smith , & A. C. Ciao , 2006 ) . To extend findings from the previous study by allowing for investigation of differential response , the authors r and omly assigned a larger sample of both higher and lower risk sorority members ( N = 188 ; age M = 18.64 years , range = 18 - 21 ; 20 % minority ) to either a cognitive dissonance ( CD ) or a media advocacy ( MA ) intervention under naturalistic conditions . Interventions were delivered by trained sorority peer leaders and consisted of two 2-hr group sessions . Participants completed question naires that assessed eating disorder risk factors at pretreatment , posttreatment , 7-week follow-up , and 8-month follow-up . Results indicate that both interventions reduced thin-ideal internalization , body dissatisfaction , dietary restraint , and bulimic pathology at 8 months , although higher and lower risk participants responded somewhat differently . Both CD and MA generally appeared effective for higher risk participants ; only CD , however , appeared to benefit lower risk participants . Results further support the viability of using peer leaders in dissonance-based prevention Efficacy trials indicate that an eating disorder prevention program involving dissonance-inducing activities that decrease thin-ideal internalization reduces risk for current and future eating pathology , yet it is unclear whether this program produces effects under real-world conditions . The present effectiveness trial tested whether this program produced effects when school staff recruit participants and deliver the intervention . Adolescent girls with body image concerns ( N = 306 ; M age = 15.7 , SD = 1.1 ) r and omized to the dissonance intervention showed significantly greater decreases in thin-ideal internalization , body dissatisfaction , dieting attempts , and eating disorder symptoms from pretest to posttest than did those assigned to a psychoeducational brochure control condition , with the effects for body dissatisfaction , dieting , and eating disorder symptoms persisting through 1-year follow-up . Effects were slightly smaller than those observed in a prior efficacy trial , suggesting that this program is effective under real-world conditions , but that facilitator selection , training , and supervision could be improved OBJECTIVE The present preliminary trials tested whether undergraduate peer leaders can effectively deliver a dissonance-based eating disorder prevention program , which could facilitate broad dissemination of this efficacious intervention . METHOD In Study 1 , female undergraduates ( N=171 ) were r and omized to peer-led groups , clinician-led groups , or an educational brochure control condition . In Study 2 , which improved a design limitation of Study 1 by using completely parallel outcome measures across conditions , female undergraduates ( N=148 ) were r and omized to either immediate peer-led groups or a waitlist control condition . RESULTS In Study 1 , participants in peer- and clinician-led groups showed significantly greater pre-post reductions in risk factors and eating disorder symptoms than controls ( M d=.64 and .98 respectively ) , though clinician- versus peer-led groups had higher attendance and competence ratings , and produced stronger effects at posttest ( M d=.32 ) and at 1-year follow-up ( M d=.26 ) . In Study 2 , participants in peer-led groups showed greater pre-post reductions in all outcomes than waitlist controls ( M d=.75 ) . CONCLUSIONS Results provide novel evidence that dissonance-based eating disorder prevention groups led by undergraduate peers are feasible and produce greater reductions in eating disorder risk factors and symptoms than minimal-intervention control conditions , but indicate that effects are smaller for peer- versus clinician-led groups OBJECTIVE To conduct a pilot effectiveness trial of a brief dissonance-based eating disorder preventative program , the Body Project , when implemented at primary care medical clinics . METHOD Sixty-six female adolescents between the ages of 13 and 17 who reported at least some body image dissatisfaction were recruited at two primary care clinics and r and omized to Body Project groups or an educational video control condition ; eating disorder risk factors and symptoms were measured at pretest , posttest , and 3-month follow-up . RESULTS Body Project versus educational video control participants showed significantly greater reductions in thin-ideal internalization , pressure to be thin , dieting , and eating disorder symptoms at posttest , which were medium to large effect sizes . Body Project participants also showed greater decreases in body dissatisfaction and negative affect at posttest , though these moderate sized effects were not significant . Effects persisted through 3-month follow-up . CONCLUSION Average pre-post effect sizes ( d = 0.58 ) compare favorably to those observed in past Body Project efficacy ( average d = 0.59 ) and effectiveness trials ( average ds of 0.43 and 0.69 ) , suggesting that primary care clinics may represent a novel venue for offering and extending the reach of this eating disorder prevention program In this trial , adolescent girls with body dissatisfaction ( N = 481 , M age = 17 years ) were r and omized to an eating disorder prevention program involving dissonance-inducing activities that reduce thin-ideal internalization , a prevention program promoting healthy weight management , an expressive writing control condition , or an assessment -only control condition . Dissonance participants showed significantly greater reductions in eating disorder risk factors and bulimic symptoms than healthy weight , expressive writing , and assessment -only participants , and healthy weight participants showed significantly greater reductions in risk factors and symptoms than expressive writing and assessment -only participants from pretest to posttest . Although these effects faded over 6-month and 12-month follow-ups , dissonance and healthy weight participants showed significantly lower binge eating and obesity onset and reduced service utilization through 12-month follow-up , suggesting that both interventions have public health potential OBJECTIVE Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women . METHOD Female college students at high-risk for these outcomes by virtue of body image concerns ( N = 398 ; M age = 18.4 years , SD = 0.6 ) were r and omized to the Healthy Weight group-based 4-hr prevention program , which promotes gradual lasting healthy improvements to dietary intake and physical activity , or an educational brochure control condition . RESULTS Compared to controls , intervention participants showed significantly greater reductions in body dissatisfaction and eating disorder symptoms , and greater increases in physical activity , at posttest and significantly greater reductions in body mass index ( BMI ) and self-reported dieting at 6-month follow-up . Moderator analyses revealed significantly greater reductions in eating disorder symptoms for those with initially elevated symptoms and pressure to be thin and significantly greater reductions in BMI for those with initially elevated eating disorder symptoms . CONCLUSIONS Results indicate that this intervention reduced both eating disorder symptoms and unhealthy weight gain , but suggest it should be improved to produce stronger and more persistent effects , and that it may be useful to target young women with both body image and eating disturbances OBJECTIVE Efficacy trials indicate that a dissonance-based prevention program in which female high school and college students with body image concerns critique the thin-ideal reduced risk factors , eating disorder symptoms , and future eating disorder onset , but weaker effects emerged from an effectiveness trial wherein high school clinicians recruited students and delivered the program under real-world conditions . The present effectiveness trial tested whether a new enhanced dissonance version of this program produced larger effects when college clinicians recruited students and delivered the intervention using improved procedures to select , train , and supervise clinicians . METHOD Young women recruited from seven universities across the US ( N = 408 , M age = 21.6 , SD = 5.64 ) were r and omized to the dissonance intervention or an educational brochure control condition . RESULTS Dissonance participants showed significantly greater decreases in risk factors ( thin-ideal internalization , body dissatisfaction , dieting , negative affect ) and eating disorder symptoms versus controls at posttest and 1-year follow-up , result ing in medium average effect size ( d = .60 ) . Dissonance participants also reported significant improvements in psychosocial functioning , but not reduced health care utilization or unhealthy weight gain . CONCLUSIONS This novel multisite effectiveness trial with college clinicians found that the enhanced dissonance version of this program and the improved facilitator selection /training procedures produced average effects that were 83 % larger than effects observed in the high school effectiveness trial OBJECTIVE To evaluate a community-based intervention aim ed at the primary prevention of disordered eating among preadolescent girls . DESIGN Girl Scout troop members were r and omized into control and intervention groups . Program feasibility and effect at postintervention and 3-month follow-up were evaluated . SUBJECTS/ SETTING 226 girls ( mean age = 10.6 years , st and ard deviation = 0.7 ) from 24 Girl Scout troops . INTERVENTION Six 90-minute sessions focusing on media literacy and advocacy skills . MAIN OUTCOME MEASURES Evaluation focused on program satisfaction and short-term effect on dieting behaviors , body image attitudes , and media knowledge , attitudes , and habits . STATISTICAL ANALYSES Performed t tests , chi 2 tests , and analyses of covariance including troop as a r and om source of variation . RESULTS At baseline , 29 % of the girls were trying to lose weight . The program had a notable positive influence on media-related attitudes and behaviors including internalization of sociocultural ideals , self-efficacy to impact weight-related social norms , and print media habits . A modest program effect on body-related knowledge and attitudes was apparent at post-intervention ( i.e. , on body size acceptance , puberty knowledge , and perceived weight status ) but not at follow-up . Significant changes were not noted for dieting behaviors , but they were in the hypothesized direction . Satisfaction with the program was high among girls , parents , and leaders . APPLICATIONS/ CONCLUSIONS It is feasible to use community youth setting s , such as the Girl Scouts , to implement interventions to prevent disordered eating behaviors . The program led to positive trends in outcome variables ; however , longer and more intensive interventions are needed for lasting changes in body image and dieting behaviors AIM We hypothesize that a reason for the infrequent uptake of treatments by people with eating disorders is poor knowledge about treatments and outcomes for eating disorders ( ED-Mental Health Literacy ; ED-MHL ) . Our aim was to test putative health benefits of a brief ED-MHL intervention . METHODS In a community-based two-phase survey , 122 young women ( mean age 28.5 SD 6.3 years ) with ED symptoms meeting DSM-IV criteria for clinical severity were r and omized to receive either a brief ED-MHL intervention ( comprising information about efficacious treatments , reputable self-help books and where to go for further information and /or services ) or information about local mental health services only . All were given feedback on their scores on measures of ED symptoms and quality of life . ED-MHL , ED symptoms and health-related quality of life were assessed prior to the intervention and at 6- and 12-month follow-up . RESULTS One hundred and two participants ( 84 % ) completed follow-up at 12 months . Symptomatic improvement and changes in specific aspects of ED-MHL , namely , less pessimism about how difficult EDs are to treat and improved recognition and knowledge , as well as increased help seeking , were observed in both groups . Differences between groups were uncommon but compared with control participants , those in the intervention group had improved health-related quality of life . CONCLUSIONS A brief community-based intervention aim ed to improve knowledge and beliefs about EDs and their treatments may be a valuable first step in improving health-related outcomes for people with ED , but more research is needed OBJECTIVE This study evaluated the effectiveness at 1-year follow-up of a psychoeducational eating disorders preventive intervention implemented by specifically trained teachers . METHOD Participating teachers participated in a 5-week training program . One hundred forty-one female students attending nine classes at a vocational training school in Mestre ( Venice ) were assessed via a structured clinical interview ( Structured Clinical Interview for DSM-IV Axis I disorders ) and via the 40-item Eating Attitudes Test ( EAT-40 ) . Three classes were r and omly selected to participate in a 6-week prevention program conducted by the trained teachers . RESULTS Our data show that a disturbing number of the girls who were asymptomatic at baseline had developed a full or partial eating disorder 1 year later . This was the case for 2 ( 5 % ) participants and 10 ( 11 % ) subjects in the control group . Subjects in the prevention group differed significantly from the control group at the 1-year follow-up . This was the case for their EAT Bulimia subscale scores , which showed a significant improvement . The intervention group also revealed a lower development of food restraint and pathologic body attitudes . DISCUSSION Given the sample size , our findings must be considered cautiously . However , they suggest that students can benefit from participation in a preventive intervention program conducted by teachers , and the benefits appear to be particularly pronounced for bulimic symptoms OBJECTIVE As cognitive dissonance is theorized to contribute to the effects of dissonance-based eating disorder prevention programs , we evaluated a high-dissonance version of this program against a low-dissonance version and a wait-list control condition to provide an experimental test of the mechanism of intervention effects . METHOD Female college students ( N = 124 , mean age = 20.9 years , SD = 3.9 ) with body image concerns were r and omized to the 3 conditions . The high-dissonance program was design ed to maximize dissonance induction , and the low-dissonance program was design ed to minimize it ; the substantive content of the 2 programs was matched . RESULTS Relative to controls , those in the high-dissonance condition showed significantly greater reductions in thin-ideal internalization , body dissatisfaction , dieting , and eating disorder symptoms by posttest , and those in the low-dissonance condition showed significantly greater reductions in the first 3 outcomes by posttest , with most of these effects persisting to 3-month follow-up . High-dissonance participants showed significantly greater reductions in eating disorder symptoms than low-dissonance participants did by posttest , but this effect was nonsignificant by 3-month follow-up . CONCLUSIONS Results suggest that dissonance induction contributes to intervention effects but imply that the intervention content , nonspecific factors , and dem and characteristics play a much more potent role in producing effects The goal of the present study was to evaluate the effectiveness of a selective prevention program design ed to reduce pressures to be thin in sport , and to promote positive body image and eating behaviors in young female athletes . Participants were competitive female gymnasts ( aged 11 to 18 years ) , parents , and coaches from 7 gymnastic clubs across Ontario , Canada . Four of the seven clubs were r and omized to receive the 3-month intervention program ( IG ) aim ed at increasing awareness and positive climate change of body image pressures for athletes in their clubs . Three clubs were r and omized to the control group ( CG ) . A total of 62 female gymnasts ( IG n = 31 ; CG n = 31 ) completed self-report question naires examining perceptions of pressure to be thin within their sports clubs , self-efficacy over dieting pressures , awareness and internalization of societal pressure to be thin , body esteem , and eating attitudes and behaviours before and following the intervention . A total of 32 mothers ( IG n = 24 ; CG n = 8) completed measures examining their perceptions of their daughter 's pressure to be thin , awareness and internalization of societal pressures to be thin , daughter 's self-efficacy over dieting pressures , in addition to mothers ' beliefs regarding thinness and success for women in society , before and following the intervention . The findings revealed that participation in the BodySense program result ed in athletes perceiving a reduction in pressure from their sports clubs to be thin , though no changes were found in body esteem , the EAT , or the SATAQ . No significant change was observed over time on mothers ' measures . The role of climate change for prevention of eating disorders in athletes is discussed 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 This study aim ed to evaluate the effect of a six-session psychoeducation ( PE ) program on young women with type 1 diabetes mellitus ( DM ) and disordered eating attitudes and behavior . METHOD Two hundred twelve young women attending a pediatric diabetes clinic were screened for signs of eating disturbance . Of these women , 130 passed the screening and were invited to participate in the intervention phase of the study . Eighty-five subjects were r and omized to the PE or treatment-as-usual group . Assessment s were conducted before and after treatment and at 6-month follow-up . RESULTS Intention-to-treat group by time multivariate analyses of variance ( MANOVAs ) indicated significant reductions following PE treatment on the Restraint and Eating Concern subscales of the Eating Disorder Examination ( EDE ) and on the Drive for Thinness and Body Dissatisfaction subscales of the Eating Disorder Inventory ( EDI ) , but no improvement in frequency of purging by insulin omission or hemoglobin A1c levels . DISCUSSION The PE group was associated with reductions in eating disturbance , but not with improved metabolic control OBJECTIVE Excessive weight or shape concerns and dieting are among the most important and well-established risk factors for the development of symptoms of disordered eating or full-syndrome eating disorders . Prevention programs should therefore target these factors in order to reduce the likelihood of developing an eating disorder . The aims of this study were to determine the short-term and maintenance effects of an internet-based prevention program for eating disorders . METHOD One hundred female students at two German universities were r and omly assigned to either an 8-week intervention or a waiting-list control condition and assessed at preintervention , postintervention , and 3-month follow-up . RESULTS Compared with the control group , the intervention produced significant and sustained effects for high-risk women . CONCLUSION Internet-based prevention is effective and can be successfully adapted to a different culture OBJECTIVE An efficacy trial found that a dissonance-based prevention program reduced risk factors , eating disorder symptoms , and future eating disorder onset , but smaller effects emerged when high school clinicians recruited students and delivered the program under real-world conditions in an effectiveness trial . The current report describes results at 2- and 3-year follow-up from an effectiveness trial that tested whether a new enhanced dissonance version of this program produced larger effects when college clinicians recruit students and deliver the intervention using improved train and supervision procedures . METHOD Young women from eight universities ( N = 408 , M age = 21.6 , SD = 5.64 ) were r and omized to the prevention program or an educational brochure control condition . RESULTS Dissonance participants showed greater decreases in risk factors , eating disorder symptoms , and psychosocial impairment by 3-year follow-up than controls , but not healthcare utilization , BMI , or eating disorder onset . CONCLUSIONS This novel multisite effectiveness trial found that the enhanced dissonance intervention and improved training and supervision procedures produced an average effect size at 3-year follow-up that was 290 % and 160 % larger than effects observed in the high school effectiveness trial and efficacy trial respectively . Yet , the lack of eating disorder onset effects may imply that factors beyond pursuit of the thin ideal now contribute to eating disorder onset Food , Mood , and Attitude ( FMA ) is a CD-ROM prevention program developed to decrease risk for eating disorders in college women . Female 1st-year students ( N = 240 ) were r and omly assigned to the intervention ( FMA ) or control group . Equal numbers of students at risk and of low risk for developing an eating disorder were assigned to each condition . Participants in the FMA condition improved on all measures relative to controls . Significant 3-way interactions ( Time x Condition x Risk Status ) were found on measures of internalization of sociocultural attitudes about thinness , shape concerns , and weight concerns , indicating that at-risk participants in the intervention group improved to a greater extent than did low-risk participants . At follow-up , significantly fewer women in the FMA group reported overeating and excessive exercise relative to controls OBJECTIVE Interpersonal psychotherapy ( IPT ) is effective at reducing binge episodes and inducing weight stabilization in obese adults with binge eating disorder . METHOD We piloted the administration of IPT to girls at-risk for excess weight gain ( BMI 75th-97th percentile ; IPT-WG ) with and without loss of control ( LOC ) eating . Thirty-eight girls ( 12 - 17 years ) were r and omized to IPT-WG or a st and ard-of-care health education group . RESULTS All 38 girls completed the programs and all follow-up visits through 6 months . Thirty-five of 38 returned for a complete assessment visit at 1 year . Among girls with baseline LOC ( n = 20 ) , those in IPT-WG experienced greater reductions in such episodes than girls in health education ( p = .036 ) . Regardless of LOC status , over 1 year girls in IPT-WG were less likely to increase their BMI as expected for their age and BMI percentile ( p = .028 ) . DISCUSSION IPT-WG is feasible and acceptable to adolescent girls at-risk for adult obesity and may prevent excess weight gain over 1 year OBJECTIVE Gay males have increased risk for eating disorders compared to heterosexual males , establishing a need to develop and empirically evaluate programs to reduce risk for this population . The present study investigated the acceptability and efficacy of a cognitive dissonance-based ( DB ) intervention ( The PRIDE Body Project ( © ) ) in reducing eating disorder risk factors among gay males in a university-based setting . METHOD Eighty-seven gay males were r and omized to either a 2-session DB intervention ( n = 47 ) or a waitlist control condition ( n = 40 ) . Participants completed eating disorder risk factor assessment s pre-intervention , post-intervention , and at 4-week follow-up , and those receiving the intervention completed post-treatment acceptability measures . RESULTS Acceptability ratings were highly favorable . Regarding efficacy , the DB condition was associated with significantly greater decreases in body dissatisfaction , drive for muscularity , self-objectification , partner-objectification , body-ideal internalization , dietary restraint , and bulimic symptoms compared to waitlist control from pre- to post-intervention . Improvements in the DB group were maintained at 4-week follow-up , with the exception of body-ideal internalization . Body-ideal internalization mediated treatment effects on bulimic symptoms . CONCLUSION Results support the acceptability and efficacy of The PRIDE Body Project ( © ) and provide support for theoretical models of eating pathology in gay men This study evaluated a synchronous Internet-delivered intervention ( chat room ) for improving eating habits and body image in college-age women at risk for developing an eating disorder . Sixty at-risk women ( mean age = 18.9 , SD = 2.4 ; 65.0 % Caucasian , 19 % Latino/Hispanic , 8 % Asian/Pacific Isl and er , 3 % African American , 5 % other ; mean body mass index = 25.6 , SD = 5.7 ) were r and omly assigned to intervention ( n = 30 ) or control ( n = 30 ) groups . Once a week for 8 weeks , participants used a private chat room for a 1-hr moderated discussion focused on improving body image and eating behaviors . Additional treatment components included psychoeducation , asynchronous support , homework , and summaries . Assessment s were conducted at baseline , posttreatment , and 10 weeks after posttreatment . Participants indicated high satisfaction with the intervention mode . Intervention participants significantly reduced eating pathology and improved self-esteem over controls at follow-up . These findings suggest that synchronous , Internet-delivered programs are efficacious and have potential to reduce problematic attitudes and behaviors that may lead to eating disorders among college-age women OBJECTIVE This study evaluated an eating disorder intervention multimedia program modeled after self-help eating disorder treatment programs . It was hypothesized that women who completed the program would increase their body satisfaction and decrease their preoccupation with weight and frequency of disordered eating behaviors . METHOD Participants were 57 undergraduate females r and omly assigned to either the intervention or control group . Psychological functioning was assessed at baseline , at 3 months postintervention , and at 3 months follow-up . RESULTS Intervention group subjects significantly improved their scores on all psychological measures over time . When compared to the control group , however , only the intervention group 's improvements on the Body Shape Question naire were statistically significant . DISCUSSION This study has demonstrated that minimally effective eating disorder intervention programs can be delivered . A revised program that eliminates interface problems and increases the structure of the intervention is likely to be even better received and more effective OBJECTIVE To develop and pilot Life Smart , an eight-lesson program aim ed at reducing risk factors for both eating disorders and obesity . METHODS Grade 7 girls and boys ( N = 115 ) from one independent school were r and omly allocated to the Life Smart ( two classes ; N = 51 ) or control ( three usual classes ; N = 64 ) conditions . Risk factors were measured at baseline and post-program ( 5 weeks later ) . RESULTS Life Smart was rated as moderately enjoyable and valuable by participants . ANCOVAs with baseline as a covariate revealed a significant main effect for group favoring Life Smart for shape and weight concern ( Effect Size [ ES ] = .54 ) , with post-hoc testing finding girls particularly benefited on this variable ( ES = .78 ) . CONCLUSIONS Feedback was generally favorable , with some suggestions for even more interactive content . The program showed more promise with girls . Informed by these findings , the program underwent revisions and is now being evaluated in a r and omized controlled trial The purpose of this experiment was to provide an empirical comparison of two dissonance-based eating disorder prevention paradigms and a no-treatment control condition . Asymptomatic and symptomatic participants ( N = 155 ) were r and omly assigned to one of three experimental conditions : high level dissonance , low level dissonance , or no-treatment control . Group × symptomatic status interactions , main effects , and pairwise comparisons were examined to assess differences in eating disorder attitudes and behaviors at postintervention and 4-week follow-up . Participants in the high level condition displayed fewer eating disorder attitudes and behaviors compared to participants in the low level condition at postintervention . Eating disorder attitudes and behaviors were not significantly lower among participants in either intervention condition compared to no-treatment control participants The purpose of this study was to test the efficacy of the Healthy Girls Project , an ecologically based , targeted prevention program aim ed at discouraging the development of body-related problems in middle-school girls via an intervention directly and only with their mothers . Participants were 31 seventh- and eighth- grade girls and their mothers . The empirically based intervention comprised a series of 4 weekly workshops that had both interactive psychoeducational components and behavioral components ( e.g. , homework to do with daughters , modeling activities ) . The study design was experimental , with mother-daughter dyads r and omly assigned to either the intervention group or a wait-list control group . Daughters completed pretest ( i.e. , pre-workshop ) measures , posttest measures , and , 3 months later , follow-up measures . Results indicated that at both posttest and follow-up , girls whose mothers were in the intervention group perceived less pressure from their mothers to be thin . At follow-up , these girls also showed a lower drive for thinness . Results were mixed regarding group differences in body dissatisfaction levels at posttest and at follow-up . Results are discussed in terms of their implication s for targeted prevention efforts aim ed at girls during their middle-school years OBJECTIVE This study examines the effect of an interactive , school-based , self-esteem education program on the body image and eating attitudes and behaviors of young male and female adolescents following the program and after 12 months . METHOD All 470 eligible students ( 63 % female ) aged 11 - 14 years volunteered to participate . The intervention group students participated in the program , whereas the control group students received their scheduled personal development and health class . RESULTS The program significantly improved the body satisfaction of the intervention students and significantly changed aspects of their self-esteem ; social acceptance , physical appearance , and athletic ability became less important for the intervention students and more important for control students . Female intervention students rated their physical appearance as perceived by others significantly higher than control students and allowed their body weight to increase appropriately by preventing the age increase in weight-losing behaviors of the control students . One year after the intervention , body image and attitude changes were still present . These findings also held for the 116 students ( 63 % females ) with low self-esteem and higher anxiety , who were considered at risk for the development of eating disorders . These students also had significantly lower drive for thinness and greater body satisfaction following the intervention and the decreased importance of physical appearance to their self-esteem was present at 12 months . Control at-risk students significantly decreased their body weight , whereas the weight of the intervention at-risk students significantly increased . The intervention program was effective , safe , having no effect on measures of students ' anxiety or depression , and was rated highly by students . DISCUSSION This is the first controlled educational intervention to successfully improve body image and to produce long-term changes in the attitudes and self-image of young adolescents . This new approach to prevent the development of eating disorders by improving self-esteem may be effective , particularly if reinforced by teachers and family PROBLEM To develop , implement , and evaluate a school personnel training program on eating disorders . METHODS The pretest-posttest control group design was used to examine effects of this training with 117 high school personnel . Both experimental ( n = 85 ) and control ( n = 32 ) groups were given a pretest and a posttest on knowledge and attitudes . The experimental group participated in a training program . Both groups were asked to keep a 3-month count of students at risk for eating disorders . FINDINGS Results included a significant difference in knowledge between the experimental and control groups . School personnel in the experimental group were more likely to identify students at risk for developing eating disorders . CONCLUSIONS Training school personnel to identify students at risk for eating disorders holds promise as a strategy for dealing with this disease . All at-risk students for eating disorders should be further evaluated and additional treatment initiated as needed Cognitive-behavioral therapy ( CBT ) was compared to a combination of aerobic/anaerobic exercise therapy ( ET ) for the treatment of elevated levels of body image disturbance in college females . CBT consisted of a modification of the 1987 Butters and Cash procedure that was tailored for group intervention ; ET consisted of weightlifting and aerobic dancing . Using a counterbalancing procedure , the same therapists conducted both 6-week interventions , which were compared to a nontreated control group . Results revealed equivalent reductions for both treatment groups when compared to controls on measures of body image disturbance reflective of trait and state body weight anxiety , cognitive-behavioral aspects of appearance , and overall body dissatisfaction . Unfortunately , few subjects were available for follow-up analyses , preventing an evaluation of the stability of changes . The findings are discussed with regard to the potential role of fitness training as an adjunct to cognitive-behavioral interventions for body image disturbance OBJECTIVE Eating-disordered behavior is prevalent among college women . Few interventions have successfully reduced risk factors for these behaviors , however . The most promising interventions are both selective and interactive . This study compared two newer types of interventions that meet these criteria : cognitive dissonance and yoga programs . METHOD This study advertised programs for women who were dissatisfied with their bodies . Participants ( N = 93 ) were r and omly assigned to dissonance , yoga , or control groups . RESULTS Hierarchical regression analyses revealed that there were no significant post-intervention differences between the yoga and control groups . Dissonance group participants had significantly lower scores than the scores of both other groups on measures of disordered eating , drive for thinness , body dissatisfaction , alexithymia , and anxiety . CONCLUSION These findings have important implication s for interventions on college campuses . In particular , dissonance interventions appear to be an efficient and inexpensive approach to reducing eating disorder risk factors . Additional research regarding the value of yoga interventions is needed The authors examine the effectiveness of norm misperception education in decreasing disordered eating . One hundred seven 1st-year college women completed question naires assessing their own and others ' actual and ideal body size as well as their own disordered eating and were then r and omly assigned to read either a norm misperception or a control brochure . Participants completed question naires immediately after reading the brochures and again 3 months later . Although there were no main effects of brochure condition at the follow-up , participants who primarily compared themselves with other college women and who read the norm misperception brochure had higher actual and ideal weight as well as less frequent disordered eating . The discussion focuses on the theoretical and applied implication s of these findings OBJECTIVE Negative body image , a common problem among college-age women in the United States , strongly correlates with low self-esteem , disturbed eating behavior , and eating disorders . Psychoeducational programs have inconsistently shown improvement in body image , thin-ideal internalization , eating behaviors , psychosocial functioning , and self-esteem . METHOD In the current study , college women with body image concerns ( N = 84 ) were r and omly assigned to a cognitive dissonance-based , thin-ideal internalization , single-session workshop ( DTI ; n = 26 ) ; a psychoeducational , healthy behavior , single-session workshop ( HB ; n = 24 ) ; or a wait-list control ( WL ; n = 34 ) . RESULTS Comparing baseline data with 4-week follow-up data , results indicated that both DTI and HB participants reported improvement in body image , thin-ideal internalization , and eating behaviors . DISCUSSION Results provide evidence that both interventions effectively reduce risk factors for eating pathology Because depressive and bulimic pathologies often co-occur among adolescent girls , a preventive program focusing on both disturbances would have clinical utility . Thus , we developed a cognitive-behavioral intervention targeting body dissatisfaction , an established risk factor for both conditions . A r and omized prevention trial with late adolescent girls suggested that the intervention reduced body dissatisfaction , negative affect , depressive symptoms , and bulimic symptoms , but not dieting . Effects persisted through 3-month follow-up , but most faded by 6-month follow-up . Intervention effects on negative affect , depressive symptoms , and bulimic symptoms appeared to be mediated by change in body dissatisfaction . Participant age , ethnicity , and body mass did not moderate intervention effects . Results suggest that an intervention that improves body satisfaction might reduce depressive and bulimic symptoms but imply that greater emphasis on preventing future symptoms might be necessary for persistent effects Computer-based delivery of health-related psychoeducational programming is increasingly popular . In the present study , 72 non-symptomatic undergraduate women were r and omized to an Internet-based prevention program for eating disorders with or without accompanying discussion groups , or a control group . Sixty-one of the women ( 84 % ) completed the Student Bodies program , and were assessed at short and eight – nine month follow-up . Participation in the program result ed in better outcomes across all groups compared to controls , and women in the unmoderated discussion group appeared to have the most reduction in risk . Benefits of the program continued at follow-up . Decrease in risk also was associated with time spent using the Internet-based program . The present study suggests that the use of Student Bodies may reduce risk of eating and body image concerns over the long term , and that moderation of discussion groups may not be essential for successful outcomes . Further research on larger sample s will help determine the degree to which discussion groups or the Student Bodies program alone are effective OBJECTIVE The aim of this study was to compare the outcomes following an eight-session , small group , therapist-led , intervention for body dissatisfaction , and disordered eating in adult women , delivered either in face-to-face or synchronous , internet mode . METHOD Community women with high body dissatisfaction and internet access were r and omly assigned to either face-to-face delivery ( N = 42 ) , internet delivery ( N = 37 ) , or delayed treatment control ( N = 37 ) . All groups were assessed at baseline and 8 - 9 weeks later . The intervention groups were reassessed at 6-months follow-up . RESULTS Both intervention groups showed large improvements in body dissatisfaction compared with the delayed treatment control and these improvements were maintained at follow-up . However , posttreatment improvements were greater in the face-to-face than internet intervention . CONCLUSION In adult women , it is desirable to deliver the body image intervention in a face-to-face mode , but the internet mode is effective and has the potential to increase access to therapy Background : To explore the impact of a prevention program on the eating and body attitudes of a sample of adolescent schoolgirls . Methods : The program involved lessons and group discussion s of general adolescent problems and eating disorders . A total of 254 16-year-old schoolgirls were evaluated , of whom 154 participated in the program and a further 154 subjects formed the control group . Variations in weight , Eating Attitudes Test and Eating Disorders Inventory at a 1-year follow-up were compared for the two groups . Results : Among high-risk subjects , no significant differences were found between the prevention and the control group . The preventive program appeared to reduce significantly body dissatisfaction and to decrease the risk of bulimic attitudes in low-risk subjects . Conclusions : Providing schoolgirls with the correct information about eating disorders did not encourage unhealthy attitudes to eating and weight regulation practice s. However , for high-risk subjects more intensive and specific intervention may be required , for which further research is needed OBJECTIVE A group-based eating disorder prevention program wherein young women explore the costs of pursuing the thin ideal reduces eating disorder risk factors and symptoms . However , it can be challenging to identify school clinicians to effectively deliver the intervention . The present study compares the effects of a new Internet-based version of this prevention program , which could facilitate dissemination , to the group-based program and to educational video and educational brochure control conditions at 1- and 2-year follow-up . METHOD Female college students with body dissatisfaction ( n = 107 ; M age = 21.6 , SD = 6.6 ) were r and omized to these 4 conditions . RESULTS Internet participants showed reductions in eating disorder risk factors and symptoms relative to the 2 control conditions at 1- and 2-year follow-up ( M -d = .34 and .17 , respectively ) , but the effects were smaller than parallel comparisons for the group participants ( M -d = .48 and .43 , respectively ) . Yet the Internet intervention produced large weight gain prevention effects relative to the 2 control conditions at 1- and 2-year follow-up ( M -d = .80 and .73 , respectively ) , which were larger than the parallel effects for the group intervention ( M -d = .19 and .47 , respectively ) . CONCLUSIONS Although the effects for the Internet versus group intervention were similar at posttest , results suggest that the effects faded more quickly for the Internet intervention . However , the Internet intervention produced large weight gain prevention effects , implying that it might be useful for simultaneously preventing eating disordered behavior and unhealthy weight gain AIM This preliminary r and omized controlled trial assessed the feasibility of a pilot mindfulness-based intervention with respect to reducing the risk of eating disorders in young women . METHODS Forty-four young adult women with body image concerns ( Mage = 20.57 , SD = 3.22 ) were r and omly allocated to a mindfulness-based or a dissonance-based intervention ( 3 × 1 h weekly sessions ) , or to assessment -only control . Self-report measures of eating disorder risk factors , symptoms and related psychosocial impairment were compared at baseline , post-intervention , and at 1- and 6-month follow up . RESULTS At post-intervention , acceptability ratings for both interventions were high . Mindfulness participants demonstrated statistically significant improvements relative to control at post-intervention for weight and shape concern , dietary restraint , thin ideal internalization , eating disorder symptoms and related psychosocial impairment ; however , these gains were largely lost over follow up . Dissonance participants did not show statistically significant improvements relative to control on any outcomes , despite small to moderate effect sizes . CONCLUSIONS These preliminary findings demonstrate the acceptability and short-term efficacy of a mindfulness-based approach to reducing the risk of disordered eating in young women . This provides support for the continued evaluation of mindfulness in the prevention and early intervention of eating disorders , with increased efforts to produce maintenance of intervention gains |
12,627 | 28,493,631 | There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT , suggesting a benefit in relation to symptom scores .
AIT is effective in improving symptom , medication , and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment , and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy | BACKGROUND The European Academy of Allergy and Clinical Immunology ( EAACI ) is in the process of developing Guidelines on Allergen Immunotherapy ( AIT ) for Allergic Rhinoconjunctivitis .
To inform the development of clinical recommendations , we undertook a systematic review to assess the effectiveness , cost-effectiveness , and safety of AIT in the management of allergic rhinoconjunctivitis . | Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG . They were r and omly assigned to two groups based on skin test titrations to grass allergens . One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU , and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo . Daily symptom and medication score sheets were completed by all patients each day of the grass season . Blocking antibody rose ninefold in the IPG group ( p less than 0.007 ) but was unchanged in the placebo group . There was no significant change in IgE against rye grass group I in either the IPG or the placebo group . Symptom-score mean in the IPG group was 217 + /- 71 ( S.E.M. ) , statistically lower ( p less than 0.02 ) than the mean in the placebo group 496 + /- 117 ( S.E.M. ) . There were no systemic reactions and only minor local reactions . There was no change in routine laboratory tests in either group . Although two prior studies with grass allergen immunotherapy reported efficacy , these studies did not use symptom-score analysis . This is the first double-blind , histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation . IPG is a safe , clinical ly effective , and potentially cost-effective therapy for grass pollinosis BACKGROUND Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis ( ARC ) , but a lack of robust evidence has deterred its use in North America . OBJECTIVE To determine the efficacy and tolerability of st and ardized glycerinated short ragweed sublingual allergen immunotherapy liquid ( RW-SAIL ) extract in subjects with ragweed-related ARC . METHODS This phase 3 , r and omized , placebo-controlled trial was conducted in North America . Subjects ( age range , 18 - 55 years ) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed . Subjects self-administered the maximum tolerated dose of RW-SAIL ( n = 218 ) or placebo ( n = 211 ) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season . The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores ( TCS ) . RESULTS During the entire season , there was a 43 % decrease in TCS in subjects treated with RW-SAIL compared with placebo . Similar decreases were observed in TCS between the 2 groups during peak season ( 42 % ) and in daily symptom scores during the entire ( 42 % ) and peak ( 41 % ) seasons . The occurrence of adverse events was similar between the treatment groups ; most were mild in severity . Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited . No anaphylaxis occurred . CONCLUSIONS This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual st and ardized ragweed allergen immunotherapy liquid extract for the treatment of ARC Background : The clinical efficacy and safety of a six‐grass pollen allergoid has been studied . The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this re appraisal Immunotherapy with polymerized ragweed ( PRW ) has been demonstrated to be safe and effective when compared with monomeric ragweed or untreated controls . To further establish the efficacy of PRW , a trial was conducted comparing PRW , placebo , and no treatment in ragweed-sensitive individuals . In a double-blind manner , 21 patients were treated before the 1981 ragweed season with 15 weekly injections of PRW totaling about 50,000 PNU and 1200 microgram antigen E , while 19 patients were treated with 15 weekly injections of a caramelized glucose and histamine placebo . An additional control group received no injections . Blood was drawn for IgE against ragweed antigen E ( IgE-a-AgE ) and for blocking antibody against AgE before treatment , after treatment ( before season ) , and after season . In the untreated patients , blood was drawn before season and after season . Daily symptom score sheets were completed by patients each day of the ragweed season . Blocking antibody rose more than 40-fold with treatment ( p = 0.0001 ) in the PRW group but was unchanged in the placebo group with treatment . IgE-a-AgE rose with PRW therapy . Clinical efficacy of PRW was again confirmed in this study . Symptom score mean in the PRW group was statistically lower than the mean in the placebo group ( p = 0.022 ) and in the untreated group ( p = 0.018 ) . There were no systemic reactions and only minor local reactions during treatment . In summary , PRW is an improved form of immunotherapy BACKGROUND There have been no data on sublingual immunotherapy ( SLIT ) in Brazilian patients sensitized to house dust mites . This study aim ed to evaluate the mucosal/systemic antibody response changes and clinical efficacy after SLIT using Dermatophagoides pteronyssinus ( Dpt ) allergens with or without bacterial extracts in mite-allergic Brazilian children . METHODS Patients with allergic rhinitis and asthma were selected for a double-blind , placebo-controlled trial r and omized to three groups : DPT ( Dpt extract , n = 34 ) , DPT+MRB ( Dpt plus mixed respiratory bacterial extracts , n = 36 ) , and Placebo ( n = 32 ) . Total symptom and medication scores for rhinitis/asthma , skin prick test ( SPT ) to Dpt , and measurements of Dpt- , Der p 1- , Der p 2-specific serum IgE , IgG4 , IgG1 , and specific salivary IgA were evaluated at baseline and after 12 and 18 months of treatment . RESULTS A significant long-term decline in total symptom/medication scores was observed only in active groups ( DTP and DPT+MRB ) . There was no significant change in SPT results in all groups . SLIT using Dpt allergen alone induced increased levels of serum IgG4 to Dpt , Der p 1 , and Der p 2 , serum IgG1 and salivary IgA to Dpt and Der p 1 . SLIT with Dpt plus bacterial extracts was able to decrease IgE levels , particularly to Der p 2 , to increase salivary IgA levels to Der p 1 , but had no changes on specific IgG4 and IgG1 levels . CONCLUSIONS All children undergoing SLIT showed clinical improvement , but a long-term reduction in symptom/medication scores with modulation of mucosal/systemic antibody responses were seen only in active groups ( DPT and DPT+MRB ) 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 This work presents a double-blind , placebo-controlled study of 27 patients with allergic rhinitis to ragweed who received preseasonal desensitization immunotherapy [ IT ] with alum-precipitated aqueous ragweed extracts . We reassessed the following parameters in relation to clinical responses : clinical scores , nasal reactivity to a provocative dose of ragweed causing a 75 % fall in airflow rate ( PD75 ) , ragweed IgE and IgG , and ragweed-induced basophil histamine release ( BHR ) . First , the nasal PD75 correlated with the severity of nasal symptoms ( p less than 0.05 ) . Second , we confirmed a significant symptomatic improvement in the IT-treated group either by clinical scores ( p less than 0.05 ) or the prevention of the seasonal fall of the PD75 ( p less than 0.005 ) . Also , IT reduced the seasonal rise of IgE ( p less than 0.02 ) and induced an increase in IgG ( p less than 0.01 ) and a decrease in BHR ( p less than 0.03 ) . There was a significant correlation between IgE and BHR ( r = 0.80 ; p less than 0.01 ) . After selecting out the effects of IgE , the BHR was still higher in the placebo-treated group than in the IT-treated group ( p less than 0.02 ) , suggesting the involvement of other modulating factors . Symptomatic improvement after IT correlated only with the summation of both IgE and BHR ( PD75 ; r = 0.64 ; p less than 0.005 ) . This observation suggests that the severity of clinical symptoms is determined by several interacting factors and not by the antibody response alone 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 The present work reports the results of a double‐blind clinical trial , comparing the effects of hyposensitization treatment versus placebo in 33 patients with allergic rhinitis , sensitive to a crude extract of the pollen of four different grasses ( Dactylis glamerata , Lolium perenne , Secale cereale , and Phlewn pratense ) . The distribution of these patients in the two groups was done r and omly and gave two comparable groups , as far as clinical and biological features are concerned . The treatment course included five low doses of the aqueous extract followed by 12 injections of Al(OH)3‐adsorbed aliquots of the same extract . Evaluation of the clinical scores was based on diary cards on which symptoms and medications were recorded . A reevaluation of the significance of the symptom and medication scores is presented and the link between both scores is studied . Particular attention is given to the method ological and statistical problems raised during this study . The non‐parametric tests reveal a significant difference ( P < 0.03 ) in the total clinical score between the treated and the placebo groups for the second half of the observation period , when the pathology was most intense BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents . OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a st and ardized allergen extract in a r and omized , double-blind , placebo-controlled , 3-year prospect i ve study of patients who were allergic to only Alternaria alternata . METHODS Fifty children and adolescents ( 25 girls ; 5 - 18 years of age ) with A alternata-induced seasonal allergic rhinoconjunctivitis and /or bronchial asthma were r and omly assigned to groups given treatment ( Novo-Helisen Depot , A alternata 100 % ) or placebo . The primary end point was the combined symptom medication score . Secondary end points included safety , quality of life , and sensitivity to allergen-specific nasal challenge . RESULTS Forty-five children completed the 3-year study . Although there was no significant change in year 1 , the combined symptom medication score decreased in years 2 and 3 of the study ( by 38.7 % and 63.5 % , respectively ; P < .001 for each ) . The reduction in symptoms was associated with a significant improvement in quality of life ( P < .05 ) and decrease in sensitivity after allergen-specific nasal challenge . Side effects were observed in 7 patients ; the most common ( edema at the site of injection ) occurred after 11 injections . CONCLUSIONS Allergen-specific immunotherapy with st and ardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects 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 BACKGROUND In North America and Europe , millions of patients experience symptoms of allergic rhinitis with or without conjunctivitis ( AR/C ) on exposure to ragweed pollen . The disease burden can be significant , with most patients relying on symptomatic medications without disease-modifying potential . However , novel sublingual immunomodulatory treatment options may potentially play an important role if efficacy and side effect profiles allow the convenience of self-administration . OBJECTIVES This study evaluated an allergy immunotherapy tablet ( AIT ; SCH 39641/MK-3641 ) for treatment of ragweed-induced AR/C in the first large r and omized , double-blind multinational trial of this therapeutic modality for ragweed allergy . METHODS Adults ( n = 784 ) with short ragweed-induced AR/C were r and omly assigned to approximately 52 weeks of daily self-administered ragweed AIT of 1.5 , 6 , or 12 units of Ambrosia artemisiifolia major allergen 1 ( Amb a 1-U ) or placebo . Subjects could use as-needed allergy rescue medication . Symptoms and medications were recorded daily . The primary efficacy end point was total combined daily symptom/medication score ( TCS ) during peak ragweed season . Safety was monitored through adverse event diaries maintained through study duration . RESULTS During peak ragweed season , ragweed AIT of 1.5 , 6 , and 12 Amb a 1-U reduced TCS by 9 % ( -0.76 ; P = .22 ) , 19 % ( -1.58 ; P = .01 ) , and 24 % ( -2.04 ; P = .002 ) compared with placebo . During the entire season , ragweed AIT of 1.5 , 6 , and 12 Amb a 1-U reduced TCS by 12 % ( -0.88 ; P = .09 ) , 18 % ( -1.28 ; P = .01 ) , and 27 % ( -1.92 ; P < .001 ) compared with placebo . Treatment was well tolerated ; no systemic allergic reactions occurred . CONCLUSIONS In this trial , ragweed AIT of 12 Amb a 1-U was effective and tolerable with a safety profile that permitted daily self-administration of ragweed allergen immunotherapy 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 Asthma and rhinitis are common chronic conditions that affect adults of working age . Little is known about their relative impacts on work loss and decreased productivity . Using r and om digit telephone dialing , we carried out a population -survey of adults in Northern California aged 18 - 50 years . We interviewed 125 persons with asthma ( with or without concomitant rhinitis ) and 175 persons with rhinitis alone . Study eligibility was based on subject report of a physician 's diagnosis of asthma and /or a rhinitis-related condition . Any adult labor force participation since condition onset was lower among those with asthma ( 88 % ) than among those with rhinitis alone ( 97 % ) ( P = 0.002 ) . In contrast , among those still employed , decreased job effectiveness was more frequently reported in the rhinitis group ( 43 of 121 ; 36 % ) compared to those with asthma ( 14 of 72 ; 19 % ) ( P = 0.02 ) . Condition-attributed lost work was common in both groups , with more than 20 % reporting one or more complete or partial work days lost in the 4 weeks previous to interview . Taking into account age , gender , race , and smoking status , those with asthma were more likely to have no labor force participation after diagnosis ( OR = 3.0 ; 95 % CI 1.1 - 7.7 ) and less likely to report decreased job effectiveness among those remaining employed ( OR = 0.4 ; 95 % CI 0.2 - 0.9 ) . Excluding subjects from the rhinitis group most likely to have unreported asthma based on past medication use had little impact on these associations . Both asthma and rhinitis negatively affect work productivity . Those with asthma are less likely to be employed at all , while among those remaining on the job , rhinitis is a more potent cause of decreased work effectiveness . The economic impact of asthma and rhinitis and related conditions may be under-appreciated 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 There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases . METHODS This r and omized , double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with st and ardized ragweed pollen extract tablets , in patients with an allergic rhinitis . A total of 110 out patients were r and omized ( immunotherapy [ I ] : 55 ; placebo [ P ] : 55 ) , of whom 99 were analyzable for efficacy ( I : 48 ; P : 51 ) and 106 analyzable for safety ( I : 53 ; P : 53 ) . After a 28-day progression phase , the patients received a maintenance treatment during 6.5 months . Efficacy variables included a global assessment of efficacy ( patient/ investigator ) , symptoms and medication scores as well as the frequency of asthma attacks . RESULTS In the active treatment group , 43 patients completed the study , versus 49 on placebo . During the whole period of pollination , the difference favoring immunotherapy was highly significant for the global assessment by the patient ( p = 0.004 ) and by the investigator ( p = 0.005 ) . Adverse reactions were reported more often in the active treatment but mild or moderate , and they abated after dose adjustment . A subgroup analysis of those patients receiving the highest dose of immunotherapy ( 3 tablets 3 times a week ) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages . CONCLUSION This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship 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 The efficacy and side effects of two approaches to the treatment of ragweed pollen-induced rhinoconjunctivitis were compared in a double-blind , parallel-group trial . Sixty ragweed-sensitive adults were r and omized either to a course of four Pollinex-R hyposensitization injections during the 6 weeks before the ragweed-pollen season , or to budesonide aqueous nasal steroid spray , 400 micrograms daily , throughout the season . A double-dummy technique was used to achieve blinding . During the ragweed-pollen season , troublesome nasal symptoms were treated with terfenadine , 60 mg , when treatment was needed , up to 240 mg daily , and eye symptoms were treated with naphazoline eye drops , when treatment was needed , up to four times daily . Every day , subjects recorded the severity of nasal and eye symptoms and medication use in a diary . Fourteen of the subjects receiving Pollinex-R were unable to complete the course of injections because of systemic or large local reactions . Eight subjects withdrew during the pollen season because of severe rhinitis ; all subjects had received Pollinex-R. Subjects in the budesonide-treated group had minimal nasal symptoms and used very little terfenadine , compared with subjects in the Pollinex-R-treated group ( p less than 0.0001 ) . Eye symptoms and eye drop use were similar in the two treatment groups . No clinical ly important side effects were reported by the subjects receiving budesonide . The results of this study suggest that aqueous budesonide nasal spray is markedly more effective than Pollinex-R in controlling symptoms of seasonal rhinitis while the side effects and inconvenience of immunotherapy are avoided 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 Specific immunotherapy with unmodified formalinized allergoids is effective in grass-pollen allergy , but systemic reactions have been observed . A high-molecular-weight formalinized allergoid ( HMW-GOID ) was fractionated by gel filtration , retaining molecules of greater than 85,000 daltons in the expectation of improving safety without sacrificing efficacy . HMW-GOID and unfractionated allergoid ( GOID ) had a similar allergenic activity assessed by RAST inhibition , but the HMW-GOID preparation was 65 times less reactive when it was tested by skin prick test than the GOID preparation . A double-blind , placebo-controlled study was carried out in grass pollen-allergic patients with placebo ( 14 patients ) , GOID ( 15 patients ) , and HMW-GOID ( 13 patients ) . An additional group of 18 patients was treated by a rush schedule with a st and ardized orchard grass-pollen extract . A similar mean cumulative dose was administered with both allergoids . The fractionated allergoid only elicited minor systemic reactions similar to reactions elicited by placebo , whereas 20 % of patients treated by GOID and 5.5 % of patients receiving the st and ardized extract had a severe systemic reaction . For rhinitis , conjunctivitis , and asthma , the HMW-GOID and the st and ardized extract had a similar efficacy , significantly greater than placebo . GOID was less effective than the other two active treatments but was significantly more effective than placebo treatment for asthma and conjunctivitis Summary A new type of desensitising vaccine , enzyme potentiated was subjected to a double-blind r and omised study during the hay fever season . The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T ( Grazax , ALK-Abelló A/S , Hørsholm , Denmark ) in children aged 5 - 12 yr . The study was r and omized , double-blinded and placebo-controlled . Sixty children aged 5 - 12 yr suffering from grass pollen-induced rhinoconjunctivitis ( with or without asthma ) from five centres in two countries ( three in Germany and two in Spain ) participated in the study . They were r and omized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season . A total of 810 treatment-related adverse events were reported in the Grazax group . The majority of these were local reactions in the mouth or throat and were mostly mild ( 71 % ) to moderate ( 27 % ) in severity and resolved within days . Thirty-five ( 78 % ) subjects treated with Grazax and five ( 33 % ) treated with placebo reported at least one treatment-related adverse event . Oral pruritus , throat irritation , mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events . 62 % ( 28 of 45 ) of the actively treated subjects reported oral pruritus , 36 % ( 16 of 45 ) throat irritation , 31 % ( 14 of 45 ) mouth oedema and 22 % ( 10 of 45 ) ear pruritus . Two actively treated subjects withdrew from the study : one subject due to four adverse events ( moderate eye pruritus , moderate pharyngolaryngeal pain , moderate non-cardiac chest pain and moderate dysphagia ) and one subject due to a serious adverse event ( asthmatic attack ) . The subjects recovered completely from the events . In conclusion , in the present study , Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children Background Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side effects , but therapeutic efficacy of such extracts requires further evaluation . The aim of this study was to evaluate the efficacy and safety of immunotherapy with PURETHAL Mites ( PM ) , a single-strength glutaraldehyde-modified aluminum hydroxide – adsorbed extract of house-dust mites ( HDM ) . Methods In a multicenter , r and omized , placebo-controlled double-blind setting , HDM-allergic subjects ( n = 140 ) were treated with modified allergen extract or placebo over a 1-year period . The primary outcome parameter was a combined symptom and medication score ( clinical index score [ CIS ] ) . Secondary efficacy parameters were the result of a titrated conjunctival provocation test ( CPT ) , rhinitis/rhinoconjunctivitis quality of life ( RQL ) score , and serum concentrations of IgE and IgG against specific HDM allergens and a documentation of adverse events ( AE ) . Results We evaluated 140 patients ( 66 treatment and 74 placebo ) for clinical efficacy . The allergoid treatment for 1 year result ed in significantly greater CIS improvement and higher RQL scores . The response threshold in the titrated CPT ( p = 0.009 ) and the serum concentrations of IgG4 ( p < 0.001 ) against Dermatophagoides pteronyssinus allergens after treatment were also significantly different between groups . In total , 88 patients ( 46 PM/42 placebo ) out of a safety population of 145 reported 278 ( 158 PM/120 placebo ) AE . Except for local reactions , no specific AE appeared to be associated with PURETHAL Mites ( HAL-Allergy , Leiden , The Netherl and s ) . Conclusion The findings of this study indicate that allergen injection therapy with modified HDM extract is superior to placebo in allergic rhinitis therapy . The treatment was well tolerated and no serious drug-related AE were observed Background Calcium phosphate‐adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants Thirty‐eight adults with allergic rhinitis have been treated with a new partially purified extract of house dust mite ( Dermatophagoides pteronyssinus ) in a double‐blind placebo‐controlled trial . Patients were r and omized to active ( Pharmalgen ® , D. pteronyssinus ) and placebo ( histamine ) treatment by sensitivity to D. pteronyssinus on nasal challenge . In the actively treated group nasal symptoms , assessed by visual analogue score , improved ( P < 0.01 ) , sensitivity on nasal challenge with allergen was reduced ( P < 0.05 ) and weal size on skin‐prick test with allergen was reduced ( P < 0.01 ) , compared with the placebo group . These results occurred after 3 months of treatment . Reduction in target organ sensitivity occurred , while the serum level of D. pteronyssinus IgE rose in the active group from 14.2 to 22.5 PRU/ml ( geometric mean ) but did not change significantly in the placebo group . As anticipated , because of the treatment schedule used , a number of generalized allergic reactions were induced by injections , but all responded promptly and easily to treatment . These results suggest this is an effective form of therapy , which now offers us the opportunity to study the immunological mechanisms of hyposensitization and to devise a modified schedule causing fewer reactions Background : The efficacy of st and ardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens . Methods : Forty adults with European cypress-allergic rhinoconjunctivitis were r and omized to receive immunotherapy or a matched placebo . Specific immunotherapy was performed with a st and ardized , aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR ( arbitrary index of reactivity ) containing 54 µg of Jun a 1/ml ( Alustal , Stallergenes , France ) . Subcutaneous injections started in October 2000 . The maintenance dose was 0.30 ml of the 100-IR concentration per month . Rhinitis and conjunctivitis symptoms were rated according to a 4-point score . Results : Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001 ; 14 in each group completed year 2002 . A statistically significant improvement ( 41 % , p < 0.02 ) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season . Improvement in rhinitis ( 17 % ) was not significant . This significant improvement was greater at the peak of the 2002 pollen season ( 63 % , p < 0.01 ) . Conclusions : This study therefore indirectly vali date s the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted 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 Background : There is only very limited documentation of the efficacy and safety of high‐dose subcutaneous birch pollen immunotherapy ( IT ) in double‐blind , placebo‐controlled ( DBPC ) studies . Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America OBJECTIVE --To evaluate the efficacy and safety of immunotherapy ( hyposensitisation ) in patients with severe summer hay fever . DESIGN --A r and omised , double blind , placebo controlled study of a biologically st and ardised depot grass pollen extract . SETTING --Allergy clinic , Royal Brompton and National Heart Hospital , London . PATIENTS --40 adults ( mean age 35 years ) with a history of severe grass pollen allergy uncontrolled by st and ard antiallergic drugs . Patients with perennial asthma were specifically excluded . INTERVENTION-- Patients were r and omised to receive either an active preparation ( Alutard SQ , a grass pollen ( Phleum pratense ) extract ) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached . This maintenance dose was given once a month . MAIN OUTCOME MEASURES -- Clinical efficacy was evaluated by symptom and drug diary cards , visual analogue scores during the grass pollen season , and a postseasonal assessment by the patients and a doctor . Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment . RESULTS --There was a highly significant decrease ( median Alutard SQ v median placebo ( 95 % confidence interval for difference between medians ] in total symptom scores ( p=0.001 ) in the Alutard SQ treated group ( 360 v 928 ( 238 to 825 ] . Significant differences were also found in total drug use ( p=0.002 , 129 v 627 ( 178 to 574 ] . Visual analogue symptom scores were also reduced in the active group ( p=0.02 , 2.2 v 5.5 ( -4.8 to -0.5 ] . The postseasonal assessment , by either the doctor or the patients , showed a large improvement ( p less than 0.001 ) in favour of Alutard SQ . Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity ( p=0.001 ) , a 40 % decrease in early phase response ( p=0.02 ) , and a 57 % decrease in the late phase ( p=0.001 ) cutaneous response after intradermal allergen . A total of 523 active injections were given . There was one systemic reaction at 10 minutes after injection , which was rapidly reversed with intramuscular adrenaline . There was one mild delayed urticarial reaction at 2 1/2 hours . CONCLUSION --Immunotherapy is effective in patients with severe summer hay fever , but immediate anaphylactic reactions limit its use to specialised centres . Patient selection is extremely important , and chronic perennial asthma should be specifically excluded . As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary BACKGROUND 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 Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation . Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions . OBJECTIVES We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy . METHODS We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a r and omized , double-blind , placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy . All subjects received grass pollen immunotherapy injections for 2 years ( n = 13 ) , followed by a further 2 years of either active ( n = 7 ) or placebo ( n = 6 ) injections . Clinical outcomes included seasonal symptoms and use of rescue medication . Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies . Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells . RESULTS Clinical improvement was maintained after 2 years of discontinuation . Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation , inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged . CONCLUSION Grass pollen immunotherapy induces a sub population of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance ObjectiveS pecific immunotherapy is the only treatment for the underlying allergic disease in patients with respiratory allergies . The primary objective of this trial was to evaluate the efficacy and safety of two maintenance doses of immunologically enhanced , st and ardised quality ( SQ+ ) grass subcutaneous immunotherapy ( SCIT ) [ 4,000 SQ+ and 15,000 SQ+ ; AVANZ ® Phleum pratense ( ALK ) ] compared with placebo . Methods This was a r and omised , double-blind , placebo-controlled , phase II/III trial . The primary evaluation was based on the combined rhinoconjunctivitis score during the entire grass pollen season . Adult subjects with grass pollen-induced allergic rhinoconjunctivitis interfering with usual activities or sleep despite symptomatic medication use , were enrolled . Results Four hundred and fifty subjects were r and omised to receive either 4,000 SQ+ ( n = 150 ) , 15,000 SQ+ ( n = 152 ) or placebo ( n = 148 ) . The average grass pollen exposure was 27 grains/m3/day . No statistically significant differences between the active groups and the placebo group were found for clinical endpoints ( p > 0.05 ) . Highly statistically significant ( p < 0.001 ) increases in IgG4 and IgE-blocking factor were found for both active groups versus placebo . The most frequently reported adverse events were mild-to-moderate local injection-site reactions ; events were generally more frequent with 15,000 SQ+ than with 4,000 SQ+ and placebo . The most common adverse events leading to premature discontinuation from the trial were anaphylactic reactions ( one subject from the placebo group and five subjects from the 15,000 SQ+ group ) . Conclusions The inconclusive results were most probably influenced by a very low grass pollen season . Other factors such as the extent of the pre-seasonal treatment could potentially have contributed . The tolerability profile was acceptable for further development Background Two different regimens of subcutaneous immunotherapy ( IT ) , perennial or preseasonal , may be used in the treatment of seasonal allergy . The aim of this study was to compare the efficacy and safety of perennial IT ( PIT ) and preseasonal IT ( PSIT ) in patients suffering from seasonal rhinoconjunctivitis . Methods The study was planned as a r and omized , double-blind , comparative study on the efficacy and safety of PIT and PSIT . The study group comprised 120 patients allergic to grass and rye pollen . After the observational season they were r and omized to receive PIT or PSIT for 3 years . The effect of IT was assessed based on symptom severity and medication use recorded in diaries . Results Ninety-nine patients completed the study . No difference was seen between the groups regarding combined symptom medication score ( SMS ) in the first season of IT . During the second season , the difference between PIT and PSIT regarding combined SMS was 27.9 % ( p = 0.063 ) and reached 42.7 % ( p = 0.012 ) in favor of PIT in the third season . Both treatments had a similar safety profile . Conclusion PIT was more effective than PSIT in the treatment of rhinoconjunctivitis in patients allergic to grass and rye pollens . Clinical trials.gov registration number NCT01555736 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 House dust mite ( HDM ) allergy is associated with persistent allergic rhinitis ( AR ) and allergic asthma . OBJECTIVE To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease and report the AR results . METHODS Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were r and omized 1:1:1:1 to double-blinded daily treatment with 1 , 3 , 6 SQ-HDM or placebo . End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points . A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score ( TCRS ) > 0 ( ie , with AR symptoms and /or AR medication use during the 4-week baseline period ) . The subgroup was comprised of 498 subjects ( 82 % ) . RESULTS In the subgroup , the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 ( 95 % confidence interval -1.47 to -0.07 , relative difference 28.8 % , P = .0357 ) . Furthermore , a significant difference was found for the total score of the Rhinitis Quality of Life Question naire with St and ardized Activities RQLQ(S ) and for the individual domains : activities , sleep , non-nose and non-eye symptoms , and nasal symptoms . For the TCRS and Rhinitis Quality of Life Question naire score , a dose response was seen , with numerically lower , nonsignificant differences for 1 and 3 SQ-HDM . The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups . No safety concerns were observed . CONCLUSION Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Question naire score in subjects with AR present at baseline . The treatment was well tolerated . TRIAL REGISTRATION EudraCT , no 2006 - 001795 - 20 ; Clinical Trials.gov , identifier NCT00389363 Cluster immunotherapy represents an interesting alternative to conventional up‐dosing schedules because it allows achieving the maintenance dose within a shorter time interval . In this study , the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a r and omized , double‐blind , placebo‐controlled , multicenter study BACKGROUND Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis , although it is question able whether there is long-term benefit after the discontinuation of treatment . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective . During the three years of this trial , primary outcome measures were scores for seasonal symptoms and the use of rescue medication . Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge . Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells ( TH2 cells ) ( as evidence d by the presence of interleukin-4 messenger RNA ) . A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease . RESULTS Scores for seasonal symptoms and the use of rescue antiallergic medication , which included short courses of prednisolone , remained low after the discontinuation of immunotherapy , and there was no significant difference between patients who continued immunotherapy and those who discontinued it . Symptom scores in both treatment groups ( median areas under the curve in 1995 , 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy ; P=0.60 ) were markedly lower than those in the group that had not received immunotherapy ( median value in 1995 , 2863 ) . Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation , there was a sustained reduction in the late skin response and associated CD3 + T-cell infiltration and interleukin-4 messenger RNA expression . CONCLUSIONS Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity BACKGROUND To assess the efficacy and safety of sublingual immunotherapy in patients with allergic rhinitis/conjunctivitis , a double blind placebo controlled study was performed . METHODS AND RESULTS Fifty-seven ( 57 ) patients with a well-documented history of seasonal grass pollen allergy were evaluated in a DBPC trial over a period of 10 months ( January to November 1995 ) with a view to investigating the efficacy and safety of sublingual immunotherapy with a grass pollen extract , 9,500 BU/ml . The course of treatment consisted of an incremental phase of approximately 3 weeks followed by a twice weekly maintenance dosage of 9,500 BU . Compared with the placebo group ( 30 patients ) , the group treated with grass pollen extract ( 27 patients ) showed a significant ( p < 0.03 ) lower mean severity of allergic complaints , i.e. sneezing , and itchy nose , a watery runny nose and itching of the eyes during the maximum pollen counts of the season . The use of anti-allergic medication was similar in the two groups . Both groups showed a significant increase in grass-pollen-specific IgG serum levels . However , the increase shown in the patients treated with grass pollen extract occurred earlier in the season and was significantly ( p < 0.002 ) higher than the increase detected in the placebo group . Side effects were limited to a small number of generally mild local reactions . CONCLUSIONS The treatment with sublingually applied grass pollen extract in patients suffering from allergic rhinoconjunctivitis caused by grass pollen was well tolerated and served to reduce the severity of allergic complaints , without reducing the consumption of anti-allergic medication Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy . Design Double blind r and omised placebo controlled parallel group study . Setting Hospital in Hampshire . Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years ; all were skin prick test positive to timothy grass pollen . 90 r and omised to active treatment ; 93 r and omised to placebo . Interventions Active treatment : two injections of enzyme potentiated desensitisation , given between eight and 11 weeks apart , each comprising 200 Fishman units of β glucuronidase , 50 pg 1,3-cyclohexanediol , 50 ng protamine sulphate , and a mixed inhaled allergen extract ( pollen mixes for trees , grasses , and weeds ; allergenic fungal spores ; cat and dog d and ers ; dust and storage mites ) in a total volume of 0.05 ml of buffered saline . Placebo : two injections of 0.05 ml buffered saline solution . Main outcome measures Proportion of problem-free days ; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season . Results The active treatment group and the placebo group did not differ in the proportion of problem-free days , quality of life scores , symptom severity scores , change in quantitative skin prick provocation threshold , or change in conjunctival provocation threshold . No clinical ly significant adverse reactions occurred . Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study Background The 300IR ( index of reactivity ) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis ( ARC ) . Here , we report maintenance of efficacy and safety over 2 years following treatment discontinuation . Methods R and omized , double-blind , placebo-controlled , parallel-group , multicenter Phase 3 trial in patients aged 18–50 years with ARC . During study years 1–3 , patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo , according to a discontinuous pre- and coseasonal protocol . Study years 4 and 5 were treatment-free . In response to health authorities ’ recommendations , the daily combined score ( DCS ) was assessed in a post-hoc analysis as the efficacy endpoint . Components of the DCS were daily rhinoconjunctivitis total symptom score ( DRTSS ) and daily rescue medication score ( DRMS ) . Results 633 patients with ARC were r and omized to placebo ( n = 219 ) or 300IR 5-grass pollen tablet , beginning 4 months ( 4 M , n = 207 ) or 2 months ( 2 M , n = 207 ) prior to the estimated start of the grass pollen season and continuing until season ’s end . During the first post-treatment year , a statistically significant difference versus placebo in least squares ( LS ) mean DCS was noted in patients previously receiving active treatment ( 300IR ( 2 M ) point estimate : −0.16 , 95 % confidence interval ( CI95 % ) : [ −0.26 , −0.06 ] , p = 0.0019 ; −31.1 % ; 300IR ( 4 M ) point estimate : −0.13 , CI95 % : [ −0.23 , −0.03 ] , p = 0.0103 , −25.3 % ) . During the second post-treatment year , patients in the 300IR ( 4 M ) group , but not the 300IR ( 2 M ) group , showed a statistically significant difference in LS mean DCS versus placebo ( point estimate : −0.11 , CI95 % : [ −0.21 ; 0.00 ] , p = 0.0478 , −28.1 % ) . This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment . A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years ( except for DRTSS in year 5 ) . In the absence of any active treatment , the safety profile was similar in the active groups versus placebo group during either post-treatment year . Conclusions In adults with grass pollen-associated ARC , 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season ’s end demonstrated efficacy across all variables during active treatment , and this effect was prolonged for up to 2 years post-treatment . Trial registration Clinical Trials.gov identifier : NCT00418379 BACKGROUND Although sublingual immunotherapy ( SLIT ) has been demonstrated to be a safe and efficient treatment in children with seasonal allergic rhinitis ( AR ) , there is little evidence on the efficacy of SLIT with house-dust-mite ( HDM ) extract in children with isolated perennial AR . OBJECTIVES We sought to assess the clinical efficacy and safety of HDM-SLIT in children with isolated allergic rhinitis-conjunctivitis mono-sensitized to HDM without asthma symptoms . METHODS Twenty-two children ( aged 5 - 10 years ) with perennial AR and conjunctivitis symptoms mono-sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae were enrolled . During a 2 months run-in period , symptom and medication scores , lung functions , bronchial hyperreactivity , nasal provocation and skin prick tests were evaluated . Subjects were r and omized to active or placebo using a double-blind method . A total of eighteen subjects were r and omised to receive either active SLIT or placebo for 12 months . Daily symptom and medication scores , baseline lung functions , bronchial hyperreactivity , nasal provocation and skin prick tests were recorded and re-evaluated at the end of treatment . RESULTS After one year of treatment , no significant differences were detected in the between groups and within group comparisons based on total rhinitis symptom/medication scores ( p > 0.05 ) . Skin reactivity to Dermatophagoides pteronyssinus was significantly reduced in HDM-SLIT compared to placebo group ( p = 0.018 ) . A significant reduction in nasal sensitivity was observed in SLIT group after one year treatment when compared to baseline ( p = 0.04 ) . Total conjunctivitis symptoms were reduced significantly in both active and lacebo group at the end of treatment compared to baseline . The proportion of patients with non-specific bronchial hyperreactivity increased to almost 3-fold in placebo group compared to baseline . CONCLUSION HDM-SLIT was not superior to placebo in reducing isolated rhinoconjunctivitis symptoms within 12 months of treatment . However , HDM-SLIT has a modulating effect on allergen-specific nasal and skin reactivity in isolated perennial AR children . CLINICAL TRIAL REGISTRATION The trial was registered at Anzctr.org.au number , ACTRN12613000315718 BACKGROUND Immunotherapy with the SQ-st and ardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis . Allergic asthma and rhinoconjunctivitis are closely linked , and a strategy combining treatment of the upper and lower airways is recommended . OBJECTIVE To investigate the efficacy of treatment with the grass tablet on grass pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children . METHODS A total of 253 children age 5 to 16 years , with grass pollen-induced rhinoconjunctivitis with/without asthma , were r and omized 1:1 to active treatment or placebo . Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season . Symptomatic medication was provided as relief medication to both groups in a stepwise fashion . Primary endpoints were rhinoconjunctivitis symptom and medication scores . RESULTS The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups . The differences in medians relative to placebo were 24 % , 34 % , and 64 % in favor of active treatment . The immunologic response was similar to that observed in adults . The most common adverse reaction was oral pruritus , reported by 40 subjects ( 32 % ) in the active and 3 ( 2 % ) in the placebo group . Six subjects withdrew because of adverse events . No serious adverse events were assessed as treatment-related . CONCLUSION Immunotherapy with the grass tablet reduced grass pollen-induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response , consistent with treatment of the underlying allergic disease . The treatment was well tolerated Background Allergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases . We and others have previously demonstrated that intralymphatic immunotherapy ( ILIT ) , a less time-consuming alternative to conventional subcutaneous immunotherapy ( SCIT ) , is safe and effective . However , this has recently been disputed . The aim of this study was therefore to exp and our previous trial , further assessing the safety and efficacy of ILIT . Methods Thirty-six patients with pollen-induced rhinoconjunctivitis were r and omised to receive three intralymphatic inguinal injections of active allergen ( 1000 SQ-U birch- or grass-pollen ) or placebo . Clinical effects , safety and circulating immunological markers were assessed before , 4 weeks after treatment and at the end of the consecutive pollen season . Results No moderate or severe reactions were recorded following ILIT . Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms , as compared to placebo ( p = 0.05 ) . In a subgroup of these patients ( “ improved ” ) , a reduction in nasal symptoms following nasal allergen provocation was also demonstrated . No changes in total IgE or IgG4 were found . However , the affinity of allergen specific IgG4 following active treatment was significantly increased , as compared to non-improved patients ( p = 0.04 ) . This could be correlated with clinical improvement , on an individual level . Conclusions This double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis , markedly reducing seasonal allergic symptoms . Trial registration EudraCT : 2009 - 016815 - Summary The present guideline ( S2k ) on allergen-specific immunotherapy ( AIT ) was established by the German , Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology , dermatology and venereology , pediatric and adolescent medicine , pneumology as well as a German patient organization ( German Allergy and Asthma Association ; Deutscher Allergie- und Asthmabund , DAAB ) according to the criteria of the Association of the Scientific Medical Societies in Germany ( Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften , AWMF).AIT is a therapy with disease-modifying effects . By administering allergen extracts , specific blocking antibodies , toler-ance-inducing cells and mediators are activated . These prevent further exacerbation of the allergen-triggered immune response , block the specific immune response and attenuate the inflammatory response in tissue . Products for SCIT or SLIT can not be compared at present due to their heterogeneous composition , nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients . Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed ( depot ) extracts , as well as chemically modified allergens ( allergoids ) as depot extracts . Allergen extracts for SLIT are used in the form of aqueous solutions or tablets . The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints . The EMA stipulates combined symptom and medication scores as primary endpoint . A harmonization of clinical endpoints , e. g. , by using the combined symptom and medication scores ( CSMS ) recommended by the EAACI , is desirable in the future in order to permit the comparison of results from different studies . The current CONSORT recommendations from the ARIA/GA2LEN group specify st and ards for the evaluation , presentation and publication of study results .According to the Therapy allergen ordinance ( TAV ) , preparations containing common allergen sources ( pollen from grasses , birch , alder , hazel , house dust mites , as well as bee and wasp venom ) need a marketing authorization in Germany . During the marketing authorization process , these preparations are examined regarding quality , safety and efficacy . In the opinion of the authors , authorized allergen preparations with documented efficacy and safety , or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA st and ards , should be preferentially used . Individual formulations ( NPP ) enable the prescription of rare allergen sources ( e.g. , pollen from ash , mugwort or ambrosia , mold Alternaria , animal allergens ) for specific immunotherapy . Mixing these allergens with TAV allergens is not permitted . Allergic rhinitis and its associated co-morbidities ( e. g. , bronchial asthma ) generate substantial direct and indirect costs . Treatment options , in particular AIT , are therefore evaluated using cost-benefit and cost-effectiveness analyses . From a long-term perspective , AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy , but is heavily dependent on patient compliance . Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups . Data from controlled studies differ in terms of scope , quality and dosing regimens and require product-specific evaluation . Therefore , evaluating individual preparations according to clearly defined criteria is recommended . A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed . The website of the German Society for Allergology and Clinical Immunology ( www.dgaki.de/leitlinien/s2k-leitlinie-sit ; DGAKI : Deutsche Gesellschaft für Allergologie und klinische Immunologie ) provides tables with specific information on available products for AIT in Germany , Switzerl and and Austria . The tables contain the number of clinical studies per product in adults and children , the year of market authorization , underlying scoring systems , number of r and omized and analyzed subjects and the method of evaluation ( ITT , FAS , PP ) , separately given for grass pollen , birch pollen and house dust mite allergens , and the status of approval for the conduct of clinical studies with these products . Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and , in childhood and adolescence , in a few trials . Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children . Only a few controlled trials , independent of age , are available for mold allergy ( in particular Alternaria ) . With regard to animal d and er allergies ( primarily to cat allergens ) , only small studies , some with method ological deficiencies are available . Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date . SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma ( GINA ) 2007 and intermittent and mild persistent asthma ( GINA 2005 ) and it is recommended as a treatment option , in addition to allergen avoidance and pharmacotherapy , provided there is a clear causal link between respiratory symptoms and the relevant allergen . The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children , whilst its efficacy in tree pollen allergy has only been shown in adults . New controlled trials ( some with high patient numbers ) on house dust mite allergy provide evidence of efficacy of SLIT in adults . Compared with allergic rhinoconjunctivitis , there are only few studies on the efficacy of SLIT in allergic asthma . In this context , newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children , adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults . Aspects of secondary prevention , in particular the reduction of new sensitizations and reduced asthma risk , are important rationale s for choosing to initiate treatment early in childhood and adolescence . In this context , those products for which the appropriate effects have been demonstrated should be considered . SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled ( DBPC ) study . At present , clinical trials are underway for the indication in asthma due to house dust mite allergy , some of the results of which have already been published , whilst others are still awaited ( see the DGAKI table “ Approved/potentially completed studies ” via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit ( according to www . clinical trialsregister.eu ) ) . When establishing the indication for AIT , factors that favour clinical efficacy should be taken into consideration . Differences between SCIT and SLIT are to be considered primarily in terms of contraindications . In individual cases , AIT may be justifiably indicated despite the presence of contraindications . SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction . Patients must be fully informed about the procedure and risks of possible adverse events , and the details of this process must be documented ( see “ Treatment information sheet ” ; available as a h and out via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit ) . Treatment should be performed according to the manufacturer‘s product information leaflet . In cases where AIT is to be performed or continued by a different physician to the one who established the indication , close cooperation is required in order to ensure that treatment is implemented consistently and at low risk . In general , it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials . Treatment adherence among AIT patients is lower than assumed by physicians , irrespective of the form of administration . Clearly , adherence is of vital importance for treatment success . Improving AIT adherence is one of the most important future goals , in order to ensure efficacy of the therapy . Severe , potentially life-threatening systemic reactions during SCIT are possible , but – providing all safety measures are adhered to – these events are very rare . Most adverse events are mild to moderate and can be treated well . Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT . Systemic reactions have been described in SLIT , but are seen far less often than with SCIT . In terms of anaphylaxis and other severe systemic reactions , SLIT has a better safety profile than SCIT.The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel , adhering to safety st and ards and prompt use of emergency measures , including early administration of i. m. epinephrine . Details on the acute management of anaphylactic reactions can be found in the current S2 guideline on anaphylaxis issued by the AWMF ( S2-AWMF-LL Registry Number 061 - 025).AIT is undergoing some innovative developments in many areas ( e. g. , allergen characterization , new administration routes , adjuvants , faster and safer dose escalation protocol s ) , some of which are already being investigated in clinical trials . Cite this as Pfaar O , Sustained efficacy over three pollen seasons of pre‐ and co‐seasonal treatment with 300IR 5‐grass pollen sublingual tablet has been demonstrated in adults with moderate‐severe grass pollen‐associated allergic rhinoconjunctivitis OBJECTIVE To observe the adverse effects of specific immunotherapy ( SIT ) with st and ardized dust mite allergen preparation in the treatment of allergic rhinitis . METHOD Three hundred and eighty-six patients with allergic rhinitis who received subcutaneous SIT with a st and ardized dust mite allergen preparation were enrolled in this study . The patients were treated for at least 15 weeks , adverse effects after each injection from dosing phase to maintenance phase were recorded and incidence of adverse effects were analyzed . RESULT Of all the patients , adverse reactions occurred in 42 patients ( 10 . 9%),10 local reactions ( 2 . 6 % ) and 36 systemic side effects ( 9 . 3 % ) which included 34 mild , 1 moderate and 1 severe side effects ( no fatal ) were reported respectively . None had anaphylactic shock . Among three treatment options , incidence of routine program was the highest (21.1%),followed by adult cluster program ( 11 . 9 % ) , adverse effects of children cluster program was the least ( 1 . 5 % ) . The adverse effects often happened in the middle and late phase of does addition period and early phase of maintenance period . CONCLUSION SIT with st and ardized dust mite allergen preparation in the treatment of allergic rhinitis is a safe and effective treatment by complying with the guidelines and taking specific interventions BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe 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 OBJECTIVE To investigate the health and monetary consequences of treating allergy with specific immunotherapy ( SIT ) compared with symptomatic treatment/st and ard care among patients with grass pollen or mite allergy . METHODS We performed an economic analysis based on 253 grass- and /or mite allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit , Aarhus University Hospital and at a specialist practice in Aarhus . Relevant data were collected before , during and after SIT treatment from the national health service based on each patient 's personal identification number and medical records and from a specifically design ed question naire . A cost-benefit analysis including direct and indirect costs before , during and after SIT was performed . In addition direct costs were related to the clinical effect ( improvement in well-being ) in the form of a cost-effectiveness analysis . RESULTS The direct cost per patient/year before SIT ( equivalent to st and ard care ) was DKK 2,580 . The investment in SIT was DKK 27,545 ( in present values ) per patient over a 4-year period . After SIT the cost was reduced to DKK 1,072 per patient/year . In the long term , prospect i ve introduction of SIT incurred additional present-value direct costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of improved well-being . However , when indirect costs were included in the economic evaluation SIT was shown to be net beneficial . CONCLUSION This study reveals that SIT is associated with initial re source investments and subsequent re source savings in the long term compared with st and ard care . When all consequences are measured in monetary terms , and assuming that sick days are associated with a loss of productivity , this analysis suggests that SIT increases societal welfare . This conclusion also holds if there is no loss of productivity Objectives To evaluate the effectiveness of specific immunotherapy ( SIT ) in patients with severe house dust mite (HDM)‐induced perennial allergic rhinitis using diary cards and objective endpoints BACKGROUND A new depot allergoid of house dust mite ( Dermatophagoides pteronyssinus - D.pt ) has been created in line with the principles and methodology established in the successful development of pollen allergoids . A two-year double-blind placebo-controlled clinical trial , with one further follow-up year of active treatment , has been conducted to assess clinical efficacy and tolerance . METHODS 40 patients ( 20 verum and 20 placebo ) with IgE-mediated mite allergy and a history of moderate to severe perennial symptoms of rhinoconjunctivitis with or without asthma participated in a 2-year r and omized , double-blind , placebo-controlled trial . Actively treated patients were included in a follow-up year . Active treatment was performed with an aluminium hydroxide adsorbed house dust mite allergoid . Parameters for baseline data and clinical efficacy : nasal challenge , quantitative skin prick testing , Visual Analog Scale ( VAS ) , patients ' diaries , physician 's assessment of patients ? health condition , symptoms and use of anti-allergic medication as well as adverse reactions and changes in specific IgG4 and IgE antibodies . RESULTS The trial detected superiority ( p < 0.05 ) of mite depot allergoid versus placebo with regard to VAS and symptom intensity sum score in patients who needed anti-allergic medication in the baseline period . Significant differences ( p < 0.05 ) between verum and placebo groups were also seen for patients ' reactivities to nasal challenges and prick tests with allergen . The blinded assessment by the physician documented a significant difference ( p < 0.05 ) between the groups in favour of active treatment . After reaching the maximum dose as well as after 12 and 24 months , specific IgG4 antibody concentrations were significantly elevated in the verum group ( p < 0.05 ) by comparison with placebo . Local reactions were less frequent in the verum group and no systemic adverse reactions occurred . A third year of active treatment result ed in further improvement and documented the advantage of booster therapy to stabilize the clinical success . CONCLUSION Specific immunotherapy with a mite depot allergoid induced significant clinical improvements versus placebo . Safety was assessed as excellent , and no systemic adverse reactions occurred Background The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America BACKGROUND Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy , there is no report of a double-blind placebo-controlled trial with st and ardized pollen extract in seasonal respiratory allergy from India . In the agricultural area of eastern India , Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season . OBJECTIVE The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with st and ardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm . Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected . A symptom-medication score ( based on a question naire and diary ) was correlated with pollen counts as recorded in a Burkard sample r. Eighteen subjects were r and omized to a specific immunotherapy ( SIT ) group receiving regular injections containing st and ardized allergen extract and 17 to a placebo control group . Changes in the level of specific immunoglobulin ( Ig ) E , IgG1 , and IgG4 were recorded at 3-month intervals . Measurement of wheal diameter , total IgE level and forced expiratory volume in 1 second ( FEV1 ) were performed before starting and a month after finishing therapy . RESULTS The SIT group showed decreases of 33.5 % and 57 % from the baseline symptom-medication scores during the first and second treatment season , respectively . This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels , and significant increases in FEV , , specific IgGI ( 1.95 - 3.2 times higher ) and IgG4 ( 21.24 - 30.83 times higher ) . There were no significant changes in total IgE levels . The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases ( to Saccharum officinarum pollen grain and Alternaria species spores ) . The rate of local adverse reactions was 0.024 % . CONCLUSION After a 2-year study , allergen immunotherapy with st and ardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization BACKGROUND Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years . OBJECTIVE We sought to improve immunotherapy by using intralymphatic allergen administration ( intralymphatic immunotherapy [ ILIT ] ) and by targeting allergen to the MHC class II pathway . METHODS Recombinant major cat d and er allergen Fel d 1 was fused to a translocation sequence ( TAT ) and to part of the human invariant chain , generating a modular antigen transporter ( MAT ) vaccine ( MAT-Fel d 1 ) . In a r and omized double-blind trial ILIT with MAT-Fel d 1 in alum was compared with ILIT with placebo ( saline in alum ) in allergic patients ( Clinical Trials.govNCT00718679 ) . RESULTS ILIT with MAT-Fel d 1 elicited no adverse events . After 3 placebo injections within 2 months , nasal tolerance increased less than 3-fold , whereas 3 intralymphatic injections with MAT-Fel d 1 increased nasal tolerance 74-fold ( P < .001 vs placebo ) . ILIT with MAT-Fel d 1 stimulated regulatory T-cell responses ( P = .026 vs placebo ) and increased cat d and er-specific IgG(4 ) levels by 5.66-fold ( P = .003 ) . The IgG(4 ) response positively correlated with IL-10 production ( P < .001 ) . CONCLUSION In a first-in-human clinical study ILIT with MAT-Fel d 1 was safe and induced allergen tolerance after 3 injections Forty-five grass pollen-allergic patients were r and omly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis . Eleven patients were treated with placebo ( group 1 ) , 19 patients ( group 2 ) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure , and 15 other patients were treated with a st and ardized orchard grass-pollen extract ( group 3 ) . Because of a different immunotherapy schedule , only patients placed in groups 1 and 2 received the extracts in a double-blind fashion . Rush immunotherapy was performed in 3 to 6 days , and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season . During the season , a coseasonal treatment was administered . Systemic reactions occurred during the rush protocol in 36.8 % of patients treated with allergoid and 20 % of patients who received the st and ardized extract . Only patients treated with allergoid had systemic reactions during maintenance dose . The reactions observed with the st and ardized extract were more severe . Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units . Symptoms and medication scores during the peak of the season were analyzed . Patients treated with the st and ardized allergen had a significant reduction of the number of days of symptoms during the month of June ( 9.5 + /- 6.7 days ; p less than 0.005 ) and of medication scores ( 1.3 + /- 1.4 ; p less than 0.01 ) compared to patients receiving placebo ( 19.4 + /- 8.1 days ; medication score , 2.8 + /- 2.1 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Immunotherapy in elderly patients is controversial , and there is still no evidence supporting this treatment 's safety and efficacy in this population . This study was performed to evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite ( HDM ) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM 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 Background Immunotherapy is a recognized treatment for allergic respiratory diseases BACKGROUND Short-term immunotherapy ( STI ) can be beneficial for patients who are noncompliant with long-term specific immunotherapy . OBJECTIVE The efficacy and tolerance of STI with seven preseasonal injections of molecular st and ardized allergens from grass and rye pollen has been investigated in a double-blind , placebo-controlled multicenter study with 87 patients at 12 German University hospitals . METHODS Symptoms of the eyes , nose , and bronchi and use of symptomatic drugs were documented daily in diaries by patients with allergic rhinitis to grass and /or rye pollen and without bronchial asthma . Patients were monitored by skin prick test titration and measurement of levels of specific IgE and IgG4 . RESULTS The median nasal score for the 10 weeks with the strongest symptoms during the grass pollen season was significantly lower ( p = 0.014 ) with 35.0 for STI ( n = 41 ) versus 69.0 for placebo ( n = 40 ) ; the overall symptom score was 54.0 for STI versus 97.5 for placebo ( p = 0.020 ) . Only STI-treated patients exposed to less than 40 pollen grains per cubic meter per week showed a significantly lower nasal symptom score of 39.0 versus 75.0 for placebo ( p = 0.006 ) ; these patients also had fewer nasal symptoms and less use of topical nasal drugs ( p < 0.001 ) . The threshold dose in skin prick tests was significantly higher , being 9.06 histamine equivalent for skin prick test ( HEP ) for STI-treated patients who received the maximum dose ( n = 22 ) versus 4.33 HEP for placebo ( p = 0.005 ) . Specific IgE levels were significantly higher , being 55.9 SU/ml for STI versus 39.2 SU/ml for placebo after seven injections ( p = 0.006 ) and level of specific IgG4 was 5.36 % for STI versus 1.28 % for placebo ( p < 0.001 ) . No severe systemic reactions were observed . CONCLUSION STI with seven preseasonal injections with molecular st and ardized allergens is effective and well tolerated Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis ; conventional regimens are lengthy , however , reducing convenience and cost-effectiveness . This study evaluated the efficacy and safety of an ultrashort course ( four doses ) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate ( Allergy Therapeutics , Worthing , U.K. ) monophosphoryl lipid A ( MATA MPL ) . Subjects were r and omized to receive four injections of either Grass MATA MPL ( n = 514 ; 300 - 2000 st and ardized units/injection ) or placebo ( n = 514 ) before the grass pollen season . They used electronic diaries to record allergy symptoms and medication use during the pollen season . The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks . The injection course was completed by 95.3 and 97.7 % of the Grass MATA MPL and placebo groups , respectively , and was well tolerated . Grass MATA MPL treatment afforded a 13.4 % benefit over placebo in the 4 peak pollen weeks ( p = 0.0038 ) . The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9 % ( p = 0.0031 ) . Significant benefits over placebo were observed in subjects with severe symptoms ( 17.1 % ; p = 0.0023 ) , in those who had a history of allergic rhinoconjunctivitis for up to 35 years ( up to 37.2 % ; p = 0.0059 ) and at sites with a higher burden of disease ( 38.3 % ; p < 0.0001 ) . The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms 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 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 The efficacy and safety of five-grass pollen 300IR sublingual immunotherapy ( SLIT ) tablets ( Stallergènes SA , France ) have previously been demonstrated in paediatric patients . This report presents additional data concerning efficacy at pollen peak , efficacy and safety according to age , nasal and ocular symptoms , use of rescue medication , satisfaction with treatment and compliance . Children ( 5 - 11 yr ) and adolescents ( 12 - 17 yr ) with grass pollen-allergic rhinoconjunctivitis were included in a multinational , r and omized , double-blind , placebo-controlled study and received either a 300IR five-grass pollen tablet or placebo daily in a pre- ( 4 months ) and co-seasonal protocol . The severity of six symptoms ( sneezing , rhinorrhoea , nasal congestion , nasal and ocular pruritis , and tearing ) was scored , and rescue medication use was recorded daily during the pollen season . Patient satisfaction was recorded at the season end . A total of 161 children and 117 adolescents were evaluated ( n = 267 ) . 300IR SLIT was effective over the whole season ( p = 0.0010 ) and at the pollen peak ( p = 0.0009 ) . The adjusted mean difference between 300IR and placebo groups was significant for both nasal ( p = 0.0183 ) and ocular ( p < 0.0001 ) symptoms . Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak ( both p < 0.05 ) . More patients in the SLIT group were satisfied with their treatment compared to placebo ( 83.2 % vs. 68.1 % , p = 0.0030 ) , and compliance was high ( SLIT 93.9 % of patients were compliant , placebo 94.8 % of patients were compliant ) . SLIT was well tolerated by children and adolescents . 300IR five-grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis BACKGROUND Allergen immunotherapy ( AIT ) has been thoroughly documented in r and omized controlled trials ( RCTs ) . It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis , allergic asthma and insect sting allergy . However , there is a high degree of clinical and method ological heterogeneity among the endpoints in clinical studies on AIT , for both subcutaneous and sublingual immunotherapy ( SCIT and SLIT ) . At present , there are no commonly accepted st and ards for defining the optimal outcome parameters to be used for both primary and secondary endpoints . METHODS As elaborated by a Task Force ( TF ) of the European Academy of Allergy and Clinical Immunology ( EAACI ) Immunotherapy Interest Group , this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis . RESULTS Based on a thorough literature review , the TF members have outlined recommendations for nine domains of clinical outcome measures . As the primary outcome , the TF recommends a homogeneous combined symptom and medication score ( CSMS ) as a simple and st and ardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner . All outcomes , grouped into nine domains , are review ed . CONCLUSION A st and ardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required . The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis BACKGROUND Allergen-specific immunotherapy uses aqueous extracts of natural source material s as a basis for preparations to down regulate the allergic response . Recombinant DNA technology has enabled the cloning of many allergens , thus facilitating investigations aim ed at improving efficacy and safety of immunotherapy . OBJECTIVE To determine the effectiveness of a mixture of 5 recombinant grass pollen allergens in reducing symptoms and need for symptomatic medication in patients allergic to grass pollen . METHODS A r and omized , double-blind , placebo-controlled study of subcutaneous injection immunotherapy was performed in subjects with allergic rhinoconjunctivitis , with or without asthma . Primary endpoint was a symptom medication score compiled from separate symptom and medication scores . Secondary endpoints included a rhinitis quality of life question naire , conjunctival provocation , and specific antibody responses . RESULTS The symptom medication score showed significant improvements in subjects receiving recombinant allergens as opposed to placebo , with reductions in both symptoms and medication usage . The rhinitis quality of life question naire revealed clinical ly relevant significant improvements in overall assessment and in 5 of 7 separate domains , and conjunctival provocation showed a clear trend in favor of active treatment . All treated subjects developed strong allergen-specific IgG(1 ) and IgG(4 ) antibody responses . Some patients were not sensitized to Ph l p 5 but nevertheless developed strong IgG antibody responses to that allergen . CONCLUSION A recombinant allergen vaccine can be a effective and safe treatment to ameliorate symptoms of allergic rhinitis . The clinical benefit is associated with modification of the specific immune response with promotion of IgG(4 ) and reduction of IgE antibodies consistent with the induction of IL-10-producing regulatory T cells Specific immunotherapy is ineffective with unst and ardized mold extracts . A double-blind , placebo-controlled study was performed in 24 patients ( 5 to 56 years of age ) only allergic to Alternaria . The extract was st and ardized by isoelectric focusing , crossed immunoelectrophoresis , crossed radioimmunoelectrophoresis , RAST inhibition , and skin tests and contained allergen Alternaria major allergen a I and antigen B. Thirteen patients received the active treatment , and 11 received the placebo . Immunotherapy was started by a 2-day rush protocol ; maintenance injections were administered for 1 year . The patient 's self-evaluation of the treatment was significantly ( p less than 0.001 ) lower in the placebo-treated group . Global symptom-medication scores , including asthma and rhinoconjunctivitis , were significantly ( p less than 0.005 ) lower in the actively treated group . Nasal challenges with Alternaria extract were performed before immunotherapy and after 1 year of treatment . There was no difference in the placebo-treated group and a significantly ( p less than 0.01 ) increased mean provocative dose in the actively treated group . Skin tests were significantly reduced in the actively treated group . Specific IgG increased significantly in the actively treated group and were stable in the placebo-treated group . There was a significant correlation between nasal challenges and nasal symptom-medication scores ( p less than 0.03 ) or the patient 's self-evaluation of efficacy ( p less than 0.05 ) . This study demonstrated that patients only sensitized to Alternaria benefit from specific immunotherapy with a st and ardized Alternaria extract 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 Specific local immunotherapy has been recently introduced as an alternative to classic subcutaneous immunotherapy in treatment of allergic rhinitis . In this study , the effects of sublingual immunotherapy ( SLIT ) on symptoms and medication score and skin prick test evaluation of patients with allergic rhinitis were investigated . In this placebo controlled trial , twenty four patients aged 5 - 18 years old with grass pollen induced rhinitis and sensitive to rye grass by positive skin prick test received r and omly sublingual extract of rye grass or placebo for 6 months . Symptom and medication scores and adverse effects of SLIT were assessed during treatment . Skin prick test induced wheal at the beginning and the end of therapy were also measured . Data were analyzed with SPSS software . We found significant reduction of symptoms in intervention group from 21st week of immunotherapy ( p<0.05 ) . Medication scores were also reduced after 16th week ( p<0.05 ) , adverse effects were low and insignificant in both groups . Erythema induced diameter with skin prick test for grass and rye grass was significantly reduced in SLI group after immunotherapy . This study indicates that SLIT in grass-pollen rhinitis is well tolerated , improves overall clinical symptoms , and reduces drug consumes . We recommend this therapy as a safe therapy in patients with allergic rhinitis 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 Background Immunotherapy ( IT ) with modified allergens reduces allergic rhinitis ( AR ) symptoms and medications requirements . Improvement of quality of life ( QOL ) is a key point in the treatment of AR . The aim of this study was to provide evidence of changes related to the patient 's QOL ( well‐being ) induced by a modified ( depigmented glutaraldehyde‐polymerized ) therapeutic vaccine and of its safety 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 The efficacy and tolerance of short‐term immunotherapy ( STI ) by seven preseasonal injections of tree‐pollen allergens ( ALK7 FrUhbltihermischung ® ) was investigated in a double‐blind , placebo‐controlled , multicenter study with 111 rhinoconjunctivitis patients . Nasal and bronchial symptoms simultaneously analyzed , and nasal symptoms as a single end point , but not the overall score of nasal , bronchial , and conjunctival symptoms , showed a significantly lower increase with STI during birch‐pollen exposure ( both P= 0.033 , n= 105 , Mann‐Whitney U‐test ) . However , a selective analysis with patients from centers with high recruitment figures ( nS10 patients , n=29 STI , n=32 placebo ) showed a significantly lower increase of nasal , bronchial , and overall symptom score ( STI 11.0 vs placebo 18.0 , P=0.001 , U‐test ) . STI had equidirected effects on conjunctival , nasal , and bronchial symptoms analyzed as multiple end points , although conjunctival symptoms were not significantly different as a single end point . The seasonal increase in drug use was reduced by 62 % in the STI group compared with placebo ( P=0.032 , Mest ) , Specific IgG4 increased only after STI ( P<0,001 ) ; IgE was not significantly different . Eosinophil cationic protein remained unchanged with STI , but significantly increased with placebo in the pollen season ( P = Qm3 ) . STI was well tolerated . In conclusion , STI was shown to be efficacious and safe for the treatment of patients with tree‐pollen rhinoconjunctivitis 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 A double‐blind , placebo‐controlled study was conducted to evaluate the efficacy and safety of immunotherapy ( IT ) with a partially purified alginate‐conjugated extract of Parietaria judaica ( Conjuvac ® Parietaria , Dome/Hollister‐Stier ) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen . Eighteen patients ( 10 women , 8 men , mean age 35 years ) received active treatment and 17 ( 10 women , 7 men , mean age 42.5 years ) received placebo . Actively treated patients had significantly lower nasal symptom/medication scores ( running nose P= 0.0087 and sneezing P= 0.048 ) during the Parietaria pollen season . Significant decreases in specific skin ( P > 0.01 ) , nasal ( P > 0.05 ) , and conjunctival ( P > 0.01 ) reactivity to the Parietaria extract and significant increases of specific IgG ( P > 0.001 ) , IgGI ( P > 0.001 ) , and IgG4 ( P > 0.001 ) in actively treated patients , but not in placebo , were found . IT was well tolerated , the active extract inducing five mild systemic reactions ( four rhinitis and one urticaria ) and placebo two ( rhinitis ) . A significant correlation was found between low skin reactivity and high specific IgG ( P= 0.0002 ) and IgG4 ( P= 0.036 ) . These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy . The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that , at least in the studied cutaneous model , these antibodies may exert a blocking effect BACKGROUND Previous trials have demonstrated the efficacy , safety , and optimal dosage of the 5-grass pollen sublingual tablet for adults and children with grass pollen-induced allergic rhinoconjunctivitis . OBJECTIVES We sought to evaluate the efficacy and safety of 300 index of reactivity ( IR ) 5-grass pollen sublingual tablet in US adults . METHODS Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater ( scale , 0 - 18 ) during the previous grass pollen season were r and omized in a double-blind , placebo-controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season . The primary efficacy end point was the daily Combined Score ( CS ; scale , 0 - 3 ) , which integrates symptoms and rescue medication use . RESULTS Four hundred seventy-three participants were r and omized . The mean daily CS over the pollen period was significantly lower in the active treatment group versus the placebo group ( least-squares mean difference : -0.13 ; 95 % CI , -0.19 to -0.06 ; P = .0003 ; relative reduction : 28.2 % ; 95 % CI , 13.0 % to 43.4 % ) . In placebo-treated participants , the daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass-specific serum IgE of less than 0.1 kU/L ( n = 23 ) and 0.46 in those with baseline timothy grass-specific serum IgE of 0.1 kU/L or greater ( n = 204 ) . The most frequent reported adverse events were oral pruritus , throat irritation , and nasopharyngitis . There were no reports of anaphylaxis , and no actively treated participant received epinephrine . CONCLUSION In US adults with grass pollen-induced allergic rhinoconjunctivitis , preseasonal and coseasonal treatment with 300IR 5-grass pollen sublingual tablet demonstrated clinical ly meaningful efficacy , especially in study subjects with measurable timothy grass-specific serum IgE. Use of 300IR 5-grass pollen sublingual tablet was safe and well tolerated . A requirement for a measurable level of allergen-specific serum IgE should be considered in future studies in this field While the prevalence of asthma in children is decreasing or remaining the same , time trends in the prevalence of rhinitis in children are not known . Underst and ing sensitisation trends may help inform about trends in asthma and rhinitis prevalence Background : Four administration schedules of immunotherapy have been reported : conventional , cluster , rush and ultra-rush . Objectives : To evaluate the safety and the clinical advantage of using st and ardized modified allergen extracts in an ultra-rush protocol without premedication and /or hospitalization . Material and Methods : One thous and and sixty-eight patients with rhinoconjunctivitis and /or asthma sensitized to mites and /or pollen were included in a prospect i ve observational study . Patients received a therapeutic vaccine containing depigmented and glutaraldehyde-modified extracts ( mites and /or pollens ) adsorbed onto alum prescribed by a specialist . The schedule of administration consisted of injecting 0.2 and 0.3 ml of the vial of maximum concentration during the first day of immunotherapy , separated by a time interval of 30 min . All patients reached the maximum dose ( 0.5 ml ) after 2 injections . Tolerance was assessed by recording all side reactions related to immunotherapy , classified according to the criteria of the EAACI . Results : The total number of injections was 2,136 . All patients reached the maximum established dose on the 1st day . No premedication was used . Seven clinical ly relevant local reactions were recorded . The systemic reactions were 5 grade -1 ( 2 immediate and 3 delayed ) and 3 delayed grade -2 reactions . Conclusions : The therapeutic vaccines containing chemically modified extracts can be administered using an alternative ultra-rush schedule in an immunotherapy unit , reaching the maximum dose on the 1st day with 2 injections , without the need of premedication and /or hospitalization Background : We present data showing that a Th1‐inducing adjuvant can reduce the number of injections required for allergy vaccination . Allergy vaccination is the only treatment for type 1 hypersensitivity that can alter the underlying disease process . A switch of specific T‐cell activity from Th2>Th1 to Th1>Th2 is believed to be an important change seen after long‐term vaccination therapy . An immunologic adjuvant that enhances such a switch could be used to reduce the number of injections required . This would improve compliance with the treatment and provide pharmacoeconomic advantages . Such an adjuvant is 3‐deacylated monophosphoryl lipid A ( MPL ® adjuvant , Corixa ) BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis 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 The IgE response of patients only allergic to grass pollens differs from response of patients allergic to multiple-pollen species . The IgE immunoblots to orchard-grass pollens confirmed that polysensitized patients had more proteins revealed than patients only allergic to grass pollens . To determine if both groups of patients present a different response toward specific immunotherapy ( IT ) , a double-blind , placebo-controlled study was performed in 70 patients . Patients receiving the active treatment had a rush IT with either a st and ardized orchard grass-pollen extract or with a st and ardized mixed-pollen extract prepared , depending on the sensitivity of the patients . The maintenance dose was defined as that dose effective in grass-pollen IT in previous experiments . The same equipotent maintenance dose was administered for all pollen species . Symptom-medication scores during the pollen season and nasal challenge with orchard grass-pollen grains demonstrated that grass pollen-allergic patients had a significantly improved efficacy by comparison to placebo treatment , whereas polysensitized patients had a nonsignificant improvement . Serum grass-pollen IgG was significantly increased after IT in both treated groups . This study demonstrate that the response toward specific IT differs in patients only allergic to grass pollens by comparison to polysensitized patients INTRODUCTION Hay fever ( allergic rhinoconjunctivitis ) is a frequent disease and 12 % of the Danish adult population suffer from grass-pollen induced hay fever . Symptomatic medication is the traditional treatment , while immunotherapy with sustained effect is an alternative . Grazax ( Phleum pratense , ALK-Abelló ) is a new tablet-based vaccination against grass-pollen induced hay fever . The aim was to investigate the cost-effectiveness of the tablet-based vaccination of grass-pollen induced hay fever in Denmark . MATERIAL S AND METHODS Based on a prospect i ve collection of data as part of a clinical trial cost and quality of life ( QALY ) data for 493 patients , the tablet-based vaccine ( Grazax ) was compared in a cost-utility analysis ( societal perspective ) with symptomatic treatment . The analysis was based on three years of immunotherapy followed by six years of sustained effect . RESULTS Significant more QALYs were gained from using the tablet-based vaccine ( 0.9799 ) compared with traditional symptomatic treatment ( 0.9567 ) , which with a nine-year time horizon corresponds to 0.19 extra QALYs . The costs of vaccination against hay fever were DKK 34,498 . With a nine-year time horizon , the cost per extra QALY from using the tablet-based vaccine was DKK 52,646 or DKK 134,105 , focussing on direct costs alone . These results are below the unofficial thresholds for what the costs of a QALY should be . CONCLUSION The analysis has shown that tablet-based immunotherapy ( Grazax ) for the treatment of hay fever results in an improved quality of life and that it is a cost-effective choice BACKGROUND Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite ( HDM ) extracts in adults with allergic rhinitis . OBJECTIVES We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year . METHODS Adults with HDM-associated allergic rhinitis were r and omized in a double-blind , placebo-controlled study to receive 500 index of reactivity ( IR ) tablets , 300IR tablets , or placebo administered once daily for 1 year and were followed for the subsequent year . The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period ( ie , October 1 to December 31 ) . Symptoms and rescue medication scores , onset of action , patient-reported outcomes , and safety were secondary variables . The same end points were evaluated during the immunotherapy-free year . The primary efficacy end point was analyzed by using analysis of covariance . RESULTS Five hundred nine participants were r and omized , and 427 continued in the immunotherapy-free year . Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2 % ( P = .0066 ) and -17.9 % ( P = .0150 ) , respectively . Efficacy of both doses was maintained during the treatment-free follow-up phase . The onset of action was at 4 months . Participants ' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group ( P = .0206 and P = .0001 , respectively ) . Adverse events were generally application-site reactions . There were no reports of anaphylaxis . CONCLUSIONS Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated . Efficacy was maintained during the treatment-free follow-up year 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 Background : Specific immunotherapy ( SIT ) is a valuable treatment for respiratory allergy , and the use of chemically modified allergens ( allergoids ) has improved its safety , as testified by several studies . We evaluated the effects of a SIT course with an allergoid extract of Parietaria pollen in a double‐blind , placebo‐controlled trial 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 We investigated the effects of immunotherapy ( IT ) on the early ( ER ) , late ( LPR ) , and rechallenge reactions ( RCRs ) to nasal challenge with antigen as well as on the cutaneous ER and LPR to intradermal skin challenge . Our expectation was that IT would have a preferential effect on the LPR , and our aim was to underst and the mechanism . Twenty-one ragweed hay fever-sensitive subjects were treated with a moderate dose of antigen extract ( maintenance dose of 1.94 micrograms of antigen E ( Amb a I ) ) during a period of 8 months ( total dose equivalent to 24 micrograms of antigen E ) , and 20 matched subjects received placebo injections in a double-blind manner . Both groups underwent identical nasal challenges and intradermal skin tests with ragweed-antigen extract both before ( 1985 ) and during ( 1986 ) IT . Symptom and medication diaries , recorded during seasonal exposure , and changes in specific serum IgE and IgG antibodies confirmed the efficacy of the administered IT dose . Between-group analysis revealed that IT significantly reduced the levels of histamine , TAME-esterase activity , and kinins , as well as symptoms of rhinorrhea and congestion generated during the ER to nasal challenge . Within-group paired analysis demonstrated ER , LPR , and RCR mediators and symptoms also to be reduced by IT . Surprisingly , the placebo-treated group demonstrated an increase in the ER . There was no decrease of the LPR without an antecedent decrease of the ER . IT did not clearly change the late cellular inflammatory response . In the case of skin challenge , IT significantly reduced the cutaneous ER . The reduction of the cutaneous LPR was more pronounced . We speculate that moderate-dose IT ameliorates seasonal symptoms of allergic rhinitis by reducing the ER , LPR , and RCR to antigen challenge but does not preferentially reduce the nasal LPR OBJECTIVES /HYPOTHESIS To investigate how quickly an allergic rhinitis ( AR ) patients ' symptoms will improve with sublingual immunotherapy ( SLIT ) . STUDY DESIGN Double-blind placebo study . METHODS This is a multicenter , r and omized , double-blind , placebo-controlled study of SLIT used to treat house dust mite-induced AR . A total of 120 AR patients , aged 4 to 60 years , were treated for 6 months and r and omized into two groups : 1 ) SLIT with Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farina ( D.f . ) extract ( n = 60 ) ; and 2 ) matched placebo controls ( n = 60 ) . Symptom , medications received , and a visual analog scale score were recorded during the whole study . Serum-specific IgE and IgG4 to D. p. and D. f. were assessed before and after the treatment . RESULTS Eighty-five patients ( 70.8 % ) completed the study . Twelve patients ( 20 % ) chose to withdraw from the SLIT group , but none because of serious adverse effects . The total symptom and visual analog scores VAS in the SLIT group decreased significantly when compared to the placebo controls ( P < 0.05 ) after week 14 , as well as for the significant ( P < 0.05 ) improvement of all individual AR symptoms in the SLIT group ( e.g. , sneezing , nasal discharge , itching , and nasal obstruction ) after week 22 . There was a significant ( P < 0.05 ) increase of IgG4 to both D.f . and D.p . in the SLIT , but not in the placebo group after treatment . CONCLUSION SLIT with a mixture of D.f . and D.p . extract is an effective and safe treatment for patients with house dust mite-induced AR . Its onset of action can be observed as early as 14 weeks after treatment 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 Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of allergic rhinitis . Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma BACKGROUND 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 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 Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements . Effects on seasonal asthma are less clear , and concerns over safety persist . OBJECTIVE The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms , bronchial hyperresponsiveness , and quality of life in seasonal rhinitis and asthma . METHODS Forty-four patients with severe summer hay fever ( of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness ) participated in a r and omized , double-blind , placebo-controlled , parallel group study . After symptom monitoring for one summer , participants received injections of a depot grass pollen vaccine ( n = 22 ) or matched placebo injections ( n = 22 ) in a rapid updosing cluster regimen for 4 weeks , followed by monthly injections for 2 years . Outcome measures included hay fever symptoms and medication use , health-related quality of life , and measurements of nonspecific bronchial responsiveness . RESULTS Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms ( 49 % , 15 % ; P = .01 ) , medication scores ( 80 % , 18 % ; P = .007 ) , and seasonal chest symptoms ( 90 % , 11 % ; P < .05 ) . Impairment of overall quality of life ( mean score of 7 domains ) during the pollen season was less in the immunotherapy group than in the placebo group ( median difference [ 95 % CI ] , 0.8 [ 0.18 - 1.5 ] ; P = .02 ) . During the pollen season there was no change in airway methacholine PC(20 ) ( provocation concentration producing a 20 % fall in FEV(1 ) ) in the immunotherapy-treated group ( P = .5 ) , compared with an almost 3 doubling-dose decrease in the placebo-treated group ( P = .01 , between-group difference ) . There were no significant local or systemic side effects during the study . CONCLUSION Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness Allergen-specific immunotherapy ( ASIT ) with fungal extracts has been beset by safety and efficacy problems , which result mainly from qualitative and quantitative variations . Little has been published on the safety and efficacy of these extracts . The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract . A total of 28 patients were selected with rhinitis and /or bronchial asthma because of Alternaria allergy and monosensitization to molds . The patients were r and omized to an active ASIT or placebo group , both groups on a conventional immunotherapy schedule ( increasing weekly doses until maintenance dose and then monthly doses ) . Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system . Clinical efficacy was analyzed for a year with symptom/medication diary cards , peak expiratory flow ( PEF ) measures , clinical severity score , severity of symptoms ( visual analog scale ) , subjective evaluation of treatment by the patient and the physician , and a quality of life question naire . Twenty-three patients completed the study ; all reached the established maintenance dose with only two mild adverse reactions in the whole sample . Significant improvements were found after 6 months in respiratory symptoms in the active treatment group , and in all symptoms in both groups . PEF increased significantly in the active treatment group but not in the placebo group . The severity of asthma decreased in the active treatment group , and the severity of rhinitis decreased in both groups . Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group , but only after 12 months in the placebo group . Physicians judged the disease course as significantly better in the active treatment group . ASIT with the A. alternata extract was safe , with clinical improvements after one year of treatment Forty patients with a well-documented history of seasonal hay fever and a positive skin-prick test specific to grass pollen , including Bermuda grass and maize pollen ( Zea maize ) , were allocated r and omly on a double-blind basis to receive either an oral mixed grass-maize pollen extract or a matched placebo during the 1981/1982 grass pollen season . After 12 months the code was broken and patients on placebo were transferred to active therapy while patients on active therapy continued with maintenance therapy for another 12 months during the 1982/1983 grass pollen season . The assessment of the effect of the orally administered grass-maize pollen extract was on the clinical symptoms . During the first year the patients on active therapy had significantly fewer hay fever symptoms during the summer months compared with the placebo group . During the second study year , with all patients on active therapy , both groups had markedly milder symptoms compared with the placebo group . Side-effects were negligible . This study concludes that oral immunotherapy with grass-maize pollen extract in grass pollen-sensitive seasonal hay fever patients is safe and effective The effect of sublingual immunotherapy on quality of life ( QoL ) was examined in patients with grass pollen-induced rhinoconjunctivitis . Patients ( n = 855 ) were r and omised to once-daily grass allergen tablets ( 2,500 ; 25,000 ; or 75,000 SQ-T Phleum pratense extract ; GRAZAX ® ) or placebo . Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout . If symptoms were present , patients received loratadine or placebo rescue medication . There were three major findings : in patients using loratadine , grass allergen tablets provided QOL benefits over placebo ; Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) score was 17 % ( p = 0.006 ) and 20 % ( p = 0.020 ) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit , respectively ; in patients not using loratadine , grass allergen tablets improved QoL more than placebo ; RQLQ score was 21 % greater ( p = 0.021 ) with 75,000 SQ-T tablet at second seasonal visit ; grass tablets ( without loratadine ) had a greater effect on QoL than loratadine alone . RQLQ score was 26 % ( p = 0.014 ) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit . These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis , reduces symptoms , and that this effect is greater than rescue antihistamine alone Immunotherapy with PRW has been demonstrated to be safe and effective . To determine whether the efficacy would remain in successive ragweed seasons without further therapy , a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously . Those patients were also compared to previously untreated ragweed-sensitive patients . In a double-blind fashion , 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy , whereas 21 previously treated patients were treated with four injections of placebo therapy . An additional control group of 21 previously untreated ragweed-sensitive patients received no injections . Daily symptom and medication score sheets were completed by patients each day of the ragweed season . Blocking antibody rose elevenfold with treatment ( p less than 0.0001 ) in the PRW group . There was a statistically significant difference in symptom score mean between untreated patients ( 1007 + /- 174 ) and previously treated patients whether they received supplemental injections ( 554 + /- 180 ) ( p less than 0.01 ) or whether they did not ( 650 + /- 168 ) ( p less than 0.03 ) . In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy BACKGROUND Allergic rhinoconjunctivitis is an increasingly common source of morbidity , with sensitivity to cats accounting for 10 % to 15 % of disease burden . Allergy to cats is also a major risk factor for the development of asthma . OBJECTIVES We sought to probe the persistence of the treatment effect of a novel F el d 1-derived peptide antigen desensitization ( Cat-PAD ) 1 year after the start of treatment in subjects with cat allergy-induced rhinoconjunctivitis after st and ardized allergen challenge . METHODS In a r and omized , double-blind , placebo-controlled , parallel-group clinical trial , subjects attended an environmental exposure chamber in which they were exposed to cat allergen before and after treatment with 2 different regimens of Cat-PAD over a 3-month period . Clinical efficacy was assessed as a change in total rhinoconjunctivitis symptom scores 18 to 22 weeks and 50 to 54 weeks after the start of treatment . RESULTS Treatment with Cat-PAD showed greater efficacy with 4 administrations of a 6-nmol dose 4 weeks apart than with 8 administrations of a 3-nmol dose 2 weeks apart . The treatment effect of 6 nmol persisted 1 year after the start of treatment and was significantly different from that of 3 nmol ( P = .0342 ) and placebo ( P = .0104 ) . The treatment effect was apparent on both nasal and ocular symptoms at 1 year . CONCLUSIONS A short course of Cat-PAD improves the ocular and nasal components of rhinoconjunctivitis symptoms in subjects with cat allergy , with the treatment effect persisting 1 year after the start of treatment Background This study evaluates the safety and efficacy of specific sublingual immunotherapy ( SLIT ) against grass pollen allergens in patients > 60 years of age with seasonal allergic rhinitis ( SAR ) and /or asthma . This study sought to assess nasal symptoms during the grass pollen season , reduce medication use , and monitor adverse reactions during immunotherapy . Methods Seventy-eight 60- to 70-year-old patients with SAR and a confirmed grass pollen allergy according to skin-prick tests , nasal provocation , and measurement of serum IgE were included in the study . The patients were individually r and omized to the act or placebo groups using a double-blind method . A total of 41 subjects in the SLIT group ( 5 grass pollen mixture ) and 37 subjects in the placebo group were monitored for 3 years . The patients were required to record each use of an antiallergy medication on a diary card . Results Thirty-eight patients completed 3 years ( preseasonal ) of SLIT , and 34 subjects finished the placebo treatment in the same time period . The total nasal symptom score decreased by 64 % in the active group and 7 % in the placebo group a SLIT . This difference was only significant in the active group ( p < 0.05 ) . At the end of therapy , the total medication score of the active group decreased significantly by a maximum of 51 % ( p < 0.05 ) , whereas the total medication score of the placebo group had an insignificant decrease . None of the study participants had systemic adverse reactions during the study period . Conclusions SLIT in elderly patients with a grass pollen allergy generated significant clinical improvement in the active group compared with the placebo group for grass pollen season . This therapy was well tolerated BACKGROUND The worldwide increased prevalence of allergic diseases , and especially of respiratory allergy , is paralleled by increased health costs . This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice . OBJECTIVE To compare the different economic relevance , over a long evaluation time , of symptomatic pharmacologic therapy and sublingual immunotherapy ( SLIT ) in patients with allergic asthma . METHODS Seventy patients with perennial allergic asthma , sensitized to dust mites , were enrolled ; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs . The patients were evaluated for 2 years after discontinuing immunotherapy , which was performed for 3 years , to obtain a more complete follow-up . Symptom scores , medication scores , and all other direct medical costs were evaluated with a specific question naire . RESULTS Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment , but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity . CONCLUSION The economic advantage measured alongside this prospect i ve observational study was long lasting and still present at the fifth year of the follow-up ( 2 years after discontinuing SLIT ) and could positively be related to the persistent good clinical control of patients To cite this article : Pfaar O , Urry Z , Robinson DS , Sager A , Richards D , Hawrylowicz CM , Bräutigam M , Klimek L. A r and omized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy . Allergy 2012 ; 67 : 272–279 Allergic rhinitis is often associated with bronchial hyperresponsiveness ( BHR ) and airway inflammation , and it seems to be an important risk factor for the development of asthma . Specific immunotherapy ( SIT ) reduces symptoms and medication requirements in subjects with allergic rhinitis , but the mechanisms by which SIT promotes these beneficial effects are less clear . We have investigated the effects of Parietaria-SIT on rhinitis symptoms , BHR to inhaled methacholine , eosinophilic inflammation and cytokine production ( interferon gamma and interleukin-4 ) in the sputum . The effect on asthma progression was also examined . Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to Parietaria judaica participated in a r and omized , double-blind , placebo-controlled , parallel group study . Participants were r and omly assigned to receive injections of a Parietaria pollen vaccine ( n = 15 ) or matched placebo injections ( n = 15 ) in a rapid updosing cluster regimen for 7 weeks , followed by monthly injections for 34 months . Throughout the 3-year study we collected data on symptoms and medication score , airway responsiveness to methacholine , eosinophilia and soluble cytokines in sputum , followed by a complete evaluation of the clinical course of atopy . Hay fever symptom and medication scores were well controlled by SIT . By the end of the study , in the placebo group , symptom and medication scores significantly increased by a median ( interquartile range ) of 121 % ( 15 - 280 % ) and 263 % ( 0 - 4400 % ) respectively ( p < 0.01 ) , whereas no significant difference was observed in the SIT group . We found no significant changes in the sputum parameters and methacholine PC15 values in both groups throughout the study . By the end of the investigation , a total of 9 out of 29 participants developed asthma symptoms ; of these , seven ( 47 % ) belonged to the placebo group , whereas only 2 ( 14 % ) to the SIT-treated group ( p = 0.056 ) . In conclusion , Parietaria-SIT is effective in controlling hay fever symptoms and rescue medications , but no changes in the BHR to methacholine or sputum eosinophilia were observed . Moreover , Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma , suggesting that SIT should be considered earlier in the management of this condition 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 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 Eighty-one patients with ragweed pollinosis were recruited for a double-blind , histamine placebo-controlled study of the safety , immunogenicity , and efficacy of 15 weekly injections of polymerized ragweed ( PRW ) immunotherapy totaling 1359 allergy units . Patients were paired on the basis of cutaneous end point titration to RAST st and ardized extracts of giant and short ragweed . One patient of each pair was r and omized to receive PRW , and the other patient , a caramelized glucose histamine placebo . Symptom and medication score diaries were completed by 68 patients . All 68 patients received the full maintenance dose . No patient dropped out because of adverse reactions , and there were no systemic reactions . Except for one patient receiving placebo who developed mildly elevated liver function tests , there were no clinical ly significant changes in routine laboratory tests associated with injections . By Student 's test on log-transformed values , blocking antibody rose significantly in the patients receiving PRW but was unchanged in those receiving placebo . By Wilcoxon paired signed-rank test , the symptom and medication scores in the patients receiving PRW were significantly lower than scores in the patients receiving placebo . This study demonstrates the safety , immunogenicity , and activity of PRW in the treatment of ragweed pollinosis BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group . Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters BACKGROUND Respiratory allergy due to Alternaria is a relevant clinical problem , and specific immunotherapy may represent a viable treatment option . Sublingual immunotherapy ( SLIT ) is safe and effective , but data for Alternaria are lacking . OBJECTIVE To assess the efficacy of st and ardized SLIT in patients sensitized to Alternaria in a r and omized , prospect i ve , double-blind , placebo-controlled trial . METHODS Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled . After a baseline season , SLIT or matched placebo was given for 10 months . Symptoms and rescue medication intake were recorded on diary cards between June and October . Skin prick testing was performed and specific IgE , IgG4 , and precipitin levels were measured at baseline and at the end of the study . RESULTS Twenty-seven patients ( age range , 14 - 42 years ) were r and omized , and 26 completed the study . The baseline characteristics were homogeneous in the 2 groups . After treatment , patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season , whereas no change was seen in the placebo group . Skin prick test reactivity significantly decreased only in the SLIT group . No change was seen in specific IgG4 levels in the 2 groups , whereas Alt a 1 specific IgE levels significantly increased in the active group . One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment . CONCLUSION SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria A study of pharmacovigilance has been performed in 522 patients suffering from allergic rhinitis and /or asthma . Sensitization was due to pollens and mites in ther majority of cases . The treatment consisted in biologically st and ardized glycerinated allergenic extracts for specific sublingual immunotherapy ( SLIT ) and , major allergens were also quantified , depending on the allergenic composition . The aims of the study were to assay the effect of the SLIT in a short- and -medium-term course and to know the adverse reactions most frequently appearing , as well as the unexpected side effects that are only possible to know through the study of a numerous sample of patients . We also evaluated the factors that can modify the tolerance of the treatment , such as the onset of patient 's disease and its severity . All the patients had a clinical history of , at least , two years of evolution and positive skin-prick test to the allergen/s cause of their atopic disorder . Exclusion criteria were immunotherapy in the last two years , pregnancy and those situations in which the immunotherapy is contraindicated according to the EAACI requirements . In order to carry out the daily record of the SLIT as well as the possible appearance of symptoms , two diaries were given to each patient . Tolerance was evaluated by the physician at the end of the build-up phase ( 3 months ) and when the maintenance phase finished ( 5 months later ) . Total administered doses were 44.021 , the final number of patients who registered any adverse reaction in relation with SLIT was 41 ( 7.9 % ) , with a number of 67 adverse reactions that means a 0.15 % over the total administered doses . ( ABSTRACT TRUNCATED AT 250 WORDS A double‐blind , placebo‐controlled study of immunotherapy was conducted in 19 patients with grass‐pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid . The patients were assessed before and during IT by clinical ( symptom‐medication scores during the grass‐ pollen season , specific nasal and skin reactivity ) and immunological ( specific IgE , IgG , IgG1 and IgG4 antibodies ) parameters . High doses of grass allergoid , corresponding to a cumulative pre‐seasonal dosage of 46050 PNU , were administered , with only one systemic reaction . The actively treated patients had significantly lower symptom‐medication scores than placebo ( p < 0.01 ) during the month of May and showed a significant decrease in specific skin ( p < 0.01 ) and nasal ( p < 0.05 ) reactivity , and a significant early increase in specific IgE ( p < 0.01 ) , IgG ( p < 0.0005 ) , IgG1 ( p < 0.001 ) and IgG4 ( p < 0.05 ) , with a subsequent decrease of IgE and IgG1 . No differences were detected in any of these parameters in the placebo group . A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease ( r = 0.691 , p < 0.05 ) , whereas a high IgG4/IgG1 , ratio was associated with higher symptom‐medication scores ( r = 0.654 , p < 0.05 ) . Possible explanations of these apparent discrepancies are proposed A double‐blind , placeo‐controlled study was performed in order to confirm the safety , suitability , and efficacy of an alum‐adsorbed Parietaria judaica‐pollen allergoid , Allergovit ® , for allergen‐specific immunotherapy . Parietaria pollen is an important cause of pollinosis , particularly in the Mediterranean zone , where it may be encountered for up to 8–9 months of the year . It is an aggressive allergen , and the doses tolerated during immunotherapy are less than those achieved with grass pollen . This factor increases the desirability of using therapeutic preparations with minimal IgE‐binding activity , such as allergoids , in order to reduce the risk of side‐effects and enable patients to tolerate a higher dose of allergen , thereby increasing the chances of successful specific immunotherapy . Forty patients with rhinitis and /or asthma were allocated at r and om to active‐ or placebo‐treatment groups at the beginning of the study . All patients received the active preparation during the second year of the study . Immunotherapy was well tolerated by all patients and the incidence of side‐effects was low . Treatment result ed in significant reductions in specific cutaneous reactivity and increases in nasal tolerance . A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation . These objective assessment s of efficacy endorsed the results from the patients ’ diary cards , which indicated significant improvements in symptoms and reductions in the use of medication . The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific‐IgG antibody response , with increases in IgG4 during the second year of treatment . We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria‐pollen‐induced rhinitis or asthma This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris ( Artemisia ) extract . We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinical ly important allergies , either to Artemisia and Betula verrucosa ( Betula ) or to Artemisia and Phleum pratense ( Phleum ) . Patient selection was r and omized and evaluation of results was conducted in double blind fashion . Twenty patients completed two years of specific immunotherapy . Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula ( n = 3 ) or Phleum ( n = 8) . Treatment with Artemisia was followed by a significant decrease in skin sensitivity ( p < 0.05 ) and eye sensitivity ( p < 0.01 ) to Artemisia but not to Betula/phleum . No significant decrease was observed in medicine consumption or symptom scores . Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum ( p < 0.001 ) , and eye sensitivity to Betula or Phleum ( p < 0.05 ) , but not to Artemisia and had significant decreases in medicine and symptom scores ( p < 0.05 ) in Betula/phleum seasons but not in the Artemisia season . The treatment was both effective and specific with the one unexplained exception that both patient groups ( Artemisia and Betula/Phleum ) decreased their skin sensitivity to Artemisia Glutaraldehyde-modified , tyrosine-adsorbed ragweed extract ( GTR ) is a modification of allergen extract to reduce allergenicity but retain immunogenicity . We evaluated the clinical efficacy and immunologic changes associated with the administration of GTR ( 16,350 protein nitrogen units ) or placebo to a group of 100 atopic subjects with ragweed hay fever . The study was carried out in a double-blind , placebo-controlled fashion . Clinical response was measured by daily symptom diaries . physician evaluations , and patient responses . Changes in ragweed-specific IgE and IgG antibody were evaluated with an amplified enzyme-linked immunosorbent assay ( alpha-ELISA ) and were compared with measurements by RAST and a protein A-binding assay for IgG antibody . Treatment with GTR result ed in a sixfold increase in blocking IgG antibody and a small increase in IgE-specific antibody . No changes occurred in the placebo treated group . Mild immediate local reactions occurred after 74 % of injections , and late-onset local reactions occurred after 62 % of injections in the treated group . The placebo-treated group experienced immediate or late local reaction after only 12 % of injections . There were two mild late-onset urticarial reactions of a generalized nature in the treatment group . The treatment group experienced significantly fewer symptoms than the placebo group throughout the season ( p less than 0.02 ) , although the difference was not dramatic . The results showed that GTR could be safely given in five preseasonal injections , with retained immunogenicity but less potential for generalized reactions . GTR is an improved method of allergy immunotherapy with the potential for clinical benefit when used in a brief preseasonal treatment regimen BACKGROUND Birch pollen is a common allergen in northern , central , and eastern Europe . Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal . Long-term , placebo-controlled studies with subcutaneously administered st and ardized birch pollen extract are lacking . OBJECTIVE The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen-allergic patients in a double-blind , placebo-controlled trial . METHODS Forty-nine patients with histories of birch pollen allergy from the upper and lower airways , positive skin prick test and conjunctival provocation test results , and in vitro specific IgE to birch pollen ( Betula verrucosa ) extract were included . Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind , r and omized , placebo-controlled study . Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season . RESULTS Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study . The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6 , respectively , in the specific immunotherapy group and 2.1 and 4.3 , respectively , in the placebo group . The differences between the groups were significant ( P = .05 in 1997 and P = .005 in 1998 ) . The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group ( P = .004 for 1997 and P = .004 for 1998 ) . CONCLUSION Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen-allergic patients during the pollen season Specific immunotherapy is still widely used in grass-pollen allergy , but its side effects may limit its use . We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind , placebo-controlled study . Eighteen patients received placebo , 19 received the low-dose schedule ( maximal dose : 2000 PNU ) and 20 received the high-dose schedule ( maximal dose : 10,000 PNU ) . Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU . Before the onset of the pollen season , patients had a nasal challenge with orchard grass-pollen grains , a skin test titration , and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo . Symptoms and medications for rhinitis and asthma were studied during the season , and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms . There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges . High-molecular-weight allergoids are safe and effective 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 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 Sublingual allergen-specific immunotherapy is a viable alternative to subcutaneous immunotherapy particularly attractive for use in children . OBJECTIVE This study investigated efficacy and safety of high-dose sublingual immunotherapy ( SLIT ) in children allergic to grass pollen in a r and omized , double-blind , placebo-controlled trial . METHODS After a baseline seasonal observation , 207 children aged 4 to 12 years with grass pollen-allergic rhinitis/rhinoconjunctivitis with/without bronchial asthma ( Global Initiative for Asthma I/II ) received either high-dose grass pollen SLIT or placebo daily for 1 pre-/co-seasonal period . The primary end point was the change of the area under the curve of the symptom-medication score ( SMS ) from the baseline season to the first season after start of treatment . Secondary outcomes were well days , responders , immunologic changes , and safety . RESULTS Mean changes in the area under the curve of the SMS from the baseline to the first grass pollen season after the start of treatment were -212.5 for the active group and -97.8 for the placebo group ( P = .0040 ) . Rhinoconjunctivitis SMS ( P = .0020 ) and separated symptom and medication scores were also statistically different between the 2 groups ( P = .0121 and P = .0226 , respectively ) . The number of well days and the percentage of responders were greater in the active group . Changes in allergen-specific IgE and IgG levels indicated a significant immunologic effect . The treatment was well tolerated , and no serious treatment-related events were reported . CONCLUSIONS This study confirmed that this SLIT preparation significantly reduced symptoms and medication use in children with grass pollen-allergic rhinoconjunctivitis . The preparation showed significant effects on allergen-specific antibodies , was well tolerated , and appeared to be a valid therapeutic option in children allergic to grass pollen . This trial was registered at www . clinical trials.gov as NCT00841256 BACKGROUND Sublingual allergen immunotherapy ( SLIT ) is a commonly used alternative route of administration to st and ard subcutaneous immunotherapy ( SCIT ) in Europe . Despite its wide use , the cost-effectiveness of SLIT vs SCIT has not been well established . OBJECTIVE To evaluate the cost and effectiveness of SLIT compared with SCIT in patients with allergic rhinoconjunctivitis during a 3-year specific allergen immunotherapy ( SIT ) from a third-party payer 's , a patient 's , and society 's perspectives . METHODS We performed an open-label r and omized clinical trial of patients receiving SLIT ( n = 19 ) , patients receiving SCIT ( n = 23 ) , and a control group ( n = 22 ) . The outcome measures were Rhinoconjunctivitis Quality of Life Question naire score , visual analog scale score , symptomatic medication reduction , and direct and indirect costs . RESULTS SLIT offered clinical benefits to patients comparable to those provided by SCIT . From the perspective of a third-party payer , the total average direct medical cost per patient of 3-year SIT was estimated at Euro 416 vs Euro 482 in the SLIT and SCIT groups , respectively . A patient who received SLIT paid less than a patient who received SCIT for all out-of-pocket costs ( Euro176 for SLIT vs Euro 255 for SCIT ) but more for sole allergen extracts ( Euro 72 for SLIT vs Euro 55 for SCIT ) . When both direct and indirect costs were considered , the 3-year SIT expenditures per patient reached Euro 684 vs Euro 1,004 in the SLIT and SCIT groups , respectively . CONCLUSIONS SLIT represents a less expensive alternative relative to subcutaneous administration from all perspectives . However , from a patient 's perspective , SCIT offers a less expensive alternative for patients who do not experience loss of income and travel costs associated with treatment 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 : 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 conventional schedule for subcutaneous immunotherapy with allergen extracts , although efficacious and safe , is slow during the dose-increase phase . OBJECTIVE We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus st and ardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase . METHODS Of 239 patients with rhinitis , allergic bronchial asthma , or both caused by D pteronyssinus , 120 were r and omly assigned to the cluster schedule , and 119 were r and omly assigned to the conventional schedule . A biologically st and ardized D pteronyssinus depot extract ( ALK-Abelló S.A. , Madrid , Spain ) was administered in a placebo-controlled , double-blind fashion during the initial phase of cluster or conventional treatment . We recorded adverse reactions , clinical efficacy , cutaneous reactivity , and serum specific immunoglobulins to D pteronyssinus before immunotherapy , when the maximum dose was reached in the cluster and conventional schedules , and after 1 year of treatment . RESULTS The cluster schedule reduced the time to maintenance dose by 46 % and caused systemic adverse reactions ( all mild ) after only 0.15 % of injections , with no differences in comparison with the conventional schedule . Cluster immunotherapy led to decreases in asthma and rhinitis symptoms , reduced the cutaneous reactivity , and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week , 6 weeks earlier than with the conventional schedule . CONCLUSION The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner 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 Rhinoconjunctivitis due to birch pollen sensitization is common in Northern Europe . A depigmented polymerized birch pollen extract – Depigoid ® has been developed for immunotherapy BACKGROUND There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective . OBJECTIVE To evaluate the safety and efficacy of pre-seasonal specific subcutaneous immunotherapy ( SCIT ) against grass pollen allergens in patients older than 65 years with seasonal allergic rhinitis and to measure the prime outcome of area under the curve for the combined symptoms and medication score during grass pollen season after 3 years of SCIT in a double-blinded , placebo-controlled trial . METHODS This study included 60 65- to 75-year-old patients with seasonal allergic rhinitis and grass pollen allergy . Patients were individually r and omized to the active or placebo group . Thirty-three subjects in the SCIT group and 27 subjects in the placebo group were monitored for 3 years . Patients were required to record each use of anti-allergy medication . RESULTS Thirty-one patients completed 3 years of pre-seasonal SCIT and 24 subjects finished placebo treatment . The median area under the curve for the combined symptoms and medication score after the third grass pollen season after SCIT was significantly decreased from 7.85 ( range 3.67 - 8.98 ) to 4.63 ( range 3.56 - 7.80 ) in the active group and did not significantly change in the placebo group . In the active group , the combined symptoms and medication score was decreased by 41 % , the symptoms score was decreased by 55 % , and the medication score was decreased by 64 % after 3 years of immunotherapy . CONCLUSION Pre-seasonal SCIT in the elderly is safe and efficacious and elicits an immune response comparable to what is found in studies of younger patients BACKGROUND Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition . OBJECTIVE To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy : recombinant birch pollen allergen vaccine ( rBet v 1a ) , licensed birch pollen extract , natural purified birch pollen allergen ( nBet v 1 ) , and placebo . Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years . RESULTS Significant reductions ( about 50 % ) in rhinoconjunctivitis symptoms ( rBet v 1 , P = .0002 ; nBet v 1 , P = .0006 ; birch extract , P = .0024 ) , rescue medication ( rBet v 1 , P = .0011 ; nBet v 1 , P = .0025 ; birch extract , P = .0063 ) , and skin sensitivities ( P < .0001 ) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons . Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels , which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups . New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract , but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients . No severe systemic adverse events were observed in the rBet v 1-treated group . CONCLUSION The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy , and induced a highly specific immune response BACKGROUND The SQ HDM SLIT-tablet ( ALK ) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease . OBJECTIVE This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis ( AR ) . METHODS The trial was a r and omized , double-blind , placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy . Subjects were r and omized 1:1:1 to 1 year of daily treatment with placebo , 6 SQ-HDM , or 12 SQ-HDM . The primary end point was the total combined rhinitis score ( ie , the sum of rhinitis symptom and medication scores ) during the efficacy assessment period ( approximately the last 8 weeks of the treatment period ) . Key secondary end points were rhinitis symptoms , medication scores , quality of life , and the combined rhinoconjunctivitis score . RESULTS Analysis of the primary end point ( observed data ) demonstrated absolute reductions in total combined rhinitis score of 1.18 ( P = .002 ) and 1.22 ( P = .001 ) compared with placebo for 6 SQ-HDM and 12 SQ-HDM , respectively . The statistically significant treatment effect was evident from 14 weeks of treatment onward . For all key secondary end points , efficacy was confirmed for 12 SQ-HDM , with statistically significant reductions of rhinitis symptoms and medication scores , improved quality of life , and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo . The treatment was well tolerated . CONCLUSION The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR . The treatment effect was present from 14 weeks of treatment onward |
12,628 | 22,161,384 | Caring for people in acute day hospitals is as effective as inpatient care in treating acutely ill psychiatric patients . | BACKGROUND Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders .
It has been proposed that many of those currently treated as in patients could be cared for in acute psychiatric day hospitals .
OBJECTIVES To assess the effects of day hospital versus inpatient care for people with acute psychiatric disorders .
Day hospital trials tend to present similar outcomes in slightly different formats , making it difficult to synthesis e data . | New psychiatric out- patients with depressive , phobic , and anxiety neurosis were r and omly allocated to out-patient care or to one of two types of day hospital treatment , one specialising in psychotherapy and the other offering all forms of day care . Of 106 patients who entered the study , 78 had assessment s of psychiatric symptomatology and social adjustment both before treatment and after 4 , 8 and 24 months . There was no significant difference in outcome between depressive , phobic , and anxiety neurosis , and no overall difference in response to treatment between the three types of care . Suicidal symptoms were significantly less common in out- patients . In many respects , neurotic disorder can be regarded as a single syndrome Schizophrenic patients referred for day treatment at the time of discharge from ten hospitals were r and omly assigned to receive day treatment plus drugs or to receive drugs alone . They were tested before assignment and at 6 , 12 , 18 , and 24 months on social functioning , symptoms , and attitudes . Community tenure and costs were also measured . The ten day centers were described on process variables every six months for the four years of the study . Some centers were found to be effective in treating chronic schizophrenic patients and others were not . All centers improved the patients ' social functioning . Six of the centers were found to significantly delay relapse , reduce sumptoms , and change some attitudes . Costs for patients in these centers were not significantly different from the group receiving only drugs . More professional staff hours , group therapy , and a high patient turnover treatment philosophy were associated with poor- result centers . More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers Day treatment remains a core component in many community mental health programs for persons with severe mental disorders throughout the United States . Many other mental health centers are moving away from day treatment toward psychosocial and vocational rehabilitation programs . Empirical research directly comparing these two systems of organizing outpatient services is needed . In this study the authors compared a rehabilitative day treatment program in one small city with a similar program in a nearby city that changed from day treatment to a supported employment model . Clients who were enrolled in community support services during a baseline year prior to the change and during a follow-up year after the change ( 71 in the program that changed and 112 in the other ) were evaluated during both intervals . In the program that changed , competitive employment improved from 25.4 % to 39.4 % for all clients , and from 33.3 % to 55.6 % for those clients who had been regular attenders of day treatment during the baseline . Hours worked and wages earned similarly improved after the program change . For all work variables , clients who had not worked during the baseline year accounted for the improvements in outcome . Meanwhile , employment remained stable in the day treatment program . No negative outcomes were detected . These results indicate that eliminating day treatment and replacing it with a supported employment program can improve integration into competitive jobs in the community A one-year cohort of patients from a defined catchment area with acute functional disorders were allocated at r and om to brief care ( experimental group ) or st and ard care ( control group ) in hospital to examine the effect of shortening hospital stay on the clinical and social functioning of patients and the distress abnormal functioning caused to others . A total of 127 patients were interviewed on entry to the study , and 106 were followed up . The brief care group had significantly shorter mean and median lengths of stay than the control group , but there was no difference between the groups in the number of days spent in hospital during subsequent admissions . The groups were well matched for clinical and social variables . Rates of improvement over 13 weeks were essentially the same by all measures of outcome , including the Present State Examination and Patient 's Behaviour Assessment Scale , which was developed for the study to measure deterioration in behaviour and social functioning and adverse effects and distress on others . There was no difference between the two groups in burden to the community supporting services , social security requirements , or GP attendances . Improvement rates were nearly identical on all measures within and across diagnostic subgroups . Brief care result ed in a 33 % reduction in average length of stay compared with the year before but was associated with a corresponding increase in day hospital use . The short-stay policy continued the year after the study finished . The findings confirm the value of shortening hospital stay and improving day care facilities for most localities 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 effects of day care therapy for a period of 6 months upon patients with schizophrenia were studied through comparison with schizophrenia out patients at four facilities in Japan . The clinical features of the 31 day care patients and 30 out patients were evaluated by the hospital staff using the Positive and Negative Syndrome Scale ( PANSS ) and Global Assessment Scale ( GAS ) , and by the patients ' close relatives using the Katz Adjustment Scale ( KAS ) before and after 6 months of treatment . Day care patients showed a significant decrease in the general pathological score of PANSS and GAS , but out patients did not show any comparable improvement . As for KAS scores , similar improvement was observed for both the day care patients and out patients After 6 months , 43 % of the day care patients improved on the post-/pre- PANSS total scores ratio , as against only 13 % of the out patients . In addition , 13 % of the out patients were readmitted due to an exacerbation of their symptoms , whereas all day care patients were able to remain at home for 6 months . This study clearly demonstrated that day care therapy for patients with schizophrenia was more effective than the usual out patients treatment setting . Further therapeutic efforts ( e.g. psycho-education ) in day care therapy are needed in order to improve family member 's evaluation of the patient Ninety-one patients admitted as emergencies , suffering from neurosis , personality disorder , or adjustment reaction , were r and omly allocated to day hospital or to continued in-patient care . Follow-up was for up to one year . Clinical outcome was similar in the day care and in-patient groups , but patient satisfaction was significantly greater in day patients . Day hospital care was only about two-thirds of the cost of the cheaper of the two in-patient regimes , even though contact with it was on average twice as long as for in- patients Emerging models of cognitive-behavioral treatment ( CBT ) offer promising new intervention strategies in the psychotherapy of schizophrenia . These models , however , have not been integrated into community support programs and evaluated in comparison to st and ard community treatments . This study examined differences in outcomes of clients who received long-term day treatment program services ( DTP ) compared to clients who received individual CBT that was included as part of their DTP treatment . Twenty-four clients were r and omly assigned to DTP treatment or CBT/DTP treatment . Data on st and ardized measures of psychosocial functioning , symptomatology and rehospitalizations were collected over the course of three years of treatment . Analysis of variance with repeated measures was conducted to evaluate the effects of type of treatment ( CBT/DTP and DTP ) and time ( dependent variable scores taken at the end of treatment years one , two and three ) on the three outcome variables . Results indicate significant improvement for the CBT/DTP group compared to the DTP group in the patterns of change over time for psychosocial functioning and symptomology . In addition to this significant group/time interaction the time factor was also significant for both variables . For rehospitalizations the time factor was significant and the group/time factor was nonsignificant . Implication s for service delivery to persons with schizophrenia and suggestions for future research are discussed BACKGROUND Postnatal depression affects one in ten women within 6 months of childbirth . The most effective treatment strategy for postnatal depression is not clear . METHODS This prospect i ve , naturalistic study of the treatment of postnatal depression compared 30 women treated at a specialised psychiatric day hospital with 30 women treated using routine primary care ( RPC ) . Clinical , marital and social adjustment were assessed on three occasions over 6 months using : the Edinburgh Postnatal Depression Question naire ( EPDS ) ; the Clinical Interview schedule ( CIS ) ; the Anxiety Subscale of the Hospital Anxiety and Depression Scale ; the Dyadic Adjustment Scale ( DAS ) ; and the Work Leisure and Family Life Question naire-Modified ( WLFLQ-M ) . RESULTS There were no significant differences between the two groups at baseline . However , there were significant differences in outcome at 3 and 6 months follow-up for all outcome measures except the DAS . At 6 month follow-up 21 of the PBDU group were no longer depressed compared with 7 of the RPC group . CONCLUSIONS A specialised day hospital is a more effective treatment setting for postnatal depression than routine primary care . LIMITATIONS OF THE STUDY The study is not an RCT , so systematic bias is possible . The sample size is relatively small and the duration of follow-up relatively short The authors r and omly assigned 79 in patients with nonchronic schizophrenia or affective disorder to either an intensive experimental day program called " transitional treatment " or a control treatment -- weekly clinical ly believed to require intensive posthospital treatment to make the transition to the community . Although initially there was a significantly higher dropout rate from the control condition , at the point of discharge from the two programs as well as at 6- and 12-month follow-up there was no difference in outcome . Direct costs for the transitional treatment , however , were much higher BACKGROUND Data on effectiveness of acute day hospital treatment for psychiatric illness are inconsistent . AIMS To establish the effectiveness and costs of care in a day hospital providing acute treatment exclusively . METHOD In a r and omised controlled trial , 206 voluntarily admitted patients were allocated to either day hospital treatment or conventional wards . Psychopathology , treatment satisfaction and subjective quality of life at discharge , 3 months and 12 months after discharge , readmissions to acute psychiatric treatment within 3 and 12 months , and costs in the index treatment period were taken as outcome criteria . RESULTS Day hospital patients showed significantly more favourable changes in psychopathology at discharge but not at follow-up . They also reported higher treatment satisfaction at discharge and after 3 months , but not after 12 months . There were no significant differences in subjective quality of life or in readmissions during follow-up . Mean total support costs were higher for the day hospital group . CONCLUSIONS Day hospital treatment for voluntary psychiatric patients in an inner-city area appears more effective in terms of reducing psychopathology in the shortterm and generates greater patient satisfaction than conventional in-patient care , but may be more costly A prospect i ve r and omized comparative study on the effectiveness of psychiatric day treatment and inpatient treatment is described . The target population consisted of patients who would normally have been admitted to an open inpatient unit . Outcome indicators were psychopathology , social functioning , interpersonal functioning , social network and social support . No differences in effectiveness were found between the two forms of treatment , although more patients accepted and completed day treatment , and day patients were more satisfied . Although a uniform treatment programme for both departments was established , distinct differences did arise in the actual treatment programme offered to the patients . The duration of treatment for the day patients was considerably longer , and the intensity of treatment was more low‐key . No striking differences in the amount of medication prescribed and in the occurrence of crisis situations ( including suicide ) were found . Day treatment turns out to be a realistic alternative for 33 % of all patients admitted for inpatient treatment . It was not possible to predict which type of patient in particular is suitable for day treatment 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 The authors compared treatment results for 141 schizophrenic patients r and omly assigned to short-term or long-term hospitalization . Test results indicated that the long-term group was functioning significantly better one year after admission according to global measures only . The authors caution that the differences between the two groups , although statistically reliable , were modest and may have been confounded by the amount of psychotherapy the patients received after hospitalization . Although there appears to be a general advantage to the long-term approach , further work will be needed to identify patient subgroups for whom this more expensive treatment is cost effective AIM To assess effectiveness of treatment in the day-care and inpatient wards within the Wrocław branch of the international multicenter EU-funded EDEN study . The authors analysed the number of rehospitalisations after discharge from the index hospitalisation as well as psychopathologic symptoms and subjective quality of life . METHODS Out of 1089 patients admitted to the mental hospital in Wroclaw , 238 were r and omly assigned to either the day-care ward ( n = 115 ) or the inpatient ward ( n = 123 ) . There were three interviews with patients : upon discharge , three and twelve months later . Scores of the extended version of Ventura 's BPRS were used for representing the psychopathology level and for calculation of between- setting differences . Subjective quality of life was measured using the MANSA question naire . Statistical parameters of effectiveness ( scores at given time-point , models adjusted for the scores at admission and for the duration of hospitalisation ) were analysed . The frequency of rehospitalisations was also investigated . Statistical analyses after discharge were performed using the r and om multiple imputations method in consecutive time-points . RESULTS There were no statistical differences between setting s in the effectiveness of treatment three months after discharge . Interviews performed one year after discharged revealed a higher level of psychopathology in patients treated in an inpatient setting ( p = 0.03 ) and it was confirmed by the model adjusted for the duration of hospitalisation ( p = 0.04 ) . Yet day-care ward patients had a higher number of rehospitalisations within one year after discharge . CONCLUSIONS The absolute superiority of treatment in an inpatient ward over day-care setting in terms of its effectiveness was not confirmed using BPRS , MANSA scores and index of rehospitalisation The feasibility of day treatment with community care for schizophrenic patients was tested by means of a longitudinal r and omized experiment with 34 experimentals and 16 controls : 38 percent could be treated satisfactorily in a day program that included a very active ambulatory service . The new approach did not improve prognosis with respect to psychiatric symptomatology , social role disabilities , or number of readmissions during the first year of followup . Total cost of treatment was less for day-treatment patients than for ordinary clinical patients A controlled , prospect i ve , two-year follow-up study examined the relative effectiveness of short-term vs long-term psychiatric hospitalization . Results of the inpatient phase for a sample of 74 nonschizophrenic patients are reported here . About four weeks after admission the patients hospitalized for a short stay were discharged , and at that time were functioning better than the patients in the long-stay group . When the patients hospitalized for a long stay were discharged , three to fur months after admission , they were then functioning as well as , but not noticeably better than , the patients in the short-stay group had been at their earlier time of discharge . Patients with affective disorders were more impaired at admission and improved more than patients with other diagnoses , regardless of length of stay OBJECTIVE The authors investigated the clinical feasibility and the outcome for patients of a program design ed as an alternative to acute hospitalization . METHOD This was a r and om- design study comparing a conventional inpatient program for urban , poor , severely ill voluntary patients who usually require hospitalization to an alternative experimental program consisting of a day hospital linked to a crisis residence . Patients were assessed with st and ardized measures of symptoms , functioning , social adjustment , quality of life , and satisfaction with clinical services upon admission to the study , at discharge from the index admission , and at follow-ups 2 , 5 , and 10 months after discharge . RESULTS One hundred ninety-seven patients were enrolled in the 2-year research program and followed for 10 months . Of the voluntary patients who would have been admitted to the hospital , 83 % were appropriate for the experimental program . The clinical , functional , social adjustment , quality of life , and satisfaction outcome measures were not statistically different for the patients in the two treatment conditions ; however , there was a slightly more positive effect of the experimental program on measures of symptoms , overall functioning , and social functioning . CONCLUSIONS The experimental condition , a combined day hospital/crisis respite community residence , seems to have had the same treatment effectiveness as acute hospital care for urban , poor , acutely ill voluntary patients with severe mental illness Previous attempts at program evaluation of partial hospitalization programs have consisted largely of descriptive and anecdotal reports of programs and patient characteristics . There have been no comparative or experimental studies of the effectiveness of differing day treatment programs . In the current study , Goal Attainment Scaling , a goal -oriented program evaluation system , was used with 56 r and omly selected partial hospitalization patients who attended two day hospitals : one program was based on behavioral-educational methods , and the other was an eclectic program based on the concepts of a therapeutic community . Patients attending the behavioral-educational program showed greater attainment of their therapeutic goals than did the patients involved in the eclectic program . The greater effectiveness of the behavioral-educational day program increased from the 3-month follow-up to the 2-year follow-up The effect of a treatment program ( E ) providing inpatient care , a day hospital , community housing , and sheltered work are compared with a program ( C ) emphasizing rapid discharge . A group of 94 male general psychiatric patients were r and omized to the two units . Outcome data collected at 18 months from admission revealed small but significant differences between the total sample s in employment , maintenance of treatment contact , use of medication , and social adjustment . More C than E patients were in the hospital after the 14th month . Program effects varied considerably with patient type . Patients with less social disability had somewhat better employment outcomes with the E program , but no differences in use of services . Patients with a better prognosis by measure of psychopathology ( Minnesota Multiphasic Personality Inventory cluster and diagnosis of schizophrenia ) spent less inpatient time in the E program , but were not helped to better employment outcomes . Patients with greater social h and icap were not differentially affected . More E patients than C with a poorer prognosis stayed in outpatient treatment and used antipsychotic medications . Patients in the E group with better previous employment and more social isolation used the E day hospital and community housing more heavily than other E subgroups OBJECTIVE The study compared the social environment of a conventional psychiatric inpatient setting with that of a combined acute day hospital and crisis respite program that functions as an alternative to hospitalization for patients judged appropriate for acute inpatient admission . METHODS As part of a r and omized controlled study comparing the clinical effectiveness and cost-effectiveness of the two setting s , the quality of the social environment in the two setting s was assessed using the Multiphasic Environmental Assessment Procedure , an empirical measure of established reliability and validity that is based on objective ratings and perceptions of staff members and patients . RESULTS Compared with the inpatient setting , the day hospital-crisis respite program had higher expectations for patients ' functioning , a lower tolerance for deviance , and more flexibility in patients ' choice of activities . The day hospital-crisis respite program also had a more attractive physical environment , and respondents rated its social milieu as more cohesive , less conflictual , and more comfortable . This setting also promoted higher levels of patient functioning and activity and more utilization of health services , assistance with daily living skills , and social and recreational re sources and encouraged fuller integration of patients in the community . CONCLUSIONS The social environment of the community-based day hospital-crisis respite program embodied several principles of community support systems , including provision of treatment in a less restrictive setting , avoiding disruption of patients ' ongoing involvement in the community , promoting activities in the community , offering patients respect and opportunities for self-determination , and enhancing their dignity OBJECTIVE The authors compared service utilization and costs for acutely ill psychiatric patients treated in a day hospital/crisis respite program or in a hospital inpatient program . METHOD The patients ( N = 197 ) were r and omly assigned to one of the two programs and followed for 10 months after discharge . Both programs were provided by a community mental health center ( CMHC ) in a poor urban community . Data were collected for developing service utilization profiles and estimates of per-unit costs of the inpatient , day hospital , and outpatient services provided by the CMHC . RESULTS On average , the day hospital/crisis respite program cost less than inpatient hospitalization . The average saving per patient was + 7,100 , or roughly 20 % of the total direct costs . There were no significant differences between programs in service utilization or costs during the follow-up phase . Cost savings accrued in the index episode because per-unit costs were lower for day hospital/crisis respite and the average stay was shorter . Significant differences in cost were found among patient groups with psychosis , affective disorders , and dual diagnoses ; psychotic patients had the highest costs in both programs . The two programs had roughly equal direct service staff and capital costs but significantly different operating costs ( day hospital/crisis respite operating costs were 51 % of inpatient hospital costs ) . CONCLUSIONS The programs were equally effective , but day hospital/crisis respite treatment was less expensive for some patients . Potential cost savings are higher for nonpsychotic patients . Cost differences between the programs are driven by the hospital 's relatively higher overhead costs . The roughly equal expenditures for direct service staff costs in the two programs may be an important clue for underst and ing why these programs provided equally effective acute care Acutely ill patients presenting for admission in two district psychiatric services were r and omly allocated to day-hospital or in-patient care . In both services a quarter of all admissions could not be allocated because they were too ill ( half of these were compulsory admissions ) ; these patients were predominantly manic and schizophrenic patients with pronounced psychotic symptoms and disturbed behaviour . In one service 80 % ( 41/51 ) of patients r and omly allocated to day-hospital treatment were successfully engaged in treatment compared with 54 % ( 19/35 ) in the other service . This difference arose because only patients with mildly disturbed behaviour could be treated at the second day hospital . For patients who were successfully allocated , the outcome of treatment was similar in terms of psychiatric symptoms and social functioning . The results of a treatment trial for acutely ill patients in one district service can not be generalised to other district services without due attention to the factors , such as staffing levels , which determine the degree of disturbed behaviour that can be tolerated in the day hospital Two long-term care setting s not now covered by Medicare — adult day care and homemaker services — were studied in a r and omized experiment to test the effects on patient outcomes and costs of using these new services . This article reports findings for day care . Patients ’ physical , psychosocial and health functions were assessed quarterly , and their Medicare bill files were obtained . Medicaid data were obtained on most patients , but few used many Medicaidcovered long-term care services . Multistage analysis was performed to mitigate effects of departures from the r and omized design . Day-care patients showed no benefits in physical functioning ability at the end of the study , compared with the control group . Institutionalization in skilled nursing facilities was lower for the experimental group than the control group , but factors other than the treatment variable appeared to explain most of the variance . There was a possibility that life was extended for some day-care patients . The new services averaged $ 52 per day or $ 3,235 per year . When costs for existing Medicare services used were added , the yearly cost of the experimental group was $ 6,501 , compared with $ 3,809 for the control group — an increase of $ 2,692 or 71 per cent Abstract Objective : To compare direct and indirect costs of day and inpatient treatment of acute psychiatric illness . Design : R and omised controlled trial with outcome and costs assessed over 12 months after the date of admission . Setting : Teaching hospital in an inner city area . Subjects : 179 patients with acute psychiatric illness referred for admission who were suitable for r and om allocation to day hospital or inpatient treatment . 77 ( 43 % ) patients had schizophrenia . Interventions : Routine inpatient or day hospital treatment . Main outcome measures : Direct and indirect costs over 12 months ; clinical symptoms , social functioning , and burden on relatives over the follow up period . Results : Clinical and social outcomes were similar at 12 months , except that in patients improved significantly faster than day patients and burden on relatives was significantly less in the day hospital group at one year . Median direct costs to the hospital were £ 1923 ( 95 % confidence interval £ 750 to £ 3174 ) per patient less for day hospital treatment than inpatient treatment . Indirect costs were greater for day patients ; when these were included , overall day hospital treatment was £ 2165 cheaper than inpatient treatment ( 95 % confidence interval of median difference £ 737 to £ 3593 ) . Including costs to informants when appropriate meant that day hospital treatment was £ 1994 per patient cheaper ( 95 % confidence interval £ 600 to £ 3543 ) . Conclusions : Day patient treatment is cheaper for the 30 - 40 % of potential admissions that can be treated in this way . Carers of day hospital patients may bear additional costs . Carers of all patients with acute psychiatric illness are often themselves severely distressed at the time of admission , but day hospital treatment leads to less burden on carers in the long term . Key messages When inpatient treatment is avoidable day hospital treatment is cheaper for acutely ill psychiatric patients Carers of acutely ill psychiatric patients experience severe distress and warrant help in their own right Inpatient treatment relieves symptoms more rapidly than day hospital treatment but may lead to increased burden on carers one year Objective : This paper describes the administrative process by which the Ottawa General Hospital ( OGH ) closed 6 beds and used the staff and space re sources thus released to set up an acute day hospital ( ADH ) for the treatment of 8 acutely ill psychiatric patients . Outcome data are presented on the first 160 patients admitted to the ADH . Methods : Demographic and clinical information including diagnostic ( DSM-III-R ; Global Assessment of Functioning [ GAF ] ) and question naire data ( Symptom Checklist-90 Revised [ SCL-90R ] ; Beck Depression Inventory [ BDI ] ; State-Trait Anxiety Inventory [ STAI ] ; patient satisfaction ) were obtained from 160 ADH patients at admission and discharge . Forty-two of these patients provided follow-up data 3 to 6 months postdischarge . The outcome of ADH patients was compared with that of a retrospectively obtained r and om sample ( n = 100 ) of in patients on selected diagnostic and demographic variables . Results : On clinician-rated and self-report clinical scales , ADH patients showed significant clinical improvement reflected in higher GAF scores and less psychological distress , depression , and anxiety at discharge relative to admission . There were no significant group differences in outcome indices except for shorter length of stay in the ADH group compared with in patients . The ADH group rated the program highly in help received and quality of service . Short-term follow-up showed that gains made during treatment were maintained 3 to 6 months later . Conclusions : These results show that a time-limited day hospital program is clinical ly effective for acutely ill psychiatric patients and leads to a more efficient use of inpatient re sources . We believe that partial hospitalization for the treatment of acute psychiatric disorders may have wide application in psychiatric hospital practice OBJECTIVE This study compared the effectiveness of psychoanalytically oriented partial hospitalization with st and ard psychiatric care for patients with borderline personality disorder . METHOD Thirty-eight patients with borderline personality disorder , diagnosed according to st and ardized criteria , were allocated either to a partially hospitalized group or to a st and ard psychiatric care ( control ) group in a r and omized controlled design . Treatment , which included individual and group psychoanalytic psychotherapy , was for a maximum of 18 months . Outcome measures included the frequency of suicide attempts and acts of self-harm , the number and duration of inpatient admissions , the use of psychotropic medication , and self-report measures of depression , anxiety , general symptom distress , interpersonal function , and social adjustment . Data analysis used repeated measures analysis of covariance and nonparametric tests of trend . RESULTS Patients who were partially hospitalized showed a statistically significant decrease on all measures in contrast to the control group , which showed limited change or deterioration over the same period . An improvement in depressive symptoms , a decrease in suicidal and self-mutilatory acts , reduced inpatient days , and better social and interpersonal function began at 6 months and continued until the end of treatment at 18 months . CONCLUSIONS Psychoanalytically oriented partial hospitalization is superior to st and ard psychiatric care for patients with borderline personality disorder . Replication is needed with larger groups , but these results suggest that partial hospitalization may offer an alternative to inpatient treatment OBJECTIVE The outcome of a day treatment program for psychiatric out patients with affective and personality disorders was evaluated . The program was dynamically oriented , intensive , group focused , and time limited ( 18 weeks ) . METHODS The prospect i ve trial used a r and omized treatment-versus-control ( delayed-treatment ) design to examine 17 outcome variables covering five areas : interpersonal functioning , symptomatology , self-esteem , life satisfaction , and defensive functioning . Those variables , plus individualized treatment objectives , were monitored before and after the treatment and control periods and at follow-up an average of eight months later . RESULTS Treated patients showed significantly better outcome than control patients for seven of the 17 outcome variables : social dysfunction , family dysfunction , interpersonal behavior , mood level , life satisfaction , self-esteem , and severity of disturbance associated with individual goals of treatment as rated by an independent assessor . The findings could not be accounted for by diagnosis or use of medication . Benefits were maintained over the follow-up period . The average treatment-versus-control effect size for all 17 variables was .71 . CONCLUSIONS The study supports the efficacy of an intensive day treatment program for patients who manifest significant difficulties associated with affective and personality disorders Severity of psychiatric illness was assessed using st and ardised clinical and social measures in 69 in- patients and 41 day patients admitted consecutively from the community . Day and in- patients differed little in terms of psychiatric symptoms and social disability , especially if compulsory admissions were excluded . Protection of self or others was a common reason for in-patient admission given by clinicians , who were otherwise prepared to treat seriously ill patients in the day hospital . Very few of the day patients had to be transferred to the in-patient facility , and at three months and one year the two groups showed similar improvements . It is concluded that day treatment is feasible for some seriously ill psychiatric patients , but a r and om-allocation study is required to assess more completely the efficacy of day treatment , and define the characteristics of those who require in-patient admission The effectiveness of day care versus out-patient care in the treatment of persistent severe anxiety and depression was compared in a controlled clinical trial . Of 96 consecutively referred patients meeting the entry criteria , 92 were followed up for six months . Patients were r and omised to day care or out-patient care , and assessed at entry and at six months using the St and ardised Psychiatric Interview and in terms of their time structuring and socialisation . Marked improvement in all three measures was seen for most of the day patients , but for few of the out- patients : this difference was highly significant for each measure . Day patients also rated themselves as coping more effectively and as more satisfied with their treatment . These differences could not be explained by differences in use of medication . Day treatment should remain an option for patients with persistent anxiety and depression resistant to outpatient treatment The course of the psychopathology and social functioning in an experimental day-treatment group referred for inpatient psychiatric treatment is compared with that of a control group receiving st and ard inpatient care . During a follow-up period of 2 years subjects were interviewed three times . The interview comprised information about psychiatric symptoms , psychological functions , psychiatric diagnosis and social-role functioning . Apart from these discrete assessment s an effort was made to map episodes of illness throughout the follow-up period . Upon entry the groups did not differ in terms of psychopathology or social functioning . At follow-up both groups had improved significantly with respect to symptomatology , psychological and social functioning . The extent to which the groups improved did not differ significantly regarding pathology , but self-care improved more in the experimental group . The average duration of episodes of illness was similar for the experimental and control group . During the 2-year follow-up patients suffered from a well-defined disorder during an average of 11 months . The fact that approximately 40 % of them were still a psychiatric case after 2 years further underscores the severity of their pathology BACKGROUND A r and omised controlled trial of day treatment with community care for patients with schizophrenic and affective disorders , referred for in-patient psychiatric treatment , was conducted to evaluate patterns of treatment and the course of illness with its psychosocial consequences over a period of two years . METHOD Seventy patients , of whom 34 had affective and 36 had schizophrenic disorder , were assigned to the experimental condition ( day treatment with ambulatory and domiciliary care ) , and 33 patients , of whom 16 had affective and 17 had schizophrenic disorder , were assigned to the control condition of st and ard clinical care . RESULTS Day treatment with community care was feasible for 40.6 % of the affective patients and 33.3 % of the schizophrenic patients . The direct treatment costs of both disorders , based on numbers of in- and day-patient days and out-patient contacts over two years , appeared more or less the same . Patients benefited equally from day treatment as from in-patient treatment , although there were some gains in self-care and in functioning in the household among experimentals . Although schizophrenics were socioeconomically worse off , and also suffered from more ( severe ) symptoms and social disabilities than the affective patients at entry into the study , they were similar at two years . This finding is unexpected , compared with other follow-up studies . Extra cost for patients and families were not observed . Patients and their families in the experimental condition were significantly more satisfied with the treatment . Experimental patients spent much more time at home during admission , remained much less time in secluded wards , and were more compliant with treatment . CONCLUSIONS Day treatment could be considered a cost-effective alternative to in-patient treatment In a prospect i ve study the criteria and characteristics associated with the admission of acutely ill psychiatric patients to in-patient or day hospital care were examined . Over a four-month period , 54 patients were admitted to hospital and 43 to a day hospital . There was significantly more schizophrenics in the hospital . Day hospital patients were significantly younger , had shorter psychiatric histories , were considered less severely ill and had more insight into their illness . Hospital patients had poorer employment histories , and perceived their families as less supportive ; admission had more often been requested by them or their families OBJECTIVE So far only five r and omized controlled trials on acute day hospital care have assessed direct health care costs and compared these with costs of conventional inpatient treatment . This paper aims to close this research gap for German speaking countries . METHOD Another trial was conducted at the Department of Psychiatry and Psychotherapy , Dresden University of Technology . Using the Client Service Receipt Inventory interviews with patients at three time-points ( admission , discharge , three months after discharge ) assessed their utilization of health care services . Based on the results of a separate regional cost-calculation project , costs of individual care packages could be calculated . 144 patients ( day care : n = 75 , inpatient care : n = 69 ) with complete data sets for all time-points of assessment were included in the intention-to-treat- analysis . Means of direct costs ( given in Euro and referred to Deutsche Mark prices in 2000 ) were computed , and t-tests and bootstrap- procedures were used for group comparison . Furthermore , missing and sensitivity analyses were conducted . RESULTS Patients in the acute day hospital caused mean direct health care costs of 12 401 per person within the entire period assessed . Thus , their cost level falls below the mean costs of inpatient care ( 15,924 euro per person ) by 22.1 % . Missing analyses showed no selection effects on cost results caused by patients who could not be assessed at all defined time-points . Costs for inpatient and day care services were the most sensitive parameters for maintaining the statistically significant differences of cost means demonstrated between the two study groups . CONCLUSION For German-speaking countries , this study shows for the first time that acute day care -- which has been demonstrated to be clinical ly at least as effective as inpatient care - is the less expensive option if these two setting s are comparatively assessed A controlled , prospect i ve study examined the relative effectiveness of short-term versus long-term psychiatric hospitalization . The results of a two-year follow-up of a sample of 141 schizophrenic patients are reported here . The differences favoring long-term subjects that were apparent at one year postadmission had decreased by two years postadmission . However , there appears to be an interaction between prehospital functioning and length of hospital stay , with subjects who had good prehospital functioning doing better at two years when assigned to long-term hospitalization . Subjects with poor prehospital functioning did about equally well , regardless of length of stay , and may even have showed some tendency to do better with a shorter hospital stay . This reversal of effect was more prominent for women , although this sex difference was not statistically significant OBJECTIVE Because previous studies of day treatment as an alternative to inpatient treatment had major disadvantages or method ological shortcomings , the authors conducted a r and omized controlled trial to estimate and predict the extent to which day treatment is feasible for unselected patients referred for inpatient treatment . METHOD Of 160 patients , 57 were r and omly assigned to the control condition and 103 were assigned to the experimental condition . Control patients received st and ard clinical care . In the experimental condition , day treatment was attempted as soon as the patient 's condition permitted . The average number of nights per week that experimental patients spent away from the hospital was compared to the average number of nights away for patients under st and ard care . RESULTS Day treatment was satisfactory for 40 % of the experimental patients but was completely infeasible for another 40 % . The level of surveillance needed in the first week , physical illness , number of previous admissions , depressive symptoms , and treatment by qualified psychiatrists versus registrars were variables predictive of these differences . CONCLUSIONS In this unselected group of patients , no absolute contraindications against day treatment were found . This suggests that the selection criteria applied in nearly all other controlled studies on the subject were unwarranted . The approach used in this study facilitated treatment in the least restrictive environment possible OBJECTIVE Acute psychiatric day care has been proposed as an alternative to conventional inpatient care , yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries . The aim of this multicenter r and omized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems . METHOD The trial was conducted from December 2000 to September 2003 in 5 European countries , with a sample of 1117 voluntarily admitted patients . Immediately before or very shortly after admission to the participating psychiatric facilities , patients were r and omly allocated to treatment in a day hospital or an inpatient ward . Psychopathology , treatment satisfaction , subjective quality of life , and social disabilities were assessed at admission , at discharge , and 3 and 12 months after discharge . An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates . RESULTS Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms , treatment satisfaction , and quality of life . It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessment s. CONCLUSION This study , which has more than doubled the existing evidence base , has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00153959 A total of 175 newly admitted in patients who lived with families were r and omly assigned to three treatment groups : st and ard inpatient care ( discharge at the therapist 's discretion ) , brief hospitalization ( one week or less ) with transitional day care available , and brief hospitalization without day care . Outpatient aftercare was offered to all patients . The three groups showed no significant differences as to amount of improvement in levels of psychopathology at 3 and 12 weeks , but the briefly hospitalized patients were able to resume their vocational roles sooner . There were no significant differences among the groups in readmission rates A r and omized trial to evaluate day hospital care as an alternative to inpatient treatment in the acute phase of psychiatric illness was ab and oned when too few patients were admitted to the trial to enable any valid generalization to be made concerning the total at-risk population . In accounting for the failure of the experimental design , attention is drawn to the inability of the research team to influence either the organization of the unit , whereby junior staff had no contact with the day hospital , or the prevailing belief among senior staff that the two treatment setting s serve distinctive , not alternative , functions . The implication s of our failure for the feasibility of conducting a successful and externally valid controlled trial in this research setting are explored OBJECTIVE --To assess the proportion of acutely ill psychiatric patients who can be treated in a day hospital and compare the outcome of day patient and inpatient treatment . DESIGN -- Prospect i ve r and omised controlled trial of day patient versus inpatient treatment after exclusion of patients precluded by severity of illness or other factors from being treated as day patients . All three groups assessed at three and 12 months . SETTING --Teaching hospital serving small socially deprived inner city area . Day hospital design ed to take acute admissions because of few beds . PATIENTS --175 Patients were considered , of whom 73 could not be allocated . Of the remaining 102 patients , 51 were allocated to each treatment setting but only 89 became established in treatment -- namely , 41 day patients and 48 in patients . 73 Of these 89 patients were reassessed at three months and 70 at one year . INTERVENTIONS --St and ard day patient and inpatient treatment . MAIN OUTCOME MEASURES --Discharge from hospital and return to previous level of social functioning ; reduction of psychiatric symptoms , abnormal behaviour , and burden on relatives . RESULTS --33 Of 48 in patients were discharged at three months compared with 17 of 41 day patients . But at one year 9 of 48 in patients and three of 41 day patients were in hospital . 18 Of 35 day patients and 16 of 39 in patients were at their previous level of social functioning at one year . The only significant difference at three months was a greater improvement in social role performance in the in patients . At one year there was no significant difference between day patients and in patients in present state examination summary scores and social role performance , burden , or behaviour . CONCLUSIONS --Roughly 40 % of all acutely ill patients presenting for admission to a psychiatric unit may be treated satisfactorily in a well staffed day hospital . The outcome of treatment is similar to that of inpatient care but might possibly reduce readmissions . The hospital costs seem to be similar but further research is required to assess the costs in terms of extra dem and s on relatives , general practitioners , and other community re sources 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 224 newly admitted in patients were r and omly allocated to two treatment groups : st and ard care ( length of stay determined by the clinical team ) and brief care ( acute treatment aim ed at effecting the patient 's discharge after about a week ) . Using a new research instrument ( the Patient Behaviour Assessment Schedule ) , information was gathered from the patient 's closest relative or friend on a sub sample of 99 patients ( the “ target group ” ) , which actually showed shortened length of hospitalization for brief care patients . There were no significant differences between groups at the two follow‐up evaluations on measures of behavioural disturbance and limited social functioning . Results for the whole “ target ” group reveal that although there was significant improvement in both behaviour and social functioning 2 weeks after admission , there was little subsequent change thereafter . Overall , individual patients demonstrated more improvement in behavioural disturbance than in social functioning at the follow‐up interview The paper presents the objectives and design of an ongoing multicenter r and omized , controlled trial EDEN ( European Day Hospital EvaluatioN ) . The EDEN- study aims to evaluate the efficacy of acute psychiatric treatment in a day hospital setting in five European centres : Dresden , London , Michalovce , Prague and Wroclaw . The main hypothesis is that day hospital treatment for acute psychiatric patients is as effective as conventional inpatient hospital care . The objectives of the study are to evaluate the viability and effectiveness of day hospitals for acute psychiatric treatment , to identify subgroups of patients with a more or less favourable outcome so that the treatment setting might be specifically applied and to ascertain the cost-effectiveness of day hospital treatment compared to conventional inpatient treatment . The study utilises a R and omised Controlled Trial ( RCT ) design with repeated measures at a maximum of six time points : at admission ( t1 ) , one week after admission ( t2 ) , four weeks after admission ( t3 ) , discharge ( t4 ) , three months after discharge ( t5 ) , and 12 months after discharge ( t6 ) . A combination of well-established st and ardised assessment instruments and open questions is used in 6 time periods . If the findings accept the main hypothesis of the study , some practical consequences could be inevitable : at a mental health policy level , these results could lead to an increase in the capacity of day hospitals ; at the clinical level clinicians could redefine their concepts of care to consider the day hospital as an alternative to conventional inpatient treatment ; from economic point of view could lead to reduction of treatment costs This study examined the ability of seven patient characteristics to predict success ( remaining , benefiting ) in a day treatment program for psychiatric out patients . The sample consisted of 165 patients , most with affective and personality disorders , who participated in an intensive psychodynamically and group-oriented program within a controlled clinical trial . Two patient personality characteristics ( psychological mindedness , quality of object relations ) emerged as the strongest predictors . Other variables that contributed to the predictions , either singly or in an interaction with quality of object relations , were age , marriage , presence of a personality disorder , and previous psychiatric hospitalization . The patient 's initial level of symptomatic disturbance was not a significant predictor . The advantage of using predictors that are relevant to the theoretical and technical orientation of a program is emphasized OBJECTIVE To assess the burden on relatives as well as their mental well-being within the context of a r and omized controlled trial on the effectiveness of acute psychiatric day hospital treatment as compared to inpatient treatment . METHOD The study was conducted at the Department of Psychiatry and Psychotherapy , Dresden University of Technology . A sample of 95 relatives was assessed at admission and after four weeks of treatment using the Involvement Evaluation Question naire ( IEQ ) and the General Health Question naire ( GHQ-28 ) , the period to be rated being the last four weeks prior to assessment . RESULTS Relatives reported a mean level of burden , which for both setting s decreased during the first four weeks of treatment . With respect to this period , burden on relatives of day hospital patients did not differ from that on relatives of in patients . The relatives ' mental well-being was markedly impaired , and only that of the in patients ' relatives did slightly improve during treatment . CONCLUSIONS Treating acute mentally ill as day hospital patients does not result in greater burden on relatives compared to treating them as in patients . Independently from treatment setting , relatives of psychiatric patients should be actively approached and offered information , coping strategies , and help . Further research should include qualitative methods Although inpatient hospitalization of very short duration for schizophrenia is currently a widely prevalent treatment approach in the United States , there are few controlled studies of such treatment . Furthermore , there are no controlled studies comparing short-term ( defined here as 21 to 28 days ) with long-term ( defined here as 90 to 120 days ) inpatient treatment . This study has been design ed to try to answer , in part , the following question : What is the relative clinical cost-effectiveness of short-term hospitalization as an alternative to long-term hospitalization for schizophrenic patients in need of hospital care and for whom both types of treatment are judged clinical ly feasible The authors report the results of their controlled study to compare the efficacy of day versus inpatient hospitalization for those patients for whom both treatments are equally feasible clinical ly . Newly admitted in patients from the catchment area were r and omly assigned to either day or inpatient care . Outcome evaluations , including measures of psychopathology and role function , were conducted at various follow-up intervals . The authors found clear evidence of the superiority of day treatment on virtually eveny measure used to evaluate outcome In a prospect i ve screening of emergency admissions of patients suffering from neurosis , personality disorder or adjustment reaction , 100 were assessed as suitable for early transfer to day hospital treatment , 101 as unsuitable , and 39 as not requiring further intervention . Of the unsuitable patients , 39 were grossly disturbed ; the remainder did not differ in severity from those thought suitable , but there was a specific reason against day treatment in all but 13 of the 62 - -most commonly alcohol abuse , physical problems , social problems or aggression . Patients ' attitudes were also important . Recruitment of patients had to be active , with regular visits to the wards by day hospital staff The authors compared treatment results for 141 schizophrenic patients r and omly assigned to short-term or long-term hospitalization . The patients received intensive treatment and were on partially fixed drug dosage schedules . Test results indicated that the short-term group was functioning better at four weeks . However , at discharge ( 21 to 28 days for short-term patients ; 90 to 120 days for long-term ) the long-term group showed significantly better functioning . There were no significant differences between the groups on symptomatology at discharge . The authors discuss the implication s of these findings for decisions regarding length and type of hospitalization for schizophrenic patients A 12‐week self‐control therapy program based on the self‐control model proposed by Rehm was added to the routine program for depressed patients in a psychiatric day‐treatment center . It was hypothesized that addition of the self‐control therapy would accelerate the recovery of depressed patients . Twenty‐five depressed patients were r and omly assigned to either st and ard treatment or st and ard treatment plus the self‐control therapy program . At post‐test , patients in the self‐control condition showed significant improvement with regard to self‐control , self‐esteem , depression , depressed mood and frequency and potential enjoyability of pleasant events , whereas the control patients did not . On 5 of 6 measures the differences between the groups were significant in the hypothesized direction . Although at the 13‐week follow‐up the positive effects of the self‐control therapy were maintained , between‐group differences were no longer significant , except for self‐control 106 patients with anxiety , phobic , and depressive neuroses referred to the outpatient clinics of 6 psychiatrists were r and omly assigned to outpatient care or two forms of psychiatric day care . Ratings of symptoms and social adjustment were recorded before treatment and after 4 and 8 months in 89 patients . There were no important differences in the outcome of day care and outpatient treatment although patients were more satisfied with the outpatient service . Because outpatient care is more economical of time and personnel it should be preferred to psychiatric day care for many neurotic disorders |
12,629 | 23,780,995 | Meta-regression revealed that hypothermia efficacy does not increase as the gross domestic product per capita rises .
There is enough evidence to support hypothermia as the st and ard care for hypoxic-ischemic encephalopathy .
Evidence from low-re source setting s is limited , but hypothermia efficacy was not shown to be associated with better re sources countries | null | null |
12,630 | 30,111,907 | A literature review was done , following which it was seen that the use of versah drills for bone OD result ed in undersized osteotomy compared to conventional drills .
It also result ed in improved bone density and increase in percentage bone volume and bone-to-implant contact , thereby improving implant stability | Primary stability in dental implants is an essential factor for achieving successful osseointegration .
Surgical procedure and bone quality are among the most common factors that affect primary stability .
It is also crucial to achieve high-insertion torque which is important for obtaining primary stability .
Maintaining sufficient bone bulk and density is essential to achieve necessary bone-to-implant contact for obtaining a biomechanically stable implant .
A new concept for osteotomy called osseodensification ( OD ) has been at the forefront of changes in surgical site preparation in implantology .
This relatively new concept with universally compatible drills has been proposed to help in better osteotomy preparation , bone densification , and indirect sinus lift and also achieve bone expansion at different sites of varying bone densities .
This procedure has also shown improvement in achieving better implant primary stability and better osteotomy than conventional implant drills .
A systematic review was undertaken to analyze if OD procedure had any advantages over conventional osteotomy on bone density and primary stability . | PURPOSE Achieving primary implant stability in areas with poor bone density is often challenging to the clinician . Previous research has suggested that modified surgical protocol s might be beneficial in such situations . The objective of the present clinical study was to evaluate the survival rate of implants placed using undersized implant site preparation in areas with poor bone density . MATERIAL S AND METHODS A total of 52 implants were placed in 29 patients . Of the 52 implants , 26 were surgically placed according to the st and ard drilling protocol ( control group ) and 26 were placed in low-density bone using an adapted bone drilling method ( test group ) . The maximum insertion torque values and resonance frequency analysis measurements were also recorded . All implants were examined clinical ly and radiographically at follow-up visits during the study period . Oral hygiene status , bleeding on probing , peri-implant probing depth , and implant survival rate were assessed . RESULTS According to the survival criteria used in the present study , no failure was recorded , and the overall survival rate was 100 % for both groups after 12 months . The mean probing depth was 2.75 ± 0.75 mm in the test group and 2.87 ± 0.79 mm in the control group . The mean insertion torque value was 35.19 ± 4.79 Ncm in the test group and 34.62 ± 5.82 Ncm in the control group . The resonance frequency analysis value was 68.58 ± 4.81 implant stability quotient and 66.69 ± 5.41 implant stability quotient in the test and control groups , respectively . The observed differences were not statistically significant ( P > .05 ) . CONCLUSIONS The results of the present study suggest that placement of implants by an adapted drilling technique in sites with poor bone density is beneficial in enhancing primary implant stability and improving the implant survival rate PURPOSE This study evaluated the survival parameters of single-tooth implants through clinical and radiographic analysis . MATERIAL S AND METHODS Implants were restored within a 24-hour period with a provisional crown design ed to receive an occlusal masticatory load . This approach was compared to implants restored after a healing period ( the control group ) . Forty-six implants were placed in 23 patients who were each treated with 2 Frialit-2 implants placed in sites between the second premolar in the maxilla or m and ible . The manufacturer 's recommended formal surgical procedure was followed , and primary stability was st and ardized with a minimum insertion torque of 20 Ncm . The sites were r and omly selected , and the clinical and radiographic parameters were st and ardized with individual templates . RESULTS Data were collected at 24 h , and at 1 , 3 , 6 , 12 , 18 , and 24 months . The experimental group included 10 failed implants ; 9 of the failed implants had been placed with an insertion torque of 20 Ncm . One implant from the control group failed during the 24-month follow-up period . The survival rate was independent of implant length , site position , and bone quality and quantity . Relative risk for implant failure was associated with insertion torque ( relative risk 0.79 [ CI : 0.66 - 0.930 ] ; Cox regression ) ( P < or = .007 ) , in the experimental group but was not significant for those in the control group ( ie , implants placed after a healing period ; relative risk 0.78 [ CI : 0.34 - 1.78 ] ; Cox regression ) ( P < or = .057 ) . To achieve osseointegration , it was found that an insertion torque above 32 Ncm was necessary ( chi2= 15.68 ; P < or = .004 ) . DISCUSSION A careful evaluation is necessary for a better underst and ing of the survival rates of immediately loaded implants . In this study , insertion torque was associated with the potential for risk , which can be decreased by 20 % per 9.8 Ncm added . CONCLUSION Given these results , and considering the number of patients treated , immediate provisional crowns should only be proposed with early loading if an appropriate initial insertion torque has been applied |
12,631 | 29,284,075 | AUTHORS ' CONCLUSIONS Low- quality evidence suggests that ART using H-GIC may have a higher risk of restoration failure than conventional treatment for caries lesions in primary teeth . | BACKGROUND Dental caries is a sugar-dependent disease that damages tooth structure and , due to loss of mineral components , may eventually lead to cavitation .
Dental caries is the most prevalent disease worldwide and is considered the most important burden of oral health .
Conventional treatment methods ( drill and fill ) involve the use of rotary burs under local anaesthesia .
The need for an electricity supply , expensive h and pieces and highly trained dental health personnel may limit access to dental treatment , especially in underdeveloped regions .
To overcome the limitations of conventional restorative treatment , the Atraumatic Restorative Treatment ( ART ) was developed , mainly for treating caries in children living in under-served areas of the world where re sources and facilities such as electricity and trained manpower are limited .
ART is a minimally invasive approach which involves removal of decayed tissue using h and instruments alone , usually without use of anaesthesia and electrically driven equipment , and restoration of the dental cavity with an adhesive material ( glass ionomer cement ( GIC ) , composite resins , resin-modified glass-ionomer cement ( RM-GICs ) and compomers ) .
OBJECTIVES To assess the effects of Atraumatic Restorative Treatment ( ART ) compared with conventional treatment for managing dental caries lesions in the primary and permanent teeth of children and adults . | Background Venous leg ulcers constitute a chronic recurring complaint that affects 1.0–1.3 % of the adult population at some time in life , and which corresponds to approximately 75 % of all chronic ulcers of the leg . Multilayer compression b and aging is , at present , the only treatment that has been proved to be effective in treating this type of ulcer . There is no consensus , however , about the dressings that may be applied , beneath the compression , to promote the healing of this type of ulcer , as there does not seem to be any added benefit from using special dressings rather than simple , low-adherence ones . As well as analgesia , acupuncture provokes peripheral vasodilation , in skin and muscles – which has been demonstrated both experimentally and in clinical practice – probably due to the axon reflex , among other mechanisms . The aim of the present study is to measure the effectiveness and cost of compression treatment for venous leg ulcers combined with special dressings , in comparison with low-adherence ones and acupuncture . Methods / design Cluster-r and omized open-labeled trial , at 15 primary healthcare clinics in the Sevilla-Sur Healthcare District , with a control group treated with compression b and aging and low-adherence dressings ; the experiment will consist , on the one h and , of the compression treatment applied in combination with special dressings ( Treatment 1 ) , and on the other , the compression treatment applied in association with low-adherence dressings , together with acupuncture ( Treatment 2 ) . Discussion The results will be measured and recorded in terms of the median time elapsed until complete healing of the ulcer , and the rate of complete healing at 3 months after beginning the treatment . An economic analysis will also be made . This study , carried out in the context of real clinical practice , will provide information for decision-taking concerning the effectiveness of special dressings . Moreover , for the first time a high- quality study will evaluate the effectiveness of acupuncture in the process of healing venous leg ulcers . Trial registration Current Controlled Trials IS RCT N26438275 The present r and omised clinical trial was aim ed at comparing three minimally invasive restorative treatment approaches for managing dental caries in occlusal surfaces using a non-gamma-2 amalgam and a low-viscosity glass-ionomer as the restorative material . The treatment approaches tested in parallel groups were : conventional in a university setting , modified-conventional and ultraconservative ( Atraumatic Restorative Treatment , ART ) approaches in a field setting . A split-mouth design was used in which the two restorative material s were r and omly placed in 430 matched contralateral pairs of permanent molar teeth . A total of 152 children from five primary schools were recruited and treated by a dental therapist . The restorations were evaluated after 6 years by 2 calibrated independent examiners . The 6-year successes for all occlusal amalgam and glass-ionomer restorations were 72.6 and 72.3 % , respectively . There were no statistically significant differences observed between the successes for both amalgam and glass-ionomer restorations placed either by the ART ( 68.6 % , with 95 % CI = 61–76 % ) approach or by the conventional ( 74.5 % , with 95 % CI = 65–82 % ) and the modified-conventional ( 75.8 % , with 95 % CI = 67–83 % ) approaches after 6 years . There was also no statistically significant difference observed between the successes of occlusal ART restorations with glass-ionomer ( 67.1 % , with 95 % CI = 56–77 % ) and occlusal conventional restorations with amalgam ( 74 % , with 95 % CI = 61–85 % ) after 6 years . ‘ Restoration fracture/marginal defects ’ and ‘ loss of material ’ were the most common causes for failure . The former was more often recorded in amalgam restorations and the latter in glass-ionomer restorations . Secondary caries was observed for 2 % of glass-ionomer and for 10 % of amalgam restorations . This difference was statistically significant ( p = 0.001 ) . The ART approach using glass-ionomer performed equally well as conventional restorative approaches using electrically driven equipment and amalgam for treating dentinal lesions in occlusal surfaces after 6 years OBJECTIVE To compare the survival of glass ionomer cement ( GIC ) restorations placed in a dental clinic setting using both the atraumatic restorative treatment ( ART ) approach with h and instruments , and conventional cavity preparation with rotary instruments . METHOD AND MATERIAL S Two encapsulated high-strength conventional GICs ( Fuji IX GP , Ketac-Molar Aplicap ) were placed in 82 Class I and 53 Class II preparations and one encapsulated non-gamma 2 amalgam alloy ( GK-amalgam ) was placed in 32 Class I preparations , in the primary molars of 60 Chinese children with a mean age of 7.40 + /- 1.24 ( SD ) years . Thus , 9 treatment groups were formed . RESULTS After two years , there were no significant survival differences found among 7 of the 9 treatment groups ( p = 0.99 ) . However , two groups comprising Fuji IX GP and Ketac-Molar Aplicap placed in Class II cavities prepared using the ART approach showed significantly lower restoration survivals ( p < 0.001 ) . Only 3 of the 72 initially sealed fissures adjacent to the restorations appeared to retain any GIC material . CONCLUSIONS In a clinic setting , both the ART h and instrument and conventional rotary instrument methods were equally suitable for high Class I restoration survival , but not for Class II restoration survival where the conventional cavity preparation method was preferable The purpose of this study was to evaluate the clinical performance of glass ionomer cement ( GIC ) restorations comparing two minimally invasive methods in permanent teeth after 12 months . Fifty pregnant women ( second trimester of pregnancy ) , mean age 22 ± 5.30 years , were treated by two previously trained operators . The treatment approaches tested were : chemomechanical method ( CarisolvTM ; MediTeam ) and atraumatic restorative treatment ( ART ) . A split-mouth study design was used in which the two treatments were r and omly placed in 50 matched pairs of permanent teeth . The chemomechanical method ( CM ) was the test group and the ART was the control group . The treatments were performed in Public Health Centers . The tested restorative material was a high-strength GIC ( Ketac Molar ; 3M/ESPE ) . The restorations were placed according to the ART guidelines . Two calibrated independent examiners evaluated the restorations in accordance with ART criteria . The interexaminer kappa was 0.97 . Data were analyzed using 95 % confidence interval on the binomial distribution and Fisher 's exact test at 5 % significance level . In a 12-month follow-up , 86 % of the restorations were evaluated . In the test group ( CM ) , 100 % ( CI=93.3 - 100 % ) of the restorations were considered successful . In the control group ( ART ) 97.6 % ( CI=87.4 - 99.9 % ) of the restorations were considered successful and 2.4 % unsuccessful ( marginal defect > 0.5 mm ) . There was no statistically significant difference between the 12-mounth success rate for both groups ( Fisher 's exact test : P=0.49 ) and between the two operators ( Fisher 's exact test : P=1.00 ) . Both minimally invasive methods , chemomechanical method and ART , showed a similar clinical performance after 12 months of follow up OBJECTIVE To compare the level of pain among children treated according to the Atraumatic Restorative Treatment ( ART ) and the Conventional Restorative Treatment ( CRT ) . STUDY DESIGN Forty children of both genders , 4- to 7-years old , presenting Class I cavitated dentin lesions in primary molars were r and omly allocated to 2 groups . One group ( CRT ) received conventional restorative treatment using rotary instruments , while in the other one ( ART ) h and instruments were used to perform the restorations . All children were treated by the same operator A high-viscosity glass-ionomer cement ( Fuji IX ) was used to restore the teeth in both groups . Children 's pain was measured at the end of the first restorative treatment session using the Wong-Baker FACES Pain Rating Scale ( dependent variable ) . Age , gender , treatment time and treatment group were independent variables . ANOVA and ANCOVA tests were used to analyze the data . RESULTS The CRT procedure took longer than the ART procedure ( p < 0.001 ) . Children from the ART group reported less pain than those from the CRT group ( p = 0.0037 ) . Four year olds reported more pain than 5- to 7-year olds ( p < 0.0001 ) in both groups . CONCLUSIONS Restorations placed using ART were less time consuming , children felt less pain when the ART approach was used , and younger children ( 4-years ) reported more pain than the older ones for both restorative treatments Successful use of atraumatic restorative treatment ( ART ) in children has been reported , but little information is available regarding its use in older adults . The hypothesis of this study was that survival rates of root restorations placed by both ART and the conventional technique were similar . Root-surface caries lesions in 103 institutionalized elders in Hong Kong were treated r and omly by either : ( 1 ) the conventional approach — caries removed by dental burs , and the cavity filled with light-cured resin-modified glass ionomer ; or ( 2 ) the ART approach — caries removed by h and instruments , and the cavity filled with chemically cured high-strength glass ionomer . In total , 84 conventional and 78 ART restorations were placed . After 12 months , 63 conventional and 59 ART restorations were review ed , and the respective 12-month survival rates were 91.7 % and 87.0 % ( p > 0.05 ) . It is concluded that the survival rates of both types of root restorations were high and similar AIMS To provide information on the frequency and distribution patterns of sealants in the Public Dental Health Service for Children ( PDHSC ) in Denmark . A further aim was to determine whether there was a correlation between DMF-S and sealants . DESIGN A cross sectional survey using data from 15-year-old Danes in 2003 . SAMPLE AND SUBJECTS : The sample consisted of 50 r and omly selected municipalities from the 204 municipalities with public clinics . Thirty-nine municipalities ( 78 % ) forwarded useful data . A total number of 3,184 15-year-olds were involved in the study . RESULTS The mean DMF-S was 2.97 ( SD = 1.40 ) and 42 % had a DMF-S = 0 . The mean number of sealants was 3.06 ( SD = 1.60 ) . Two-thirds of all participants had one or more sealed surfaces . At the individual level the correlation coefficient ( rs ) between sealants and DMF-S was -0.05 ( p < 0.01 ) . The mean number of sealants in one municipality was 0.26 , in another 6.00 . The surfaces most often sealed , were the occlusal surfaces on permanent second molars ( 35 % ) , closely followed by the occlusal surfaces on permanent first molars ( 32 % ) . Sealants on premolars were rare ( 1.5 % ) . At the municipality level there was no significant correlation between mean DMF-S , % 15-year-olds with a DMF-S = 0 and mean number of sealants ( rs = 0.02 ( p = 0.90 ) and rs = 0.06 ( p = 0.73 ) , respectively ) . CONCLUSION The data indicate a high use of sealants on molar teeth , a very large inter-municipality variation , no correlation between sealants and DMF-S. These findings suggest that there are no clear guidelines for use of sealants in the PDHSC in Denmark BACKGROUND The authors undertook a study to evaluate the effect of two cavity preparation methods on the initial survival of two more-viscous glass ionomer cements , or GICs , placed in the occlusal surfaces of permanent molar teeth . METHODS Three dentists placed 149 restorations in 68 adult patients in a hospital clinic . They used either atraumatic restorative treatment , or ART , or conventional cavity preparation methods to place two encapsulated esthetic conventional GICs : Fuji IX GP ( GC International Corp. , Tokyo ) and Ketac-Molar Aplicap ( 3 M ESPE , Seefeld , Germany ) . For comparison , they used high-copper-content GK Amalgam Alloy ( Advanced Technology & Material s Co. Ltd. , Beijing ) in conventional preparations . They evaluated the restorations using both direct and indirect observation methods . RESULTS Cavity preparations for which the authors used ART h and instruments took approximately twice as long to complete as did those for which they used conventional rotary instruments . After 12 months , no restorations had failed , but restorations comprising both GICs showed early losses of adjacent sealant material . Both GICs also showed relatively high restoration wear . At 12 months , the mean cumulative net occlusal wear for Fuji IX GP was 77 + /- 47 micrometers , and for Ketac-Molar 83 + /- 51 microm , without statistical significance ( P > .05 ) . Color matching improved significantly with time ( P < .001 ) , without significant differences in color between the two GICs by 12 months ( P = .09 ) . The amalgam alloy had minor surface tarnishing and marginal discrepancies increased with time ( P < .00 1 ) . CONCLUSIONS All of the occlusal restorations were rated as satisfactory after 12 months . The method of cavity preparation did not affect the restoration performance of the GICs . However , their deterioration requires long-term monitoring . Clinical Implication s. The more viscous GICs appear initially suitable for restricted use in clinical practice when placed using either of two cavity preparation methods in the occlusal surfaces of permanent molar teeth in adults Pain during invasive treatment of dental caries is a common phenomenon , if no local analgesia has been used before cavity preparation . Atraumatic restorative technique ( ART ) is a suggested procedure which is at least less traumatic for the patient . Although the ART approach has been received well by both children and adults who belong to population groups hardly ever exposed to regular oral health care , it has not yet been proven that this particular procedure really causes less pain , compared to more conventional techniques with rotating instruments . In the present study , pain was reported in connection with tooth restoration in 19.3 percent of the cases , when the ART technique was used , which is significantly less than with a conventional restorative technique ( 35.7 percent ) . Finally the results show a clear relationship in the pain reports between the first and the following treatments in both ART and the conventional technique groups Aim : To assess the effectiveness of three treatment methods ( ART , CarisolvTM and rotary instruments ) in caries removal and sealing capability of h and -mixed glass ionomer in the management of proximal caries in deciduous molars . Methods : In a clinical study 217 dentally naïve children ( age 7.5 , SD 0.57 ) were r and omly divided in three treatment groups and among 4 operators . Each child received one class II glass ionomer restoration . Immediately after restoration bitewings were made . The dependent variables were : residual caries and marginal adaptation . Independent variables were operator effect , child ’s behaviour and time to remove caries . Results : There was no statistical significant difference in residual caries between the three treatment methods ( p > 0.05 ) . In 33 % of the cases a clear radiolucency underneath the restoration was visible on the bitewings . In 26 % doubt existed on the presence of residual caries . A clear cervical gap was seen in 16 % of the restorations , while in 18 % signs of cervical gaps were less obvious . Between the four operators a significant difference in relation to residual caries ( p=0.015 ) was found as well as a significant difference between the operators for the preparation time in the three treatment methods ( p<0.05 ) . The child ’s behaviour seems to have no influence on residual caries and marginal gaps . Conclusion : This study indicates that there is no preparation method superior to another , though the treatment methods seem to be sensitive for operator effects . Using h and -mixed glass ionomer cement result ed in considerable number of cervical gaps found This study compared the survival of restorations produced through the atraumatic restorative treatment ( ART ) approach using glass-ionomer with those produced through the traditional approach using amalgam ( MTA ) in deciduous dentitions over a period of 3 years . Using a parallel group design , 835 grade 1 children , aged 6–7 years , participated . A total of 482 children were treated through the ART and 353 children through the MTA approach . Eight dentists produced a total of 1,891 single- and multiple-surface restorations . After 3 years , 22.1 % of the restorations were lost for evaluation . There was a statistically significant difference in the combined survival of all single- and multiple-surface restorations between the two approaches in favour of the ART approach ( p = 0.04 ) . The study revealed a 3-year cumulative survival percentage of single-surface ART and MTA restorations of 86.1 and 79.6 % , respectively . The difference was statistically significant ( p = 0.03 ) . The main reasons for both single-surface ART and MTA restorations to fail was ‘ restoration missing ’ followed by ‘ gross marginal defect ’ . The 3-year cumulative survival percentages of multiple-surface ART and MTA restorations were 48.7 and 42.9 % , respectively . The difference was not statistically significant ( p > 0.05 ) . The 3-year survival percentages of single- and multiple- surface ART and MTA restorations varied widely amongst the 8 operators with an operator effect ( p = 0.001 ) for multiple-surface MTA restorations . It can be concluded that the ART approach using glass-ionomer yielded better results in treating dentinal lesions in deciduous teeth than did the traditional approach using amalgam after 3 years . It is recommended to select the ART approach to complement the other activities of the school oral health programme Atraumatic Restorative Treatment , ART , is a method of minimal caries intervention that uses only h and instruments . The aim of the present study was to explore a possible difference between the extent of discomfort experienced during dental treatment according to the ART approach and a method using rotary instruments . The study was performed in Indonesia . A total of 403 children were r and omly divided in two groups . In each child , one class II restoration in a deciduous molar was made . One group received treatment using rotary instruments ( 750 r.p.m . ) . The other group was treated according to the ART approach . Glass ionomer cement was used for restoration in both groups . Discomfort scores were determined using both physiological measurements ( heart rate ) and behavioral observations ( Venham ) on specific moments during the treatment . Venham scores showed a marked difference between the two groups at most time points . Heart rate measurements were different at deep excavation . Also , a clear relation between Venham scores and heart rate measurements could be found at all time points . Confounding could be shown for operating dentist , gender of the patient and initial anxiety , not for age . No effect modification could be shown . It can be concluded that children treated according to the ART approach using h and instruments alone experience less discomfort than those treated using rotary instruments Dental caries continues to be a highly prevalent disease among Brazilian preschoolers , especially those with low socioeconomic status . The purpose of this r and omized , controlled trial was to evaluate in vivo 245 simplified restorations in deciduous molars using glass ionomer cements ( Vidrion R and Ketac-Molar ) . Dental restorations were evaluated at 6- and 12-month follow-ups . The teeth restored with Vidrion R ( SS White ) on a single tooth surface were successful in 87 % of the cases evaluated at 6 months and in 63 % at 12 months . The teeth restored with Ketac-Molar on one surface achieved a success rate of 95 % at 6 months and 82 % at 12 months . No recurrent caries or pulpal infection was evident . Logistic regression analysis demonstrated that teeth with cavities restricted to the occlusal surface on sclerotic dentin showed the best adhesion to the restorative material . The restorations with Ketac-Molar had a better clinical performance than those with Vidrion The present study was aim ed at comparing the effectiveness of three minimally invasive restorative treatment approaches for dentinal lesions in occlusal surfaces . The approaches tested comprised a conventional and a modified – conventional treatment and a modified Atraumatic Restorative Treatment ( ART ) . The conventional approach was performed in a university dental clinic whilst the modified – conventional , employing portable equipment , and the modified ART , using h and instruments and a caries removal solution ( Caridex ® ) , were carried out in the field . Using the split – mouth design , 430 matched contralateral pairs of occlusal cavities were restored with amalgam or glass – ionomers in permanent molars of 152 school children by one dental therapist . The restorations were assessed using a modified USPHS – Ryge criteria . After 2 years , the cumulative survival percentages for occlusal amalgam and glass – ionomer restorations were 92 and 96 % , respectively . The survival of all restorations in the conventional , modified – conventional and the modified ART group was 96 , 96 and 91 % , respectively . The survival of occlusal amalgam and glass – ionomer restorations per treatment group was as follows : 94 and 99 % , respectively ( conventional group ) ; 95 and 97 % , respectively ( modified – conventional group ) , and 89 and 93 % , respectively ( modified ART group ) . The differences in survival percentage between restorations with amalgam and glass – ionomer , and between the three restorative treatment approaches were not statistically significant . In countries facing scarcity in re sources for dental care , ART seems a promising restorative approach to occlusal caries in posterior teeth . However , a longer clinical observation period is required to substantiate this initial conclusion Extraction is the most common dental treatment provided for people in rural and suburban areas in many less-industrialised countries . By comparison , restorative care is rarely provided . In order to improve such situations , a treatment technique has been developed based only on h and excavation of carious lesions and using glass-ionomer cement as a filling material and a sealant . This Atraumatic Restorative Treatment ( ART ) technique follows the concept of minimal intervention and does not require electrically driven equipment . This paper reports on the longevity of fillings and sealants placed using the technique under field conditions in rural Thail and . Dental caries was treated using the ART technique in one village , whilst the population in a second village received restorative care ( amalgam fillings ) through mobile dental units . A third village was the control . After one year , 79 per cent of single surface ART fillings and 55 per cent of ART fillings of greater than one surface placed in deciduous teeth were judged successful . The success rate of ART fillings in the permanent dentition ( mainly single surface fillings ) was 93 per cent and the retention rate for sealants was 78 per cent . Children were pleased at having received treatment by this technique and showed little fear . The ART technique is a promising caries treatment procedure for use in rural and sub-urban areas in less-industrialised countries OBJECTIVE This study compares the quality of class I restorations made with the atraumatic restorative treatment ( ART ) technique and conventional class I amalgam restorations . METHODS The study was carried out among secondary school students in Mzuzu , Malawi . First-year students in 1987 who needed at least two class I restorations were selected . Based on a split-mouth design , each participant received both ART and conventional restorations . The 89 pairs of class I cavities were divided r and omly into two groups , since two different cermet ionomer cement ( CIC ) filling material s were used . Impressions of the restorations and subsequent models were made shortly after restoration , after six months , one year , two years , and three years . The quality of the restorations was determined on the models following the US Public Health Service criteria . Bulk fracture , contour , marginal integrity , and surface texture of the restorations were recorded and evaluated separately . Survival rates were determined by the result ant score of all criteria . RESULTS Though conventional amalgam restorations performed better on all criteria , this difference was significant only for the contour criterion . The survival rates of ART restorations after three years ( 81.0 % ) were lower than those of amalgam restorations ( 90.4 % ) ( P=.067 ) . CONCLUSIONS The quality of ART class I restorations is competitive with that of conventional amalgam restorations OBJECTIVE The purpose of this study was to compare the success rates of glass-ionomer cement restorations placed with the atraumatic restorative treatment approach and conventional cavity preparation methods . METHOD AND MATERIAL S Two encapsulated , high-strength , esthetic conventional glass-ionomer cements were placed in 82 Class I and 53 Class II atraumatic restorative treatment and conventional cavity preparations , and an encapsulated amalgam alloy was placed in 32 Class I conventional preparations , in vital primary molars of 60 Chinese children aged 7 to 9 years . RESULTS The atraumatic restorative treatment preparations , made with h and instruments only , took approximately 50 % longer to complete than did the preparations completed with conventional rotary instrumentation . After 1 year , there were no amalgam failures . For the glass-ionomer cement restorations , when the atraumatic restorative treatment method was used , significantly better survival rates were found for Class I ( 92.9 % ) than for Class II ( 64.7 % ) cavity preparations . There was also a strong trend for relatively better survival rates for the conventional cavity preparation method ( 86.7 % ) than for the atraumatic restorative treatment ( 64.7 % ) method for Class II cavity preparations . However , both the atraumatic restorative treatment and conventional methods appeared equally effective for Class I preparations . CONCLUSION In a clinic setting , the use of atraumatic restorative treatment h and instruments for cavity preparation is more time consuming , and the method may also provide less mechanical retention and /or bulk of glass-ionomer cement for some Class II preparations in primary molars than does the use of conventional rotary instruments The atraumatic restorative treatment technique ( ART ) is based on removing infected tooth material using only h and instruments and filling the subsequently cleaned cavity with adhesive material such as glass ionomer . As its name suggests , the ART technique should be atraumatic during treatment , as well as for the tooth itself as for the patient . It was primarily developed for treating people living in underserved areas of the world where re sources and facilities such as electricity and trained manpower are limited . Many studies have evaluated the ART technique and the results have supported its application . However , a very limited number of studies have compared ART with more conventional techniques . For that reason , a study was conducted in Pakistan , to compare the ART technique with another more conventional treatment technique . The results of this study show that the preparations with h and instruments result ed in smaller sized cavities and therefore may be less traumatic to the tooth . It was also associated with less pain reactions compared to the more conventional technique . Although preparations with h and instruments required more time , this did not seem to affect the survival of restorations . The survival of glass ionomer cement restorations made with h and instruments was comparable with single surface amalgam restorations made with a more conventional technique . Recurrent caries was not associated with any glass ionomer cement restorations made with h and instruments . The retention rate of glass ionomer sealants was low , however one dentist had a sealant retention rate of 81.5 percent that suggests that this procedure can be performed satisfactorily in conjunction with a glass ionomer cement restoration . Operator variances did seem to affect the restorations . Survival of glass ionomer restorations made with both h and and rotary instruments varied for different operators . Similarly , the retention of fissure sealant also varied amongst operators . Operator differences also influenced the extent of tooth substance lost due to cavity preparation . The ART technique is a feasible approach towards the treatment of dental caries especially of one-surface lesions for underserved population Atraumatic restorative treatment ( ART ) is an approach to the management of carious lesions that uses only h and instruments to remove carious tissue and to restore the tooth involved . The name ART implies that the approach is atraumatic to both the patient and the tooth . This study set out to evaluate whether ART is atraumatic in terms of both patient discomfort and tooth tissue conservation . Three hundred and fifty-nine patients were divided in two groups : one group was treated with h and instruments and the other with rotary equipment . Each patient received two restorations : one using amalgam and one using glass ionomer as the restorative material , placed without the use of anaesthesia . Less discomfort was reported with the ART approach compared to conventional restorations made using rotary instruments and amalgam . Moreover , preparations with h and instruments were smaller than those produced with rotary instruments . Reported discomfort was associated with the size of the preparation , although the influence of the operator on both criteria was considerable . A patient effect was also observed since patients who reported discomfort during the first treatment were more likely to report discomfort after the second treatment . In conclusion , the choice of the term " ART " as an atraumatic procedure is defensible Aim : To assess the influence of different variables on the survival of class II glass ionomer cements ( GIC ) in a clinical study among 6–7 year old schoolchildren in and around Dar es Salaam , Tanzania . Methods : 217 children were r and omly divided into three groups . In the conventional group , Class-II cavities were excavated with burs , in the ART group they were excavated with h and instruments and in the Carisolv ™ group excavation took place with a chemical solution and special blunt h and instruments . The preparations in all groups were restored with h and mixed GIC ( Fuji IX ) by 4 operators . After restoration , residual caries and cervical gaps were assessed on bite-wing radiographs . The quality of the restorations was established and the survival rate determined in two subsequent evaluations . Results : 195 children ( 90 % ) were present at the first evaluation which took place after 7 months and 194 ( 89 % ) were present at the second evaluation , after one year . At the first evaluation the survival rate of the ART-restorations was 38 % , of the conventional restorations 50 % , and of the Carisolv ™ restorations 35 % . Survival rates at the time of the second evaluation were 30 % , 42 % and 28 % respectively . The differences between the three treatment groups were , however , not significant ( p=0.200 at t=1 and p=0.247 at t=2 ) . In the first evaluation 161 bitewings were available of the 195 restorations , while for the second evaluation 130 . There was no significant relation between residual caries and the success/failure rate ( p=0.140 at t=1 and p=0.201 at t=2 ) . Also , cervical gaps appeared to have no relation with the failure rate ( p=0.057 at t=1 and p=0.833 at t=2 ) However , together those variables have a significant influence on the survival rate ( p = 0.025 ) . Conclusion : The combination of two variables ( residual caries and cervical gaps ) has considerable influence on the survival rate of class II GIC restorations compared to each variable alone OBJECTIVES The Atraumatic Restorative Treatment ( ART ) approach was compared with the traditional amalgam ( TA ) approach in order to test their appropriateness to complement a preventive and educational school oral health programme in Syria . METHODS Using a parallel group design , 370 and 311 grade 2 children were r and omly assigned to the ART and the TA group respectively . Eight dentists placed 1117 single- and multiple-surface restorations . A modified actuarial method was used to estimate survival curves . The jackknife method was applied to calculate the st and ard error in the cumulative survival percentages . RESULTS A statistically significant difference in cumulative survival percentages between single-surface non-occlusal ART and comparable amalgam restorations was observed after 4.3 , 5.3 and 6.3 years . The survival of single-surface non-occlusal ART posterior restorations ( 80.2 + /- 4.9 % ) was statistically significantly higher than that of occlusal posterior ART restorations ( 64.8 + /- 3.9 % ) at evaluation year 6.3 . There was no statistically significant difference observed between survival percentages of large ( 55.8 + /- 10 % ) and that of small ( 69.2 + /- 4.6 % ) single-surface posterior ART restorations after 6.3 years . There was an operator effect observed for single-surface ART and comparable amalgam restorations . Secondary caries was observed in 2.3 % of single-surface ART restorations and in 3.7 % of single-surface amalgam restorations during the 6.3 year observation period . CONCLUSIONS The ART approach provided higher survival percentages for single-surface restorations than the TA approach over 6.3 years and is therefore appropriate for use in school oral health programmes . Secondary caries was only a minor reason for ART restorations to fail . An operator effect was observed for both treatment approaches Background : The prevalence of proximal caries in primary molar teeth is high in many countries . Aims : ( 1 ) To study by means of a split-mouth design the 1- and 2.5-year efficacy of sealing proximal lesions vs. flossing instructions ( control ) on primary molar teeth . ( 2 ) To assess children ’s behaviour and pain perception during the procedure . Methods : Ninety-one 4- to 6-year-old children from Bogotá , Colombia participated . Participants had to have at least two proximal lesions scored according to the following radiographic classification system : radiolucency ( 1 ) in enamel outer half , ( 2 ) restricted to enamel-dentine junction , or ( 3 ) restricted to dentine outer third . Baseline , 1- and 2.5-year follow-up bitewing radiographs were taken . Test and control lesions were r and omly selected . After temporary separation test lesions were sealed ( adhesive ) . Parents/caregivers received a flossing leaflet for their children . Progression of the lesions was assessed by means of independent reading of conventional bitewing radiographs . Results : One-year ( n = 73 ) test vs. control lesion progression was 27.4 vs. 50.7 % , respectively ( p < 0.01 , McNemar ’s test ) , and 2.5-year ( n = 56 ) test vs. control lesion progression was 46.4 vs. 71.4 % , respectively ( p < 0.01 ) . The dropouts did not differ from those who remained in the study regarding relevant caries baseline data . More than 88 % of the participants presented positive to definitively positive behaviour and very low or low pain intensity at both first and second appointments . Conclusion : The sealing technique was superior to flossing instructions both after 1 and 2.5 years of follow-up and the majority of the participants had no anxiety or pain during the treatment The null hypothesis tested was that there is no difference in the survival percentages of all restorations placed through the Atraumatic Restorative Treatment ( ART ) approach , with high-viscosity glass ionomer , and those produced through the traditional approach , with amalgam ( TA ) , in the permanent dentitions of children after 6.3 years . Using a parallel group design , we r and omly assigned a total of 370 children , aged 6 to 9 years , to the ART group and 311 children , also aged 6 to 9 years , to the TA group . Eight dentists placed a total of 1117 single- and multiple-surface restorations . The cumulative survival percentages for ART glass-ionomer restorations were statistically significantly higher than those of amalgam restorations at all time intervals except the first ( p ≤ 0.044 ) . After 6.3 years , the cumulative survival percentages of ART and amalgam restorations were 66.1 % ( SE = 3.1 % ) and 57.0 % ( SE = 3.3 % ) , respectively . We concluded that the restorations produced with the ART approach , with high-viscosity glass ionomer , survived longer than those produced with the traditional approach , with amalgam , in the permanent teeth of young children PURPOSE To test the null-hypothesis that there was no difference in the survival percentages of Class II composite restorations in primary teeth produced through either ART or conventional approaches after 2 years . METHODS 157 children with 325 Class II cavitated dentin lesions were included in a split-mouth study design . A computer program r and omly assigned cavitated dentin lesions to treatment groups stratified for gender , operator , upper/lower jaw and left/right side of the mouth . Three operators placed resin composite ( Pertac II ) restorations using a self-etch adhesive ( Prompt L-Pop ) . Two independent examiners evaluated the restorations after 0.5 , 1 and 2 years using the modified Ryge criteria . A modification of the actuarial survival method was applied to estimate survival percentages . RESULTS There was no statistically significant difference ( P > 0.05 ) observed between the cumulative survival percentages of Class II composite restorations in primary teeth produced by the two approaches after 2 years ( ART : 34.9 % + /- 4.7 % ; conventional : 35.1 % + /- 4.7 % ) . The cumulative survival percentages of ART and conventional Class II restorations of one of the operators were lower than for ART restorations of the other two operators and for conventional restorations of one of the operators ( P < or = 0.001 ) . The main reason for Class II composite restorations to fail over the 2-year period was complete loss of retention ; ART : 75 % ; conventional : 77 % . The null-hypothesis was accepted as there was no difference in the cumulative survival percentages of ART and conventional Class II composite restorations in primary teeth after 2 years . It appears that the low survival results obtained may have been caused by poor bonding of the self-etch adhesive Controversy exists as to whether there is less secondary caries at the margins of glass ionomer restorations compared with other material s that do not release fluoride . This study examined the incidence of secondary caries for three types of restorative material s in Class V restorations in xerostomic patients . The study group consisted of 45 high caries-risk adult patients who had undergone head and neck irradiation for the treatment of cancer . All were substantially xerostomic and in need of at least three restorations in the same arch . Every patient received a restoration with each of the test material s , a conventional glass ionomer ( GI ) , a resin modified glass ionomer ( RMGI ) and a resin composite ( C ) . Patients were instructed in the daily use of a neutral pH sodium fluoride gel in custom trays . Recall appointments were made at 6 , 12 , 18 and 24 months , and the restorations were examined for material loss , marginal integrity and recurrent caries at the restoration margin . Fluoride compliance was determined at each recall period and recorded as the percentage of recommended use during that interval . Patients were categorized at the end of the study as fluoride non-users if their average compliance was 50 % or less . Those with greater than 50 % compliance were categorized as fluoride users . In the latter group , no recurrent caries was found for any of the restorations , whereas a material -dependent incidence of recurrent caries was found in the fluoride non-user group . None of the GI , one RMGI and eight C restorations failed due to recurrent caries . For the fluoride non-user patients , Fishers exact test ( p=0.05 ) showed no statistical difference between GI and RMGI but statistical differences were found among those material s and resin composite at each recall period . Recurrent caries reductions for GI and RMGI relative to C were greater than 80 % in xerostomic patients not using topical fluoride supplementation |
12,632 | 26,805,876 | Currently , there is a lack of convincing evidence to show a cognitive enhancing effect of CE | Chicken essence ( CE ) is a popular traditional remedy in Asia , which is believed to improve cognitive functions .
CE company cl aim ed that the health benefits were proven with research studies .
A systematic review was conducted to determine the cognitive-enhancing effects of CE . | BACKGROUND Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia . One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses . Animal and human data suggest NMDA antagonists worsen executive cognitive controls -- e.g . increase perseverative responses and impair set-shifting . We conducted a preliminary study to test the hypothesis that L-carnosine , an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction , a cognitive domain associated with glutamate . METHODS Seventy-five symptomatically stable adults with chronic schizophrenia were r and omly assigned to L-carnosine as adjunctive treatment ( 2 g/day ) or a matched placebo in a double-blind manner for 3 months . Cognitive domains ( executive dysfunction , memory , attention and motor speed ) were assessed using a computerized battery at baseline , 4 and 12 weeks , along with psychopathology ratings and safety parameters . RESULTS The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments . On the strategic target detection test , the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo . Other cognitive tests showed no significant differences between treatments . Psychopathology scores remained stable . The carnosine group reported more adverse events ( 30 % ) compared with the placebo group ( 14 % ) . Laboratory indices remained within acceptable ranges . CONCLUSIONS These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia Background Fatigue is a common symptom in modern society . There has been a recent resurgence of interest in traditional remedies for fatigue . Chicken essence , which is rich in anserine and carnosine , has been widely taken in Asian countries as a traditional remedy with various aims , including attenuation of physical and mental fatigue . However , the evidence for its efficacy specifically for mental fatigue remains unclear . We examined the effect of essence of chicken on mental fatigue in humans , using our established fatigue-inducing task and evaluation methods . Material / Methods In this placebo-controlled crossover study , 20 healthy male volunteers were r and omized to receive daily oral administration of essence of chicken or placebo drink provided by Cerebos Pacific Ltd. via Suntory holdings Ltd. for 4 weeks . The participants performed 2-back test trials as a fatigue-inducing mental task and then had a rest session . Just before and after each session , they completed cognitive task trials focusing on selective attention to evaluate the level of mental fatigue . Results After essence of chicken intake for 1 and 4 weeks , the reaction times on the cognitive task trials after the rest session were significantly shorter than those at baseline , and significant changes were not observed with placebo intake . The reaction times before and after the fatigue-inducing session were not altered by either essence of chicken or placebo intake . Conclusions We showed that daily intake of essence of chicken could be effective for the recovery from mental fatigue and is a promising c and i date for use as an anti-fatigue food Background It has long been postulated that the relative abundance of specific nutrients can affect cognitive processes and emotions . Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that could be responsible for the action of diet on brain health and cognitive function . Here , through a double-blind , r and omized , placebo-controlled trial , we asked if the newly discovered chicken meat ingredient-168 ( CMI-168 ) could be beneficial to the cognitive function in healthy adults . Methods Normal , healthy subjects were supplemented with either placebo or CMI-168 for 6 weeks . The subjects were given a series of cognitive tests to examine their levels of cognitive functioning at the beginning and end of supplementation , as well as two weeks after termination of supplementation . The combination of these tests , namely Digit Span Backwards , Letter-Number Sequencing , and the Rey Auditory Verbal Learning Test ( RAVLT ) , was used to assess the subjects ’ attention and working memory . For all comparisons , the probability level of p < 0.05 was taken as statistically significant using repeated measure 2-way ANOVA followed by Bonferroni post-hoc test . Results Overall , subjects supplemented with CMI-168 showed significantly ( p < 0.01 ) better performance in all cognitive tests after 6 weeks ’ supplementation compared to control and such superior performance was maintained even 2 weeks after termination of supplementation . Conclusions The present study reveals the cognition-enhancing properties of a recently developed chicken meat ingredient , likely arising from the promotion of attention and prefrontal cortex functions Stress is a common phenomenon . Every individual experiences it . There are many ways of combating stress . Stress is necessary for preparation against challenging situations and danger . It is necessary to have stress before a test so that we are prepared . For instance , stress actually motivates students to prepare for examination but excessive stress can lead to poor performance . This study evaluates the effect of a commercial essence of chicken ( CEC ) on the various parameters related to stress and cognition of human volunteers . CEC is produced by a hot-water extraction process from chicken meat under high pressure condition . It contains concentrated amounts of proteins , amino acids and peptides such as carnosine compared to homemade traditional chicken soup . Due to the unique extraction process , it has been postulated that readily absorbed amino acids and bioactive peptides are present in CEC . In this experiment , we evaluated the effect of CEC in comparison with a placebo and carageenan on a group of stressed medical students before their examinations . Students were divided into three groups at r and om and given either CEC , placebo or a carageenan drink daily for two weeks . Before and after the two weeks , the students were given a series of tests to assess their mental and physical well-being as well as attention and memory . The tests were the general health question naire ( GHQ ) , SF36 , digit span , construction of figures , 3-min memory test , comprehension and mental arithmetic . The students who ingested essence of chicken fared significantly better than the other two groups of students . The ability of essence of chicken to control anxiety by distraction and promoting attention and memory is discussed About 25 % of 1990 - 1991 Persian Gulf War veterans experience disabling fatigue , widespread pain , and cognitive dysfunction termed Gulf War illness ( GWI ) or Chronic Multisymptom Illness ( CMI ) . A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species ( ROS ) and central nervous system injury . The endogenous antioxidant L-carnosine ( β-alanyl-L-histidine ) is a potential treatment since it is a free radical scavenger in nervous tissue . To determine if nutritional supplementation with L-carnosine would significantly improve pain , cognition and fatigue in GWI , a r and omized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed . L-carnosine was given as 500 , 1000 , and 1500 mg increasing at 4 week intervals . Outcomes included subjective fatigue , pain and psychosocial question naires , and instantaneous fatigue and activity levels recorded by ActiWatch Score devices . Cognitive function was evaluated by WAIS-R digit symbol substitution test . Carnosine had 2 potentially beneficial effects : WAIS-R scores increased significantly , and there was a decrease in diarrhea associated with irritable bowel syndrome . No other significant incremental changes were found . Therefore , 12 weeks of carnosine ( 1500 mg ) may have beneficial cognitive effects in GWI . Fatigue , pain , hyperalgesia , activity and other outcomes were resistant to treatment Folk wisdom suggests that chicken extract is useful for recovery from physical and mental fatigue . To explore this question , the physiological effect of Br and 's Essence of Chicken ( BEC ) , a popular chicken extract used as a traditional remedy , was assessed during recovering from mental stress . We quantitated the blood levels of stress-related substances , and examined the task performance and subjects ' mood states during mental workloads . Subjects were 20 , healthy male students who have never tasted BEC . They took two bottles of BEC or a placebo ( 70 ml/bottle ) daily in the morning for 7 days . On the final experimental day , two mental workload tests were performed : ( A ) a mental arithmetic test ( MAT ; 1600 trials of two or three figure-addition or subtraction for 40 min ) . ( B ) a short-term memory test ( SMT ; 20 trials of memorizing 9 digit numbers ) . Blood was collected before and after each workload task . After the mental workload , the recovery of mean cortisol level of subjects who consumed BEC was significantly faster than that for those consuming the placebo . The task performance of subjects performing the MAT and SMT was also improved with BEC consumption compared with placebo . According to the profile of mood state question naire , subjects felt more active and less fatigued during the workload when they took BEC regularly . We conclude that the extract of chicken has the potential to metabolize stress-related substance in blood and to promote recovery from mental fatigue |
12,633 | 24,310,236 | Conclusion In terms of the IOP lowering effect , there is no difference between SLT and ALT .
It is inconclusive whether 90 ° is less efficacious than 180 ° SLT . | Purpose Systemic review to compare selective laser trabeculoplasty ( SLT ) to other glaucoma treatment options in terms of their intraocular pressure (IOP)-lowering effect . | Aim : To compare 90 ° , 180 ° , and 360 ° selective laser trabeculoplasty ( SLT , 532 nm Nd : YAG laser ) with latanoprost 0.005 % for the control of intraocular pressure ( IOP ) in ocular hypertension ( OHT ) and open angle glaucoma ( OAG ) . Methods : A prospect i ve , r and omised clinical trial in the Department of Ophthalmology , St Thomas ’s Hospital , London , and Clayton Eye Centre , Wakefield , West Yorkshire . 167 patients ( 167 eyes ) with either OHT or OAG were r and omised to receive 90 ° , 180 ° , and 360 ° SLT or latanoprost 0.005 % at night and were evaluated at 1 hour , 1 day , 1 week and 1 , 3 , 6 , and 12 months . Results : The mean follow up was 10.3 months ( range 1–12 months ) . Early , transient , complications such as postoperative ocular pain , uveitis , and 1 hour IOP spike occurred in a number of eyes after SLT , with pain being reported more frequently after 360 ° than 90 ° treatments ( p>0.001 ) . Success rates defined in terms of both a 20 % or more and a 30 % or more IOP reduction from baseline measurements with no additional antiglaucomatous interventions were better with latanoprost than 90 ° ( p<0.001 ) and 180 ° SLT ( p<0.02 ) treatments . Differences in success rates between latanoprost and 360 ° SLT did not reach statistical significance ( p<0.5 ) . Success rates were greater with 180 ° and 360 ° compared to 90 ° SLT ( p<0.05 ) . With 360 ° SLT , 82 % of eyes achieved a > 20 % IOP reduction and 59 % a > 30 % reduction from baseline . Although success rates were better with 360 ° than 180 ° SLT treatments , differences did not reach statistical significance . There were no differences with regard to age , sex , race , pretreatment IOP , OHT versus OAG , laser power setting s , and total laser energy delivered between eyes which responded , in terms of a > 20 % and a > 30 % IOP reduction , and those that did not respond with 180 ° and 360 ° SLT treatments . Conclusions : Success rates were higher with latanoprost 0.005 % at night than with 90 ° and 180 ° SLT treatments . 90 ° SLT is generally not effective . 360 ° SLT appears to be an effective treatment with approximately 60 % of eyes achieving an IOP reduction of 30 % or more . Transient anterior uveitis with associated ocular discomfort is not unusual in the first few days after SLT . Late complications causing ocular morbidity after SLT were not encountered Purpose To compare the efficacy of selective laser trabeculoplasty ( SLT ) to argon laser trabeculoplasty ( ALT ) as treatment and retreatment to lower intraocular pressure ( IOP ) in patients with uncontrolled open-angle glaucoma ( OAG ) on maximally tolerated medication therapy with a follow-up of 12 months . Methods A total of 120 eyes of 120 patients with uncontrolled OAG were enrolled in the study . Group A included patients with IOP > 22 mmHg on maximal medical therapy . A total of 43 eyes underwent SLT treatment and 41 eyes underwent ALT treatment . At the end of the follow-up IOP was < 18 mmHg . Group B included patients with IOP > 20 mmHg at 3 months follow-up after SLT or ALT treatment . These patients were retreated r and omly , 18 with SLT and 18 with ALT . Results In Group A at the end of the follow-up there was no statistically significant difference in IOP lowering between SLT ( 6.01 mmHg ) and ALT ( 6.12 ) ( p=0.794 ) . In Group B at the end of the follow-up patients undergoing SLT presented IOP lowering statistically significant to ALT treatment ( 6.24 mmHg and 4.65 mmHg , respectively , p<0.01 ) . Discussion SLT is effective as treatment for patients with OAG and appears to be equivalent to ALT in IOP lowering at 12 months only in patients without a prior treatment . In case of retreatment SLT appears to be better than ALT in IOP lowering Purpose : To study the effectiveness and safety of selective laser trabeculoplasty ( SLT ) on primary open‐angle glaucoma and ocular hypertension in Chinese eyes INTRODUCTION The falling success rate of ALT ( Argon Laser Trabeculoplasty ) has raised the interest in some new laser techniques , such as q-switched Nd : YAG laser trabeculoplasty ( Coherent Selecta 7000 ) . The " selective " laser trabeculoplasty destroys melanosomes of pigmented trabecular meshwork cells , sparing adjacent non-pigmented cells and tissues . AIM Our goal was to establish the IOP lowering effect of selective laser trabeculoplasty ( SLT -- Selecta Laser Trabeculoplasty ) in comparison with ALT . MATERIAL AND METHODS We have examined 27 patients ( 10 men , 17 women ) aged 35 - 82 , with open angle glaucoma and visual field deterioration despite maximal tolerated topical therapy ( 21 patients --POAG , 3 - -NPG , 1 - -pigmentary glaucoma , 1 - -pseudoexfoliative glaucoma , 1 - -juvenile glaucoma ) . One eye of each patient was r and omly chosen for SLT , the other eye underwent ALT . In each method 50 burns were applied in 180 degrees angle with power setting s of 600 - 1000 mW for ALT and energy setting s of 0.5 - 1.4 mJ for SLT . The IOP was measured 1 hour before laser treatment and 1 , 2 , 24 hours and 3 months after treatment . RESULTS The mean initial IOP in eyes selected for SLT was significantly higher ( 21.26 + /- 4.82 mm Hg ) than in eyes selected for ALT ( 20.26 + /- 4.01 mm Hg ) , t-test : p = 0.037 . However , there was no statistically significant difference in the IOP lowering effect between eyes treated with SLT and eyes treated with ALT . The mean IOP drop from the pre-treatment values was -2.85 + /- 4.62 mm Hg after SLT and -2.63 + /- 3.60 mm Hg after ALT ( t-test , p = 0.84 ) . All values : 2 , 24-hours and 3 months after treatment were significantly lower than pre-treatment values in both groups ( t-test , p < 0.03 ) . Only in the 1st hour after SLT the IOP drop was not significant . There was a significant correlation between the amount of pigment on the trabecular meshwork and the IOP fall ( U Mann-Whitney test ) . In SLT group 6 patients ( 21 % ) developed mild iritis during 1st day after laser treatment , which disappeared after fluorometholon drop therapy . CONCLUSION Both methods --SLT and ALT -- have equivalent IOP lowering effect in short time observation ( 3 months ) . Due to entirely novel mode of Selecta laser action , long term results may show significant differences AIMS To compare the effectiveness of selective laser trabeculoplasty ( SLT , a 532 nm Nd : YAG laser ) with argon laser trabeculoplasty ( ALT ) in lowering the intraocular pressure ( IOP ) in patients with medically uncontrolled open angle glaucoma . METHODS A prospect i ve r and omised clinical trial was design ed . Patients were r and omised to treatment with either SLT or ALT and were evaluated at 1 hour , 1 week , 1 , 3 , and 6 months post-laser . RESULTS There were 18 eyes in each group . Baseline characteristics were similar in both groups . In the SLT group the mean IOP at baseline , 1 , 3 , and 6 months was 22.8 ( SD 3.0 ) , 20.1 ( 4.6 ) , 19.3 ( 6.0 ) , and 17.8 ( 4.8 ) mm Hg , respectively . In the ALT group , the mean IOP at baseline , 1 , 3 , and 6 months was 22.5 ( 3.6 ) , 19.5 ( 4.7 ) , 19.6 ( 5.6 ) , and 17.7 ( 3.3 ) mm Hg , respectively . There was a greater anterior chamber reaction , 1 hour after SLT v ALT ( p < 0.01 ) . Patients with previous failed ALT had a better reduction in IOP with SLT than with repeat ALT ( 6.8 ( 2.4 ) v 3.6 ( 1.8 ) mm Hg ; p = 0.01 ) . CONCLUSION SLT appears to be equivalent to ALT in lowering IOP during the first 6 months after treatment . There is a slightly greater anterior chamber reaction 1 hour after SLT . Patients with previous failed ALT had a significantly greater drop in IOP when treated with SLT vALT . These results need to be confirmed with a larger sample size Objective To compare the effectiveness of argon laser trabeculoplasty ( ALT ) and selective laser trabeculoplasty ( SLT ) in lowering intraocular pressure ( IOP ) in younger patients ( age 60 or less ) . Methods This was a prospect i ve r and omized control trial . Forty-two young patients ( age 29 to 60 y ) had 1 eye r and omized to ALT ( n=22 ) or SLT ( n=20 ) . IOP was measured before laser and 1 hour , 1 day , 6 weeks , 3 months , every 3 months until 2 years , and then yearly postlaser . Chi-square analysis and Student t test were used to determine statistical significance . Results The mean IOP before treatment was 21.9 mm Hg for ALT and 19.1 mm Hg for SLT with no statistical difference between the groups ( P>0.05 ) . At 2 years , 86.4 % of ALT and 75.0 % of SLT eyes required no further surgical intervention ( laser trabeculoplasty or trabeculectomy ) . During the same time period , there was a statistically significant IOP decrease of 11.1 % after ALT ( P=0.01 ) and 7.7 % after SLT ( P=0.01 ) with no statistical difference between the lasers ( P>0.05 ) . Conclusions In younger patients , both ALT and SLT have a significant ocular hypotensive effect 2 years after treatment , with no differences in outcome identified between the laser modalities BACKGROUND Argon laser trabeculoplasty ( ALT ) and selective laser trabeculoplasty ( SLT ) are treatments for open-angle glaucoma . Many patients have previously received ALT but could benefit from further treatment . The purpose of this study was to examine whether SLT provided clinical benefit for patients who had previously received complete argon treatment . METHODS This was a prospect i ve , partially r and omized , comparison study . The study compared the effect after 1 year of SLT in patients with open-angle glaucoma ( primary , pigmentary , or pseudoexfoliation ) who had previously received 360 degrees of ALT with the effect of laser treatment ( ALT or SLT ) given for the first time in patients with this condition . Ninety-six subjects were given 180 degrees of laser trabeculoplasty . When both eyes qualified for treatment , the first eye treated was included in the analysis . Twenty-seven subjects were treated with SLT after previously receiving 360 degrees of ALT therapy ; the remainder were given their first laser treatment , 30 being r and omly assigned by coin toss to receive SLT and 39 to receive ALT . RESULTS The mean intraocular pressure ( IOP ) before treatment was 21.5 mm Hg ( SLT after ALT ) , 22.9 mm Hg ( SLT ) , and 22.0 mm Hg ( ALT ) , with no statistical difference among the groups ( p > 0.05 ) . The mean IOP at 1 year was 16.7 mm Hg ( SLT after ALT ) , 17.1 mm Hg ( SLT ) , and 16.4 mm Hg ( ALT ) . The IOP for all 3 groups was statistically significantly lower than at baseline ( p < 0.001 ) , but there were no differences among the groups in this respect ( p > 0.05 ) . At 1 year , the percentage IOP reductions from baseline were 23 % ( SLT ) , 19.3 % ( SLT after ALT ) , and 24 % ( ALT ) . There were no differences among the groups in the number of medications used before the laser , although there was a small but statistically significant decrease in the number of medications used before or after the laser treatment in both the SLT and the SLT after ALT group , but not the ALT group . INTERPRETATION SLT retreatment can produce a clinical ly useful decrease in IOP at 1 year , similar to that obtained by ALT , in patients who have had prior argon laser treatment . SLT may be a useful adjunctive therapy when 360 degrees of ALT has already been performed Introduction : This study evaluated and compared the efficacy of selective laser trabeculoplasty ( SLT ) and argon laser trabeculoplasty ( ALT ) in terms of intraocular pressure (IOP)-lowering effects in pseudophakic patients at various time points after treatment . The primary aim was to compare the efficacy of SLT and ALT in reducing the IOP of pseudophakic glaucoma patients who recently underwent successful cataract extraction surgery . The secondary endpoint was to determine the percentage of SLT and ALT patients whose IOP was successfully reduced by at least 15 % from baseline . Patients and methods : This study was a follow-up of a prospect i ve r and omized clinical trial . Fifty-two eyes from 52 glaucoma patients with uncontrolled IOP who had previously undergone successful phacoemulsification-assisted cataract excision surgery with intracapsular lens implantation were r and omly assigned to treatment with either ALT ( n = 30 ) or SLT ( n = 22 ) . Fifteen patients were excluded due to adverse events encountered during the study , leaving a total of 18 and 19 patients in the ALT and SLT groups , respectively . IOP measurements were carried out at scheduled intervals until 12 months post-laser treatment . Results : There were no significant differences in the IOP-lowering effects between the two methods at any time point during the follow-up period . The greatest differences between the two groups were observed at 1 week posttreatment and at the 3-month time point , but neither reached a level of significance . At the final checkup , the mean IOP reduction from baseline was 3.23 mmHg in the ALT group and 4.30 mmHg in the SLT group ( P = 0.269 ) . At that visit , six ( 35.3 % ) patients in the ALT group and 15 ( 75 % ) patients in the SLT group had a reduction of ≥15 % from their baseline IOP . Conclusion : SLT and ALT are equally effective in their IOP-lowering capabilities in new pseudophakic glaucoma patients during the first 12 months after treatment Purpose To compare the effectiveness and safety of excimer laser trabeculotomy ( ELT ) ab interno vs selective laser trabeculoplasty ( SLT ) over 24 months of follow-up in patients with primary open-angle glaucoma ( POAG ) refractory to medical therapy . Patients and methods This prospect i ve , r and omized study included 30 consecutive eyes assigned r and omly to either ELT or SLT group . ELT was carried out using a XeCl Excimer Laser with an emission wavelength of 308 nm . Eight spots were equally distributed at a distance of 500 μm from one another over the anterior trabeculum . The SLT patients were treated with a frequency-doubled q-switched neodymium : yytrium – aluminum – garnet laser ( wavelength 532 nm ) . Approximately 50 adjacent , but not overlapping , laser spots were distributed over 180 ° of the trabecular meshwork , using an energy level ranging from 0.7 to 1.0 mJ per pulse . The main outcome measure was intraocular pressure ( IOP ) lowering after ELT and SLT . Success was defined as ⩾20 % reduction in IOP without further glaucoma intervention . Results At 24 months , complete success rates were 53.3 % for the ELT group and 40 % for the SLT group ( P=0.35 , Fisher 's exact test ) ; qualified success rates were 33.3 % for the ELT and 26.6 % for the SLT group ( P=0.5 , Fisher 's exact test).Mean IOP decreased from 25.0±1.9 to 17.6±2.2 mmHg ( −29.6 % ; P<0.0001 ) in the ELT group and from 23.9±0.9 to 19.1±1.8 mmHg ( −21%;P<0.0001 ) in the SLT group . Conclusions Both ELT and SLT proved to be effective techniques in the treatment of POAG refractory to medical therapy PURPOSE To compare two regimens of SLT , ie , SLT with 25 laser spots on 90 degrees of trabecular meshwork and SLT with 50 laser spots on 180 degrees of trabecular meshwork in patients with open-angle glaucoma . PATIENTS AND METHODS In a prospect i ve clinical study , the authors compared pressure-lowering effect of SLT in 2 groups of patients ; 1 group ( 32 patients ) received SLT with 25 laser spots on 90 degrees of trabecular meshwork , the other group ( 32 patients ) SLT with 50 laser spots on 180 degrees of trabecular meshwork . RESULT There was no difference in the pressure reduction between these two treatment regimens . Moreover , the pressure reduction was not influenced by previous ALT treatments . The pigmentation in the trabecular meshwork is related to a delayed effect on the pressure lowering after SLT . CONCLUSION SLT with 25 laser spots on 90 degrees of trabecular meshwork has a similar pressure-lowering effect to SLT with 50 laser spots on 180 degrees of trabecular meshwork . The new treatment regimen with less laser spots could increase the repeatability of SLT and reduce potential tissue damage in the trabecular meshwork Abstract Purpose To compare selective laser trabeculoplasty ( SLT ) with conventional argon laser trabeculoplasty ( ALT ) in terms of hypotensive efficacy , anterior chamber inflammation , and pain reported by the patients treated . Methods A prospect i ve study performed on 40 consecutive patients . Group I ( n=20 ) : SLT 180 ° . Group II ( n=20 ) : ALT 180 ° . Intraocular pressure , flare ( Laser-Flare-Meter , Kowa FM-500 , Japan ) , and pain ( Visual Analogue Scale ) were measured before treatment and 1 h , 24 h , 1 week , and 1 , 3 and 6 months after treatment . Statistically significant differences were determined by an independent- sample Student 's t-test . Results At 6 months after treatment , pressure reduction was similar in both groups : SLT 22.2 % ( range 0–36.3 % ) and ALT 19.5 % ( range 0–30.2 % ) , P=0.741 . The energy released during treatment was significantly lower in SLT ( 48.3 SD 7.4 mJ ) than in ALT ( 4321 SD 241.7 mJ ) , P<0.001 . At 1 h after treatment , anterior chamber flare was also lower in SLT ( 13.3 SD 6.3 vs 20.7 SD 7.4 photons/ms ) , P=0.003 . Pain reported by the patients during the treatment was significantly lower in SLT ( 2.0 SD 0.7 vs 4.3 SD 1.3 ) , P<0.001 . Conclusions The hypotensive efficacy of both lasers at the end of follow-up was similar . The energy released during treatment and inflammation produced in the anterior chamber in the immediate postoperative period were significantly lower for SLT . The SLT procedure was better tolerated , producing less discomfort during treatment than conventional trabeculoplasty with argon Aims : To evaluate the effect of selective laser trabeculoplasty ( SLT ) on intraocular pressure ( IOP ) control and diurnal tension curves of patients with open-angle glaucoma ( OAG ) and ocular hypertension ( OHT ) , and to compare this effect with that of latanoprost . Methods : Forty patients were r and omised to receive either SLT or latanoprost . IOP control was evaluated by comparing pretreatment values with post-treatment measurements on day 3 , week 1 , month 1 and 4–6 months ; success was defined as 20 % decrease in IOP . Tension curves were plotted prior to treatment and 4–6 months afterwards ; success was 50 % reduction in fluctuation . Results : SLT decreased pressure by 4.7 mm Hg on average ( 95 % CI 3.6 to 5.7 mm Hg ; p<0.01 ) . The reduction was similar for latanoprost at all follow-ups except month 1 ; 75 % of SLT patients and 73 % of latanoprost patients achieved success in IOP control ( p = 0.4 ) . SLT significantly reduced IOP fluctuation , but latanoprost was more effective ( 3.6 mm Hg , 95 % CI 3.2 to 3.9 mm Hg vs 2.5 mm Hg , 95 % CI 2.2 to 2.9 mm Hg for SLT ; p = 0.04 ) . Success in fluctuation reduction was 50 % for SLT and 83 % for latanoprost ( p = 0.045 ) . Conclusions : Both SLT and latanoprost had a significant impact on IOP control and fluctuation . While latanoprost may be more likely to reduce IOP fluctuation , SLT has the benefit of being a one-time intervention not requiring ongoing patient compliance Purpose To investigate the effect of 180 ° versus 360 ° primary selective laser trabeculoplasty ( SLT ) on tonographic outflow facility and intraocular pressure ( IOP ) . Design Prospect i ve , single masked r and omised clinical trial . Participants Patients with untreated primary open angle glaucoma or ocular hypertension both with IOP > 21–35 mmHg . Methods 40 patients r and omly treated with 180 ° or 360 ° SLT after baseline tonographic outflow facility ( electronic Schiøtz tonography ) and IOP measurements were repeated after 1 month . One eye from each patient was r and omly selected for analysis . Eight untreated eyes were included as a control group . Main Outcome Measures Tonographic outflow facility and IOP difference . Responders were defined as having at least a 20 % reduction in IOP . Results Three patients were excluded due to poor tonography . There were 18 eyes in the 180 ° group and 19 eyes in the 360 ° group . Tonographic outflow facility increased significantly ( 180 ° p=0.003 , 360 ° p=0.005 ) and IOP decreased significantly ( 180 ° and 360 ° p<0.001 ) from baseline . There were no significant differences between the two groups as regards the increase in tonographic outflow facility ( 180 ° group 37.5 % , 360 ° group 41 % , p=0.23 ) and decrease in IOP ( 180 ° group 24 % , 360 ° group 35 % , p=0.35 ) . There were similar number of responders in 180 ° group ( 72 % ) as compared to 360 ° group ( 89.5 % , p=0.23 ) . Tonographic outflow facility and IOP did not change significantly from baseline in the control group ( tonographic outflow facility : 8 % increase p=0.48 , IOP : 4 % decrease p=0.33 ) . Conclusions Primary SLT significantly increased the tonographic outflow facility and decreased IOP in patients with primary open angle glaucoma and ocular hypertension but no statistically significant differences were found between the 360 ° and 180 ° groups . The level of IOP reduction due to primary SLT treatment could not be explained by the increase in tonographic outflow facility alone . Clinical trial registration IS RCT N66330584 , Current Controlled Trials . OBJECTIVE Selective laser trabeculoplasty ( SLT ) and argon laser trabeculoplasty ( ALT ) are used to lower intraocular pressure ( IOP ) in patients with open-angle glaucoma ( OAG ) . We report long-term follow-up data comparing SLT to ALT . DESIGN Follow-up of prospect i ve r and omized clinical trial . PARTICIPANTS Patients with glaucoma from the practice s of three ophthalmologists at the University of Ottawa . METHODS We r and omized 176 eyes of 152 patients with uncontrolled IOP on maximal tolerated medical therapy ( MTMT , with or without previous ALT ) to undergo either SLT or ALT . Data were available for 142 eyes at 3 years , 134 eyes at 4 years , and 120 eyes at 5 years . The primary outcome was change in IOP from pretreatment baseline . RESULTS Comparison of baseline parameters was similar in the two groups . Lowering of IOP were similar at 3 years ( SLT -6.7 ± 7.1 vs ALT -6.1 ± 5.1 ) ; at 4 years ( SLT 7.0 ± 7.7 vs ALT -6.3 ± 5.0 ) ; and at 5 years ( SLT -7.4 ± 7.3 vs ALT -6.7 ± 6.6 ) . There was no statistically significant change in IOP in either of the two groups . Medication changes were equivalent in each group . A number of interventions were required in both groups , cumulatively , over the 5-year follow-up period ( 49 SLT and 33 ALT ) . Survival analysis indicated that the time to 50 % failure in each group was approximately 2 years . CONCLUSIONS The IOP-lowering effect of SLT and ALT was similar over 5 years in this group of patients with open-angle glaucoma on MTMT Purpose To compare the intraocular pressure ( IOP ) response of uncontrolled capsular glaucoma ( CG ) and primary open-angle glaucoma ( POAG ) to selective laser trabeculoplasty ( SLT ) in a prospect i ve clinical trial . Methods Ten eyes of ten patients suffering from uncontrolled CG ( CG Group ) and ten eyes of ten patients with uncontrolled POAG ( POAG Group ) were treated with a frequency-doubled , Q-switched Nd : YAG laser ( 532 nm ) . The baseline characteristics were similar in both groups . IOP was measured before and 1 day , 1 week , 1 month and 3 , 6 , 9 , 12 , 15 and 18 months after treatment . Success was defined as IOP more than 20 % lower than before treatment . Any change of hypotensive medication led to the subjects ' exclusion from the study . The two groups were compared using the independent- sample t test for continuous variables and the log-rank test for survival analysis . A value of p<0.05 was considered significant . Results The mean follow-up was 12.0 months ( SD 5.5 ) for the CG group and 13.5 months ( SD 4.3 ) for POAG ( n.s . ) . No significant difference was found between the two groups for mean pretreatment IOP ( 23.6 mmHg ± 5.70 in the CG group and 22.8 mmHg ± 2.44 in the POAG group ) or for mean IOP and mean IOP reductions during the follow-up . At all follow-up visits , IOP was reduced less in the CG group than in the POAG group ( 24.8 % ± 11.15 vs. 27.7 % ± 9.91 at 6 months , 22.0 % ± 6.66 vs. 30.6 % ± 6.35 at 12 months , and 31.4 % ± 5.55 vs. 35.1 % ± 1.75 at 18 months ) , but the difference was significant only at 12 months . Kaplan-Meier survival analysis gave an 18-month success rate of 64 % in the CG group and 78 % in the POAG group , with no significant differences between the groups . Conclusions SLT is an effective procedure for lowering IOP in CG and POAG eyes , although the effect seems to last less in CG eyes Purpose To compare outcomes of selective laser trabeculoplasty ( SLT ) with drug therapy for glaucoma patients in a prospect i ve r and omized clinical trial . Patients and Methods Sixty-nine patients ( 127 eyes ) with open-angle glaucoma or ocular hypertension were r and omized to SLT or medical therapy . Target intraocular pressure ( IOP ) was determined using the Collaborative Initial Glaucoma Treatment Study formula . Patients were treated with SLT ( 100 applications 360 degrees ) or medical therapy ( prostagl and in analog ) . Six visits over 1 year followed initial treatment . If target IOP range was not attained with SLT , additional SLT was the next step , or in the medical arm additional medications were added . Primary outcome : IOP ; secondary : number of steps . Results Sixty-nine patients were treated . Data collection terminated with 54 patients reaching 9 to 12-months follow-up . Twenty-nine patients were in the SLT group , 25 patients in the medical group . Baseline mean IOP for all eyes was 24.5 mm Hg in the SLT group , 24.7 mm Hg in the medical group . Mean IOP ( both eyes ) at last follow-up was 18.2 mm Hg ( 6.3 mm Hg reduction ) in the SLT arm , 17.7 mm Hg ( 7.0 mm Hg reduction ) in the medical arm . By last follow-up , 11 % of eyes received additional SLT , 27 % required additional medication . There was not a statistically significant difference between the SLT and medication groups . Conclusions IOP reduction was similar in both arms after 9 to 12-months follow-up . More treatment steps were necessary to maintain target IOP in the medication group , although there was not a statistically significant difference between groups . These results support the option of SLT as a safe and effective initial therapy in open-angle glaucoma or ocular hypertension Background / aims : The efficacy and safety of selective laser trabeculoplasty ( SLT ) has been found to be equivalent to argon laser trabeculoplasty ( ALT ) . Since SLT produces significantly less disturbance to the trabecular meshwork and is theoretically more repeatable than ALT , it has potential to replace ALT as the st and ard procedure to treat medically uncontrolled open angle glaucoma . This study ’s objective is to determine factors that predict successful SLT at 1 year post-treatment . Methods : As part of a r and omised clinical trial comparing the efficacy and safety of SLT to ALT , data on 72 SLT patients were collected , and successful SLT defined as having an SLT induced intraocular pressure ( IOP ) reduction of ⩾20 % at 1 year post-treatment follow up . Results : 43 out of the 72 patients who had completed their 1 year follow up visit had an IOP reduction of ⩾20 % from baseline . No glaucoma risk factors studied predicted successful SLT . The amount of trabecular meshwork pigmentation was not a significant predictor . However , it was discovered that baseline IOP strongly predicted SLT success ( odds ratio = 1.16 ; p = 0.0001 ) . Conclusion : SLT success was significantly predicted by baseline IOP but not by age , sex , other glaucoma risk factors , type of open angle glaucoma , or by degree of trabecular meshwork pigmentation BACKGROUND AND OBJECTIVE To determine whether the use of postoperative topical anti-inflammatory therapy affects the intraocular pressure (IOP)-lowering efficacy of selective laser trabeculoplasty in eyes with primary open-angle glaucoma . PATIENTS AND METHODS In this prospect i ve , r and omized , observer-masked study , 25 participants with primary open-angle glaucoma following bilateral 360 degrees selective laser trabeculoplasty used prednisolone acetate 1 % four times daily in one r and omly selected eye for 1 week . IOP was assessed at baseline and 1 week , 1 month , and 3 months after selective laser trabeculoplasty . RESULTS Baseline IOP and selective laser trabeculoplasty treatment parameters were comparable in both groups . Mean IOP was similar in eyes that did and did not receive steroid therapy at 1 week ( 17.0 vs 16.3 mm Hg , respectively , P = .613 ) , 1 month ( 16.8 vs 16.2 mm Hg , respectively ; P = .571 ) , and 3 months ( 16.0 vs 15.8 mm Hg , respectively ; P = .819 ) . CONCLUSION A 1-week course of topical prednisolone acetate 1 % four times daily did not affect the IOP-lowering effect of selective laser trabeculoplasty in eyes with primary open-angle glaucoma BACKGROUND Selective laser trabeculoplasty ( SLT ) is a new method to reduce intraocular pressure in eyes with primary open angle glaucoma . The laser parameters of a Q-switched , frequency-doubled Nd : YAG-laser are set to selectively target pigmented trabecular meshwork cells without visible damage to the adjacent non-pigmented tissue . SLT acts non-thermally , the intracellular microdisruptions triggered by the laser are confined to the targeted cells , the laser pulses are so short that heat caused within the targeted cells does not have time to spread to the surrounding tissue . A controlled prospect i ve r and omised clinical study was conducted to compare the long-term results , safety and efficacy after SLT with two different laser systems and after ALT in the treatment of ocular hypertension and medically uncontrolled open angle glaucoma . PATIENTS AND METHODS About two years ago the authors performed a selective laser trabeculoplasty in 119 eyes using the SLT laser unit Otello ( Glautec AG , ARC , EC ) , here named as SLT-I , and in 124 eyes using the SLT laser unit Selecta II ( Lumenis , Palo Alto , CA ) , here named as SLT-II . In 41 eyes the authors performed argon laser trabeculoplasties using the argon laser Argus ( Aesculap Meditec , EC ) . RESULTS Two months after treatment mean IOP reduction from baseline was 1.9 mmHg or , respectively , 8.8 % after SLT with the SLT-System I , 2.0 mmHg or , respectively , 9.5 % after SLT with SLT-System II , and 2.2 mmHg or , respectively , 9.9 % after ALT with the argon laser . Twelve months after LTP mean pressure reductions were 1.7 mmHg ( 7.9 % ) after SLT-I , 1.8 mmHg ( 8.5 % ) after SLT-II , and 2.1 mmHg ( 9.4 % ) after ALT . The response curve of the eyes with SLT-I greatly resembled that of the eyes with SLT-II and those eyes with ALT . CONCLUSIONS Pressure reduction was highest after ALT , followed by SLT-II , in SLT-I reduction was the least , but the differences were not significant . Our findings did not correspond with those of other authors reporting an average IOP reduction of 25 % after SLT and ALT . SLT has shown reasonable efficacy in lowering IOP in eyes with ocular hypertension and primary open angle glaucoma , SLT achieves about the same level of IOP reduction compared with ALT . As a result of the preservation of the structure of the trabecular meshwork and low rate of complications , SLT is a safe alternative to ALT . The exact biological effect induced with SLT is still not yet understood . For the early glaucoma stages SLT provides an alternative to drug treatment , for the advanced glaucomas SLT is an additional option for further pressure reduction . More long-term follow-up studies are needed to determine whether the IOP lowering effect is sustained over time , and to assess the efficacy of repeated SLT |
12,634 | 7,779,475 | Firm recommendations for clinical practice are not possible because existing evidence neither confirms nor refutes the hypothesis that treatment during the acute phase of herpes zoster reduces pain later | Although a number of r and omized controlled trials of treatment for herpes zoster have been performed , there is no consensus on how it should be managed in general practice .
A systematic review of existing trials , including meta- analysis , was performed to determine the efficacy of available therapies in reducing the incidence of postherpetic neuralgia . | A double-blind r and om selection comparison was made of the therapeutic effects in acute herpes zoster of 40 % idoxuridine ( IDU ) dissolved in dimethyl sulphoxide ( DMSO ) compared with DMSO and saline flavoured with garlic . Thoracic ( 80 patients ) and trigeminal ( 42 patients ) zoster were investigated separately . The patients were evaluated daily until skin healing and then at 1 , 3 and 6 months by registering pain , paraesthesia and sensitivity disturbances as well as by clinical and photographic evaluation of the skin lesions . Duration of pain was positively correlated to age , to delayed healing and to elevated temperature in the acute phase of zoster . The period of pain before skin eruption was considerably longer in thoracic than in trigeminal zoster , while the latter was associated with a more severe inflammatory reaction , more neurologic sequelae , but also by a faster healing of the skin lesions . IDU was highly effective in shortening the period of pain and improving skin healing in trigeminal zoster , while no effect of IDU was observed in thoracic zoster . The reason for this difference is presently not understood The antiviral effect of 5 % idoxuridine in dimethyl sulphoxide intermittently applied and of 40 % idoxuridine in dimethyl sulphoxide continuously applied for four days to the lesions in patients with zoster of recent onset was studied in two double-blind controlled trials . Most , but not all , of the patients receiving intermittent active treatment had pain for a short period only . The effect of continuous treatment was striking : pain had disappeared within nine days in all the patients and healing was accelerated . The results were statistically significant A double-blind , r and om selection comparison was made of the therapeutic effects in acute herpes zoster of ( A ) 40 % idoxuridine ( IDU ) dissolved in dimethyl sulphoxide ( DMSO ) , or one of the following ointments : ( B ) a basis of polyethylene glycol , ( C ) a basis with 60 % DMSO , ( D ) a basis with 5 % IDU and 60 % DMSO , and ( E ) a basis with 40 % IDU and 60 % DMSO . Each group comprised 20 patients . The patients were evaluated daily until skin healing and then at 1,3 , and 6 months by registering 4 neurological signs , 5 clinical evaluations of skin pathology and 4 photographic evaluations of the skin lesions . A ' profile ' of the effect of each treatment was computed by calculating normalized means for each of the 13 variables . A non-r and om distribution of the clinical and photographic variables indicated a statistically significant , but small therapeutic effect of treatment A on skin healing , whereas no convincing effect on pain or sensitivity disturbances was established . Treatments B-E were without positive effects . The information given by the highly interdependent variables were computed for each variable and for groups of variables after appropriate scoring . It was found that the photographic evaluation contributed evidence independent of the clinical evaluation of skin pathology . A multiple correlation analysis revealed that age was positively correlated to the duration of pain and to delayed healing , that rapid healing was intimately connected to no or short-lived pain , and surprisingly that zoster in the trigeminal area healed faster than in other locations without being correlated to less pain . Treatment A must necessarily be reevaluated taking into account proper controls as well as age and affected dermatomes Oral acyclovir , 800 mg five times per day for seven days , was compared with placebo in a r and omized , double-blind trial conducted at three centers in the United Kingdom . The study group consisted of 364 elderly immunocompetent patients with herpes zoster who were entered within 72 hours of the onset of rash . Acyclovir significantly reduced the times to last new lesion formation ( p less than 0.01 ) , loss of vesicles ( p less than 0.01 ) , and full crusting ( p = 0.03 ) . No significant hastening of rash healing was seen in those who started therapy later than 48 hours after the onset of rash . There was also a significant reduction pain during treatment with acyclovir ( p = 0.02 ) . Acyclovir produced no effects on the frequency or severity of post-herpetic neuralgia . No clinical ly important adverse effects of acyclovir were reported In a double-blind r and omised trial , 38 elderly patients with acute herpes zoster received either isoprinosine ( IP ) or placebo . IP neither shortened the acute phase of herpes zoster nor prevented postherpetic neuralgia . Transient asymptomatic hyperuricaemia affected one third of IP treated patients . Shortcomings in study design and misleading interpretation of results are common in previously published clinical trials of herpes zoster and postherpetic neuralgia . Guidelines for future studies are proposed Oral acyclovir therapy for herpes zoster has been studied in double-blind , placebo-controlled trials of two dosages , 400 mg and 800 mg five times per day for 10 days . Compared with placebo recipients , recipients of the high-dosage acyclovir experienced a significantly shortened period of viral shedding , significantly accelerated time to 50 percent scabbing , significantly accelerated time to 50 percent healing , and after two days of therapy , significantly less frequent formation of new lesions . The duration and severity of acute pain were less in acyclovir recipients , with differences in pain severity achieving statistical significance ( p = 0.03 ) between Days 3 and 10 and correlating with the treatment differences in new lesion formation . In studies of the 400 mg five times per day dose schedule , differences between acyclovir and placebo recipients were not significant . In a six-month follow-up of recipients in the higher dosage study , the acyclovir recipients experienced less post-zoster pain than placebo recipients ; differences in the prevalence of pain were most significant for the presence of a persistent pain in the first three months of follow-up . Oral acyclovir at these dosages appears to be free of adverse reactions . In summary , oral acyclovir at a dosage of 800 mg five times per day for 10 days for treatment of acute herpes zoster is superior to 400 mg five times per day and favorably alters the course of the disease Healthy patients with early painful herpes zoster were treated with corticosteroid orally or lactose tablets in a double-blind fashion . The duration of postherpetic neuralgia was shortened by treatment with the corticosteroid . Corticosteroid therapy did not affect pain during the first two weeks or the rate of skin healing . The duration of postherpetic neuralgia could not be predicted by the healing rate of the skin . Control patients less than 60 years old had rapid resolution of their neuralgia while those more than 60 years old had slower resolution of the pain . Corticosteroid therapy did not cause generalization of the eruption Zoster is a common disease that may be associated with severe and protracted pain . Antiviral therapy with acyclovir intravenously has been shown to modify the course of the disease and reduce pain during the acute phase . The results of two studies using doses of 400 mg and 800 mg of acyclovir orally are outlined . The data suggest a significant benefit of the higher dose treatment on the course of the illness and the pain A double-blind , r and omised trial evaluated the efficacy of oral acyclovir , 800 mg 5 times daily for 7 days , in acute herpes zoster and postherpetic neuralgia . Forty patients aged 16 years or over , presenting to their general practitioners within 3 days of rash onset , received acyclovir , while 43 patients received placebo . Acyclovir reduced the extent and duration of the rash , the spread of the rash to adjacent dermatomes and the incidence of disseminated lesions . It shortened the period of new lesion formation and reduced the incidence of ulceration . The weekly prevalence of pain was reduced on acyclovir by the fourth week , with a reduction in the monthly prevalence of chronic pain in the second and third months and a reduction in associated local neurological symptoms between months 3 - 6 . Total analgesic use in the first 4 weeks was reduced by acyclovir , but during follow up there was no difference in the prevalence of analgesic use between groups . There were slightly fewer medical events on acyclovir in the second week , but the frequency was the same in each group for the rest of the 6 months . Biochemical and haematological tests showed no adverse effects of treatment In a r and omised , double-blind , controlled study of the effect of prednisolone on the development of post-herpetic neuralgia 78 patients with herpes zoster whose pain and exanthema had been present for less than 96 h were given 800 mg acyclovir five times daily for 7 days and prednisolone in a total dose of 575 mg , starting with 40 mg daily in the first week and tapering off over the next 2 weeks . 18 ( 23 % ) of the patients had post-herpetic neuralgia at 6 months after the acute zoster , 9 ( 24.3 % ) having received prednisolone and 9 ( 22.5 % ) placebo . The 95 % CI for the difference between the placebo and prednisolone groups in the proportion of patients having pain at 6 months was minus 17 % to plus 20 % . Prednisolone , however , relieved pain for the first 3 days . The 1 - 2 week interval between admission and reappearance of pain and development of triggered pain seems to be the time needed to establish neuralgia . Once established , the type and intensity of pain remained largely unaltered Sixty-four patients with herpes zoster were entered into a r and omised double-masked , placebo-controlled trial of 5 % acyclovir cream applied five times daily for 5 days . Of these patients , 56 were included in the final analysis ( 26 acyclovir , 30 placebo ) . Significant and objective differences in either progression of the rash , severity of acute pain or incidence of post-herpetic neuralgia were not observed . Although significantly more rashes involuted in the acyclovir group , this isolated finding can not be explained . Twenty-two patients ( 12 acyclovir , 10 placebo ) experienced erythema or desquamation or both during treatment with the cream . The similar incidence of skin reactions in both groups suggests that they were related to the cream base rather than the acyclovir Seventy-one nonimmunocompromised patients with herpes zoster ophthalmicus , presenting within seven days of onset of characteristic skin eruption , were enrolled in a prospect i ve , longitudinal , r and omized , double-masked , placebo-controlled trial with oral acyclovir . In a previous interim report we noted more prompt resolution of dermatomal signs and symptoms with acyclovir treatment . There was also a reduction of viral shedding in acyclovir-treated patients coupled with a trend to greater rate of microdissemination of the virus in placebo-treated patients ( Cobo LM , et al. Ophthalmology 1985 ; 92:1574 - 83 ) . While further substantiating these findings , we report that a ten-day course of treatment with oral acyclovir ( 600 mg , five times a day ) is well-tolerated and significantly reduces the incidence and severity of the most common complications of herpes zoster ophthalmicus : dendritiform keratopathy , stromal keratitis , and uveitis . While this acyclovir treatment regimen reduces the zoster-related pain during the acute phase of the disease , especially in patients treated within 72 hours of onset of skin lesions , it has no evident effect on either incidence , severity , or duration of post-herpetic neuralgia in the patients studied In an uncontrolled open assessment of one patient , cimetidine relieved the pain and shortened the course of herpes zoster . A subsequent uncontrolled trial of cimetidine in 21 patients with herpes zoster produced encouraging results in all but three patients . More recently , Mavligit and Talpaz[3 ] reported that cimetidine 300 mg q.d.s . for seven days produced a rapid improvement in the pain and pruritus of herpes zoster in four cancer patients whose immune systems were profoundly suppressed . Herpes zoster is thought to be associated with a state of depressed cellular immune function[4 ] . It is theoretically possible for H2 receptor antagonists such as cimetidine to modify cell-mediated immune responses since thymus dependent T-lymphocytes have been shown to possess H2 receptors[5 - 7 ] . In addition to a possible direct anti-viral effect[2 ] , cimetidine may augment the immune defences of the body which produce early control of the herpes zoster virus Sixty immunocompetent patients with herpes zoster of various dermatomes were treated 5 times a day for 5 days with either acyclovir at a dose of 400 mg or placebo A double-blind , placebo-controlled trial of amantadine hydrochloride ( Symmetrel ) in acute herpes zoster ( shingles ) was carried out in 100 patients in general practice . The cases were serologically proved . There was no difference in duration of pain between the drug and placebo groups when pain disappeared during the 28 days ' observation period . However , pain lasted more than 28 days in a significantly greater proportion of patients receiving placebo than of those on amantadine . Patients with pain after the 28-day observation period were significantly older than those whose pain disappeared during the study . The drug had no effect on rate of healing or appearance of new lesions Forty-seven out patients with herpes zoster , seen within five days of onset of the eruption , received ten days ' administration of oral levodopa and benserazide or placebo in a double-blind controlled study . Both the total patient group and high-risk group , eg , those with either ophthalmic zoster or those older than 65 years , were analyzed . Both groups were comparable in terms of demographic and pathological criteria . Vomiting was the only side effect observed in both groups . A significant decrease in intensity of pain was seen in the group receiving levodopa from the third day , and complete cessation of both pain and sleep disturbances was more frequent in the patients . Two months later , postherpetic neuralgia was also less frequent in the group that received levodopa Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews The effect of ACTH ( Synacthen‐depot ® ) versus prednisone and placebo in the treatment of herpes zoster ( HZ ) was studied in a controlled clinical trial comprising 60 consecutive patients . The treatment groups were comparable regarding sex , age and pre‐entry symptom duration . The skin changes , patients ' pain scores and the consumption of analgesics were monitored . Regarding objective symptoms and the development of postherpetic neuralgia there was no difference between the two treatment groups and placebo , while the ACTH group showed a decrease in pain score and consumption of analgesics during the first 4 days of the trial . Whether this finding will justify the application of ACTH in early HZ is arguable . Neither ACTH nor prednisone influenced the development of postherpetic neuralgia but this negative finding may be inaccurate due to the small number of patients in the three groups . Severe side‐effects did not occur |
12,635 | 27,792,142 | Meals with a high protein or carbohydrate content had a higher DIT than high fat , although this effect was not always significant .
Unclear or inconsistent findings were found by comparing the consumption of meals quickly or slowly , and palatability was not significantly associated with DIT .
These findings indicate that the magnitude of the increase in DIT is influenced by the energy intake , macronutrient composition , and eating pattern of the meal | This systematic review investigated the effects of differing energy intakes , macronutrient compositions , and eating patterns of meals consumed after an overnight fast on Diet Induced Thermogenesis ( DIT ) . | The effects of meal size and frequency on thermic effect of food ( TEF ) were examined in seven healthy normal-weight young women . Each volunteer consumed in r and om order one of two identical meals [ 3138 kJ ( 750 kcal ) , 54.5 % carbohydrate , 14.0 % protein , 31.5 % fat ] . One meal was taken over 10 min [ large meal ( LM ) ] whereas the other was taken in six equal portions of 523 kJ ( 125 kcal ) at 30-min intervals over a 3-h period [ small meals ( SM ) ] . Metabolic rate was measured for 1 h before and every 30 min after the meal started for 5 h. When expressed as either kJ/min ( kcal/min ) or kJ/5h ( kcal/5h ) , TEF was significantly higher in the LM day than in the SM day ( P less than 0.05 ) . We conclude that the temporal pattern in which a mixed caloric load is eaten affects the thermogenic response and may be an important determinant of energy balance after a meal Fifty-two moderately obese adult women were stratified according to their baseline breakfast-eating habits and r and omly assigned a weight-loss program . The no-breakfast group ate two meals per day and the breakfast group ate three meals per day . The energy content of the two weight-loss programs was identical . After the 12-wk treatment , baseline breakfast eaters lost 8.9 kg in the no-breakfast treatment and 6.2 kg in the breakfast treatment . Baseline breakfast skippers lost 7.7 kg in the breakfast treatment and 6.0 kg in the no-breakfast treatment . This treatment-by-strata-by-time interaction effect ( P less than 0.06 ) suggests that those who had to make the most substantial changes in eating habits to comply with the program achieved better results . Analyses of behavioral data suggested that eating breakfast helped reduce dietary fat and minimize impulsive snacking and therefore may be an important part of a weight-reduction program BACKGROUND Different dietary fats are metabolized differently in humans and may influence energy expenditure , substrate oxidation , appetite regulation , and body weight regulation . OBJECTIVE We examined the short-term effects of 4 triacylglycerols ( test fats ) on subjective appetite , ad libitum energy intake , meal-induced thermogenesis , and postpr and ial substrate oxidation . DESIGN Eleven healthy , normal-weight men ( mean age : 25.1 + /- 0.5 y ) consumed 4 different test fats [ conventional fat ( rapeseed oil ) and 3 modified fats ( lipase-structured fat , chemically structured fat , and physically mixed fat ) ] in a r and omized , double-blind , crossover design . RESULTS No significant differences in appetite sensations or ad libitum energy intakes were observed between the 4 test fats . Overall , the 4 fats exerted different effects on energy expenditure ( meal effect : P < 0.01 ) and substrate oxidation ( interaction between meal and time : P < 0.05 ) . In post hoc tests , the 3 modified fats result ed in significantly higher postpr and ial energy expenditure and fat oxidation than did the conventional fat ( P < 0.008 , Bonferroni adjusted ) ; no significant differences were observed between the 3 modified fats . CONCLUSIONS Structured fats do not change short-term postpr and ial appetite sensations or ad libitum energy intakes but do result in higher postpr and ial energy expenditure and fat oxidation than do conventional fats and hence promote negative energy and fat balance . In humans , a physically mixed fat ( trioctanoate + rapeseed oil ) is metabolized as quickly as are structured fats . The position of medium-chain fatty acids on the glycerol backbone of triacylglycerols does not seem to affect energy expenditure or appetite Background : Popular beliefs that breakfast is the most important meal of the day are grounded in cross-sectional observations that link breakfast to health , the causal nature of which remains to be explored under real-life conditions . Objective : The aim was to conduct a r and omized controlled trial examining causal links between breakfast habits and all components of energy balance in free-living humans . Design : The Bath Breakfast Project is a r and omized controlled trial with repeated- measures at baseline and follow-up in a cohort in southwest Engl and aged 21–60 y with dual-energy X-ray absorptiometry – derived fat mass indexes ≤11 kg/m2 in women ( n = 21 ) and ≤7.5 kg/m2 in men ( n = 12 ) . Components of energy balance ( resting metabolic rate , physical activity thermogenesis , energy intake ) and 24-h glycemic responses were measured under free-living conditions with r and om allocation to daily breakfast ( ≥700 kcal before 1100 ) or extended fasting ( 0 kcal until 1200 ) for 6 wk , with baseline and follow-up measures of health markers ( eg , hematology/biopsies ) . Results : Contrary to popular belief , there was no metabolic adaptation to breakfast ( eg , resting metabolic rate stable within 11 kcal/d ) , with limited subsequent suppression of appetite ( energy intake remained 539 kcal/d greater than after fasting ; 95 % CI : 157 , 920 kcal/d ) . Rather , physical activity thermogenesis was markedly higher with breakfast than with fasting ( 442 kcal/d ; 95 % CI : 34 , 851 kcal/d ) . Body mass and adiposity did not differ between treatments at baseline or follow-up and neither did adipose tissue glucose uptake or systemic indexes of cardiovascular health . Continuously measured glycemia was more variable during the afternoon and evening with fasting than with breakfast by the final week of the intervention ( CV : 3.9 % ; 95 % CI : 0.1 % , 7.8 % ) . Conclusions : Daily breakfast is causally linked to higher physical activity thermogenesis in lean adults , with greater overall dietary energy intake but no change in resting metabolism . Cardiovascular health indexes were unaffected by either of the treatments , but breakfast maintained more stable afternoon and evening glycemia than did fasting . This trial was registered at www.is rct n.org as IS RCT N31521726 OBJECTIVE : To study the effect of diet composition on diet-induced thermogenesis ( DIT ) over 24 h in a respiration chamber . SUBJECTS : Eight healthy female volunteers ( age 27±3 y ; body mass index , BMI 23±3 kg/m2).DIETS : A high protein and carbohydrate ( HP/C ) ( 60:10:30 ; percentage energy (E%)carbohydrate , fat and protein , respectively ) and high fat ( HF ) ( 30:60:10 respectively ) diet , both isoenergetic , isovolumetric , composed of normal food items and matched for organoleptic properties ( taste , smell , appearance ) . DESIGN : Subjects spent two 36 h periods each in a respiration chamber consuming both test diets in r and om order . Components of 24 h energy expenditure ( 24 h EE ) : sleeping metabolic rate , DIT and activity induced energy expenditure were measured . RESULTS : DIT was higher in all subjects while on the HP/C diet ( 1295 kJ/d vs 931 kJ/d ; 14.6 % vs 10.5 % of energy intake ; P<0.02 ) . There was no significant difference in other components or total 24 h EE , although there was a trend towards higher EE on the HP/C diet . CONCLUSION : A high protein and carbohydrate diet induces a greater thermic response in healthy individuals when compared to a high fat diet BACKGROUND & AIMS To compare the acute effects of three fatty meals with different fat quality on postpr and ial thermogenesis , substrate oxidation and satiety . METHODS Twenty-nine healthy men aged between 18 and 30 years participated in a r and omised crossover trial comparing the thermogenic effects of three isocaloric meals : high in polyunsaturated fatty acids from walnuts , high in monounsaturated fatty acids from olive oil , and high in saturated fatty acids from fat-rich dairy products . Indirect calorimetry was used to determine resting metabolic rate , respiratory quotient , 5-h postpr and ial energy expenditure and substrate oxidation . Satiety was estimated by using visual analogue scales and measuring caloric intake in a subsequent ad libitum meal . RESULTS Five-h postpr and ial thermogenesis was higher by 28 % after the high-polyunsaturated meal ( p=0.039 ) and by 23 % higher after the high-monounsaturated meal ( p=0.035 ) compared with the high-saturated meal . Fat oxidation rates increased nonsignificantly after the two meals rich in unsaturated fatty acids and decreased nonsignificantly after the high-saturated fatty acid meal . Postpr and ial respiratory quotient , protein and carbohydrate oxidation , and satiety measures were similar among meals . CONCLUSIONS Fat quality determined the thermogenic response to a fatty meal but had no clear effects on substrate oxidation or satiety We investigated the effects of food palatability on the thermic effect of feeding ( TEF ) , substrate oxidation and circulating glucose and insulin . Healthy young men ( 23.4+/-1.0 , SD , years , n=10 ) and older men ( 69.4+/-1.3 , years , n=9 ) were resident in a metabolic unit for two 2-day study periods . On the second day of each period , they consumed in r and om order either a palatable test meal containing 2.93 MJ or a nonpalatable control meal containing the same foods in identical amounts but blended and freeze-dried into biscuit form . TEF and respiratory quotient ( RQ ) were measured over 6 h and blood sample s were taken for measurement of glucose and insulin . Age group had no effect on TEF , RQ or circulating glucose other than to delay the time of peak TEF ( P<0.002 for both meals ) . There was no significant effect of meal type on TEF , but RQ and circulating glucose were higher following consumption of the palatable meal ( P<0.001 for both parameters ) . These results suggest that over 6 h postpr and ial , consumption of palatable foods does not increase TEF , but is instead associated with increased glycemic response and increased carbohydrate oxidation . These changes , combined with previous work on the glycemic index , predict an accelerated return of hunger and increased energy intake at subsequent meals following consumption of palatable vs. control foods . Further studies are needed to examine the possible mechanism for this previously suggested " second meal " effect of diet palatability on energy intake OBJECTIVE To determine whether medium-chain triglycerides , in low-to-moderate amounts consumed with meals ( at breakfast , lunch and dinner ) , can increase daily energy expenditure ( EE ) and 24-h urinary excretion of catecholamines in humans . DESIGN Dose-response study conducted under double-blind r and omised design . SETTING Respiratory chamber at the Faculty of Medicine , University of Geneva . SUBJECTS Eight healthy young men were recruited from the student population by advertisement in our Faculty . METHODS 24-h EE and urinary catecholamines were measured in each subject during stay in a respiratory chamber on four separate occasions . These were r and omised between four different combinations of medium-chain triglycerides ( MCT ) and long-chain triglycerides ( LCT ) , a total 30g/day , which was consumed with their habitual diet in three equal parts ( 10 g each ) at breakfast , lunch , and dinner in the following ratio of MCT : LCT ( g/g ) 0:30 , 5:25 , 15:15 and 30:0 . RESULTS 24-h EE increased significantly with increasing MCT : LCT ratio ( ANOVA , P < 0.001 ) , with the diet providing a total of 15 - 30 g MCT per day stimulating 24-h EE by 5 % : this corresponds to a mean absolute increase in daily EE of approximately 500kJ , with individual values varying between 268 kJ and 756 kJ. No significant differences were observed in respiratory quotient nor in urinary nitrogen losses across diets , but 24-h urinary noradrenaline was significantly increased ( ANOVA , P < 0.025 ) , whereas adrenaline and dopamine were unaltered . CONCLUSIONS This study suggests that relatively low-to-moderate intake of MCT ( 15 - 30 g per day ) as part of habitual diet may play a role in the control of human body composition by enhancing daily EE , and that this effect is mediated at least in part through activation of the sympathetic nervous system Objective : To compare postpr and ial whole-body fat oxidation rates in humans , following high-fat ( 43 % of total energy ) mixed breakfast meals , of fixed energy and macronutrient composition , rich in either monounsaturated fat ( MUFA ) from extra virgin olive oil or saturated fat ( SFA ) from cream . Design : Paired comparison of resting metabolic rate ( RMR ) , thermic effect of a meal and substrate oxidation rates following consumption of isocaloric breakfast meals , differing only in the type of fat , administered in r and om order 1–2 weeks apart . Subjects : Fourteen male volunteers , body mass index ( BMI ) in the range 20–32 kg/m2 , aged 24–49 y and resident in Melbourne , Australia , were recruited by advertisement in the local media or by personal contact . Measurements : Body size and composition was determined by anthropometry and dual energy X-ray absorptiometry ( DEXA ) . Indirect calorimetry was used to measure RMR , thermic effect of a meal , post-meal total energy expenditure and substrate oxidation rate . Blood pressure and pulse rates were measured with an automated oscillometric system . Fasting and 2 h postpr and ial glucose and insulin concentrations and the fasting lipid profile were also determined . Results : In the 5 h following the MUFA breakfast , there was a significantly greater postpr and ial fat oxidation rate ( 3.08±4.58 g/5 h , P=0.017 ) , and lower postpr and ial carbohydrate oxidation rate ( P=0.025 ) , than after the SFA breakfast . Thermic effect of a meal was significantly higher ( 55 kJ/5 h , P=0.034 ) after the MUFA breakfast , in subjects with a high waist circumference ( HWC≥99 cm ) than those with a low waist circumference ( LWC<99 cm ) . This difference was not detected following the SFA breakfast ( P=0.910 ) . Conclusion : If postpr and ial fat oxidation rates are higher after high MUFA , rather than SFA meals , then a simple change to the type of dietary fat consumed might have beneficial effects in curbing weight gain in men consuming a relatively high-fat diet . This may be particularly evident in men with a large waist circumference The impact of variation in palatability on diet- and sucrose-induced thermogenesis was studied in two experiments with 24 healthy young normal-weight subjects , 12 men and 12 women . In the first study , subjects received at r and om in duplicate either a normal liquid test meal ( 2,000 kJ , 12 % protein , 33 % fat , 55 % carbohydrate ) , or an iso-energetic test meal made highly unpalatable with kinin . The difference in palatability did not have a significant impact on postpr and ial metabolism . In the second study subjects received at r and om either a palatable sucrose solution ( 900 kJ ) , an iso-energetic st and ard sucrose solution , or an iso-energetic unpalatable sucrose solution . Kinin and a citrus flavour were used to vary palatability . Postpr and ial energy expenditure over a period of 150 min was not significantly affected by differences in palatability . A separate control experiment to assess the effect of kinin on energy expenditure was carried out in eight subjects . Kinin had no significant effect on energy expenditure over a period of 120 min after ingestion The purpose of this study was to investigate the effect of 5 - 10 g of medium-chain triacylglycerols ( MCT ) on diet-induced thermogenesis in healthy humans . The study compared diet-induced thermogenesis after ingestion of test foods containing MCT and long-chain triacylglycerols ( LCT ) , using a double-blind , crossover design . Eight male and eight female subjects participated in study 1 and study 2 , respectively . In both studies , the LCT was a blend of rapeseed oil and soybean oil . In study 1 , the liquid meals contained 10 g MCT ( 10 M ) , a mixture of 5 g MCT and 5 g LCT ( 5M5L ) , and 10 g LCT ( 10L ) . In study 2 , the subjects were given a meal ( s and wich and clear soup ) with the mayonnaise or margarine containing 5 g of MCT or LCT . Postpr and ial energy expenditure was measured by indirect calorimetry before and during the 6 h after ingestion of the test meals . Diet-induced thermogenesis was significantly greater after 5M5L and 10 M Ingestion as compared to 10L ingestion . Ingestion of the mayonnaise or margarine containing 5 g MCT caused significantly larger diet-induced thermogenesis as compared to that of LCT . These results suggest that , in healthy humans , the intake of 5 - 10 g of MCT causes larger diet-induced thermogenesis than that of LCT , irrespective of the form of meal containing the MCT |
12,636 | 22,470,067 | There was no difference in the rates of wound breakdown between the 2 groups ( OR = 1.07 ; 95 % CI : 0.21 - 5.43 ; P = 0.93 ; I = 44 % ) CONCLUSIONS Triclosan-impregnated sutures do not decrease the rate of SSIs or decrease the rate of wound breakdown . | OBJECTIVE To determine the efficacy and safety of triclosan-impregnated sutures .
BACKGROUND Surgical-site infections ( SSIs ) produce considerable morbidity and increase health care costs .
A potential strategy to decrease the rates of SSIs may be the use of triclosan-impregnated sutures .
These have been endorsed and /or funded by professional and governmental bodies in numerous countries .
Laboratory studies and non systematic review s have suggested that these sutures may reduce SSIs but there has been no summative assessment of this intervention with regard to clinical efficacy and safety . | OBJECT Implantation of cerebrospinal fluid ( CSF ) shunting devices is associated with a 5 - 15 % risk of infection as cited in contemporary pediatric neurosurgical literature . Shunt infections typically require complete removal of the device and prolonged antibiotic treatment followed by shunt replacement . Moreover , shunt infections are commonly associated with prolonged hospital stays , potential comorbidity , and the increased risk of neurological compromise due to ventriculitis or surgical complications . The authors prospect ively evaluated the incidence of CSF shunt infection following shunt procedures performed using either antimicrobial suture ( AMS ) or conventional suture . METHODS In a single-center , prospect i ve , double-blinded , r and omized controlled trial , the authors enrolled 61 patients , among whom 84 CSF shunt procedures were performed over 21 months . R and omization to the study ( AMS ) or control ( placebo ) group was stratified to minimize the effect of known shunt infection risk factors on the findings . Antibacterial shunt components were not used . The primary outcome measure was the incidence of shunt infection within 6 months of surgery . RESULTS The shunt infection rate in the study group was 2 ( 4.3 % ) of 46 procedures and 8 ( 21 % ) of 38 procedures in the control group ( p = 0.038 ) . There were no statistically significant differences in shunt infection risk factors between the groups ( procedure type and time , age < 6 months , weight < 4 kg , recent history of shunt infection ) . No suture-related adverse events were reported in either group . CONCLUSIONS These results support the suggestion that the use of AMS for CSF shunt surgery wound closure is safe , effective , and may be associated with a reduced risk of postoperative shunt infection . A larger r and omized controlled trial is needed to confirm this association Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies OBJECTIVE To evaluate the efficacy and safety of new antibacterial suture ( Vicryl Plus ) compared with a traditional braided suture ( Vicryl ) in a clinical study . The primary goal was to study effectiveness on reduced surgical site infection in an appendectomy operation . The authors ' secondary goal was to analyze the safety and physical properties of Vicryl plus . MATERIAL AND METHOD This was a prospect i ve , r and omized , controlled , double blind , comparative , single-center study . After appendectomy was done , the patients were r and omized in two groups : Vicryl Plus and Vicryl to selected suture for suturing the abdominal sheath . The surgical site infection was evaluated for 30 days , 6 months , and 1 year . The surgeons and attending doctor were blind to the type of suture . This is the primary report of the first 100 patients . RESULTS There was no difference in demographic and preoperative clinical in both groups . Although there was no statistical difference in the surgical site infection of Vicryl and Vicryl Plus ( 8 and 10 % , p = 0.05 ) , one case of deep surgical site infection was detected in the Vicryl group . No complications and no difference in related suture material s were detected . CONCLUSION Coated polyglactin 910 with tricosan ( Vicryl Plus ) is safe and satisfactory in surgical practice . Surgical site infection of appendectomy seemed too to be comparable between coated polyglactin 910 with tricosan ( Vicryl Plus ) and traditional polyglactin 910 ( Vicryl ) group BACKGROUND Coated polyglactin 910 suture with triclosan was developed recently in order to imbue the parent suture , coated polyglactin 910 , with antibacterial activity against the most common organisms that cause surgical site infections ( SSI ) . Because such alterations could alter the physical properties of the suture , this study sought to compare the intraoperative h and ling and wound healing characteristics of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture in pediatric patients undergoing various general surgical procedures . METHODS This was a prospect i ve , r and omized , controlled , open-label , comparative , single-center study . Pediatric patients ( age 1 - 18 years ) undergoing various surgical procedures were r and omized in a 2:1 ratio to treatment with either coated polyglactin 910 suture with triclosan or coated polyglactin 910 suture . The primary endpoint was the surgeon 's assessment of the overall intraoperative h and ling of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture without triclosan . The secondary endpoints included specific intraoperative suture h and ling measures and wound healing assessment s. The suture h and ling measures were ( 1 ) ease of passage through tissue ; ( 2 ) first-throw knot holding ; ( 3 ) knot tie-down smoothness ; ( 4 ) knot security ; ( 5 ) surgical h and ling ; ( 6 ) surgical h and ; ( 7 ) memory ; and ( 8) suture fraying . Assessment of wound healing included the following : Healing progress , infection , edema , erythema , skin temperature , seroma , suture sinus , and pain . Adverse events were recorded . RESULTS Scores for intraoperative h and ling were favorable and not significantly different for both sutures , although coated polyglactin 910 suture with triclosan received more " excellent " scores ( 71 % vs. 59 % ) . Wound healing characteristics were comparable for both sutures except for pain on postoperative day 1 . Significantly fewer patients treated with polyglactin 910 suture with triclosan reported pain on day 1 than patients who received the other suture ( 68 % vs. 89 % , p = 0.01 ) . The overall incidence of adverse events was 18 % ; none was devicerelated . CONCLUSIONS Coated polyglactin 910 suture with triclosan performed as well or better than traditional coated polyglactin 910 suture in pediatric patients undergoing general surgical procedures . The incidence of postoperative pain was significantly less in patients treated with coated polyglactin 910 suture with triclosan than the traditional suture . We speculate that polyglactin 910 suture with triclosan , by inhibiting bacterial colonization of the suture , reduced pain that can be an indicator of " sub clinical " infection . Coated polyglactin 910 suture with triclosan may be a useful alternative in patients at increased risk of developing SSI BACKGROUND Wound infection and dehiscence are both major contributors to postoperative morbidity . One potential cause or co-factor is the use of suture material . A recently introduced subcutaneous suture is coated with triclosan ( TC ) , an antiseptic drug . It is suggested to reduce wound complications . METHODS To investigate the effect of TC on wound healing a double blind prospect i ve pilot study in women undergoing a breast reduction was performed . Each patient was her own control . After r and omisation the TC-coated sutures were used either on the left or right side . The contralateral side was used as the control . The incidence of dehiscence was studied . RESULTS Twenty-six patients were included . In the TC breasts there was a wound dehiscence in 16 cases , whereas in the control breasts in seven cases a dehiscence was observed ( P=0.023 ) . CONCLUSION These results suggest that TC-coated sutures should be used with caution . These sutures have already been introduced on to the market without good clinical studies and might have potential adverse effects as shown by these data OBJECTIVES To describe the results of the first year of the Dutch national surveillance of surgical-site infections ( SSIs ) and risk factors , which aims to implement a st and ardized surveillance system in a network of Dutch hospitals , to collect comparable data on SSIs to serve as a reference , and to provide a basic infrastructure for further intervention research . DESIGN Prospect i ve multicenter cohort study . SETTING Acute-care hospitals in The Netherl and s from June 1996 to May 1997 . RESULTS 38 hospitals participated , with a slight over-representation of larger hospitals . Following a total of 18,063 operations , 562 SSIs occurred , of which 198 were deep . Multivariate analysis of pooled procedures shows that age , preoperative length of stay , wound contamination class , anesthesia score , and duration of surgery were independent risk factors for SSI . When analyzed by procedure , the relative importance of these risk factors changed . Bacteriological documentation was available for 56 % of the SSIs ; 35 % of all isolates were Staphylococcus aureus . Multiple regression analysis computed the mean extra postoperative length of stay associated with SSI to be 8.2 days . CONCLUSION The first year of national surveillance has shown that it is feasible to collect comparable data on SSI , which are already used for education , policy , and decision making in the network of participating hospitals . This gives room to effectuate the next aim , namely to use the network as an infrastructure for intervention research . Multivariate analysis shows that feedback on a procedure-specific level is important Research on surgical interventions is associated with several method ological and practical challenges of which few , if any , apply only to surgery . However , surgical evaluation is especially dem and ing because many of these challenges coincide . In this report , the second of three on surgical innovation and evaluation , we discuss obstacles related to the study design of r and omised controlled trials and non-r and omised studies assessing surgical interventions . We also describe the issues related to the nature of surgical procedures -for example , their complexity , surgeon-related factors , and the range of outcomes . Although difficult , surgical evaluation is achievable and necessary . Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential |
12,637 | 17,083,853 | However , the data they provided on effectiveness was poorer than the evidence from the review of effectiveness .
In terms of incremental cost per life-year , laparoscopic surgery was found to be more costly and no more effective than open surgery .
Laparoscopic resection is associated with a quicker recovery ( shorter time to return to usual activities and length of hospitalisation ) and no evidence of a difference in mortality or disease-free survival up to 3 years following surgery .
However , operation times are longer and a significant number of procedures initiated laparoscopically may need to be converted to open surgery .
The rate of conversion may be dependent on experience in terms of both patient selection and performing the technique .
In terms of relative cost-effectiveness , laparoscopic resection is associated with a modest additional cost , short-term benefits associated with more rapid recovery and similar long-term outcomes in terms of survival and cure rates up to 3 years .
Assuming equivalence of long-term outcomes , a judgement is required as to whether the benefits associated with earlier recovery are worth this extra cost . | OBJECTIVE The aim of this study was to determine the clinical effectiveness and cost-effectiveness of laparoscopic , laparoscopically assisted ( hereafter together described as laparoscopic surgery ) and h and -assisted laparoscopic surgery ( HALS ) in comparison with open surgery for the treatment of colorectal cancer . | Laparoscopy-assisted colectomy istechnically feasible , but objective evidence of its benefits remainsscarce . This study was done to evaluate the outcomes and operativestress of laparoscopy-assisted colectomy versus the traditional open method in the management of sigmoid complex polyps that can not besafely or adequately removed by colonofibroscopy . Between January 1997 and December 1999 , a total of 42 patients were equally r and omizedto the laparoscopy group and the laparotomy group by the blockedr and omization method . Three patients r and omized to the laparoscopygroup did not complete the trial ; therefore 18 patients treated bylaparoscopy-assisted sigmoidectomy and the other 21 treated by the open method were prospect ively evaluated . These two groups of patients werewell matched in age , gender , symptoms , tumor location , localization method , tumor size , morphology , histopathology , and the accuracy of the clinical diagnosis . Two st and ardized surgical strategies , thelateral-to-medial and medial-to-lateral dissection sequences , wereperformed in 14 and 4 patients of the laparoscopy group , respectively , according to whether their tumors were located above or below 20 cmabove the anal verge . After evaluating the surgical outcomes , we foundthat the laparoscopy group was significantly better than the laparotomygroup in regard to parameters that included severity of postoperativepain , wound size , postoperative complication rate , and the duration ofpostoperative ileus , hospitalization , and disability . There was nosignificant difference in the operating times for these two groups . However , the costs of the laparoscopy group were significantly higher . To evaluate the surgical stress , we measured the serum C-reactiveprotein ( CRP ) level , erythrocyte sedimentation rate ( ESR ) , totallymphocyte count , and CD4+/CD8 + ratio 24 hoursbefore and after surgery . We found that the postoperative serum CRPlevel and the ESR were significantly less elevated and the totallymphocyte counts and CD4+/CD8 + ratio weresignificantly less depressed in the laparoscopy group than in thelaparotomy group . We thus concluded that laparoscopy-assistedsigmoidectomy can be safely performed with shorter convalescence and less operative stress but at a higher cost . We strongly recommended theuse of this technique in the management of sigmoid complex polyps ifthe patient 's economic status permits Background and aims : Reduced fibrinolytic activity of the peritoneum seems to be the main cause of postoperative adhesions . This prospect i ve r and omized trial compared the peritoneal fibrinolytic activity between laparoscopic and conventional colorectal resection . Methods : Parietal peritoneal biopsy specimens were taken in st and ardized elective laparoscopic ( n=14 ) and conventional ( n=16 ) colorectal resections at the beginning and at the end of surgery . Activities and concentrations of tissue-plasminogen activator ( tPA ) , plasminogen activator ( PAI ) type 1 , and tPA/PAI complex were determined by ELISA kits . Results : There was no difference in age , sex , or body mass index between the two groups . Perioperative tPA activity decreased in both groups without differences between the groups . Concentrations and activities of tPA , PAI-1 , and tPA/PAI complex did not differ between the groups at any time . Conclusion : Peritoneal concentrations and activities of tPA , PAI-1 , and tPA/PAI complex are similar during laparoscopic and conventional colorectal resections . A capnoperitoneum of 12 mmHg over 3 h did not affect the peritoneal fibrinolytic BACKGROUND Adjuvant chemotherapy ( 5-fluorouracil , levamisole ) is now st and ard practice in the treatment of Dukes ' B and C coloretal carcinoma ( CRC ) , and this has increased the financial burden on health care systems world-wide . PATIENTS AND METHODS Between 1993 and 1996 , 95 patients in northern Norway were included in a national r and omised CRC study , and assigned to surgery plus adjuvant chemotherapy or surgery alone . In April 1996 , 94 of the patients were evaluable and 82 were still alive . The total treatment costs ( hospital stay , surgery , chemotherapy , administrative and travelling costs ) were calculated . A question naire was mailed to all survivors for assessment of the quality of their lives ( QoL ) ( EuroQol question naire , a simple QoL-scale , global QoL-measure of the EORTC QLQ-C30 ) , and 62 of them ( 76 % ) responded . RESULTS Adjuvant chemotherapy in Dukes ' B and C CRC raised the total treatment costs by 3,369 pounds . The median QoL was 0.83 ( 0 - 1 scale ) in both arms . Employing a 5 % discount rate and an improved survival of adjuvant therapy ranging from 5 % to 15 % , we calculated the cost of one gained quality -adjusted life-year ( QALY ) to be between 4,800 pounds and 16,800 pounds . CONCLUSION Using a cut-off point level of 20,000 pounds per QALY , adjuvant chemotherapy in CRC appears to be cost-effective only when the improvement in 5-year survival is > or = 5 % . Adjuvant chemotherapy does not affect short-term PURPOSE : Traumatic manipulation of cancer specimens during laparoscopic colectomy may increase exfoliation of malignant cells into the peritoneal cavity , causing an early occurrence of peritoneal carcinomatosis or port-sites recurrence . Because of this concern , the routine use of intraperitoneal chemotherapy after laparoscopic colectomy for cancer was suggested recently . We assessed if laparoscopicvs . conventional surgery increases exfoliated malignant cells in the peritoneal cavity during resection of colorectal cancer . METHODS : In a prospect i ve , r and omized fashion , 38 colorectal cancer patients undergoing an elective , curative operation were assigned to either a conventional or laparoscopic procedure between June 1996 and May 1997 . In either group ( n=19 ) , after the abdominal cavity was entered , saline was instilled into the peritoneal cavity , and the fluid was collected ( Specimen 1 ) . During surgery , all irrigating fluids were collected ( Specimen 2 ) . Both specimens were assessed for malignancy using four techniques : filtration process ( ThinPrep ® ) , smear , cell block , and immunochemistry using Ber-EP4 . The change in the amount of tumor cells in both specimens was compared between surgical groups . A pilot study was performed to vali date the proposed cytologic method . RESULTS : In the pilot study of 20 consecutive patients with colorectal cancer , postresectional peritoneal cytology was positive in six patients , including two Stage II ( T3,N0,M0 ) patients . The pilot study also vali date d that our semiquantitative scoring system can be reliably used to assess the amount of free peritoneal cancer cells . In the main study , 16 right colectomies , 3 extended right colectomies , 17 proctosigmoidectomies , and 1 left colectomy were performed . The T and N stages were T1 ( n=13 ) , T2 ( n=5 ) , T3 ( n=8 ) , T4 ( n=11 ) ; N0 ( n=22 ) , N1 ( n=8 ) , N2 ( n=7 ) . Malignant cells were not detected in any Specimens 1 or , more importantly , in Specimens 2 in either surgical group . CONCLUSION : When performed according to strict oncologic surgical principles , laparoscopic techniques in curative colorectal cancer surgery did not have an increased risk of intraperitoneal cancer cell spillage , compared with conventional techniques . We hope that these results can decrease some of the concerns about tumors cell spillage and seeding during laparoscopy BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery . To date , the effect has not been studied in a r and omized clinical trial of colorectal cancer Background : We compared the perioperative parameters and outcomes achieved with h and -assisted laparoscopic colectomy ( HALC ) vs open colectomy ( OC ) for the management of benign and malignant colorectal disease , including cancer patients treated with curative intent . Methods : Sixty eligible patients were r and omized to either HALC ( n = 30 ) or OC ( n = 30 ) treatment groups . We used Pearson ’s chi-square and two- sample t-tests to compare the differences in demographics and perioperative parameters . Results : There were no significant differences in age , gender distribution , disease pattern , operative procedure , comorbidity , or history of abdominal surgery . The HALC patients had significantly shorter hospital stays and incision lengths , faster recovery of gastrointestinal function , less analgesic use and blood loss , and lower pain scores on postoperative days 1 , 3 , and 14 . There were no significant differences in operative time , complications , or time to return to normal activity . Conclusion : H and -assisted laparoscopic colectomy ( HALC ) is safe and produces better therapeutic results in terms of perioperative parameters than OC BACKGROUND Laparotomy causes a significant reduction of pulmonary function , and atelectasis and pneumonia occur after elective conventional colorectal resections . OBJECTIVE To evaluate the hypothesis that pulmonary function is less restricted after laparoscopic than after conventional colorectal resection . DESIGN A r and omized clinical trial . SETTING The surgical department of an academic medical center . PATIENTS Sixty patients underwent laparoscopic ( n = 30 ) or conventional ( n = 30 ) resection of colorectal tumors . The 2 groups did not differ significantly in age , sex , localization or stage of tumor , or preoperative pulmonary function . MAIN OUTCOME MEASURES Forced vital capacity , forced expiratory volume in 1 second , peak expiratory flow , mid-expiratory phase of forced expiratory flow , and oxygen saturation of arterial blood . RESULTS The forced vital capacity ( mean + /- SD values : conventional resection group , 1.73+/-0.60 L ; laparoscopic surgery group , 2.59+/-1.11 L ; P<.01 ) and the forced expiratory volume in 1 second ( conventional resection group , 1.19+/-0.51 L/s ; laparoscopic surgery group , 1.80+/-0.80 L/s ; P<.01 ) were more profoundly suppressed in the patients having conventional resection than in those having laparoscopic surgery . Similar results were found for the peak expiratory flow ( conventional resection group , 2.51+/-1.37 L/s ; laparoscopic resection group , 3.60+/-2.22 L/s ; P<.05 ) and the midexpiratory phase of forced expiratory flow ( conventional resection group , 1.87+/-1.12 L/s ; laparoscopic surgery group , 2.67+/-1.76 L/s ; P<.05 ) . The oxygen saturation of arterial blood , measured while the patients were breathing room air , was lower after conventional than after laparoscopic resections ( P<.01 ) . The recovery of the forced vital capacity and forced expiratory volume in 1 second to 80 % of the preoperative value took longer in patients having conventional resection than in those having laparoscopic resection ( P<.01 ) . Pneumonia developed in 2 patients having conventional resection , but no pulmonary infection occurred in the laparoscopic resection group ( P>.05 ) . CONCLUSIONS Pulmonary function is better preserved after laparoscopic than after conventional colorectal resection . Pulmonary complications may be reduced after laparoscopic resections because of the better postoperative pulmonary function Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization PURPOSE : All types of trauma to the organism produce a systemic response that is proportional to the severity of the lesion caused . The more rapid clinical recovery during the postoperative period of patients undergoing laparoscopic-assisted colectomyvs . patients receiving conventional surgery suggests that laparoscopic surgery produces less surgical trauma . The aim of this r and omized , prospect i ve study was to compare acute phase postoperative response in patients diagnosed with colon neoplasm undergoing open segmentary colectomyvs . laparoscopic-assisted colectomy . METHODS : From June 1994 to July 1997 the results of 97 patients ( 58 su bmi tted to open colectomy and 39 undergoing laparoscopic-assisted colectomy ) were analyzed . Blood determinations of cortisol , prolactin , C-reactive protein and interleukin-6 were performed before surgery and at 4 , 12 , 24 , and 72 hours after surgery . RESULTS : The plasma levels of cortisol and prolactin were higher in the postoperative period with both surgical techniques with no significant differences being observed . The levels of interleukin-6 achieved a maximum peak at 4 hours after surgery , later showing a decrease and practically achieving basal levels at 72 hours in both groups . The levels of interleukin-6 were higher with significant differences at 4 , 12 , and 24 hours in the patients undergoing open colectomy . The plasma levels of C-reactive protein were significantly lower at 72 hours in patients receiving laparoscopic-assisted colectomy . CONCLUSIONS : The results obtained in this r and omized , prospect i ve study suggest that acute phase systemic response is attenuated in patients undergoing laparoscopic-assisted colectomy in comparison with patients receiving open colectomy We present 20 cases of laparoscopically assisted colon resection . Ten patients were operated on for various benign lesions of the large bowel , and the remaining 10 for malignancy . Three fourths of the patients were over 65 years of age . The operative technique described herein involved laparoscopic mobilization of the colon and then its delivery through a relatively small incision through the anterior abdominal wall . Direct mobilization of the segment of bowel containing the malignant lesion was usually accomplished via the accessary incision made directly over the lesion . After eviscerating the specimen onto the abdominal wall , the involved segment of large intestine was resected along with its accompanying mesentery . The anastomosis was done by conventional linear stapling devices . No operative-related mortality occurred . Postoperative nasogastric tube suction was required in only one patient . Return of gastrointestinal function occurred an average of 2.5 days after the surgery . Average postoperative hospital stay was less than 5 days Background : Multimodal rehabilitation with epidural analgesia , early oral nutrition and mobilization , and laxative use has decreased the duration of ileus after colonic surgery to about 2 days , as compared with the usual 3 to 5 days of rehabilitation required after open surgery and the slightly shorter time required with laparoscopic surgery . Gastrointestinal transit after colonic resection with laparoscopy or laparotomy was assessed . Methods : In this study , 32 patients r and omized to laparoscopic or open colonic resection received 4 MBq of 111indium diethylenetriamine pentaacetic acid , a tracer , at the end of surgery . Images of the abdomen were obtained 24 and 48 h postoperatively . An opaque abdominal dressing blinded care personnel and patients to the procedure . Results : Defecation occurred on median day 2 postoperatively in both groups . At 48 h postoperatively , 53 % of the tracer was excreted by patients in the laparoscopic group , as compared with 26 % in the open group ( p > 0.05 ) . Conclusion : Postoperative ileus and gastrointestinal transit normalized within 48 h after colonic resection in the patients who received multimodal rehabilitation . No significant difference was observed between the patients who underwent the laparoscopic procedure and those who underwent the open procedure PURPOSE To determine the most efficient technique for performing a colectomy , we used the methodology of time-motion analysis . METHODS The efficiency of five h and -assisted and six regular laparoscopic colectomies and one open colectomy , performed by four surgeons in three different hospitals , was measured . The open colectomy was analyzed as a reference procedure . RESULTS AND CONCLUSIONS The h and -assisted laparoscopic technique was the most efficient . H and -assisted laparoscopy was therefore less time consuming than laparoscopic surgery . Open surgery was the fastest technique , because the time for every surgical motion is a factor of three shorter than for the two laparoscopic techniques BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes PURPOSE In the last ten years , several robotic systems have been developed to overcome the loss of the three-dimensional view and dexterity characteristic of laparoscopic surgery . The aim of this study was to compare the traditional laparoscopic approach and robotic techniques in the treatment of colorectal diseases . METHODS The study compares a consecutive series of patients treated surgically for colorectal disease from June 2001 to May 2003 with the da Vinci ™ robotic system ( Intuitive Surgical ® ) and a matched number of patients who underwent conventional laparoscopy during the same time interval . The factors analyzed were the time required to prepare the patient and the room , total time of surgery , length of specimens , number of lymph nodes retrieved , blood loss , complications , and postoperative results . RESULTS The study included 106 patients ( 53 in each group ) . No differences were observed in total time of surgery ( laparoscopic group , 222 ± 77 minutes vs. robotic group , 240 ± 61 minutes ) , specimen length ( laparoscopic group , 29 ± 11 cm vs. robotic group , 27 ± 13 cm ) , or number of lymph nodes retrieved ( laparoscopic group , 16 ± 9 vs. robotic group , 17 ± 10 ) . It took significantly longer to prepare the operating room and patient in the robotic group ( 24 ± 12 minutes ) than in the laparoscopic group ( 18 ± 7 minutes ) . There were three conversions to laparotomy in the laparoscopic group ; in the robotic group , two cases were converted to laparoscopy and three to h and -assisted laparoscopy . No significant differences were observed between the two groups in terms of recovery of bowel function and postoperative hospital stay . CONCLUSIONS Robot-assisted surgery proved to be as safe and effective as laparoscopic techniques in the treatment of colorectal diseases . Because of its dexterity and three-dimensional view , the da Vinci ™ system was particularly useful in specific stages of the procedure , e.g. , takedown of the splenic flexure , dissection of a narrow pelvis , identification of nervous plexus , and h and sewn anastomosis . The cost-effectiveness of the procedure still needs to be evaluated BACKGROUND : This study was conducted to determine if laparoscopic colon surgery has changed the incidence of wound complications after colon resection . METHODS : Eighty-three patients were r and omized to undergo either laparoscopic ( LCR ) or open colon resection ( OCR ) for cancer at our institution as part of a multicenter trial . Data were tabulated from review of the prospect i ve data base and physician records . RESULTS : Thirty-seven patients were r and omized to LCR and 46 to OCR . Seven patients in the LCR group were converted to OCR . LCR was performed using a limited midline incision for anastomosis and specimen extraction . Incision length was significantly greater ( p < 0.001 ) in the OCR group ( 19.4 ± 5.6 cm ) compared to the LCR extraction site ( 6.3 ± 1.4 cm ) . Wound infections occurred in 13.5 % of patients after LCR ( 2.7 % trocar , 10.8 % extraction sites ) and in 10.9 % of patients after OCR . Over a mean follow-up period of 30.1 ± 17.8 months , incisional hernias developed in 24.3 % of patients after LCR and 17.4 % after OCR . In the LCR group , extraction sites accounted for 85.7 % of all wound complications . CONCLUSIONS : The extraction site for LCR is associated with a high incidence of complications , comparable to open colectomy . Strategies to alter operative technique should be considered to reduce the incidence of these complications Bladder and sexual dysfunction , secondary to pelvic nerve injury , are recognized complications of rectal resection . This study investigated the frequency of these complications following laparoscopically assisted and conventional open mesorectal resection for cancer Background : After confirming a favorable outcome of laparoscopic surgery for early colorectal cancer , we conducted a r and omized controlled trial to compare short-term outcomes of laparoscopic and open colectomy for advanced colorectal cancer . Methods : Fifty-nine patients with T2 or T3 colorectal cancer were r and omized to undergo laparoscopic ( n = 29 ) or open ( n = 30 ) colectomy . Median follow-up was 20 months ( range , 6–34 months ) . Results : Operative time was longer ( p < 0.0001 ) and blood loss ( p = 0.0034 ) and postoperative analgesic requirement were less in the laparoscopic group than in the open group . An earlier return of bowel motility and earlier discharge from the hospital ( p = 0.0164 ) were observed after laparoscopic surgery . Serum C-reactive protein levels on postoperative days 1 ( p < 0.0001 ) and 4 ( p = 0.0039 ) were lower in the laparoscopic group than in the open group . Postoperative complications did not differ between the two groups . Conclusion : Laparoscopic surgery for advanced colorectal cancer is feasible , with favorable short-term outcome PURPOSE The aim of this study was to evaluate whether laparoscopic colorectal surgery can modify the risk factors for the occurrence of postoperative morbidity . METHODS A total of 384 consecutive patients with colorectal disease were r and omized to laparoscopic resection ( n = 190 ) or open resection ( n = 194 ) . On admission , demographics , comorbidity , and nutritional status were recorded . Operative variables , patient outcome , and length of stay were also recorded . Postoperative complications were registered by four members of staff not involved in the study . RESULTS The overall morbidity rate was 27.1 percent , with the rate in the laparoscopic group ( 18.7 percent ) being less than that in the open group ( 31.5 percent ; P = 0.003 ) . Patients who underwent laparoscopic resection had a faster recovery of bowel function ( P = 0.0001 ) and a shorter length of stay ( P = 0.0001 ) . In the whole cohort of patients , multivariate analysis identified open surgery ( P = 0.003 ) , duration of surgery ( P = 0.01 ) , and homologous blood transfusion ( P = 0.01 ) as risk factors for postoperative morbidity . In the open group , blood loss ( P = 0.01 ) , homologous blood transfusion ( P = 0.01 ) , duration of surgery ( P = 0.009 ) , weight loss ( P = 0.06 ) , and age ( P = 0.08 ) were related to postoperative morbidity . In the laparoscopic group the only risk factor identified was duration of surgery ( P = 0.005 ) . CONCLUSION In the laparoscopic group , both postoperative morbidity and length of stay were significantly reduced and most risk factors for postoperative morbidity disappeared BACKGROUND Uncontrolled studies using laparoscopic techniques in colorectal surgery have not demonstrated clear advantages to these procedures compared with conventional ones , and surgeons are concerned about unusual early recurrences reported after laparoscopic colorectal cancer surgery . STUDY DESIGN We conducted a prospect i ve , r and omized trial in one surgical department comparing laparoscopic ( LAP ) and conventional ( CON ) techniques in 109 patients undergoing bowel resection for colorectal cancers or polyps . Postoperatively , all patients underwent measurement of pulmonary function tests every 12 hours , and were treated identically on a highly controlled protocol with regard to analgesic administration , feeding , and postoperative care . RESULTS Of the 55 patients assigned to LAP and 54 to the CON group , there were 42 and 38 with cancer , respectively ( the other patients had large adenomas ) . Overall recovery of 80 % of forced expiratory volume in 1 second and forced vital capacity was a median of 3 days for LAP and 6.0 days for CON ( p = 0.01 ) . LAP patients used significantly less morphine than CON patients up to the second day after surgery ( 0.78 + /- 0.32 versus 0.92 + /- 0.34 mg/kg per day , p = 0.02 ) . Flatus returned a median of 3.0 days after LAP versus 4.0 days after CON surgery ( p = 0.006 ) . Tumor margins were clear in all patients . After a median followup of 1.5 years ( LAP ) and 1.7 years ( CON ) , there were no port site recurrences in the LAP group . Seven cancer-related deaths have occurred ( three in the LAP group , four in the CON group ) . CONCLUSIONS Within this prospect i ve , r and omized trial , laparoscopic techniques were as safe as conventional surgical techniques and offered a faster recovery of pulmonary and gastrointestinal function compared with conventional surgery for selected patients undergoing large bowel resection for cancer or polyps . There were no apparent shortterm oncologic disadvantages . Longer followup is needed to fully assess oncologic outcomes Background : Although the pneumoperitoneum decreases venous reflux from the lower extremities , the rate of thromboembolic complcations seems to be lower after laparoscopic than after conventional procedures . Therefore , it has been assumed that laparoscopic surgery better preserves the intravasal fibrinolytic capacity . The aim of this study was to determine the influence of the operative technique on intravasal fibrinolytic capacity in colorectal resection . Methods : R and omized controlled trial conducted in parallel with the multicenter trial LAPKON II comparing the long-term effects of elective laparoscopic ( group I ) and conventional ( group II ) resections for colorectal cancer . Blood sample s were taken from 30 patients preoperatively , at the beginning and end of surgery as well as 2 , 8 , and 24 hr postoperatively . Activities and concentrations of tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI-1 ) , tPA/PAI complex , fibrinogen , and D-dimers were determined in all specimen with ELISA tests . Area under the curve values ( AUC ) were calculated for all parameters . Results : Patient characteristics and indication for surgery were not different between both groups . Preoperative values of fibrinolytic parameters were similar in both groups . Postoperatively , tPA activity decreased significantly in both groups , but AUC values for tPA and PAI-1 activity ( p = 0.23 ; p = 0.68 ) ; concentration of tPA , PAI-1 , and tPA/PAI complex ( p = 0.52 ; p = 0.78 ; p = 0.95 ) ; and concentration of fibrinogen and D-dimers ( p = 0.67 ; p = 0.71 ) did not differ between the groups . Conclusions : An intravasal fibrinolytic " shutdown " occurs not only after conventional but also after laparoscopic colorectal resection . Both operative techniques had similar effects on postoperative intravasal fibrinolytic capacity . Therefore , the lower incidence of thromboembolic complications after laparoscopic colorectal resections does not seem to be caused by a lesser depression of the intravasal fibrinolytic capacity Abstract PURPOSE : This study was design ed to evaluate differences in both the peritoneal and systemic immune response after laparoscopic and conventional surgical approaches . METHODS : Patients with a primary carcinoma were prospect ively r and omized to curative laparoscopic ( n = 12 ) or conventional ( n = 14 ) colon resection . The proinflammatory cytokines interleukin-6 , interleukin-8 , and tumor necrosis factor-alpha were measured in the peritoneal drain fluid and in the serum . C-reactive protein and leukocyte counts and the differences in leukocyte sub population s and expression of human leukocyte antigen-DR on monocytes were measured perioperatively . RESULTS : Significantly higher levels of proinflammatory cytokine were found in the peritoneal drain fluid than in the circulation after both procedures . Serum interleukin-6 and interleukin-8 levels were significantly lower 2 hours after laparoscopic surgery than with the conventional procedure . Postoperative cellular immune counts and human leukocyte antigen-DR expression normalized earlier after the laparoscopic approach . CONCLUSIONS : The systemic proinflammatory concentrations after both surgical approaches represent only a small fragment of what is generated in the peritoneal drain fluid . Even if the immediate levels of proinflammatory cytokines in the serum are significantly lower in the laparoscopic group , the same cytokines locally produced showed no differences , which suggests that the two intra-abdominal approaches are equally traumatic . No differences in cellular response were observed between the groups OBJECTIVE To evaluate the feasibility and potential benefits of h and -assisted laparoscopic surgery with the H and Port System , a new device . SUMMARY BACKGROUND DATA In h and -assisted laparoscopic surgery , the surgeon inserts a h and into the abdomen while pneumoperitoneum is maintained . The h and assists laparoscopic instruments and is helpful in complex laparoscopic cases . METHODS A prospect i ve nonr and omized study was initiated with the participation of 10 laparoscopic surgical centers . Surgeons were free to test the device in any situation where they expected a potential advantage over conventional laparoscopy . RESULTS Sixty-eight patients were entered in the study . Operations included colorectal procedures ( sigmoidectomy , right colectomy , resection rectopexy ) , splenectomy for splenomegaly , living-related donor nephrectomy , gastric b and ing for morbid obesity , partial gastrectomy , and various other procedures . Mean incision size for the H and Port was 7.4 cm . Most surgeons ( 78 % ) preferred to insert their nondominant h and into the abdomen . Pneumoperitoneum was generally maintained at 14 mmHg , and only one patient required conversion to open surgery as a result of an unmanageable air leak . H and fatigue during surgery was noted in 20.6 % . CONCLUSIONS The h and -assisted technique appeared to be useful in minimally invasive colorectal surgery , splenectomy for splenomegaly , living-related donor nephrectomy , and procedures considered too complex for a laparoscopic approach . This approach provides excellent means to explore , to retract safely , and to apply immediate hemostasis when needed . Although the data presented here reflect the authors ' initial experience , they compare favorably with series of similar procedures performed purely laparoscopically Background : Laparoscopically assisted resection of colorectal carcinoma is technically feasible and minimally invasive . Postoperative immunosuppression also may be reduced . This study compared the lymphocyte subsets and natural killer ( NK ) cell cytotoxicity in patients after laparoscopically assisted resection with those after open resection of rectosigmoid carcinoma . Methods : In this study , 40 patients with rectosigmoid carcinoma , but no evidence of metastasis , were r and omized to receive either laparoscopically assisted or conventional open resection of the tumor . Blood was collected before the operation , then 24 h , 72 h , and 8 days after the operation for studies of lymphocyte subsets and NK cell cytotoxicity . Results : The lymphocyte subsets and NK cell cytotoxicity of both groups showed typical suppression after surgery . The suppression of T cell activation and NK-like T cells was significantly less after laparoscopically assisted resection than in after open resection , whereas the difference in other lymphocyte subsets and NK cell cytotoxicity was not significant . Conclusion : This study showed that some cellular components of the immune system are less suppressed after laparoscopically assisted than after conventional open resection of rectosigmoid carcinoma . This may have implication s for tumor recurrence and long-term patient survival The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas . The role of laparoscopic techniques in the treatment of colon carcinomas is question able . Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections . A prospect i ve , r and omized study was conducted comparing laparoscopic assisted colectomy ( LAC ) open colectomy ( OC ) for colon cancer . We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging . Benefit has been demonstrated with LAC in this setting . Passing flatus , oral intake , and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group . The overall morbidity was significantly lower in the LAC group . No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification . The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer . However , the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome In a prospect i ve r and omised study the influence of the operative technique on postoperative quality of life was evaluated in 60 patients undergoing laparoscopic ( n = 30 ) or conventional ( n = 30 ) resection of colorectal tumors . Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Core 30 Question naire ( EORTC-QLQ-C30 ) before surgery as well as 1 week , 4 weeks and 3 months after surgery . Age , sex , sociological parameters , tumor characteristics and type of resection were comparable in both groups . There were no significant differences in preoperative global quality of life , the functional aspects of quality of life and the severity of disease related symptoms . The global quality of life was significantly better in the laparoscopic group compared to the conventional group 1 week and 4 weeks after surgery ( p = 0.05 ) . Physical and emotional function were more impaired 1 week after conventional compared to laparoscopic surgery ( p < 0.05 ) . Pain , dyspnea and loss of appetite were more severe 1 week after conventional than laparoscopic surgery ( each p < 0.05 ) . There were no differences in quality of life in the further postoperative course . Laparoscopic resection of colorectal tumor is related with a better short-term quality of life than conventional resection , but a longer lasting effect of the laparoscopic technique on quality of life could not be detected with the EORTC-QLQ-C30 Background : Surgical trauma and anesthesia are known to cause transient postoperative suppression of the immune system . In r and omized controlled trials , it has been shown that laparoscopic colorectal resections have short-term benefits not observed with conventional colorectal resections . We hypothesized that these benefits were due to the reduction in surgical trauma , leading to a diminished cytokine response and less depression of cell-mediated immunity after laparoscopy . Methods : In a prospect i ve r and omized trial , colorectal cancer patients without evidence of metastatic disease underwent either laparoscopic ( n = 20 ) or conventional ( n = 20 ) tumor resection . Postoperative immune function was assessed by measuring the white blood cell ( WBC ) count , the CD4 + and CD8 + lymphocytes , the CD4+/CD8+/ratio , and the HLA-DR expression of CD14 + monocytes . In addition , the production of interleukin-6 ( IL = 6 ) and TNF-a were measured after ex vivo stimulation of mononuclear blood cells with lipopolysaccharide ( LPS ) and compared to the plasma levels of these cytokines . Postoperative mean levels of the immunologic parameters for the two groups were calculated and compared using the Mann-Whitney U test . Results : Preoperatively , there were no differences between the two groups in terms of patient characteristics or immunologic parameters . Although the postoperative peak concentrations of white blood cells were significant lower in the laparoscopic group than the conventional group ( p < 0.05 ) , there were no differences between the two groups in the sub population of lymphocytes ( CD4 + , CD8 + ) . HLA-DR expression of CD14 + monocytes was lower in the conventional group on the 4th postoperative day ( p < 0.05 ) . The laparoscopic group showed higher values in cytokine production of mononuclear blood cells after LPS stimulation . Postoperative plasma peak concentrations of IL-6 and TNF-a were lower after laparoscopic resection . Conclusion : Postoperative cell-mediated immunity was better preserved after laparoscopic than after conventional colorectal resection . Cellular cytokine production was preserved only in the laparoscopic group , while cytokine plasma levels were significantly higher in the conventional group . These findings may have important implication s for the use of laparoscopic colorectal resection , especially in patients with malignant disease Abstract Background : Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue . The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue , and may improve postoperative recovery after colorectal resections . Methods : Sixty patients were included into a prospect i ve r and omized trial to determine the influence of laparoscopic ( n= 30 ) or conventional ( n= 30 ) resection of colorectal tumors on postoperative pain and fatigue . Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia ( PCA ) , visual analog scale for pain while coughing ( VASC ) , and visual analogue scale for fatigue ( VASF ) . Efficacy of pain medication was assessed by visual analogue score at rest ( VASR ) . Results : Preoperative age , sex , stage , and localization of tumors were comparable in both groups . The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group ( median , 1.37 mg/kg ; 5–95 percentile 0.71–2.46 mg/kg ) than the laparoscopic group ( 0.78 mg/kg ; 0.24–2.38 mg/kg , p < 0.01 ) . Postoperative VASR was comparable between both groups , but VASC was higher from the first to the seventh postoperative day ( p < 0.01 ) . Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day ( p < 0.05 ) . Conclusions : This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection . Patients also experience less fatigue after minimal invasive surgery . Because of these differences , the duration of recovery is shortened , and the postoperative quality of life is improved after laparoscopic colorectal resections Objective Comparison of outcome and costs after laparoscopic and open colectomy . Summary Background Data Previous studies comparing laparoscopic and open colectomy report conflicting results with regard to clinical outcome and costs . Methods Laparoscopic colectomy patients from a prospect i ve data base were matched for age , gender , and disease-related grouping to patients who underwent the same operation by the open approach over the same period ( 2000 to 2001 ) . Data for the latter group was gathered by retrospective analysis and the 2 groups were compared for outcome and direct costs . Results Laparoscopic colectomy patients ( n = 150 ) were compared with the same number of open colectomy patients . American Society of Anesthesiologists classification ( P = 0.09 ) , body mass index ( P = 0.17 ) , diagnosis ( P = 0.12 ) , complications ( P = 0.14 ) , and rate of readmission within 30 days ( P = 0.44 ) were similar for both groups . Operating room costs were significantly higher after laparoscopic colectomy ( P < 0.0001 ) , but length of hospital stay was significantly lower ( P < 0.0001 ) . This result ed in significantly lower total costs ( P = 0.0007 ) owing to lower pharmacy ( P < 0.0001 ) , laboratory ( P < 0.0001 ) , and ward nursing costs ( P = 0.0004 ) . Conclusions Laparoscopic colectomy results in significantly lower direct costs compared with open colectomy for carefully matched patients A general approach is discussed to assess the uncertainty surrounding the cost effectiveness ratio ( C/E-ratio ) estimated on the basis of data from a r and omised clinical trial . The approach includes the calculation of a 95 % probability ellipse and introduces the concept of a so called C/E-acceptability curve . This last curve defines for each predefined C/E-ratio the probability that the C/E-ratio found in the study is acceptable . The approach is illustrated by estimates of costs per life saved and costs per patient discharged alive on the basis of data from a phase II trial addressing the value of anakinra in treating sepsis syndrome PURPOSE : Our aim was to test the hypothesis that laparoscopic‐assisted resection for colorectal cancer has an immunologic advantage over traditional open surgery . METHODS : Sixteen patients with colorectal cancer were r and omized to undergo laparoscopic‐assisted resection or open surgery . Basic patient data were recorded , and serum interleukin‐6 levels , relative proportions of lymphocytes , and human leukocyte antigen‐DR expression on monocytes were determined at specific time intervals . RESULTS : Operating time was longer for laparoscopic‐assisted resection ( P=0.02 ) , but analgesic requirements were less ( P=0.04 ) . All patients exhibited the following : interleukin‐6 levels increased to a maximum at 4 hours and returned to preoperative levels within 48 hours . This response appeared greater for open resection ( mean peak level , 313 vs. 173 pg/ml ; P=0.25 ) . Relative granulocytosis ( P<0.001 ) was seen within 48 hours , which was offset by a decrease in percentage of lymphocytes ( P<0.001 ) . Changes in lymphocyte subfractions were most significant seven days post‐surgery : natural killer cells decreased ( P=0.003 ) ; T cells increased ( P=0.008 ) , with elevation in the CD4/CD8 ratio ( P=0.003 ) . B cells were largely unchanged at all time periods . Human leukocyte antigen‐DR expression on monocytes was significantly less at 48 hours postsurgery ( P<0.001 ) . All changes were reversed within three weeks of surgery . There were no differences when comparing laparoscopic‐assisted resection with open surgery . CONCLUSIONS : Both laparoscopic‐assisted resection and open surgery affect the immune response . It would appear that laparoscopic‐assisted resection does not have an immunologic advantage over open surgery in patients with colorectal cancer Abstract Background : Short-term benefits of laparoscopic relative to conventional colorectal resections have been demonstrated in r and omized controlled trials . It has been suggested that a diminished cytokine and acute-phase response may be responsible for these advantages . Methods : In a r and omized controlled trial , patients underwent laparoscopic ( n=30 ) or conventional ( n=30 ) resection of colorectal tumors . Plasma levels of interleukin-1 receptor antagonist ( IL-1RA ) , interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , and C-reactive protein ( CRP ) were analyzed repeatedly . Postoperative peak levels and area under the curve values were calculated and compared between groups using the Mann-Whitney U-test . Results : Patient characteristics , preoperative cytokine , and CRP plasma levels were not different between each group . Postoperative peak concentrations of IL-6 ( P=0.05 ) and CRP ( P<0.001 ) and the overall postoperative plasma concentrations of IL-6 ( P=0.03 ) and CRP ( P=0.002 ) were lower in the laparoscopic than in the conventional group . Peak and overall IL-1RA ( P=0.2 ; P=0.2 ) and IL-10 ( P=0.4 ; P=0.6 ) plasma concentrations , respectively , were not different between groups . Conclusions : IL-6 and CRP plasma levels were lower after laparoscopic than conventional colorectal resections . The less intense inflammatory response may be an indicator of the milder surgical trauma inflicted by laparoscopic than conventional colorectal resection PURPOSE Surgery remains the primary treatment of colorectal cancer . Data are lacking to delineate the optimal surveillance strategy following resection . A large-scale multi-center European study is underway to address this issue ( Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA ) . METHODS Following primary surgery with curative intent , stratification , and r and omization at GILDA headquarters , colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen . Rectal cancer patients undergoing curative resection are similarly r and omized , with their follow-up regimens placing more emphasis on detection of local recurrence . Target recruitment for the study will be 1500 patients to achieve a statistical power of 80 % ( assuming an alpha of 0.05 and a hazard-rate reduction of > 24 % ) . RESULTS Since the trial opened in 1998 , 985 patients have been r and omized from 41 centers as of February 2004 . There were 496 patients r and omized to the less intensive regimens , and 489 r and omized to the more intensive regimens . The mean duration of follow-up is 14 months . 75 relapses ( 15 % ) and 32 deaths ( 7 % ) had been observed in the two more intensive follow-up arms , while 64 relapses ( 13 % ) and 24 deaths ( 5 % ) had been observed in the two less intensive arms as of February 2004 . CONCLUSIONS This trial should provide the first evidence based on an adequately powered r and omized trial to determine the optimal follow-up strategy for colorectal cancer patients . This trial is open to US centers , and recruitment continues OBJECTIVE To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma . SUMMARY BACKGROUND DATA Laparoscopic resection of colorectal carcinoma is technically feasible , but objective evidence of its benefit is scarce . Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response . METHODS Thirty-four patients with rectosigmoid carcinoma , without evidence of metastatic disease and suitable for laparoscopic resection , were r and omized to undergo either laparoscopic ( n = 17 ) or conventional open ( n = 17 ) resection of the tumor . Clinical parameters were recorded . Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta , tumor necrosis factor-alpha , interleukin-6 , and C-reactive protein . The primary end points were the cytokine and C-reactive protein levels . Data were analyzed by intention to treat . RESULTS The demographic data of the two groups were comparable . The clinical outcome of both groups was satisfactory , with no surgical deaths and a reasonable complication rate . Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery , with the responses in the laparoscopic group significantly less than those in the open group . C-reactive protein levels peaked at 48 hours , and the difference was also statistically significant . Levels of tumor necrosis factor-alpha were not elevated after surgery , and there was no difference between the groups . CONCLUSIONS Tissue trauma , as reflected by systemic cytokine response , was less after laparoscopic resection than after open resection of rectosigmoid carcinoma . The difference in the systemic cytokine response may have implication s on the long-term survival PURPOSE : Operating room time and anastomosis-related morbidity of laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision or laparoscopically after re-establishing pneumoperitoneum were compared . METHODS : A r and omized trial was performed on patients with recurrent uncomplicated diverticulitis of the sigmoid colon during a 14-month period . Inclusion criteria were persistence of symptoms despite medical treatment and two previous admissions . Exclusion criteria included complicated diverticulitis , suspected cancer , and previous extensive abdominal surgery . Because skin incisions were similar and patients were r and omly assigned in the operating room , the trial was performed as double blind . RESULTS : There were no deaths . Two patients were excluded before r and omization . Three patients were not treated as allocated because of conversion to open surgery . Aside from previous abdominal-surgery rates , 16 patients with laparoscopic-assisted sigmoid resections after re-establishing pneumoperitoneum and 15 patients with laparoscopic-assisted sigmoid resections with anastomosis performed in an open fashion through a horizontal suprapubic incision were well-matched for age , gender , weight , American Society of Anesthesiology class , previous admissions , skin-incision length , size of circular stapler , and mobilization of splenic flexure . There were no significant differences in morbidity rates ( 3/16vs . 3/15 ) , complete doughnuts ( 16/16vs . 15/15 ) , blood loss ( 300vs . 200 ml ) , flatus ( 4vs . 4 days ) , solid-food resumption ( 5vs . 6 days ) , stay ( 8.5vs . 9 days ) in laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum and laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision groups , respectively . Patients with laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum had statistically longer operating room time ( 295vs . 190 minutes;P<0.01 ) . Median follow-up was 12 and 10 months in 10 patients with laparoscopic-assisted sigmoid resection after reestablishing pneumoperitoneum and 11 patients with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision , respectively . One patient with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision had an anastomotic stenosis endoscopically dilated . CONCLUSIONS : Nonrestoration of pneumoperitoneum after laparoscopic-assisted sigmoid resection allows a decrease in operating room time and a similar outcome OBJECTIVES A prospect i ve r and omized trial was design ed to test the hypothesis that disease-free survival and overall survival are equivalent regardless of whether patients receive laparoscopic assisted colectomy ( LAC ) or open colectomy . Secondary and tertiary aims will test the safety of LAC and the impact of LAC on quality of life and costs , respectively . METHODS 1200 patients will be accrued and r and omly assigned to LAC or open colectomy . Consenting adults with primary colon cancer without previous or concurrent malignancies and with tumors considered resectable for cure are eligible for enrollment . Patients will be followed postoperatively for evidence of recurrence and for survival and perioperatively for morbidity , mortality , quality of life , and cost end points . RESULTS Over 800 patients have been enrolled to date . Early trial results are available for 408 patients , 203 open and 205 LAC . As anticipated , patients are evenly distributed within the two treatment arms according to age , gender , and anesthesia risk ( ASA classification ) . In the open arm , the mean age is 69 with 52 percent females , 87 percent ASA I/II and 13 percent ASA III . In the laparoscopic arm , the mean age is 67 , with 48 percent females , 87 percent ASA I/II , and 13 percent ASA III . A total of 160 right and 117 sigmoid colectomies have been performed . Extent of resection data is also available and all parameters tested show no difference between the LAC and open cases : for the laparoscopic vs open colectomy , total bowel length 26 cm vs 27 cm ; proximal margins 12 cm vs 11 cm ; distal margins 10 cm vs 12 cm ; mesenteric length 9 cm vs 8 cm . Similarly , the number of nodes resected for laparoscopic colectomy is essentially the same ( mean 12 lymph nodes ) to that for open surgery ( mean 13 nodes ) . CONCLUSIONS Although this study is ongoing ; preliminary results suggest that open and LAC provide for the same extent of resection . The quality of life portion of the study is now complete and data will soon be available There has been no r and omized clinical trial of the costs of laparoscopic colonic resection ( LCR ) compared with those of open colonic resection ( OCR ) in the treatment of colonic cancer BACKGROUND The role of laparoscopic colon resection in the management of colon cancer is unclear . The aims of this study were to compare perioperative results and long-term outcomes in patients r and omized to either open ( O ) or laparoscopically assisted ( LA ) colon resection for colon cancer . METHODS A prospect i ve r and omized trial comparing O to LA colon resection was conducted from January 1993 to November 1995 . Preoperative workup , intraoperative results , complications , length of stay , pathologic findings , and long-term outcomes were compared between the two groups . Statistical analysis was performed with t-test . Follow-up periods ranged from 3.5 to 6.3 years ( mean , 4.9 years ) . RESULTS No port-site or abdominal wall recurrences were noted in any patients . [ table : see text ] CONCLUSIONS These results suggest that laparoscopically assisted colon resection for malignant disease can be performed safely , with morbidity , mortality , and en bloc resections comparable with those of open laparotomy . Long-term ( 5-year ) follow-up assessment shows similar outcomes in both groups of patients , demonstrating definite perioperative advantages with LA surgery and no perioperative or long-term disadvantages PURPOSE Although laparoscopic-assisted colectomy ( LAC ) has evolved as a technical option in the treatment of benign colonic diseases , its role in the treatment of malignancies remains controversial . The purpose of this prospect i ve r and omized trial was to compare perioperative parameters and outcomes between LAC vs. open colectomy ( OC ) in patients with stage I-III colon cancer . PATIENTS AND METHODS Eligible patients with colon cancer who were scheduled for an elective colon resection from January 1995 to February 2001 were r and omized to either the LAC or the OC treatment group . The two groups were compared with regard to operative time , blood loss , complications , pathologic findings and lymph node yield , length of postoperative hospital stay , gastrointestinal function , use of analgesic drugs , recurrence , and survival rates . The median follow-up was 35 months ( range , 3 - 69 months ) . RESULTS A total of 49 patients were enrolled in the study : 20 were r and omized to OC and 29 to LAC , one of whom was lost to follow-up . Thirteen patients in the LAC group had to be converted to OC ( COC ) , and were analyzed in a separate group . The three patient groups were comparable with regard to age , gender distribution , tumor site , lymph node harvest , operative procedure , anastomotic type , perioperative complication , recurrence , and survival rates . Tumor margins were clear in all patients . No incidence of port-site recurrence in the LAC group , or wound recurrence in the OC and COC groups , was found . Three patients died of cancer-related causes , one in each patient group . The LAC patients had significantly shorter hospital stay , faster recovery of gastrointestinal function , and less use of intravenous analgesia . CONCLUSION Short-term outcomes revealed that LAC could be performed safely and has therapeutic results similar to OC for colon cancer . Conversion of LAC to an open procedure was frequent but was not associated with a negative outcome BACKGROUND Laparoscopic surgery has proven to be safe and effective . However , the value of laparoscopic resection for malignancy in terms of cancer outcome can only be assessed by large prospect i ve r and omized clinical trials with sufficient follow-up . METHODS COLOR ( COlon carcinoma Laparoscopic or Open Resection ) is a European multicenter r and omized trial that began in 1997 . In 27 hospitals in Sweden , The Netherl and s , Germany , France , Italy , Spain , and the United Kingdom , 1200 patients will be included . The primary endpoint of the study is cancer-free survival after 3 years . RESULTS In < 3.5 YEARS , > 850 patients have been r and omized for right hemicolectomy ( 47 % ) , left hemicolectomy ( 11 % ) , and sigmoidectomy ( 42 % ) . Fifty seven patients were excluded after r and omization . Forty six months after the start of the trial , the overall recurrence rate is 6.8 % . The distribution of stage of disease is as follows : stage I , 25 % ; stage II , 41 % ; stage III , 32 % ; stage IV , 2 % . CONCLUSION Although laparoscopic surgery appears to be of value in the treatment of colorectal cancer , the final , results of r and omized trials need to be considered to determine its definitive role . Given the current accrual rate , the COLOR study will be completed in 2002 BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
12,638 | 30,238,227 | Use of dexmedetomidine significantly increased the risks of bradycardia and hypotension .
Conclusion Findings suggest that dexmedetomidine reduces incidence and duration of ICU delirium .
Furthermore , our systematic search es show that there is limited evidence if a delirium shall be treated with dexmedetomidine | Background To determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit ( ICU ) delirium . | Objectives : The purpose of this study was to determine analgesic efficacy of dexmedetomidine used as a continuous infusion without loading dose in postcardiac surgery patients . Setting s and Design : A prospect i ve , r and omized , double-blind clinical study in a single tertiary care hospital on patients posted for elective cardiac surgery under cardiopulmonary bypass . Interventions : Sixty-four patients who underwent elective cardiac surgery under general anesthesia were shifted to intensive care unit ( ICU ) and r and omly divided into two groups . Group A ( n = 32 ) received a 12 h infusion of normal saline and group B ( n = 32 ) received a 12 h infusion of dexmedetomidine 0.4 μg/kg/h . Postoperative pain was managed with bolus intravenous fentanyl . Total fentanyl consumption , hemodynamic monitoring , Visual Analogue Scale ( VAS ) pain ratings , Ramsay Sedation Scale were charted every 6 th hourly for 24 h postoperatively and followed-up till recovery from ICU . Student′s t-test , Chi-square/Fisher′s exact test has been used to find the significance of study parameters between the groups . Results : Dexmedetomidine treated patients had significantly less VAS score at each level ( P < 0.001 ) . Total fentanyl consumption in dexmedetomidine group was 128.13 ± 35.78 μg versus 201.56 ± 36.99 μg in saline group ( P < 0.001 ) . A statistically significant but clinical ly unimportant sedation was noted at 6 and 12 h ( P < 0.001 , and P = 0.046 respectively ) . Incidence of delirium was less in dexmedetomidine group ( P = 0.086 + ) . Hemodynamic parameters were statistically insignificant . Conclusions : Dexmedetomidine infusion even without loading dose provides safe , effective adjunct analgesia , reduces narcotic consumption , and showed a reduced trend of delirium incidence without undesirable hemodynamic effects in the cardiac surgery patients Rationale : Dexmedetomidine is associated with less delirium than benzodiazepines and better sleep architecture than either benzodiazepines or propofol ; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear . Objectives : To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults . Methods : This two‐center , double‐blind , placebo‐controlled trial r and omized 100 delirium‐free critically ill adults receiving sedatives to receive nocturnal ( 9:30 p.m. to 6:15 a.m. ) intravenous dexmedetomidine ( 0.2 & mgr;g/kg/h , titrated by 0.1 & mgr;g /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of −1 or maximum rate of 0.7 & mgr;g/kg/h was reached ) or placebo until ICU discharge . During study infusions , all sedatives were halved ; opioids were unchanged . Delirium was assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission . Sleep was evaluated each morning by the Leeds Sleep Evaluation Question naire . Measurements and Main Results : Nocturnal dexmedetomidine ( vs. placebo ) was associated with a greater proportion of patients who remained delirium‐free during the ICU stay ( dexmedetomidine [ 40 ( 80 % ) of 50 patients ] vs. placebo [ 27 ( 54 % ) of 50 patients ] ; relative risk , 0.44 ; 95 % confidence interval , 0.23‐0.82 ; P = 0.006 ) . The average Leeds Sleep Evaluation Question naire score was similar ( mean difference , 0.02 ; 95 % confidence interval , 0.42‐1.92 ) between the 34 dexmedetomidine ( average seven assessment s per patient ) and 30 placebo ( six per patient ) group patients able to provide one or more assessment s. Incidence of hypotension , bradycardia , or both did not differ significantly between groups . Conclusions : Nocturnal administration of low‐dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay ; patient‐reported sleep quality appears unchanged . Clinical trial registered with www . clinical trials.gov ( NCT01791296 ) Background : Peripheral nerve block is a preferable method for elderly patients receiving hip arthroplasty . Sedation with dexmedetomidine may reduce postoperative delirium ( POD ) . The aim of this study was to investigate whether intraoperative sedation with dexmedetomidine , as a supplementary to peripheral nerve block for elderly patients receiving total hip arthroplasty , can decrease the prevalence of POD . Methods : A prospect i ve , r and omized controlled study was conducted with patients 65 years of age or older who underwent total hip arthroplasty between June 2016 and June 2017 . The patients were r and omly assigned to receive a lumbosacral plexus plus T12 paravertebral block supplemented with propofol or dexmedetomidine for sedation . Incidence of POD was the primary endpoint and was determined with the confusion assessment method , and incidence of postoperative cognitive dysfunction ( POCD ) was assessed with the mini-mental state examination . The time of ambulation , discharge time , and complications over a 30-day postsurgery period were also recorded . Results : A total of 296 patients were r and omly assigned to 2 groups . The patients se date d with dexmedetomidine had lower incidences of POD and POCD and were out of bed and discharged sooner than the patients se date d with propofol . There was no difference in complications between the 2 groups . Conclusions : As a supplementary to peripheral nerve block , intraoperative sedation with dexmedetomidine could be associated with a lower incidence of POD , which may have benefits on reducing the incidence of early POCD and offering a better short-term recovery for elderly patients receiving hip arthroplasty BACKGROUND Delirium is a postoperative complication that occurs frequently in patients older than 65 years , and presages adverse outcomes . We investigated whether prophylactic low-dose dexmedetomidine , a highly selective α2 adrenoceptor agonist , could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery . METHODS We did this r and omised , double-blind , placebo-controlled trial in two tertiary-care hospitals in Beijing , China . We enrolled patients aged 65 years or older , who were admitted to intensive care units after non-cardiac surgery , with informed consent . We used a computer-generated r and omisation sequence ( in a 1:1 ratio ) to r and omly assign patients to receive either intravenous dexmedetomidine ( 0·1 μg/kg per h , from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1 ) , or placebo ( intravenous normal saline ) . Participants , care providers , and investigators were all masked to group assignment . The primary endpoint was the incidence of delirium , assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days . Analyses were done by intention-to-treat and safety population s. This study is registered with Chinese Clinical Trial Registry , www.chictr.org.cn , number ChiCTR-TRC-10000802 . FINDINGS Between Aug 17 , 2011 , and Nov 20 , 2013 , of 2016 patients assessed , 700 were r and omly assigned to receive either placebo ( n=350 ) or dexmedetomidine ( n=350 ) . The incidence of postoperative delirium was significantly lower in the dexmedetomidine group ( 32 [ 9 % ] of 350 patients ) than in the placebo group ( 79 [ 23 % ] of 350 patients ; odds ratio [ OR ] 0·35 , 95 % CI 0·22 - 0·54 ; p<0·0001 ) . Regarding safety , the incidence of hypertension was higher with placebo ( 62 [ 18 % ] of 350 patients ) than with dexmedetomidine ( 34 [ 10 % ] of 350 patients ; 0·50 , 0·32 - 0·78 ; p=0·002 ) . Tachycardia was also higher in patients given placebo ( 48 [ 14 % ] of 350 patients ) than in patients given dexmedetomidine ( 23 [ 7 % ] of 350 patients ; 0·44 , 0·26 - 0·75 ; p=0·002 ) . Occurrence of hypotension and bradycardia did not differ between groups . INTERPRETATION For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery , prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery . The therapy is safe . FUNDING Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation , Beijing , China . Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co , Ltd , Jiangsu , China Background Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes . The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery . Methods This r and omized , double-blinded , and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1 , 2014 and July 19 , 2015 . Eligible patients were r and omized into two groups . Dexmedetomidine ( DEX ) was administered during anesthesia and early postoperative period for patients in the DEX group , whereas normal saline was administered in the same rate for the same duration for patients in the control ( CTRL ) group . The primary endpoint was the incidence of delirium during the first five days after surgery . Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30 , the overall incidence of non-delirium complications within 30 days after surgery , and the all-cause 30-day mortality . Results Two hundred eighty-five patients were enrolled and r and omized . Dexmedetomidine did not decrease the incidence of delirium ( 4.9 % [ 7/142 ] in the DEX group vs 7.7 % [ 11/143 ] in the CTRL group ; OR 0.62 , 95 % CI 0.23 to 1.65 , p = 0.341 ) . Secondary endpoints were similar between the two groups ; however , the incidence of pulmonary complications was slightly decreased ( OR 0.51 , 95 % CI 0.26 to 1.00 , p = 0.050 ) and the percentage of early extubation was significantly increased ( OR 3.32 , 95 % CI 1.36 to 8.08 , p = 0.008 ) in the DEX group . Dexmedetomidine decreased the required treatment for intraoperative tachycardia ( 21.1 % [ 30/142 ] in the DEX group vs 33.6 % [ 48/143 ] in the CTRL group , p = 0.019 ) , but increased the required treatment for postoperative hypotension ( 84.5 % [ 120/142 ] in the DEX group vs 69.9 % [ 100/143 ] in the CTRL group , p = 0.003 ) . Conclusions Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery . However , considering the low delirium incidence , the trial might have been underpowered . Trial Registration Clinical Trials.gov PURPOSE To determine whether dexmedetomidine sedation in the postanesthesia care unit ( PACU ) could decrease agitation and delirium after free flap surgery . MATERIAL S AND METHODS Eighty patients were r and omly divided into 2 groups . In the experimental group , dexmedetomidine was given at an hourly infusion rate of 0.5 μg/kg for 1 hour before the operation was completed and continued in the PACU at 0.2 to 0.7 μg/kg continuously until the next morning . In the control group , normal saline was given during the same periods . Patients in the 2 groups received sufentanil and midazolam for sedation and pain relief when necessary . Agitation was monitored with the Riker Sedation-Agitation Scale in the PACU and delirium was monitored with the Confusion Assessment Method for the Intensive Care Unit for 5 days postoperatively . RESULTS The overall incidence of agitation was similar between the 2 groups . However , when the influence of patient shifting was excluded , the incidence of agitation in the dexmedetomidine group was apparently lower than that in the control group ( 10.3 vs 30 % ; P = .029 ) . No difference was found in the occurrence of delirium between the experimental and control groups ( 5.1 vs 12.5 % ; P = .432 ) . CONCLUSION Dexmedetomidine does not change the overall incidence of agitation after free flap surgery ; however , it does decrease agitation after PACU admission . It does not prevent delirium within 5 days postoperatively CONTEXT Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit ( ICU ) patients , but this and other benzodiazepine drugs may contribute to acute brain dysfunction , ie , delirium and coma , associated with prolonged hospital stays , costs , and increased mortality . Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction . OBJECTIVE To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam . DESIGN , SETTING , PATIENTS , AND INTERVENTION Double-blind , r and omized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006 . Patients were se date d with dexmedetomidine or lorazepam for as many as 120 hours . Study drugs were titrated to achieve the desired level of sedation , measured using the Richmond Agitation-Sedation Scale ( RASS ) . Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU ( CAM-ICU ) . MAIN OUTCOME MEASURES Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal . RESULTS Sedation with dexmedetomidine result ed in more days alive without delirium or coma ( median days , 7.0 vs 3.0 ; P = .01 ) and a lower prevalence of coma ( 63 % vs 92 % ; P < .001 ) than sedation with lorazepam . Patients se date d with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients se date d with lorazepam ( median percentage of days , 80 % vs 67 % ; P = .04 ) . The 28-day mortality in the dexmedetomidine group was 17 % vs 27 % in the lorazepam group ( P = .18 ) and cost of care was similar between groups . More patients in the dexmedetomidine group ( 42 % vs 31 % ; P = .61 ) were able to complete post-ICU neuropsychological testing , with similar scores in the tests evaluating global cognitive , motor speed , and attention functions . The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group ( P = .48 ) . CONCLUSION In mechanically ventilated ICU patients managed with individualized targeted sedation , use of a dexmedetomidine infusion result ed in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00095251 Background Delirium after cardiac surgery is associated with serious long-term negative outcomes and high costs . The aim of this study is to evaluate neurobehavioral , hemodynamic , and sedative characteristics of dexmedetomidine , compared with the current postoperative sedative protocol ( remifentanil ) in patients undergoing open heart surgery with cardiopulmonary bypass ( CPB ) . Methods One hundred and forty two eligible patients who underwent cardiac surgery on CPB between April 2012 and March 2013 were r and omly divided into two groups . Patients received either dexmedetomidine ( range , 0.2 to 0.8 μg/kg/hr ; n=67 ) or remifentanil ( range , 1,000 to 2,500 μg/hr , n=75 ) . The primary end point was the prevalence of delirium estimated daily via the confusion assessment method for intensive care . Results When the delirium incidence was compared with the dexmedetomidine group ( 6 of 67 patients , 8.96 % ) and the remifentanil group ( 17 of 75 patients , 22.67 % ) it was found to be significantly less in the dexmedetomidine group ( p<0.05 ) . There were no statistically significant differences between two groups in the extubation time , ICU stay , total hospital stay , and other postoperative complications including hemodynamic side effects . Conclusion This preliminary study suggests that dexmedetomidine as a postoperative sedative agent is as sociated with significantly lower rates of delirium after cardiac surgery CONTEXT In the intensive care unit ( ICU ) , delirium is a common yet underdiagnosed form of organ dysfunction , and its contribution to patient outcomes is unclear . OBJECTIVE To determine if delirium is an independent predictor of clinical outcomes , including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001 . Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale . MAIN OUTCOME MEASURES Primary outcomes included 6-month mortality , overall hospital length of stay , and length of stay in the post-ICU period . Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge . RESULTS Of 275 patients , 51 ( 18.5 % ) had persistent coma and died in the hospital . Among the remaining 224 patients , 183 ( 81.7 % ) developed delirium at some point during the ICU stay . Baseline demographics including age , comorbidity scores , dementia scores , activities of daily living , severity of illness , and admission diagnoses were similar between those with and without delirium ( P>.05 for all ) . Patients who developed delirium had higher 6-month mortality rates ( 34 % vs 15 % , P = .03 ) and spent 10 days longer in the hospital than those who never developed delirium ( P<.001 ) . After adjusting for covariates ( including age , severity of illness , comorbid conditions , coma , and use of sedatives or analgesic medications ) , delirium was independently associated with higher 6-month mortality ( adjusted hazard ratio [ HR ] , 3.2 ; 95 % confidence interval [ CI ] , 1.4 - 7.7 ; P = .008 ) , and longer hospital stay ( adjusted HR , 2.0 ; 95 % CI , 1.4 - 3.0 ; P<.001 ) . Delirium in the ICU was also independently associated with a longer post-ICU stay ( adjusted HR , 1.6 ; 95 % CI , 1.2 - 2.3 ; P = .009 ) , fewer median days alive and without mechanical ventilation ( 19 [ interquartile range , 4 - 23 ] vs 24 [ 19 - 26 ] ; adjusted P = .03 ) , and a higher incidence of cognitive impairment at hospital discharge ( adjusted HR , 9.1 ; 95 % CI , 2.3 - 35.3 ; P = .002 ) . CONCLUSION Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma , sedatives , and analgesics in patients receiving mechanical ventilation 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 Dexmedetomidine , a highly selective and potent α2‐adrenergic agonist , has a potentially useful role as a sedative agent in patients requiring intensive care . As part of a larger European multicentre trial , a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom . One hundred and five patients were r and omly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine , respectively . Compared with the control group , intubated patients receiving dexmedetomidine required 80 % less midazolam [ mean 4.9 ( 5.8 ) μg.kg−1.h−1 vs. 23.7 ( 27.5 ) μg.kg−1.h−1 , p < 0.0001 ] , and 50 % less morphine [ 11.2 ( 13.4 ) μg.kg−1.h−1 vs. 21.5 ( 19.4 ) μg.kg−1.h−1,p = 0.0006 ] . Cardiovascular effects and adverse events could be predicted from the known properties of alpha‐2 agonists . In conclusion , dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation BACKGROUND Although known to be an independent predictor of poor outcomes in medical intensive care unit ( ICU ) patients , limited data exist regarding the prevalence of and risk factors for delirium among surgical ( SICU ) and trauma ICU ( TICU ) patients . The purpose of this study was to analyze the prevalence of and risk factors for delirium in surgical and trauma ICU patients . METHODS SICU and TICU patients requiring mechanical ventilation ( MV ) > 24 hours were prospect ively evaluated for delirium using the Richmond Agitation Sedation Scale ( RASS ) and the Confusion Assessment Method for the ICU ( CAM-ICU ) . Those with baseline dementia , intracranial injury , or ischemic/hemorrhagic strokes that would confound the evaluation of delirium were excluded . Markov models were used to analyze predictors for daily transition to delirium . RESULTS One hundred patients ( 46 SICU and 54 TICU ) were enrolled . Prevalence of delirium was 73 % in the SICU and 67 % in the TICU . Multivariable analyses identified midazolam [ OR 2.75 ( CI 1.43 - 5.26 , p = 0.002 ) ] exposure as the strongest independent risk factor for transitioning to delirium . Opiate exposure showed an inconsistent message such that fentanyl was a risk factor for delirium in the SICU ( p = 0.007 ) but not in the TICU ( p = 0.936 ) , whereas morphine exposure was associated with a lower risk of delirium ( SICU , p = 0.069 ; TICU p = 0.024 ) . CONCLUSION Approximately 7 of 10 SICU and TICU patients experience delirium . In keeping with other recent data on benzodiazepines , exposure to midazolam is an independent and potentially modifiable risk factor for the transitioning to delirium Objective : Dexmedetomidine ( DEX ) may provide a sedation level that enables sleep and communication , with less amnesia and pain medication requirements , during mechanical ventilation . Our study directly assessed patient-perceived satisfaction with coronary artery bypass graft surgery after administration of DEX or propofol for intensive care unit ( ICU ) sedation . Design : Prospect i ve , r and omized clinical study with subsequent question naire administration . Setting : Tertiary care surgical ICU . Patients : A total of 89 adult , nonemergent , coronary artery bypass graft patients with an expected length of intubation of < 24 hrs . Interventions : Patients were r and omized to either DEX or propofol ; drug administration was performed via st and ardized anesthesia and nursing protocol s. Measurements : Patients reported perceptions of their ICU experience after mechanical ventilation with a modified numerical-scale Hewitt question naire , vali date d specifically for ICU patients . Patients were question ed regarding awareness , recall , generalized comfort , level of pain , ability to interact with healthcare providers and family , feelings of agitation and anxiety , perceived ease of extubation , ability to sleep or rest , and satisfaction with ICU experience . Main Results : Groups were well matched at baseline , with a mean ± sd age of 63.0 ± 10.4 yrs and weight of 88.7 ± 16.7 kg . No difference was observed for length of surgery , length of intubation , or ICU stay ( p > .05 ) . DEX patients perceived a shorter length of intubation ( p = .044 ) . A deeper sedation level was found in the propofol group ( p = .021 ) , with similar morphine and midazolam requirements ( p = .317 ) . Patient-rated level of overall awareness as a marker of amnesia did not differ between groups ( p = .653 ) . The ability to rest or sleep trended toward significance favoring propofol ( p = .051 ) . On evaluation of question naire ratings , DEX patients expressed more discomfort ( p = .046 ) , pain ( p = .096 ) , and sleeping difficulty ( p = .036 ) . Similar comfort levels were reported during extubation ( p = .179 ) . Conclusions : Despite theoretical advantages of DEX to improve overall patient satisfaction , the two agents provide similar responses to amnesia and pain control . According to our findings , DEX does not seem to have any advantage compared with propofol for short-term sedation after coronary artery bypass graft surgery Introduction Agitated delirium is common in patients undergoing mechanical ventilation , and is often treated with haloperidol despite concerns about safety and efficacy . Use of conventional sedatives to control agitation can preclude extubation . Dexmedetomidine , a novel sedative and anxiolytic agent , may have particular utility in these patients . We sought to compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation . Methods We conducted a r and omised , open-label , parallel-groups pilot trial in the medical and surgical intensive care unit of a university hospital . Twenty patients undergoing mechanical ventilation in whom extubation was not possible solely because of agitated delirium were r and omised to receive an infusion of either haloperidol 0.5 to 2 mg/hour or dexmedetomidine 0.2 to 0.7 μg/kg/hr , with or without loading doses of 2.5 mg haloperidol or 1 μg/kg dexmedetomidine , according to clinician preference . Results Dexmedetomidine significantly shortened median time to extubation from 42.5 ( IQR 23.2 to 117.8 ) to 19.9 ( IQR 7.3 to 24 ) hours ( P = 0.016 ) . Dexmedetomidine significantly decreased ICU length of stay , from 6.5 ( IQR 4 to 9 ) to 1.5 ( IQR 1 to 3 ) days ( P = 0.004 ) after study drug commencement . Of patients who required ongoing propofol sedation , the proportion of time propofol was required was halved in those who received dexmedetomidine ( 79.5 % ( 95 % CI 61.8 to 97.2 % ) vs. 41.2 % ( 95 % CI 0 to 88.1 % ) of the time intubated ; P = 0.05 ) . No patients were reintubated ; three receiving haloperidol could not be successfully extubated and underwent tracheostomy . One patient prematurely discontinued haloperidol due to QTc interval prolongation . Conclusions In this preliminary pilot study , we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation , and we suggest this warrants further testing in a definitive double-blind multi-centre trial . Trial registration Clinical trials.gov BACKGROUND We evaluated the use of dexmedetomidine to facilitate the weaning of delirious postoperative patients from mechanical ventilation . METHODS We included 72 consecutive patients who underwent elective cardiac surgery in this prospect i ve observational study . Each patient had failed at least 1 trial of continuous positive airway pressure ( CPAP ) and had agitation . Patients were assessed with the Richmond Agitation-Sedation Scale ( RASS ) and the Confusion Assessment Method for the Intensive Care Unit ( CAMICU ) 12 to 18 hours after their admission to the ICU . Midazolam and fentanyl were then given to all patients according to the sedation protocol . At 36 hours in the ICU , patients who had agitation and an inability to wean were r and omly divided into 2 groups : group M , 34 patients who continued to follow the routine sedative protocol ; and group D , 38 patients who were given dexmedetomidine . Arterial blood gas measurements , hemodynamic parameters , and time to extubation were recorded . Statistical analysis was performed with GraphPad InStat ( version 2.02 for DOS ) . RESULTS All patients tested positive in the CAM-ICU assessment , and all had a delirium diagnosis . The 38 patients in group D tolerated a spontaneous breathing trial with CPAP and were extubated after a mean ( ±SD ) of 49.619 ± 6.96 hours . The 2 groups had significantly different extubation times ( 58.389 ± 3.958 hours versus 49.619 ± 6.96 hours ) . The 2 groups had significantly different RASS scores at 48 and 60 hours and significantly different heart rates and PO2 values at 12 and 24 hours . The 2 groups showed no significant differences with regard to hemodynamic parameters . CONCLUSIONS Dexmedetomidine may help to eliminate the emergence of agitation and can be a good treatment choice for the delirium state after cardiac surgery OBJECTIVES To compare the effects of dexmedetomidine and propofol on sublingual microcirculation in patients after cardiac surgery . DESIGN A prospect i ve , r and omized , single-blind study . SETTING University hospital . PARTICIPANTS Adult patients undergoing elective valve surgery with cardiopulmonary bypass . INTERVENTIONS On arrival in the intensive care unit ( ICU ) , patients were assigned r and omly to receive either dexmedetomidine ( 0.2 - 1.5 μg/kg/h ) or propofol ( 5 - 50 μg/kg/min ) with open-label titration to a target Richmond Agitation-Sedation Scale of 0 to -3 . MEASUREMENTS AND MAIN RESULTS Sublingual microcirculation was recorded using sidestream dark-field imaging at ICU admission ( baseline [ T1 ] ) and 4 hours ( T2 ) and 24 hours after ICU admission ( T3 ) . At T2 , median changes in perfused small-vessel density and the De Backer score from baseline were significantly greater in the dexmedetomidine group ( n = 29 ) than in the propofol group ( n = 32 ) ( 1.3 v 0 mm/mm2 , p = 0.025 ; 0.9 v -0.1/mm , p = 0.005 , respectively ) ; median changes in small-vessel density and the proportion of perfused small vessels from baseline also tended to be higher in the dexmedetomidine group compared with the propofol group ( 1.0 v -0.1 mm/mm2 , p = 0.050 ; 2.1 % v 0.5 % , p = 0.062 , respectively ) . At T3 , there still was a trend toward greater improvements in the small-vessel density , proportion of perfused small-vessels , perfused small-vessel density , and De Backer score from baseline in the dexmedetomidine group than in the propofol group . CONCLUSIONS This trial demonstrated that dexmedetomidine sedation may be better able to improve microcirculation in cardiac surgery patients during the early postoperative period compared with propofol Background and aims Postoperative delirium ( POD ) is a common and serious surgical complication among the elderly , especially in those with amnestic mild cognitive impairment ( aMCI ) . Dexmedetomidine ( DEX ) is neuroprotective for delirium . In this study , we determined the effect of intravenously administered DEX during general anesthesia on POD in elderly aMCI patients undergoing elective hip joint or knee joint or shoulder joint replacement surgery . Methods This was a prospect i ve , r and omized parallel-group study of aMCI ( n = 80 ) and normal elderly patients ( n = 120 ) . Prior to surgery , all subjects underwent neuropsychological assessment and were assigned to one of four groups : the aMCI DEX group ( MD group , n = 40 ) , the aMCI normal saline group ( MN group , n = 40 ) , the control DEX group ( CD group , n = 60 ) , and the control normal saline group ( CN group , n = 60 ) . The confusion assessment method was used to screen POD on postoperative days 1 , 3 , and 7 . Results We found patients age was positively correlated with POD incidence in the MN group ( p < 0.05 ) but not in the CN group ( p < 0.05 ) . DEX treatment significantly decreased POD incidence in both control and aMCI groups relative to their respective placebo groups ( all p < 0.05 ) . The fraction of patients whose normal cognitive function was not restored by day 7 after surgery was significantly higher in the MN group than the MD and CN groups ( all p < 0.05 ) . Conclusions These findings suggested that DEX treatment during surgery significantly reduced POD incidence in both normal and aMCI elderly patients , suggesting that it may be an effective option for the prevention of POD BACKGROUND Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances . OBJECTIVE The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures . METHODS Patients underwent elective cardiac surgery with a st and ardized intraoperative anesthesia protocol , followed by r and om assignment to one of three postoperative sedation protocol s : dexmedetomidine , propofol , or midazolam . RESULTS The incidence of delirium for patients receiving dexmedetomidine was 3 % , for those receiving propofol was 50 % , and for patients receiving midazolam , 50 % . Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization . CONCLUSION The findings of this open-label , r and omized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs Purpose To compare dexmedetomidine ( DEX ) with st and ard care ( SC , either propofol or midazolam ) for long-term sedation in terms of maintaining target sedation and length of intensive care unit ( ICU ) stay . Methods A pilot , phase III , double-blind multicenter study in r and omized medical and surgical patients ( n = 85 ) within the first 72 h of ICU stay with an expected ICU stay of ≥48 h and sedation need for ≥24 h after r and omization . Patients were assigned to either DEX ( ≤1.4 μg kg−1 h−1 ; n = 41 ) or SC ( n = 44 ) , with daily sedation stops . Results Non-inferiority of DEX versus SC was not confirmed . Target Richmond agitation – sedation score ( RASS ) was reached a median of 64 % ( DEX ) and 63 % ( SC ) of the sedation time ( ns ) . The length of ICU stay was similar in DEX and SC . Patients with RASS target 0–3 ( DEX 78 % , SC 80 % ) were at target sedation 74 % ( DEX ) and 64 % ( SC ) of the time ( ns ) , whereas those with RASS target −4 or less reached the target 42 % ( DEX ) and 62 % ( SC ) of the time ( P = .006 ) . Post hoc analyses suggested shorter duration of mechanical ventilation for DEX ( P = 0.025 ) . Conclusions This pilot study suggests that in long-term sedation , DEX is comparable to SC in maintaining sedation targets of RASS 0 to −3 but not suitable for deep sedation ( RASS −4 or less ) . DEX had no effect on length of ICU stay . Its effects on other relevant clinical outcomes , such as duration of mechanical ventilation , should be tested further OBJECTIVES To prospect ively develop and vali date a predictive model for delirium based on precipitating factors during hospitalization , and to examine the interrelationship of precipitating factors and baseline vulnerability . DESIGN Two prospect i ve cohort studies , in t and em . SETTING General medical wards , university teaching hospital . PATIENTS For the development cohort , 196 patients aged 70 years and older with no delirium at baseline , and for the validation cohort , 312 comparable patients . MAIN OUTCOME MEASURE New-onset delirium by hospital day 9 , defined by the Confusion Assessment Method diagnostic criteria . RESULTS Delirium developed in 35 patients ( 18 % ) in the development cohort . Five independent precipitating factors for delirium were identified ; use of physical restraints ( adjusted relative risk [ RR ] , 4.4 ; 95 % confidence interval [ CI ] , 2.5 to 7.9 ) , malnutrition ( RR , 4.0 ; 95 % CI , 2.2 to 7.4 ) , more than three medications added ( RR , 2.9 ; 95 % CI , 1.6 to 5.4 ) , use of bladder catheter ( RR , 2.4 ; 95 % CI , 1.2 to 4.7 ) , and any iatrogenic event ( RR , 1.9 ; 95 % CI , 1.1 to 3.2 ) . Each precipitating factor preceded the onset of delirium by more than 24 hours . A risk stratification system was developed by adding 1 point for each factor present . Rates of delirium for low-risk ( 0 points ) , intermediate-risk ( 1 to 2 points ) , and high-risk groups ( > or equal to 3 points ) were 3 % , 20 % , and 59 % , respectively ( P < .001 ) . The corresponding rates in the validation cohort , in which 47 patients ( 15 % ) developed delirium , were 4 % , 20 % , and 35 % , respectively ( P < .001 ) . When precipitating and baseline factors were analyzed in cross-stratified format , delirium rates increased progressively from low-risk to high-risk groups in all directions ( double-gradient phenomenon ) . The contributions of baseline and precipitating factors were documented to be independent and statistically significant . CONCLUSIONS A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium . Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive , and cumulative ways OBJECTIVE To compare the efficacy and safety of sedation with dexmedetomidine vs. midazolam for patients with acute cardiogenic pulmonary edema and hypoxemia during the treatment of non-invasive ventilation ( NIV ) . METHODS The intensive care unit ( ICU ) patients treated in our hospital between March 2008 and August 2011 who had acute pulmonary edema and hyoxemia in NIV failure due to patient refusal to continue the NIV sessions ( due to discomfort ) were enrolled in this study . The patients were divided into two groups by the r and om numerical table method . They were treated with either midazolam ( 29 cases ) or dexmedetomidine ( 33 cases ) . The patients were se date d ( Ramsay scale 2 - 3 ) by a continuous perfusion of midazolam or dexmedetomidine during the NIV session . Cardiorespiratory and ventilatory parameters , the results of the blood gas analysis , and adverse events were prospect ively recorded . The main outcome measure was the percentage of endotracheal intubation during NIV . Secondary endpoints included the duration of non-invasive mechanical ventilation , length of ICU stay , and adverse events . RESULTS In both groups of patients , the expected sedative scores were obtained . The cardiorespiratory symptoms and signs ( oxygenation index , pH value , and respiratory rate ) were significantly improved in both groups . In the dexmedetomidine-treated group , the patients had a further decreased percentage of failure of NIV requiring endotracheal intubation ( ETI ) and a more prolonged mean time to ETI ( p=0.042 , p=0.024 ) . Furthermore , when compared with the group treated with midazolam , the overall duration of mechanical ventilation and the duration of ICU hospitalization in the group treated with dexmedetomidine were markedly decreased , and weaning from mechanical ventilation was easier ( p=0.010 , p=0.042 ) . Despite the fact that more dexmedetomidine-treated patients developed bradycardia ( 18.2 % vs. 0 , p=0.016 ) , no patients required an intervention or interruption of study drug infusion . Conversely , the incidence of respiratory infections and vomiting was lower in the dexmedetomidine-treated patients ( p=0.026 , p=0.010 ) . CONCLUSION Dexmedetomidine led to a more desired level of awaking sedation , shortened the duration of mechanical ventilation and the length of the ICU stay , and further reduced the prevalence of nosocomial infection for NIV sedation in patients with acute cardiogenic pulmonary edema . It appears to provide several advantages and safe control compared with the γ-amino butyric acid ( GABA ) agonist midazolam Background : Commonly used sedatives/analgesics can increase the risk of postoperative complications , including delirium . This double-blinded study assessed the neurobehavioral , hemodynamic , and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia . Methods : A total of 306 patients at least 60 yr old were r and omized to receive dexmedetomidine ( 0.1–0.7 & mgr;g · kg−1 · h−1 ) or morphine ( 10 - 70 & mgr;g · kg−1 · h−1 ) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2–4 . Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care . Secondary outcomes included ventilation time , additional sedation/analgesia , and hemodynamic and adverse effects . Results : Of all sedation assessment s , 75.2 % of dexmedetomidine and 79.6 % ( P = 0.516 ) of morphine treatment were in the target range . Delirium incidence was comparable between dexmedetomidine 13 ( 8.6 % ) and morphine 22 ( 15.0 % ) ( relative risk 0.571 , 95 % confidence interval [ CI ] 0.256–1.099 , P = 0.088 ) , however , dexmedetomidine-managed patients spent 3 fewer days ( 2 [ 1–7 ] versus 5 [ 2–12 ] ) in delirium ( 95 % CI 1.09–6.67 , P = 0.0317 ) . The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine ( 3 of 20 [ 15 % ] versus 9 of 25 [ 36 % ] ) ( relative risk 0.416 , 95 % CI 0.152–0.637 , P = 0.001 ) . Dexmedetomidine-treated patients were more likely to be extubated earlier ( relative risk 1.27 , 95 % CI 1.01–1.60 , P = 0.040 , log-rank P = 0.036 ) , experienced less systolic hypotension ( 23 % versus 38.1 % , P = 0.006 ) , required less norepinephrine ( P < 0.001 ) , but had more bradycardia ( 16.45 % versus 6.12 % , P = 0.006 ) than morphine treatment . Conclusion : Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation , less hypotension , less vasopressor requirement , and more bradycardia versus morphine regimen Background : Postoperative delirium ( POD ) is a serious complication after cardiac surgery . Use of dexmedetomidine to prevent delirium is controversial . The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD . Methods : After institutional ethics review board approval , and informed consent , a single-blinded , prospect i ve , r and omized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery . Patients with a history of serious mental illness , delirium , and severe dementia were excluded . Upon admission to intensive care unit ( ICU ) , patients received either dexmedetomidine ( 0.4 & mgr;g/kg bolus followed by 0.2 to 0.7 & mgr;g kg−1 h−1 infusion ) or propofol ( 25 to 50 & mgr;g kg−1 min−1 infusion ) according to a computer-generated r and omization code in blocks of four . Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days . Primary outcome was the incidence of POD . Results : POD was present in 16 of 91 ( 17.5 % ) and 29 of 92 ( 31.5 % ) patients in dexmedetomidine and propofol groups , respectively ( odds ratio , 0.46 ; 95 % CI , 0.23 to 0.92 ; P = 0.028 ) . Median onset of POD was on postoperative day 2 ( 1 to 4 days ) versus 1 ( 1 to 4 days ) , P = 0.027 , and duration of POD 2 days ( 1 to 4 days ) versus 3 days ( 1 to 5 days ) , P = 0.04 , in dexmedetomidine and propofol groups , respectively . Conclusions : When compared with propofol , dexmedetomidine sedation reduced incidence , delayed onset , and shortened duration of POD in elderly patients after cardiac surgery . The absolute risk reduction for POD was 14 % , with a number needed to treat of 7.1 Subjects se date d by noradrenergic alpha2 agonists can switch rapidly from a state of extremely low to almost full consciousness following phasic increases in arousal or cognitive dem and . Such flexibility is not displayed by traditional sedatives , such as the benzodiazepine diazepam . Experimentally , the phasic modulation of alpha2 effect by arousing or distracting stimuli can counteract the deleterious cognitive effects of alpha2 agonists . We used behavioural and fMRI indices of brain function to investigate the phasic modulatory effect that presentation of loud white noise would have on attentional dysfunction induced by administration of dexmedotomidine , an alpha2 agonist . Dexmedotomidine and midazolam were compared to placebo during performance of a target detection task , which was presented in the presence or absence of white noise . Compared to placebo , both dexmedotomidine and midazolam impaired task performance . This impairment was significantly attenuated by presentation of white noise in the dexmedotomidine condition only . This functional improvement corresponded to selective increase in activity of left medial pulvinar nucleus of the thalamus . This regional increase is suggested to index increases in phasic arousal , which counteract dexmedotomidine 's detrimental attentional effects . Finally , despite sedating subjects to equivalent degrees , dexmedotomidine and midazolam had strikingly different regional effects on task-induced brain activity . Therefore , for the same level of sedation , the behavioural and anatomical attributes identifying the quality of sedation can vary Introduction : Sedation with dexmedetomidine may facilitate ventilator liberation and limit the occurrence of delirium . No trial has assessed patient recall or the development of psychological outcomes after dexmedetomidine sedation . This pilot study evaluated whether transitioning benzodiazepine sedation to dexmedetomidine alters patient recall and the incidence of anxiety , depression , or acute stress disorder ( ASD ) . Methods : This investigation was a r and omized , double-blind , single-center study . Existing continuous benzodiazepine sedation was converted to dexmedetomidine or midazolam when patients qualified for daily awakenings . Sedation was titrated to achieve Riker sedation agitation scores of 3 to 4 . The intensive care unit ( ICU ) Stressful Experiences Question naire , hospital anxiety and depression scale , and the impact of event scale-revised were administered before hospital discharge to assess recall , anxiety , depression , and manifestations of ASD . Results : A total of 11 patients received dexmedetomidine , and 12 patients received midazolam . Median dosing was 0.61 µg/kg/h for 3.5 days for dexmedetomidine and 3.7 mg/h for 3 days for midazolam . Attainment of goal sedation and analgesia was similar ; however , more dexmedetomidine patients experienced agitation and pain . The median duration of mechanical ventilation from study drug initiation to extubation was 3.4 days in dexmedetomidine patients and 2.9 days in midazolam patients . Dexmedetomidine patients remembered 18.5 experiences compared with 8.5 in midazolam patients ( P = .015 ) . Rates of anxiety and depression were similar . In all , 5 ( 62.5 % ) dexmedetomidine patients and 1 ( 12.5 % ) midazolam patient manifested ASD ( P = .063 ) , and 1 dexmedetomidine patient and 5 midazolam patients developed new-onset delirium ( P = .07 ) . Hypotension occurred in 10 ( 90.9 % ) dexmedotomidine patients and 6 ( 50 % ) midazolam patients ( P = .069 ) . Conclusions : Transitioning benzodiazepine sedation to dexmedetomidine when patients qualify for daily awakenings may reduce the development of delirium and facilitate remembrance of ICU experiences but may lead to manifestations of ASD . Monitoring hypotension is required for both the sedatives . Additional comparative studies focusing on the long-term impact of ICU recall and psychological outcomes are needed CONTEXT Long-term sedation with midazolam or propofol in intensive care units ( ICUs ) has serious adverse effects . Dexmedetomidine , an α(2)-agonist available for ICU sedation , may reduce the duration of mechanical ventilation and enhance patient comfort . OBJECTIVE To determine the efficacy of dexmedetomidine vs midazolam or propofol ( preferred usual care ) in maintaining sedation ; reducing duration of mechanical ventilation ; and improving patients ' interaction with nursing care . DESIGN , SETTING , AND PATIENTS Two phase 3 multicenter , r and omized , double-blind trials carried out from 2007 to 2010 . The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries ; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia . Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours ( midazolam , n = 251 , vs dexmedetomidine , n = 249 ; propofol , n = 247 , vs dexmedetomidine , n = 251 ) . INTERVENTIONS Sedation with dexmedetomidine , midazolam , or propofol ; daily sedation stops ; and spontaneous breathing trials . MAIN OUTCOME MEASURES For each trial , we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level ( measured by Richmond Agitation-Sedation Scale ) and superior to control with respect to duration of mechanical ventilation . Secondary end points were patients ' ability to communicate pain ( measured using a visual analogue scale [ VAS ] ) and length of ICU stay . Time at target sedation was analyzed in per- protocol population ( midazolam , n = 233 , vs dexmedetomidine , n = 227 ; propofol , n = 214 , vs dexmedetomidine , n = 223 ) . RESULTS Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 ( 95 % CI , 0.97 - 1.18 ) and dexmedetomidine/propofol , 1.00 ( 95 % CI , 0.92 - 1.08 ) . Median duration of mechanical ventilation appeared shorter with dexmedetomidine ( 123 hours [ IQR , 67 - 337 ] ) vs midazolam ( 164 hours [ IQR , 92 - 380 ] ; P = .03 ) but not with dexmedetomidine ( 97 hours [ IQR , 45 - 257 ] ) vs propofol ( 118 hours [ IQR , 48 - 327 ] ; P = .24 ) . Patients ' interaction ( measured using VAS ) was improved with dexmedetomidine ( estimated score difference vs midazolam , 19.7 [ 95 % CI , 15.2 - 24.2 ] ; P < .001 ; and vs propofol , 11.2 [ 95 % CI , 6.4 - 15.9 ] ; P < .001 ) . Length of ICU and hospital stay and mortality were similar . Dexmedetomidine vs midazolam patients had more hypotension ( 51/247 [ 20.6 % ] vs 29/250 [ 11.6 % ] ; P = .007 ) and bradycardia ( 35/247 [ 14.2 % ] vs 13/250 [ 5.2 % ] ; P < .001 ) . CONCLUSIONS Among ICU patients receiving prolonged mechanical ventilation , dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation . Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients ' ability to communicate pain compared with midazolam and propofol . More adverse effects were associated with dexmedetomidine . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00481312 , NCT00479661 Background / objectives Delirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit ( ICU ) population . It was first described more than half a century ago , where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay , reduced quality of life and increased mortality . However , in most cases , there is still lack of proof for causal relationship . Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form . Furthermore , in the general ICU population , it has been shown that the duration of delirium is associated with worse long-term cognitive function . Due to the multifactorial origin of delirium , we have several but no incontestable treatment options . Nonetheless , delirium bears a high burden for patient , family members and the medical care team . The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients . We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan . Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general . This could further contribute to higher patient safety . The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU . We hypothesise that dexmedetomidine , compared with propofol administered at night , shortens both the duration and severity of delirium . Methods / design The Basel ProDex Study is an investigator-initiated , one-institutional , two-centre r and omised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium . The primary outcome measure is delirium duration in hours . Secondary outcomes include delirium-free days at day 28 , death at day 28 , delirium severity , amount of ventilator days , amount of rescue sedation with haloperidol , length of ICU and hospital stay , and pharmaceutical economic analysis of the treatments . Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours . The trial will be externally monitored according to good clinical practice ( GCP ) requirements . There are no interim analyses planned for this trial . Ethics and dissemination This study will be conducted in compliance with the protocol , the current version of the Declaration of Helsinki , the International Conference on Harmonization- Good Clinical Practice ( ICH-GCP ) or Europäische Norm International Organization for St and ardization ( ISO EN 14155 ; as far as applicable ) as well as all national legal and regulatory requirements . Only the study team will have access to trial specific data . Anonymisation will be achieved by a unique patient identification code . Trial data will be archived for a minimum of 10 years after study termination . We plan to publish the data in a major peer- review ed clinical journal . Trials registration Clinical Trials.gov Identifier : NCT02807467 Protocol version Clinical Study Protocol Version 2 , Delirium , defined as an acute disorder of attention and cognition , occurs in 14 % to 56 % of elderly , hospitalized patients [ 1 - 16 ] and may be the most frequent complication of hospitalization in this population [ 6 ] . Delirium is associated with increased rates of morbidity , mortality , and nursing home placement and with longer , costlier hospitalizations [ 17 - 29 ] . Effective prevention requires the identification of risk factors for delirium . Seven prospect i ve studies have systematic ally examined risk factors for delirium in elderly , hospitalized patients [ 9 , 12 - 14 , 16 , 30 , 31 ] . The risk factors generally identified included age , dementia , severe illness , metabolic and electrolyte imbalance , the use of psychoactive medications , and infections . However , most studies failed to distinguish prevalent cases of delirium at admission from incident cases occurring during hospitalization , a necessary step to define risk factors that truly precede the onset of delirium . In addition , only one of the previous studies [ 16 ] used a st and ardized , vali date d instrument to identify delirium . Finally , no study proposed a predictive model for delirium that was vali date d in an independent sample . Previous studies focused on identifying precipitating factors for delirium ( hospitalization-related factors such as medications , procedures , and intercurrent infections ) or have simultaneously examined precipitating and predisposing conditions [ 9 , 12 - 14 , 16 , 30 , 31 ] . Although identifying these precipitating factors is undoubtedly important , an essential , prerequisite step is elucidation of baseline ( or host ) characteristics that indicate a particular vulnerability to delirium . The focus of our study was to better define host or baseline vulnerability factors that would assist clinicians in identifying , at admission , those patients with a high risk for developing delirium during hospitalization . Our objectives were to estimate the incidence of delirium in an elderly hospitalized cohort using a st and ardized , vali date d instrument ; to identify admission characteristics associated with the new occurrence of delirium ; and to develop and vali date a predictive model for the occurrence of delirium in the hospital based on the characteristics present at admission . Methods Patients The potential study patients were consecutive weekday admissions from the emergency service to six general medicine floors at Yale-New Haven Hospital from June 1988 through March 1989 . Eligibility criteria , which were met by 135 patients , included age of 70 years or more ; no evidence of delirium at admission by clinical evaluation ; and no history of severe dementia reported by the admitting attending physician or nurse or documented in the medical record . The latter criterion was selected to exclude patients with severe underlying dementia ; patients with mild-to-moderate cognitive impairment were still eligible for the study . Exclusion criteria included an inability to undergo interviewing for such reasons as terminal illness , violent behavior , or intubation ( n = 14 ) ; brief hospitalization ( < 48 hours ) ( n = 5 ) ; language barrier ( n = 2 ) ; refusal by the patient , family , or physician ( n = 3 ) ; and other reasons ( n = 4 ) . Of the 135 eligible patients , 107 ( 79 % ) were enrolled in the study . Clinical Evaluation Trained clinician- research ers carried out daily structured interviews with the patients and their primary nurses from entry until hospital discharge . The baseline patient interview , completed within 48 hours of admission , was design ed to gather demographic information ; to discover whether the patient had a history of confusion ; and to determine the patient 's pre-illness social activity level , activities of daily living [ 32 ] , instrumental activities of daily living [ 33 ] , and social network and supports [ 34 ] . The interview also included the Mini-Mental State Examination [ 35 ] , the Geriatric Depression Scale [ 36 ] , st and ard vision ( Jaeger- and Snellen-type tests ) and hearing tests ( Welch-Allyn audioscope ) , and questions design ed to screen for hearing loss [ 37 , 38 ] . Baseline information obtained from the nurses included an overall rating of illness severity [ 39 ] . Early in the hospital admission , family members or caregivers underwent a structured interview that included a modified Blessed Dementia Rating Scale [ 40 , 41 ] and an estimation of the duration of any cognitive impairment . Thereafter , the clinician- research ers interviewed the patients and their nurses daily and review ed medical records to detect any new cases of delirium . The discharge assessment included determination of discharge location . Medical records were review ed for admission medical diagnoses ( inclusive list based on review of all admission notes ) , medications , and laboratory data . Informed consent was obtained from the patient or , for those with significant cognitive impairment , from the closest relative . The study was approved by the institutional review board of Yale University School of Medicine . Identification of Delirium Suspected cases of delirium were identified during the daily patient and nurse interviews . The Confusion Assessment Method [ 42 ] question naire , a previously vali date d instrument with a sensitivity rate ranging from 94 % to 100 % and a specificity rate ranging from 90 % to 95 % , was completed daily by two observers ( a clinician- research er and a nurse ) . The principal investigator ( SKI ) saw each patient with suspected delirium within 24 hours and established all final diagnoses of delirium based on fulfillment of the Confusion Assessment Method diagnostic criteria , which included the following : acute onset and fluctuating course ; inattention ; and either disorganized thinking or altered level of consciousness [ 42 ] . A case of delirium developing at any time during hospitalization was included in the analysis ; however , a given patient could only develop delirium once ( recurrent episodes of delirium were not counted when determining the relative-risk estimates ) . Definition of Variables We used clinical ly meaningful cutpoints to categorize variables . Patients were considered to have vision impairment if their corrected vision was worse than 20/70 on both near and distant binocular tests . Patients were considered to have hearing loss if they heard fewer than three of eight tones on the audioscope test ( tones at a hearing level of 40 dB and at frequencies of 500 , 1000 , 2000 , and 4000 Hz ) , had a score of 4 of 8 or less on the questions screening for hearing loss [ 37 , 38 ] , or wore a hearing aid . Patients were considered to have chronic cognitive impairment if they scored less than 24 of 30 on the Mini-Mental State Examination at admission [ 35 ] . The chronicity of the cognitive impairment in each patient with a score of less than 24 was confirmed by a modified Blessed Dementia Rating Scale score of 4 or more or by a duration of cognitive symptoms of at least 6 months . Illness severity was rated at admission using an APACHE II score [ 43 ] and a subjective overall rating by the nurse ( adapted from Charlson and colleagues ' observer-rated ordinal scale [ 39 ] ) trichotomized as mild , moderate , or severe . Severe illness was considered present if the nurse gave a rating of severe or the APACHE score exceeded 16 . An abnormal blood urea nitrogen/creatinine ratio , used as an index of dehydration , was defined as 18 or more [ 4 ] . Prominent depressive symptoms were considered present if the Geriatric Depression Scale score was equal to or exceeded the median score of 8 of 30 . The size of a patient 's social support network was estimated by the sum of the number of children , close relatives , and friends he or she saw at least once a month . A low number of social supports was indicated by six or fewer such contacts per month . Three social support typesinstrumental support , emotional support , and presence of a confidantewere rated as present or absent . Having a few support types was indicated by the presence of one or none of these support types . Validation Study To vali date the predictive model in an independent sample , a second cohort of patients was assembled . Patients Potential participants in the validation study included 202 patients who were enrolled from November 1989 through June 1990 in another ongoing study examining the frequency of functional decline in hospitalized elderly persons at Yale-New Haven Hospital . The inclusion and exclusion criteria for this study were identical to those for the study in the development cohort , except that patients with preexisting dementia were not excluded . For comparability with the initial development cohort , therefore , 25 patients ( 12 % ) with a documented history of dementia , Alzheimer disease , or chronic organic brain syndrome in their medical record were not considered eligible for the validation sample . Of the 177 eligible patients , 174 ( 98 % ) were included in the validation sample ; 3 patients were excluded because missing data did not allow assessment of the outcome of delirium . Procedure The clinical evaluation and identification of patients with delirium were similar in the two cohorts . In all but three instances , the same assessment instruments were used . Only near binocular vision ( Jaeger-type test ) , not distant vision , was tested in the validation cohort . For assessment of hearing , the Whisper test [ 44 ] was used . Hearing impairment was defined as present if the patient heard correctly fewer than 7 of 12 numbers on the Whisper test or wore a hearing aid . A shortened 15-item version of the Geriatric Depression Scale [ 45 ] was used . Significant depressive symptoms were considered present if the patient had a score that was equal to or exceeded the median of 4 of 15 . Statistical Analyses In bivariate analyses , rates of delirium were calculated when each risk factor was present or absent . Crude relative risks were determined as the number of events ( delirium ) per person-days of observation in the group with the risk factor present relative to the number of such events per person-days Background : Delirium is very common among patients with polytrauma , although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients . Recent reports have suggested that continuous intravenous ( IV ) infusions of dexmedetomidine , rather than benzodiazepine , be administered for sedation to reduce the duration of delirium in this population . However , serum neuron-specific enolase ( NSE ) , S100 calcium binding protein B ( S100B ) , and brain-derived neurotrophic factor ( BDNF ) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives . The aim of this study was to assess the association of blood BDNF , NSE , and S100B with the occurrence of delirium among polytrauma patients who had been se date d with dexmedetomidine . Material s and Methods : Consecutive patients were r and omly assigned to 1 of 2 treatment study groups , namely the “ dexmedetomidine group ” or the “ common group . ” This case – control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit ( ICU ) . Blood sample s were collected from all patients upon ICU admission , on the day when delirium was diagnosed , and on days 3 and 5 following diagnosis . The serum levels of S100B , BDNF , and NSE were determined by enzyme-linked immunosorbent assay . The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU . Results : The median BDNF , NSE , and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed . The rate of delirium was significantly lower in the dexmedetomidine group than in the common group . There were clear differences in the BDNF , NSE , and S100B levels between the 2 groups on the fifth day after delirium was diagnosed . Conclusions : Our r and omized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF , S100B , and NSE levels , which appear to be associated with the occurrence of delirium in the dexmedetomidine group Background : Dexmedetomidine , a selective α2‐adrenoceptor agonist , induces a unique , sleep‐like state of sedation . The objective of the present work was to study human electroencephalogram ( EEG ) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep , to test the hypothesis that dexmedetomidine exerts its effects via normal sleep‐promoting pathways Objective : Delirium , an acute organ dysfunction , is common among critically ill patients leading to significant morbidity and mortality ; its epidemiology in a mixed cardiology and cardiac surgery ICU is not well established . We sought to determine the prevalence and risk factors for delirium among cardiac surgery ICU patients . Design : Prospect i ve observational study . Setting : Twenty-seven-bed medical-surgical cardiac surgery ICU . Patients : Two hundred consecutive patients with an expected cardiac surgery ICU length of stay > 24 hrs . Interventions : None . Measurements : Baseline demographic data and daily assessment s for delirium using the vali date d and reliable Confusion Assessment Method for the ICU were recorded , and quantitative tracking of delirium risk factors were conducted . Separate analyses studied the role of admission risk factors for occurrence of delirium during the cardiac surgery ICU stay and identified daily occurring risk factors for the development of delirium on a subsequent cardiac surgery ICU day . Main Results : Prevalence of delirium was 26 % , similar among cardiology and cardiac surgical patients . Nearly all ( 92 % ) exhibited the hypoactive subtype of delirium . Benzodiazepine use at admission was independently predictive of a three-fold increased risk of delirium ( odds ratio 3.1 [ 1 , 9.4 ] , p = 0.04 ) during the cardiac surgery ICU stay . Of the daily occurring risk factors , patients who received benzodiazepines ( 2.6 [ 1.2 , 5.7 ] , p = 0.02 ) or had restraints or devices that precluded mobilization ( 2.9 [ 1.3 , 6.5 ] , p < 0.01 ) were more likely to have delirium the following day . Hemodynamic status was not associated with delirium . Conclusions : Delirium occurred in one in four patients in the cardiac surgery ICU and was predominately hypoactive in subtype . Chemical restraints via use of benzodiazepines or the use of physical restraints/restraining devices predisposed patients to a greater risk of delirium , pointing to areas of quality improvement that would be new to the vast majority of cardiac surgery ICUs OBJECTIVE To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft ( CABG ) surgery in the intensive care unit ( ICU ) . DESIGN R and omized , open label . SETTING Twenty-five centers in the United States and Canada . PARTICIPANTS Two hundred ninety-five adults undergoing CABG surgery . INTERVENTIONS At sternal closure , patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or = 2 after extubation . Patients could be given propofol for additional sedation if necessary ; group B patients received propofol-based care according to each investigator 's st and ard practice . MEASUREMENTS AND MAIN RESULTS Mean sedation levels were within target ranges in both groups . Mean times to weaning and extubation were similar , although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours . Morphine use was significantly reduced in the dexmedetomidine group . Only 28 % of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69 % of propofol-based patients ( p < 0.001 ) . Propofol patients required 4 times the mean dose of morphine while in the ICU . Mean blood pressure increased initially in both groups , then decreased to 3 mmHg below baseline in dexmedetomidine patients ; mean arterial pressure remained at 9 mmHg above baseline in propofol patients . No ventricular tachycardia occurred in the dexmedetomidine-se date d patients compared with 5 % of the propofol patients ( p = 0.007 ) . Respiratory rates and blood gases were similar . Fewer dexmedetomidine patients received beta-blockers ( p = 0.014 ) , antiemetics ( p = 0.015 ) , nonsteroidal anti-inflammatory drugs ( p < 0.001 ) , epinephrine ( p = 0.030 ) , or high-dose diuretics ( p < 0.001 ) . CONCLUSION Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics , beta-blockers , antiemetics , epinephrine , and diuretics BACKGROUND Sedation with dexmedetomidine and propofol may cause hypotension or bradycardia . This study aim ed to compare the effects of dexmedetomidine and propofol on hemodynamics and clinical outcomes in surgical intensive care unit ( ICU ) patients after major abdominal surgery . MATERIAL S AND METHODS Enrolled patients were r and omly allocated to the dexmedetomidine or propofol group . Cardiac index was measured using a continuous noninvasive cardiac output monitor on the basis of chest bioreactance . Heart rate , blood pressure , opioid requirement , urine output , delirium incidence , ICU length of stay , and total hospital length of stay were compared between the two groups . The incidences of bradycardia , hypotension , and severe low cardiac index were compared . RESULTS We enrolled 60 patients . Heart rate and mean arterial pressure were significantly lower in the dexmedetomidine group than in the propofol group . Cardiac index did not differ significantly between the two groups ( dexmedetomidine group 3.1 L/min/m2 , [ 95 % confidence interval { 95 % CI } 2.8 - 3.3 ] versus propofol group 3.2 L/min/m2 [ 95 % CI 2.9 - 3.5 ] , P = 0.578 ) . The incidences of bradycardia , hypotension , and severe low cardiac index did not differ significantly between the two groups . CONCLUSIONS Cardiac index did not differ significantly between the dexmedetomidine and propofol groups in surgical ICU patients after major abdominal surgery Background : The use of intravenous sedation during cardiac surgery to reduce awareness has been practised routinely during past few years and the two most commonly used drugs include propofol and dexmedetomidine , but their effects on hemodynamics and postoperative outcomes in cardiac surgery is continually being evaluated . Aims : The aim of this study was to compare the effects of anesthesia by dexmedetomidine and propofol on the hemodynamic variables and postoperative outcomes in patients who were planned for elective cardiac surgery . Setting s : Cardiac operating room of a tertiary care hospital . Design : A prospect i ve , r and omized controlled , double-blind clinical trial . Material s and Methods : Sixty patients were r and omized to receive either a continuous infusion of propofol ( 0.25–1 mg/kg/h ) or dexmedetomidine bolus of 1 μg/kg over 10 min followed by infusion ( 0.2–0.6 μg/kg/h ) after induction of anesthesia . The anesthesia technique and physiological monitoring including bispectral index monitoring were similar among both the groups . Hemodynamic variables ( mean heart rate [ HR ] , mean arterial pressure [ MAP ] ) were noted at predefined time intervals , intraoperative vasopressor or inotrope requirements and postoperative outcomes including postoperative ventilation time and length of stay in the Intensive Care Unit ( ICU ) were also recorded . Statistical Analysis : Statistics was done using SPSS V 20 ( IBM , NY ) using Student 's t-test , analysis of variance , and Mann – Whitney U-test , and a P < 0.05 was considered to indicate a significant difference . Results and Conclusions : HR and MAP were significantly less in dexmedetomidine group compared to propofol group ( P < 0.05 ) . Both the groups had a similar requirement of vasopressors and inotropes . The duration of postoperative ventilation and length of stay in the ICU were significantly shorter in the dexmedetomidine group ( P < 0.05 ) . The risk of delirium was significantly less in dexmedetomidine group ( P < 0.05 ) . From our study we concluded , that the perioperative infusion of dexmedetomidine produces better hemodynamic stability , reduces the risk of postoperative delirium , and leads to shorter ICU stay IMPORTANCE Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation . OBJECTIVE To determine the effectiveness of dexmedetomidine when added to st and ard care in patients with agitated delirium receiving mechanical ventilation . DESIGN , SETTING , AND PARTICIPANTS The Dexmedetomidine to Lessen ICU Agitation ( DahLIA ) study was a double-blind , placebo-controlled , parallel-group r and omized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium . The study was conducted at 15 intensive care units in Australia and New Zeal and from May 2011 until December 2013 . Patients with advanced dementia or traumatic brain injury were excluded . INTERVENTIONS Bedside nursing staff administered dexmedetomidine ( or placebo ) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals . The study drug or placebo was continued until no longer required or up to 7 days . All other care was at the discretion of the treating physician . MAIN OUTCOMES AND MEASURES Ventilator-free hours in the 7 days following r and omization . There were 21 reported secondary outcomes that were defined a priori . RESULTS Of the 74 r and omized patients ( median age , 57 years ; 18 [ 24 % ] women ) , 2 withdrew consent later and 1 was found to have been r and omized incorrectly , leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis . Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo ( median , 144.8 hours vs 127.5 hours , respectively ; median difference between groups , 17.0 hours [ 95 % CI , 4.0 to 33.2 hours ] ; P = .01 ) . Among the 21 a priori secondary outcomes , none were significantly worse with dexmedetomidine , and several showed statistically significant benefit , including reduced time to extubation ( median , 21.9 hours vs 44.3 hours with placebo ; median difference between groups , 19.5 hours [ 95 % CI , 5.3 to 31.1 hours ] ; P < .001 ) and accelerated resolution of delirium ( median , 23.3 hours vs 40.0 hours ; median difference between groups , 16.0 hours [ 95 % CI , 3.0 to 28.0 hours ] ; P = .01 ) . Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics , allocation to dexmedetomidine was significantly associated with earlier extubation ( hazard ratio , 0.47 [ 95 % CI , 0.27 - 0.82 ] ; P = .007 ) . CONCLUSIONS AND RELEVANCE Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit , the addition of dexmedetomidine to st and ard care compared with st and ard care alone ( placebo ) result ed in more ventilator-free hours at 7 days . The findings support the use of dexmedetomidine in patients such as these . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01151865 Importance Dexmedetomidine provides sedation for patients undergoing ventilation ; however , its effects on mortality and ventilator-free days have not been well studied among patients with sepsis . Objectives To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation . Design , Setting , and Participants Open-label , multicenter r and omized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours . Interventions Patients were r and omized to receive either sedation with dexmedetomidine ( n = 100 ) or sedation without dexmedetomidine ( control group ; n = 101 ) . Other agents used in both groups were fentanyl , propofol , and midazolam . Main Outcomes and Measures The co– primary outcomes were mortality and ventilator-free days ( over a 28-day duration ) . Sequential Organ Failure Assessment score ( days 1 , 2 , 4 , 6 , 8) , sedation control , occurrence of delirium and coma , intensive care unit stay duration , renal function , inflammation , and nutrition state were assessed as secondary outcomes . Results Of the 203 screened patients , 201 were r and omized . The mean age was 69 years ( SD , 14 years ) ; 63 % were male . Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group ( 19 patients [ 22.8 % ] vs 28 patients [ 30.8 % ] ; hazard ratio , 0.69 ; 95 % CI , 0.38 - 1.22 ; P = .20 ) . Ventilator-free days over 28 days were not significantly different between groups ( dexmedetomidine group : median , 20 [ interquartile range , 5 - 24 ] days ; control group : median , 18 [ interquartile range , 0.5 - 23 ] days ; P = .20 ) . The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation ( range , 17%-58 % vs 20%-39 % ; P = .01 ) ; other outcomes were not significantly different between groups . Adverse events occurred in 8 ( 8 % ) and 3 ( 3 % ) patients in the dexmedetomidine and control groups , respectively . Conclusions and Relevance Among patients requiring mechanical ventilation , the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days . However , the study may have been underpowered for mortality , and additional research may be needed to evaluate this further . Trial Registration clinical trials.gov Identifier : Importance Postoperative delirium occurs in 10 % to 60 % of elderly patients having major surgery and is associated with longer hospital stays , increased hospital costs , and 1-year mortality . Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium . However , intraoperative use of dexmedetomidine for prevention of delirium has not been well studied . Objective To evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium . Design , Setting , and Participants This study was a multicenter , double-blind , r and omized , placebo-controlled trial that r and omly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room . Patients were assessed daily for postoperative delirium ( primary outcome ) and secondarily for postoperative cognitive decline . Participants were elderly ( > 68 years ) patients undergoing major elective noncardiac surgery . The study date s were February 2008 to May 2014 . Interventions Dexmedetomidine infusion ( 0.5 µg/kg/h ) during surgery and up to 2 hours in the recovery room . Main Outcomes and Measures The primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium . Secondarily , the study examined the correlation between dexmedetomidine use and postoperative cognitive change . Results In total , 404 patients were r and omized ; 390 completed in-hospital delirium assessment s ( median [ interquartile range ] age , 74.0 [ 71.0 - 78.0 ] years ; 51.3 % [ 200 of 390 ] female ) . There was no difference in postoperative delirium between the dexmedetomidine and placebo groups ( 12.2 % [ 23 of 189 ] vs 11.4 % [ 23 of 201 ] , P = .94 ) . After adjustment for age and educational level , there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months . Adverse events were comparably distributed in the treatment groups . Conclusions and Relevance Intraoperative dexmedetomidine does not prevent postoperative delirium . The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed , which underscores the importance of timing when administering the drug to prevent delirium . Trial Registration clinical trials.gov Identifier |
12,639 | 31,013,841 | The home-based intervention positively reduced BMI . | Childhood obesity has adverse impacts on premature mortality and morbidity .
Managing obesity could prevent premature mortality and several types of complications among high-risk groups .
This study aim ed to review and examine the effects of home-based interventions to treat and prevent childhood obesity . | The objective of the present study was to evaluate the effectiveness of a one-year multi-component immersive day-camp weight-loss intervention for children with overweight and obesity . The study design was a parallel-group r and omized controlled trial . One hundred fifteen 11 - 13-year-old children with overweight and obesity were r and omized into either : A six-week day-camp intervention arm focusing on increased physical activity , and healthy diet followed by a subsequent one-year family-based intervention , or a st and ard intervention arm consisting of one weekly exercise session for six weeks . Body mass index ( BMI ) was the primary outcome . BMI z-score , clustered cardiovascular risk z-score , and body composition were secondary outcomes . All outcomes were measured at baseline , six week- , and 52 week follow-up . After six weeks , children from the day-camp intervention arm had improved their BMI ( -2.2 kg/m2 ( 95 % CI -2.6 to -1.7 , P<0.001 ) ) and all secondary outcomes when compared to the children from the st and ard intervention arm . After 52 weeks , the day-camp intervention arm had a lower BMI ( -1.2 kg/m2 ( 95 % CI -1.8 to -0.5 , P = 0.001 ) ) , and BMI z-score ( -0.20 ( 95 % CI -0.35 to -0.05 , P = 0.008 ) ) , and clustered cardiovascular risk z-score ( -0.23 ( 95 % CI -0.37 to -0.08 , P = 0.002 ) ) compared to the st and ard intervention arm . No group differences were detected in body composition after 52 weeks . This study shows that the day-camp intervention arm is effective in reducing BMI and improving the metabolic health of children with overweight and obesity . However , the effects seem to be diminishing over time OBJECTIVE The study presents the immediate post-intervention results of Kids and Adults Now - Defeat Obesity ! , a r and omized controlled trial to enhance healthy lifestyle behaviors in mother-preschooler ( 2 - 5 years old ) dyads in North Carolina ( 2007 - 2011 ) . The outcomes include change from baseline in the child 's diet , physical activity and weight , and in the mother 's parenting behaviors , diet , physical activity , and weight . METHOD The intervention targeted parenting through maternal emotion regulation , home environment , feeding practice s , and modeling of healthy behaviors . 400 mother-child dyads were r and omized . RESULTS Mothers in the intervention arm , compared to the control arm , reduced instrumental feeding ( -0.24 vs. 0.01 , p<0.001 ) and TV snacks ( -.069 vs. -0.24 , p=0.001 ) . There were also improvements in emotional feeding ( p=0.03 ) , mother 's sugary beverage ( p=0.03 ) and fruit/vegetable ( p=0.04 ) intake , and dinners eaten in front of TV ( p=0.01 ) ; these differences were not significant after adjustment for multiple comparisons . CONCLUSION KAN-DO , design ed to maximize the capacity of mothers as agents of change , improved several channels of maternal influence . There were no group differences in the primary outcomes , but differences were observed in the parenting and maternal outcomes and there were trends toward improvement in the preschoolers ' diets . Long-term follow-up will address whether these short-term trends ultimately improve weight status OBJECTIVE : To determine whether a 2-year family-based intervention using frequent contact and limited expert involvement was effective in reducing excessive weight compared with usual care . METHODS : Two hundred and six overweight and obese ( BMI ≥85th percentile ) children aged 4 to 8 years were r and omized to usual care ( UC ) or tailored package ( TP ) sessions at university research rooms . UC families received personalized feedback and generalized advice regarding healthy lifestyles at baseline and 6 months . TP families attended a single multidisciplinary session to develop specific goals suitable for each family , then met with a mentor each month for 12 months , and every third month for another 12 months to discuss progress and provide support . Outcome measurements ( anthropometry , question naires , dietary intake , accelerometry ) were obtained at 0 , 12 , and 24 months . RESULTS : BMI at 24 months was significantly lower in TP compared with UC children ( difference , 95 % confidence interval : –0.34 , –0.65 to –0.02 ) , as was BMI z score ( –0.12 , –0.20 to –0.04 ) and waist circumference ( –1.5 , –2.5 to –0.5 cm ) . TP children consumed more fruit and vegetables ( P = .038 ) and fewer noncore foods ( P = .020 ) than UC children , and fewer noncore foods were available in the home ( P = .002 ) . TP children were also more physically active ( P = .035 ) . No differences in parental feeding practice s , parenting , quality of life , child sleep , or behavior were observed . CONCLUSIONS : Frequent , low-dose support was effective for reducing excessive weight in predominantly mild to moderately overweight children over a 2-year period . Such initiatives could feasibly be incorporated into primary care Background Obesity is mainly attributed to environmental factors . In developed countries , the time spent on physical activity tasks is decreasing , whereas sedentary behaviour patterns are increasing . The purpose of the intervention is to evaluate the effectiveness of an intensive family-based behavioural multi-component intervention ( Nereu programme ) and compared it to counselling intervention such as a health centre intervention programme for the management of children ’s obesity . Methods / Design The study design is a r and omized controlled multicenter clinical trial using two types of interventions : Nereu and Counselling . The Nereu programme is an 8-month intensive family-based multi-component behavioural intervention . This programme is based on a multidisciplinary intervention consisting of 4 components : physical activity sessions for children , family theoretical and practical sessions for parents , behaviour strategy sessions involving both , parents and children , and lastly , weekend extra activities for all . Counselling is offered to the family in the form of a monthly physical health and eating habits session . Participants will be recruited according the following criteria : 6 to 12 year-old-children , referred from their paediatricians due to overweight or obesity according the International Obesity Task Force criteria and with a sedentary profile ( less than 2 hours per week of physical activity ) , they must live in or near the municipality of Lleida ( Spain ) and their healthcare paediatric unit must have previously accepted to cooperate with this study . The following variables will be evaluated : a ) cardiovascular risk factors ( anthropometric parameters , blood test and blood pressure ) , b ) sedentary and physical activity behaviour and dietary intake , c ) psychological aspects d ) health related quality of life ( HRQOL ) , e ) cost-effectiveness of the intervention in relation to HRQOL . These variables will be then be evaluated 4 times longitudinally : at baseline , at the end of the intervention ( 8 months later ) , 6 and 12 months after the intervention . We have considered necessary to recruit 100 children and divide them in 2 groups of 50 to detect the differences between the groups . Discussion This trial will provide new evidence for the long-term effects of childhood obesity management , as well as help to know the impact of the present intervention as a health intervention tool for healthcare centres . Trial registration Clinical Trials.gov , Background Childhood obesity has been increasing rapidly worldwide . There is limited evidence for effective lifestyle interventions to prevent childhood obesity worldwide , especially in developing countries like China . The objective of this study was to assess the effectiveness of a school-based multi-component lifestyle childhood obesity prevention program ( the CLICK-Obesity study ) in Mainl and China . Methods A cluster r and omized controlled trial was developed among grade 4 students from 8 urban primary schools ( 638 students in intervention , 544 as control ) in Nanjing City , China . Students were r and omly allocated to the control or intervention group at school-level . A one-year multi-component intervention program ( classroom curriculum , school environment support , family involvement and fun programs/events ) together with routine health education was provided to the intervention group , while the control group received routine health education only . The main outcome variables assessed were changes in body mass index , obesity occurrence , obesity-related lifestyle behaviors and knowledge . Results Overall , 1108 ( 93.7 % ) of the 1182 enrolled students completed the intervention study . The intervention group had a larger marginal reduction than did the control group in overall mean BMI value ( -0.32±1.36 vs. -0.29±1.40 , p = 0.09 ) , although this was not significant . Compared with the control group , the intervention group was more likely to decrease their BMI ( OR = 1.44 , 95%CI = 1.10 , 1.87 ) by 0.5 kg/m2 or above , increase the frequency of jogging/running ( OR = 1.55 , 95%CI = 1.18 , 2.02 ) , decrease the frequency of TV/computer use ( OR = 1.41 , 95%CI = 1.09 , 1.84 ) and of red meat consumption ( OR = 1.50 , 95%CI = 1.15 , 1.95 ) , change commuting mode to/from school from sedentary to active mode ( OR = 2.24 , 95%CI = 1.47 , 3.40 ) , and be aware of the harm of selected obesity risk factors . Conclusions The school-based lifestyle intervention program was practical and effective in improving health behaviors and obesity-related knowledge for children in China . This study provides important policy implication s on school-based intervention programs for modifications of obesity-related lifestyles . Trial Registration Chinese Clinical Trial Registry BACKGROUND Few successful treatment modalities exist to address childhood obesity . Given Latinos ' strong identity with family , a family-focused intervention may be able to control Latino childhood obesity . PURPOSE To assess the feasibility and effectiveness of a family-centered , primary care-based approach to control childhood obesity through lifestyle choices . DESIGN R and omized waitlist controlled trial in which control participants received the intervention 6 months after the intervention group . SETTING / PARTICIPANTS Forty-one Latino children with BMI > 85 % , aged 9 - 12 years , and their caregivers were recruited from an urban community health center located in a predominantly low-income community . INTERVENTION Children and their caregivers received 6 weeks of interactive group classes followed by 6 months of culturally sensitive monthly in-person or phone coaching to empower families to incorporate learned lifestyles and to address both family and social barriers to making changes . MAIN OUTCOMES MEASURES Caregiver report on child and child self-reported health-related quality of life ( HRQoL ) ; metabolic markers of obesity ; BMI ; and accelerometer-based physical activity were measured July 2010-November 2011 and compared with post-intervention assessment s conducted at 6 months and as a function of condition assignment . Data were analyzed in 2012 . RESULTS Average attendance rate to each group class was 79 % . Socio-environmental and family factors , along with knowledge , were cited as barriers to changing lifestyles to control obesity . Caregiver proxy and child self-reported HRQoL improved for both groups with a larger but not nonsignificant difference among intervention vs control group children ( p=0.33 ) . No differences were found between intervention and control children for metabolic markers of obesity , BMI , or physical activity . CONCLUSIONS Latino families are willing to participate in group classes and health coaching to control childhood obesity . It may be necessary for primary care to partner with community initiatives to address childhood obesity in a more intense manner . TRIAL REGISTRATION This study is registered at Clinical trials.partners.org 2009P001721 Background : The best outcomes for treating childhood obesity have come from comprehensive family-based programmes . However there are questions over their generalizability . Objective : To examine the acceptability and effectiveness of ‘ family-based behavioural treatment ’ ( FBBT ) for childhood obesity in an ethnically and socially diverse sample of families in a UK National Health Service ( NHS ) setting . Methods : In this parallel group , r and omized controlled trial , 72 obese children were r and omized to FBBT or a waiting-list control . Primary outcomes were body mass index ( BMI ) and BMI s.d . scores ( SDSs ) . Secondary outcomes were weight , weight SDSs , height , height SDSs , waist , waist SDSs , FM index , FFM index , blood pressure ( BP ) and psychosocial measures . The outcomes were assessed at baseline and after treatment , with analyses of 6-month data performed on an intent-to-treat ( ITT ) basis . Follow-up anthropometric data were collected at 12 months for the treatment group . Results : ITT analyses included all children with baseline data ( n=60 ) . There were significant BMI SDS changes ( P<0.01 ) for the treatment and control groups of −0.11 ( 0.16 ) and −0.10 ( 1.6 ) . The treatment group showed a significant reduction in systolic BP ( −0.24 ( 0.7 ) , P<0.05 ) and improvements in quality of life and eating attitudes ( P<0.05 ) , with no significant changes for the control group . However the between-group treatment effects for BMI , body composition , BP and psychosocial outcomes were not significant . There was no overall change in BMI or BMI SDSs from 0–12 months for the treatment group . No adverse effects were reported . Conclusions : Both treatment and control groups experienced significant reductions in the level of overweight , but with no significant difference between them . There were no significant group differences for any of the secondary outcomes . This trial was registered at http://www.controlled-trials.com/ under IS RCT N 51382628 The one-year outcome of the r and omized controlled T.A.F.F. ( Telephone based Adiposity prevention For Families ) study is presented . Screening of overweight ( BMI -SDS > 90th centile ) children 3.5–17.4 years was performed via the German CrescNet data base , and c and i date s were r and omized to an intervention group ( IG ) and control group ( CG ) . The intervention consisted of computer-aided telephone counselling for one year , supported by mailed newsletters . The primary endpoint was change in BMI -SDS ; secondary endpoints were eating behavior , physical activity , media consumption , quality of life . Data from 289 families ( 145 IG ( 51 % females ) ; 144 CG ( 50 % females ) ) were analyzed ( Full Analysis Set : FAS ; Per Protocol Set : PPS ) . Successful intervention was defined as decrease in BMI -SDS ≥ 0.2 . In the FAS , 21 % of the IG was successful as compared to 16 % from the CG ( 95 % CI for this difference : ( −4 , 14 ) , p = 0.3 , mean change in BMI -SDS : −0.02 for IG vs. 0.02 for CG ; p = 0.4 ) . According to the PPS , however , the success rate was 35 % in the IG compared to 19 % in the CG ( mean change in BMI -SDS : −0.09 for IG vs. 0.02 for CG ; p = 0.03 ) . Scores for eating patterns ( p = 0.01 ) , media consumption ( p = 0.007 ) , physical activity ( p = 9 × 10−9 ) , quality of life ( p = 5 × 10−8 ) decreased with age , independent of group or change in BMI -SDS . We conclude that a telephone-based obesity prevention program suffers from well-known high attrition rates so that its effectiveness could only be shown in those who adhered to completion . The connection between lifestyle and weight status is not simple and requires further research to better underst and OBJECTIVE The goal of this study was to evaluate the effect of a parent-focused behavioral intervention on parent and child eating changes and on percentage of overweight changes in families that contain at least one obese parent and a non-obese child . RESEARCH METHODS AND PROCEDURES Families with obese parents and non-obese children were r and omized to groups in which parents were provided a comprehensive behavioral weight-control program and were encouraged to increase fruit and vegetable intake or decrease intake of high-fat/high-sugar foods . Child material s targeted the same dietary changes as their parents without caloric restriction . RESULTS Changes over 1 year showed that treatment influenced targeted parent and child fruit and vegetable intake and high-fat/high-sugar intake , with the Increase Fruit and Vegetable group also decreasing their consumption of high-fat/high-sugar foods . Parents in the increased fruit and vegetable group showed significantly greater decreases in percentage of overweight than parents in the decreased high-fat/high-sugar group . DISCUSSION These results suggest that focusing on increasing intake of healthy foods may be a useful approach for nutritional change in obese parents and their children Background Obesity amongst children is a growing problem worldwide . In contrast to adults , little is known on the effects of controlled weight loss on components of the metabolic syndrome in children . The primary aim of the study was to evaluate the effects of a 20-week exercise and diet guidance intervention on body mass index ( BMI ) in a group of overweight children . Our hypothesis was an observed reduction in BMI and secondarily in body fat content , insulin insensitivity , and other components of the metabolic syndrome in the intervention group . Methods School children from Copenhagen were r and omly allocated to an intervention group ( n = 19 ) or a control group ( n = 19 ) . Anthropometric assessment , whole body dual-energy X-ray absorptiometry scan , two hours oral glucose tolerance test , steps measured by pedometer , and fitness tests were measured at baseline and at 20 weeks . Results Thirty-seven children ( 30 girls ) participated at baseline , aged 8.7 ± 0.9 years with a BMI of 21.8 ± 3.7 kg/m2 ( mean ± SD ) , and 36 children completed the study . The intervention group decreased their BMI ( the intervention effect is the difference in change between the groups adjusted for the respective baseline values ( DELTA ) = -2.0 kg/m2 , 95 % CI : -2.5 ; -1.5 , P < 0.001 ) , total body mass ( DELTA = -4.0 kg , 95 % CI : -4.9 ; -3.0 , P < 0.001 ) , and fat mass ( DELTA = -3.3 kg , 95 % CI : -4.2 ; -2.7 , P < 0.001 ) compared to the control group after the intervention . The intervention group displayed decreased waist , hip and waist-to-height ratio ( WHtR ) ( all three variables ; P < 0.001 ) , area under curve for plasma insulin ( P < 0.05 ) , and increased mean and minimum steps/day ( P < 0.05 and P < 0.01 , respectively ) . Conclusions The multicomponent intervention had significant favorable effects on BMI , weight , WHtR , mean and minimum steps/day , and fat mass . In addition , similar beneficial metabolic effects were found in the children as shown in adults , e.g. increase in peripheral insulin sensitivity . Trial registration Clinical trials.gov Identifier number NCT01660789 Background Reversing the obesity epidemic requires the development and evaluation of childhood obesity intervention programs . Lifestyle Triple P is a parent-focused group program that addresses three topics : nutrition , physical activity , and positive parenting . Australian research has established the efficacy of Lifestyle Triple P , which aims to prevent excessive weight gain in overweight and obese children . The aim of the current r and omized controlled trial is to assess the effectiveness of the Lifestyle Triple P intervention when applied to Dutch parents of overweight and obese children aged 4–8 years . This effectiveness study is called GO4fit . Methods / Design Parents of overweight and obese children are being r and omized to either the intervention or the control group . Those assigned to the intervention condition receive the 14-week Lifestyle Triple P intervention , in which they learn a range of nutritional , physical activity and positive parenting strategies . Parents in the control group receive two brochures , web-based tailored advice , and suggestions for exercises to increase active playing at home . Measurements are taken at baseline , directly after the intervention , and at one year follow-up . Primary outcome measure is the children ’s body composition , operationalized as BMI z-score , waist circumference , and fat mass ( biceps and triceps skinfolds ) . Secondary outcome measures are children ’s dietary behavior and physical activity level , parenting practice s , parental feeding style , parenting style , parental self-efficacy , and body composition of family members ( parents and siblings ) . Discussion Our intervention is characterized by a focus on changing general parenting styles , in addition to focusing on changing specific parenting practice s , as obesity interventions typically do . Strengths of the current study are the r and omized design , the long-term follow-up , and the broad range of both self-reported and objective ly measured outcomes .Trial Registration Current Controlled Trials NTR 2555MEC AzM/UMNL 31988.068.10 / MEC 10 - 3 - Purpose : To compare the impact of adhering to a Mediterranean diet plus mixed physical exercise program ( Move‐It ) implemented by means of printed instructions or via a web‐platform ( with or without e‐mail support ) on body composition , physical fitness , and blood pressure . Design and Methods : R and omized clinical trial . Fifty‐two overweight or obese Spanish children and adolescents were r and omly assigned to the print‐based ( n = 18 ) , Move‐It ( n = 18 ) , or Move‐It plus support ( n = 16 ) intervention groups . Two‐way mixed ANOVA tests were used to compare any changes between the groups in terms of percentage body fat , physical fitness ( VO2peak ) , h and grip strength , and systolic and diastolic blood pressure . The measurements were taken before and after a three‐month mixed‐exercise ( aerobic and resistance ) and Mediterranean‐diet program which was either implemented by means of printed instructions or via a web‐platform ( with or without e‐mail support ) . Results : No statistical differences were found between groups . However , the results highlighted significant improvements in body fat percentage metrics over time for all three groups ( print‐based : −1.8 % , 95%CI −3.3 % to −0.3 % ; Move‐It : −1.8 % , 95%CI −3.3 % to −0.3 % ; Move‐It plus support : −2.0 % , 95%CI −3.7 % to −0.4 % , P < 0.05 ) . We also observed a tendency towards improvement in the VO2peak , h and grip strength , and blood pressure variable values 10 min after the exercise‐stress test in these three groups . Conclusions : The program improved the body composition , regardless of the way it is implemented . Practice Implication s : A mixed physical exercise program lasting for three months , combined with a Mediterranean diet , improves the body composition of children and adolescents with overweight/obesity . Highlights : Move‐It improves the body composition in three months . Move‐It improves the body composition , regardless of the way it is implemented . Move‐It shows a tendency towards improvement in physical fitness and blood pressure The purpose of the present study was to evaluate an intervention to prevent weight gain among households ( HHs ) in the community . Ninety HHs were r and omized to intervention or control group for 1 year . Intervention consisted of six face-to-face group sessions , placement of a television ( TV ) locking device on all home TVs , and home-based intervention activities . Measures were collected in person at baseline and 1 year . Weight , height , eating behaviors , physical activity ( PA ) , and TV viewing were measured among HH members ages ≥ 12 years . Follow-up rate at 1 year was 96 % . No significant intervention effects were observed for change in HH BMI -z score . Intervention HHs significantly reduced TV viewing , snacks/sweets intake , and dollars per person spent eating out , and increased ( adults only ) PA and self-weighing frequency compared with control HHs . A 1 year obesity prevention intervention targeting entire HHs was effective in reducing TV viewing , snack/sweets intake and eating out purchases . Innovative methods are needed to strengthen the home food environment intervention component . Longer intervention duration s also need to be evaluated INTRODUCTION Family- and school-based interventions for childhood obesity have been widely applied ; however , the prevalence of childhood obesity remains high . The purpose of this RCT is to evaluate the effectiveness of a family-individual-school-based comprehensive intervention model . DESIGN Cluster RCT . SETTING / PARTICIPANTS Fourteen primary schools were selected from 26 primary schools in a district of Shanghai , China , and then r and omly divided into intervention and control groups with seven schools in each . The trial started with first- grade students . A total of 1,287 students in the intervention group and 1,159 in the control group were studied overall . INTERVENTION The baseline study was conducted in January 2011 , and family-individual-school-based interventions started in March 2011 and ended in December 2013 for intervention group students . Three follow-up studies were conducted in January 2012 , January 2013 , and January 2014 . Data analysis was conducted in March 2014 . MAIN OUTCOME MEASURES Students ' weight and height were measured . The prevalence of obesity/overweight and BMI z-scores were calculated and analyzed using a generalized estimating equation approach . RESULTS The overall prevalence of overweight/obesity declined from 28.92 % in 2011 to 24.77 % in 2014 , with a difference of 4.15 % in the intervention group compared with a 0.03 % decline ( from 30.71 % to 30.68 % ) in the control group . The intervention group had significantly lower odds of developing obesity or overweight and had decreased average BMI z-scores compared with the control group , especially for obese or overweight students . CONCLUSIONS The family-individual-school-based comprehensive intervention model is effective for controlling childhood obesity and overweight BACKGROUND Interventions to prevent and control childhood obesity have shown mixed results in terms of short- and long-term changes . OBJECTIVES ' MOVE/me Muevo ' was a 2-year family- and recreation centre-based r and omized controlled trial to promote healthy eating and physical activity among 5- to 8-year-old children . It was hypothesized that children in the intervention group would demonstrate lower post-intervention body mass index ( BMI ) values and improved obesity-related behaviours compared with the control group children . METHODS Thirty recreation centres in San Diego County , California , were r and omized to an intervention or control condition . Five hundred forty-one families were enrolled and children 's BMI , diet , physical activity and other health indicators were tracked from baseline to 2 years post-baseline . Analyses followed an intent-to-treat approach using mixed-effects models . RESULTS No significant intervention effects were observed for the primary outcomes of child 's or parent 's BMI and child 's waist circumference . Moderator analyses , however , showed that girls ( but not boys ) in the intervention condition reduced their BMI . At the 2-year follow-up , intervention condition parents reported that their children were consuming fewer high-fat foods and sugary beverages . CONCLUSIONS Favourable implementation fidelity and high retention rates support the feasibility of this intervention in a large metropolitan area ; however , interventions of greater intensity may be needed to achieve effects on child 's BMI . Also , further research is needed to develop gender-specific intervention strategies so that both genders may benefit from such efforts The aim of this study was to evaluate the effectiveness of the Mind , Exercise , Nutrition , Do it ( MEND ) Program , a multicomponent community-based childhood obesity intervention ( www.mend central .org ) . One hundred and sixteen obese children ( BMI > or= 98 th percentile , UK 1990 reference data ) were r and omly assigned to intervention or waiting list control ( 6-month delayed intervention ) . Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools , followed by a 12-week free family swimming pass . Waist circumference , BMI , body composition , physical activity level , sedentary activities , cardiovascular fitness , and self-esteem were assessed at baseline and at 6 months . Children were followed up 12 months from baseline ( 0 and 6 months postintervention for the control and intervention group , respectively ) . Participants in the intervention group had a reduced waist circumference z-score ( -0.37 ; P < 0.0001 ) and BMI z-score ( -0.24 ; P < 0.0001 ) at 6 months when compared to the controls . Significant between-group differences were also observed in cardiovascular fitness , physical activity , sedentary behaviors , and self-esteem . Mean attendance for the MEND Program was 86 % . At 12 months , children in the intervention group had reduced their waist and BMI z-scores by 0.47 ( P < 0.0001 ) and 0.23 ( P < 0.0001 ) , respectively , and benefits in cardiovascular fitness , physical activity levels , and self-esteem were sustained . High-attendance rates suggest that families found this intensive community-based intervention acceptable . Further larger controlled trials are currently underway to confirm the promising findings of this initial trial OBJECTIVE The aim of this study was to compare the effect of a hospital clinic group- versus home-based combined exercise-diet program for the treatment of childhood obesity . METHODS One hundred ten overweight/obese Spanish children and adolescents ( 6 - 16 years ) in 2 intervention groups ( hospital clinic group-based [ n = 45 ] and home-based [ n = 41 ] ) and a sex-age-matched control group ( n = 24 ) were r and omly assigned to participate in a 6-month combined exercise ( aerobic and resistance training ) and Mediterranean diet program . Anthropometric values ( including body weight , height , body mass index , BMI -Z score , and waist circumference ) were measured pre- and postintervention for all the participants . Percentage body fat was also determined with a body fat analyzer ( TANITA TBF-410 M ) . RESULTS Our study showed a significant reduction in percentage body fat and body mass index Z-score among both intervention-group participants ( 4 % , 0.16 , hospital clinic group-based ; 4.4 % , 0.23 , home-based ; P < .0001 ) . There was also a significant reduction in waist circumference in the home-based group ( 4.4 cm ; P = .019 ) . Attendance rates at intervention sessions were equivalent for both intervention groups ( P = .805 ) . CONCLUSIONS The study findings indicate that a simple home-based combined exercise and Mediterranean diet program may be effective among overweight and obese children and adolescents , because it improves body composition , is feasible and can be adopted on a large scale without substantial expenses BACKGROUND Effective treatment of childhood obesity requires a multi-factorial approach and should target factors impacting on a child 's environment . OBJECTIVE To explore the impact of three treatment programs on parental child-feeding practice s at 6 , 12 and 24 months post-program . SUBJECTS/INTERVENTION : Overweight children ( n=159 ) aged 5 - 7 years , recruited to the Hunter Illawarra Kids Challenge Using Parent Support ( HIKCUPS ) r and omized controlled trial with three treatment arms ; a dietary modification program , a physical activity skill development program or a combination of both programs . Main outcome measures . The Child Feeding Question naire ( CFQ ) , a vali date d 31-item question naire measuring child-feeding practice s , completed by parents . Statistical analysis . Linear mixed models were used to assess change over time and to determine differences by intervention group . RESULTS A significant decrease ( p<0.01 ) in CFQ domain scores were reported and sustained at 24 months for all groups , in the domain of pressure to eat ( mean+/-SEM , 1.8+/-0.06 , 1.6+/-0.06 ) with increases in degree of monitoring ( 4.0+/-0.07 , 4.2+/-0.06 ) . The domain of restriction showed significant decreases in dietary intervention groups only ( baseline 3.9+/-0.05 , 24 months 3.7+/-0.06 ) , the domain scores for concern were found to be strongly associated with child BMI z-score ( r=0.73 , p < 0.001 ) at baseline only . CONCLUSIONS This study provides evidence that specific child-feeding domains are modifiable in the context of a targeted obesity intervention and further that changes can be sustained over time . HIKCUPS study : National Centre for Clinical Trials ( NCT ) : 00107692 clinical trials.gov Identifier : NCT00107692 http:// clinical trials.gov/ct2/home OBJECTIVE Tested two family-based behavioral treatments for obesity in preschool children , one meeting the Expert Committee guidelines for Stage 3 obesity intervention criteria ( LAUNCH-clinic ) and one exceeding Stage 3 ( LAUNCH with home visit [ LAUNCH-HV ] ) , compared with a Stage 1 intervention , pediatrician counseling ( PC ) . METHODS In all , 42 children aged 2 - 5 years with a body mass index ( BMI ) percentile of ≥95th were r and omized . A total of 33 met intent-to-treat criteria . Assessment s were conducted at baseline , Month 6 ( posttreatment ) , and Month 12 ( 6-month follow-up ) . RESULTS LAUNCH-HV demonstrated a significantly greater decrease on the primary outcome of change in BMI z-score ( BMI z ) pre- to posttreatment compared with PC ( p = .007 ) , whereas LAUNCH-clinic was not significantly different from PC ( p = .08 ) . Similar results were found for secondary outcomes . CONCLUSIONS LAUNCH-HV , but not LAUNCH-clinic , significantly reduced BMI z compared with PC by posttreatment , indicating the need for intensive behavioral intervention , including home visitation , to address weight management in obese preschool children Background Community-based interventions are needed to reduce the burden of childhood obesity . Purpose To evaluate the impact of a multi-level promotora-based ( Community Health Advisor ) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children . Methods Thirteen elementary schools were r and omized to one of four intervention conditions : individual/family level ( Family-only ) , school/community level ( Community-only ) , combined ( Family + Community ) , or a measurement-only condition . Participants were 808 Latino parents and their children enrolled in kindergarten through 2nd grade . Measures included parent and child body mass index ( BMI ) and a self-administered parent survey that assessed several parent and child behaviors . Results There were no significant intervention effects on children ’s BMI z-score . The family intervention changed several obesity-related child behaviors ( e.g. , fruit/vegetable consumption ) and these were mediated by changes in parenting variables ( e.g. , parent monitoring ) . Conclusion A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors |
12,640 | 23,633,350 | Aspirin 1000 mg is an effective treatment for acute migraine headaches , similar to sumatriptan 50 mg or 100 mg .
Addition of metoclopramide 10 mg improves relief of nausea and vomiting .
Adverse events were mainly mild and transient , and were slightly more common with aspirin than placebo , but less common than with sumatriptan 100 mg | BACKGROUND This is an up date d version of the original Cochrane review published in Issue 4 , 2010 ( Kirthi 2010 ) .
Migraine is a common , disabling condition and a burden for the individual , health services and society .
Many sufferers choose not to , or are unable to , seek professional help and rely on over-the-counter analgesics .
Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine headaches .
OBJECTIVES To determine the efficacy and tolerability of aspirin , alone or in combination with an antiemetic , compared to placebo and other active interventions in the treatment of acute migraine headaches in adults . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Summary The pharmacokinetics of aspirin ( ASA ) in acute migraine attacks , and the influence of metoclopramide on ASA disposition , were studied in 32 attacks in 30 patients . An intergroup comparison was made between normal volunteers , and the migraineurs , who were assigned at r and om to one of three treatment groups : a ) oral ASA only ( 900 mg ) ; b ) 10 mg oral metoclopramide + oral ASA 900 mg ; c ) 10 mg i. m. metoclopramide + oral ASA 900 mg . Plasma ASA and SA levels were measured serially over 2 h , and the result ant data evaluated pharmacokinetically . Metoclopramide plasma levels were also determined over 2 h , and the results compared with a second group of normal volunteers . The rates of oral ASA absorption and elimination were unaffected by migraine . Mean absorption rate constants of 14.15±9.48 h−1 ( normals ) , 7.91±3.42 h−1 ( ASA only ) , 6.74±3.26 h−1 ( ASA + oral metoclopramide ) and 8.12±2.82 h−1 ( ASA + i. m. metoclopramide ) were calculated . Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1 , and did not differ significantly between controls and migrainous patients . Values for absorption lag time , however , were higher in migraine patients treated with ASA alone than in any other group . The amount of ASA absorbed unhydrolysed was also lower in this group . SA levels appeared unaffected either by the migraine attack , or by metoclopramide administration , over the period of study . Metoclopramide plasma levels were significantly lower during migraine attacks , and the amount of drug absorbed up to 2 h from dosing was also reduced , as compared with non-migrainous subjects . It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites , probably as a result of gastric stasis , and may have decreased the amount of ASA absorbed . The prior administration of metoclopramide , either orally or intramuscularly , reduced the absorption lag time , and thus promoted the early absorption of ASA , probably by restoring alimentary tract motility Objective : To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia . Methods : A countrywide population -based r and om sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously vali date d diagnostic question naire . Results : Of the 2725 eligible adults contacted , 2025 ( 74.3 % ) responded ( females 52.6 % , mean age 39.5 ± 13.4 years ) . Of these , 1273 ( 62.9 % ) reported headache ‘ not related to flu , hangover , cold , head injury ’ occurring at least once in the previous year . The gender- and age-st and ardized 1-year prevalence of migraine was 20.8 % . Female gender ( odds ratio ( OR ) = 3.8 ; 95 % confidence interval ( CI ) 2.8–5.1 ) and obesity ( OR = 1.5 ; 1.1–2.1 ) were positively associated with this type of headache . The gender- and age-st and ardized 1-year prevalence of tension-type headache ( TTH ) was 30.8 % . TTH was more prevalent in urban than in rural areas ( OR = 1.6 ; 1.3–2.0 ) . Headache on ≥15 days/month was reported by 213 ( 10.5 % ) respondents ( gender- and age-st and ardized prevalence 10.4 % ) , and associated with low socioeconomic status ( OR = 3.4 ; 2.4–4.9 ) , obesity ( OR = 3.0 ; 2.1–4.3 ) , female gender ( OR = 2.9 ; 2.1–4.1 ) and age over 40 years ( OR = 2.6 ; 1.9–3.6 ) . The majority of these respondents ( 68.1 % ) overused acute headache medications . Conclusion : The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month , and revealed unmet health-care needs of people with headache in Russia 1 The absorption of effervescent aspirin was studied in two groups of patients during attacks of migraine . The first group received effervescent aspirin alone whilst the second group received intramuscular metoclopramide before effervescent aspirin . 2 After effervescent aspirin alone there was significant impairment in the rate of aspirin absorption during migraine attacks compared with the rate of aspirin absorption in normal volunteers and in the same patients when headache-free . 3 When metoclopramide was given before effervescent aspirin the rate of aspirin absorption during migraine attacks was not significantly different from that obtained in normal volunteers given effervescent aspirin alone or from that obtained in the patients themselves when given both metoclopramide and effervescent aspirin when headache-free . 4 It is concluded that the impairment of absorption of effervescent aspirin during migraine attacks is related to impaired gastro-intestinal motility with delayed gastric emptying and that this impaired motility can be overcome by parenteral metoclopramide & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
12,641 | 22,942,329 | In general , there were no differences in safety and withdrawals due to inadequate analgesia between combination and monotherapy .
Based on 23 trials , all at high risk of bias , there is insufficient evidence to establish the value of combination therapy over monotherapy for pain management in IA . | OBJECTIVE To assess the efficacy and safety of combination pain therapy for people with inflammatory arthritis ( IA ) . | The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III Preliminary studies in man of benorylate , 4-(acetamido)phenyl-2-acetoxy-benzoate , have shown that it has antipyretic actions ( Weill , Gaillon , Rendu , and Lejeune , 1968 ; Alex and er , Flahaut , Raveschot , Drykonigen , 1970 ) and an analgesic action significantly superior to placebo and in some instances superior to aspirin ( Vialatel and Gaillon , 1968 ; Hart and Nicholson , 1971 ) . In rheumatoid arthritis , Bain and Burt ( 1970 ) and Cardoe ( 1970 ) have shown that the drug is well tolerated and effective , although the results suggested that their initial dose of 4 g . was inadequate . The pharmacology of benorylate has been reported by Rosner , Malhie , and Mottot ( 1968 ) and the pharmacodynamics of the drug have been described by Robertson ( 1971 ) . Benorylate is well absorbed when taken orally and unlike aspirin its absorption is not influenced by pH. After absorption the molecule undergoes hydrolysis to provide salicylic acid ( SA ) and n-acetyl paraminophenol ( NAPA ) . When compared with aspirin and paracetamol , the peak plasma concentrations ofSA and NAPA are achieved later and more smoothly after benorylate administration . The plateau levels of SA and NAPA obtained after continuous medication are very similar with the three drugs . Excretion of metabolites occurs through the kidney ( 85 per cent . and faeces ( 15 per cent ) . These findings , and the preliminary clinical results , suggested that benorylate merited further assessment in the treatment of rheumatoid arthritis The effectiveness of dothiepin ( a tricyclic anti-depressant ) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis . Patients were classified as either ‘ depressed ’ or ‘ not depressed ’ . The week before , during and 2 weeks after the study , 600 mg ibuprofen was given orally three times daily to all patients . Compared with placebo , dothiepin produced a significant reduction in daytime pain by the end of the treatment period . The Hamilton rating scale in ‘ depressed ’ patients was significantly improved in patients given dothiepin . The Cassano – Castrogiovanni self-evaluation rating scale in both ‘ depressed ’ and ‘ not depressed ’ patients showed a tendency ( not significant ) to be improved following dothiepin treatment compared with placebo . These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood . Therapy with tricyclic anti-depressants , such as dothiepin , therefore , may determine an improvement of pain indexes besides having an anti-depressant effect The authors describe a simple non-crossover-blind test for the evaluation of subjective indices . A table for recording pains during the 14 days ' study is described . The patient 's satisfaction with the treatment and the number of days until withdrawal from the trial are recorded . The statistical procedure takes into consideration differences between the treatment groups and makes possible a valuable comparison with drugs tested in other clinical trials . The three dose schedules of antirheumatic treatment were tested on 122 patients and the results compared with those of 342 patients treated with the 6 other antirheumatic drugs ( enteric-coated aspirin , paracetamol , indomethacin , flurbiprofen , mefenamic acid , and prednisolone ) and those of 41 patients who received placebos . The results show that Safapryn ( 3,6 g aspirin + 3.0 g paracetamol daily ) compared with 3.9 g enteric coated aspirin does not offer any advantage in its analgesic effect , although it gives rise to fewer side effects . Phenylbutazone ( 3000 mg ) was almost as effective as 15 mg prednisolone daily . Between the effects of this dosage of phenylbutazone and other non-steroidal antirheumatic drugs , however , no significant difference could be detected . 50 mg phenylbutazone daily and placebo treatment could not be distinguished . The authors thank the Arthritis and Rheumatism Council for Research in Great Britain for its financial support . One of the authors ( PL ) was a Merck , Sharp , and Dohme Research Fellow and another one ( PMB ) received a Robins research scholarship Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis ( RA ) have yielded conflicting results . We used st and ard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations . We used doses of choline magnesium trisalicylate , adjusted to achieve therapeutic serum salicylate concentrations , and naproxen in a r and omized , double-blind , placebo-controlled cross-over study of full dose trisalicylate ( CMT ) , full dose naproxen ( N ) , full dose of both ( CMT-N ) , and half dose of both ( cmt-n ) to examine their relative efficacy and toxicity in treating RA . CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables , but was equal to N and better than CMT or cmt-n for 7 variables . There were minimal differences among treatments for the other 4 efficacy variables . The mean percentage difference for the efficacy variables between CMT-N and N was 3 % , between CMT-N and CMT was 10.6 % , and between CMT-N and cmt-n was 10.5 % . Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase . During the double-blind phases of the study , CMT-N was more toxic than N , CMT , or cmt-n ( 7.5 % versus 3.4 % , 1.8 % , and 3.7 % , respectively ) . Tinnitus was more common when full-dose CMT was used ; N ( N or CMT-N ) was associated with increased skin toxicity . Gastrointestinal complaints were equally common with all regimens . CMT-N , although sometimes statistically superior to CMT , N , or cmt-n , showed no clinical ly important additive or synergistic effect versus N or CMT alone Twelve rheumatic patients were given 2.0 and 4.5 g acetylsalicylic acid daily in two 3-week periods . On days 13 and 20 of each period the patients took a suppository containing either placebo or 50 mg of indomethacin . The study was performed double-blind . Indomethacin had a significant additive effect during ASA therapy with 2 g daily as estimated by articular index and subjective ratings of pain and morning stiffness . On the 4.5 g ASA dose there was a significant improvement only for articular index . The patients experienced less pain during maintenance therapy with 4.5 g of ASA compared with 2.0 g daily . Both ASA doses induced complete inhibition of prostagl and in PGF2 alpha release from platelets . Thus the suppression of PGF2 alpha release does not reflect the therapeutic response of these drugs . Side effects observed comprised tinnitus , dizziness and gastritis . In 2 of the patients the aminotransferase levels increased , indicating hepatotoxicity . The protein binding of salicylate decreased with increasing salicylate concentration . As the dose was increased from 2.0 to 4.5 g/day the unbound concentration increased 5 to 24 times . This reflects the combined effect of capacity-limited metabolism and capacity-limited protein binding of salicylate Actions on performance of dextropropoxyphene ( DXP ) alone and in combination with amitriptyline ( AMI ) , indomethacin ( IN ) , and placebo were compared in 15 patients with rheumatoid arthritis . The patients were on their prescribed maintenance regimen excluding analgesics . In four r and omized test sessions at two-week intervals , they received double blind and crossover single oral doses of DXP 130 mg , IN 50 mg , DXP 65 mg + AMI 25 mg or placebo , each after two days ' pretreatment with the same drug . Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration . DXP impaired critical flicker discrimination , symbol copying and body balance without modifying tracking , choice reactions or attention . It rendered the subjects elated , muzzy , mentally slow and calm . Actions of AMI + DXP were about the same . IN impaired body balance and critical flicker recognition . Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low . We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills . Small doses of AMI may not enhance the mild psychomotor effects of DXP . Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance In a double-blind between-patient study of aspirin and benorylate carried out in 72 out patients with rheumatoid arthritis , benorylate 4 g twice daily was shown to be an effective analgesic and anti-inflammatory drug , its effects being indistinguishable from those of aspirin 1·2 g four times daily . Compared with the pretreatment values both drugs produced a statistically significant improvement ( P < 0·01 ) in functional grade , overall pain , articular index , and grip strength at the end of the first and second weeks . The overall incidence of side effects was less with benorylate , though this difference was not significant at the 5 % level & NA ; R and omized , double‐blind , placebo‐controlled trials on neuropathic pain treatment are accumulating , so an up date d review of the available evidence is needed . Studies were identified using MEDLINE and EMBASE search es . Numbers needed to treat ( NNT ) and numbers needed to harm ( NNH ) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions . One hundred and seventy‐four studies were included , representing a 66 % increase in published r and omized , placebo‐controlled trials in the last 5 years . Painful poly‐neuropathy ( most often due to diabetes ) was examined in 69 studies , postherpetic neuralgia in 23 , while peripheral nerve injury , central pain , HIV neuropathy , and trigeminal neuralgia were less often studied . Tricyclic antidepressants , serotonin noradrenaline reuptake inhibitors , the anticonvulsants gabapentin and pregabalin , and opioids are the drug classes for which there is the best evidence for a clinical relevant effect . Despite a 66 % increase in published trials only a limited improvement of neuropathic pain treatment has been obtained . A large proportion of neuropathic pain patients are left with insufficient pain relief . This fact calls for other treatment options to target chronic neuropathic pain . Large‐scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism‐based classification may help improve treatment of the individual patients The therapeutic and adverse effects of 2 weeks of treatment with high-dose indomethacin ( 150 mg/day ) were compared with those of low-dose indomethacin ( 50 mg/day ) combined with paracetamol ( 4 g/day ) in a double-blind , double-dummy , cross-over study in 17 patients with active rheumatoid arthritis . Grip strength , Ritchie 's index , joint circumference , joint pain , and patient 's and physician 's global assessment s were estimated , and conventional laboratory parameters were followed . In addition , the time-concentration profiles of indomethacin and paracetamol were assessed during steady state . All patients had measurable plasma drug levels , indicating adequate compliance , and responders and nonresponders ( five on each treatment ) had equal drug levels , indicating that the variation in therapeutic efficacy was not secondary to pharmacokinetic differences . While there were fewer and milder side-effects during treatment with the drug combination , there was no difference in therapeutic efficacy . Hence , it appears that the main therapeutic profit of indomethacin in daily doses greater than 50 mg is enhanced analgesia . As such dosage involves pronounced side-effects , it seems more appropriate to employ the combination of 50 mg indomethacin and 4 g paracetamol , whereby similar analgesia can be obtained without an increase in side-effects The importance of pain in the health status and health behavior of patients with chronic rheumatic disease was evaluated . The Arthritis Impact Measurement Scales were used to estimate physical disability , psychological status , and pain in a large set of rheumatic disease patients . Explanatory regression models were built to explore the contribution of pain in physician and patient assessment s of overall health , medication usage , and changes in health status over time . Results confirm that pain makes a highly significant contribution to explaining both physician and patient overall health assessment s ( P less than 0.001 ) . Pain is also the most important of the 3 health status components in explaining medication usage ( P less than 0.001 ) . Finally , using prospect i ve data , it is shown that current pain , rather than current physical or psychological disability , is the best predictor of subsequent pain ( P less than 0.001 ) . Current pain also is most associated with subsequent physical disability ( P less than 0.05 ) . These findings confirm the importance of pain in determining the health status and health behavior of individuals with chronic rheumatic disease , and suggest that doctors and other health professionals should continue to solicit and address the patient 's complaints of pain A double-blind controlled trial was carried out in 18 in- patients with classical or definite rheumatoid arthritis to assess the effectiveness of night-time medication with 100 mg indomethacin plus 10 mg diazepam , 200 mg sulindac , and 200 mg sulindac plus 10 mg diazepam in improving sleep and reducing night pain and the duration of morning stiffness . Patients received each treatment regimen for 1 night . The results from the 17 patients completing the full trial protocol indicated that indomethacin plus diazepam was the most effective of the three regimens , although the differences did not reach conventional statistical significance . It is suggested that in further such studies with sulindac a larger dose and a longer duration of treatment should be used Seventeen of eighteen patients hospitalized for active rheumatoid arthritis completed a three-day r and omized , double-blind comparison of 100 mg indomethacin , 100 mg indomethacin with 10 mg diazepam and matching placebo as night medication . The results showed a consistent pattern in the four functions measured -- pain , morning stiffness , sleep score and patient preference . In each , indomethacin proved superior to placebo and the combined therapy better than indomethacin alone . From this it has been concluded that the combination of indomethacin and diazepam should now be considered the treatment of choice for maximum control of night pain and morning stiffness in rheumatoid arthritis A double-blind , crossover trial was carried out to assess the clinical efficacy of 3.6 g aspirin , 1200 mg azapropazone and the two drugs together in 24 adult patients with classical or definite rheumatoid disease . Pain score , morning stiffness and patients ' assessment of pain were significantly improved for each drug regimen when compared to placebo . There was no significant difference among the individual drug regimens . Azapropazone was the best drug regimen in terms of improving pain score , morning stiffness and patient assessment of pain , but this was not statistically significant . It is concluded that there is no justification for prescribing aspirin with azapropazone in patients with rheumatoid disease 1 This was a double-blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis . Two dosage regimes were tested . 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate ( 1600 mg ibuprofen and 3.6 g aspirin daily ) but not low ( 800 mg ibuprofen and 2.4 g aspirin daily ) dosages of both drugs . 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial . 4 No consistent effect of ibuprofen administration on serum salicylate levels was found . 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half-lives of the drug The clinical effect and plasma naproxen levels were studied in 20 patients with RA receiving three doses of naproxen and two naproxen doses combined with paracetamol ( acetaminophen ) in a r and omized , double-blind , comparison in five 2-wk treatment periods . A significant dose-concentration effect relationship was found for the three naproxen doses ( 500 , 1000 and 1500 mg daily ) . The following variables were measured : global clinical effect , joint index , morning stiffness , activity of daily living ( ADL ) , pain during movement and at rest . The naproxen dose-concentration effect relationship curve was moved to the left by the addition of 4 g paracetamol daily . No major side effects were observed , but complaints concerning the gastrointestinal tract were fewer on lower naproxen doses and these were not increased by concomitant paracetamol treatment . The results show that the clinical effect of naproxen in RA may be significantly increased by concomitant paracetamol administration A series of experiments has been carried out with single doses of simple analgesics in patients with rheumatoid arthritis using a consistent polyad design . This method proved to be both valid and useful . Pain relief scores were a better measure of the effectiveness of analgesics than preference . Aspirin , Codis , and Distalgesic were the most effective analgesics tested , with paracetamol , pentazocine , and Ciba 44,328 intermediate between these agents and placebo . Placebo given after an active analgesic was more effective than when given before ; this phenomenon was not abolished by telling the patients that apparently identical tablets were , in fact , different or by making them different in colour . The effectiveness of soluble placebo depended on its colour , red being the most effective Part I of this report appeared in the previous issue ( Br . J. Cancer ( 1976 ) 34,585 ) , and discussed the design of r and omized clinical trials . Part II now describes efficient methods of analysis of r and omized clinical trials in which we wish to compare the duration of survival ( or the time until some other untoward event first occurs ) among different groups of patients . It is intended to enable physicians without statistical training either to analyse such data themselves using life tables , the logrank test and retrospective stratification , or , when such analyses are presented , to appreciate them more critically , but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses |
12,642 | 31,744,140 | Due to the variety of formats and no consistent model , no perfect model or activity has been identified .
However , CPD showed increased practice outcomes versus CE .
Although an increasing amount of technology is being utilized , face-to-face learning is still preferred . | Continuing Education ( CE ) or Continuing Professional Development ( CPD ) are used by pharmacists globally to maintain up-to- date knowledge and skills throughout their careers .
The primary aim of this study was to identify the formats or models used by pharmacists for CE and CPD globally .
The secondary aim was to identify preferences of pharmacists , in relation to the variety of formats or models used to fulfil m and atory requirements , in order to support future planning of lifelong learning events . | Introduction : The United Kingdom 's pharmacy regulator contemplated using continuing professional development ( CPD ) in pharmacy revalidation in 2009 , simultaneously asking pharmacy professionals to demonstrate the value of their CPD by showing its relevance and impact . The idea of linking new CPD requirements with revalidation was yet to be explored . Our aim was to develop and vali date a framework to guide pharmacy professionals to select CPD activities that are relevant to their work and to produce a score sheet that would make it possible to quantify the impact and relevance of CPD . Methods : We adapted an existing risk matrix , producing a CPD framework consisting of relevance and impact matrices . Concepts underpinning the framework were refined through feedback from 5 pharmacist teacher‐practitioners . We then asked 7 pharmacists to rate the relevance of the framework 's individual elements on a 4‐point scale to determine content validity . We explored views about the framework through focus groups with 6 participants and interviews with 17 participants who had used it formally in a study . Results : The framework 's content validity index was 0.91 . Feedback about the framework related to 3 themes of penetrability of the framework , usefulness to completion of CPD , and advancement of CPD records for the purpose of revalidation . Discussion : The framework can help professionals better select CPD activities prospect ively , and makes assessment of CPD more objective by allowing quantification , which could be helpful for revalidation . We believe the framework could potentially help other health professionals with better management of their CPD irrespective of their field of practice BACKGROUND Continuing professional development ( CPD ) continues to gain acceptance as a model for health care professionals to engage in lifelong learning . Little is known about how CPD participants use the experience to develop learning plans and implement new knowledge into practice . OBJECTIVE The primary objective of this study was to evaluate the effectiveness of instruments design ed to guide the pharmacist through a CPD process to plan and participate in continuing professional education activities at a national meeting . METHODS The study was a case-control study of pharmacists r and omized from the participants of the 2010 American Pharmacists Association Annual Meeting . The test group ( n=47 ) was instructed to complete CPD planning worksheets design ed to facilitate planning of their continuing pharmacy education activities before the meeting . The control group ( n=58 ) did not have instructions beyond the meeting program . Both groups completed 3 surveys assessing components of the CPD processes : 1 before and 2 after the meeting . The surveys focused on confidence in abilities to identify , plan , and evaluate learning as well as implementation of practice change . RESULTS Nearly all the test groups reported successful application of learning ( 95 % ) and achieving their design ed learning plan ( 87 % ) . Practice changes were implemented in more than half ( 60 % ) of the test groups after using a CPD process to plan their learning activities . There were no significant differences among groups regarding the outcome measures . CONCLUSIONS Participants successfully used a CPD approach to meet their learning plans and achieve meaningful learning outcomes . Integration of CPD components into educational activities may help to promote practice change Objective . To determine whether a structured educational intervention would support pharmacists ' utilization of a continuing professional development ( CPD ) model compared to pharmacist control subjects . Methods . A prospect i ve , r and omized , observational case-control study of CPD was conducted in which pharmacists participated in several educational interventions , and study and control groups completed pre study and post study survey instruments . Results . Survey data from 57 pharmacists ( n = 28 study , n = 29 control ) were analyzed and significant outcomes from the CPD stages of reflect , plan , act , evaluate , and record were found between matched study subjects and study and control group comparisons . Conclusions . With appropriate training and support , pharmacists can utilize a CPD approach to their lifelong learning and professional development Background : The Institute of Medicine states that the new vision for continuing education ( CE ) for health-care professionals will be based on continuing professional development ( CPD ) ; however , information on the utility of CPD is lacking . Objective : To assess the effect of CPD , compared with that of traditional continuing pharmacy education ( CPE ) , on perceptions of factors related to pharmacy practice . Methods : This 10-month , nonblinded , r and omized controlled study recruited licensed pharmacists employed at a health maintenance organization ( HMO ) . After completing a basic CPD course , participants were r and omized to the intervention or control group . The control group was instructed to continue with traditional CPE . The intervention group participants completed 3 CPD workshops and were instructed to utilize the CPD approach for their learning needs . At baseline and follow-up , all participants completed a study question naire on perceptions of their pharmacy practice s. The outcome measures were comparisons on follow-up and changes from baseline to follow-up in responses to the study question naire . Results : One hundred pharmacists were enrolled . The intervention ( n = 44 , 7 lost to follow-up ) and control ( n = 47 , 2 lost to follow-up ) groups were similar at baseline . At follow-up , a higher percentage of intervention participants reported that they had better interactions with other health-care providers ( always/frequently 32 % vs 6 % , respectively ) and initiated practice /work changes ( always/frequently 21 % vs 0 % , respectively ) ( both p < 0.01 ) as a result of their education activities . Compared with control participants at follow-up , intervention participants reported that their education activities improved patient care changes ( 46 % vs 23 % ) , professional knowledge ( 34 % vs 6 % ) , skills ( 48 % vs 17 % ) , and attitudes/values ( 43 % to 11 % ) ( all p < 0.05 ) . However , intervention participants reported more often that time was a barrier to completing education activities ( 75 % vs 32 % , p < 0.001 ) . Conclusions : Pharmacists who participated in CPD reported more often that their perceptions of various aspects of their pharmacy practice improved as a result of their education activities compared with pharmacists who participated in traditional CPE OBJECTIVES To explore factors associated with Scottish pharmacists ' views and attitudes to continuing professional development ( CPD ) . METHODS A retrospective principal component analysis of 552 ( 22.8 % ) question naires returned from a sample of 2420 Scottish pharmacists r and omly selected from the 4300 pharmacists registered with the Royal Pharmaceutical Society of Great Britain and with a Scottish address . KEY FINDINGS Principal component analysis of question naire items ( n = 19 ) revealed four factors associated with Scottish pharmacists ' views and attitudes to CPD : having positive support in the workplace , having access to re sources and meeting learning needs , having confidence in the CPD process and motivation to participate in the CPD process . Community pharmacists were identified as the subgroup of pharmacists that needed most support for CPD regarding all four factors , while pharmacists working in primary care felt that they had most support in the workplace in comparison to other sectors ( P < 0.05 ) and better access to re sources and meeting learning needs when compared to community ( P < 0.001 ) and hospital ( P = 0.008 ) colleagues . Pharmacists working in primary care also felt more motivated to participate in the CPD process than those in the community ( P < 0.001 ) , and hospital pharmacists reported having more confidence in the CPD process compared to community pharmacists ( P < 0.05 ) . CONCLUSION Using principal component analysis has identified four factors associated with Scottish pharmacists ' views and attitudes to CPD . This may provide an approach to facilitate comparison of CPD views and attitudes with intra and inter professional groupings . Further study may allow identification of good practice and solutions to common CPD issues Background Contemporary pharmaceutical care requires sustained pharmacist competency through maintenance and improvement of knowledge , skills , and performance . Existing continuing education ( CE ) models reflect a wide spectrum of international approaches to life-long learning . Objective The objective of this study was to determine CE preferences of pharmacists in Egypt before implementing a plan for compulsory annual CE activities and events for licensure renewal . Setting A question naire containing questions about continuing education needs and preferences of Egyptian pharmacists was distributed to 400 pharmacies in Cairo . The sample was drawn r and omly from the address list in yellow pages . The survey was conducted by personal interview . Method The question naire was design ed and vali date d. Questions were divided into specific domains of interest including pharmacist demographics ; access to internet re sources ; frequency and characteristics of past CE activities ; preferences for delivery and content ; motivation to participation ; and plans for future CE activities . All data analyses were conducted using SPSS for Windows version 18.0 . All statistical tests were 2-tailed and based on a significance level of p value ≤ 0.05 . Results During the six months of question naire distribution , 400 pharmacists ( one from each r and omly selected pharmacies ) were asked to complete the question naire . The response rate was 359 out of 400 pharmacists ( 89.75 % ) . Twenty three percent of respondents had held their highest pharmacy degree to practice for less than 5 years and 19 % had obtained their initial degree more than 15 years ago . More than half of the respondents were female ( 53.3 % ) . Topics related to therapeutics were of highest interest to 85.3 % , closely followed by clinical skills topics . Pharmacists working in community pharmacies had attended less CE events ( 15 vs. 28 % , p = 0.034 within the past 2 years ) when compared to their hospital-based counterparts . Conversely , hospital pharmacists generally reported less satisfaction with current CE ( 21 vs. 33 % , p = 0.021 ) . Conclusion Respondents of the survey expressed enthusiasm towards CE activity , but cited common barriers to participation , as well , such as employer- and technology-based obstacles . These results confirm that features of a successful CE program must be flexible to meet preferences and perceived needs of Egyptian pharmacists |
12,643 | 28,266,113 | Mechanical plaque control procedures are effective in reducing plaque and gingivitis .
The addition of fluoride to mechanical plaque control is significant for caries management .
Chlorhexidine rinse has a positive effect on gingivitis and inconclusive role in caries | AIM To report the evidence on the effect of mechanical and /or chemical plaque control in the simultaneous management of gingivitis and caries . | OBJECTIVE This study evaluates the effectiveness of a multi-component oral health intervention in preschool children in a non-r and omized intervention study with a complementary baseline control . METHODS Participants in the main study were 2137 children born between October 2003 and July 2004 in Fl and ers , Belgium . In the intervention group ( 50.5 % of participants ) , an oral health education program was added to a st and ard preventive care program during the first 3 years of life . Oral health examinations were performed by trained dentists when the children were 3 ( 2007 ) and 5 ( 2009 ) years old . Data on dietary habits , oral hygiene habits and dental attendance were obtained through structured question naires . Regression analyses were applied to compare the results of the intervention and control group with baseline measurements obtained before the intervention ( 2003 ) in other cohorts of 3- ( N = 1291 ) and 5-year-olds ( N = 1325 ) living in the same regions . RESULTS The prevalence of caries experience was generally lower in the main study compared with the baseline cohorts , with little differences between the intervention and control group . For the oral health-related behaviours , the control group scored mostly better . Nevertheless , compared with baseline , limited differences were observed in dental attendance , tooth brushing , helping with tooth brushing and consuming in-between drinks ( P < 0.05 ) . CONCLUSION The study illustrates that a multi-component , theory-based intervention at community level had only a limited and temporary effect on oral health-related behaviours in the community under study . Further research is needed to determine how oral health in young children can be improved in the long term OBJECTIVE To assess the impact of oral health promotion integrated with a health promoting school ( HPS ) initiative on the oral health outcomes of secondary school students . MATERIAL S AND METHOD Using an urban-rural stratified cluster r and omized approach , the intervention was applied to secondary school students in Arusha , Tanzania . In the urban , three control ( n = 315 ) and two intervention ( n = 214 ) schools performed oral clinical examination and question naires at baseline . In rural the corresponding figures at baseline were two ( n = 188 ) and three ( n = 360 ) schools . After 2 years , 374 and 358 students remained in the intervention and control arms . RESULTS Mean number of decayed teeth ( DT ) increased in the intervention ( mean score 1.0 vs 1.7 , p < 0.001 ) and control schools ( mean score 1.2 vs 1.7 , p < 0.001 ) . Mean number of teeth with plaque decreased significantly in intervention and control schools . No significant difference in caries increment and plaque decline scores was observed between groups . Mean number of teeth with bleeding decreased ( 0.5 vs 0.3 , p < 0.05 ) in intervention schools , whereas no change was observed in the control schools ( 0.4 vs 0.5 , p = 0.051 ) . Increment in mean number of DT between baseline and follow-up was largest and smallest in students who , respectively , deteriorated and improved their plaque and bleeding scores . CONCLUSION The intervention activities did not show any effect with respect to dental caries , calculus and plaque status among the students investigated . Compared with the control group , more favorable changes in the intervention group occurred with respect to bleeding on probing , suggesting a weak but positive effect on students ' oral hygiene status Background School based oral health education through traditional lecturing has been found successful only in improving oral health knowledge , while has low effectiveness in oral hygiene and gingival health . The aim of this study was to evaluate the effectiveness of experiential learning ( EL ) oral health education to traditional lecturing ( TL ) , on enhancing oral health knowledge , attitude and behavior as well as oral hygiene , gingival health and caries of 10-year-old children . Methods Eighty-four children were recruited for the EL and 100 for the TL group from 3 locations in Greece . Data regarding oral health knowledge , attitude and behavior were collected via question naires . Data regarding dental plaque , gingivitis and caries were collected by clinical examination . The evaluation using question naires and clinical examination was assessed at baseline and 6 and 18 months afterwards . Two calibrated pediatric dentists examined the students using a periodontal probe and artificial light . Modified hygiene index ( HI ) was used for dental plaque recording , the simplified gingival index ( GI-S ) was used for gingivitis and DMFT , based on BASCD criteria , for dental caries . Based on a dedicated manual , the teacher applied in the classroom the oral health educational program using EL . Results EL group had statistically significant better hygiene than the TL at 6 months ( p < 0.05 ) . Within the same group , both groups had enhanced oral health knowledge at 6 and 18 months ( p < 0.05 ) and improved oral health behavior ( p > 0.05 ) and attitude ( p > 0.05 ) at 6 months in comparison to baseline . Conclusion EL program was found more successful than TL in oral hygiene improvement . Both oral health education programs improved the oral health knowledge , attitude and behavior of children . Trial registration Clinical Trials.gov ( NCT02320162 ) Even though there is no “ gold st and ard ” for determining caries lesion activity , it is nonetheless possible to evaluate the validity of such diagnostic measures . The aim of this study was to estimate the construct and predictive validity of caries lesion activity assessment s by means of their ability to reflect known effects of fluoride on caries . A three-year trial of the effect of daily supervised brushing with fluoride toothpaste was carried out among 273 12-year-old children . All children were examined clinical ly according to diagnostic criteria for activity assessment . The relative risk ( fluoride vs. control ) for caries lesion transitions among diagnostic categories was calculated . Fluoride inhibited progression of caries at all stages of lesion formation while at the same time enhancing lesion regression . The effects were most pronounced for active non-cavitated lesions . It is concluded that the clinical diagnostic criteria have construct and predictive validity for the assessment of caries lesion activity The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11 - 13-year-old Berkshire schoolchildren were divided into three groups ; Group 1 were allocated a low abrasivity paste containing 0.8 % sodium monofluorophosphate , Group 2 a paste of conventional abrasivity also containing 0.8 % sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste . After 3 years the net DMFS increments ( clinical and radiographic scores combined ) were 4.22 in Group 1 , 4.72 in Group 2 and 6.43 in Group 3 . The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant ( P less than 0.001 ) . The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance . Reducing the abrasivity of the toothpaste had no meaningful effect on the st and ard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices BACKGROUND Prophylaxis efforts for the maintenance of tooth health led to a distinctive decrease in caries frequency with children and young persons . Because the toothbrush can still be described as the most important oral hygiene aid , possible differences between the effectivity of electric and manual toothbrushes should be tested in the present study . Elementary school children had been instructed -- within a special prophylaxis program -- over a period of three years to clean their teeth partly with electric partly with manual toothbrushes . MATERIAL AND METHODS In two parallel classes ( 1st class ) of the same elementary school ( Private Martinusschule Mainz-Gonsenheim ) the A-class ( n = 24 children ) was instructed to clean their teeth with a manual toothbrush suitable for children ( Oral-B , Power Tip , Braun AG , Kronberg , Germany ) whereas the B-class ( n = 26 ) received electric toothbrushes ( Oral-B-7 EB 5 K , Braun AG , Kronberg , Germany ) . Every three months the children were instructed in group-preventive methods in school , followed by cleaning instructions , remotivations and the distribution of new electric respectively manual toothbrushes . In order to record the influence of the intensive quarterly oral hygiene instruction , elementary school children ( 1st class ) of the same school type were looked after and examined within the yearly group prophylaxis ( n = 40 ) . The yearly dental examinations included the recording of carious frequency ( DMF-T , dmf-t ) , approximal plaque accumulation ( API ) , and the evaluation of the gingival state ( GI-Index ) as well as the present dental restorative material s. RESULTS After an investigation period of three years no essential differences regarding caries frequency , proportion of dentitions of natural state of health and plaque involvement were found with the children of the respective classes . Children using electric toothbrushes showed after 3 years 27 % of healthy-natured dentitions on average ( 46 % of the children had got API-values of up to 30 % ) and the children who used manual toothbrushes showed 22 % of nature-healthy dentitions ( 52 % of the children had got API-values of up to 30 % ) and in 33 % of the control children who received instructions only once a year healthy-natured dentitions were found after 3 years ( 75 % of the children had got API-values of up to 35 % ) . CONCLUSIONS With regard to caries and gingivitis prevalence modern electric toothbrushes for children can be considered equally efficient like conventional manual toothbrushes for children with children of normal caries risk The clinical effects of different preventive regimens provided for young people in their early and middle teens were studied during a 2-year period . The regimens studied during the 1st year of the trial were professional tooth-cleaning plus fluoride mouth-rinsing every 3rd week versus fluoride varnish treatment every 6 months . During the 2nd year , the preventive measures were given in accordance with the estimated needs of each individual . The results were related to the individuals ' previous experience with dental prevention to determine whether this had a significant influence . The results showed that fairly good or excellent effects on the individuals ' oral hygiene and gingival status were readily achieved and maintained with a professional tooth-cleaning plus fluoride mouth-rinsing regimen . The study failed to demonstrate any superior caries-preventive effect of the fluoride varnish treatments . Subsequent individualized prevention produced similar average end results in all groups . Differences in the results in accordance with the individuals ' previous experience with dental prevention indicate a superior and prolonged influence on dental health of professional tooth-cleaning plus fluoride mouth-rinsing in comparison with a fluoride-based program alone Abstract The effect of a dental prophylactic program based on systematic plaque control has been tested during a 3-year period on youths aged 16–19 years . During their last year at comprehensive school they received professional tooth cleaning every third week by specially trained dental hygiene nurses . At the end of this first experimental year the subjects were offered continued prophylaxis of the same type against caries and gingivitis during 2 more years . Interested subjects were divided equally at r and om into test groups A and B. In the second year group A received professional tooth cleaning once a month and in the third year once each 6 months . Group B was offered , both in the second and third years , only two prophylactic sessions each year according to this model . Test group C comprised the subjects who expressed no interest in continued professional tooth cleaning . A control group , group D , consisted of pupils of the same ages from a neighboring school area . These received in the first experimental year a prophylactic program based on mouthrinsing each second week with 0.2 % sodium fluoride solution . After this first year neither test group C nor the control group D participated in any organized dental health care program . After the first year there were significant differences among the groups , the plaque and gingival indices in the control group D being significantly higher than in test groups A , B and C. At the end of the third year significant improvements in these indices had taken place in groups A and B. The corresponding values in groups C and D did not differ significantly at the three recordings . Significant correlations existed between the plaque and gingivitis scores at the end of the experimental period within the respective groups . Significantly more dental caries ( new DPS ) developed in the control group D than in test groups A and B during the period of the experiment : on average 3.3 versus 1.0 and 1.2 new DFS , respectively . The figure for caries increment in group C was 2.0 . Regardless of grouping , individuals with caries increment during the experimental period had a significantly higher number of risk factors , here defined as the total of upper or lower quartile values for lactobacillus counts , secretion rate and buffering capacity of the saliva , than individuals without caries increment The preset study was performed to assess the effect on caries and gingivitis of plaque control measures such as oral hygiene instruction , toothcleaning practice and professional toothcleaning . 104 children , 13 - 14 years old , participated in the trial . Prior to the start of the preventive treatment all children were examined regarding oral hygiene , gingivitis and caries . The caries examintion was limited to the proximal surfaces of molars and premolars . Following this baseline examination the children were r and omly divided into two treatment groups A , and B. Both groups of children were recalled for professional toothcleaning once every 2 weeks during an 18-month period . In each child the professional toothcleaning was restricted to either the right or the left jaws by r and om selection . In addition , the children of Group A at each recall appointment received careful oral hygiene instruction and practice in proper toothcleaning methods . In conjunction with the professional toothcleaning an abrasive paste was used including fluoride . The children were re-examined 18 months after the baseline examination . The result of the present investigation demonstrated that professional toothcleaning repeated every second and week is a prophylactic measure which in children substantially improves the oral hygiene status , and effectively reduces clinical signs of gingivitis and caries . It was also observed that while oral hygiene instruction and practice in proper toothcleaning techniques reduced plaque and gingivitis , no such effect could be detected regarding the development of caries Root caries is prevalent in elderly disabled nursing home residents in Denmark . This study aim ed to compare the effectiveness of tooth brushing with 5,000 versus 1,450 ppm of fluori date d toothpaste ( F-toothpaste ) for controlling root caries in nursing home residents . The duration of the study was 8 months . Elderly disabled residents ( n = 176 ) in 6 nursing homes in the Copenhagen area consented to take part in the study . They were r and omly assigned to use one of the two toothpastes . Both groups had their teeth brushed twice a day by the nursing staff . A total of 125 residents completed the study . Baseline and follow-up clinical examinations were performed by one calibrated examiner . Texture , contour , location and colour of root caries lesions were used to evaluate lesion activity . No differences ( p values > 0.16 ) were noted in the baseline examination with regards to age , mouth dryness , wearing of partial or full dentures in one of the jaws , occurrence of plaque and active ( 2.61 vs. 2.67 ; SD , 1.7 vs.1.8 ) or arrested lesions ( 0.62 vs. 0.63 ; SD , 1.7 vs. 1.7 ) between the 5,000 and the 1,450 ppm fluoride groups , respectively . Mean numbers of active root caries lesions at the follow-up examination were 1.05 ( 2.76 ) versus 2.55 ( 1.91 ) and mean numbers of arrested caries lesions were 2.13 ( 1.68 ) versus 0.61 ( 1.76 ) in the 5,000 and the 1,450 ppm fluoride groups , respectively ( p < 0.001 ) . To conclude , 5,000 ppm F-toothpaste is significantly more effective for controlling root caries lesion progression and promoting remineralization compared to 1,450 ppm F-toothpaste Chlorhexidine digluconate in 0.1 % and 0.4 % concentrations was added to dentifrices to evaluate its effect on plaque formation , gingival conditions and caries in 73 dental students over a 2-year period . No differences were found in the Pl I and the G I indices between the active and the placebo dentifrices , but a possible effect on caries was demonstrated . Discolorations of anterior teeth and fillings were the only side effects observed The goal of this study was to evaluate a 15-month educational program design ed to children . The sample consisted of 60 six-year olds , r and omly assigned into control and experimental group . The control consisted of tooth brushing training , once a year . The experimental group received intensive individual tooth brushing training every three months and guidance on oral health . Initially , both groups were assessed using plaque , gingival , dmfs and DMF-S indexes every three months . In the control , no statistically significant difference was observed for plaque and gingival indexes . The experimental group showed a statistically significant reduction in mean values for two indexes . The caries indexes showed no statistically significant difference . The proposed educational program developed was efficient in reducing gingival and plaque indexes as well caries incidence OBJECTIVE To compare the effectiveness of fluoride varnish and 2 % chlorhexidine gel for controlling active white spot lesions ( WSLs ) adjacent to orthodontic brackets . STUDY DESIGN Thirty-five orthodontic patients ( 17.2 ± 2.3 years old ) presenting 60 WSLs adjacent to orthodontic brackets were enrolled in this r and omized , blind , 3-armed and controlled clinical trial . The patients were r and omly allocated to 1 of 3 arms : ( 1 ) two applications of 5 % NaF varnish- F , with one-week interval , ( 2 ) two applications of 2 % chlorhexidine gel-CHX , with one-week interval and ( 3 ) usual home care-control ( CO ) . The WSLs were scored by using a DIAGNOdent pen . An independent examiner scored the surfaces using Nyvad criteria for caries assessment . RESULTS A total of thirty patients presenting 51 lesions completed the study . All treatments reduced the fluorescence values during the experimental period ; however , F induced faster remineralization than CHX . After 3 months , 70.58 % were inactive considering all groups . DIAGNOdent pen and Nyvad presented a significant correlation . CONCLUSION After 3 months of treatment , F , CHX and CO were capable of controlling the WSLs adjacent to the orthodontic brackets . However , the treatment with F was capable of controlling the progression of the WSLs in a shorter period of time The study tested the effects of supervised chlorhexidine digluconate ( CH ) mouthrinses on plaque and gingivitis in school children . 158 children ( aged 10–12 years ) participated in the study . They were divided into four groups matched according to age , sex . DMFS , and GI . Following a sealing and prophylaxis procedure . Group A was assigned to daily mouthrinses 6 times per week using a .2 % solution of CH . Group B used the same solution only twice per week , and Group C was assigned to daily rinsing using a .1 % solution of CH . Group D served as control and rinsed daily with a placebo solution . All the rinsings were supervised and timed for 30 seconds . No attempt was made to influence the oral hygiene habits of the children . Prior to the initial prophylaxis and after 6 months of supervised rinsing , plaque was scored using the Plaque Index ( PII ) , and gingivitis was assessed using the Gingival Index ( GI ) . Calculus was scored according to the Calculus Surface Index ( CSI ) , and stain was also grade d. DMFS indices were assessed using clinical and radiographic examinations . At the end of the study plaque was significantly reduced in all CH groups when compared with the controls , and calculus increased significantly in all CH groups . In Group A the GI dropped from .88 to .15 and in Group C from .80 to .24 . In Group B the GI dropped from .79 to .38 . In the control group a slight reduction from GI = .93 to GI = .75 was noted . The study has shown that gingivitis can be controlled successfully on a longitudinal basis using .1 % or .2 % mouthrinses of CH as an adjunct to daily toothbrushing In September 1973 , a three-year school-based study was initiated in East Hampton , Connecticut , a rural nonfluori date d community . The purpose of the study is to determine the effect on dental decay , gingival inflammation and oral hygiene of removing dental plaque through supervised daily toothbrushing and flossing in school during a three-year period . To establish baseline data , three indexes were used : the DHC Index to evaluate gingivitis ; the DMF Surface Index to quantify dental caries and the PHP Index to measure dental plaque . The examinations for dental caries , including radiographs , are scheduled annually in September , whereas the plaque and gingival examinations are done biannually , in September and June . After the baseline examinations the 481 children were blocked according to grade and sex and then were r and omly assigned to either a treatment group or to a control group . In November , the treatment group was provided 10 sessions of instruction in plaque removal . For the remainder of the year ( six months ) they practice d daily plaque removal , supervised by a dental hygienist and a nurse . The control group was not instructed in oral hygiene procedures . In the treatment group , mean plaque and gingival scores at the June ( first follow-up ) examination were 14 percent and 29 percent lower , respectively , than at baseline . No change was seen in the control group . At the second follow-up examination in September ( after summer vacation ) , the same indexes were nearly at baseline levels in the treatment group . There was no treatment effect on dental caries increments after one year of study . Considering the nature of the treatment regimen and the few treatments during the first year of the study , it is not surprising that there were no caries-preventive benefits demonstrated among children in the treatment group after one year . The total number of the plaque removal sessions will be greater during the second year of the study . Therefore , the possibility of detecting a caries preventive effect at the twenty-four month examinations , should one exist , will be enhanced |
12,644 | 22,162,476 | The current limited clinical experience suggests potential beneficial cognitive effects of intranasal insulin .
Analyses provide clinical considerations for future research aim ed at elucidating whether intranasal insulin may be used to improve cognitive functions | AIM Epidemiological and mechanistic studies raised the possibility that cognitive function may be affected by brain responses to insulin .
We systematic ally review ed and analyzed existing clinical trials that assessed the potential beneficial effects of intranasal insulin administration on cognitive functions . | Background : The 22q13 deletion syndrome ( Phelan – McDermid syndrome ) is characterised by a global developmental delay , absent or delayed speech , generalised hypotonia , autistic behaviour and characteristic phenotypic features . Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease . Aims : To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome . Methods : We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year . Short-term ( during the first 6 weeks ) and long-term effects ( after 12 months of treatment ) on motor skills , cognitive functions , or autonomous functions , speech and communication , emotional state , social behaviour , behavioural disorders , independence in daily living and education were assessed . Results : The children showed marked short-term improvements in gross and fine motor activities , cognitive functions and educational level . Positive long-term effects were found for fine and gross motor activities , nonverbal communication , cognitive functions and autonomy . Possible side effects were found in one patient who displayed changes in balance , extreme sensitivity to touch and general loss of interest . One patient complained of intermittent nose bleeding . Conclusions : We conclude that long-term administration of intranasal insulin may benefit motor development , cognitive functions and spontaneous activity in children with 22q13 deletion syndrome Summary Dementia and non-insulin-dependent diabetes mellitus ( NIDDM ) are highly prevalent disorders in the elderly . Diabetes has repeatedly been reported to affect cognition , but its relation with dementia is uncertain . We therefore studied the association between diabetes and dementia in the Rotterdam Study , a large population -based study in the elderly . Of 6330 participants , aged 55 to 99 years old , complete information on diabetes and presence of dementia was available . Diabetes was diagnosed as use of anti-diabetes medication or r and om or post-load serum glucose over 11 mmol/l . Dementia was diagnosed through a stepped approach , including a sensitive screening of all participants and a comprehensive diagnostic work-up . Diabetes was present in 724 ( 11.4 % ) subjects . Of the 265 dementia patients 59 ( 22.3 % ) had diabetes . Multiple logistic regression analyses , adjusting for age and sex differences , revealed a positive association between diabetes and dementia ( odds ratio : 1.3 , 95 % confidence interval : 1.0–1.9 ) . In particular , strong associations were found between dementia and diabetes treated with insulin ( odds ratio : 3.2 , 95 % confidence interval : 1.4–7.5 ) . The relation was strongest with vascular dementia , but was also observed with Alzheimer 's disease . These associations were independent of educational attainment , smoking , body mass index , atherosclerosis , blood pressure and antihypertensive drug treatment , and could not be explained by clinical cerebral infa rct ions . The results suggest that NIDDM is associated with dementia . Alzheimer 's disease may be more frequent in elderly diabetic patients treated with insulin . [ Diabetologia ( 1996 ) 39 : 1392–1397 Previous studies have suggested an acutely improving effect of insulin on memory function . To study changes in memory associated with a prolonged increase in brain insulin activity in humans , here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment . Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration , we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function . Also , improvements in mood were expected . We investigated the effects of 8 weeks of intranasal administration of insulin ( human regular insulin 4 x 40 IU/d ) on declarative memory ( immediate and delayed recall of word lists ) , attention ( Stroop test ) , and mood in 38 healthy subjects ( 24 males ) in a double blind , between-subject comparison . Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions . Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration ( words recalled , Placebo 2.92 + /- 1.00 , Insulin 6.20 + /- 1.03 , p < 0.05 ) . Moreover , subjects after insulin reported signs of enhanced mood , such as reduced anger ( p < 0.02 ) and enhanced self-confidence ( p < 0.03 ) . Results indicate a direct action of prolonged intranasal administration of insulin on brain functions , improving memory and mood in the absence of systemic side effects . These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer 's disease Raising insulin acutely in the periphery and in brain improves verbal memory . Intranasal insulin administration , which raises insulin acutely in the CNS without raising plasma insulin levels , provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes . Based on prior research with intravenous insulin , we predicted that the treatment response would differ between subjects with ( epsilon4 + ) and without ( epsilon4- ) the APOE-epsilon4 allele . On separate mornings , 26 memory-impaired subjects ( 13 with early Alzheimer 's disease and 13 with amnestic mild cognitive impairment ) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline ( placebo ) or insulin ( 20 or 40 IU ) . Cognition was tested 15 min post-treatment , and blood was acquired at baseline and 45 min after treatment . Intranasal insulin treatment did not change plasma insulin or glucose levels . Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults . These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4 + subjects and normal adults . Unexpectedly , memory-impaired epsilon4 + subjects showed poorer recall following insulin administration on one test of memory . These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E ( APOE ) related differences in insulin metabolism Insulin receptors have been detected in several structures of the brain , yet the biological significance of insulin acting on the brain remains rather unclear . In humans , direct central nervous effects of insulin are difficult to distinguish from alterations in neuronal functions because of insulin-induced decrease in blood glucose levels . Since several intranasally administered viruses , peptides , and hormones have been shown to penetrate directly from the nose to the brain , we tested whether insulin after intranasal administration likewise has access to the brain . After a 60-min baseline period , insulin ( 20 IU H-Insulin 100 Hoechst ) or vehicle ( 2.7 mg/ml m-Cresol ) was intranasally administered every 15 min to 18 healthy subjects according to a double-blind within-subject crossover design . Auditory-evoked potentials ( AEP ) indexing cortical sensory processing were recorded while the subjects performed a vigilance task ( oddball paradigm ) during the baseline phase and after 60 min of intranasal treatment with insulin or placebo . Blood glucose and serum insulin levels were not affected by intranasal insulin . Compared with placebo , intranasal administration of insulin reduced amplitudes of the N1 ( P < 0.005 ) and P3 ( P < 0.02 ) components of the AEP and increased P3 latency ( P < 0.05 ) . The reduction in P3 amplitude was most pronounced over the frontal recording site ( 2.42 + /- 1.00 vs. 4.92 + /- 0.79 microV , P < 0.0005 ) . At this site , after insulin administration , a broad negative shift developed in the AEP between 280 and 500 ms poststimulus ( area under the curve -166.0 + /- 183.8 vs. 270.8 + /- 138.7 microV x ms after placebo , P < 0.01 ) . The results suggest that after intranasal administration , insulin directly enters the brain and exerts distinct influences on central nervous functions in humans The crucial role of the medial temporal lobe ( MTL ) in episodic memory is well established . Although there is little doubt that its anatomical subregions-the hippocampus , peri- , entorhinal and parahippocampal cortex (PHC)-contribute differentially to mnemonic processes , their specific functions in episodic memory are under debate . Data from animal , human lesion , and neuroimaging studies suggest somewhat contradictory perspectives on this functional specialization : a general participation in declarative memory , an exclusive involvement in associative mnemonic processes , and a specific contribution to spatial memory are reported for the hippocampus , adjacent cortices , and the PHC . A functional lateralization in humans dependent on the verbalizability of the material is also discussed herein . To further eluci date the differential contributions of the various MTL subregions to encoding , we employed an object-location association memory paradigm . The memory for each of the studied associations was tested twice : by the object , and by the location serving as retrieval cue . The memory accuracy in response to both cue types was also assessed parametrically . Brain activity during encoding which leads to different degrees of subsequent memory accuracy under the two retrieval conditions was compared . We found the bilateral posterior PHC to participate in encoding of both the object associated with a location and the location associated with an object . In contrast , activity in an area in the left anterior PHC and the right anterior MTL was only correlated with the memory for the location associated with an object |
12,645 | 24,972,732 | No significant difference was found in terms of short-term efficacy between bipolar transurethral resection of the prostate ( B-TURP ) and monopolar transurethral resection of the prostate ( M-TURP ) .
However , B-TURP was associated with a lower rate of perioperative complications .
Better short-term efficacy outcomes , fewer immediate complications , and a shorter hospital stay were found after holmium laser enucleation of the prostate ( HoLEP ) compared with M-TURP .
Compared with M-TURP , GreenLight photoselective vaporization of the prostate ( PVP ) was associated with a shorter hospital stay and fewer complications but no different short-term efficacy outcomes .
This meta- analysis shows that HoLEP is associated with more favorable outcomes than M-TURP in published RCTs .
B-TURP and PVP have result ed in better perioperative outcomes without significant differences regarding efficacy parameters after short-term follow-up compared with M-TURP .
PATIENT SUMMARY Bipolar transurethral resection of the prostate , photovaporization of the prostate , and holmium laser enucleation of the prostate have shown efficacy outcomes comparable with conventional techniques yet reduce the complication rate . | CONTEXT A number of transurethral ablative techniques based on the use of innovative medical devices have been introduced in the recent past for the surgical treatment of benign prostatic obstruction ( BPO ) .
OBJECTIVE To conduct a systematic review of the literature and a meta- analysis of available r and omized controlled trials ( RCTs ) , and to evaluate the efficacy and safety of transurethral ablative procedures for BPO . | BACKGROUND The comparative outcome with GreenLight ( GL ) photoselective vaporisation of the prostate and transurethral resection of the prostate ( TURP ) in men with lower urinary tract symptoms due to benign prostatic obstruction ( BPO ) has been question ed . OBJECTIVE The primary objective of the GOLIATH study was to evaluate the noninferiority of 180-W GL XPS ( XPS ) to TURP for International Prostate Symptom Score ( IPSS ) and maximum flow rate ( Qmax ) at 6 mo and the proportion of patients who were complication free . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve r and omised controlled trial at 29 centres in 9 European countries involving 281 patients with BPO . INTERVENTION 180-W GL XPS system or TURP . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measurements used were IPSS , Qmax , prostate volume ( PV ) , postvoid residual ( PVR ) and complications , perioperative parameters , and reintervention rates . Noninferiority was evaluated using one-sided tests at the 2.5 % level of significance . The statistical significance of other comparisons was assessed at the ( two-sided ) 5 % level . RESULTS AND LIMITATIONS The study demonstrated the noninferiority of XPS to TURP for IPSS , Qmax , and complication-free proportion . PV and PVR were comparable between groups . Time until stable health status , length of catheterisation , and length of hospital stay were superior with XPS ( p<0.001 ) . Early reintervention rate within 30 d was three times higher after TURP ( p=0.025 ) ; however , the overall postoperative reintervention rates were not significantly different between treatment arms . A limitation was the short follow-up . CONCLUSIONS XPS was shown to be noninferior ( comparable ) to TURP in terms of IPSS , Qmax , and proportion of patients free of complications . XPS results in a lower rate of early re interventions but has a similar rate after 6 mo . TRIAL REGISTRATION Clinical Trials.gov , identifier NCT01218672 PURPOSE To our knowledge we report the first single center , prospect i ve , r and omized study comparing holmium laser enucleation and high performance GreenLight ™ prostate photoselective vaporization as surgical treatment of prostatic adenomas greater than 60 ml . MATERIAL S AND METHODS A total of 80 patients with a large prostatic adenoma were r and omly assigned to surgical treatment with holmium laser enucleation or photoselective vaporization . International Prostate Symptom Score , International Index of Erectile Function-15 , maximum flow rate , post-void residual urine , serum prostate specific antigen and transrectal ultrasound volume were recorded . RESULTS Patient baseline characteristics were similar for holmium laser enucleation and photoselective vaporization . Operative time and catheter removal time were almost equal in the 2 groups ( p = 0.7 and 0.2 , respectively ) . Eight vaporization cases were converted to transurethral prostate resection or holmium laser enucleation intraoperatively due to bleeding . A significantly higher maximum flow rate and lower post-void residual urine were noted in holmium laser cases during the entire followup ( at 1 year each p = 0.02 ) . However , no significant difference in International Prostate Symptom Score , quality of life or International Index of Erectile Function-15 was detected . Prostate volume and serum PSA decreased 78 % and 88 % in the holmium laser group , and 52 % and 60 % in the vaporization group , respectively . CONCLUSIONS Holmium laser enucleation and photoselective vaporization are effective for lower urinary tract symptoms due to a large prostatic adenoma . Early subjective functional results ( maximum flow rate and post-void residual urine ) of holmium laser enucleation appear to be superior to those of photoselective vaporization . In our h and s cases intended to be treated with photoselective vaporization were at 22 % risk of conversion to another modality . This could reflect our determination to vaporize to the capsule in all vaporization cases BACKGROUND Plasmakinetic enucleation of the prostate ( PKEP ) has recently been proved a safe and technically feasible procedure for benign prostatic hyperplasia ( BPH ) . However , its long-term safety , efficacy , and durability in comparison with the gold-st and ard transurethral resection of the prostate ( TURP ) have not yet been reported . OBJECTIVE To report the 3-yr follow-up results of a prospect i ve , r and omised clinical trial comparing PKEP with st and ard TURP for symptomatic BPH . DESIGN , SETTING , AND PARTICIPANTS A total of 204 patients with bladder outflow obstruction ( BOO ) secondary to BPH were prospect ively r and omised 1:1 into either the PKEP group or the TURP group . INTERVENTION The patients in each group underwent the procedure accordingly . MEASUREMENTS All patients were assessed perioperatively and followed at 1 , 3 , 6 , 12 , 18 , 24 , and 36 mo postoperatively . The preoperative and postoperative parameters included International Prostate Symptom Score ( IPSS ) , quality of life ( QoL ) scores , the International Index of Erectile Function ( IIEF ) question naire , maximum urinary flow rates ( Q(max ) ) , transrectal ultrasound (TRUS)-assessed prostate volume , postvoid residual urine ( PVRU ) volume , and serum prostate-specific antigen ( PSA ) level . Patient baseline characteristics , perioperative data , and postoperative outcomes were compared . All complications were recorded . RESULTS AND LIMITATIONS PKEP was significantly superior to TURP in terms of the drop in haemoglobin ( 0.74±0.33 g/dl vs 1.88±1.06 g/dl ; p<0.001 ) , intraoperative irrigation volume ( 11.7±4.5 l vs 15.4±6.2 l ; p<0.001 ) , postoperative irrigation volume and time ( 18.5±7.6 l vs. 30.0±11.4 l and 16.6±5.2 h vs 25.3±8.5 h ; all p<0.001 ) , recovery room stay ( 67.3±11.1 min vs 82.0±16.4 min ; p<0.001 ) , catheterisation time ( 51.7±26.3 h vs 80.5±31.6 h ; p<0.001 ) , hospital stay ( 98.4±20.4 h vs 134.2±31.5 h ; p<0.001 ) , and resected tissue ( 56.4±12.8 g vs 43.8±15.5 g ; p<0.001 ) . There were no statistical differences in operation time and sexual function between the two groups . At 36 mo postoperatively , the PKEP group had a maintained and statistically significant improvement in IPSS ( 2.4±2.2 vs 4.3±2.9 ; p<0.001 ) , QoL ( 0.6±0.5 vs 1.6±1.4 ; p<0.001 ) , Q(max ) ( 28.8±10.1 ml/s vs 25.1±8.0 ml/s ; p=0.017 ) , and TRUS volume ( 21.0±7.3 ml vs 26.4±6.8 ml ; p<0.001 ) , with urodynamically proven deobstruction ( Schäfer grade 0.2±0.02 vs 0.8±0.1 ; p<0.001 ) . More extensive clinical trials are required to vali date these results . CONCLUSIONS PKEP is a safe and highly effective technique for relieving BOO . At 3-yr follow-up , the clinical efficacy of PKEP is durable and compares favourably with TURP OBJECTIVE Prospect ively evaluate perioperative outcomes and 2-yr follow-up after holmium laser enucleation ( HoLEP ) and st and ard open prostatectomy ( OP ) for treating benign prostatic hyperplasia-related obstructed voiding symptoms , with prostates > 70 g. METHODS From March 2003 to December 2004 , 80 consecutive patients were r and omised for surgical treatment with HoLEP ( n=41 ) or st and ard OP ( n=39 ) . All patients were preoperatively assessed with International Prostate Symptom Score and International Index of Erectile Function question naires and complete urodynamic evaluation . Intraoperative and perioperative parameters such as blood loss , catheter removal , and hospital stays were assessed . Early and late complications were recorded . Patients were evaluated at 1- , 3- , 12- , and 24-mo follow-ups with the same tests . RESULTS Operating room time was significantly shorter for the OP group ( 72.09+/-21.22 min vs. 58.31+/-11.95 min , p<0.0001 ) ; catheter removal ( 1.5+/-1.07 d and 4.1+/-0.5 d , p<0.001 ) and hospital stay ( 2.7+/-1.1 d vs. 5.4+/-1.05 d , p<0.001 ) were shorter in the HoLEP group . Blood loss was less and blood transfusions fewer in the HoLEP group ( p<0.001 ) . In both groups urodynamic and uroflowmetry findings improved from baseline , were still evident at the 24-mo follow-up , and were comparable between the two groups . Late complications were also comparable . CONCLUSIONS HoLEP is a feasible technique for treating large prostates . Functional results are similar to OP at the 2-yr follow-up . Reduced catheterisation , hospital stay , and blood loss make HoLEP an attractive option for the treatment of large prostates OBJECTIVES To compare the effectiveness and the safety of photoselective vaporization of the prostate ( PVP ) to open prostatectomy ( OP ) for the surgical treatment of large prostatic adenomas . METHODS A total of 125 patients with prostate gl and s > 80ml were r and omly allocated to PVP ( n=65 ) or OP ( n=60 ) and prospect ively evaluated at 1 , 3 , 6 , and 12 mo postoperatively . International Prostate Symptom Score ( IPSS ) and peak urinary flow rate ( Q(max ) ) were chosen as primary treatment-related end points . RESULTS The patients who underwent PVP experienced a longer length of operation time , shorter time of catheterization , and shorter hospital stay . Adverse events were minor and of similar profiles in both groups , although patients who underwent OP showed a higher transfusion rate . All functional parameters improved significantly compared to baseline values in both groups . The IPSS did not differ between the two groups at 3 , 6 , and 12 mo postoperatively . Patients who underwent OP scored better in the IPSS quality of life score at 6 and 12 mo postoperatively . No significant differences between the two groups in the Q(max ) , postvoid residual urine volume , and International Index for Erectile Function-5 question naire were detected . At 3 mo prostate volume was significantly lower in the OP group compared to the PVP group ( median value 10ml vs. 50ml ; p<0.001 ) and remained as such throughout follow-up , whereas prostate-specific antigen values reached statistical difference at 6 mo ( median value 2ng/ml vs. 2.4ng/ml ; p=0.028 ) . CONCLUSIONS Our results indicate that for a 12-mo period PVP is a highly acceptable treatment alternative to OP OBJECTIVE To perform a prospect i ve , r and omized , long-term comparison between bipolar plasma vaporization of the prostate ( BPVP ) , bipolar transurethral resection in saline ( TURis ) , and monopolar transurethral resection of the prostate ( TURP ) concerning the perioperative and follow-up parameters . METHODS A total of 510 patients with benign prostatic hyperplasia ( BPH ) , Q(max ) < 10 mL/s , International Prostate Symptom Score ( IPSS ) > 19 , and prostate volume between 30 and 80 mL were enrolled in the trial . All cases were evaluated preoperatively and at 1 , 3 , 6 , 12 , and 18 months after surgery by IPSS , quality of life , Q(max ) , and ultrasonography . RESULT Each study arm including 170 cases emphasized similar preoperative parameters . The capsular perforation and intraoperative bleeding rates as well as the mean hemoglobin drop were significantly decreased for BPVP by comparison with TURis and TURP . The postoperative hematuria , blood transfusion , and clot retention rates were significantly higher in the TURP group . The operation time was significantly shorter only for BPVP patients , whereas the catheterization period and hospital stay were significantly reduced for BPVP , followed by TURis . The rates of irritative symptoms and urethral strictures were similar in the 3 series . The recatheterization , bladder neck sclerosis , and retreatment rates were significantly lower in the BPVP group . During the 1 , 3 , 6 , 12 , and 18 months ' follow-up , the BPVP series emphasized significantly superior parameters in terms of IPSS and Q(max ) . CONCLUSION BPVP represents a valuable endoscopic treatment alternative for BPH patients , with superior efficacy and satisfactory complication rate . The long-term follow-up emphasized durable improvements of the postoperative parameters for BPVP OBJECTIVES To compare the short term outcomes of photoselective vaporization ( PVP ) and transurethral resection of the prostate ( TURP ) for gl and s larger than 70 mL in a prospect i ve r and omized trial . METHODS Seventy-six consecutive patients with enlarged prostatic adenomas of 70 to 100 mL were r and omly assigned for surgical treatment with TURP ( n = 37 ) or PVP ( n = 39 ) . International Prostate Symptom Score ( IPSS ) , International Index of Erectile Function ( IIEF-5 ) scores , maximum flow rates ( Qmax ) , postvoid urine residues ( PVR ) , and transrectal ultrasound ( TRUS ) volumes were recorded . Operative data , complications , catheter removal , and hospitalization periods were also recorded . Patients were reassessed at 3 and 6 months . RESULTS Baseline characteristics of both groups were similar . Mean preoperative TRUS volume was 88 + /- 9.2 mL in the TURP group and 86.1 + /- 8.8 mL in the PVP group . The procedure was significantly shorter for the TURP group ( 51 + /- 17.2 minutes versus 87 + /- 18.3 minutes , P < 0.05 ) , catheter removal ( 3.9 + /- 1.2 days and 1.7 + /- 0.8 days , P < 0.05 ) , and hospital stay ( 4.8 + /- 1.2 days versus 2 + /- 0.7 days , P < 0.05 ) were shorter in the PVP group . A significant difference in IPSS , Qmax and PVR values was observed within the follow-up period in favor of the TURP . The percentage volume reduction was significantly higher in TURP group . Reoperation was necessary in 7 patients in PVP but none in TURP group . CONCLUSIONS Although PVP offers advantageous over TURP with regard to intraoperative and perioperative safety , early functional results of TURP are superior to PVP in patients with enlarged prostates larger than 70 INTRODUCTION Transurethral resection syndrome is an uncommon but potentially life threatening complication . Various irrigating solutions have been used , normal saline being the most physiological . The recent availability of bipolar cautery has permitted the use of normal saline irrigation . MATERIAL AND METHODS In a r and omized prospect i ve study , we compared the safety and efficacy of bipolar cautery ( using 0.9 % normal saline irrigation ) versus conventional monopolar cautery ( using 1.5 % glycine irrigation ) . Pre and postoperative hemoglobin ( Hb ) and hematocrit values were compared . Hemodynamics and arterial oxygen saturation were monitored throughout the study . Safety end points were changes in serum electrolytes , osmolarity and Hb/PCV ( packed cell volume ) . Efficacy parameters were the International Prostate Symptom Score ( IPSS ) and Qmax ( maximum flow rate in mL/sec ) values . RESULTS Mean preoperative prostate size on ultrasound was 60 + /- 20cc . Mean resected weight was 17.6 + /- 10.8 g ( glycine ) and 18.66 + /- 12.1 g ( saline ) . Mean resection time was 56.76 + /- 14.51 min ( glycine ) and 55.1 + /- 13.3 min ( saline ) . The monopolar glycine group showed a greater decline in serum sodium and osmolarity ( 4.12 meq/L and 5.14 mosmol/L ) compared to the bipolar saline group ( 1.25 meq/L and 0.43 mosmol/L ) . However , this was not considered statistically significant . The monopolar glycine group showed a statistically significant decline in Hb and PCV ( 0.97 gm % , 2.83 , p < 0.005 ) as compared to the bipolar saline group ( 0.55 gm % and 1.62 , p < 0.05 ) . Patient follow- up ( 1,3,6 and 12 months postoperatively ) demonstrated an improvement in IPSS and Qmax in both the groups . CONCLUSION We concluded that bipolar transurethral resection of prostate is clinical ly comparable to monopolar transurethral resection of prostate with an improved safety profile . However , larger number of patients with longer follow up is essential BACKGROUND Transurethral resection of prostate ( TURP ) has been considered as the st and ard treatment for benign prostatic hyperplasia ( BPH ) . However , issues that have not yet been overcome for TURP include bleeding and absorption of irrigation fluid . Thus , novel improvement of the surgery is necessary . This study aim ed to evaluate the efficacy and safety of bipolar plasma vaporization of the prostate ( BPVP ) with " button-type " electrode against st and ard TURP for BPH . METHODS From January 2009 to January 2012 , 30 patients who scheduled for surgical treatment of BPH surgical treatment were enrolled in the trial with provided consent for the study . Patients were prospect ively r and omized 1:1 to undergo either BPVP or TURP . Participants were blinded to the r and omization scheme . All cases were assessed preoperatively and followed at 1 , 3 , and 6 months postoperatively by indwelling catheter time , blood loss , hospital stays , International Prostate Symptom Score ( IPSS ) , quality of life ( QOL ) , and Qmax . RESULTS BPVP was significantly superior to TURP in terms of indwelling catheter time ( ( 4.1 ± 4.1 ) days vs. ( 6.8 ± 6.8 ) days , P = 0.000 ) , blood loss ( ( 64.7 ± 103.8 ) ml vs. ( 254.7 ± 325.4 ) ml , P = 0.040 ) , hospital stay ( ( 8.7 ± 1.0 ) days vs. ( 11.7 ± 1.5 ) days , P = 0.000 ) , IPSS ( ( 4.2 ± 8.0 ) vs. ( 9.3 ± 3.7 ) , P = 0.049 ) , QOL ( ( 1.5 ± 0.8 ) vs. ( 2.6 ± 1.4 ) , P = 0.027 ) , Qmax ( ( 16.3 ± 5.7 ) ml/s vs. ( 12.5 ± 3.1 ) ml/s , P = 0.038 ) , hemoglobin ( ( 130.7 ± 9.4 ) g/L vs. ( ( 122.1 ± 11.9 ) g/L , P = 0.047 ) , Na(+ ) level ( ( 138.6 ± 2.1 ) mmol/L vs. ( ( 137.2 ± 2.0 ) mmol/L , P = 0.046 ) and operation time ( ( 39.0 ± 15.5 ) minutes vs. ( ( 69.3 ± 24.8 ) minutes , P = 0.004 ) . And there were no statistical differences between BPVP group and TURP group in preoperatively assessment : patient 's age ( ( 70.9 ± 7.1 ) years vs. ( 71.9 ± 6.1 ) years , P = 0.736 ) , IPSS ( ( 24.6 ± 4.7 ) vs. ( 27.3 ± 5.9 ) , P = 0.100 ) , QOL ( ( 5.1 ± 0.8 ) vs. ( 5.1 ± 1.0 ) , P = 0.940 ) , Qmax ( ( 4.4 ± 2.7 ) ml/s vs. ( 5.3 ± 2.6 ) ml/s , P = 0.314 ) , hemoglobin ( ( 137.4 ± 8.7 ) g/L vs. ( 139.2 ± 10.4 ) g/L , P = 0.623 ) , Na(+ ) level ( ( 140.5 ± 1.8 ) mmol/L vs. ( 141.3 ± 1.4 ) mmol/L , P = 0.192 ) and prostate volume ( ( 59.0 ± 17.4 ) ml vs. ( 70.1 ± 28.8 ) ml , P = 0.276 ) . CONCLUSIONS Compared with TURP , BPVP with " button-type " electrode shows superior efficacy and safety . Therefore , BPVP with " button-type " electrode represents a valuable endoscopic treatment alternative for BPH patients Objectives : We conducted this study to compare the safety and efficacy of transurethral resection of the prostate ( TURP ) and holmium laser prostatectomy . Methods : A total of 30 patients eligible for surgery for symptomatic benign prostatic hyperplasia were included in the study . They were r and omized into two groups of 15 each . The patients were evaluated at 3 weeks , 3 and 9 months . Results : Preoperative parameters were comparable between the 2 groups . The mean operative time was longer in the holmium laser enucleation of prostate ( HoLEP ) group ( 53 ± 9.84 vs. 43 ± 9.36 min ; p = 0.001 ) . The intraoperative adverse events were comparable . The mean traction time ( 26.80 ± 5.9 vs. 19.60 ± 3.6 h ; p = 0.0001 ) , irrigation time ( 30 ± 7.68 vs. 19.40 ± 1.15 h ; p = 0.0001 ) , and duration of indwelling catheter ( 78.20 ± 17.84 vs. 46.42 ± 14.25 h ; p = 0.0001 ) were significantly less in the HoLEP group as compared to the TURP group . Two patients ( 13.66 % ) in the TURP group had significant hematuria . Two patients in the HoLEP group vs. none in the TURP group developed urinary incontinence ( p < 0.05 ) . Significant improvements were observed in IPSS score , PFRs and PVRs in both the groups and maintained at 9 months . Conclusions : HoLEP is safe and effective in the surgical management of benign prostatic hyperplasia , with the advantage of reduced intraoperative hemorrhage and perioperative morbidity OBJECTIVE To compare the clinical outcomes between thulium laser transurethral enucleation of the prostate ( ThuLEP ) and plasmakinetic bipolar resection of the prostate ( PKRP ) for treating benign prostatic hyperplasia ( BPH ) in a prospect i ve r and omized trial with 18 months of follow-up . METHODS The study r and omized 158 consecutive patients with BPH to ThuLEP ( n = 79 ) or PKRP ( n = 79 ) . All patients were evaluated preoperatively and at 1 , 3 , 6 , 12 , and 18 months after surgery by International Prostate Symptom Score ( IPSS ) , quality of life score ( QOLS ) , maximum flow rate ( Qmax ) , and postvoid residual urine volume ( PVR ) . RESULTS The 79 patients in each study arm each showed no significant difference in preoperative parameters . Compared with PKRP , ThuLEP required a longer operation time ( 65.4 vs 47.4 minutes , P = .022 ) but result ed in less hemoglobin decrease ( 0.15 vs 0.30 g/dL , P = .045 ) . ThuLEP also needed less catheterization time ( 2.1 vs 3.5 days , P = .031 ) , irrigation volume ( 12.4 vs 27.2 L , P = .022 ) , and hospital stay ( 2.5 vs 4.6 days , P = .026 ) . During the 1 , 3 , 6 , 12 , and 18 months of follow-up , the procedures did not demonstrate a significant difference in Qmax , IPSS , PVR , and QOLS . CONCLUSION ThuLEP and PKRP both relieve lower urinary tract symptoms equally , with high efficacy and safety . ThuLEP was statistically superior to PKRP in blood loss , catheterization time , irrigation volume , and hospital stay but inferior to PKRP in operation time . However , procedures did not differ significantly in Qmax , IPSS , PVR , and QOLS through the 18 months of follow-up The Gyrus ™ system uses bipolar electrocautery with saline irrigation to vaporize prostatic tissue and is compared to transurethral resection of the prostate ( TURP ) in a r and omized prospect i ve study with 1 y follow-up . Outcomes measured were fluid absorption , blood loss , period of catheterization , hospital stay , symptom scores , quality of life , flow rates , and post-void residual volumes at 3 , 6 , and 12 months . All measured parameters were similar , although re-catheterization rates were higher ( 30 % vs 5 % ) in the Gyrus group . Clot evacuation rates were higher in the TURP group ( 19 % vs 0 % ) . The Gyrus ™ device is safe and produces results that are similar to TURP at 1 Objectives : To compare clinical results of plasmakinetic ( PK ) resection vs. st and ard monopolar resection of the prostate , i.e. transurethral resection of the prostate ( TURP ) . Material s and Methods : 48 patients were included in this study between January 2003 and October 2003 . They were r and omized into two groups ( TURP : PK ) with a ratio of 1:1 . PK resections ( n = 24 ) were carried out by using PlasmaKinetic Tissue Management System ( Gyrus Medical Ltd , Cardiff , UK ) and PlasmaSect electrodes . TURPs ( n = 24 ) were done by using a 26-Fr continuous-flow resectoscope and Karl Storz 27040 electrodes . Patients were assessed for safety and efficacy by measuring the IPSS and maximum flow rates at 1 , 3 , 6 and 12 months and residual urine measurement at 3 , 6 and 12 months and transrectal ultrasonography at 6 months . Results : The patients ’ ages ranged from 50 to 82 ( mean 64 ± 10 ) years . Groups were similar for operation time , bleeding score , resected tissue , catheterization time and irrigated volume . Mean serum Na levels at the end of the operation were 141.7 ± 5.1 in the TURP group and 145.2 ± 4.4 in the PK group ( p = 0.013 ) . The IPSS , QOL score and Qmax had improved significantly in the postoperative period without any differences in either group . Conclusions : The main advantage of PK resection seems to be decreasing the risk of TUR syndrome , thus , larger prostates could be treated without a time limitation , theoretically . However , this technique brings no advantages in terms of intra- and postoperative bleeding , hospital stay , operation time and late complications OBJECTIVE To compare the clinical outcomes between thulium laser transurethral enucleation of the prostate ( ThuLEP ) ( 70 W ) and holmium laser transurethral enucleation of the prostate ( HoLEP ) ( 90 W ) in a prospect i ve r and omized trial with 18 months of follow-up . Both ThuLEP and HoLEP effectively relieve the obstructive symptoms due to benign prostatic hyperplasia ( BPH ) . METHODS A total of 133 consecutive patients with BPH were r and omized to either ThuLEP ( n = 71 ) or HoLEP ( n = 62 ) . An energy setting of 70 W and 90 W was used for the thulium and holmium laser in the enucleation procedure , respectively . The mushroom technique was used to fragment the enucleated lobes with the resection loop . The preoperative and postoperative parameters were compared . RESULTS ThuLEP required a longer operation time ( 72.4 vs 61.5 minutes , P = .034 ) but result ed in less blood loss than HoLEP ( 130.0 vs 166.6 mL , P = .045 ) . The catheterization time was comparable . At 18 months , the lower urinary tract symptom indexes were improved significantly in both groups compared with the baseline values . The International Prostate Symptom Score decreased to 5.2 in the ThuLEP group and 6.2 in the HoLEP group . The quality of life score and peak urinary flow rate were similar between the 2 groups ( 1.3 vs 1.2 and 23.4 vs 24.2 mL/s ) and the postvoid residual urine volume decreased by 82.50 % and 81.73 % in the ThuLEP and HoLEP groups , respectively . The mean prostate-specific antigen decrease after HoLEP and ThuLEP was 30.43 % and 43.36 % , respectively . No urethral or bladder neck stricture were found in either group . CONCLUSION Both ThuLEP ( 70 W ) and HoLEP ( 90 W ) relieve lower urinary tract symptoms equally with high efficacy and safety . ThuLEP was statistically superior to HoLEP in blood loss and inferior to HoLEP in operation time , although the differences were clinical ly negligible . The mushroom technique could be adequate , without an additional mechanical tissue morcellator BACKGROUND Photoselective vaporization ( PVP ) with the GreenLight HPS 120-W laser ( GLL ) was recently introduced for treatment of benign prostatic hyperplasia ( BPH ) . OBJECTIVE To compare results of GLL PVP and transurethral resection of the prostate ( TURP ) for treatment of BPH . DESIGN , SETTING , AND PARTICIPANTS A total of 120 patients with BPH were r and omly assigned to two equal groups : TURP or PVP . MEASUREMENTS Both groups were compared regarding all relevant preoperative , operative , and postoperative parameters . Functional results in terms of improvement of International Prostate Symptom Score ( IPSS ) , maximum flow rate ( Q(max ) ) , and postvoid residual ( PVR ) urine were assessed at 1 , 3 , 6 , 12 , 24 , and 36 mo . A total of 55 and 54 patients completed 36 mo of follow-up in the TURP and PVP groups , respectively . RESULTS AND LIMITATIONS Baseline characteristics were comparable . Mean operative time was significantly shorter for TURP . Compared to preoperative values , there was significant reduction in hemoglobin and serum sodium levels at the end of TURP only . A significant difference in favor of PVP was achieved regarding the duration of catheterization and hospital stay . In the PVP , no major intraoperative complications were recorded and none of the patients required blood transfusion . Among TURP patients , 12 ( 20 % ) required transfusion , 3 ( 5 % ) developed TUR syndrome , and capsule perforation was observed in 10 patients . There was dramatic improvement in Q(max ) , IPSS , and PVP compared with preoperative values and the degree of improvement was comparable in both groups at all time points of follow-up . Storage bladder symptoms were significantly higher in PVP . By the end of 36 mo , five patients in TURP and six in PVP were lost to follow-up . A redo procedure was required in one TURP patient and six PVP patients ( p<0.05 ) . Two TURP patients and four PVP patients developed bladder neck contracture ( p>0.05 ) treated by bladder neck incision ; none in either group experienced urethral stricture or urinary incontinence . CONCLUSIONS Compared with TURP , 120-W GLL PVP is safe and effective in treatment of BPH PURPOSE To compare bipolar resection with the conventional monopolar transurethral resection of the prostate ( TURP ) with respect to peri- and postoperative complications and long-term outcome . PATIENTS AND METHODS Patients with consecutive benign prostatic hyperplasia needing surgery ( n=185 ) from the hospital 's waiting list were r and omized to TURP using either a bipolar or a monopolar system . Peri- and postoperative parameters were monitored , complications were registered , and timed micturition/International Prostate Symptom Score ( TM/IPSS ) forms were collected at 3 and 6 weeks and at 6 and 18 months . RESULTS Bipolar surgery was followed by a 16 % to 20 % higher percentage of the patients reporting ongoing improvement ( fractional IPSS change > 2 ) at 3 and 6 weeks after the surgery ( p<0.05 ) . There were fewer readmissions in the bipolar group than in the monopolar ( 5 vs. 13 , p<0.05 ) . No differences between the groups with respect to hospital stay and catheter duration was recorded . Bipolar and monopolar TURP result ed in marked and sustained improvements of IPSS , bother score , and TM . CONCLUSIONS Bipolar TURP , using the transurethral resection in saline ( TURis ) system , result ed in significantly fewer postoperative readmissions , faster postoperative recovery , and equally long-lasting good results in TM/IPSS and bother score , as in monopolar TURP Objectives : To evaluate in a prospect i ve , r and omized study , the efficacy and safety profile of photoselective vaporization of prostate ( PVP ) using a 80W potassium titanyl phosphate ( KTP ) laser when compared to st and ard transurethral resection of prostate ( TURP ) in patients with lower urinary tract symptoms ( LUTS ) due to benign prostatic enlargement ( BPE ) . Material s and Methods : Between February 2009 and August 2009 , 117 patients satisfying the eligibility criteria underwent surgery [ 60 PVP{Group A } ; 57 TURP{Group B } ] . The groups were compared for functional outcome ( both subjective and objective parameters ) , perioperative parameters and complications , with a follow up of one year . P value<0.05 was considered statistically significant . Results : The baseline characteristics of the two groups were comparable . Mean age was 66.68 years and 65.74 years , mean IPSS score was 19.98 and 20.88 , mean prostate volume was 44.77 cc and 49.02 cc in Group A and B , respectively . Improvements in IPSS , QOL , prostate volume , Q max and PVRU at 12 months were similar in both groups . PVP patients had longer operating time , lesser perioperative blood loss , shorter catheterization time and a higher dysuria rate when compared to TURP patients . The overall complication rate was similar in the two groups . Conclusions : In patients with LUTS due to BPE , KTP-PVP is an equally efficacious alternative to TURP with durable results at one year follow up with additional benefits of lesser perioperative blood loss , lesser transfusion requirements and a shorter catheterization time . Long term comparative data is awaited to clearly define the role of KTP-PVP in such patients PURPOSE To our knowledge we report the first multicenter , prospect i ve , r and omized study comparing holmium laser enucleation ( HoLEP ) and transurethral prostate resection ( TURP ) for obstructive benign prostatic hyperplasia . MATERIAL S AND METHODS From January to October 2002 , 100 consecutive patients with symptomatic obstructive benign prostatic hyperplasia were r and omized at 2 centers to surgical treatment with HoLEP ( 52 in group 1 ) or TURP ( 48 in group 2 ) . Patients in the 2 groups were preoperatively assessed by scoring subjective symptoms question naires . Preoperative and perioperative parameters were also evaluated , the latter at 1 , 6 and 12 months of followup . RESULTS At baseline all patients had obstruction ( Schäfer grade greater than 2 ) . At the 1 , 6 and 12-month followups no statistically significant differences were observed between the 2 groups in terms of urodynamic findings and subjective symptom scoring . In the HoLEP group mean total time in the operating room + /- SD was significantly longer than for TURP ( 74 + /- 19.5 vs 57 + /- 15 minutes , p < 0.05 ) , while catheterization time ( 31 + /- 13 vs 57.78 + /- 17.5 minutes , p < 0.001 and hospital stay ( 59 + /- 19.9 vs 85.8 + /- 18.9 hours , p < 0.001 ) were significantly shorter in the HoLEP group . Transient stress and urge incontinence were more common in the HoLEP group , although at the 12-month followup results were comparable . The overall complication rate was comparable in the 2 groups . Erectile function was also maintained in the followup period from baseline in each group , as expected . CONCLUSIONS HoLEP and TURP were equally effective for relieving obstruction and lower urinary tract symptoms . HoLEP was associated with shorter catheterization time and hospital stay . At 1 year of followup complications were similar in the 2 groups PURPOSE We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospect i ve r and omized clinical trial . MATERIAL S AND METHODS A total of 280 patients were r and omly treated with plasmakinetic resection or holmium laser enucleation of the prostate . Perioperative and postoperative outcome data were obtained during a 2-year followup . RESULTS No significant differences between the 2 surgical groups were observed in the preoperative data . Both groups displayed significant improvements after surgery . However , we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS ( International Prostate Symptom Score ) , quality of life scores or maximum flow rate values . Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage , shorter bladder irrigation and catheter times , and shorter hospital stays . A larger amount of prostate tissue was retrieved in the holmium laser enucleation group , but the operation time was longer for this group than for the plasmakinetic resection group . CONCLUSIONS Plasmakinetic resection and holmium laser enucleation of the prostate are effective and safe treatments for benign prostatic hyperplasia . Holmium laser enucleation of the prostate can be applied to prostates of all sizes , and involves less risk of hemorrhage , decreased bladder irrigation and catheter times , as well as reduced hospital stay . Thus , we believe holmium laser enucleation of the prostate should be proposed as a potential new gold st and ard surgical therapy instead of transurethral resection of the prostate for patients with benign prostatic hyperplasia OBJECTIVE To prospect ively evaluate perioperative results and 12-month follow-up after plasmakinetic enucleation of the prostate ( PKEP ) and transvesical open prostatectomy ( OP ) for benign prostatic hyperplasia ( BPH ) > 80 mL. METHODS A total of 83 patients with a prostate > 80 mL were r and omized to either PKEP or OP . Perioperative and postoperative outcome data were obtained during a 12-month follow-up . RESULTS No statistical differences were observed in the preoperative data . Both groups result ed in a similar and significant postoperative improvement in International Prostate Symptom Score ( IPSS ) , quality of life ( QOL ) , maximum uroflow rate ( Qmax ) , postvoid residual ( PVR ) urine volume and prostate specific antigen ( PSA ) , but no significant difference was found between the groups at the 12-month follow-up . Compared to OP , operation time ( 111.2 ± 27.1 minutes vs 109.6 ± 28.2 minutes , P = .708 ) were not significantly different between the groups , but blood loss was significantly less ( 10.2 ± 4.5 g/l vs 15.1 ± 4.3 g/l , P < .001 ) , and bladder irrigation ( 2.4 ± 1.0 days vs 4.3 ± 1.1 days , P < .001 ) , catheterization time ( 3.3 ± 1.1 days vs 6.2 ± 1.3 days , P < .001 ) , and hospital stay ( 5.4 ± 1.2 days vs 9.3 ± 1.1 days , P < .001 ) were significantly shorter in the PKEP group . Effects on erectile function were similar in both groups , but adverse events were less frequent in the PKEP group . CONCLUSION PKEP can be performed safely and is an equally effective procedure for treatment of large BPH with OP , with minimal complications and faster postoperative recovery . The PKEP helps to reduce the morbidity associated with OP and may become the attractive alternative to OP for patients with large BPH PURPOSE We compared the safety and efficacy of diode laser enucleation of the prostate ( DiLEP ) with plasmakinetic enucleation and resection of the prostate ( PKERP ) . PATIENTS AND METHODS A total of 80 patients with bladder outflow obstruction from benign prostatic hyperplasia ( BPH ) were r and omly assigned to either DiLEP or PKERP prospect ively . All patients were assessed preoperatively and followed up at 3 , 6 , and 12 months postoperatively . Baseline characteristics of the patients , perioperative data , and postoperative outcomes were compared . The operative data and perioperative and postoperative complications were also recorded . RESULTS The preoperative data were comparable between the two groups . The DiLEP group had significantly shorter operative time , postoperative irrigation , time and catheterization time than the PKERP group ( P=0.000 , P=0.000 and P=0.000 ) . The drop in hemoglobin level was statistically significantly less in the DiLEP group ( P=0.002 ) . There were no statistical differences in complications between the two groups except irritative symptoms ( P=0.018 ) . At the 3 , 6 , and 12-month follow-up , no statistically significant differences were observed between the two groups in International Prostate Symptom Score , maximum flow rate , quality of life , postvoid residual , prostate volume , and prostate-specific antigen level ( P>0.05 ) . CONCLUSIONS The efficacy of DiLEP and PKERP were similar for relieving obstruction and low urinary tract symptoms . DiLEP provides less risk of hemorrhage , reduced bladder irrigation , and catheter times . The downward morcellation technique is more efficient than the resection technique . Future well design ed r and omized trials with extended follow-up and larger sample sizes may be needed to better verify the advantage of DiLEP in treating patients with symptomatic BPH BACKGROUND AND PURPOSE Today , urologists around the world are encountering greater numbers of larger prostate gl and s , probably because of an initial trial of pharmacotherapy . The present study was performed to assess the safety and efficacy of bipolar transurethral resection of large prostate gl and s using the PlasmaKinetic ( PK ) Superpulse System . PATIENTS AND METHODS This single-blind , r and omized study included 70 patients with prostate gl and > 60 g seen on three-dimensional transrectal ultrasonography . Patients were r and omized 1:1 using envelopes into either a PK Superpulse transurethral resection of the prostate ( TURP ) group or conventional TURP group , and underwent the procedure accordingly . Perioperative and postoperative parameters included operative time , blood loss , need for blood transfusion , clinical transurethral resection ( TUR ) syndrome , and duration of catheterization and hospitalization . Of 70 patients , 67 were followed for a minimum of 9 months , and data were analyzed using SPSS software . RESULTS Both groups were comparable in terms of preoperative parameters , which included American Urological Association Symptom Score , Qmax , gl and size , and postvoid residual . A statistically significant difference between the two groups was found in terms of perioperative blood loss , change in serum sodium , and duration of catheterization . These complications were significantly less in the PK Superpulse group , with an obvious reduction in the duration of hospitalization in that group . CONCLUSION The PK Superpulse System can be used as safely and effectively in the resection of the large gl and ( > 60 g ) as it has been reported to be in the resection of small and medium-sized gl and s. By using physiologic saline ( 0.9 % NaCl ) as irrigation fluid , it eliminates any danger of TUR syndrome and thus eliminates the conventional time limit of resection . PK Superpulse TURP is a promising treatment modality in the management of large prostate gl and s. It has all the features of gold-st and ard monopolar TURP , along with added safety and efficacy . It is ready to be included in the urologist 's armamentarium Objectives : A prospect i ve r and omized study was conducted to evaluate the safety and effectiveness of bipolar plasma vaporization with a novel electrode that produces vaporization of the tissue ( transurethral vaporization of the prostate , TUVP ) immersed in isotonic saline compared to the st and ard transurethral resection of the prostate ( TURP ) in the treatment of benign prostatic hyperplasia ( BPH ) . Patients and Methods : From February 2009 to February 2010 , 90 patients with BPH were r and omized into two groups , and underwent conventional TURP ( group 1 ) or TUVP ( group 2 ) utilizing bipolar plasma vaporization with an innovative electrode ( Olympus Winter & Ibe GmbH , Hamburg , Germany ) . International Prostate Symptom Scores ( IPSS ) , transrectal ultrasonographic findings , maximal urine flow rates ( Qmax ) , and postvoiding residual urine ( PVRU ) volumes of all cases were evaluated preoperatively and 1 month , 3 months , and 1 year postoperatively . Preoperative and postoperative serum hemoglobin , hematocrit and sodium concentrations of all patients were measured . All patients included in the study were monitored for 1 year . Results : In patients in group 1 ( n = 47 ; mean age : 64.7 ± 7.3 years ) TURP was performed . The patients in group 2 ( n = 43 ; mean age : 65.4 ± 8.9 years ) underwent bipolar TUVP . Cases in the two study groups matched for demographic characteristics and clinical parameters were assessed . The evaluation of IPSS scores , PVRU , Qmax , and prostatic volumes of the patients 1 month , 3 months , and 1 year postoperatively did not reveal any significant differences between the two groups . In group 2 ( TUVP ) , postoperative catheter indwelling times were significantly shorter , and Na serum concentrations were also markedly lower ( p < 0.005 ) . Conclusion : We detected similar effectiveness and morbidity rates in both groups . Bipolar TUVP has advantages such as shorter catheter indwelling times and hospital stays , and fewer bleeding episodes without any risk of transurethral resection syndrome . We believe that TUVP might be an alternative to TURP which is currently the ‘ gold st and ard ’ treatment in BPH PURPOSE We compared st and ard transurethral prostate resection with bipolar PlasmaKinetic prostate vaporization for bladder outflow obstruction using a Gyrus PlasmaKinetic Plasma V bar . MATERIAL S AND METHODS A total of 160 men were enrolled in a prospect i ve , r and omized trial . Those at higher risk for cancer were excluded by prostate specific antigen and digital rectal examination with or without transrectal ultrasound biopsy . A total of 81 men underwent prostate vaporization and 79 underwent transurethral prostate resection . Preoperative International Prostate Symptom Score and quality of life score , uroflowmetry , post-void residual urine and transrectal ultrasound prostate volume were recorded . Preoperative and postoperative serum hemoglobin , hematocrit and sodium were measured . Perioperative fluid absorption was calculated using weighing on table and blood loss using the Hemocue system . Longer followup of International Prostate Symptom Score and quality of life score , uroflowmetry and post-void residual urine was available in 149 men , including 76 who underwent prostate vaporization and 73 who underwent transurethral prostate resection . Data were analyzed using the 1 or 2- sample t and chi-square tests . RESULTS The 2 groups were comparable in all preoperative parameters . Perioperative fluid absorption , intraoperative blood loss , preoperative and postoperative serum hematocrit , and sodium changes were not statistically different . Mean resection time was 4 minutes shorter for transurethral prostate resection ( 28.5 vs 32.6 minutes , p = 0.08 ) . Patients with transurethral prostate resection showed a greater hemoglobin decrease ( 1.39 vs 0.8 gm/dl , p = 0.002 ) and required more irrigation postoperatively ( 28.3 vs 20.4 l , p = 0.001 ) . Four patients with transurethral prostate resection required transfusion compared with none who underwent prostate vaporization . After transurethral prostate resection hospital stay was longer ( 3.36 vs 3.02 days , p = 0.03 ) . Cancer was detected in 8 patients with transurethral prostate resection ( 10 % ) , of whom 7 are under prostate specific antigen surveillance and 1 received radical radiotherapy . Mean long-term followup was 258 days ( range 82 to 884 ) . Prostate vaporization and transurethral prostate resection were equally effective at followup , as evidence d by changes in maximum urine flow , International Prostate Symptom Score , quality of life score and post-void residual urine . CONCLUSIONS The 2 operations are highly effective in experienced h and s. PlasmaKinetic prostate vaporization result ed in less postoperative bleeding and a slightly shorter hospital stay . The lack of a histological specimen with this version of PlasmaKinetic prostate vaporization may mean that clinical ly significant cancers are missed Introduction : This r and omized prospect i ve study was conducted to compare the efficacy and safety of the Gyrus Plasmasect loop bipolar transurethral resection of prostate ( TURP ) and conventional monopolar TURP in the treatment of benign prostatic hyperplasia ( BPH ) . Material s and Methods : A total of 117 men were enrolled in this study . Fifty-eight patients underwent Gyrus Plasmasect TURP and 59 patients underwent monopolar TURP . They were followed up for 3 months after surgery . Results : Significant improvements were seen postoperatively in both the Gyrus and monopolar groups in terms of prostatic volume , International Prostate Symptom Score , quality of life score , peak flow rate , and post-void residual urine volume . However , the degree of improvement was not statistically different between the 2 groups . Significantly less blood loss , shorter postoperative catheterization time and length of hospital stay were seen in the Gyrus group . Conclusions : Gyrus Plasmasect TURP yielded comparable results to monopolar TURP ; however , this is only a preliminary study and follow-up is necessary to assess its long-term efficacy PURPOSE To compare the efficacy and safety of the PlasmaKinetic ( PK ) Superpulse system with that of conventional transurethral resection of the prostate ( TURP ) in terms of restoration of urinary flow and early postoperative course . PATIENTS AND METHODS One hundred five men older than 45 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia ( BPH ) were r and omized , 51 undergoing st and ard TURP with glycine as the irrigation fluid and 53 TURP with the PK Superpulse system with normal saline as irrigant . The operative time , intraoperative blood loss , catheter time , change in serum electrolytes ( particularly sodium ) , and uroflowmetry and American Urological Association ( AUA ) Symptom Scores were compared . RESULTS The blood loss as well as the catheter time observed in the PK Superpulse arm were significantly less than those in the conventional-TURP arm . The mortality rate was 0 in both the arms . The mean operative time was less in the PK Superpulse arm , although not significantly so . Hyponatremia was statistically insignificant . Significant changes were observed in the AUA Scores in both arms . CONCLUSION The PK Superpulse system provides faster removal of tissue in a bloodless field with better views and a safer environment of saline irrigation with efficacy comparable to that of conventional TURP . However , further r and omized trials with extended follow-up may be needed to better define the role of the PK Superpulse system in treating patients with symptomatic BPH INTRODUCTION This was a prospect i ve , r and omized clinical trial to compare the safety , efficacy , and medium-term durability of holmium laser enucleation of the prostate ( HoLEP ) combined with mechanical morcellation versus st and ard transurethral resection of the prostate ( TURP ) for the surgical treatment of patients with bladder outlet obstruction due to benign prostatic hyperplasia ( BPH ) . The patients had prostates that were greater than 30 g and less than 100 g and were followed for 1 year . PATIENTS AND METHODS From April 2008 to December 2009 , 80 consecutive patients with lower urinary tract obstruction ( LUTS ) due to BPH were r and omized to either surgical treatment with HoLEP ( group 1 , n = 40 ) or st and ard TURP ( group 2 , n = 40 ) . Preoperative assessment s included American Urological Association ( AUA ) symptom score , serum prostate-specific antigen ( PSA ) , post-voiding residual ( PVR ) urine volume , transrectal ultrasound ( TRUS ) , and urodynamic studies . Perioperative parameters included total operating time , resected tissue weight , hemoglobin loss , presence or absence of blood transfusion , time of catheter removal , and duration of hospital stay . Postoperative evaluations were conducted at 1 , 6 , and 12 months . RESULTS Patients in the HoLEP group had shorter catheterization times and hospital stays than patients in the TURP group . There was no significant difference in operating times between the two groups . Mean hemoglobin loss was lower in the HoLEP group ( 1.8 ± 1.3 g/dL versus 2.9 ± 1.5 g/dL ) . There was a significantly greater improvement from baseline AUA symptom scores and PVR urine volumes in the HoLEP group versus the TURP group , at all postoperative assessment s. Postoperatively , 25 % of patients in group 1 ( HoLEP ) and 20 % of patients in group 2 ( TURP ) had irritative voiding symptoms . Urethral stricture occurred in three cases ( one case in the HoLEP group and two cases in the TURP group ) . CONCLUSION HoLEP proved to be a safe and highly effective technique for surgical treatment of bladder outlet obstruction due to BPH PURPOSE The first prospect i ve r and omized study to compare the safety and short-term efficacy of monopolar transurethral resection of the prostate ( TURP ) , bipolar TURP , and photoselective vaporization of the prostate ( PVP ) using GreenLight high-performance system 120W laser in patients who presented with benign prostatic obstruction ( BPO ) . PATIENTS AND METHODS The 186 consecutive patients who presented with BPO and who were planned for surgery were r and omized into three groups : Group A , patients who underwent monopolar TURP ; group B , patients who underwent bipolar TURP ; and group C , patients who underwent PVP . All three groups were subdivided into two subgroups based on prostate volume : Subgroup 1 > 20 cc and < 50 cc , and subgroup 2 , between 50 and 80 cc . Patients preoperative , perioperative , and follow-up data were recorded and analyzed . RESULTS The baseline characteristics of the three groups and subgroups 1 and 2 were comparable . The number of patients in whom postoperative irrigation was instituted , amount of fluid used for postoperative irrigation , duration of postoperative irrigation , postoperative hemoglobin concentration , and duration of catheterization were significantly in favor of group C patients except for the mean operative time , which was significantly longer among them . All three groups demonstrated an increase in International Prostate Symptom Score , quality of life score , and maximum flow rate and decrease in prostate volume and postvoid residual urine at 12-month follow-up . The mean Intgernational Index of Erectile Function-5 score did not show improvement in any group . The need for blood transfusion and clot retention necessitating intervention were significantly lower among group C patients compared with group A , whereas these values for group B patients did not reach significant level compared with either group A or C. These complications were comparable among subgroup 1 patients , whereas subgroup 2 patients had shown results in favor of subgroup C2 . CONCLUSION Monopolar TURP , bipolar TURP , and PVP are equally efficacious at 12-month follow-up . PVP has added advantages of lesser blood loss , lesser need for blood transfusion ( especially for prostate volume 50 - 80 cc ) , and shorter catheterization time BACKGROUND No data have been published on the midterm efficacy of bipolar transurethral resection of the prostate ( TURP ) . OBJECTIVE To evaluate 4-yr results from a prospect i ve r and omised trial comparing bipolar TURP with st and ard monopolar TURP . DESIGN , SETTING , AND PARTICIPANTS Seventy patients with symptomatic benign prostatic hyperplasia were enrolled in this prospect i ve r and omised controlled trial in a tertiary-care institution . Inclusion criteria were age > 50 yr , good performance status , urinary retention , International Prostate Symptom Score ( IPSS ) > or = 18 , and maximal flow rate ( Q(max ) ) < or = 15 ml/s . Exclusion criteria were prostate volume < 30 cm(3 ) , documented or suspected prostate cancer , neurogenic bladder , bladder stone or diverticula , urethral stricture , and maximal bladder capacity > 500 ml . INTERVENTION Patients underwent st and ard or bipolar plasmakinetic TURP performed by the same surgeon using the same surgical technique . MEASUREMENTS Treatment efficacy was evaluated at 1 , 2 , 3 , and 4 yr by comparing urinary flow rates , IPSS , and estimated postvoid residual ( PVR ) urine volume . Midterm complications were also recorded . RESULTS AND LIMITATIONS The number of dropouts was not statistically significantly different in the two groups ( p=0.2 ) . The significant improvements in both groups were maintained at 4 yr for the IPSS , quality of life score , Q(max ) , and PVR versus baseline values . The main outcome variables at 4 yr for bipolar and monopolar TURP were mean IPSS 6.9 and 6.4 ( p=0.58 ) ; mean Q(max ) 19.8 ml/s and 21.2 ml/s ( p=0.44 ) , and mean PVR volume 42 ml and 45 ml ( p=0.3 ) . Overall , 2 of 32 ( 6.2 % ) and 3 of 31 ( 9.6 % ) patients required reoperation because of late complications ( p=0.15 ) . The major study limitation was the small sample size . CONCLUSIONS This study represents the secondary , midterm analysis of a previously published trial . Our 4-yr data confirm our initial positive findings for the efficacy and safety of bipolar plasmakinetic TURP . Larger well- design ed studies are needed to corroborate these findings OBJECTIVE To investigate the hemostatic capability of mono- and bipolar transurethral resection of the prostate by comparing the perioperative blood loss with the coagulation depth achieved with mono- and bipolar transurethral resection of the prostate . METHODS A total of 136 patients with lower urinary tract symptoms associated with benign prostatic hyperplasia were r and omized to undergo transurethral resection of the prostate using either a monopolar system ( Karl Storz , Co. , Tuttlingen , Germany ) or a gyrus PlasmaKinetic bipolar system ( Gyrus-ACMI Corporation , Maple Grove , MN ) . The operative time , resected tissue weight , decline in serum sodium and hemoglobin , postoperative bleeding , and the coagulation depth were compared . RESULTS There were no statistically significant differences in operative time , resected tissue weight , and capsular perforation . The decline in hemoglobin and serum sodium was 1.15 ± 0.53 g/dL and 4.57 ± 0.71 mmol/L in monopolar transurethral resection of the prostate group , respectively , whereas they fell only 0.71 ± 0.42 g/dL and 2.02 ± 0.53 mmol/L in the bipolar transurethral resection of the prostate group , respectively ( P < .001 ) . The rate of postoperative bleeding was significantly higher in the monopolar transurethral resection of the prostate group ( P = .027 ) . The coagulation depths with mono- and bipolar transurethral resection of the prostate were 127.56 ± 27.76 and 148.48 ± 31.64 μm , respectively ( P < .001 ) . CONCLUSION Our results demonstrate that bipolar transurethral resection of the prostate causes less intraoperative hemoglobin drop and postoperative bleeding than monopolar transurethral resection of the prostate , which may be associated with the deeper coagulation depth of bipolar transurethral resection of the prostate BACKGROUND AND PURPOSE Transurethral resection of prostate ( TURP ) using bipolar electrocautery and physiologic saline is a new technical advancement in the field of surgical management of benign prostatic hyperplasia . The purpose of this study was to assess the efficacy and safety of this new technique and to compare the results with those of conventional monopolar TURP . PATIENTS AND METHODS This study included 60 patients who were r and omized 1:1 to bipolar ( group 1 ) or monopolar ( group 2 ) TURP . Bipolar TURP was performed with the Vista CTR resectoscope and generator ( ACMI Corp. ) . Preoperatively , patients were assessed by symptom score , uroflow , and transrectal sonography , and the two groups were comparable with regard to these measures and age . The preoperative and postoperative parameters studied included resection time , amount of tissue resected , irrigant amount , blood loss , fluid absorption , and change in serum sodium and hemoglobin . Postoperatively , patients were assessed for symptoms , symptom score , and uroflow rate at 1 and 3 months . RESULTS There was no difference in resected tissue amount , irrigant amount , fluid absorption , duration and amount of postoperative irrigation , or fall in hemoglobin . The mean resection rate was 0.61 g/min in group 1 and 0.74 g/min in group 2 . Serum Na dropped by 4.6 Eq/L in group 2 , whereas it fell only 1.2 mEq/L in group 1 ( P < 0.001 ) . Improvement in symptom and QoL scores and Q(max ) were similar in the two groups . Postoperative dysuria was less common with bipolar resection . CONCLUSION Bipolar resection of the prostate is as effective as monopolar TURP . Moreover , it does not lead to any change in serum Na and causes less postoperative dysuria OBJECTIVE Thulium laser resection of the prostate-tangerine technique ( TmLRP-TT ) is a transurethral procedure that uses thulium laser fiber to dissect whole prostatic lobes off the surgical capsule , similar to peeling a tangerine . To our knowledge we report the first prospect i ve , r and omized study comparing TmLRP-TT and st and ard TURP for symptomatic BPH . METHODS From November 2004 to December 2005 , 100 consecutive BPH patients were r and omized for surgical treatment with TmLRP-TT ( n=52 ) or TURP ( n=48 ) . All patients were preoperatively assessed with subjective symptoms score , International Index of Erectile Function question naire , and complete urodynamic evaluation . Preoperative and perioperative parameters at 1- , 6- , and 12-mo follow-up were also evaluated . All complications were recorded . RESULTS TmLRP-TT was significantly superior to TURP in terms of catheterization time ( 45.7+/-25.8h vs. 87.4+/-33.8h , p<0.0001 ) , hospital stay ( 115.1+/-25.5h vs. 161.1+/-33.8h , p<0.0001 ) , and drop in hemoglobin ( 0.92+/-0.82 g/dl vs. 1.46+/-0.65 g/dl , p<0.001 ) , whereas it required equivalent time to perform ( 46.3+/-16.2 vs. 50.4+/-20.7 min , p>0.05 ) . TmLRP-TT and TURP result ed in a significant improvement from baseline in terms of subjective symptoms scoring and urodynamic finding , but no significant difference was found between the two groups . Late complications were also comparable . CONCLUSIONS TmLRP-TT is an almost bloodless procedure with high efficacy and little perioperative morbidity . TmLRP-TT is superior to TURP in safety and is as efficacious as TURP in 1-yr follow-up . It is a promising technology in the clinical practice field BACKGROUND Evidence supporting the widespread use of GreenLight High Performance System ( HPS ) 120-W photoselective vaporization of the prostate ( PVP ) is lacking . OBJECTIVE To assess the noninferiority of PVP compared with transurethral resection of the prostate ( TURP ) on urinary symptoms and the superiority of PVP over TURP on length of hospital stay . DESIGN , SETTING , AND PARTICIPANTS A multicenter r and omized controlled trial was conducted . INTERVENTION Patients underwent monopolar TURP or PVP with the GreenLight HPS 120-W laser . MEASUREMENTS International Prostate Symptom Score ( IPSS ) , Euro-QOL question naire , uroflowmetry , Danish Prostate Symptom Score Sexual Function Question naire , sexual satisfaction , and adverse events were collected at 1 , 3 , 6 , and 12 mo . The two groups were compared using the 95 % confidence interval ( CI ) of median difference for testing noninferiority of the IPSS at 12 mo and the student t test for testing the difference in length of hospital stay . RESULTS AND LIMITATIONS A total of 139 patients ( 70 vs 69 men in each group ) were r and omized . Median IPSS scores at 12-mo follow-up were 5 ( interquartile range [ IQR ] : 3 - 8 ) for TURP versus 6 ( IQR : 3 - 9 ) for PVP , and the 95 % CI of the difference of the median was equal to -2 to 3 . Because the upper limit of the 95 % CI was > 2 ( the noninferiority margin ) , the hypothesis of noninferiority could not be considered demonstrated . Median length of stay was significantly shorter in the PVP group than in the TURP group , with a median of 1 ( IQR : 1 - 2 ) versus 2.5 ( IQR : 2 - 3.5 ) , respectively ( p<0.0001 ) . Uroflowmetry parameters and complications were comparable in both groups . Sexual outcomes were slightly better in the PVP group without reaching statistical significance . CONCLUSIONS The present study failed to demonstrate the noninferiority of 120-W GreenLight PVP versus TURP on prostate symptoms at 1 yr but showed that PVP was associated with a shorter length of stay in the hospital . TRIAL REGISTRATION NCT01043588 OBJECTIVE Transurethral resection of the prostate ( TURP ) is the current optimal thera- py for the relief of bladder outflow obstruction , with subjective and objective success rate of 85 to 90 % . Aim of this study was to evaluate efficacy and safety of Plasmakinetic ener- gy ( Gyrus electro surgical system ) , which produces vaporization of tissue immersed in isotonic saline against st and ard monopolar transurethral resection of the prostate . METHODS From January 2002 to April 2002 , 160 consecutive patients , who had low urinary tract symptoms ( LUTS ) of benign prostatic hyperplasia ( BPH ) were enrolled in this study . Patients were r and omised to undergo bipolar TURP ( 80 patients ) or monopolar TURP ( 80 patients ) . Preoperative work-up was assessed by administering IPSS , IIEF-5 and Qol question naires . All patients were su bmi tted to uroflowmetry , transrectal ultrasound ( TRUS ) , post-voidal residual urine measurement and PSA determination . In the two groups , IPSS , IIEF-5 and Qol , uroflowme- try , TRUS , post-voidal residual urine measurement , PSA determination and number of reopera- tions were evaluated at 1 , 3 , 6 , 12 , 18 , 24 , 30 and 36 months follow up , and then every year . Furthermore , in both groups operative time , resected tissue weight and perioperative complica- tions were analysed . Total postoperative catheter time , total post-operative hospital stay , haemo- globin loss were also recorded in the two groups . RESULTS Comparative data on IPSS symptom score , IIEF-5 , Qol , PSA , peak urinary flow rate and post-void residual urine volume were similar in the two groups but showed a significant improve- ment respect to baseline values . The postoperative haemoglobin levels , postoperative catheteri- zation time , hospital stay and 3-year overall surgical re-treatment-free rate were significantly better in the bipolar group . CONCLUSIONS Bipolar TURP has a comparable outcome to st and ard monopolar TURP at short and medium term regard to subjective and objective outcome measurements . Its impact on blad- der outlet function is also similar to that of monopolar TURP . Improvement in IPSS , Qol index , IIEF-5 , Qmax and post-void residual urine volume were comparable in both group denoting sim- ilar efficacy of the techniques OBJECTIVES To report 5-year follow-up results of a r and omised clinical trial comparing holmium laser enucleation of the prostate ( HoLEP ) with open prostatectomy ( OP ) . METHODS One hundred twenty patients with prostates greater than 100 g in weight according to transrectal ultrasound were r and omised to either the HoLEP or the OP group ( ie , 60 patients to each group ) . Preoperative and postoperative assessment s included American Urological Association Symptom Score ( AUA-SS ) , maximum urinary flow rates ( Qmax ) , and postvoid residual urine ( PVRU ) volumes . Measurements were performed at 1 , 3 , 6 , 12 , 18 , 24 , 36 , 48 , and 60 mo . Postoperative outcome data were compared . All complications were recorded . RESULTS Five years postoperatively , a total of 46 patients ( 38.3 % ) were lost to follow-up or had to be excluded from the study . All the remaining 74 patients ( 42 HoLEP vs. 32 OP patients , p=0.11 ) had undergone the 5-yr follow-up assessment s. Mean AUA-SS was 3.0 in both groups ( p=0.98 ) , mean Qmax was 24.4 ml/s in both groups ( p=0.97 ) and PVRU volume was 11 ml in the HoLEP and 5 ml in the OP group ( p=0.25 ) . Late complications consisted of urethral strictures and bladder-neck contractures ; reoperation rates were 5 % in the HoLEP and 6.7 % in the OP group ( p=1.0 ) . No patient developed benign prostatic hyperplasia recurrence . CONCLUSIONS Five years after the operation , the improvements in micturition obtained with HoLEP and OP were equally good , and reoperation rates similarly low . HoLEP seems to be a true endourological alternative to OP OBJECTIVES To report our experience with the clinical effectiveness of endoscopic resection of the prostate using the bipolar Gyrus PlasmaKinetic System . METHODS A total of 120 patients with lower urinary tract symptoms were observed from 2002 to 2005 . Of these 120 patients , 90 developed benign prostatic hyperplasia and were considered to have obstruction , and 51 of these 90 were scheduled for prostate surgery . The patients were r and omized 1:1 , using envelopes , into two groups : bipolar transurethral resection of the prostate ( TURP ) using the Gyrus PlasmaKinetic System ( PK group ) and monopolar TURP ( st and ard TURP group ) . All patients were evaluated at baseline and follow-up ( 12 months after treatment ) by medical history , International Prostate Symptom Score , inclusive of the question on quality of life , and physical examination , including digital rectal examination , transrectal ultrasonography , and pressure flow study . Statistical analysis was applied on the change in International Prostate Symptom Score and urodynamic parameters comparing the endpoints with baseline and comparing the baseline and follow-up characteristics between the two groups . RESULTS The mean resection time was 39.1 minutes and 31.7 minutes for the PK and st and ard TURP groups , respectively ( P = 0.437 ) . The mean postoperative hemoglobin reduction at 24 hours of follow-up was 1.25 g/dL , with a 2.1 % hematocrit reduction , in the PK group and 1.81 g/dL , with a 3.2 % hematocrit reduction , in the st and ard TURP group ( P = 0.716 ) . Improvements in flow rate , International Prostate Symptom Score , quality -of-life score , and bladder outlet obstruction grade were comparable between the two groups . CONCLUSIONS Bipolar TURP using the bipolar Gyrus PlasmaKinetic System seems to be a safe and effective procedure that is potentially associated with fewer side effects and could result in this procedure being more attractive for high-risk patients or , as recently proposed , for training purpose PURPOSE We ascertained the safety and efficacy of the 1,318 nm diode Eraser laser ( Rolle and Rolle , Salzburg , Austria ) for transurethral enucleation of the prostate . This laser has been successfully used to resect lung metastasis . It cuts and coagulates vascular rich tissue safely and effectively . We describe a prospect i ve , r and omized trial of Eraser laser prostate enucleation vs bipolar transurethral prostate resection . MATERIAL S AND METHODS A total of 60 patients with lower urinary tract symptoms suggesting bladder outlet obstruction and a mean prostate size of 59.5 ml on transrectal ultrasound were r and omized to Eraser laser prostate enucleation or bipolar transurethral prostate resection . Patients were assessed preoperatively , and 1 and 6 months postoperatively . RESULTS Eraser laser prostate enucleation was equivalent to bipolar transurethral prostate resection in improvement in International Prostate Symptom Score , maximal flow rate and quality of life . Laser enucleation was significantly superior to bipolar transurethral resection for measured blood loss ( mean ± SD 116.83 ± 97.02 vs 409.83 ± 148.61 ml ) , catheter time ( mean 32.80 ± 8.74 vs 65.73 ± 13.72 hours ) and hospital time ( mean 45.13 ± 14.77 vs 91.20 ± 11.76 hours , each p < 0.05 ) . Using the vali date d Clavien-Dindo system there were 3 grade I d and 1 grade II complications . CONCLUSIONS Eraser laser prostate enucleation and bipolar transurethral prostate resection were equally safe and effective to relieve bladder outflow obstruction and lower urinary tract symptoms . This laser technique has the advantage of less blood loss , and shorter catheter time and hospital stay PURPOSE We compared the impact of HoLEP and TURP on sexual function . MATERIAL S AND METHODS Between January 2002 and January 2003 , 120 patients with a mean age + /- SD of 65.2 + /- 7.1 years who had benign prostatic hyperplasia were enrolled in this 2-center , prospect i ve , r and omized study . A total of 60 patients with a mean age of 65.25 + /- 6.9 years underwent HoLEP ( group 1 ) and 60 with a mean age of 64.18 + /- 7.2 years underwent TURP ( group 2 ) . Patients were assessed before surgery , and at 12 and 24-month followup visits . Subjective symptoms were scored by the International Prostate Symptom Score , the International Prostate Symptom Score quality of life question , IIEF , 10 nonvali date d general assessment questions , physical examination , serum prostate specific antigen and transrectal ultrasonography . RESULTS A total of 32 patients ( 53.3 % ) in group 1 and 31 ( 51.6 % ) in group 2 reported various degrees of erectile dysfunction before surgery according to the IIEF-EF score . Differences between preoperative and postoperative orgasmic domain scores in each group were significant ( p < 0.001 ) . A slight but not significant increase in the mean IIEF-EF domain score was reported in each group at postoperative assessment s without any difference between the 2 surgical approaches . According to general assessment question analysis the prevalence of subjectively reported postoperative retro grade ejaculation was significantly higher than at baseline assessment in the 2 groups with no differences between the 2 surgical procedures . CONCLUSIONS TURP and HoLEP significantly lowered the IIEF orgasmic function domain with no differences between techniques . This was caused by retro grade ejaculation . Marginal , nonsignificant erectile function improvement was reported after surgery in the 2 groups Background and Objective : For treatment of benign prostatic hyperplasia ( BPH ) , Plasma Kinetic loop Resection of the Prostate ( PKRP ) is an alternative to conventional monopolar transurethral resection of prostate ( TURP ) . We compared outcomes with the two treatments in a r and omized trial . Patients and Methods : Over a one-year period , we r and omly assigned patients with an indication for surgery for BPH and who met inclusion criteria to treatment with either PKRP or TURP . We measured prostate volume by transrectal ultrasound , relief of bladder outlet obstruction , operative time , decline in serum sodium and hemoglobin , weight of resected prostatic chips , duration of catheterization and hospital stay . Patients were evaluated one month after discharge for obstructive symptoms . Complications were also recorded . Results : Of 102 patients enrolled , 51 underwent PKRP and 51 underwent TURP . Relief of obstructive symptoms and mean operative time showed no statistically significant difference . The PKRP group had a smaller decline in hemoglobin than the TURP group ( 0.6 g/dL vs 1.8 g/dL , P=.01 ) , a lower reduction in serum sodium levels ( 1.03 mmol/L vs 5.01 mmol/L , P=.01 ) , a shorter catheterization time ( 37.2 hours versus 57.7 hours , P=.03 ) and a shorter hospital stay ( 1.5 days versus 2.6 days , P=.02 ) . One patient in the bipolar PKRP group needed recatheterization versus four patients in the TURP group . Conclusion : PKRP reduces morbidity with an outcome similar to conventional monopolar TURP in the treatment of BPH OBJECTIVES To compare transurethral resection of prostate ( TURP ) using monopolar and bipolar transurethral resection in saline ( TURIS ) system . MATERIAL S AND METHODS A prospect ively r and omized study was conducted between January 2004 and January 2005 . Patient demographics and indications for surgery were recorded . The safety end points studied were occurrence of complications and decline in postoperative serum sodium ( Na(+ ) ) and hemoglobin ( Hb ) levels . Efficacy end points were resection time , weight of resected prostate tissue , and improvement in International Prostate Symptoms Score ( IPSS ) and maximum flow rate ( Q(max ) ) in patients ' uroflow over 12 mo . RESULTS One hundred consecutive patients were r and omized and completed the study , with 52 patients in the monopolar TURP group and 48 in the TURIS group . At baseline , the two groups were comparable ; they had at least 12 mo of follow-up . Mean resection time and mean weight of resected prostate tissue were comparable for both groups . Declines in the mean postoperative serum Na(+ ) for TURIS and monopolar TURP groups were 3.2 and 10.7 mmol/l , respectively ( p<0.01 ) . However , there was no statistical difference in the decline in postoperative Hb between the two groups . There were two cases of clinical ly significant transurethral resection syndrome in the monopolar group . Urethral strictures were observed in three cases of TURIS and one patient in the monopolar group . The IPSS and Q(max ) improvements were comparable between the two groups at 12 mo of follow-up . CONCLUSIONS Bipolar TURP using the TURIS system is clinical ly comparable to monopolar TURP at 1 yr with an improved safety profile PURPOSE We compared the perioperative and postoperative characteristics of prostate PlasmaKinetic ™ enucleation and bipolar transurethral resection for large volume benign prostatic hyperplasia . MATERIAL S AND METHODS In this prospect i ve , r and omized , controlled trial 80 patients with benign prostatic hyperplasia and a prostate of larger than 70 ml were r and omly assigned to prostate bipolar transurethral resection or PlasmaKinetic enucleation . Operative time , resected adenoma weight , changes in hemoglobin , catheterization time and postoperative hospital stay were recorded and compared . Patients were followed 1 , 6 , 12 , 24 , 36 , 48 and 60 months after surgery . RESULTS Greater resected prostate weight ( mean ± SD 64.2 ± 19.0 vs 50.6 ± 20.0 gm , p = 0.03 ) , less blood loss ( mean 0.87 ± 0.42 vs 1.74 ± 0.63 gm , p < 0.01 ) , and shorter catheterization time ( mean 35.5 ± 5.8 vs 60.1 ± 5.8 hours , p < 0.01 ) and postoperative hospital stay ( mean 3 vs 4 days , [ corrected ] p < 0.01 ) were recorded in the enucleation group than in the resection group . The postoperative improvement in International Prostate Symptom Score , quality of life , maximal flow rate and post-void residual urine volume was similar in the 2 groups at 1 , 6 , 12 and 24 months but significantly better in the enucleation group at 36 , 48 and 60 months . During the 5-year followup no patient in the enucleation group but 2 in the resection group experienced recurrence . CONCLUSIONS For large volume benign prostatic hyperplasia PlasmaKinetic enucleation of the prostate is associated with less blood loss , shorter hospital stay and catheterization time than bipolar transurethral resection of the prostate . Moreover , PlasmaKinetic enucleation seems to be superior at long-term followup with fewer reoperations necessary PURPOSE The transurethral resection in saline system uses bipolar energy for transurethral prostate resection , thus , avoiding the need for glycine irrigation and its associated complications . We compared the clinical efficacy and safety of bipolar transurethral resection in saline and of monopolar transurethral prostate resection for symptomatic benign prostate hyperplasia . MATERIAL S AND METHODS From January 2005 to June 2006 , 238 consecutive patients with symptomatic benign prostate hyperplasia were r and omized into a prospect i ve , controlled trial comparing the 2 treatment modalities . Patient demographics , operative time , hospital stay and complications were noted . Serum hemoglobin and electrolytes were determined in all patients immediately before and after the endoscopic procedure . RESULTS During 18 months 120 patients were r and omized to the conventional transurethral prostate resection group and 118 were r and omized to the transurethral resection in saline group . Patient profiles , weight of resected prostatic tissue and duration of hospitalization were similar in the 2 groups . The decrease in serum sodium and serum chloride was statistically significantly greater in the transurethral prostate resection group than in the transurethral resection in saline group ( each p = 0.05 ) . The transurethral resection in saline procedure required significantly more time ( mean 56 vs 44 minutes , p < 0.01 ) . There was 1 case ( 0.8 % ) of transurethral resection syndrome in the transurethral prostate resection group but none in the transurethral resection in saline group . Postoperative bleeding did not significantly differ between the 2 groups . Clot retention was observed in 6 ( 5 % ) and 4 patients ( 3 % ) in the transurethral prostate resection and transurethral resection in saline group , respectively . Two repeat interventions were required in the transurethral prostate resection group . CONCLUSIONS The bipolar transurethral resection in saline system is as efficacious as monopolar transurethral prostate resection but it is safer than the latter because of the lesser decrease in postoperative hypernatremia and the smaller risk of transurethral resection syndrome . However , probably due to technical reasons , transurethral resection in saline operative time is significantly longer INTRODUCTION A few studies have investigated the impact of photovaporization of the prostate ( PVP ) on sexual function and were mainly focused on erectile function . AIMS To comprehensively evaluate the impact of PVP on sexual function . METHODS A prospect i ve evaluation involved sexually active patients needing surgical relief of bladder outlet obstruction due to benign prostatic enlargement in a single center between August 2007 and November 2011 . All patients underwent PVP using the GreenLight HPS ™ 120W system ( AmericanMedicalSystems , Minnetonka , MN , USA ) . MAIN OUTCOME MEASURES Patients were evaluated preoperatively and postoperatively by International Prostate Symptom Score ( I-PSS ) , I-PSS question 8 , uroflowmetry parameters ( maximum urinary flow rate [ Qmax ] and postvoid residual [ PVR ] volume ) , Danish Prostate Symptom Score Sexual items ( DAN-PSSsex ) , and overall sexual satisfaction using a seven- grade Likert scale . Operative parameters and postoperative complications were also assessed . Preoperative and postoperative values were compared using the Pearson chi-square test and the Wilcoxon paired test . A multivariable model was used to investigate the determinants of variation of global sexual satisfaction . RESULTS One hundred and two consecutive patients with 12-month follow-up data were included in the analysis . Urinary parameters ( I-PSS , Qmax , and PVR ) were significantly improved compared with preoperative values . Compared with baseline , postoperative erection symptom score was not significantly different , whereas ejaculation symptom score was significantly worse . Global DAN-PSSsex score was unchanged , but DAN-PSSsex symptom score was worse ( P = 0.04 ) and DAN-PSSsex bother score was significantly improved ( P < 0.0001 ) . Global sexual satisfaction was significantly improved compared with baseline ( P = 0.02 ) and was significantly associated with I-PSS but not with erection and ejaculation score in a multivariable model . CONCLUSION Ejaculation is the main sexual function impacted by PVP . Despite this , sexual satisfaction and bother due to sexual symptoms were significantly improved , probably due to the positive impact of urinary symptom relief OBJECTIVES To compare the cost of open transvesical prostatectomy ( OP ) with that of holmium laser enucleation ( HoLEP ) in the treatment of bladder outlet obstruction ( BOO ) attributed to benign prostatic hyperplasia . METHODS From February to May 2004 , 63 consecutive patients with symptomatic benign prostatic hyperplasia in a large prostate ( 70 to 220 g ) and documented BOO were r and omized to surgical treatment with OP ( 29 in group 1 ) or HoLEP ( 34 in group 2 ) . All costs associated with the procedures during the hospital stay were recorded prospect ively , and a cost-effectiveness analysis of the critical perioperative ( ie , intraoperative and postoperative to hospital discharge ) data was performed . RESULTS The cost analysis showed a mean perioperative cost of 2868.9 euros ( 3556.3 dollars ) for group 1 and 2356.5 euros ( 2919.4 dollars ) for group 2 . A direct comparison analysis showed that the most significant cost factors were the operative time ( average 16.1 % and 25.1 % to the cost of OP and HoLEP , respectively ) , operating room surgical setup/disposables , including laser fiber and resectoscope loop in group 2 ( average 13.3 % and 29.3 % to the cost of OP and HoLEP , respectively ) , and length of postoperative hospital stay ( average 53.3 % and 32.0 % to the cost of OP and HoLEP , respectively ) . Overall , the hospitalization cost of HoLEP was 9.6 % less than that for OP . CONCLUSIONS Our data have demonstrated that HoLEP is associated with a significant hospital net cost savings compared with OP in patients undergoing surgery for symptomatic benign prostatic hyperplasia in large gl and The effect of TURP on overall sexual function and particularly erectile function ( EF ) is controversial with conflicting results based on a low level of evidence . The effects of monopolar and bipolar TURP ( M‐TURP and B‐TURP , respectively ) on EF are similar , as has been shown in a few non‐focused r and omized control trials ( RCTs ) . For the first time , the present study offers focused results of a comparative evaluation of the effects of B‐TURP and M‐TURP on overall sexual function , as quantified with the International Index of Erectile Function Question naire ( IIEF‐15 ) in an international , multicentre , double‐blind RCT setting BACKGROUND Pooled data from r and omised controlled trials ( RCTs ) with short-term follow-up have shown a safety advantage for bipolar transurethral resection of the prostate ( B-TURP ) compared with monopolar TURP ( M-TURP ) . However , RCTs with follow-up > 12 mo are scarce . OBJECTIVE To compare the midterm safety/efficacy of B-TURP versus M-TURP . DESIGN , SETTING , AND PARTICIPANTS From July 2006 to June 2009 , TURP c and i date s with benign prostatic obstruction were consecutively recruited in four centres , r and omised 1:1 into the M-TURP or the B-TURP arm and regularly followed up to 36 mo postoperatively . A total of 295 patients were enrolled . INTERVENTION M-TURP or B-TURP using the AUTOCON II 400 electrosurgical unit . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Safety was estimated by complication rates with a special emphasis on urethral strictures ( US ) and bladder neck contractures ( BNCs ) recorded during the short-term ( up to 12 mo ) and midterm ( up to 36 mo ) follow-up . Efficacy quantified by changes in maximum urine flow rate , postvoid residual urine volume , and International Prostate Symptom Score was compared with baseline , and reintervention rates in each arm were also evaluated . RESULTS AND LIMITATIONS A total of 279 patients received treatment after allocation . Mean follow-up was 28.8 mo . A total of 186 of 279 patients ( 66.7 % ) completed the 36-mo follow-up . Posttreatment withdrawal rates did not differ significantly between arms . Safety was assessed in 230 patients ( 82.4 % ) at a mean follow-up of 33.4 mo . Ten US cases were seen in each arm ( M-TURP vs B-TURP : 9.3 % vs 8.2 % ; p=0.959 ) ; two versus eight BNC cases ( M-TURP vs B-TURP : 1.9 % vs 6.6 % ; p=0.108 ) were collectively detected at the midterm follow-up . Resection type was not a significant predictor of the risk of US/BNC formation . Efficacy was similar between arms and durable . A total of 10 of 230 patients ( 4.3 % ) experienced failure to cure and needed reintervention without significant differences between arms . High overall reintervention rates , withdrawal rates , and sample size determination not based on US/BNC rates represent potential limitations . CONCLUSIONS The midterm safety and efficacy of B-TURP and M-TURP are comparable . TRIAL REGISTRATION Netherl and s Trial Register , NTR703 ( http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=703 ) The aim of this study was to compare the clinical results of plasmakinetic resection of the prostate ( PRP ) with st and ard transurethral resection ( TUR ) of the prostate ( TURP ) . A total of 240 patients ( mean age 63.5 ; age range 52–90 years ) , with symptomatic benign prostatic hyperplasia were r and omized into two groups and treated with two different techniques ( TURP and PRP ) . We evaluated pre-operative , per-operative and post-operative ( first and 12th months ) findings of all patients . The mean catheterization time was 3 and 4.5 days in the PRP and st and ard TURP groups , respectively ( P<0.001 ) . We observed the improvements in maximum flow rates in PRP group were significantly higher than TURP group ( P<0.001 ) . TUR of the prostate using plasmakinetic energy seems to be a promising treatment alternative to conventional TURP . It has the advantages of low intraoperative and post-operative complications , short convalescence , excellent intraoperative hemostasis , absence of fluid absorption and TUR syndrome INTRODUCTION Monopolar transurethral resection of the prostate ( TURP ) is the gold st and ard surgical therapy for men with lower urinary tract symptoms due to benign prostatic hyperplasia . Although generally considered safer , TURP experience is limited in Canada . METHODS Forty-three patients from 5 Canadian centres were r and omized to TURP with either bipolar or monopolar platforms . Patients underwent baseline determinations of American Urological Association ( AUA ) symptom score , peak urinary flow rate , post-void residual bladder volume and transrectal ultrasound prostate volume . Primary outcome measures were improvement in AUA symptom score , quality of life assessment and bother assessment . Secondary outcomes included procedural times , duration of catheterization , length of hospitalization , complications and the degree of thermal artifact in tissue specimens . Patients were followed for 6 months . RESULTS Twenty-two patients were treated with bipolar and 21 with monopolar TURP . Preoperative demographics were not statistically different between groups . Postoperative data collection times were equivalent in AUA symptom , quality of life , bother and sexual function assessment s. No differences were observed in the procedure time ( 60.7 min , bipolar vs. 47.4 , monopolar ) or the duration of urethral catheterization ( 1.5 days , bipolar vs. 1.1 , monopolar ) . More patients in the bipolar group were discharged on the same day of surgery . There were no differences in the degree of tissue thermal artifact or complication rate . CONCLUSION This trial suggests equivalent short-term outcomes for men undergoing monopolar or bipolar TURP OBJECTIVES To report 3-yr follow-up results of a r and omised clinical trial comparing holmium laser enucleation of the prostate ( HoLEP ) with transurethral resection of the prostate ( TURP ) . METHODS A total of 200 patients with urodynamic obstruction and a prostate volume of less than 100 cc were prospect ively r and omised and assigned to HoLEP or TURP . All patients were assessed preoperatively and followed at 1 , 6 , 12 , 18 , 24 , and 36 mo postoperatively . American Urological Association Symptom Score ( AUA SS ) , maximum flow rate ( Q(max ) ) , and postvoid residual ( PVR ) [ urine ] volume were obtained at each follow-up . Perioperative data and postoperative outcome were compared . All complications were recorded . RESULTS AUA SS were significantly better 2 yr postoperatively in the HoLEP group ( 1.7 vs. 3.9 , p<0.0001 ) and similar at 3 yr ( 2.7 vs. 3.3 , p=0.17 ) . PVR volume was significantly better 2 yr ( 5.6 vs. 19.9 ml , p<0.001 ) and 3 yr ( 8.4 vs. 20.2 ml , p=0.012 ) postoperatively in HoLEP patients . Q(max ) was similar in the HoLEP and TURP groups at 2 yr ( 28.0 vs. 29.1 ml/s , p=0.83 ) and at 3 yr ( 29.0 vs. 27.5 ml/s , p=0.41 ) postoperatively . Late complications consisted of urethral strictures , bladder-neck contractures , and BPH recurrence ; reoperation rates were 7.2 % in the HoLEP and 6.6 % in the TURP group ( p=1.0 ) . CONCLUSIONS After 2 and 3 yr of follow-up , HoLEP micturition outcomes compare favourably with TURP . Late complications are equally low . HoLEP may be a real alternative to TURP OBJECTIVES To compare the alternative energy sources of the holmium : yttrium-aluminum-garnet laser and bipolar plasmakinetic energy for endoscopic enucleation . METHODS A prospect i ve , r and omized controlled trial was undertaken , with 20 patients assigned to each group . The preoperative and postoperative measures included transrectal ultrasound-assessed prostate volume , postvoid residual urine volume , and urodynamic evaluation findings . The intraoperative measures included procedure length , energy use , and specimen weight . All adverse events were recorded at each postoperative visit in a 1 , 3 , 6 , and 12-month protocol . RESULTS No differences were found in the preoperative characteristics between the two groups . The significant differences favoring holmium laser enucleation of the prostate compared with plasmakinetic enucleation of the prostate were seen in the operative time ( 43.6 versus 60.5 minutes ) , recovery room time ( 47.1 versus 65.6 minutes ) , and bladder irrigation requirement ( 5 % versus 35 % ) . The outcomes after holmium laser enucleation of the prostate and plasmakinetic enucleation of the prostate were in all other respects similar by the postoperative outcome measures assessed . CONCLUSIONS Plasmakinetic enucleation of the prostate is a safe and technically feasible procedure for the enucleation of prostatic adenomata . Plasmakinetic enucleation of the prostate is limited by the longer operative and recovery room times , as well as a more pronounced postoperative irrigation requirement because of reduced visibility and a greater propensity for bleeding . The transfusion rates and catheterization and hospitalization times were similar . The optimal energy source for enucleation should still be considered the holmium laser , but bipolar energy can be considered by users already experienced with holmium laser enucleation of the prostate AIM In our r and omized prospect i ve study , we aim ed to evaluate the efficiency of plasmakinetic resection of prostate ( PKRP ) by comparing the preoperative and postoperative results of the transurethral resection of prostate ( TURP ) and PKRP techniques which we administered in patients with benign prostate hyperplasia ( BPH ) in our clinic . METHODS Of 57 patients for whom we thought an operative intervention was necessary , 30 cases in the first group had a TURP and 24 cases in the second group had a PKRP . International prostate symptom scores ( I-PSS ) , uroflowmetry , measurement of residual urine amount and ultrasonography were performed for each patient both preoperatively and postoperatively ( first month and first year ) . Operation times , urethral catheterization times , preoperative and postoperative Hb , Htc and serum Na values of the patients were compared and the complications of the groups were also compared . RESULTS On first month and first year follow up between the groups , there was no significant statistical difference in I-PSS , maximum flow rate , average flow , residual urine and size of the prostate . The decrease in serum Na level was found to be significantly higher in the TURP group ( P < 0.05 ) . The operation times were not significantly different between the groups . While the postoperative catheterization time was 75.7 h in TURP group , it was found to be 42 h in PKRP group and it was clear that catheterization time was significantly shorter ( P < 0001 ) . CONCLUSION It is obvious that PKRP is as efficient as TURP and it has a similar morbidity . In our opinion , PKRP makes a promising treatment for BPH with its advantages , such as early removal of postoperative urethral catheter , a shorter hospital stay and the absence of TUR syndrome risk OBJECTIVES To characterize the hemodynamics comparing thulium laser vaporesection of the prostate with traditional transurethral resection of the prostate . METHODS A total of 80 consecutive patients with benign prostatic hyperplasia were r and omly assigned into the thulium laser vaporesection of the prostate group or transurethral resection of the prostate group . Transpulmonary thermodilution hemodynamic monitoring was used before and 1 h after surgery to assess patient hemodynamics . Acute complications and treatment efficiency were evaluated after surgery . RESULTS There were no statistical differences in age , prostate volume , anticoagulants and International Prostate Symptom Score between the two groups . The postoperative Stroke Volume Index was significantly higher in the thulium laser vaporesection of the prostate group ( P = 0.007 ) . The extravascular lung water and intrathoracic blood volume indices differed significantly pre- and postoperatively , and were similar in both groups . Decreases in serum sodium and hemoglobin concentrations after surgery were lower in the thulium laser vaporesection of the prostate group ( P < 0.01 ) . Acute complications , and improvements in International Prostate Symptom Score and maximum urinary flow rates , were similar in both groups . CONCLUSIONS Transpulmonary thermodilution hemodynamic monitoring provides additional safety measures during surgical procedures . Thulium laser vaporesection of the prostate is associated with fewer hemodynamic changes and provides similar efficacy to transurethral resection of the prostate . Thus , it can be considered a safe and effective procedure St and ard monopolar transurethral resection of prostate ( TURP ) remains the gold st and ard surgical treatment of benign prostatic hyperplasia‐related lower urinary tract symptoms . Bipolar salin TURP offers rapid tissue removal and haemostasis during resection with better vision under saline irrigation while eliminating risk of TUR syndrome . Few prospect i ve r and omized studies have investigated the effect of bipolar and monopolar TURP on erectile function . The study found that bipolar saline TURP is a safe and effective procedure that is associated with a significantly shorter operating time , a smaller reduction in serum sodium levels and similar efficacy compared with conventional monopolar TURP BACKGROUND AND PURPOSE Holmium enucleation of the prostate ( HoLEP ) has been established as an effective therapy for patients with benign prostatic hyperplasia ( BPH ) , with less bleeding , shorter catheterization time , and shorter hospital stay . The evolution of the bipolar transurethral resection of the prostate ( TURP ) raised a question : Would it be able to provide all the advantages of HoLEP and compensate for all its drawbacks , including the higher costs and the steep learning curve ? PATIENTS AND METHODS A r and omized study was performed that compared HoLEP with bipolar TURP . The study included 60 patients with BPH who were r and omized in two groups ( 1:1 fashion ) . The mean age , International Prostate Symptom Score , serum prostate-specific antigen value , maximum urinary flow rate , residual urine , prostate size , operative time , blood loss , resected volume , catheterization time , hospital stay , and intraoperative and postoperative complications were compared in both groups , with a follow-up period of 6 months postoperatively . RESULTS Both techniques were comparable to each other . They shared the same advantages of decreased perioperative morbidity . The longer operative time in the HoLEP group , however , was still statistically significant . In addition , the expense of performing HoLEP was nearly double that of bipolar TURP . CONCLUSION HoLEP and bipolar TURP are effective in treating patients with lower urinary tract symptoms due to BPH , however ; the long operative time , the steep learning curve , as well as the higher expenses of HoLEP are in favor of bipolar TURP BACKGROUND AND PURPOSE In comparison with monopolar transurethral resection of the prostate ( TURP ) , bipolar TURP has been shown to have similar efficacy and complication profiles . Whether the hybrid technique of bipolar resection and vaporization of the prostate further improves catheterization time , dysuria , and complication profiles has not been defined , however . The objective of this study was to compare the efficacy and safety profile of bipolar hybrid prostate surgery using both resection and vaporization modes , with bipolar resection undertaken using the transurethral resection in saline bipolar system . PATIENTS AND METHODS This was a r and omized controlled trial that compared bipolar hybrid surgery and bipolar resection of the prostate among men aged ≥ 50 years with benign prostatic hyperplasia ( BPH ) whose course of medical therapy had failed or who had recurrent urinary retention ( CUHK_CCT00623 ) . Patients were r and omly assigned to receive either bipolar hybrid surgery or bipolar resection of the prostate . Both patients and assessors were blinded to the type of surgery performed . The primary study end point was catheter time . The secondary end points included postoperative hospital stay and dysuria score . We report the interim results for 86 patients . RESULTS Forty-six patients were in the hybrid group and 40 were in the resection group . There were no differences between the two groups in prostate volumes ( 61.5 cc , st and ard deviation [SD]=34.5 vs 61.0 cc , SD=23.8 ) , preoperative prostate-specific antigen levels ( 8.7 ng/mL , SD=8.5 vs 9.5 ng/mL , SD=8.4 ) , or preoperative retention status ( 56.5 % vs 70 % ) . The mean operative time was 46.2 minutes for the hybrid group ( SD=20.2 ) and 39.2 minutes for the resection group ( SD=17.5 ) . The hybrid group had a significantly shorter postoperative catheter time ( 34.5 h , SD=15.8 vs 44.7 h , SD=24.5 , P=0.027 ) . There was a significant difference between the two groups in the postoperative pain score on day 1 postsurgery ( 3.5 in the hybrid group vs 1.0 in the resection group , P=0.028 ) . There was no difference between the groups in terms of changes in serum hemoglobin and serum sodium levels or the reintervention rate . All patients voided well after operation , with maximal flow improvements of 9.9 mL/s ( SD 8.1 ) and 8.2 mL/s ( SD 10.0 ) for the hybrid and resection groups , respectively , 1 month postsurgery . CONCLUSION Transurethral bipolar resection and vaporization of the prostate reduces catheterization time and facilitates postoperative care |
12,646 | 24,626,286 | Low to moderate grade evidence exists regarding the efficacy of non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy .
Oral anti-inflammatory drugs are effective in reducing short-term pain but not function .
In terms of pain and function , oral anti-inflammatory drugs in the short term are as effective as corticosteroid injections | OBJECTIVE To conduct a systematic review and meta- analysis on the efficacy of oral non-steroidal anti-inflammatory drugs for rotator cuff tendinopathy . | A double-blind , parallel trial of 40 patients with chronic shoulder pain was carried out to compare alleviation of pain and improvement in mobility after treatment with 20 mg piroxicam each morning or 250 mg naproxen twice daily . During the 3-week study , patients also underwent conservative treatment of therapeutic exercise . Piroxicam was better than naproxen at relieving pain at night , but time , rather than a drug effect , seemed responsible for the improvement in shoulder abduction . No difference between the drugs was demonstrated regarding their effect on pain on active movement of the shoulder and external rotation Objectives : To evaluate the short-term symptomatic efficacy of rofecoxib and diclofenac versus placebo in acute episodes of shoulder pain . Design : R and omized controlled trial of 7 days . Setting : Rheumatologists and /or general practitioners totaling 47 . Participants : Acute shoulder pain . Interventions : Rofecoxib 50 mg once daily , diclofenac 50 mg three times daily , and placebo . Outcome measures : Pain , functional impairment , patient 's global assessment of his/her disease activity , and local steroid injection requirement for persistent pain . The primary variable was the Kaplan-Meier estimates of the percentage of patients at day 7 fulfilling the definition of success ( improvement in pain intensity and a low pain level sustained to the end of the 7 days of the study ; log-rank test ) . Results : There was no difference in the baseline characteristics between the three groups ( rofecoxib n = 88 , placebo n = 94 , and diclofenac n = 89 ) . At day 7 , the Kaplan-Meier estimates of successful patients was higher in the treatment groups than in the placebo ( 54 % , 56 % , and 38 % in the diclofenac , rofecoxib , and placebo groups respectively , p = 0.0070 and p = 0.0239 for placebo versus rofecoxib and diclofenac , respectively ) . During the 7 days of the study , there was a statistically significant difference between placebo and both active arms ( rofecoxib and diclofenac ) in all the evaluated outcome measures A local steroid injection had to be performed in 33 ( 35 % ) and 19 ( 22 % ) patients in the placebo and rofecoxib group respectively . Number needed to treat to avoid such rescue therapy was 7 patients ( 95 % confidence interval 5–15 ) . Conclusion : This study highlights the method ological aspects of clinical trials , e.g. , eligibility criteria and outcome measures , in acute painful conditions . The data also establish that diclofenac and rofecoxib are effective therapies for the management of acute painful shoulder and that they reduce the requirement for local steroid injection OBJECTIVE Shoulder tendinitis and subacromial bursitis are acute , painful inflammatory musculoskeletal conditions that may recur as a result of overuse . We investigated the efficacy of celecoxib in managing patients with acute shoulder tendinitis/bursitis . METHODS In this double blind , placebo controlled , parallel group study , patients with acute onset shoulder tendinitis and /or subacromial bursitis were r and omized to receive one of : celecoxib 400 mg followed by 200 mg bid , naproxen 500 mg bid , or placebo bid for 14 days . The primary measure of efficacy was the mean reduction in Maximum Pain Intensity at Rest , measured using a 100 mm visual analog scale , from baseline to Days 7 and 14 . RESULTS Of the 306 patients r and omized to treatment , 254 completed the study . On Day 7 , the mean reduction from baseline in Maximum Pain Intensity at Rest was significantly greater in the celecoxib group compared with the placebo group ( -27.7 + /- 2.75 mm vs -18.4 + /- 2.63 mm , respectively ; p < 0.05 ) . Similarly , on Day 14 , the mean reduction from baseline in Maximum Pain Intensity at Rest was greater in the celecoxib group compared with placebo ( -35.0 + /- 3.06 mm vs -25.0 + /- 3.05 mm ; p < 0.05 ) . The mean reduction from baseline in Maximum Pain Intensity at Rest was also greater in the naproxen group compared with the placebo group at Day 7 ( -26.4 + /- 2.70 mm vs -18.4 + /- 2.63 mm ; p < 0.05 ) , but not on Day 14 . Secondary measures of efficacy also showed treatment with celecoxib to be significantly better than placebo treatment and similar to treatment with naproxen . In addition , celecoxib was well tolerated in these patients . CONCLUSION Celecoxib showed comparable efficacy to naproxen in relieving the pain of patients with acute shoulder tendinitis and /or subacromial bursitis Using a prospect i ve , double blind , double dummy protocol , we compared the efficacy of subacromial injection of 40 mg of triamcinalone acetonide versus oral indomethacin , 100 mg/day , in 40 patients with acute rotator cuff tendinitis . Repeat injection and refill of medication was given after 3 weeks , if necessary . At 6 weeks , there was no significant difference between the 2 groups with respect to the percentage of patients who improved ( 60 vs 66 % ) or the magnitude of the change of pain and motion variables . This study suggests that there is essentially no difference in the short term efficacy of oral nonsteroidal therapy compared to local corticosteroid injection(s ) in the treatment of rotator cuff tendinitis Background Tendon injuries that occur at the osteotendinous junction are commonly seen in clinical practice and range from acute strain to rupture . Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of these conditions , but the effect that these agents may have on the healing response at the bone-tendon junction is unclear . Hypothesis In response to an acute injury at the osteotendinous junction , the healing patellar tendon will have inferior biomechanical properties with administration of anti-inflammatory drugs as compared with acetaminophen and control . Study Design Controlled laboratory study . Methods A total of 215 Sprague-Dawley rats underwent transection of the patellar tendon at the inferior pole of the patella , which was subsequently stabilized with a cerclage suture . The animals were then r and omized into 7 groups and administered 1 of the following analgesics for 14 days ibuprofen , acetaminophen , naproxen , piroxicam , celecoxib , valdecoxib , or control . At 14 days , all animals were sacrificed , and the extensor mechanism was isolated and loaded to failure . Biochemical analysis of the repair site tissue was performed . Animal activity throughout the study was monitored using a photoelectric sensor system . Results The control group demonstrated greater maximum load compared with the celecoxib , valdecoxib , and piroxicam groups ( P < .05 ) . The acetaminophen and ibuprofen groups were also significantly stronger than the celecoxib group ( P < .05 ) but not statistically different than the control group . A total of 23 specimens had failure of the cerclage suture with the following distribution control ( 0/23 ) , ibuprofen ( 0/23 ) , acetaminophen ( 0/24 ) , naproxen ( 3/24 ) , piroxicam ( 4/24 ) , celecoxib ( 6/22 ) , and valdecoxib ( 10/24 ) . The difference in distribution of the failures was significant ( P < .001 ) . Conclusions Anti-inflammatory drugs , with the exception of ibuprofen , had a detrimental effect on healing strength at the bone-tendon junction as demonstrated by decreased failure loads and increased failures of the cerclage suture . Acetaminophen had no effect on healing strength . The biomechanical properties paralleled closely with the total collagen content at the injury site , suggesting that these agents may alter healing strength by decreasing collagen content . Clinical Relevance Selective and nonselective cyclooxygenase ( COX ) inhibitors should be used judiciously in the acute period after injury or surgical repair at the bone-tendon junction This study compared the analgesic efficacy and safety of the cyclo-oxygenase-2 specific inhibitor celecoxib with the non-specific non-steroidal anti-inflammatory drug , naproxen , in patients with acute shoulder pain . Adult patients with shoulder pain , onset within the previous 14 days and shoulder pain of ≥ 40 mm on a 100 mm visual analogue scale ( VAS ) , were treated with oral doses of celecoxib or naproxen for 14 days and followed by a visit at day 42 in a double-blind , r and omized study . The primary efficacy assessment was change in maximum pain at rest on a 100 mm VAS at day 14 compared with baseline . In addition , secondary efficacy pain and functional assessment s were analysed at baseline , day 14 and day 42 . A total of 202 patients were included in the trial ( 99 celecoxib 400 mg/day ; 103 naproxen 1 g/day ) . The difference in change from baseline at day 14 in maximum pain at rest was not statistically significant between the two treatment groups , but was numerically higher for celecoxib than for naproxen ( −47.9 ± 2.5 versus −42.3 ± 2.5 , respectively ) . According to the limits of the 95 % confidence interval of the difference between groups ( −12.52 ; 1.38 ) , celecoxib appeared to be at least as effective as naproxen . All secondary efficacy measures followed the same pattern , showing similarity between the two treatments with a trend in favour of celecoxib . The incidences of adverse events were similar for both groups . Fewer patients experienced epigastric pain with celecoxib ( seven patients versus 14 with naproxen ) . This adverse event led to discontinuation in two patients receiving celecoxib and five receiving naproxen . Celecoxib 400 mg/day was at least as effective as naproxen 1 g/day in managing pain in this condition 30 patients with supraspinatus or bicipital tendonitis were r and omly allocated to active infrared laser therapy at 904 nm three times weekly for 2 weeks , dummy laser or drug treatment for 2 weeks . Objective ly maximum active extension , flexion and abduction of the shoulder , and subjectively pain stiffness movement and function were measured at 0 and 2 weeks . Significant improvement of active over dummy laser was noted for all seven assessment s. Active laser therapy produced significant improvement over drug therapy for all three objective measures and pain . Naproxen sodium significantly improved only movement and function compared to dummy laser . These results demonstrate the effectiveness of laser therapy in tendonitis of the shoulder Summary This was a double-blind study design ed to compare the efficacy and tolerability of diclofenac/misoprostol and diclofenac in patients with acute tendinitis/bursitis of the shoulder . Diclofenac 50mg/misoprostol 200μg ( n=185 ) or diclofenac 50 mg ( n=187 ) was administered twice or 3 times daily for 14 days . Various physician ’s and patient ’s assessment s performed during and at the end of treatment showed similar improvements with both treatments . Abdominal pain , nausea and vomiting occurred somewhat more frequently with diclofenac/misoprostol , but patient withdrawals due to adverse events did not differ markedly between the groups . Thus , in the short term treatment of acute tendinitis/bursitis of the shoulder diclofenac/misoprostol possesses efficacy similar to that with diclofenac alone and provides the gastroprotective benefit of misoprostol . Previous studies in Osteoarthritis and rheumatoid arthritis have established diclofenac/misoprostol to be as effective as diclofenac but with significantly less gastrointestinal damage ( Verdickt et al. 1992 The effect of triamcinolone subacromial bursa injection versus naproxen therapy was compared in a r and omized , double-blind , placebo-controlled study of 100 patients who had painful shoulders . Outcome was compared using degree of active abduction , pain , limitation of function , and a clinical index that combined equally weighted measures of all of these . In a time-adjusted analysis , triamcinolone was superior to placebo in all clinical variables . Naproxen was superior to placebo in all variables except pain . Triamcinolone was superior to naproxen in the relief of pain ( P = 0.04 ) and the clinical index ( P = 0.04 ) . Multiple linear regression analysis showed that naproxen and triamcinolone treatment accounted for only 16 % of the variation in outcome , compared with 44 % accounted for by the clinical index prior to treatment . Thus , patients with a poor pretreatment clinical index ( those with the most room for improvement ) were least likely to improve . We conclude that both triamcinolone ( P = 0.00005 ) and naproxen ( P = 0.02 ) are superior to placebo in the treatment of the painful shoulder Summary In order to compare the efficacy and tolerance of two drug formulations of ibuuprofen , conventional tablets 600 mg QID ( CI ) and sustained-release tablets 1200 mg BID ( SRI ) , a total of 147 patients in 7 centres in Denmark with nontraumatic shoulder pain were included in a double-blind dummy study . Initially all patients received a local injection of corticosteroid and local anaesthetic , and were r and omly allocated either drug ( CI or SRI ) for a period of 3 weeks . Complete relief was recorded from significantly more of the patients in the CI group ( 21 % ) than in the SRI group ( 7 % ) while a similar number of patients improved viz . , 67 % of the SRI treated ground and 77 % of the CI treated group . Based on doctor 's assessment improvement in the two groups was equal . 44 % of the patients recorded side effects , the number and pattern being the same in the two groups . No serious side effects were recorded . It is concluded that the two treatment regimens can be rated as clinical ly equivalent A multi-dose , double-blind , r and omized , placebo-controlled , multicenter study was conducted to evaluate 68 patients with acute bursitis or tendinitis following treatment with flurbiprofen ( Ansaid , Upjohn ) or placebo . Flurbiprofen was administered in a total daily dosage of 200 to 300 mg four times daily . Based on efficacy rating scales , flurbiprofen-treated patients had the greatest proportion of improvement at almost all time periods . They also showed statistically significant improvement compared with placebo-treated patients , according to investigators ' overall assessment s at all time periods . Most patients showed improvement within three to four days of treatment . Flurbiprofen was both well tolerated and effective for the relief of pain caused by bursitis or tendinitis of the shoulder A double-blind comparison of fentiazac and placebo was carried out in 40 adult out patients with acute nonarticular rheumatism . By r and om assignment patients received either 100 mg of fentiazac four times a day for one week or an identical-looking placebo in the same dosage . Evaluation was based on improvements in movement-induced pain , pressure-induced pain , and patient 's and physician 's ratings of therapeutic effect . Fentiazac was significantly better than placebo and produced a similar incidence of side effects , both agents being well tolerated Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac , given once daily , with the st and ard tablet formulations of 100 mg , given 4-times daily , or 200 mg , given twice daily . A total of 60 patients suffering from acute bicipital tendinitis and /or subdeltoid bursitis was studied , 15 patients on the slow-release and 15 on one of the two st and ard tablets in each of the two trials . Patients were assessed on entry and at Days 7 and 14 of treatment . The results in both studies showed that there was significant improvement in tenderness , pain on movement , overall pain and in the range of movement after treatment , there being no significant difference between those receiving the slow-release form or the st and ard tablets . Tolerance was good in all groups and only a few minor or moderate side-effects , mainly of a gastro-intestinal type , were reported OBJECTIVE The objective of this study was to conduct an economic evaluation of rofecoxib and celecoxib compared with high-dose acetaminophen or ibuprofen with and without misoprostol for patients with symptomatic knee osteoarthritis ( OA ) . METHODS A decision analysis model was design ed over 6 months using two measures of effectiveness : 1 ) number of upper gastrointestinal ( GI ) adverse events averted ; and 2 ) number of patients who achieved perceptible pain relief . Separate analyses were conducted for all patients and for those who did not respond to acetaminophen . Outcome probabilities were obtained from a comprehensive review of r and omized controlled trials and observational studies . Costs were derived from actual re source utilization of OA patients . RESULTS In terms of averting GI events , acetaminophen dominates the other options for an average risk patient population . For patients who did not respond to acetaminophen , rofecoxib had the lowest incremental cost-effectiveness ratio ( ICER ) per GI event avoided ( 32,000 US dollars ) relative to ibuprofen . In terms of pain control , ibuprofen had an ICER of 610.77 US dollars per additional patient achieving minimal perceptible clinical improvement ( MPCI ) relative to acetaminophen , while rofecoxib had an ICER of 12,000 US dollars relative to ibuprofen . For patients who did not respond to acetaminophen and who are at high risk of developing an adverse GI event , rofecoxib dominates ibuprofen as the preferred alternative for both measures of effectiveness . One-way , two-way , and probabilistic sensitivity analyses established that these results were generally robust . CONCLUSIONS Our results suggest that for average-risk knee OA patients , acetaminophen dominates the other therapies in terms of cost per GI event averted . In terms of pain relief , cost-effectiveness acceptability curves indicate that if one values pain relief below 275 US dollars per patient achieving MPCI , acetaminophen is the therapy most likely to be optimal ; between 275 US dollars and 14,150 US dollars , ibuprofen is most likely to be optimal ; and above 14,150 US dollars , rofecoxib is most likely to be optimal A prospect i ve double blind placebo controlled study was carried out to compare the effects of subacromial injection of triamcinolone and oral diclofenac in patients with rotator cuff tendinitis over a 4-week period . Both forms of treatment were superior to placebo in reducing pain , improving active abduction and reducing functional limitation . Triamcinolone showed the greatest effect in these respects , and was significantly superior to diclofenac when patients showing improvements in all 3 variables together ( responders ) were considered The efficacy and tolerability of nimesulide , a non-steroidal anti-inflammatory drug ( NSAID ) 100 mg twice daily were compared with diclofenac 75 mg b.i.d . in short term treatment of acute shoulder ( acute subdeltoid bursitis and bicipital tendinitis ) in adult patients . In this double-blind ( double-dummy ) , r and omised , parallel group study over two weeks , 122 patients were included . The Mann-Whitney statistics revealed therapeutic equivalence of both treatments with a slight superiority for nimesulide . The tolerability of nimesulide , judged by investigators and patients and analysed statistically , was superior to that of diclofenac . Thus , the benefit-risk relationship was better for the test drug than for the reference drug |
12,647 | 29,326,180 | Conclusion In Africa , CKD is a public health problem , mainly attributed to high-risk conditions as hypertension and diabetes . | Objectives While increasing attention is paid to the rising prevalence of chronic diseases in Africa , there is little focus on chronic kidney disease ( CKD ) .
This systematic review assesses CKD burden among the general population and high-risk groups on the entire African continent . | Context As life expectancy improves among Human Immunodeficiency Virus ( HIV ) patients , renal and cardiovascular diseases are increasingly prevalent in this population . Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria . Underst and ing the interactions between HIV , cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV . Methods In a rural primary health care centre , 903 HIV-infected adult patients were r and omly selected and data on HIV-infection and cardiovascular risk factors were collected . Glomerular filtration rate ( eGFR ) was estimated . Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g . Multivariate logistic regression analysis was used to analyse albuminuria and demographic , clinical and HIV-associated variables . Results The study population consisted of 903 HIV-infected patients , with a median age of 40 years ( Inter-Quartile Range ( IQR ) 34–48 years ) , and included 625 ( 69 % ) women . The median duration since HIV diagnosis was 26 months ( IQR 12–58 months ) and 787 ( 87 % ) received antiretroviral therapy . Thirty-six ( 4 % ) of the subjects were shown to have diabetes and 205 ( 23 % ) hypertension . In the cohort , 21 % had albuminuria and 2 % an eGFR < 60 mL/min/1.73m2 . Albuminuria was associated with hypertension ( adjusted odds ratio ( aOR ) 1.59 ; 95 % confidence interval ( CI ) 1.05–2.41 ; p<0.05 ) , total cholesterol ( aOR 1.31 ; 95 % CI 1.11–1.54 ; p<0.05 ) , eGFR ( aOR 0.98 ; 95 % CI 0.97–0.99 ; p<0.001 ) and detectable viral load ( aOR 2.74 ; 95 % CI 1.56–4.79 ; p<0.001 ) . Hypertension was undertreated : 78 % were not receiving treatment , while another 11 % were inadequately treated . No patients were receiving lipid-lowering medication . Conclusion Glomerular filtration rate was well conserved , while albuminuria was common amongst HIV-infected patients in rural South Africa . Both cardiovascular and HIV-specific variables were associated with albuminuria . Improved cardiovascular risk prevention as well as adequate virus suppression might be the key to escape the vicious circle of renal failure and cardiovascular disease and improve the long-term prognosis of HIV-infected patients Aim : To identify whether the more recently developed equation for estimated glomerular filtration rate ( eGFR ) [ Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) ] is more closely associated with end-organ changes than previous equations in a group of black African descent . Methods : In 1221 r and omly recruited participants of black African ancestry in South Africa , we evaluated serum creatinine concentrations , echocardiographic left ventricular mass index ( n = 833 ) , carotid-femoral ( aortic ) pulse wave velocity ( PWV ) ( n = 1053 ) and carotid intima – media thickness ( n = 633 ) . We calculated eGFR from the Jelliffe , five Cockcroft – Gault , Salazar – Corcoran , Modification of Diet in Renal Disease ( MDRD ) and CKD-EPI equations . Results : After multivariate adjustments , eGFR calculated from all formulae was inversely associated with left ventricular mass index ( P < 0.0001 ) and PWV ( P < 0.05 to < 0.001 ) , but not with carotid intima – media thickness ( P > 0.08 ) . However , although eGFR determined from all equations except Cockcroft – Gault lean body weight or adjusted body weight was independently associated with left ventricular hypertrophy ( n = 390 of 833 ) , CKD-EPI-derived eGFR , but not eGFR determined from alternative equations , was independently associated with an increased PWV ( n = 88 of 1053 ) . eGFR derived from the CKD-EPI and MDRD equations showed a better performance ( area under the receiver operator characteristic curve ) for the detection of left ventricular hypertrophy ( P < 0.0005 ) than eGFR determined from alternative equations . Conclusions : In black Africans , eGFR derived from the CKD-EPI equation is better at detecting end-organ measures than eGFR derived from either the MDRD or alternative equations . To enhance risk prediction in black African communities , eGFR calculated from the CKD-EPI equation may be preferred to other equations Background and Objectives There have been few large population -based studies of the association between rheumatoid arthritis ( RA ) and chronic kidney disease ( CKD ) and glomerulonephritis . This nationwide cohort study investigated the risks of developing CKD and glomerulonephritis in patients with RA , and the associated risks for cardiovascular complications . Methods From the Taiwan National Health Insurance Research Data base , we identified a study cohort of 12,579 patients with RA and r and omly selected 37,737 subjects without RA as a control cohort . Each subject was individually followed for up for 5 years , and the risk of CKD was analyzed using Cox proportional hazards regression models . Results During the follow-up period , after adjusting for traditional cardiovascular risk factors RA was independently associated with a significantly increased risk of CKD ( adjusted hazard ratio [ aHR ] 1.31 ; 95 % confidence interval [ CI ] 1.23–1.40 ) and glomerulonephritis ( aHR 1.55 ; 95 % CI 1.37–1.76 ) . Increased risk of CKD was also associated with the use of non-steroidal anti-inflammatory drugs , cyclosporine , glucocorticoids , mycophenolate mofetil , and cyclophosphamide . Patients with comorbidities had even greater increased risk of CKD . Moreover , RA patients with concurrent CKD had significantly higher likelihood of developing ischemic heart disease and stroke . Conclusions RA patients had higher risk of developing CKD and glomerulonephritis , independent of traditional cardiovascular risk factors . Their increased risk of CKD may be attributed to glomerulonephritis , chronic inflammation , comorbidities , and renal toxicity of antirheumatic drugs . Careful monitoring of renal function in RA patients and tight control of their comorbid diseases and cardiovascular risk factors are warranted Background In the United States , HIV-related kidney disease disproportionately affects individuals of African descent ; however , there are few estimates of kidney disease prevalence in Africa . We evaluated the prevalence of kidney disease among HIV-infected and uninfected Rw and an women . Methods The Rw and an Women 's Interassociation Study and Assessment prospect ively enrolled 936 women . Associations with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 and proteinuria were assessed in separate logistic regression models . Results Among 891 non-pregnant women with available data , 2.4 % had an eGFR<60 mL/min/1.73 m2 ( calculated by the Modification of Diet in Renal Disease equation , MDRD eGFR ) and 8.7 % had proteinuria ≥1 + . The prevalence of decreased eGFR varied markedly depending on the estimating method used , with the highest prevalence by Cockcroft-Gault . Regardless of the method used to estimate GFR , the proportion with decreased eGFR or proteinuria did not differ significantly between HIV-infected and -uninfected women in unadjusted analysis . After adjusting for age and blood pressure , HIV infection was associated with significantly higher odds of decreased MDRD eGFR but not proteinuria . Conclusion In a well-characterized cohort of Rw and an women , HIV infection was associated with decreased MDRD eGFR . The prevalence of decreased eGFR among HIV-infected women in our study was lower than that previously reported in African-Americans and in other Central and East African HIV population s , although there was substantial variability depending on the equation used to estimate GFR . Future studies are needed to optimize GFR estimates and to determine the impact of antiretroviral therapy on kidney disease in this population The objective is to investigate the accrual rate and risk factors of chronic kidney disease ( CKD ) in an inception cohort of patients with systemic lupus erythematosus ( SLE ) followed at a single tertiary center . A prospect ively collected data base of 256 consecutive patients with SLE followed over a 25-year period was systematic ally interrogated for demographic , disease manifestations , co-morbidities , and outcome . St and ardized SLE activity and damage scores were determined for the first and last study visits , and estimated glomerular filtration rate ( eGFR ; MDRD formula ) was calculated at the time of diagnosis and at each year of the follow-up . CKD was defined as eGFR < 60 ml/min/1.73 m2 . Results were analyzed with univariate and multivariate models and Kaplan-Meier curves , as appropriate . The cohort was predominantly female ( 90 % ) and Jewish ( 91.1 % ) . Mean age at diagnosis was 38 ± 15.5 years , mean SLE activity score 6.4 ± 3.8 , mean disease duration 8.8 ± 6.6 years , and mean damage score 0.2 ± 0.6 . Seventy-five patients ( 30.8 % ) were diagnosed with American College of Rheumatology (ACR)-defined lupus renal disease during the study period . There was a progressive decrease in eGFR over time . The prevalence of CKD was 46.7 % in patients with ACR-defined renal lupus disease and 16.4 % in those without . The hazards ratio for CKD was significantly higher in patients with lupus nephritis ( LN ) than without ( p < 0.001 ) . Earlier CKD was positively associated with hypertension ( p = 0.01 ) , older age at diagnosis ( p = 0.01 ) , and LN ( p < 0.001 ) , and negatively associated with hydroxychloroquine treatment ( p < 0.001 ) . The prevalence of CKD increases cumulatively in patients with SLE , also in those without overt lupus renal disease . Lupus renal disease poses a significant hazard for earlier development of CKD , and hypertension is a major risk factor for patients with and without nephritis . Antimalarial treatment is associated with renal preservation only in patients with lupus nephritis BACKGROUND We sought to investigate renal function in previously untreated symptomatic human immunodeficiency virus (HIV)-infected adults with CD4(+ ) cell counts of < 200 cells/mm(3 ) who were undergoing antiretroviral therapy ( ART ) in Africa . METHODS The study was an observational analysis within a r and omized trial of ART management strategies that included 3316 participants with baseline serum creatinine levels of < or = 360 micromol/L. Creatinine levels were measured before ART initiation , at weeks 4 and 12 of therapy , and every 12 weeks thereafter . We calculated estimated glomerular filtration rate ( eGFR ) using the Cockcroft-Gault formula . We analyzed the incidence of severely decreased eGFR ( < 30 mL/min/1.73 m(2 ) ) and changes in eGFR to 96 weeks , considering demographic data , type of ART , and baseline biochemical and hematological characteristics as predictors , using r and om-effects models . RESULTS Sixty-five percent of the participants were women . Median values at baseline were as follows : age , 37 years ; weight , 57 kg ; CD4(+ ) cell count , 86 cells/mm(3 ) ; and eGFR , 89 mL/min/1.73 m(2 ) . Of the participants , 1492 ( 45 % ) had mild ( > or = 60 but < 90 mL/min/1.73 m(2 ) ) and 237 ( 7 % ) had moderate ( > or = 30 but < 60 mL/min/1.73 m(2 ) ) impairments in eGFR . First-line ART regimens included zidovudine-lamivudine plus tenofovir disoproxil fumarate ( for 74 % of patients ) , nevirapine ( 16 % ) , and abacavir ( 9 % ) ( mostly nonr and omized allocation ) . After ART initiation , the median eGFR was 89 - 91 mL/min/1.73 m(2 ) for the period from week 4 through week 96 . Fifty-two participants ( 1.6 % ) developed severe reductions in eGFR by week 96 ; there was no statistically significant difference between these patients and others with respect to first-line ART regimen received ( P = .94 ) . Lower baseline eGFR or hemoglobin level , lower body mass index , younger age , higher baseline CD4(+ ) cell count , and female sex were associated with greater increases in eGFR over baseline , with small but statistically significant differences between regimens ( P < .001 for all ) . CONCLUSIONS Despite screening , mild-to-moderate baseline renal impairment was relatively common , but these participants had greatest increases in eGFR after starting ART . Severe eGFR impairment was infrequent regardless of ART regimen and was generally related to intercurrent disease . Differences between ART regimens with respect to changes in eGFR through 96 weeks were of marginal clinical relevance , but investigating longer-term nephrotoxicity remains important Background In sub-Saharan Africa , kidney failure has a high morbidity and mortality . Despite this , population -based estimates of prevalence , potential etiologies , and awareness are not available . Methods Between January and June 2014 , we conducted a household survey of r and omly-selected adults in Northern Tanzania . To estimate prevalence we screened for CKD , which was defined as an estimated glomerular filtration rate ≤ 60 ml/min/1.73m2 and /or persistent albuminuria . We also screened for human immunodeficiency virus ( HIV ) , diabetes , hypertension , obesity , and lifestyle practice s including alcohol , tobacco , and traditional medicine use . Awareness was defined as a self-reported disease history and subsequently testing positive . We used population -based age- and gender-weights in estimating prevalence , and we used generalized linear models to explore potential risk factors associated with CKD , including living in an urban environment . Results We enrolled 481 adults from 346 households with a median age of 45 years . The community-based prevalence of CKD was 7.0 % ( 95 % CI 3.8 - 12.3 ) , and awareness was low at 10.5 % ( 4.7 - 22.0 ) . The urban prevalence of CKD was 15.2 % ( 9.6 - 23.3 ) while the rural prevalence was 2.0 % ( 0.5 - 6.9 ) . Half of the cases of CKD ( 49.1 % ) were not associated with any of the measured risk factors of hypertension , diabetes , or HIV . Living in an urban environment had the strongest crude ( 5.40 ; 95 % CI 2.05 - 14.2 ) and adjusted prevalence risk ratio ( 4.80 ; 1.70 - 13.6 ) for CKD , and the majority ( 79 % ) of this increased risk was not explained by demographics , traditional medicine use , socioeconomic status , or co-morbid non-communicable diseases ( NCDs ) . Conclusions We observed a high burden of CKD in Northern Tanzania that was associated with low awareness . Although demographic , lifestyle practice s including traditional medicine use , socioeconomic factors , and NCDs accounted for some of the excess CKD risk observed with urban residence , much of the increased urban prevalence remained unexplained and will further study as demographic shifts reshape sub-Saharan Africa Background In order to begin to address the burden of non-communicable diseases ( NCDs ) in sub-Saharan Africa , high quality community-based epidemiological studies from the region are urgently needed . Cluster- design ed sampling methods may be most efficient , but design ing such studies requires assumptions about the clustering of the outcomes of interest . Currently , few studies from Sub-Saharan Africa have been published that describe the clustering of NCDs . Therefore , we report the neighborhood clustering of several NCDs from a community-based study in Northern Tanzania . Methods We conducted a cluster- design ed cross-sectional household survey between January and June 2014 . We used a three-stage cluster probability sampling method to select thirty-seven sampling areas from twenty-nine neighborhood clusters , stratified by urban and rural . Households were then r and omly selected from each of the sampling areas , and eligible participants were tested for chronic kidney disease ( CKD ) , glucose impairment including diabetes , hypertension , and obesity as part of the CKD-AFRiKA study . We used linear mixed models to explore clustering across each of the samplings units , and we estimated absolute-agreement intra-cluster correlation ( ICC ) coefficients ( ρ ) for the neighborhood clusters . Results We enrolled 481 participants from 346 urban and rural households . Neighborhood cluster sizes ranged from 6 to 49 participants ( median : 13.0 ; 25th–75th percentiles : 9–21 ) . Clustering varied across neighborhoods and differed by urban or rural setting . Among NCDs , hypertension ( ρ = 0.075 ) exhibited the strongest clustering within neighborhoods followed by CKD ( ρ = 0.440 ) , obesity ( ρ = 0.040 ) , and glucose impairment ( ρ = 0.039 ) . Conclusion The neighborhood clustering was substantial enough to contribute to a design effect for NCD outcomes including hypertension , CKD , obesity , and glucose impairment , and it may also highlight NCD risk factors that vary by setting . These results may help inform the design of future community-based studies or r and omized controlled trials examining NCDs in the region particularly those that use cluster-sampling methods Background There is limited knowledge of Chronic Kidney Disease ( CKD ) among high risk population s , especially in the developing countries . We report our study of testing for CKD in at-risk subjects . Methods In a cross-sectional study , 527 people from primary and secondary health care areas in the city of Kinshasa were studied from a r and om sample of at-risk out- patients with hypertension , diabetes , obesity , or HIV+ . We measured blood pressure ( BP ) , blood glucose level , proteinuria , body mass index , and estimated glomerular filtration rate ( eGFR by MDRD equation ) using calibrated creatinine levels based on one r and om measurement . The associations between health characteristics , indicators of kidney damage ( proteinuria ) and kidney function ( < 60 ml/min/1.73 m2 ) were also examined . Results The prevalence of CKD in this study was 36 % , but only 12 % were aware of their condition . 4 % of patients had stage 1 CKD , 6 % stage 2 , 18 % stage 3 , 2 % stage 4 , and 6 % had stage 5 . 24 hour quantitative proteinuria ( > 300 mg/day ) was found in 19 % . In those with the at-risk conditions , the % of CKD was : 44 % in patients with hypertension , 39 % in those with diabetes ; 16 % in the obese and 12 % in those who were HIV+ . 82 % of those with a history of diabetes had elevated serum glucose levels at screening ( ≥ 126 mg/dl ) . Only 6 % of individuals with hypertension having CKD had reduced BP to lower than 130/80 mmHg . In multivariate analysis , diabetes , proteinuria and hypertension were the strongest determinants of CKD 3 + . Conclusion It appears that one out of three people in this at-risk population has undiagnosed CKD and poorly controlled CKD risk factors . This growing problem poses clear challenges to this developing country . Therefore , CKD should be addressed through the development of multidisciplinary teams and improved communication between traditional health care givers and nephrology services . Attention to CKD risk factors must become a priority Abstract Objectives Data on renal dysfunction in sub‐Saharan Africa , comparing urban and rural areas , have not yet been reported . Therefore , we aim ed to determine the distribution of low estimated glomerular filtration rates ( eGFRs ) in urban and rural Tanzania , to describe factors associated with low eGFR and to quantify fractions attributable to common risk factors . Methods We conducted a community‐based survey of 1095 r and omly selected Tanzanian adults ( ≥18 years ) . A structured question naire and examinations were used to document sociodemographic characteristics , diet , physical activity , anthropomorphic measurements and blood pressure . Blood tests were performed for HIV infection , diabetes mellitus and creatinine . eGFR was calculated using two equations recommended for African adults . Results Serum creatinine was available for 1043 participants : 170 in Mwanza city , 326 in district towns and 547 in rural areas . Mean age was 35.5 years and 54 % were females . The prevalence of eGFR < 60 ml/min/1.73 m2 in these 3 strata was 2.3 % ( 95 % CI = 0.8–6.6 % ) , 7.5 % ( 4.7–11.8 % ) and 7.4 % ( 5.1–10.6 % ) , respectively . When age st and ardised to the WHO world population , prevalences were 3.8 % , 10.1 % and 8.1 % . Factors associated with low eGFR included district town residence , older age , greater wealth , less physical activity and hypertension . Only 21 % of cases with eGFR < 60 ml/min/1.73 m2 were attributable to HIV , hypertension or diabetes . Conclusions Decreased renal function is common in Tanzania , particularly in district towns , and unique risk factors for kidney disease may exist in this population . Population ‐specific strategies for prevention , early diagnosis and treatment of kidney disease are needed for Africa BACKGROUND Delivery of diabetes services in re source -poor areas of Africa is difficult . Control is often poor and complications are common . However , adequate robust surveys are uncommon , particularly in remote rural areas . This makes needs assessment difficult and health-care planning impossible . AIM To accurately assess the glycaemic control and burden of complications in a group of diabetic patients from a remote area of a re source -limited north African country . DESIGN Prospect i ve cohort study . METHODS Over a 6-week period , all patients attending the diabetic clinic at Mekelle Hospital in northern Ethiopia were intensively assessed , using imported western technology as necessary . Glycated haemoglobin ( HbA(1c ) ) , lipid profile , serum creatinine and urinary albumin-creatinine ratio were measured . Complications were assessed as accurately as possible , including examination of fundi by an ophthalmic specialist , and biosthesiometry for neuropathy . RESULTS There were 105 patients , mean ( + /- SD ) age 41 + /- 16 years and diabetes duration 7 + /- 6 years . There were 74 ( 70 % ) males , and 69 ( 66 % ) on insulin . Median body mass index was low at 20.6 kg/m(2 ) , but mean HbA(1c ) high at 11.3 + /- 2.8 % ( 68 % had an HbA(1c ) over 10.0 % ) . Cataract ( 12 % ) , retinopathy ( 21 % ) , neuropathy ( 41 % ) and microalbuminuria ( 51 % ) were common ; but nephropathy ( 2 % ) was rare , as was large vessel disease ( 6 % had peripheral vascular disease , and none had coronary artery disease or cerebrovascular disease ) . Risk factors such as hypertension ( 5 % ) and smoking ( 2 % ) were uncommon , and lipid profiles were generally good . DISCUSSION We conclude that in this severely re source -limited area of North Africa , glycaemic control amongst diabetic patients is very poor . Neuropathy , retinopathy and microalbuminuria are common ; but large vessel disease risk factors are beneficial , and macroangiopathy prevalence is low . Scattered population s , shortage of drugs and insulin and lack of diabetes team care are major factors behind these serious issues of diabetic control and complications BACKGROUND The patterns of glomerular diseases have been widely reported from different regional and national biopsy registries worldwide . However , there are scant studies on the epidemiology of biopsy-proven renal disease , particularly glomerular diseases in sub-Saharan Africa . METHODS We retrospectively analysed the reports of 1284 native renal biopsies , review ed by the same pathologist and performed at the Groote Schuur Hospital in Cape Town from 1 January 2000 to 31 December 2009 . RESULTS The mean age of all the patients biopsied was 36.8 ± 14.0 years with 61.8 % of the patients being under 40 years of age . There was a preponderance of females ( 54.8 % ) . There were more coloured patients ( 53.7 % ) than blacks ( 42.2 % ) or whites ( 3.9 % ) . The frequencies of clinical indications for a renal biopsy were nephrotic range proteinuria ( 52.5 % ) , acute renal failure ( 21.3 % ) , asymptomatic urinary abnormalities ( 13.6 % ) , chronic renal failure ( 6.4 % ) , acute nephritic syndrome ( 5.8 % ) and haematuria ( 0.3 % ) . The frequencies of the primary glomerulonephritis ( GN ) include mesangiocapillary GN ( 20.4 % ) , mesangial proliferative GN ( 19.2 % ) , membranous GN ( 18.5 % ) , crescentic and necrotizing GN ( 11.4 % ) , focal and segmental glomerulosclerosis ( 10.5 % ) , post-infectious GN ( 8.2 % ) , minimal change disease ( 6.0 % ) and IgA nephropathy ( 5.8 % ) . Lupus nephritis was the most frequent secondary glomerular disease ( 39.0 % ) and was also the most frequent cause of the nephrotic range proteinuria ( 17.2 % ) . HIV-associated nephropathy increased from 6.6 % in 2000 to 25.7 % in 2009 ( P < 0.0001 ) . CONCLUSION Our data are an important contribution to the epidemiology of renal disease in Africa . We hope that this will form the basis for developing a renal biopsy registry in South Africa and across the continent Background The extent and the distribution of end stage kidney disease ( ESKD ) in Libya have not been reported despite provision of dialysis over 4 decades . This study aim ed to develop the first comprehensive description of the epidemiology of dialysis-treated ESKD in Libya . Methods Structured demographic and clinical data were obtained regarding all adult patients treated at all maintenance dialysis facilities ( n=39 ) in Libya from May to September 2009 . Subsequently data were collected prospect ively on all new patients who started dialysis from September 2009 to August 2010 . Population estimates were obtained from the Libyan national statistics department . The age and gender breakdown of the population in each region was obtained from mid-2009 population estimates based on 2006 census data . Results The prevalence of dialysis-treated ESKD was 624 per million population ( pmp ) . 85 % of prevalent patients were aged < 65 years and 58 % were male . The prevalence of ESKD varied considerably with age with a peak at 55–64 years ( 2475 pmp for males ; 2197 pmp for females ) . The annual incidence rate was 282 pmp with some regional variation and a substantially higher rate in the South ( 617 pmp ) . The most common cause of ESKD among prevalent and incident patients was diabetes . Other important causes were glomerulonephritis , hypertensive nephropathy and congenital or hereditary diseases . Conclusions Libya has a relatively high prevalence and incidence of dialysis-treated ESKD . As the country prepares to redevelop its healthcare system it is hoped that these data will guide strategies for the prevention of CKD and planning for the provision of renal replacement therapy BACKGROUND Proteinuria during pregnancy has been associated with increased pregnancy complications . Furthermore , even low- grade proteinuria has been associated with increased mortality in the general population and in non-pregnant HIV-infected women . METHODS Urine dipstick protein was measured prospect ively on HIV-infected and trace protein or more and quantified by urine protein : creatinine measurement ( P : C ) . Logistic regression modeling was used to identify factors associated with proteinuria . RESULTS About 199 human immunodeficiency virus (HIV)-infected and 190 HIV-uninfected normotensive pregnant women were evaluated . The median age was 27 years in both groups and 37 % presented in the third trimester . Among HIV-infected women , median CD4 cell count was 417 cells/mm(3 ) ; 27 % were on combination antiretroviral therapy ( cART ) . Proteinuria was present in 39.2 % of HIV-infected and 20.9 % of uninfected women ( P < 0.001 ) . HIV infection was independently associated with proteinuria [ adjusted odds ratio ( OR ) = 2.45 ; confidence interval ( CI ) = 1.56 - 3.85 ] . Among HIV-infected pregnant women , cART was protective ( adjusted OR = 0.39 ; CI = 0.19 - 0.82 ) . Results were qualitatively similar when urine P : C was evaluated as a continuous outcome variable . CONCLUSIONS The prevalence of low- grade proteinuria in both HIV-infected and -uninfected Cameroonian pregnant women is high . HIV-infected pregnant women are at increased risk for proteinuria , and cART appears to exert a protective effect . Further studies are needed to eluci date the causes of increased proteinuria in African pregnant women , both HIV-infected and -uninfected Background Non-communicable diseases ( NCDs ) are a leading cause of death among adults in sub-Saharan Africa , and chronic kidney disease ( CKD ) is a growing public health threat . Underst and ing knowledge , attitudes , and practice s associated with NCDs is vital to informing optimal policy and public health responses in the region , but few community-based assessment s have been performed for CKD . To address this gap , we conducted a cross-sectional survey of adults in northern Tanzania using a vali date d instrument . Methods Between January and June 2014 , we administered a structured survey to a r and om sample of adults from urban and rural communities . The vali date d instrument consisted of 25 items design ed to measure knowledge , attitudes , and practice s associated with kidney disease . Participants were also screened for CKD , diabetes , hypertension , and human immunodeficiency virus . Results We enrolled 606 participants from 431 urban and rural households . Knowledge of the etiologies , symptoms , and treatments for kidney disease was low ( mean score 3.28 out of 10 ; 95 % CI 2.94 , 3.63 ) . There were no significant differences by CKD status . Living in an urban setting and level of education had the strongest independent associations with knowledge score . Attitudes were characterized by frequent concern about the health ( 27.3 % ; 20.2 , 36.0 % ) , economic ( 73.1 % ; 68.2 , 77.5 % ) , and social impact ( 25.4 % ; 18.6 , 33.6 % ) of kidney disease . Practice s included the use of traditional healers ( 15.2 % ; 9.1 , 24.5 % ) and traditional medicines ( 33.8 % ; 25.0 , 43.9 % ) for treatment of kidney disease as well as a willingness to engage with mobile-phone technology in CKD care ( 94.3 % ; 90.1 , 96.8 % ) . Conclusions Community-based adults in northern Tanzania have limited knowledge of kidney disease . However , there is a modest knowledge base upon which to build public health programs to exp and awareness and underst and ing of CKD , but these programs must also consider the variety of means by which adults in this population meet their healthcare needs . Finally , our assessment of local attitudes suggested that such public health efforts would be well-received Chronic kidney disease ( CKD ) often remains clinical ly silent and therefore undiagnosed until a progressed stage is reached . Our aim was to estimate the prevalence of CKD in a primary care setting in Switzerl and . A multicenter , cross-sectional study with r and omly selected general practitioners was performed . Adults visiting their general physician ’s cabinet during defined periods were asked to participate . Baseline information was reported on a question naire , urine and blood sample s were analyzed in a central laboratory . Renal status was assessed using the Kidney Disease : Improving Global Outcomes ( KDIGO ) classification . Extrapolation of results to national level was adjusted for age and gender . One thous and individuals ( 57 % females ) with a mean age of 57±17 years were included . Overall , 41 % of the patients had normal estimated glomerular filtration rate ( eGFR ) and albumin creatinine ratio ( ACR ) , whereas 36 % of the subjects had slightly reduced excretory renal function with physiological albuminuria based on normal ACR . Almost one fourth of the subjects ( 23 % ) had either a substantially reduced eGFR or high levels of ACR . About 10 % of the patients had a substantially reduced eGFR of < 60 ml/min/1.73 m2 , and 17 % showed relevant proteinuria ( ACR > 30 mg/g creatinine ) . Extrapolation to national level suggests that about 18 % of primary care patients may suffer from CKD . CKD prevalence in a primary care population is therefore high , and preventive interventions may be advisable , in particular as CKD prevalence is likely to rise over the next decades Background Diabetic patients with chronic kidney disease ( CKD ) , as defined by a reduced glomerular filtration rate ( GFR ) , are at greater risk for cardiovascular and renal events and mortality . The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia , and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine . Methods A total of 214 r and omly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31 , 2013 . All patients completed an interviewer-administered question naire and underwent clinical assessment . The simplified Modification of Diet in Renal Disease ( MDRD ) and Cockroft-Gault ( C-G ) equations were used to estimate GFR ( eGFR ) from serum creatinine . Results CKD , defined as eGFR < 60 ml/min/1.73 m2 , was present in 18.2 % and 23.8 % of the study participants according to the MDRD and Cockcroft-Gault ( C-G ) equations , respectively . Only 9.8 % of the total participants , and 48.7 % ( for the MDRD ) and 37.3 % ( for C-G ) of those with eGFR < 60 ml/min/1.73 m2 had abnormal serum creatinine values , i.e. > 1.5 mg/dl . Normal serum creatinine was observed in 90.2 % of participants attending the hospital . A large proportion of participants ranging from 38.9 - 56.5 % have shown to have mild to moderate renal insufficiency ( stage 2–3 CKD ) despite normal creatinine levels . CKD , eGFR < 60 ml/min/1.73 m2 , was found in 10.4 and 16.9 % of participants with normal serum creatinine using the MDRD and C-G equations , respectively . Conclusion CKD is present in no less than 18 % of diabetics attending the hospital , but it is usually undiagnosed . A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels . Therefore , GFR should be considered as an estimate of renal insufficiency , regardless of serum creatinine levels being in normal range BACKGROUND The aim of this study was to investigate long-term renal function in HIV-infected adults initiating antiretroviral therapy ( ART ) with a CD4(+ ) T-cell count < 200 cells/mm³ in Africa . METHODS This was an observational analysis within the DART trial r and omizing 3,316 adults to routine laboratory and clinical monitoring ( LCM ) or clinical ly driven monitoring ( CDM ) . Serum creatinine was measured pre-ART ( all ≤ 360 μmol/l ) , at weeks 4 and 12 , then every 12 weeks for 4 - 5 years ; estimated glomerular filtration rate ( eGFR ) was determined using the Cockcroft-Gault formula . We analysed eGFR changes , and cumulative incidences of eGFR < 30 ml/min/1.73 m² and chronic kidney disease ( CKD ; < 60 ml/min/1.73 m² or 25 % decrease if < 60 ml/min/1.73 m² pre-ART ; confirmed > 3 months ) . RESULTS At ART initiation , median CD4(+ ) T-cell count was 86 cells/mm³ ; 1,492 ( 45 % ) participants had mild ( 60- < 90 ml/min/1.73 m² ) , 237 ( 7 % ) moderate ( 30-<60 ml/min/1.73 m² and 7 ( 0.2 % ) severe ( 15-<30 ml/min/1.73 m² ) decreases in eGFR . First-line ART was zidovudine/lamivudine plus tenofovir ( 74 % ) , abacavir ( 9 % ) or nevirapine ( 17 % ) . By 4 years , cumulative incidence of eGFR<30 ml/min/1.73 m² was 2.8 % ( n=90 ) and CKD was 5.0 % ( n=162 ) . Adjusted eGFR increases to 4 years were 1 , 9 and 6 ml/min/1.73 m² with tenofovir , abacavir and nevirapine , respectively ( P<0.001 ) , and 4 and 2 ml/min/1.73 m² for LCM and CDM , respectively ( P=0.005 ; 2 and 3 ml/min/1.73 m² to 5 years ; P=0.81 ) . CONCLUSIONS On all regimens and monitoring strategies , severe eGFR impairment was infrequent ; differences in eGFR changes were small , suggesting that first-line ART , including tenofovir , can be given safely without routine renal function monitoring We studied 92 HIV-positive patients retrospectively between January 1994 and December 1996 and prospect ively from January to July 1997 . We determined serum creatinine and 24-hour proteinuria . The median age of the patients was 22 ( + /- 4 ) years and most patients were aged between 25 and 45 years . The sex ratio was 2.17 and most patients were infected with HIV-1 ( 67.39 % ) . Renal failure occurred in 27.16 % of cases , due to changes in blood pressure and infectious diseases . Three patients had a nephrotic syndrome caused by HIV . Thirty-eight cases of lung infection , ten of urinary infection , twelve infections of the digestive system and fifteen cases of skin infection were recorded . The median duration of stay in hospital was 23 ( + /- 8) days and the median cost of hospitalization was 147,450 F CFA ( + /- 31,057 ) . The treatment given was purely symptomatic and three patients died during the study . One patient suffered chronic renal failure and is now undergoing hemodialysis . Preventive treatment would be of great value BACKGROUND The burden of chronic kidney disease ( CKD ) in sub-Saharan Africa is unknown . The aim of this study was to investigate the prevalence and the risk factors associated with CKD in Kinshasa , the capital of the Democratic Republic of Congo ( DRC ) . METHODS In a cross-sectional study , 503 adult residents in 10 of the 35 health zones of Kinshasa were studied in a r and omly selected sample . Glomerular filtration rate was estimated using the simplified Modification of Diet in Renal Disease Study equation ( eGFR ) and compared with the Cockcroft-Gault equation for creatinine clearance . The associations between health characteristics , indicators of kidney damage ( proteinuria ) and kidney function ( < 60 ml/min/1.73 m(2 ) ) were examined . RESULTS The prevalence of all stages of CKD according to K/DOQI guidelines was 12.4 % [ 95 % confidence interval ( CI ) , 11.0 - 15.1 % ] . By stage , 2 % had stage 1 ( proteinuria with normal eGFR ) , 2.4 % had stage 2 ( proteinuria with an eGFR of 60 - 89 ml/min/1.73 m(2 ) ) , 7.8 % had stage 3 ( eGFR , 30 - 59 ml/min/1.73 m(2 ) ) and 0.2 % had stage 5 ( eGFR < 15 ml/min/1.73 m(2 ) ) . Hypertension and age were independently associated with CKD stage 3 . The prevalences of major non-communicable diseases considered in this study were 27.6 % ( 95 % CI , 25.7 - 31.3 % ) for hypertension , 11.7 % ( 95 % CI , 10.3 - 14.4 % ) for diabetes mellitus and 14.9 % ( 95 % CI , 13.3 - 17.9 % ) for obesity . Hypertension was also independently associated with proteinuria . CONCLUSION More than 10 % of the Kinshasa population exhibits signs of CKD , which is affecting adults in their productive years . Risk factors for CKD , including hypertension , diabetes and obesity , are increasing . These alarming data must guide current and future healthcare policies to meet the challenge raised by CKD in this city and hopefully in the whole country Aims . Previous studies of type 2 diabetes mellitus have indicated a benign renal outcome after long-term follow-up . The aim of this study was to determine how often renal failure due to diabetic nephropathy was a cause of death in patients with type 2 diabetes . Methods . Prospect i ve observational study of 59 South African patients with type 2 diabetes over a 12-year period . During the study repeated clinical evaluations were accompanied by measurements of serum creatinine , serum cholesterol , r and om blood sugar , and urine protein/creatinine ratios . Results .The mean duration of diabetes at the end of the study was 17.8 years . There was a wide variation in the time from clinical diagnosis of diabetes to macroproteinuria ( mean 9.7 years , SD 5.9 , range 0–21 ) and the rate of deterioration of renal function . This rate correlated with poor control of blood pressure , a glucose level of > 14 mmol/l , heavy proteinuria , a high retinopathy score , a body mass index of < 28 and the number of pack years of smoking . At the end of the study 47 patients ( 79.7 % ) had died . Of these deaths 17 ( 28.8 % ) were due to chronic renal failure . Conclusions . In contrast to other studies we have shown that in a developing country renal failure in type 2 diabetic patients is a major cause of death . Determining the prognosis for an individual patient is difficult as there are wide ranges in the time of onset of proteinuria , the rise in serum creatinine and the time to ultimate progression to end-stage renal failure BACKGROUND Chronic kidney disease ( CKD ) has an increased risk of not only end-stage renal disease ( ESRD ) , but majority of moderate CKD patients do die from cardiovascular disease ( CVD ) before reaching ESRD . The prognosis of these patients is very poor in most developing countries because of late presentation , inadequate diagnostic facilities , and inability to pay for treatment . Knowledge about CVD in CKD is crucial because of unpredictable progressive nature of the disease and increased risk of premature death from cardiovascular events . We sought to determine prevalence and pattern of electrocardiographic abnormalities in dialysis naïve CKD patients . MATERIAL S AND METHODS This is a 10-year prospect i ve cross-sectional study carried out at the University of Ilorin Teaching Hospital , Ilorin . Patients were recruited from the nephrology clinic and renal wards and all who met diagnostic criteria for stages 4 and 5 CKD were included . All had their st and ard 12-lead electrocardiogram ( ECG ) recorded and various findings were critically studied and interpreted independently by two consultant physician including a cardiologist . Data analysis was done using SPSS version 16 . RESULTS Overall , 86 % of the patients had at least one form of ECG abnormality , with hypertension ( HTN ) and anemia being the main contributory factors . These include left ventricular hypertrophy ( LVH ) ( 27.6 % ) , left atrial enlargement ( LAE ) ( 21.6 % ) , combination of LVH and LAE ( 17.2 % ) , and ventricular premature contractions ( 6 % ) . Etiology of CKD appears to have influence on ECG changes as prevalence of LVH and LAE were high among hypertensive renal disease , chronic glomerulonephritis ( CGN ) , and diabetic nephropathy patients . CONCLUSION LVH and LAE were very common ECG abnormalities in our dialysis naïve CKD patients . HTN , CGN , anemia , late presentation , and male gender appear to be the main risk factors for the ECG abnormalities . There is need for gender-specific intervention strategies directed at early detection and treatment of HTN , anemia , and underlying kidney disease , especially in re source poor nations where the burden of CKD is assuming epidemic proportion Renal dysfunction is a severe complication of advanced HIV disease . We evaluated the impact of highly active antiretroviral therapy ( HAART ) on renal function among HIV-infected Ug and ans in the Home-Based AIDS Care clinical trial . The patients presented with symptomatic HIV disease or CD4 cell count < or = 250 cells/mm(3 ) and creatinine clearances above 25 ml/min determined by the Cockcroft-Gault equation . Of the 508 patients at baseline , 8 % had a serum creatinine over 133 micromol/l and about 20 % had reduced renal function evidence d by a creatinine clearance between 25 and 50 ml/min . After 2 years of HAART , the median serum creatinine was significantly decreased by 16 % while the median creatinine clearance significantly increased 21 % . The median creatinine clearance of patients with renal dysfunction at baseline , increased by 53 % during 2 years of treatment . In multivariable analysis , a baseline creatinine above 133 micromol/l , a weight gain of more than 5 kg over the 2 years , female gender and a WHO stage 4 classification were all associated with greater improvements in creatinine clearance on HAART . Our study shows that renal dysfunction was common with advanced HIV disease in Ug and a but this improved following 2 years of HAART BACKGROUND Several commonly used antiretrovirals ( ARVs ) require dose adjustments to prevent toxicities in the presence of renal insufficiency . Because no prospect i ve studies of the prevalence or risk factors for kidney disease in stable outpatient human immunodeficiency virus (HIV)-infected indigenous African population s have been published to date , it is not known if already scarce re sources should be allocated to detect renal dysfunction , in those without risk factors for kidney disease , prior to initiation of increasingly available antiretrovirals in developing countries . METHODS A cross-sectional study to determine the prevalence of and risk factors for renal disease in a cohort of medically stable , HIV-infected , antiretroviral-naïve adults , without diabetes or hypertension , presenting to an HIV clinic in western Kenya . RESULTS Of 373 patients with complete data , renal insufficiency ( CrCl < 60 ml/min ) was identified in 43 ( 11.5 % ) [ 18 ( 4.8 % ) had a CrCl < 50 ml/min ] . Despite high correlation coefficients between the three renal function estimating equations used , when compared to creatinine clearance as calculated by Cockcroft-Gault , lower rates of moderate to severe renal insufficiency were identified by the Modification of Diet in Renal Disease equations . Proteinuria , defined as a urine dipstick protein of equal to or greater than 1 + , was detected in only 23 subjects ( 6.2 % ) . CONCLUSIONS Renal insufficiency is not uncommon , even in stable patients without diabetes or hypertension . Conversely , proteinuria was unexpectedly infrequent in this population . Utilizing re sources to assess renal function prior to initiation of antiretrovirals in order to identify those likely to benefit from dosage adjustment is justified OBJECTIVE To evaluate the prevalence and predictors of microalbuminuria in diabetics in Kumasi , Ghana . DESIGN Prospect i ve , cross-sectional study of diabetic patients . SUBJECTS Patients with diabetes , 20 to 78 years of age . MAIN OUTCOME MEASURES Microalbuminuria METHODS All patients ( 109 ) attending an outpatient diabetic clinic at the Komfo Anokye Teaching Hospital Diabetes Centre in Kumasi , Ghana from January to July 2005 were enrolled in the study . RESULTS The mean overall age of the cohort was 54.1 + /- 10.9 years , and 28 % were male . The proportion of subjects who had microalbuminuria was 43.1 % ( n=47 ) . The median duration of diabetes before development of microalbuminuria was 10 years . Duration of diabetes , blood urea nitrogen , serum concentration of creatinine , and triglyceride were significantly higher in patients with microalbuminuria ( P<.05 ) . Urinary potassium concentration and fractional excretion of potassium were also significantly higher in the patients with microalbuminuria . CONCLUSIONS The prevalence of microalbuminuria in patients with diabetes in this study was 43 % . Significant predictors of microalbuminuria included duration of diabetes and serum concentration of creatinine . To reduce renal failure among these patients , strategies to mitigate its occurrence are needed . This includes strict glycemic control , control of hypertension , and the early blockade of the renin-angiotensin system |
12,648 | 27,847,678 | The strongest evidence was for perioperative teriparatide .
Conclusion : There are 15 articles evaluating osteoporosis in patients undergoing lumbar fusion and the highest level of evidence is for perioperative use of teriparatide | Purpose : To evaluate the current evidence in the literature on treatment strategies for degenerative lumbar spine fusion in patients with osteoporosis . | Summary The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis . Treatment for up to 8 years was associated with persistent reduction of bone turnover , continued increases in bone mineral density , low fracture incidence , and a favorable benefit/risk profile . Introduction This study aims to report the results through year 5 of the FREEDOM Extension study , representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis . Methods Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab , since placebo assignment was discontinued for ethical reasons . A total of 4550 women enrolled in the Extension ( 2343 long-term ; 2207 cross-over ) . In this analysis , women in the long-term and cross-over groups received denosumab for up to 8 and 5 years , respectively . Results Throughout the Extension , sustained reduction of bone turnover markers ( BTMs ) was observed in both groups . In the long-term group , mean bone mineral density ( BMD ) continued to increase significantly at each time point measured , for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip , respectively . In the cross-over group , mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip , respectively . The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups . The incidence of adverse and serious adverse events did not increase over time . Through Extension year 5 , eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed . Conclusions Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs , continued BMD gains , low fracture incidence , and a consistent safety profile Study Design . Retrospective case-control study . Objective . To determine the association of Hounsfield unit ( HU ) measurements with adjacent segment fractures after spinal fusion . Summary of Background Data . Adjacent segment fracture is a potentially devastating complication after spinal fusion surgery in osteoporotic patient . Recently , a technique for assessing bone mineral density using HU measurements from computed tomography was described and correlated with both dual-energy x-ray absorptiometry – assessed bone mineral density and compressive strength in an osseous model . Methods . Patients with adjacent segment fractures after spinal fusion were identified from a prospect ively collected patient data base and matched 1:1 with nonfracture controls on the basis of age , sex , and fusion construct . Minimum follow-up was 6 months . Patients with metabolic bone disease other than osteoporosis or those taking medications known to negatively alter bone strength were excluded . HU assessment was done according to the previously published protocol using the preoperative computed tomography . Results . Twenty patients had complete imaging data and could be matched to nonfracture controls . The groups were well matched with respect to age , sex , body mass index , and number of levels fused . Following the index surgical procedure , the fracture group had more positive sagittal balance than the control group ( 10.7 cm vs. 9.1 cm ) . Analysis of HU values at the fracture level showed a significantly lower value in the fracture group than in the controls ( 145.6 vs. 199.4 , P = 0.006 ) . Similarly , global assessment of HU across the thoracic and lumbar spines was significantly lower in the fracture group ( 139.9 vs. 170.1 , P = 0.032 ) . Conclusion . HU was significantly lower both locally and globally in the fracture cohort . Because computed tomographic scans are frequently part of preoperative planning for spinal fusion , this information should be incorporated in preoperative planning . Studies to prospect ively vali date HU as a predictor of adjacent segment fracture risk and to assess the effect of increasing HU preoperatively with medications for osteoporosis are needed . Level of Evidence : Osteoporosis is a major global health problem , with over 10 million people currently diagnosed with the disease . Although 80 % of osteoporotic patients are women , a considerable number of men are also affected . Also , due to increasing life expectancy , the number of elderly patients with osteoporosis affected by degenerative and traumatic spinal diseases will increase further . Osteoporosis reduces bone quality through negative bone remodelling . Low bone quality can reduce the pull-out strength of pedicle screw , and negative bone remodelling can cause delayed bone fusion . However , pedicle screw instrumentation of the osteoporotic spine carries an increased risk of screw loosening , pull-out , and fixation failure . Our preliminary study aims to investigate the efficiency of exp and able pedicle screws ( OsseoScrew-Spinal Fixation System , Alphatec Spine Inc. , Carlsbad , CA ) in osteoporotic spinal patients . All osteoporotic patients with degenerative and traumatic spinal diseases admitted in our department underwent a pre-operative spinal x-Ray and MRI or CT . Pre-operative clinical assesment of patients was based on the visual analog scale ( VAS ) and Owestry Disability ( ODI ) question naire-a disease-specific outcome measure . Ten osteoporotic patients were treated with exp and able pedicle screws ( OsseoScrew ) . Post-operative clinical assessment of patients was based on the VAS and ODI question naire at 3 months and 1 year of follow-up . Post-operative radiologic follow-up was performed after 3 days ( CT , x-ray ) ; 3 months ( x-ray ) ; 6 months ( spinal CT ) ; and 1 year ( spinal CT ) . Exp and able pedicle screws improved pull-out strength as compared to st and ard pedicle screws in osteoporotic patients with degenerative and traumatic spinal diseases Purpose The LLIF procedure is a useful st and -alone and adjunct surgical approach for many spinal conditions . One complication of LLIF is subsidence of the interbody graft into the vertebral bodies , result ing in severe pain , impaired arthrodesis and potentially fracture of the body . Low bone density , as measured by T score on DEXA scanning , has also been postulated to increase the risk of subsidence . Methods A retrospective review of prospect ively collected data was performed on all patients who underwent LLIF at this institution consisting of 712 levels in 335 patients . Patients with subsidence following LLIF were recorded . We utilized the T score obtained from the femoral neck DEXA scans , which is used to determine overall fracture risk . The T score of patients with subsidence was compared to those without subsidence . Results 20 of 57 ( 35 % ) patients without subsidence had a DEXA T score between −1.0 and −2.4 consistent osteopenia , one patient ( 1.8 % ) exhibited a T score less than −2.5 , consistent with osteoporosis . 13 patients of 23 ( 57 % ) with subsidence exhibited a T score between −1.0 and −2.4 , consistent with osteopenia , five ( 22 % ) exhibited a T score of −2.5 or less , consistent with osteoporosis . The mean DEXA T score in patients with subsidence was −1.65 ( SD 1.04 ) compared to −0.45 ( SD 0.97 ) in patients without subsidence ( p < 0.01 ) . The area under the receiver operating characteristic curve for patients with a T score of −1.0 or less was 80.1 % . Conclusions Patients with DEXA T scores less than −1.0 who undergo st and -alone LLIF are at a much higher risk of developing graft subsidence . Further , they are at an increased risk of requiring additional surgery . In patients with poor bone quality , consideration could be made to supplement the LLIF cage with posterior instrumentation Study Design . Prospect i ve trial . Objective . To examine the clinical efficacy of teriparatide for bone union after instrumented lumbar posterolateral fusion using local bone grafting in women with postmenopausal osteoporosis . Summary of Background Data . Intermittent parathyroid hormone ( PTH ) treatment increases bone mass and reduces the risk for osteoporotic vertebral fractures . Recombinant human PTH ( 1–34 ) has already been approved as a treatment for severe osteoporosis . Pre clinical data support the efficacy of PTH for lumbar spinal fusion . However , clinical results of PTH for spinal fusion have not yet been reported . Methods . Fifty-seven women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 2 treatment groups , a teriparatide group ( n = 29 ; daily subcutaneous injection of 20 & mgr;g of teriparatide ) and a bisphosphonate group ( n = 28 ; weekly oral administration of 17.5 mg of risedronate ) . All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft . Fusion rate , duration of bone union , and pain scores were evaluated 1 year after surgery . Results . Pain scores improved after surgery ; however , no significant difference was noted between the groups after surgery . The rate of bone union was 82 % in the teriparatide group and 68 % in the bisphosphonate group . Average duration of bone union was 8 months in the teriparatide group and 10 months in the bisphosphonate group . The rate of bone union and average of duration of bone union in the teriparatide group patients were significantly superior to those in the bisphosphonate group . Conclusion . Daily subcutaneous injection of teriparatide for bone union using local bone grafting after instrumented lumbar posterolateral fusion in women with postmenopausal osteoporosis was more effective than oral administration of bisphosphonate Type of study A 2 to 4-year clinical and radiologic prospect i ve study was conducted for 39 patients over the age of 65 treated by lumbar arthrodesis . Objectives Evaluate the quality of lumbar arthrodesis results in elderly patients , in which the bone osteoporosis ( poor quality of the spine 's anatomic components ) and general factors ( frequent comorbidity ) are likely to make this surgery difficult if not dangerous and evaluate a dedicated instrumentation for osteoporotic bone . Material s and Methods Thirty-nine patients over 65 years of age ( average 73 y ) underwent arthrodesis surgery in 2001 and 2002 and were followed for at least 2 years . The instrumentation used ( Equation , Medtronic , Memphis , USA ) was selected for its mechanical properties adapted for bone of poor mechanical quality . The clinical analysis was based on Oswestry , Visual Analog Scale , and Japanese Orthopaedic Association scores . Radiologic results were evaluated on st and ard anteroposterior , lateral , and 3/4 radiographs , and computed tomography scans if necessary . Results All the patients were followed for 2 to 4 years . Clinical analysis confirmed a very satisfactory progression of the clinical parameters such as lumbar and radicular pain , and the results were maintained between the first and second years and at last follow-up . No serious general complication or need for reoperation was seen in this series . On x-rays , 35 grafts appear to have fused . The anchors did not come out nor did the instrumentation come apart . On the other h and , 2-year radiographs revealed that 2 screws and 2 rods had failed , but this did not affect correction in the 4 completely asymptomatic patients . These 4 cases are considered stable at last follow-up . Conclusions Arthrodesis for elderly patients will undoubtedly increase in the coming years . The conditions for this surgery are different than those for younger patients and it is desirable to try to provide reliable surgical techniques and solutions regarding options for instrumentation and overall perioperative care for these fragile patients . Dedicated instrumentation for osteoporotic bone seems to allow good clinical outcomes BACKGROUND CONTEXT Pedicle screw fixation in osteoporotic bone and in revision of previous pedicle screw fixation cases presents a significant challenge to spine surgeons . Biomechanical tests have shown that a pedicle screw that exp and s within the vertebrae body can substantially improve fixation in the presence of compromised bone . PURPOSE To review the clinical and radiographic results with the use of exp and able pedicle screws . STUDY DESIGN One hundred forty-five patients received one or more exp and able pedicle screws from the Omega21 spinal fixation system ( EBI , L.P. , Parsippany , NJ ) to obtain thorocolumbar or lumbosacral stabilization . PATIENT SAMPLE The indications for use of the exp and able screws were osteoporosis ( 21 cases ) , reoperation of previous pedicle instrumentation ( 27 cases ) , intraoperative screw relocation ( 17 cases ) , construct reinforcement ( 23 cases ) , and sacral anchoring to avoid the necessity of anterior penetration of the sacral cortex ( 57 cases ) . OUTCOME MEASURES The presence of radiographic fusion and complications arising from the instrumentation were review ed at a mean follow-up period of 35 months ( range , 24 - 72 months ) . METHODS A retrospective clinical and radiographic review was performed . Fusion was evaluated based on anterior-posterior and lateral radiographs as well as dynamic radiographs in flexion and extension . RESULTS Radiographic evidence of fusion was obtained in 125 of the 145 cases ( 86 % ) . Eighty-six percent of patients with osteoporosis and 89 % of reoperations fused . There were no instances of screw loosening or pullout of the exp and able screws . Screw breakage occurred in four patients ( 2.8 % ) , including three patients where fusion was not obtained . In six patients the exp and able screws were removed without difficulty after fusion because of local discomfort . CONCLUSION The results of this study have shown that exp and able pedicle screws can be efficacious in cases in which pedicle screw fixation is difficult and adds a valuable tool to the growing armamentarium of spinal instrumentation Introduction Lumbar fusion in elderly patients is increasingly common . This study prospect ively investigated the clinical and radiological outcome of osteoporotic patients > 70 years with degenerative lumbar instability treated with fusion using a new cannulated , cemented , pedicle screw instrumentation augmented with PMMA . Material s and Methods The surgical protocol s , patient records , densitometry , imaging studies , and pre- and postoperative patient-reported outcome question naires of 23 patients ( mean age , 77 years ) with a follow-up of 20–49 months were review ed . All patients underwent postoperative 3D CT scan control to assess cement leakage and instrumentation position . Serial radiological controls were analyzed for secondary complications , i.e. , adjacent fractures , hardware mobilization and radiological evidence of fusion . Results Pain and function improved at 6 months and were maintained at the final follow-up . No clinical complications secondary to PMMA leakage developed . No clinical or radiological cases of non-union were observed with a mean of 1.8 levels fused . No fractures occurred in adjacent segments . There were four cases of adjacent disc disease . Three deep infections required surgical revision without removal of material and one superficial infection , all with complete remission . Conclusion This new instrumentation for degenerative lumbar disease in elderly patients is safe and effective Study Design . A prospect i ve cohort study . Objective . To demonstrate the changes in vitamin D status after surgery in female patients with lumbar spinal stenosis ( LSS ) , and its correlation with surgical outcomes . Summary of Background Data . In patients with LSS , general health including walking ability and nutritional status can be markedly improved by decompressive surgery . It can be hypothesized that such improvement may have a positive effect on their vitamin D status . Methods . In total , 31 female patients who underwent decompression and instrumented posterolateral fusion for LSS were enrolled . Serum 25-hydroxyvitamin D ( 25-OHD ) level was measured before the surgery and at 1 year postoperative visit . According to serum 25-OHD level , patients were classified into 3 groups : ( 1 ) deficient group , when 25-OHD level was less than 20 ng/mL ( < 50 nmol/L ) ; ( 2 ) insufficient group , when 25-OHD level was between 20 to 30 ng/mL ( 50 nmol/L ⩽ 25-OHD < 75 nmol/L ) ; ( 3 ) and normal group , when 25-OHD level was 30 ng/mL or more ( ≥75 nmol/L ) . The Oswestry Disability Index ( ODI ) score and health-related quality of life ( EQ-5D ) were compared according to the level of 25-OHD at 1 year postoperatively . Results . Preoperatively , there were 20 patients in the deficient group , 11 patients in the insufficient group and no patient in the normal group . There were no differences in age , body mass index , preoperative ODI scores , preoperative EQ-5D index scores , and EQ-5D visual analogue scale scores between the 2 groups . Mean preoperative 25-OHD level was 15.8 ng/mL ( range , 5.2–29.4 ng/mL ) and increased to 19.5 ng/mL ( range , 6.3–47.7 ng/mL ) 1 year after surgery ( P = 0.075 ) . Significant increase of 25-OHD was noted only in the deficient group ( P = 0.017 ) . Postoperatively , there were 18 patients in the deficient group , 8 patients in the insufficient group , and 5 patients in the normal group . In the postoperative deficient group , postoperative ODI scores and EQ-5D index scores showed significantly worse outcomes than those in the other groups . The changes in serum 25-OHD level were significantly correlated with the changes in ODI scores ( r = −0.580 ; P = 0.001 ) and with the changes in EQ-5D index scores ( r = 0.379 ; P = 0.035 ) . In all the groups , postoperative ODI scores ( r = −0.665 ; P < 0.001 ) and EQ-5D index scores ( r = 0.601 ; P < 0.001 ) were significantly correlated with postoperative 25-OHD level . Conclusion . Vitamin D deficiency was common in patients with LSS . However , vitamin D status was improved after decompressive surgery , and postoperative 25-OHD level was significantly correlated with surgical outcomes BACKGROUND CONTEXT Bisphosphonates affect bone remodeling and increase bone mass through the inhibition of osteoclasts . Their effect on osteoblasts , and the balance between osteoblastic and osteoclastic activity on bone turnover and healing , is not completely understood . Specifically , the effect of bisphosphonates on spinal fusion has yet to be determined . With the increasing use of bisphosphonates in the elderly population , this effect needs to be delineated . PURPOSE To evaluate the effect of alendronate sodium after an intertransverse process spinal fusion in a rabbit model . STUDY DESIGN / SETTING R and omized double-blinded in vivo study of the effect of alendronate sodium in a spinal fusion model . METHODS Fifty New Zeal and white rabbits underwent a posterolateral L5-L6 intertransverse process arthrodesis with autogenous iliac crest bone graft . The rabbits were then r and omly divided into two groups . Group I received 3 cc of saline placebo per oral gavage , and Group II received 200 micrograms ( approximately 0.05 mg/kg/day ) of alendronate sodium dissolved in 3 cc of saline per day for 8 weeks . Upon completion , the rabbits were sacrificed and the lumbar spines harvested , radiographed and grade d for motion across the fusion site with manual palpation . Two independent pathologists then prepared and sectioned each left and right fusion mass . Three r and om x10 fields were examined and grade d for both the cephalad and caudad ends of each section ( 516 fields ) . Fusion quality was grade d using an established histological scoring scale ( score 0 to 7 based on fibrous and bone content of the fusion mass ) . RESULTS Two rabbits died on the day of operation , and 48 rabbits survived the operation . Five additional rabbits died within the first 2 postoperative weeks . Thus , 43 rabbits ( 21 in Group I , 22 in Group II ) completed the 8-week course of treatment . Grading each side separately , 26 of 42 fusion masses ( 62 % ) in Group I and 24 of 44 fusion masses ( 55 % ) in Group II had radiographic evidence of fusion ( p=.76 ) . With gross palpation , 11 of 21 motion segments ( 52 % ) in Group I versus 13 of 22 motion segments ( 59 % ) in Group II were determined to have a solid fusion ( p=.76 ) . Histologically , Group I had a higher median score ( 6.0 ; range , 0 to 7 vs. 1.0 ; range , 0 to 7 ; p<.0001 ) and a higher fusion rate ( 76 % vs. 45 % ; p=.004 ) than Group II . CONCLUSIONS Alendronate sodium appears to inhibit or delay bone fusion in a rabbit model . Presumably , this occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing . These findings suggest that a discontinuance of alendronate sodium postoperatively during the acute fusion period may be warranted OBJECT Bisphosphonate medications are widely used for the treatment of osteoporosis , but they might disturb the healing process of spinal fusion . The object of this prospect i ve r and omized controlled study was to evaluate the effect of bisphosphonate medication on spinal fusion through radiographic , clinical , and biological assessment s. METHODS A total of 40 patients with osteoporosis who were c and i date s for single-level posterior lumbar interbody fusion were r and omly assigned to the alendronate group ( alendronate sodium 35 mg/week ) or the control group ( vitamin D , alfacalcidol 1 μg/day ) . Pedicle screw fixation and carbon polyetheretherketone cages were used for all the patients . Bone graft material was prepared as a mixture of local bone and β-tricalcium phosphate in a ratio of 2:1 . Functional radiography and CT scans were used to evaluate fusion status and cage subsidence . The incidence of vertebral compression fractures ( VCFs ) occurring after surgery ( subsequent VCFs ) was assessed by means of MR imaging . Bridging bone formation was grade d into 3 categories : Grade A ( bridging bone through bilateral cages ) , Grade B ( bridging bone through a unilateral cage ) , or Grade C ( incomplete bony bridging ) . A solid fusion was defined as less than 5 ° of angular motion in flexion-extension radiographs and the presence of bridging bone through the cage ( Grade A or B ) . Clinical outcome was evaluated by means of the Oswestry Disability Index . Bone metabolic markers ( serum bone alkaline phosphatase , serum and urine Type I collagen cross-linked N-telopeptides ) were measured to investigate the biological effects of alendronate on spinal fusion . RESULTS Bridging bone formation ( Grade A or B ) was more frequently observed in the alendronate group at all postoperative assessment periods . At 1-year postoperative follow-up , a solid fusion was achieved in 95 % of the patients in the alendronate group and 65 % of those in the control group . Cage subsidence ( > 2 mm ) was observed in 5 % of the alendronate group and 29 % of the control group . No vertebral fractures were observed in the alendronate group , whereas 24 % of patients in the control group showed subsequent VCFs . There was no statistically significant between-groups difference in clinical outcomes , but poor clinical results in the control group were associated with pseudarthrosis and subsequent VCFs . Biochemical analysis of bone turnover demonstrated that alendronate inhibited bone resorption from the early phase of the fusion process and also suppressed bone formation after 6 months postoperatively . CONCLUSIONS Favorable mechanical circumstances provided by alendronate overcame its detrimental biological effect on the healing process of spinal fusion . The authors recommend that osteoporosis patients undergoing spinal fusion take bisphosphonates throughout the postoperative period Study Design . Prospect i ve study . Objective . To examine the efficacy of teriparatide or bisphosphonate treatment to reduce pedicle screw ( PS ) loosening after instrumented lumbar posterolateral fusion in postmenopausal women with osteoporosis . Summary of Background Data . Failure of fixation caused by loosening of PSs in osteoporosis is a problem in spinal surgery . Oral administration of bisphosphonate or intermittent injection of parathyroid hormone treatment increases bone mass and reduces the risk of osteoporotic vertebral fractures . Although these treatments may be factor in improving bone quality , a clinical study of the efficacy of bisphosphonate or parathyroid hormone for reducing PS loosening that addresses the quality of the bone marrow and pedicle cortex has not yet been reported . Methods . Sixty-two women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 3 groups : a teriparatide group ( daily subcutaneous injection of 20 & mgr;g of teriparatide , n = 20 ) , a bisphosphonate group ( daily oral administration 2.5 mg of risedronate , n = 20 ) , and a control group ( without medication for osteoporosis , n = 22 ) . All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft . Loosening of PSs and surgical outcome were evaluated radiographically , clinical ly , and by computed tomography 12 months after surgery . Results . At 12-month follow-up , the incidence of PS loosening was 7 % to 13 % in the teriparatide group , 13 % to 26 % in the risedronate group , and 15 % to 25 % in the control group . The incidence of PS loosening in the teriparatide group was significantly lower than that in the risedronate or the control group ( P < 0.05 ) . In contrast , the extent of PS loosening in the risedronate group was not significantly different from that in the control group ( P > 0.05 ) . Conclusion . Our findings suggest that administration of teriparatide increased the quality of the lumbar spine bone marrow and pedicle cortex . Level of Evidence : PURPOSE To compare denosumab-induced changes in lumbar spine ( LS ) and femoral neck ( FN ) bone mineral density ( BMD ) , bone markers and free soluble receptor activator of nuclear factor kappaB lig and ( sRANKL ) between treatment naïve postmenopausal women with low bone mass ( naïve group ) and those who were previously treated with a single zoledronic acid infusion ( post-Zol group ) . PROCEDURES Procollagen type 1N-terminal propeptide ( P1NP ) , C-terminal cross-linking telopeptide of type 1 collagen ( CTx ) and sRANKL levels were measured in serum sample s obtained at baseline and 3 , 6 and 12months after denosumab initiation . LS and FN BMD were measured at baseline and 12months . RESULTS LS and FN BMD increased significantly in both naïve and post-Zol group ( p<0.001 and p=0.025 vs. p<0.001 and p=0.017 , respectively ) . Despite the higher P1NP and CTx levels in naïve patients at baseline ( both p<0.001 ) , denosumab caused comparable decreases in both groups at month 3 , which returned to post-Zol group baseline levels at month 6 and 12 in all patients . Similarly , sRANKL levels decreased significantly at month 3 in both groups and returned to baseline levels at months 6 and 12 . CONCLUSIONS In patients previously treated with zoledronic acid , sequential denosumab treatment is effective in terms of BMD increases and bone turnover suppression . Despite the lower baseline levels in patients pre-treated with zoledronic acid , bone markers are similarly decreased in both groups following denosumab administration and maintain their reversibility . Denosumab reversibly suppresses endogenous free sRANKL levels in both naïve and zoledronic acid pre-treated patients |
12,649 | 21,150,188 | In addition , there is strong evidence that cancer patients receiving ESAs have an increased risk of thromboembolic and cardiovascular events . | Anemia associated with cancer and cancer therapy is a common and important issue in the treatment of patients with malignant disease .
Conventionally , blood transfusions are used to treat severe cancer-related anemia .
Short- and long-acting preparations of recombinant human erythropoiesis-stimulating agents ( ESAs ) offer an alternative treatment option .
Multiple studies and subsequent meta-analyses have demonstrated that ESA treatment increases hemoglobin levels and reduces the likelihood of transfusion for a proportion of treated patients .
However , studies that attempted to evaluate whether ESAs improve tumor response and survival have generated conflicting evidence . | Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer 6007 Background : The study aim ed to evaluate if correction of low hemoglobin ( Hb ) levels by means of the erythropoietin stimulating agent : darbepoetin alpha ( Aranesp ) during radiotherapy ( RT ) improves outcome in patients with HNSCC . Following a planned interim analysis which showed inferiority of the experimental treatment , the trial was stopped in November 2006 . METHODS Pts with HNSCC eligible for primary RT alone and with Hb values below 14.0 g/dl were r and omized to receive Aranesp together with accelerated fractionated RT . Pts . were stratified according to gender , T and N staging , tumor site , and institution . Aranesp was given subcutaneously in a dose of 150 micrograms weekly during RT , or stopped earlier if the Hb exceeded 15.5 g/dl . RESULTS In total , 522 patients ( of a planned intake of 600 ) were included at the time of the interim analysis . Of these 514 pts were eligible for analysis ( 255 pts treated with Aranesp and 259 pts in the control group ) with a median follow up of 49 months . Among these , 201 developed a loco-regional failure ( primary endpoint ) . There have been 238 deaths of which 176 are due to HNSCC . The patients were evenly distributed according to the stratification parameters ( gender , T and N staging , tumor site , institution).Aranesp result ed in the expected increase in Hb in more than 81 % of the patients . The compliance to Aranesp was good with no significant difference in serious ( cardiovascular ) adverse events ( 3 % vs. 1 % ) . Overall , the results showed a poorer outcome in 5-year loco-regional control ( 59 % vs. 68 % ( p = 0.04 , RR : 1.47 [ 1.14 - 1.94 ] ) for the Aranesp vs. control arm . This was also seen for the endpoint of disease-free survival ( 37 % vs. 47 % , p = 0.02 , RR : 1.32 [ 1.04 - 1.68 ] ) , whereas there was no significant difference in overall survival ( 40 % vs. 51 % , p = 0.16 , RR : 1.20 [ 0.93 - 1.55 ] ) . There were no differences in radiation related morbidity . All univariate analyses were confirmed in a multivariate setting . CONCLUSIONS Correction of the Hb level with Aranesp in patients with HNSCC result ed in a significantly poorer tumor control after radiotherapy . The treatment principle was ab and oned and the difference in outcome is being subjected to further examination . No significant financial relationships to disclose BACKGROUND Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life ( HRQOL ) . We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL . PATIENTS AND METHODS These analyses were based on five r and omized trials . Patients completed the Functional Assessment of Cancer Therapy ( FACT ) Anemia scales and numeric rating scales of Energy , Activity and Overall Health at baseline and after the 12-week treatment period . t-tests and linear regression models were used to evaluate associations . Analyses were stratified into three groups : solid tumor chemotherapy patients , lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients . RESULTS Adjusted mean differences ( 95 % CI ) in FACT Fatigue change scores between hemoglobin responders ( > or = 2 g/dl increase ) and non-responders were 3.0 ( 1.2 , 4.7 ) , 2.8 ( 0.6 , 5.0 ) and 5.8 ( 2.2 , 9.5 ) among the solid tumor , lymphoproliferative malignancy and non-chemotherapy groups , respectively . Significantly greater improvements ( P < 0.01 ) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue ( FACT Fatigue change score > or =3 points ) . After controlling for other factors , patients whose fatigue improved reported substantially greater improvements in energy , ability to perform usual activities and overall health ( P < 0.0001 ) . CONCLUSIONS Across five trials of cancer patients on and off chemotherapy , hemoglobin response was associated with meaningful improvements in fatigue , which , in turn , was associated with improved physical , functional , emotional and overall well-being A recent study in dogs suggested that erythropoietin ( EPO ) not only promotes the synthesis of increased numbers of reticulated platelets but that these newly produced platelets are hyperreactive compared with controls . Because of the increasing use of EPO in the perioperative setting , we characterized the effects of EPO on platelet reactivity in healthy human volunteers . In a r and omized , controlled trial , we studied the effects of EPO on platelet reactivity , thrombopoiesis , and endothelial activation in circumstances similar to those of autologous blood donation . Thirty healthy male volunteers received placebo or EPO ( 100 or 500 U/kg of body weight given intravenously ) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15 . Thrombin receptor-activating peptide induced expression of P-selectin , and CD63 increased 2- to 3-fold during EPO treatment . The enhanced platelet reactivity was also reflected by a 50 % increase in soluble P-selectin in plasma . Plasma E-selectin levels increased in a dose-dependent fashion by more than 100 % during EPO treatment , indicating substantial activation of endothelial cells . A 10 % to 20 % increase in platelet counts was observed in both EPO groups on day 5 . In the placebo group , platelets increased only several days after the first phlebotomy . The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells . In summary , we found that EPO markedly enhances endothelial activation and platelet reactivity , which may adversely affect patients at cardiovascular risk . However , the increased platelet reactivity could be exploited in patients with platelet dysfunction . ( Blood . 2000;95:2983 - 2989 BACKGROUND AND OBJECTIVES Continuous erythropoietin receptor activator ( C.E.R.A. ) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life , which has the potential for administration at extended dosing intervals . The objectives of this dose-finding study were to evaluate the hemoglobin ( Hb ) dose-response , pharmacokinetics , and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma ( MM ) receiving chemotherapy . DESIGN AND METHODS This was an exploratory two-stage , open-label , parallel-group , multicenter study . Patients received C.E.R.A. doses of 1.0 , 2.0 , 3.5 , 4.2 , 5.0 , 6.5 , or 8.0 mg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks , followed by a 12-week optional extension period . The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period , based on values of the slope of the linear regression analysis and the area under the curve . Rates of Hb response ( defined as an increase in Hb of > or = 2 g/dL without transfusion ) and blood transfusion were also evaluated . RESULTS Sixty-four patients entered the study . Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0 - 4.2 mg/kg , with a similar response observed at higher doses . At least 70 % of patients receiving 2.0 - 8.0 mg/kg of C.E.R.A. had Hb responses during the 18-week study . The elimination half-life of C.E.R.A. was found to be long ( 6.3 - 9.7 days [ 151.2 - 232.8 hours ] ) . All doses were generally well tolerated . INTERPRETATION AND CONCLUSIONS Based on its unique , long elimination half-life , C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy PURPOSE To determine the effect of darbepoetin alfa ( DA ) on progression-free survival ( PFS ) and overall survival ( OS ) in patients with chemotherapy-induced anemia ( CIA ) . PATIENTS AND METHODS Two 16-week r and omized , double-blind , placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer ( n = 314 ) or lymphoproliferative malignancies ( LPMs ; n = 344 ) undergoing chemotherapy were analyzed with prospect ively defined long-term PFS and OS end points . Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding , double-blind , placebo-controlled studies in anemic patients with multiple tumor types ( n = 405 ) and LPMs ( n = 66 ) . RESULTS Median follow-up is 15.8 months ( lung cancer ) and 32.6 months ( LPM ) . Median duration of PFS was comparable between DA and placebo : 5.1 months ( 95 % CI , 4.1 to 6.9 months ) versus 4.4 months ( 95 % CI , 3.7 to 5.3 months ) for lung cancer and 14.2 months ( 95 % CI , 12.2 to 17.5 months ) versus 15.9 months ( 95 % CI , 13.1 to 19.0 months ) for LPMs . The estimated hazard ratio ( HR ) of death related to DA use for lung cancer was 0.77 ( 95 % CI , 0.59 to 1.01 ) and 1.26 ( 95 % CI , 0.92 to 1.71 ) for LPMs . In the pooled analyses of all four studies ( n = 1,129 ) , no differences in PFS or OS were observed between DA and placebo ( HR = 0.92 ; 95 % CI , 0.78 to 1.07 ; and HR = 0.95 ; 95 % CI , 0.78 to 1.16 , respectively ) . CONCLUSION Treatment with DA does not seem to influence PFS or OS in patients with CIA . Prospect i ve , r and omized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL , or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa 150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P < .001 ) . Improvement of all primary cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P < .01 ) greater for epoetin alfa versus placebo patients . Although the study was not powered for survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa . Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings GUIDELINE QUESTIONS 1 ) Does erythropoietin ( EPO ) reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer ? 2 ) Does the administration of EPO improve the quality of life of these cancer patients ? OBJECTIVE To make recommendations regarding the use of EPO to reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer . OUTCOMES First transfusion requirement from the start of chemotherapy is the main outcome of interest . Quality of life and costs are also considered . PERSPECTIVE ( VALUES ) Evidence was selected and review ed by 5 members of the Ontario Cancer Treatment Practice Guidelines Initiative ( OCTPGI ) and the Systemic Treatment Program Committee ( STPC ) . Drafts of this document have been circulated to and review ed by members of the STPC . The STPC comprises medical oncologists , pharmacists , supportive care personnel and administrators . No community representative participated in the development of this practice guideline . QUALITY OF EVIDENCE Eleven r and omized controlled trials ( RCTs ) , most placebo-controlled , were available for review . A meta- analysis was performed with 8 trials that shared a clinical ly relevant outcome measure . Only 1 trial assessed quality of life . BENEFITS The meta- analysis showed a relative risk for transfusion among EPO patients of 0.64 ( 95 % confidence interval 0.53 - 0.78 ) , which translates into a 36 % relative reduction in the proportion of patients requiring transfusion ( p = 0.00001 ) . Reduction in transfusion requirements was similar across strata defined by method ological quality , EPO dose , hematologic status , tumour type at trial entry and chemotherapy regimen . In the 1 trial that assessed quality of life , EPO was associated with improved quality of life . HARMS Hypertension has been noted rarely in EPO-treated cancer patients . The RCTs did not report adverse effects in EPO-treated patients compared with control patients during the follow-up period . Long-term adverse effects are unknown . EPO is more costly than transfusion , but formal cost-effectiveness studies are unavailable . PRACTICE GUIDELINE For patients receiving chemotherapy for nonhematologic cancer in whom symptoms of anemia are expected and in whom transfusion of red blood cells is not considered an acceptable treatment option , EPO can be recommended as a safe , effective treatment alternative . The evidence in support of using EPO is stronger for patients receiving platinum-based chemotherapy regimens that for those receiving non-platinum-based regimens . CLINICAL PRACTICE GUIDELINE DATE : Apr. 4 , 1997 PURPOSE A placebo-controlled , double-blind , r and omized , phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival . PATIENTS AND METHODS Darbepoetin alpha ( 300 microg ) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy ( carboplatin plus etoposide or cisplatin plus etoposide ) plus 3 weeks after the last dose of chemotherapy . Patients with disease progression were observed until death or until all patients completed their end-of- study visit and 496 deaths had occurred . The two co primary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival ; statistical testing of survival was done if change in hemoglobin was significant at P < .05 . RESULTS The study enrolled 600 patients . Patients ' hemoglobin levels dropped due to the myelosuppressive chemotherapy ; however , treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo ( P < .001 ) . There was no statistically significant difference in overall survival between the treatment groups ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.78 to 1.11 ; P = .431 ) . As expected , darbepoetin alpha was associated with a higher incidence of thromboembolic events ( darbepoetin alpha , 9 % ; placebo , 5 % ) . The transfusion risk was lower in the darbepoetin versus placebo group ( HR , 0.40 ; 95 % CI , 0.29 to 0.55 ) . CONCLUSION The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha ; however , they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia PURPOSE Chemotherapy-induced anemia is widely treated in the United States with darbepoetin alfa ( DA ) or epoetin alfa ( EA ) . This noninferiority study systematic ally compares efficacy and safety of DA and EA using common doses and schedules used in clinical practice . METHODS Patients had a diagnosis of nonmyeloid malignancy with > or = 8 weeks of planned chemotherapy , age > or = 18 years , and anemia ( hemoglobin < or = 11 g/dL ) . Patients were r and omly assigned 1:1 to DA 200 microg every two weeks ( Q2W ) or EA 40,000 units every week ( QW ) for up to 16 weeks with identical dose adjustment rules . Efficacy was assessed by the incidence of RBC transfusion ( Kaplan-Meier estimate ) . The definition of noninferiority was that the upper 95 % CI limit of the observed difference in RBC transfusions between groups was less than 11.5 % ; this noninferiority margin was based on the treatment effect observed in placebo-controlled EA studies . RESULTS Of 1,220 patients r and omly assigned , 1,209 received > or = one dose of the study drug . Common tumor types were lung ( 26 % ) , breast ( 21 % ) , and gastrointestinal ( 18 % ) . Transfusion incidence from week 5 to the end of the treatment phase ( the primary end point ) was 21 % in the DA group and 16 % in the EA group ; noninferiority was concluded because the upper 95 % CI limit of the difference between groups ( 10.8 % ) was below the prespecified noninferiority margin . Sensitivity analyses using alternate statistical methods and analysis sets yielded similar results . Hemoglobin , quality of life , and safety end points further support equivalency of the erythropoietic therapies . CONCLUSION This large , phase III study demonstrates comparable efficacy of DA Q2W and EA QW . Less frequent dosing offers potential benefits for patients , caregivers and health care providers Abstract Objectives : To determine the extent to which publication is influenced by study outcome . Design : A cohort of studies su bmi tted to a hospital ethics committee over 10 years were examined retrospectively by review ing the protocol s and by question naire . The primary method of analysis was Cox 's proportional hazards model . Setting : University hospital , Sydney , Australia . Studies : 748 eligible studies su bmi tted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988 . Main outcome measures : Time to publication . Results : Response to the question naire was received for 520 ( 70 % ) of the eligible studies . Of the 218 studies analysed with tests of significance , those with positive results ( P<0.05 ) were much more likely to be published than those with negative results ( P0.10 ) ( hazard ratio 2.32 ( 95 % confidence interval 1.47 to 3.66 ) , P=0.0003 ) , with a significantly shorter time to publication ( median 4.8 v 8.0 years ) . This finding was even stronger for the group of 130 clinical trials ( hazard ratio 3.13 ( 1.76 to 5.58 ) , P=0.0001 ) , with median times to publication of 4.7 and 8.0 years respectively . These results were not material ly changed after adjusting for other significant predictors of publication . Studies with indefinite conclusions ( 0.05 P<0.10 ) tended to have an even lower publication rate and longer time to publication than studies with negative results ( hazard ratio 0.39 ( 0.13 to 1.12 ) , P=0.08 ) . For the 103 studies in which outcome was rated qualitatively , there was no clear cut evidence of publication bias , although the number of studies in this group was not large . Conclusions : This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor . The study results support the need for prospect i ve registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic review s. Key messages This retrospective cohort study of clinical research projects confirms the findings of publication bias found in previous studies Delay in the publication of studies with negative results has been identified as an additional important factor in publication bias With the recognised importance of evidence based medicine , these results have important implication s for the selection of studies included in systematic review s Prospect i ve registration of clinical research projects will avoid many of the problems associated with publication bias However , it is also important to restrict inclusion in systematic review s to studies started before a certain date to allow for the delay in completing studies with negative AIMS To assess the effect of epoetin delta on anaemia in patients with cancer who were receiving chemotherapy . MATERIAL S AND METHODS This report includes data from two 12-week studies of epoetin delta : a r and omised , double-blind , placebo-controlled study of three times weekly epoetin delta ( 150 or 300IU/kg ) and an open-label extension collecting further efficacy and safety information , in which patients initially received epoetin delta 150IU/kg . Co- primary end points for the double-blind study were an increase in haemoglobin levels and a reduction in the requirement for red blood cell transfusions compared with placebo . RESULTS Double-blind study : 313 cancer patients were r and omised to epoetin delta or placebo . Epoetin delta was associated with a significantly greater increase in haemoglobin levels from baseline compared with placebo ( epoetin delta 150 and 300IU/kg vs placebo : 2.5 and 2.5g/dl vs 0.6g/dl ; P<0.0001 for both comparisons ) , meeting one co- primary end point . However , there were no significant differences between groups in the proportion of patients requiring red blood cell transfusions ( epoetin delta 150 and 300IU/kg vs placebo : 26.0 and 21.9 % vs 26.9 % ) , the second co- primary end point . Open-label study : 149 patients entered the extension study . During the extension , haemoglobin levels were maintained and a higher proportion of patients who previously received placebo required transfusions than those who had previously received epoetin delta ( previous epoetin delta 150 and 300IU/kg : 7.1 and 11.4 % vs previous placebo : 15.9 % ) . Adverse events were as expected for this population in both studies . CONCLUSION Epoetin delta shows potential as a treatment for anaemia in cancer patients receiving chemotherapy The European Cancer Anaemia Survey ( ECAS ) was conducted to prospect ively evaluate the prevalence , incidence and treatment of anaemia ( haemoglobin < 12.0 g/dL ) in European cancer patients , including the relationship of mild , moderate and severe anaemia to performance status . Patients were evaluated for up to 6 months . Data ( N=15367 ) included demographics , tumour type , performance status , haemoglobin levels , cancer treatments and anaemia treatments . Prevalence of anaemia at enrollment was 39.3 % ( haemoglobin < 10.0 g/dL , 10 % ) , and 67.0 % during the survey ( haemoglobin < 10.0 g/dL , 39.3 % ) . Low haemoglobin levels correlated significantly with poor performance status . Incidence of anaemia was 53.7 % ( haemoglobin < 10.0 g/dL , 15.2 % ) . Anaemia was treated in 38.9 % of patients ( epoetin , 17.4 % ; transfusion , 14.9 % ; and iron , 6.5 % ) . Mean haemoglobin to initiate anaemia treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are high . Anaemia significantly correlates with poor performance status and many anaemic patients are not treated |
12,650 | 28,361,446 | No strong associations were observed for IGF-II , IGFBP-1 or IGFBP-2 with either milk intake or prostate cancer risk .
There was additional evidence to suggest that the suppression of IGF-II can reduce tumor size , and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumor progression .
Conclusion IGF-I is a potential mechanism underlying the observed associations between milk intake and prostate cancer risk | Purpose To establish whether the association between milk intake and prostate cancer operates via the insulin-like growth factor ( IGF ) pathway ( including IGF-I , IGF-II , IGFBP-1 , IGFBP-2 , and IGFBP-3 ) . | BACKGROUND Plasma levels of insulin-like growth factor-I ( IGF-I ) have been associated with the risk of prostate cancer . However , the association of IGF-I with specific tumor stage and grade at diagnosis , which correlate with risk of recurrence and mortality , has not been studied rigorously . To determine whether plasma levels of IGF-I and its main circulating binding protein , IGF binding protein-3 ( IGFBP-3 ) , predict more aggressive forms of prostate cancer , we investigated the association between plasma levels of each and specific stages and grade s of prostate cancer . METHODS We examined 530 case patients and 534 control subjects in a nested case-control study in the prospect i ve Physicians ' Health Study . Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status . IGF-I and IGFBP-3 were measured in prospect ively collected plasma sample s. Conditional logistic regression models were used to estimate the relative risks ( RRs ) for prostate cancer associated with IGF-I and IGFBP-3 , stratified on grade ( Gleason score > or = 7 versus < 7 ) and stage ( early = stage A or B prostate cancer versus advanced = stage C or D prostate cancer ) . All statistical tests were two-sided . RESULTS Plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer ( RR = 5.1 , 95 % confidence interval [ CI ] = 2.0 to 13.2 for highest versus lowest quartiles of IGF-I ; RR = 0.2 , 95 % CI = 0.1 to 0.6 for highest versus lowest quartiles of IGFBP-3 ) but not of early-stage prostate cancer . Neither was differentially associated with Gleason score . Men with high IGF-I levels and low IGFBP-3 levels had an RR for advanced-stage prostate cancer of 9.5 ( 95 % CI = 1.9 to 48.4 ) compared with men with low levels of both . Combining IGF-I and IGFPB-3 measurements with a st and ard prostate-specific antigen ( PSA ) measurement for prostate cancer screening increased the specificity ( from 91 % to 93 % ) but decreased sensitivity ( from 40 % to 36 % ) compared with measurement of PSA alone . CONCLUSIONS Circulating levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer , but their utility for screening patients with incident prostate cancer may be limited Recent studies have suggested that IGF-I and IGF-binding protein (IGFBP)-3 , in combination with prostate-specific antigen ( PSA ) , may enhance prostate cancer detection . In this study , we sought to determine the effect on the prediction of future prostate cancer occurrence by incorporating ratios of total and free PSA , IGF-I , IGFBP-3 into PSA testing . Within a population -based prospect i ve cohort study , we investigated the validity ( sensitivity and specificity ) of plasma concentrations of total and free PSA , IGF-I , and IGFBP-3 and combinations thereof , in 114 cases and 97 controls , in the range of 1.75 - 13.5 microg/l for PSA , as used by Khosravi et al. ( See Ref . 7 ) . Validity estimated by the area under the curve in receiver operator characteristics analysis ( with 95 % confidence interval ) for total PSA was 0.78 ( range , 0.71 - 0.84 ) ; total/free PSA , 0.69 ( range , 0.62 - 0.76 ) ; total PSA/IGF-I , 0.72 ( range , 0.65 - 0.79 ) ; free PSA/IGF-I , 0.55 ( range , 0.48 - 0.63 ) ; total PSA/IGFBP-3 , 0.74 ( range , 0.68 - 0.81 ) ; and free PSA/IGFBP-3 , 0.57 ( range , 0.49 - 0.64 ) . Analysis of ratios of IGF-I , IGFBP-3 , and free and total PSA did not improve validity of PSA testing in the prediction of future occurrence of prostate cancer . It is unlikely that these combinations will improve prostate cancer detection Background : The acid-labile subunit ( ALS ) acts in the insulin-like growth ( IGF ) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier . Given the role of the IGF system in prostate cancer , ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability . Methods : We undertook a prospect i ve study nested in the Physicians ' Health Study to examine ALS , free IGF-I , and prostate cancer . We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls . We calculated relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) adjusted for life-style factors , total IGF-I , and IGFBP3 . Results : ALS was positively correlated with total IGF-I ( r = 0.58 ) , IGFBP3 ( r = 0.68 ) , and free IGF-I ( r = 0.36 ) . Comparing highest versus lowest quartiles , we found no association between free IGF-I and prostate cancer risk ( RR , 0.9 ; 95 % CI , 0.6 - 1.3 ) . In contrast , ALS was positively associated with risk among men in the 2nd ( RR , 1.5 ; 94 % CI , 1.0 - 2.3 ) , 3rd ( RR , 1.6 ; 94 % CI , 1.1 - 2.5 ) , and 4th quartiles ( RR , 1.4 ; 94 % CI , 0.9 - 2.1 ) compared with lowest quartile . The association was stronger for advanced stage tumors ( RR , 2.0 ; 94 % CI , 0.8 - 4.6 ) . There was a suggestion of an interaction between ALS and total IGF-I , whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels . Discussion : Plasma ALS is positively associated with prostate cancer risk , and may interact biologically with IGF-I to affect carcinogenesis . These data provide further support for the role of the IGF axis in prostate cancer . Cancer Epidemiol Biomarkers Prev ; 19(2 ) ; A major problem in review ing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways . The purpose of this paper is to exemplify methods by which results expressed either as risks ( or rates ) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner , as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study . An important assumption of the methods is that the quantitative variable has an approximately normal distribution , and a way of investigating the appropriateness of this assumption is given . The methods can be applied to both prospect i ve and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality . In some applications , these methods can be used as a precursor to formal meta- analysis , for example , when differential control of potential confounding factors is not a problem . At the least , the methods can be useful either in quantitatively review ing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors ( IGF ) and of IGF-binding proteins ( IGFBP ) and prostate cancer risk . We assessed the association of prediagnostic plasma levels of IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial . The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France . One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period . For each case , four age-matched controls were selected r and omly . Frozen baseline plasma sample s were used to measure IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 . Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk . After controlling for the intervention group in the trial and the other IGF axis variables , the odds ratios and 95 % confidence interval ( 95 % CI ) comparing the upper quartile to the baseline quartile were 1.83 ( 95 % CI , 0.85 - 3.95 ) , 1.05 ( 95 % CI , 0.35 - 3.18 ) , 0.79 ( 95 % CI , 0.39 - 1.58 ) , and 0.42 ( 95 % CI , 0.12 - 1.52 ) for IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 , respectively . More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers . Our results are consistent with those of some previous prospect i ve studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer Circulating concentrations of insulin-like growth factor I ( IGF-I ) and IGF binding proteins ( IGFBP ) have been associated with the risk of several types of cancer . Dietary correlates of IGF-I and IGFBPs are not yet well established . The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I , IGFBP-1 , IGFBP-2 , and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospect i ve Investigation into Cancer and Nutrition . Diet was assessed using country-specific vali date d dietary question naires . Serum concentrations of IGF-I , IGFBP-1 , IGFBP-2 and IGFBP-3 were measured , and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex , age , body mass index , smoking status , and alcohol and energy intake . Each 1 SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5 % , 2.4 % , and 3.3 % , respectively ( P for trend < 0.001 for all ) and a decrease in IGFBP-2 of 3.5 % , 3.5 % , and 5.4 % ( P for trend < 0.001 for all ) , respectively . There were no significant associations between the intake of protein or calcium from nondairy sources and IGF-I. The results from this large cross-sectional analysis show that either the intake of dairy protein or calcium is an important dietary determinant of IGF-I and IGFBP-2 concentrations ; however , we suggest that it is more likely to be protein from dairy products . ( Cancer Epidemiol Biomarkers Prev 2009;18(5):1333–40 OBJECTIVE To quantify the level of insulin-like growth factor ( IGF-1 ) in serum and investigate its role in the diagnosis of prostate cancer . METHODS IGF-1 immunoradiometric assay ( IRMA ) was set up and used to determine serum IGF-1 level in patients with prostate cancer ( n = 81 ) , benign prostate hyperplasia ( BPH , n = 55 ) , uroepithelial tumor ( n = 32 ) and healthy male controls ( n = 84 ) . Furthermore , the levels of IGF-1 and prostate-specific antigen ( PSA ) in 38 patients with BPH were determined every three months for one year . RESULTS Linearity was well demonstrated for IGF-1 in the range of 8 - 1000 ng ( r = 0.98 ) , the lowest limit for detecting IGF-1 being 2 mg/L and the mean recovery for detecting IGF-1 being 94.5 % . The within-replicate coefficient of variance ( CV ) of IGF-1 detection was 7.2 % for a higher level ( 382.4 mg/L ) and 4.2 % for a low level ( 32.5 mg/L ) of IGF-1 . Insulin , growth factor or IGF-2 did not interfere with the detection of IGF-1 ( < 3 ml/L ) . There was high level of IGF-1 in patients with prostate cancer than in healthy controls , patients with BPH and uroepithelial tumor ( P < 0.05 ) ; the odds ratio and its 95 % confidence intervals were 2.86 and 1.38 - 5.34 , respectively ; the specificity and sensitivity of IGF-1 determination were 0.68 and 0.58 , respectively ; furthermore , the level of IGF-1 was increased during the development of prostate cancer . CONCLUSIONS These findings demonstrate that IGF-1 may serve prospect ively as an important tumor marker in the diagnosis and prediction of prostate cancer Background Nutrients , hormones and growth factors in dairy foods may stimulate growth hormone ( GH ) , insulin-like growth factor I ( IGF-I ) , and raise the ratio of IGF-I to its binding protein , IGFBP-3 . We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children . Methods In Ulaanbaatar , we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10–11 year old schoolchildren . In a r and omized cross-over study in Boston , we compared plasma hormone levels of 28 6–8 year old girls after one week of drinking 710 ml lowfat ( 2 % ) milk with their hormone levels after one week of consuming a macronutrient substitute for milk . Results After a month of drinking whole milk , Mongolian children had higher mean plasma levels of IGF-I ( p < 0.0001 ) , IGF-I/IGFBP-3 ( p < 0.0001 ) , and 75th percentile of GH levels ( p = 0.005 ) . After a week of drinking lowfat milk , Boston girls had small and non-significant increases in IGF-1 , IGF-1/IGFBP-3 and GH . Conclusion Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys . The finding that milk intake may raise GH levels is novel , and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production A western lifestyle , characterised by low rates of energy expenditure and a high-energy diet rich in animal protein , saturated fats and refined carbohydrates , is associated with high incidence of prostate cancer in men . A high-energy nutritional status results in insulin/IGF signalling in cells , which in turn stimulates synthesis of fatty acids . We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospect i ve Investigation on Cancer ( EPIC ) . Using a tagging approach and selecting 252 SNPs in 22 genes , we covered all the common genetic variation of this pathway . None of the SNPs reached statistical significance after adjusting for multiple comparisons . Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk Some recent epidemiologic studies have failed to confirm positive associations between insulin-like growth factor-I ( IGF-I ) and the risk of prostate cancer observed in earlier studies but have reported suggestive evidence for a positive association between IGF-binding protein-3 ( IGFBP-3 ) and prostate cancer risk , a result contradicting the earlier assumption that high levels of IGFBP-3 would be protective against prostate cancer . We tested the association between IGF-I and IGFBP-3 and prostate cancer risk by measuring the two peptides in plasma sample s collected at baseline in a prospect i ve cohort study of 17,049 men . We used a case-cohort design , including 524 cases diagnosed during a mean of 8.7 years follow-up and a r and omly sample d subcohort of 1,826 men . The association between each peptide level and prostate cancer risk was tested using Cox models adjusted for country of birth and alcohol consumption . The risk of prostate cancer was not associated with baseline levels of IGF-I or the molar ratio IGF-I/IGFBP-3 ( all odds ratios are between 0.82 and 1.08 ; Ptrend ≥ 0.2 ) , whereas the risk increased with baseline levels of IGFBP-3 ( Ptrend = 0.008 ) , the hazard ratio ( HR ) associated with a doubling of the concentration of IGFBP-3 being 1.70 ( 95 % confidence interval , 1.15 - 2.52 ) . The HR for quartile 4 relative to quartile 1 of IGFBP-3 was 1.49 ( 95 % confidence interval , 1.11 - 2.00 ) . The HRs did not differ by tumor aggressiveness or age at onset ( all Ps ≥ 0.4 ) . In our study , high levels of IGFBP-3 but not IGF-I were associated with an increased risk of prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2006;15(6):1137–41 Insulin-like growth factors ( IGFs ) have potent mitogenic and antiapoptotic effects on prostate epithelial cells . Through modulation of IGF bioactivity and other mechanisms , IGF-binding proteins ( IGFBPs ) also have growth-regulatory effects on prostate cells . Recently , IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western population s. To assess whether IGF-I , IGF-II , IGFBP-1 , or IGFBP-3 are also associated with prostate cancer in a low-risk population , we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 r and omly selected population controls in Shanghai , China . Relative to the lowest quartile of IGF-I levels , men in the highest quartile had a 2.6-fold higher prostate cancer risk , with a significant trend [ odds ratio ( OR ) = 2.63 ; 95 % confidence interval ( 95 % CI ) = 1.19 - 5.79 ; P(trend ) = 0.01 ] . In contrast , men in the highest quartile of IGFBP-3 levels had a 46 % decreased risk relative to the lowest quartile ( OR = 0.54 ; 95 % CI = 0.26 - 1.15 ; P(trend ) = 0.08 ) . A similar but less distinct result was observed for IGFBP-1 ( OR = 0.60 ; 95 % CI = 0.31 - 1.17 ; P(trend ) = 0.25 ) . Men in the highest quartile for the IGF-I : IGFBP-3 molar ratio ( an indirect measure of free IGF-I ) had a 2.5-fold higher risk compared with the lowest quartile ( OR = 2.51 ; 95 % CI = 1.32 - 4.75 , P(trend ) < 0.001 ) . These associations were more pronounced after adjustment for serum 5alpha- and rostane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels . There was no significant association with IGF-II levels . Our findings in a low-risk population provide evidence that IGF-I , IGFBP-3 , and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to eluci date carcinogenic mechanisms Abstract Circulating insulin-like growth factor binding protein 1 ( IGFBP-1 ) , leptin , and insulin are 3 proteins modified by obesity and have been associated with cancer at several sites in past studies . We conducted a cross-sectional study to describe the correlation of these proteins with gender , race/ethnicity , anthropometric indexes , and dietary and lifestyle factors . We measured fasting plasma levels of IGFBP-1 , leptin , and C-peptide , used here as a stable measure of insulin secretion , in a r and om sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles Multiethnic Cohort Study ( MEC ) participants ( age range 47–82 yr at blood draw ) . Through a series of multiple linear regressions , we found that the most parsimonious model for plasma IGFBP-1 included inverse associations with age , body mass index ( BMI ) , and regular soda intake . A term for interaction between age and BMI was positively associated with plasma IGFBP-1 . Adjusted mean plasma leptins were highest among Whites and African Americans and lowest among Hawaiians and Japanese Leptin was also inversely associated with age and positively associated with the interaction between age and race/ethnicity , female gender , and BMI . A model with only race/ethnicity and BMI ( positive association ) was best for plasma C-peptide . Adjusted means for C-peptide were highest for Japanese and Whites and lowest for African Americans . The overall percent of variance in protein levels explained by these models was low for IGFBP-1(R2 = 0.17 ) and C-peptide ( R2 = 0.11 ) and higher for leptin ( R2 = 0.57 ) . We saw no clear correlation between racial/ethnic trends in protein levels with those of colorectal , breast , or prostate cancer incidence rates in the MEC . Research to clarify factors associated with determination of these proteins and their relationship with cancer etiology is warranted Context Many studies have reported associations of insulin-like growth factors ( IGFs ) and IGF-binding proteins ( IGFBPs ) with prostate cancer development , but none have investigated their association with fatal progression of prostate cancer . Objective We investigated associations of circulating IGF-I , IGF-II , IGFBP-2 and IGFBP-3 with all-cause and prostate cancer mortality in men with clinical ly identified prostate cancer , stratified by whether localised ( stage T1 or T2 ) or advanced ( T3 , T4 , N1 or M1 ) at diagnosis . Design , setting and participants UK hospital-based cohort study of 396 men with prostate cancer , diagnosed between 1990 and 2008 , with mean follow-up of 3.7 years . Main outcome measures All-cause and prostate cancer – specific mortality . Results In men with advanced cancer , there was some evidence that IGF-I was positively associated ( HR 1.20 ; 95 % CI : 0.96 , 1.49 ; p = 0.11 ) and IGFBP-3 was inversely associated ( HR 0.84 ; 95 % CI : 0.70 , 1.01 ; p = 0.07 ) with all-cause mortality after controlling for age , treatment status , smoking , prostate-specific antigen and Gleason grade at diagnosis . There was some evidence that IGF-I was positively associated with prostate cancer mortality in advanced cases ( HR 1.23 ; 95 % CI : 0.94 , 1.62 ; p = 0.13 ) . In advanced cancers , associations of IGF-I with all-cause ( HR 1.68 ; 95 % CI : 1.28 , 2.23 ; p < 0.001 ) and prostate cancer – specific ( HR 1.59 ; 95 % CI : 1.11 , 2.28 ; p = 0.01 ) mortality strengthened ( and were conventionally statistically significant ) after further controlling for IGFBP-3 . Conclusions Measures of IGF-I and IGFBP-3 may have potential as prognostic markers in predicting risk of death in men with advanced prostate cancer . Large , prospect i ve studies with repeat IGFs and IGFBPs are now required Recent studies have reported that serum IGF-I levels in the highest quartile of the normal range and IGF binding protein-3 ( IGFBP-3 ) in the lowest quartile of the normal range are associated with an increased risk of future prostate cancer and /or presence of prostate cancer . It has also been suggested that the measurement of circulating total IGF-I concentrations might be a useful tool for the early detection of prostate cancer in men with moderately increased prostate-specific antigen ( PSA ) levels . To determine whether circulating free IGF-I , total IGF-I , and IGFBP-3 levels can predict future prostate cancer risk , we prospect ively studied prostate cancer characteristics in a cohort of men during two rounds ( mean interval , 4 yr ) of a population -based screening study for prostate cancer . Two hundred one prostate cancer cases were detected at the second-round screening ( aged 55 - 70 yr ) , and all these subjects were enrolled in the case group for the present study . Prostate cancer had been confirmed by biopsy in all cases . These 201 subjects were matched with the 201 nonprostate cancer cases by age , serum PSA range at the first-round screening ( PSA < 2 ng/ml , n = 67 ; PSA = 2 - 3 ng/ml , n = 67 ; and PSA = 3 - 4 ng/ml , n = 67 ) , and residence area . At baseline , total IGF-I , free IGF-I , and IGFBP-3 levels and prostate volume of cases with prostate cancer were not different from those of healthy controls . PSA velocity was significantly different between cases and controls ( P < 0.001).Stepwise forward logistic regression analysis showed that only PSA levels at baseline and PSA at round 2 after 4 yr are good predictors of prostate cancer , whereas total IGF-I , free IGF-I , and IGFBP-3 did not predict the development of prostate cancer . Only one of the 201 subjects with prostate cancer had metastases . Within the subjects with prostate cancer , there were no differences of IGF-I parameters with different tumor node metastasis categories and /or Gleason scores . Our study suggests that the measurement of serum IGF-I and /or IGFBP-3 concentrations in addition to PSA does not improve the identification of men at high risk to develop early stages of prostate cancer . In addition , our results indicate that the endocrine IGF-I system is not directly involved in the growth of the early stages of prostate cancer Background : High circulating insulin-like growth factor-I ( IGF-I ) concentrations have been associated with increased risk for prostate cancer in several prospect i ve epidemiological studies . In this study , we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Methods : In a nested case – control design , 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center , age at recruitment , duration of follow-up , time of day , and duration of fasting at blood collection . Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration , overall and by various subgroups . Results : Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [ OR for highest vs. lowest quartile , 1.69 ; 95 % confidence interval ( CI ) , 1.35–2.13 ; Ptrend = 0.0002 ] . This positive association did not differ according to duration of follow-up [ ORs for highest vs. lowest quartile were 2.01 ( 1.35–2.99 ) , 1.37 ( 0.94–2.00 ) , and 1.80 ( 1.17–2.77 ) for cancers diagnosed < 4 , 4—7 , and > 7 years after blood collection , respectively ( Pheterogeneity = 0.77 ) ] or by stage , grade , and age at diagnosis or age at blood collection ( all subgroups Pheterogeneity > 0.05 ) . Conclusion : In this European population , high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term . Impact : As IGF-I is the only potentially modifiable risk factor so far identified , research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted . Cancer Epidemiol Biomarkers Prev ; 21(9 ) ; 1531–41 . © 2012 AACR 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 Insulin-like growth factors ( IGFs ) may play a role in prostate growth , hyperplasia , and malignancy . High plasma IGF-I has been associated with increased prostate cancer risk . In a prospect i ve , cohort , case-control study in the Baltimore Longitudinal Study on Aging population , we examined prostate volume by magnetic resonance imaging , and prostate-specific antigen ( PSA ) , IGF-I , IGF-II , and IGF-binding protein-3 ( IGFBP-3 ) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases ( n = 72 ) or age-matched controls ( n = 127 ) and in 76 additional Baltimore Longitudinal Study on Aging men ( normal subjects ) with measured prostate volumes and no prostate cancer . We calculated adjusted odds ratios ( OR ) by logistic regression , relative risks for significant ORs , and receiver operator curves for prostate cancer , using serum measures alone and in combination . Adjusted ORs for the high vs. low tertile were : for IGF-I , 3.1 [ confidence interval ( CI ) , 1.1 - 8.7 ] ; for IGF-II , 0.2 ( CI , 0.07 - 0.6 ) ; for IGFBP-3 , 0.71 ( CI , 0.3 - 1.7 ) ; and for PSA , 12.5 ( CI , 3.8 - 40.9 ) . For significant ORs , relative risk estimates remained significant at 2.0 for IGF-I , 0.3 for IGF-II , and 5.5 for PSA . Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer . Adding IGF-II to PSA improved prediction . IGF-II was significantly and inversely related ( r = -0.219 ; P < 0.01 ) and PSA was directly and significantly related ( r = 0.461 ; P < 0.0001 ) to prostate volume , whereas IGF-I and IBFBP-3 were not . High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer , but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II . The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer The role of the insulin-like growth factor ( IGF ) axis and whether IGFs interact with and rogen-suppressing agents in relation to prostate carcinogenesis is unclear . This nested case – control study ( n = 1,652 cases/1,543 controls ) examined whether serum IGF1 , IGF2 , IGFBP2 , IGFBP3 , and the IGF1:IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial ( PCPT ) , a r and omized , placebo-controlled trial of finasteride for prostate cancer prevention . Presence or absence of cancer was determined by prostate biopsy . Baseline serum was assayed for IGF-axis analytes using ELISA . Logistic regression estimated ORs and 95 % confidence intervals for risk of total , low- grade ( Gleason 2–6 ) and high- grade ( Gleason 7–10 ) cancers . Results were stratified by intervention assignment . In both the placebo and finasteride arms , serum IGF1 , IGF2 , IGFBP3 , and the IGF1:IGFBP3 ratio were not associated with prostate cancer . However , men in the highest versus lowest quartile of serum IGFBP2 had a 48 % ( Ptrend = 0.02 ) and 55 % ( Ptrend = 0.01 ) increased risk for total and low- grade cancers , respectively . These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm . Our results suggest that in general , serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined . The exception was the finding that high serum IGFBP2 is a risk factor for low- grade disease , which was attenuated for men on finasteride . Further research is needed to underst and better the risk incurred by high IGFBP2 and whether and rogen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis . Cancer Prev Res ; 6(2 ) ; 91–9 . © 2013 AACR Background There is evidence of associations between insulin-like growth factor I ( IGF-I ) , IGF-II , insulin-like binding protein-2 ( IGFBP-2 ) , IGFBP-3 , and prostate cancer risk . This study examines the association between dietary factors associated with prostate cancer and serum levels of these peptides . Methods A cross-sectional analysis of self-reported 12-month dietary intake with serum IGF and IGFBP levels was performed using data from 1,798 subjects screened negative for prostate cancer as part of a UK multicenter trial comparing treatments for this condition . Multivariable linear regression models tested associations of diet with IGFs and IGFBPs . Results For a one st and ard deviation ( SD ) increase in dairy product and dairy protein intake , IGF-I increased by 5.28 ng/mL ( 95 % confidence interval : 2.64 , 7.92 ng/mL ) and 6.02 ng/mL ( 3.34 , 8.71 ng/mL ) , respectively . A 25 % increase in calcium and selenium intake was associated with an increase in IGF-I of 5.92 ng/mL ( 3.77 , 8.07 ng/mL ) and 2.61 ng/mL ( 1.10 , 4.13 ng/mL ) , respectively . A one SD increase in animal protein was associated with a decrease in IGFBP-2 of 6.20 % ( −8.91 , −3.41 % ) , and there was some evidence of an inverse association with dairy protein and calcium . There was no evidence of any dietary associations with IGFBP-3 or IGF-II . Conclusions Diet is associated with IGF-I and IGFBP-2 levels in men in the UK , and these peptides warrant further investigation as part of r and omized trials of dietary interventions to reduce the risk or progression of prostate cancer . There is no evidence that IGF-II or IGFBP-3 are mediators of dietary associations with prostate cancer PURPOSE Insulin-like growth factor 1 ( IGF-1 ) is an important mitogenic and antiapoptotic peptide that affects the proliferation of normal and malignant cells . Contradictory reports on the association between serum IGF-1 level and prostate cancer have been highlighted in the recent literature . The purpose of this study was to investigate the relation between serum levels of IGF-1 and prostate cancer . MATERIAL S AND METHODS We analyzed a population of 57 patients who underwent radical prostatectomy ( RP ) for adenocarcinoma . Serum sample s were collected before RP ( T0 ) , 6 months after RP ( T6 ) , and from 39 age-matched controls . IGF-1 levels were determined by the active IGF-1 Elisa kit ( Diagnostic Systems Laboratories , Inc. ) . Parallel sample s were evaluated for prostate-specific antigen ( PSA ) levels . Data between groups were analyzed using Welch 's t-test and levels before RP and after 6 months were compared by paired t-test . RESULTS The normal mean serum IGF-1 for case patients at T0 ( 124.6+/-58.2 ng/mL ) was significantly lower than the control subjects ( 157.5+/-70.8 ng/mL ; p = .0192 ) . The normal mean serum IGF-1 for case patients at T0 ( 124.91+/-58.6 ng/mL ) also was significantly lower when it was compared with the T6 group ( 148.49+/-57.2 ng/mL ; p = .0056 ) . No association was found between IGF-1 and PSA blood levels , or IGF-1 and patient weight ( p = 0.2434 ) . An inverse relation between IGF-1 levels and age in the normal controls ( p = .0041 ) was observed . CONCLUSION Findings of this study indicate a significant association between low serum levels of IGF-1 and prostate cancer NKX3.1 is a tumor suppressor down-regulated in early prostate cancers . A SNP ( rs2228013 ) , which represents a polymorphic NKX3.1(C154 T ) coding for a variant protein NKX3.1(R52C ) , is present in 10 % of the population and is related to prostatic enlargement and prostate cancer . We investigated rs2228013 in prostate cancer risk for 937 prostate cancer cases and 1,086 age-matched controls from a nested case-control study within the prospect i ve Physicians ' Health Study ( PHS ) and among 798 cases and 527 controls retrospectively collected in the Risk Factors for Prostate Cancer Study of the Victoria Cancer Council ( RFPCS ) . We also investigated the interaction between serum IGF-I levels and NKX3.1 genotype in the population s from PHS and RFPCS . In the PHS , we found no overall association between the variant T allele in rs2228013 in NKX3.1 and prostate cancer risk ( odd ratio = 1.25 ; 95 % confidence interval = 0.92 - 1.71 ) . A subgroup analysis for cases diagnosed before age 70 showed an increased risk ( relative risk = 1.55 ; 95 % confidence interval = 1.04 - 2.31 ) of overall prostate cancer . In this age-group , the risk of metastatic cancer at diagnosis or of fatal cancer was even higher in carriers of the T allele ( relative risk = 2.15 ; 95 % confidence interval = 1.00 - 4.63 ) . These associations were not replicated in the RFPCS . Serum IGF-I levels were found to be a risk factor for prostate cancer in both study population s. The wild type NKX3.1 protein can induce IGFBP-3 expression in vitro . We report that variant NKX3.1 can not induce IGFBP-3 expression , but the NKX3.1 genotype does not modify the association between serum IGF-I levels and prostate cancer risk Background / objectives : Previous studies have suggested that milk consumption during pregnancy may have growth-promoting effects on the offspring in utero . Whether this effect tracks beyond the prenatal period remains unclear . We examined whether milk consumption during pregnancy is associated with infant size at birth and offspring ’s height- and growth-related biomarkers at ∼20 years of age . Subject/ methods : A prospect i ve cohort of 809 Danish pregnant women was recruited in 1988–1989 , with offspring follow-up at ∼20 years of age ( n=685 ) . Milk consumption was assessed at gestational week 30 using a food frequency question naire . Birth weight and birth length were measured according to st and ard procedures at delivery and converted to specific z-scores , adjusted for gestational age and gender . Results : In adjusted models , maternal milk consumption of ⩾150 ml/day vs < 150 ml/day was associated with 0.32 higher z-scores for birth weight ( 95 % confidence interval ( CI ) 0.06 ; 0.58 ) and 0.34 higher z-scores for birth length ( 95 % CI 0.04 ; 0.64 ) . At follow up , ∼20 years later , those offspring whose mothers had consumed ⩾150 ml milk/day tended to have 0.19 higher z-scores for height ( P=0.16 ) , ∼8 % higher levels of insulin-like growth factor I ( P=0.12 ) and ∼14 % higher insulin levels ( P=0.11 ) compared with offspring whose mothers consumed < 150 ml milk/day . Conclusions : Our findings add to recent observations that maternal milk consumption may have a growth-promoting effect with respect to weight and length at birth . Furthermore , the results provide some suggestion that this effect may even track into early adult age , although further studies with more statistical power are needed for that purpose OBJECTIVE To determine whether dietary counseling to increase milk intake could produce useful changes in the calcium economy and what , if any , other nutrition-related changes might be produced . DESIGN R and omized , open trial . SUBJECTS/ SETTING Two hundred four healthy men and women , aged 55 to 85 years , who habitually consumed fewer than 1.5 servings of dairy foods per day . Six academic health centers in the United States . INTERVENTION Subjects were instructed to consume 3 servings per day of nonfat milk or 1 % milk as a part of their daily diets , or to maintain their usual diets , for a 12-week intervention period , which followed 4 weeks of baseline observations . MAIN OUTCOME MEASURES Energy and nutrient intake assessed from milk intake logs and 3-day food records ; serum calciotrophic hormone levels at baseline and at 8 and 12 weeks ; urinary excretion of calcium and N-telopeptide at 12 weeks . STATISTICAL ANALYSES Repeated- measures analysis of variance . RESULTS In the milk-supplemented group , calcium intake increased by 729 + /- 45 mg/day ( mean + /- st and ard error ) , serum parathyroid hormone level decreased by approximately 9 % , and urinary excretion of N-telopeptide , a bone resorption marker , decreased by 13 % . Urine calcium excretion increased in milk-supplemented subjects by 21 + /- 7.6 mg/day ( mean + /- st and ard error ) , less than half the amount predicted to be absorbed from the increment in calcium intake . All of these changes were significantly different from baseline values in the milk group and from the corresponding changes in the control group . Bone-specific alkaline phosphatase level ( a bone formation marker ) fell by approximately 9 % in both groups . Serum level of insulin-like growth factor-1 ( IGF-1 ) rose by 10 % in the milk group ( P < .001 ) , and the level of insulin-like growth factor binding protein-4 ( IGFBP-4 ) fell slightly ( 1.9 % ) in the milk group and rose significantly ( 7.9 % ) in the control group ( P < .05 ) . APPLICATIONS/ CONCLUSIONS The changes observed in the calcium economy through consumption of food sources of calcium are similar in kind and extent to those reported previously for calcium supplement tablets . The increase in IGF-1 level and the decrease in IBFBP-4 level are new observations that are beneficial for bone health . Important improvements in skeletal metabolism can feasibly occur in older adults by consumption of food sources of calcium . Dietitians can be confident that food works , and that desired calcium intakes can be achieved using food sources Objective The insulin-like growth factor ( IGF ) axis is thought to contribute to the growth and progression of prostate cancer . Some prospect i ve studies support a direct association between IGF-1 and prostate cancer , in particular advanced disease , whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 ( IGFBP-3 ) , the major IGF-1 binding protein in circulation . We prospect ively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era . Methods : We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993 , but before January 1998 among men in the Health Professionals Follow-up Study . Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen . We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA . Conditional logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) of prostate cancer . Results : Men with higher concentrations of IGF-1 ( comparing extreme quartiles OR=1.37 , 95 % CI 0.92–2.03 , p-trend=0.05 ) and IGFBP-3 ( OR=1.62 , 95 % CI 1.07–2.46 , p-trend=0.08 ) had a higher risk of prostate cancer . After mutual statistical adjustment , these associations were attenuated for both IGF-1 ( OR=1.17 , 95 % CI 0.69–1.99 , p-trend=0.29 ) and IGFBP-3 ( OR=1.40 , 95 % CI 0.80–2.44 , p-trend=0.56 ) . We found no significant association of IGF-1 with regionally invasive or metastatic ( ≥T3b , N1 , or M1 ) prostate cancer , although the number of these cases was small ( n=42 ) . Conclusions : Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies , albeit weaker in magnitude . Our suggestive positive findings for IGFBP-3 are similar to some studies , but in direct contrast to others BACKGROUND Insulin-like growth factor-1 ( IGF-1 ) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) play an important role in regulation of prostate cancer cell growth . We studied the prognostic significance of serum IGF-1 and IGFBP-3 levels , and IGF-1/prostate-specific antigen ( PSA ) and IGFBP-3/PSA ratios in patients with prostate cancer . METHODS Serum levels of IGF-1 , IGFBP-3 , and PSA were determined in 112 patients diagnosed with prostate cancer . Serum sample s from 32 patients with histologically confined benign prostatatic hyperplasia ( BPH ) served as control . RESULTS Serum IGF-1 levels were significantly higher in advanced prostate cancer ( n = 84 ) than in BPH patients ( P < 0.01 ) . IGFBP-3 levels were significantly lower in patients with advanced prostate cancer than in localized tumor ( n = 28 ) or BPH ( P < 0.05 , each ) . Univariate analysis showed that serum PSA , IGF-1/PSA ratio , IGFBP-3/PSA ratio , T , N and M classifications correlated significantly with relapse-free survival of advanced prostate cancer patients treated with hormonal therapy . Multivariate analysis identified IGFBP-3/PSA ratio as the only significant variable for relapse-free survival ( odds ratio 5.81 , 95 % CI 1.57 - 21.51 ) . IGFBP-3/PSA ratio was also an independent predictor of cause-specific survival ( stepwise analysis , odds ratio 4.86 , P < 0.01 ) . CONCLUSIONS Our results suggested that IGFBP-3/PSA ratio might be a useful prognostic marker of advanced prostate cancer Despite strong indirect evidence that and rogens stimulate prostate cancer development , data from most analytical studies on this association have been negative . To further investigate this issue , we studied the interrelationships between and rogenicity and insulin-like growth factor I ( IGF-I ) , insulin and leptin . Within a prospect i ve cohort study , we measured testosterone , sex hormone-binding globulin ( SHBG ) and IGF-I , IGF-binding protein (IGFBP)-1 , IGFBP-3 , insulin and leptin , in plasma from 149 cases and 298 controls . Testosterone correlated positively with SHBG , whereas testosterone and SHBG correlated inversely with IGF-I , IGFBP-3 , insulin , leptin and body mass index ( BMI ) . Indices of free testosterone showed an inverse linear correlation with leptin ( P<0.01 ) , and a strong drop in the 5th quintile of BMI . However , levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I , with a significant increase in the second quintile of IGF-I compared with other levels . The absence of an association between plasma levels of and rogens and prostate cancer risk in analytical studies , despite the strong indirect evidence of their tumour-stimulating effects , may reflect the complex and mostly inverse associations of and rogenicity to IGF-I , insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer Background / Aim : To compare serum chromogranin A ( CgA ) and insulin-like growth factor 1 ( IGF-1 ) with the classical prostate-specific antigen ( PSA ) marker in clinical ly localized prostate adenocarcinomas . Material s and Methods : This is a prospect i ve single-center study that included 64 consecutive men with newly diagnosed clinical ly localized prostate adenocarcinoma and 20 consecutive men with histologically confirmed benign prostatic hyperplasia ( BPH ) . A blood sample for the determination of serum total PSA , CgA and IGF-1 levels ( RIA ) was obtained from all cases . Analysis of variance was performed to evaluate their variations according to disease and the pathological characteristics of prostate adenocarcinoma . Results : Only serum PSA levels ( p < 0.0001 ) and not IGF-1 ( p = 0.5475 ) or CgA ( p = 0.5043 ) were significantly higher in the prostate cancer ( PCa ) group as compared to the BPH group . A significant variance between BPH and PCa divided on the basis of pT stage was found for PSA levels ( p < 0.0001 ) but not for CgA ( p = 0.0869 ) and IGF-1 ( p = 0.6883 ) levels . Dividing PCa on the basis of Gleason score , a significant variance was found for CgA ( p = 0.0100 ) and for PSA ( p < 0.001 ) , but not for IGF-1 ( p = 0.6895 ) levels . Conclusions : In our population the quantification of PSA and CgA serum levels and not of IGF-1 provides independent significant information in the diagnosis and aggressiveness of PCa , respectively Objective : Insulin-like growth factors ( IGF ) are increasingly recognized as important determinants of adult health , in particular risk of certain cancers . However , little is known about the determinants of adult IGFs and to what degree they may be programmed by early life influences . Design : R and omized controlled trial of prenatal and postnatal milk supplementation among 951 subjects born in 1972 to 1974 in South Wales . Main outcome measure : Measures of IGF-I , IGF binding protein 3 , and the molar ratio . Results : Data on adult IGFs were available from 663 subjects at a mean age of 25 years . Subjects in the intervention arm had lower IGF-I ( −8.5 ng/mL ; 95 % confidence interval , −15.1 to −1.8 , P = 0.01 ) and ratio ( −1.20 ; 95 % confidence interval , −2.33 to −0.04 , P = 0.04 ) . These differences could not be explained by follow-up bias or confounding factors . Conclusions : These results provide experimental data on the role of early life programming either in the intrauterine or postnatal period that may have long-term influences on the IGF axis , with potential implication s for disease risk High serum levels of insulin-like growth factor I ( IGF-I ) and low levels of IGF-binding protein-3 ( IGFBP-3 ) have been shown to correlate with increased prostate cancer risk . To evaluate this , IGF-I , IGFBP-3 , and prostate-specific antigen ( PSA ) were measured in serum from 665 consecutive men ( 179 with prostate cancer ) , aged 55 - 67 yr , with elevated serum prostate-specific antigen ( PSA ; > or = 4 microg/L ) in a screening trial . Men in the highest quartile of IGF-I levels had an odds ratio ( OR ) for prostate cancer of 0.50 [ 95 % confidence interval ( CI ) 0.26 - 0.97 ] when adjusting for serum IGFBP-3 . IGFBP-3 itself was not significantly associated with prostate cancer risk ( OR , 1.24 ; 95 % CI , 0.68 - 2.24 ) . Prostate volume was larger in men without than in those with prostate cancer ( P < 0.001 ) , and after adjustment for prostate volume , the negative association between serum IGF-I and prostate cancer risk was no longer significant ( OR , 0.57 ; 95 % CI , 0.28 - 1.16 ) . In screen-positive men with elevated serum PSA , serum IGF-I is not a useful diagnostic test for prostate cancer , but it may be associated with benign prostatic hyperplasia and enlargement Objective : The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I ( IGF-I ) and IGF-binding protein-3 in women . Design : Cross-sectional study . Setting and subjects : The population are 2109 women who were control subjects in a case – control study of breast cancer nested in the European Prospect i ve Investigation into Cancer and Nutrition . Control subjects were r and omly chosen among risk sets consisting of female cohort members alive and free of cancer ( except non-melanoma skin cancer ) at the time of diagnosis of the index case . Matching criteria were age at enrolment , follow-up time , time of the day of blood collection and study centre . Diet was measured through vali date d question naires . Serum hormone concentrations were measured by enzyme-linked immunosorbent assays . The relationship between serum IGF-I , IGFBP-3 , and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake , age , body mass index , smoking , physical activity , centre and laboratory batch . Results : Serum IGF-I levels were positively related to protein intake ( P trend<0.001 ) , but not related to energy , fat or carbohydrate intake . Positive relationships were observed with the intake of milk ( P trend=0.007 ) , calcium ( P trend<0.001 ) , magnesium ( P trend=0.003 ) , phosphorus ( P trend<0.001 ) , potassium ( P trend=0.002 ) , vitamin B6 ( P trend=0.03 ) , vitamin B2 ( P trend=0.001 ) and inverse relationships with vegetables ( P trend=0.02 ) and beta-carotene ( P trend=0.02 ) . IGFBP-3 was not related with most of the nutrients and foods in this study . Conclusions : In this population , circulating IGF-I is modestly related with the intake of protein and minerals , and with milk and cheese , while IGFBP-3 does not appear to be related with diet IGF‐1 and IGFBP‐3 may influence risk of prostate cancer through their roles in cellular growth , metabolism and apoptosis , however , epidemiologic results have been inconsistent . The role of obesity in prostate cancer risk is not clearly understood , but hyperinsulinemia‐related increases in bioactive IGF‐1 levels , associated with obesity , could be a component of the relationship between the IGF‐axis and prostate cancer . We conducted a nested case – control study in the prospect i ve Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF‐1 and IGFBP‐3 and risk of prostate cancer . A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis . There was no clear overall association between IGF‐1 , IGFBP‐3 and IGF‐1:IGFBP‐3 molar ratio ( IGFmr ) and prostate cancer risk , however , IGFmr was associated with risk in obese men ( BMI > 30 , p‐trend = 0.04 ) , with a greater than 2‐fold increased risk in the highest IGFmr quartile ( OR 2.34 , 95 % CI 1.10–5.01 ) . Risk was specifically increased for aggressive disease in obese men ( OR 2.80 , 95 % CI 1.11–7.08 ) . In summary , our large prospect i ve study showed no overall association between the insulin‐like growth factor axis and prostate cancer risk , however , IGFmr was related to risk for aggressive prostate cancer in obese men . © 2007 Wiley‐Liss , High circulating concentration of insulin-like growth factor-I ( IGF-I ) and low circulating concentration of IGF binding protein-3 ( IGFBP-3 ) have been associated with increased risk for breast , prostate , and colorectal cancers . Building on previous work in the Multiethnic Cohort ( MEC ) showing significant differences in IGF-I levels across racial/ethnic groups , we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a r and om sample of 1,000 MEC participants , which included Native Hawaiian , African American , Japanese , Latino , and White men and women . Crude analyses confirmed the existence of differences in protein levels with race/ethnicity , sex , age , and body size . Reproductive , physical activity , smoking , and diet variables had less consistent effects . In multivariate analyses , IGF-I levels were lower and IGFBP-3 were higher in females versus males . IGF-I and IGFBP-3 declined with increasing age in both genders . Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels ; in men , height was significantly positively associated with both proteins . In women , alcohol was directly associated with IGFBP-3 . Both proteins were lowest among female Latinos . IGF-I was highest among female African Americans . In men , IGFBP-3 was lowest among African Americans . Overall , although these factors were statistically significant determinants of IGF-related protein levels , they did not explain much of the variation in these levels . A positive correlation was found between IGF-I levels ( ng/mL ) and colon cancer incidence rates ( per 100,000 ) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer Abstract Objectives : To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls . Design : 18 month , open r and omised intervention trial . Subjects : 82 white girls aged 12.2 ( SD 0.3 ) years , recruited from four secondary schools in Sheffield . Intervention : 568 ml ( one pint ) of whole or reduced fat milk per day for 18 months . Main outcome measures : Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry . Outcome measures to evaluate mechanism included biochemical markers of bone turnover ( osteocalcin , bone alkaline phosphatase , deoxypyridinoline , N-telopeptide of type I collagen ) , and hormones important to skeletal growth ( parathyroid hormone , oestradiol , insulin-like growth factor I ) . Results : 80 subjects completed the trial . Daily milk intake at baseline averaged 150 ml in both groups . The intervention group consumed , on average , an additional 300 ml a day throughout the trial . Compared with the control group , the intervention group had greater increases of bone mineral density ( 9.6 % v 8.5 % , P=0.017 ; repeated measures analysis of variance ) and bone mineral content ( 27.0 % v 24.1 % , P=0.009 ) . No significant differences in increments in height , weight , lean body mass , and fat mass were observed between the groups . Bone turnover was not affected by milk supplementation . Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group ( 35 % v 25 % , P=0.02 ) . Conclusion : Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass . Key messages Osteoporosis is a major public health problem ; 40 % of women will sustain an osteoporotic fracture Maximising peak bone mass at skeletal maturity may be one of the most important protective measures against fracture in later life Adolescence is a critical time for bone mineral acquisition An increase in milk consumption among adolescent girls result ed in significant gains in bone mineral over an 18 month period This simple intervention indicates that increased milk consumption may be associated with higher peak bone Objectives To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin‐like growth factor 1 ( IGF‐1 ) Insulin-like growth factor-I ( IGF-I ) is a mitogen for prostate epithelial cells . To investigate associations between plasma IGF levels and prostate cancer risk , a nested case-control study within the Physicians ' Health Study was conducted on prospect ively collected plasma from 152 cases and 152 controls . A strong positive association was observed between IGF-I levels and prostate cancer risk . Men in the highest quartile of IGF-I levels had a relative risk of 4.3 ( 95 percent confidence interval 1.8 to 10.6 ) compared with men in the lowest quartile . This association was independent of baseline prostate-specific antigen levels . Identification of plasma IGF-I as a predictor of prostate cancer risk may have implication s for risk reduction and treatment |
12,651 | 22,266,271 | EVIDENCE SYNTHESIS For stones that do not pass spontaneously or with MET , shock wave lithotripsy ( SWL ) and ureteroscopy ( URS ) are the most common and efficient treatment modalities .
Both techniques have obvious advantages and disadvantages as well as different patterns of complications .
For select cases or patients , other modalities may be useful .
Ureteral stones of up to 10 mm and eligible for observation may be offered MET . | CONTEXT Ureteral calculi represent a common condition that urologists encounter in everyday practice .
Several treatment options are available for calculi that do not pass spontaneously or are unlikely to do so .
OBJECTIVE In this non systematic review , we summarize the existing data on contemporary management of ureteral stones focusing on medical expulsive therapy ( MET ) and different treatment modalities . | PURPOSE A prospect i ve r and omized controlled trial was performed to determine whether stents may be eliminated after uncomplicated ureteroscopic lithotripsy for ureteral stones . MATERIAL S AND METHODS A total of 58 patients underwent uncomplicated ureteroscopic intracorporeal lithotripsy . After stone fragmentation patients were r and omized to a nonstented ( 29 ) or a stented ( 29 ) treatment group . Intracorporeal lithotripsy was performed with the holmium laser in 57 cases and by electrohydraulic lithotripsy in 1 without balloon dilation or the extraction of stone fragments . Patients were followed 1 , 6 and 12 weeks postoperatively . In stented cases the stent was removed at 1 week . Outcome measures included postoperative symptoms assessed with a visual analog scale , postoperative analgesic requirements , complications and the stone-free rate . RESULTS At 1 week the symptoms of flank pain , abdominal pain , dysuria and frequency were significantly greater in the stented group ( p < 0.005 ) . There were no differences in symptoms in the groups at subsequent followup visits . There was no difference in treatment groups in terms of the amount of analgesic required in the recovery room or during 1 week after ureteroscopy . Similarly there was no difference in the number of patients requiring antiemetics . One patient in the stented group required hospitalization for genitourinary sepsis and 1 patient in the nonstented group visited the emergency room for postoperative vomiting . The stone-free rate was 100 % in each group . CONCLUSIONS These results demonstrate that after ureteroscopic intracorporeal lithotripsy with the holmium laser patients with a stent have significantly greater irritative and painful symptoms than those without a stent in the early postoperative period . There was no difference in nonstented and stented ureteroscopy with respect to complications or stone-free status . Therefore , we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not required as long as the procedure is uncomplicated and performed without balloon dilation of the ureteral orifice Retro grade calculus migration during ureteroscopic lithotripsy remains a problem in 5–40 % of cases . We assessed the safety and efficacy of the Stone Cone device , in comparison with the st and ard flat wire basket . A total of 56 consecutive patients with ureteral calculi , suitable for ureteroscopic extraction and /or lithotripsy , where included in this prospect i ve study . Patients were r and omly allocated into two groups . In group A ( 30 patients ) , we used the Stone Cone , while in group B ( 26 patients ) we used the st and ard flat wire basket . The Stone Cone was placed through a cystoscope under fluoroscopic guidance , or when necessary under direct ureteroscopic control . Whenever necessary , intracorporeal electrohydraulic lithotripsy took place in both groups . Statistical significance was assessed by the paired t-test . The mean operative time was 48.5 min in group A , and 42.4 min in group B. Intact calculus extraction was possible in 16.6 % in group A , and in 7.6 % in group B ( P<0.01 ) . Retro grade stone migration was revealed in 23 % in group B only ( P<0.001 ) . Also , residual fragments > 3 mm were recorded in 30.7 % in group B only ( P<0.001 ) . None of the patients in group A required auxiliary procedures , in contrary to 23 % in group B ( P<0.001 ) . No major complications were recorded in group A , while in group B a case of major ureteral mucosal abrasion was recorded . The Stone Cone is safe and efficient in preventing retro grade stone migration and in minimizing residual fragments during ureteroscopic lithotripsy in comparison with the flat wire basket PURPOSE We present the first r and omized clinical study using BackStop , a novel reverse thermosensitive water-soluble polymer that is dispensed above the stone(s ) and temporarily occludes the ureter to prevent retropulsion of stone fragments during ureteroscopic lithotripsy . After fragmentation is completed and concretions are extracted , conventional irrigation with saline dissolves the polymer , which is then flushed out . MATERIAL S AND METHODS A total of 68 subjects with a single stone in the proximal ureter and an indication for ureteroscopic lithotripsy were enrolled in this prospect i ve , r and omized , single-blind , controlled , multisite clinical study . Each subject was r and omly assigned to the BackStop group ( 34 ) or the control group ( 34 with no antiretropulsion device ) . For subjects in the experimental group BackStop was dispensed into the ureter above the stone using a 3Fr or 5Fr catheter . Ureteroscopic lithotripsy was performed in all subjects using pneumatic or laser energy . Measured end points included the retropulsion rate , the need for subsequent procedures , the stone-free rate at followup , the occurrence of adverse events and ureteral occlusion , if any , and post-stone fragmentation and extraction . RESULTS Subjects r and omized to the BackStop group experienced a statistically significant ( p = 0.0002 ) lower rate of retropulsion ( 8.8 % , 3 of 34 ) vs the control group ( 52.9 % , 18/34 ) . There were no adverse events in the BackStop group and BackStop was successfully dissolved in every subject , result ing in a patent ureter . CONCLUSIONS BackStop appears to be a novel , safe and effective means of preventing stone fragment retropulsion during ureteroscopic lithotripsy for the management of ureteral stones OBJECTIVES To evaluate our experience in treating 155 patients with upper urinary tract calculi ureteroscopically . The treatment of urinary calculi has remained the most frequent application of ureteroscopy . Miniaturization of semirigid and flexible ureteroscopes has permitted easier access to calculi throughout the urinary tract . METHODS Ureteroscopic stone treatment was attempted in 155 patients with upper urinary tract calculi between November 1995 and March 1997 . Fifty-nine ( 38.1 % ) patients had renal calculi , 82 ( 52.9 % ) ureteral , and 14 ( 9 % ) had both renal and ureteral calculi . Both semirigid and flexible ureteroscopes were used for treatment ( rigid alone in 21 [ 13.5 % ] , flexible in 64 [ 41.3 % ] , and both rigid and flexible in 70 [ 45.2 % ] patients ) . Lithotripsy was required in 122 ( 79 % ) of the patients . The holmium : yttrium-aluminum-garnet laser was used in 113 ( 92.6 % ) of these patients . RESULTS All patients with ureteral calculi ( 29 proximal , 19 mid , and 34 distal ) were successfully cleared after one endoscopic procedure except for 1 patient with a proximal ureteral calculus who had a 4-mm residual fragment in the kidney . Of the 59 patients with renal calculi , 47 ( 79.7 % ) were totally clear of stones 1 month after treatment . The remaining 12 ( 20.3 % ) patients had evidence of residual calculi 3 to 4 mm or less in diameter . In patients with combined renal and ureteral calculi , 1 1 of 14 ( 78.6 % ) were rendered stone free . The remaining 3 ( 21.4 % ) patients had evidence of residual calculi 4 mm in diameter . Overall , 95 % of the patients were treated in an outpatient setting . Morbidity was low , with no evidence of stricture . CONCLUSIONS Ureteroscopy and laser lithotripsy in experienced h and s are a safe and reliable method for the treatment of ureteral and even intrarenal calculi OBJECTIVE A series of experiments were conducted to test the hypothesis that the mechanism of holmium : YAG lithotripsy is photothermal . METHODS AND RESULTS To show that holmium : YAG lithotripsy requires direct absorption of optical energy , stone loss was compared for 150 J Ho : YAG lithotripsy of calcium oxalate monohydrate ( COM ) stones for hydrated stones irradiated in water ( 17+/-3 mg ) and hydrated stones irradiated in air ( 25+/-9 mg ) v dehydrated stones irradiated in air ( 40+/-12 mg ) ( P < 0.001 ) . To show that Ho : YAG lithotripsy occurs prior to vapor bubble collapse , the dynamics of lithotripsy in water and vapor bubble formation were documented with video flash photography . Holmium : YAG lithotripsy began at 60 microsec , prior to vapor bubble collapse . To show that Ho : YAG lithotripsy is fundamentally related to stone temperature , cystine , and COM mass loss was compared for stones initially at room temperature ( approximately 23 degrees C ) v frozen stones ablated within 2 minutes after removal from the freezer . Cystine and COM mass losses were greater for stones starting at room temperature than cold ( P < or = 0.05 ) . To show that Ho : YAG lithotripsy involves a thermochemical reaction , composition analysis was done before and after lithotripsy . Postlithotripsy , COM yielded calcium carbonate ; cystine yielded cysteine and free sulfur ; calcium hydrogen phosphate dihydrate yielded calcium pyrophosphate ; magnesium ammonium phosphate yielded ammonium carbonate and magnesium carbonate ; and uric acid yielded cyanide . To show that Ho : YAG lithotripsy does not create significant shockwaves , pressure transients were measured during lithotripsy using needle hydrophones . Peak pressures were < 2 bars . CONCLUSION The primary mechanism of Ho : YAG lithotripsy is photothermal . There are no significant photoacoustic effects BACKGROUND To establish the best treatment modality in our hospitals for patients with proximal-ureteral calculi 5 to 10 mm , we compared the treatment outcome in those who underwent primary ureteroscopy ( URS ) with that in patients who underwent primary in-situ SWL . The primary endpoints were stone-free rates at 3 weeks and 3 months and the subjective patient experience . PATIENTS AND METHODS The study was a prospect i ve patient-preference trial . From September 2002 to May 2005 , 80 patients were included , of whom 71 could be evaluated . Thirty-three patients were treated with SWL and 38 with semirigid or flexible URS . Stone status was evaluated with excretory urography or noncontrast helical CT . The bother score of urinary-tract symptoms was recorded on a visual analog scale . RESULTS The stone-free rate at 3 weeks was 58 % and 78 % ( P = 0.061 ) and at 3 months 88 % and 89 % ( P = 1 ) for SWL and URS , respectively . The percentage of patients in need of analgesics was 30 % and 49 % ( P = 0.118 ) at 3 weeks and 9 % and 21 % ( P = 0.181 ) at 3 months for the SWL and the URS group , respectively . The bother score regarding dysuria , hematuria , and flank pain were statistically significant in favor of SWL . CONCLUSION Ureteroscopy tends to make patients stone free faster , but SWL is preferred by most patients because there is less discomfort after treatment We performed a prospect i ve , non-r and omised study to determine the appropriate first-line treatment modality for distal ureteral stones . Between 2003 and 2004 , a total of 124 patients with distal ureteral calculi were entered into the study ( mean age 48 years , 35 women and 99 men ) . Sixty-two patients were treated with shock wave lithotripsy ( SWL ) and 62 patients with ureteroscopy ( URS ) . The average stone size was 6.9 mm ( 3–33 mm ) for SWL and 7.2 mm ( 3–30 mm ) for URS . The treatment decision depended on the patients ’ preference and clinical parameters ( i.e. contraindications for anaesthesia ) . URS was performed under general anaesthesia , using semirigid 8 Fr instruments . SWL was performed under analgo-sedation using a Modulith SLX . Of patients treated with SWL , 84 % had a treatment success within 7 days , 98 % after URS . These results show a significant success ( P=0.005 ) in favour of URS . The average in-patient stay after SWL was 3 days and for URS 4 days ( not significant ) . The results show a high efficacy and a low complication rate for both modalities . The attained stone-free rate shows a significant advantage for primary URS INTRODUCTION The aim of this study was to investigate and compare the success and complication rates of extracorporeal shockwave lithotripsy ( SWL ) in three cohorts of patients older than 60 years . PATIENTS AND METHODS Our study included 444 patients older than 60 years who were treated with SWL between May 2001 and May 2008 at the Croatian Referential Center for Urolythiasis in Osijek . Three groups were formed : group I ( 60 - 65 years old ) , group II ( 66 - 70 ) , and group III ( > 70 ) . There were 175 , 151 , and 118 patients in groups I , II , and III , respectively , with a mean age of 67.7 ± 5.4 years for all patients . Demographic data , comorbidities , kidney function , stone characteristics , treatment details , complications , and stone-free rate ( SFR ) were analyzed . RESULTS We performed 1.7 ± 1.12 sessions per patient , with 3166 ± 571.3 impulses per session and a mean energy of 18.78 ± 0.64 kV. Three groups did not differ in number of SWL sessions ( p = 0.78 ) , number of impulses ( p = 0.34 ) , energy level ( p = 0.5 ) , stone size ( p = 0.3 ) , and pretreatment creatinine level ( p = 0.88 ) . Comorbidities were found in 55 % of patients , with almost every third patient having two or more ones present . Complications were noted in 6 % of patients , with no significant difference when comparing complication rates between the groups . An overall SFR of 67.98 % was found . There was no statistically significant difference when comparing SFRs between the studied groups , even after dividing patients into those with renal and ureteral stones . CONCLUSION Our study shows that good SFR and low rate of complications can be achieved with proper patient selection for SWL , regardless of patients ' age and comorbidities INTRODUCTION Before the 1980s , ureteric stones were managed by open ureterolithotomy . Since the introduction of shock-wave lithotripsy ( SWL ) and ureteroscopy , the use of an open surgical approach for the removal of ureteric stones has rapidly declined . Open surgery , which is currently being replicated by laparoscopic techniques , is generally indicated for failed endourologic procedures , particularly in centers that do not have flexible ureteroscopy or laser lithotripter , and in patients with larger stones . Considering this , we conducted a retrospective study to compare the different modalities for the management of midureteric calculi of more than 1.5 cm . MATERIAL S AND METHODS Between August 2000 and July 2005 , a total of 71 patients with large midureteric calculi ( > 1.5 cm in size ) were treated with the three different modalities ; SWL , ureteroscopic pneumatic lithotripsy ( URS ) , and laparoscopic ureterolithotomy at AMAI Trust 's Institute of Urology . Data were collected and all the patients were analyzed for stone-free rate , intraoperative and immediate postoperative complications , and the results were calculated . RESULTS Stone clearance was 39.1 % with SWL ( group 1 ) , 79.2 % with ureteroscopic pneumatic lithotripsy ( group 2 ) , and 100 % with the laparoscopic method ( group 3 ) , with a statistically significant difference between groups 1 and three and groups 1 and 2 , but there was no statistical significance in groups 2 and three . However , hospital stay and hence morbidity was significantly greater in group 3 , when compared to the other two groups . CONCLUSION SWL gives the least clearance for large midureteric calculi . Statistically , URS and laparoscopic ureterolithotomy give equal results ; hence , URS still remains the treatment of choice for the treatment of large midureteric calculi considering the low morbidity and acceptable stone-free rate of the procedure . Though laparoscopic ureterolithotomy can be considered as a treatment option , prospect i ve , r and omized trials are needed to confirm the efficacy of one modality of treatment over the other Objectives : To compare the outcome of outpatient ureteroscopic laser lithotripsy ( URSL ) for ureteral stone larger than 10 mm in longest diameter ( group 1 ) with those less than or equal to 10 mm ( group 2 ) . Methods : 134 patients with solitary ureteral stone were treated by outpatient URSL . No exclusion criteria with regards to stone size , level or composition were applied . Semirigid ureteroscopy and holmium – YAG laser lithotripsy was performed under general anaesthesia as outpatient procedure . Radiological follow – up by intravenous urogram was performed 3 months postoperatively . Patients ’ demographic data , stone parameters , operative details and treatment outcome were collected prospect ively and compared between the two groups . Results : Among the 134 ureteral stones , 41(31 % ) were larger than 10 mm . Group 1 contained more upper and middle ureteral stones than group 2 ( 68 vs. 40 % p = 0.001 ) . Operating time was significantly longer for group 1 ( 68.9 vs. 46.8 min , p<0.001 ) and postoperative stenting rate was higher ( 83 vs. 60 % , p = 0.01 ) . There was no difference between the groups in terms of 3 months stone clearance rate ( 92.7 vs. 91.4 % , p = 0.8 ) . Complication rate was higher in group 1 ( 22 vs. 5.4 % , p = 0.004 ) especially for lower stones ( 46.2 vs. 5.4 % , p = 0.001 ) but most of which were minor complications that were treated conservatively . One patient in group 1 ( 2.4 % ) developed ureteral stricture at the longst and ing stone impaction site despite postoperative stenting . The stricture resolved subsequent to balloon dilatation . Conclusions : URSL can treat stones larger than 10 mm in longest diameter at all levels safely and effectively in an outpatient setting Objectives To review our experience of retroperitoneoscopic ureterolithotomy ( RPUL ) and to compare the results with those from open surgery BACKGROUND AND PURPOSE The optimal treatment option for ureteral calculi is a controversial issue . In this study , we present our experience of 60 patients , divided into three groups , who were treated using open surgery , laparoscopic surgery , or transureteral lithotripsy ( TUL ) . PATIENTS AND METHODS We enrolled 60 patients who had upper ureteral calculi > l0 mm in diameter from June 2008 to August 2009 in our center . In a prospect i ve study , preoperative and postoperative data were evaluated , and for statistical analyses , the chi-square test , one-way analysis of variance , and post hoc test were used . RESULTS The mean operative time was 70 , 191 , and 162.5 minutes in the TUL , laparoscopic , and open groups , respectively . The mean hospital stay was 1.65 , 4.2 , and 4.35 days in the three groups , respectively . The stone-free rate was 90 % , 95 % , and 100 % in the three groups , respectively . Flank pain was reported as 15 % , 5 % , and 15 % , in the three groups , respectively . Hemoglobin decrease necessitating blood transfusion was not reported in the TUL and laparoscopic groups , but blood transfusion was reported in 15 % in the open group . The lowest dose of analgesic was used in the TUL group . There was no damage to the ureter and adjacent organs and wound infection in the three groups . CONCLUSION Our study showed that the complications after laparoscopic surgery were lower than in open surgery . We recommend laparoscopic surgery for upper ureteral stones > 1 cm because of lower postoperative complications , shorter hospital stay , and shorter time to convalescence , and better cosmetic results We conducted a prospect i ve , r and omized study to evaluate whether postoperative ureteral stenting is necessary after ureteroscopic holmium laser lithotripsy . A total of 115 consecutive patients with distal or middle ureteral calculi amenable to ureteroscopic holmium laser lithotripsy were prospect ively r and omized into stented group ( n = 58 ) and nonstented group ( n = 57 ) . The stent was routinely placed in the treated ureter for 2 weeks . The outcomes were measured with postoperative patient symptoms , stone-free rates , early and late postoperative complications , and cost-effectiveness . The postoperative symptoms were measured with Ureteral Stent Symptom Question naire ( USSQ ) . All patients completed a 12-week follow-up . There was no significant difference between two groups with respect to the patient age , stone size , stone location and mean operative time . According to the USSQ , the symptoms of the stented group were significantly worse compared to the nonstented group ( P = 0.0001 ) . In the stented group , two patients had high fever for 1 week after the operation , stent migration was found in two patients , and the stents had to be removed earlier in five patients because of severe pain or hematuria . The cost of the stented group was significantly higher than the nonstented group . The stone-free rate was 100 % in both groups . No hydronephrosis or ureteral stricture was detected by intravenous pyelogram in the 12th week postoperative follow-up . In conclsion , we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not necessary as long as the procedure is uncomplicated for distal or middle ureteral calculis less than 2 cm BACKGROUND AND PURPOSE Shockwave lithotripsy ( SWL ) is the least invasive treatment for ureteral calculi and is the best accepted by patients and clinicians . This prospect i ve study was performed to evaluate the results of SWL for all ureteral calculi . PATIENTS AND METHODS Between April 1999 and May 2000 , there were 150 SWL treatments for ureteral calculi at our center . All patients who completed treatment ( 24 females , 126 males with an average age of 54 + /- 14 years ) were entered in the study and were assessed at 1 and 3 months with a plain film of the kidneys , ureters , and bladder and an ultrasound scan or intravenous urogram if clinical ly indicated . The outcome has been analyzed according to stone size , location ( lower ureter [ LU ] , midureter [ MU ] , and upper ureter [ UU ] , number of treatments per stone , number of shocks per stone , and stone-free rate ( SFR ) . The analgesia requirements during each treatment and complications have also been analyzed . RESULTS The SFR in the UU was 77 % at 1 month and 85 % at 3 months . The SFR in the MU was 74 % at both 1 and 3 months . The SFR in the LU was 65 % at 1 month and 74 % at 3 months . Overall , the SFR for all calculi was 72 % at 1 month and 79 % at 3 months . Ureteroscopic extraction was necessary in 19 % of the patients and conservative management for the remaining asymptomatic fragments , which were 2 mm or smaller . All of these asymptomatic fragments were seen to have passed spontaneously on follow-up imaging studies . Ureteral stents were not placed routinely prior to SWL , but there were 32 calculi ( 21 % ) for which stents had been placed prior to SWL : 29 ( 19 % ) in the UU , 3 ( 2 % ) in the MU , and 0 in LU . There was no difference in the SFR or ureteroscopy rate in UU calculi treated with or without stents and no difference in the number of treatments needed to achieve these SFRs . The efficiency quotient for the UU was 55 % , 45 % for the MU , and 45 % for the LU . Oral analgesia was given routinely ; however , additional intravenous analgesia was necessary in 24 % of treatments . No serious complications were seen . CONCLUSIONS The Dornier Compact Delta lithotripter provides an effective noninvasive treatment for ureteral calculi that is achieved with minimal anesthesia and a low complication rate . Placement of ureteral stents prior to SWL does not enhance the SFR or obviate intervention if SWL fails . We recommend a low threshold for ureteroscopic treatment if significant progress is not made in fragmenting the stone with SWL PURPOSE We compare the efficacy and result ing kidney trauma of the HM3 ( Dornier Medical Systems , Inc. , Marietta , Georgia ) and Lithostar Plus ( Siemens , Issaquah , Washington ) lithotriptors in a prospect i ve r and omized trial treating calix and renal pelvis stones . MATERIAL S AND METHODS Patients with a solitary renal pelvic stone 2 cm . or less in diameter or a solitary calix stone 1 cm . or less in diameter were r and omized for treatment with the HM3 or Lithostar Plus . Stone disintegration and dilatation of the pyelocaliceal system were evaluated by abdominal plain x-ray and renal ultrasound 1 day and 3 months after treatment . Kidney trauma was determined by measurement of N-acetyl-beta-glucosaminidase and beta-galactosidase ( NAG ) in pretreatment urine and 4 , 12-hour urine sample s collected within the first 2 days after extracorporeal shock wave lithotripsy ( ESWL , Dornier Medical Systems , Inc. ) . RESULTS Of 167 patients with 176 stones 91 were r and omized to the HM3 and 85 to the Lithostar Plus lithotriptor group . The preoperative stone burden was comparable in both groups . On postoperative day 1 patients treated with the HM3 or Lithostar Plus were stone-free or had fragments 2 mm . or less ( 91 % and 65 % , p < 0.001 ) , 3 to 5 mm . ( 8 % and 25 % , p = 0.003 ) and 6 mm . or greater ( 1 % and 10 % , p = 0.008 ) , respectively . Patients treated with the HM3 had less posttreatment dilatation of the collecting system ( p = 0.01 ) . Obstructive pyelonephritis occurred in 1 % of the HM3 and 8 % of the Lithostar Plus group ( p = 0.02 ) . Re-treatment rate was 4 % in the HM3 and 13 % in the Lithostar Plus group ( p = 0.05 ) . Mean excretion of urinary NAG per treatment ( including re-treatments ) was comparable in both groups but NAG excretion in relation to stone volume and shock wave number 12 to 24 hours after ESWL was significantly higher in the HM3 group ( p < 0.05 ) . At 3-months postoperatively 89 % of the patients treated with the HM3 and 87 % treated with the Lithostar plus were stone-free with no dilatation of the collecting system . CONCLUSIONS This prospect ively r and omized study indicated that the HM3 is still the gold st and ard in regard to disintegration of pelvicaliceal stones . Stone disintegration with the HM3 is better with fewer shock waves , re-treatment rate is lower , and posttreatment dilatation of the collecting system and complications such as obstructive pyelonephritis are less than those with the Lithostar Plus . ESWL induced kidney trauma is minor and resolves within 2 days . The HM3 delivers more energy per shock wave into the kidney as assessed by urinary NAG PURPOSE We assessed the effectiveness and safety of holmium : YAG laser lithotripsy for managing upper urinary tract calculi in a prospect i ve cohort of 598 patients . MATERIAL S AND METHODS Ureteroscopic holmium : YAG laser lithotripsy was performed in 598 patients between 1993 and 1999 . Calculi were located in the distal ureter in 39.6 % of cases , mid ureter in 18.6 % , proximal ureter in 32.4 % and kidney in 9.4 % . Patients were treated on an outpatient basis with various flexible and semirigid endoscopes . Of the cases 59 % were referred as previous treatment failures . Patients were assessed 6 to 12 weeks postoperatively with repeat plain x-ray and ultrasound or excretory urography for late obstructive complications . RESULTS The overall stone-free rate was 97 % . As stratified by location , the stone-free rate was 98 % in the distal ureter , 100 % in the mid ureter , 97 % in the proximal ureter and 84 % in the kidney . Fragmentation was incomplete in 6 % of cases and secondary intervention was required in 6 % . The overall complication rate was 4 % . New onset ureteral stricture developed postoperatively in 0.35 % of patients . CONCLUSIONS Holmium : YAG laser lithotripsy is a highly effective and safe treatment modality for managing ureteral and a proportion of intrarenal calculi on an outpatient basis . The effectiveness and versatility of the holmium laser combined with small rigid or flexible endoscopes make it our modality of choice for ureteroscopic lithotripsy OBJECTIVE To assess the effectiveness of the Dornier Compact Delta lithotriptor on the management of in situ primary ureteric stones . PATIENTS AND METHODS 137 patients with primary ureteric stones were treated at a tertiary urological center using the latest Dornier Compact Delta lithotriptor between January 1999 and January 2002 . Effectiveness of lithotripsy , retreatment rate , reasons for failure and complications were assessed . RESULTS 102 males and 35 females with primary ureteric stones underwent ESWL treatment at our center . 74 patients had upper , 37 middle and 26 lower ureteric locations respectively . Mean stone size was 10 mm ( range 8 - 25 mm ) . Mean numbers of sessions required were 1.8 ( range 1 - 3 ) . The retreatment rate was 33 % in upper ureteric , 29 % in mid ureteric and 26 % in lower ureteric locations respectively . Complete clearance rate at 3 months was 86 % for upper ureteric , 79 % for mid ureteric and 79 % for lower ureteric . 29 patients had auxiliary treatment in the form of double J ureteric stenting or percutaneous nephrostomies . 26 patients failed treatment and underwent ureteroscopic or ante grade percutaneous removal . Stone size was the only significant factor correlating with failure . The mean size of stones in the successful group was 12 mm as compared to 17 mm in failure group . The likelihood of success following a failed second session ( no disintegration or disintegration with fragments more than 6 mm ) of treatment was 13.4 % . Complications including , steinstrasse , colic , UTI and petechial haemorrhage were seen in 35 patients . One patient developed pyonephrosis and subsequently required nephrectomy . CONCLUSION An electromagnetic shock wave lithotriptor using the EMSE-150 shock wave emitter is an effective in situ treatment of primary ureteric stones . Patients with large stone size are likely to have a higher retreatment rate , more auxiliary procedures and complications . Having a failed second treatment session , the likelihood of a successful outcome after third session of ESWL is poor PURPOSE Retro grade stone migration during ureteroscopic lithotripsy occurs in 5 % to 40 % of proximal and distal ureteral stone cases . This migration increases morbidity and the need for auxiliary procedures . The Dretler stone cone ( Med source , Norwell , Massachusetts ) is a novel device to prevent proximal stone migration and facilitate fragment extraction during ureteroscopic lithotripsy . We assessed the safety and efficacy of the Dretler stone cone in the clinical setting and compared it prospect ively with a conventional flat wire basket during ureteroscopy for ureteral calculi . MATERIAL S AND METHODS To our knowledge we report the initial clinical use of the Dretler stone cone in 50 consecutive patients with ureteral calculi undergoing ureteroscopic extraction . Calculi were situated above the sacroiliac joint in 24 cases , over the sacroiliac joint in 15 and below the sacroiliac joint in 11 . Pneumatic lithotripsy was done in 42 cases . In the remaining 8 cases ureteroscopic ( 3 ) or fluoroscopic ( 5 ) intact stone extraction was performed . The later 23 cases using the Dretler stone cone were prospect ively compared with 20 of ureteroscopic intracorporeal lithotripsy using a st and ard flat wire basket . RESULTS The Dretler stone cone was successfully placed in all 50 cases . In 41 patients it was placed via cystoscopy under fluoroscopic guidance , while 9 impacted stones required ureteroscopic placement . Six patients in whom the Dretler stone cone was used had residual fragments less than 3 mm . No patient required auxiliary procedures . In the prospect i ve trial no patients in Dretler stone cone group had residual fragments greater than 3 mm . or required auxiliary procedures . However , in the flat wire basket group residual stones greater than 3 mm . were present in 6 cases ( 30 % , p < 0.001 ) , while auxiliary procedures were required in 4 ( 20 % , p < 0.01 ) . CONCLUSIONS The Dretler stone cone represents a new generation of basketry that minimizes proximal ureteral stone migration and allows safe extraction of fragments during ureteroscopic lithotripsy . In our experience it is associated with a lower incidence of significant residual fragments and fewer auxiliary procedures than conventional flat wire baskets PURPOSE We evaluated the effectiveness and safety of holmium : YAG laser lithotripsy with a semirigid ureteroscope for ureteral calculi in a prospect i ve cohort of 697 patients . PATIENTS AND METHODS Holmium : YAG laser lithotripsy was performed with a semirigid ureteroscope in 697 in patients between September 2002 and January 2006 . Calculi were located in the distal ureter in 382 patients ( 54.8 % ) , the midureter in 143 ( 20.5 % ) , and the proximal ureter in 172 ( 24.7 % ) . Patients were assessed 2 to 24 weeks postoperatively with repeat plain radiography , ultrasonography , intravenous urography , or some combination . RESULTS The overall stone-free rate was 92.2 % , the rate being 100 % for calculi in the distal ureter ( N = 382 ) , 97.9 % for calculi in the midureter ( N = 140 ) , and 70.3 % for calculi in the proximal ureter ( N = 121 ) . Complications occurred in 13 patients ( 1.9 % ) . Postoperative ureteral stricture developed in five patients ( 0.72 % ) and was managed surgically . CONCLUSIONS Holmium : YAG laser lithotripsy with a semirigid ureteroscope is a highly effective and safe treatment for ureteral calculi , especially those in the distal ureter and midureter OBJECTIVES We conducted a study to assess the need for routine ureteral stenting after ureteroscopic stone removal using Lithoclast pneumatic intracorporeal lithotripsy . MATERIAL S AND METHODS A total of 104 patients , prospect ively divided in two groups to receive ( group A , 52 patients ) or not ( group B , 52 patients ) a stent after stone removal , underwent ureteroscopy for the treatment of ureteral lithiasis . The procedure was performed with the patient under either general or epidural anesthesia . A semirigid ureteroscope ( Wolf 8.9 Fr ) was used in all cases and intracorporeal lithotripsy with ballistic energy was performed . In group A a double pigtail ureteral 4.8 or 6 Fr polyurethane stent was placed following ureteroscopy . All patients were closely evaluated on follow-up examinations . The outcomes measured were postoperative patient pain , lower urinary tract symptoms , the need for hospital care as a result of the postoperative pain and late postoperative complications . RESULTS The two patient groups were comparable with respect to the baseline variables of patient gender and age , stone location and mean stone size . Mean operative time plus or minus st and ard deviation ( S.D. ) in group A was 42 + /- 15 minutes ( range 20 - 65 ) compared to 37 + /- 20 ( range 15 - 60 ) in group B. Operative time was not significantly longer when a stent was placed ( p = 0.17 ) . At day 3 the mean visual analog pain score in group B was much higher than in group A ( p = 0.01 ) . Dysuria , hematuria and frequency/urgency were more prevalent in the stented group , although without statistically significant difference . Readmission to the hospital for unremitting pain was necessary in 12 of 104 patients ( 11.5 % ) all being in unstented group ( p < 0.05 ) . The incidence of anatomical ureteral narrowing on IVP at 6 months follow-up was not statistically different between the two groups . CONCLUSIONS In our experience , using Swiss Lithoclast ballistic energy to fragment stones , routine stent placement is advisable also after uncomplicated ureteroscopic lithotripsy without ureteral dilation . Further prospect i ve r and omized studies are needed to assess the role of stenting after ureteroscopic lithotripsy , considering different energies sources , scopes , diameter and site of the stones in the ureter AIM To compare the efficacy and complications of extracorporeal shock-wave lithotripsy ( SWL ) and pneumatic ureteroscopic lithotripsy ( URS ) in the treatment of lower ureteral calculi . METHODS From August 1997 to June 1999 , 210 patients with calculi in the distal third of the ureter were treated with SWL and the other 180 with URS . The stones were fragmented with either HB-ESWL-V lithotripter or JML-93 pneumatic lithotripter through Wolf 7.5 approximately 9.0 Fr ureteroscope . The outcome was assessed in terms of stone clearance rate , re-treatment rate and complication incidence . RESULTS The stone clearance rate was 78.1 % with SWL and 93.3 % with URS ( P<0.05 ) . SWL had a re-treatment rate of 11.9 % , vs 2.2 % in the URS group ( P<0.05 ) . URS caused ureteral perforation in 3.3 % of patients , while it was 0 with SWL ( P<0.05 ) . The differences in the incidence of other complications such as infection and stricture between the two groups were insignificant . CONCLUSION Though the selection of these two options depends on equipments available and the expertise of the operator , we recommend URS as the optimal treatment for distal ureteral calculi Some reports have shown a decreased effectiveness of extracorporeal shock wave lithotripsy ( ESWL * ) with newer lithotriptors . We used a first generation unmodified Dornier HM3 lithotriptor to treat 5,698 patients with renal and ureteral calculi and a second generation Medstone STS device to treat 8,166 patients with renal and ureteral calculi . The treatment results were compared using the chi-square test to determine statistical significance . The stone-free rate , retreatment rate and post-ESWL secondary procedure rate were 69.5 % , 4.4 % and 3.1 % , respectively , with the Dornier HM3 device and 72.1 % , 4.9 % and 2.3 % , respectively , with the Medstone lithotriptor for single renal stones , and 81.5 % , 5.2 % and 5.5 % , respectively , with the Dornier HM3 and 83.2 % , 5.2 % and 5.0 % , respectively , with the Medstone device for single ureteral stones . There were no statistically significant different results between a second generation tubless Medstone STS lithotriptor and the gold st and ard unmodified Dornier HM3 instrument OBJECTIVES To report a matched comparison of patients with and without stenting after ureteroscopy for calculi , including middle or proximal ureteral and renal calculi . The elimination of routine stenting after ureteroscopy would prevent stent pain , minimize the need for re-instrumentation , and reduce costs-as long as efficacy and safety are not diminished . METHODS Of 318 patients who underwent ureteroscopy , 81 ( 25 % ) did not have a ureteral stent placed . Of those , 51 were suitable for analysis and included patients with distal ureteral ( n = 22 ) , middle or proximal ureteral ( n = 11 ) , and renal calculi ( n = 18 ) . This cohort was matched to a stented group by stone size and location . RESULTS The preoperative characteristics of the groups were similar . A stone-free rate of 86 % and 94 % was achieved in the stented and nonstented groups , respectively ( P = 0.32 ) . Complications in the nonstented group were less frequent ( flank pain in 3 and postoperative nausea in 1 ) than in the stented group ( hospital visits for flank pain in 12 , persistent nausea and vomiting in 1 , sepsis in 1 , perinephric hematoma in 1 , and urinary retention in 1 ) ( total of 4 versus 16 , P = 0.025 ) . CONCLUSIONS Ureteroscopy for distal ureteral stones without ureteral stent placement has been previously described . Our experience exp and s to include the elimination of stent placement after ureteroscopy for middle or proximal ureteral ( 22 % ) and renal ( 35 % ) calculi . Our data suggest that after ureteroscopies with short operative times and minimal ureteral trauma , ureteral stents may not be necessary , even if proximal ureteral or renal ureteroscopy has been performed PURPOSE To compare blind access and totally tubeless percutaneous ante grade removal and pneumatic transurethral ureterolithotripsy for the management of impacted upper-ureteral calculi > 1 cm . PATIENTS AND METHODS Seventy patients ( 41 male , 29 female ) with impacted upper-ureteral calculi > 1 cm were selected in r and omized order for pneumatic transurethral ureterolithotripsy ( 35 patients ) or blind access and totally tubeless percutaneous nephrolithotomy ( PCNL ) ( 35 patients ) . Ultrasonography and intravenous urography were performed for all patients before surgery . After operation , plain films and ultrasonography were done . RESULTS In the PCNL group , blind access was achieved from the lumbar notch area in all 35 patients , but in 3 patients , the exposure was not optimal for approaching the ureteropelvic junction ( UPJ ) . So we injected contrast material into the collecting system , and , under fluoroscopic control , another access was achieved . In 33 patients ( 94.3 % ) , intact removal of the stones was performed . In the other two patients , we fragmented the stones with the Swiss Lithoclast by an ante grade approach . The success rate thus was 100 % . The mean operative time was 38 minutes ( range 25 - 48 minutes ) . In the transurethral lithotripsy group , 12 stones ( 34.2 % ) migrated upward to the pelvis of kidney , and 5 stones ( 14.2 % ) fragmented incompletely . In these cases , a double- J stent was inserted , and SWL was performed . In follow-up , plain films and ultrasonography showed complete clearance in these patients . Eighteen calculi ( 51.4 % ) fragmented completely with the Lithoclast . The mean operative time in this group was 34 minutes ( range 20 - 58 minutes ) . CONCLUSION In the presence of moderate to severe hydronephrosis , blind access and totally tubeless PCNL is an effective option for large , impacted upper-ureteral calculi . Flexible ureteroscopy with laser lithotripsy is expensive and not readily available . Pneumatic transurethral ureterolithotripsy has a back-pressure effect and pushes back the calculi to the kidney . Thus , this procedure does not have satisfactory results in the management of these calculi PURPOSE A prospect i ve r and omized controlled trial was conducted to evaluate whether postoperative ureteral stenting is necessary after ureteroscopic laser lithotripsy . MATERIAL S AND METHODS A total of 58 patients with unilateral ureteral stones were r and omized into either stented or unstented groups . Ureteroscopic laser lithotripsy was performed using a semirigid ureteroscope ( 6.5/7Fr ) and holmium laser without ureteral orifice dilation . There were no selection criteria regarding stone size , location , preoperative ureteral obstruction and hydronephrosis . Endoscopic evidence of stone impaction or mucosal edema/damage did not exclude a patient from the study . Ureteral perforation on completion retro grade pyelogram was the only intraoperative criterion for study exclusion . Postoperative pain scores and symptoms were recorded . Excretory urography was performed to document stone-free status and stricture formation . Radionuclide scan was performed selectively to exclude functional obstruction when ureteral narrowing was found on excretory urogram . RESULTS Mean stone size + /- SD was 9.7 + /- 4.0 mm . ( range 4 to 27 ) . Proximal ureteral stones accounted for 43 % of all stones . Stented and unstented groups were comparable with respect to demographic data , stone parameters , preoperative obstruction and hydronephrosis . There was no significant difference in operating time , laser energy used , stone impaction and mucosal edema/damage between the 2 groups . Postoperative pain and symptoms were more severe and frequent ( p < 0.05 ) in the stented group . However , there was no difference in the incidence of postoperative sepsis and unplanned medical visits . The stone-free and stricture formation rates showed no statistical difference between the 2 groups . CONCLUSIONS Ureteral stenting is not necessary after uncomplicated ureteroscopic laser lithotripsy for ureteral stones . Ureteral stent increases the incidence of pain and urinary symptoms but does not prevent postoperative urinary sepsis and unplanned medical visits . Severity of preoperative obstruction and intraoperative ureteral trauma were not shown to be determining factors for stenting |
12,652 | 23,834,881 | Interventions that combined parent education with clinician behaviour change decreased antibiotic prescribing rates by between 6 - 21 % ; structuring the parent-clinician interaction during the consultation may further increase the effectiveness of these interventions .
Automatic computerised prescribing prompts increased prescribing appropriateness , while passive information , in the form of waiting room educational material s , yielded no benefit .
Conflicting evidence from the included studies found that interventions directed towards parents and /or clinicians can reduce rates of antibiotic prescribing .
The most effective interventions target both parents and clinicians during consultations , provide automatic prescribing prompts , and promote clinician leadership in the intervention design | BACKGROUND Respiratory tract infections ( RTIs ) in children are common and often result in antibiotic prescription despite their typically self-limiting course .
AIM To assess the effectiveness of primary care based interventions to reduce antibiotic prescribing for children with RTIs . | Objective To establish whether an interactive booklet on respiratory tract infections in children reduces reconsultation for the same illness episode , reduces antibiotic use , and affects future consulting intentions , while maintaining parental satisfaction with care . Design Pragmatic cluster r and omised controlled trial . Setting 61 general practice s in Wales and Engl and . Participants 558 children ( 6 months to 14 years ) presenting to primary care with an acute respiratory tract infection ( 7 days or less ) . Children with suspected pneumonia , asthma or a serious concomitant illness , or needing immediate hospital admission were excluded . Three withdrew and 27 were lost to follow-up , leaving 528 ( 94.6 % ) with main outcome data . Interventions Clinicians in the intervention group were trained in the use of an interactive booklet on respiratory tract infections and asked to use the booklet during consultations with recruited patients ( and provide it as a take home re source ) . Clinicians in the control group conducted their consultations as usual . Main outcome measures The proportion of children who attended a face-to-face consultation about the same illness during the two week follow-up period . Secondary outcomes included antibiotic prescribing , antibiotic consumption , future consulting intentions , and parental satisfaction , reassurance , and enablement . Results Reconsultation occurred in 12.9 % of children in the intervention group and 16.2 % in the control group ( absolute risk reduction 3.3 % , 95 % confidence interval −2.7 % to 9.3 % , P=0.29 ) . Using multilevel modelling ( at the practice and individual level ) to account for clustering , no significant difference in reconsulting was noted ( odds ratio 0.75 ; 0.41 to 1.38 ) . Antibiotics were prescribed at the index consultation to 19.5 % of children in the intervention group and 40.8 % of children in the control group ( absolute risk reduction 21.3 % , 95 % confidence interval 13.7 to 28.9 ) , P<0.001 ) . A significant difference was still present after adjusting for clustering ( odds ratio 0.29 ; 0.14 to 0.60 ) . There was also a significant difference in the proportion of parents who said they would consult in the future if their child developed a similar illness ( odds ratio 0.34 ; 0.20 to 0.57 ) . Satisfaction , reassurance , and parental enablement scores were not significantly different between the two groups . Conclusions Use of a booklet on respiratory tract infections in children within primary care consultations led to important reductions in antibiotic prescribing and reduced intention to consult without reducing satisfaction with care . Trial registration Current Controlled Trials IS RCT Background To explore ways to reduce the overuse of antibiotics for acute respiratory infections ( ARIs ) , we conducted a pilot clustered r and omized controlled trial ( RCT ) to evaluate DECISION+ , a training program in shared decision making ( SDM ) for family physicians ( FPs ) . This pilot project demonstrated the feasibility of conducting a large clustered RCT and showed that DECISION+ reduced the proportion of patients who decided to use antibiotics immediately after consulting their physician . Consequently , the objective of this study is to evaluate , in patients consulting for ARIs , if exposure of physicians to a modified version of DECISION+ , DECISION+2 , would reduce the proportion of patients who decide to use antibiotics immediately after consulting their physician . Methods / design The study is a multi-center , two-arm , parallel clustered RCT . The 12 family practice teaching units ( FPTUs ) in the network of the Department of Family Medicine and Emergency Medicine of Université Laval will be r and omized to a DECISION+2 intervention group ( experimental group ) or to a no-intervention control group . These FPTUs will recruit patients consulting family physicians and residents in family medicine enrolled in the study . There will be two data collection periods : pre-intervention ( baseline ) including 175 patients with ARIs in each study arm , and post-intervention including 175 patients with ARIs in each study arm ( total n = 700 ) . The primary outcome will be the proportion of patients reporting a decision to use antibiotics immediately after consulting their physician . Secondary outcome measures include : 1 ) physicians and patients ' decisional conflict ; 2 ) the agreement between the parties ' decisional conflict scores ; and 3 ) perception of patients and physicians that SDM occurred . Also in patients , at 2 weeks follow-up , adherence to the decision , consultation for the same reason , decisional regret , and quality of life will be assessed . Finally , in both patients and physicians , intention to engage in SDM in future clinical encounters will be assessed . Intention-to-treat analyses will be applied and account for the nested design of the trial will be taken into consideration . Discussion DECISION+2 has the potential to reduce antibiotics use for ARIs by priming physicians and patients to share decisional process and empowering patients to make informed , value-based decisions . Trial Registration Clinical Trials.gov : OBJECTIVES . To determine whether we could increase adherence to the Centers for Disease Control and Prevention ( CDC ) recommendations with well-accepted approaches to improving quality of care and adherence to the CDC recommendations result ed in improved outcomes for acute otitis media ( AOM ) . METHODS . A cluster r and omization study was conducted in 12 pediatric practice s ( 6 intervention and 6 control sites ) . The main outcome measures were adherence to the CDC recommendations ( modified to include 2 additional antimicrobial agents ) and a subsequent antibiotic prescription for AOM within 30 days after diagnosis . RESULTS . Of 3152 patients referred to research assistants , 2584 ( 82 % ) were eligible . Of those eligible , 1368 ( 99 % ) of 1382 at the intervention sites and 1138 ( 99 % ) of 1146 at the control sites consented to participate . Rates of adherence to the CDC recommendations were not significantly higher at the intervention sites than at the control sites , for initial enrollment episodes ( 78.2 % vs 70.6 % ) or second episodes ( 62.6 % vs 59.9 % ) . After controlling for clustering according to site and covariates , children who were not treated in adherence to the CDC recommendations for both episodes had 1.60 times the odds of a subsequent prescription within 12 days , compared with those treated in adherence at both episodes . CONCLUSIONS . Despite using evidence -based approaches that are known to influence physician behavior , we were unable to increase adherence to the CDC recommendations for treatment of AOM . However , we did establish that prescription of antimicrobial therapy consistent with the CDC recommendations for a second episode of AOM was associated with improved outcomes , measured as the need for subsequent antibiotic prescription . Because of the selection of resistant otopathogens , adherence to the CDC recommendations is likely more important in subsequent episodes of AOM than in the initial episode Abstract Objective : To assess the medicalising effect of prescribing antibiotics for sore throat . Setting : 11 general practice s in Engl and . Design : R and omised trial of three approaches to sore throat : a 10 day prescription of antibiotics , no antibiotics , or a delayed prescription if the sore throat had not started to settle after three days . Patients : 716 patients aged 4 and over with sore throat and an abnormal physical sign : 84 % had tonsillitis or pharyngitis . Outcome measures : Number and rate of patients making a first return with sore throat , pharyngitis , or tonsillitis . Early returns ( within two weeks ) and complications ( otitis media , sinusitis , quinsy ) . Outcomes were documented in 675 subjects ( 94 % ) . Results : Mean follow up time was similar ( antibiotic group 1.07 years , other two groups 1.03 years ) . More of those initially prescribed antibiotics initially returned to the surgery with sore throat ( 38 % v 27 % , adjusted hazard ratio for return 1.39 , 95 % confidence interval 1.03 to 1.89 ) . Antibiotics prescribed for sore throat during the previous year had an additional effect ( hazard ratio 1.69 , 1.20 to 2.37 ) . Longer duration of illness ( > 5 days ) was associated with increased return within six weeks ( hazard ratio 2.90 , 1.70 to 4.92 ) . Prior attendance with upper respiratory conditions was also associated with increased reattendance . There was no difference between groups in early return ( 13/238 ( 5.5 % ) v 27/437 ( 6 % ) ) , or complications ( 2/236 ( 0.8 % ) v3/434 ( 0.7 % ) ) . Conclusions : Complications and early return result ing from no or delayed prescribing of antibiotics for sore throat are rare . Both current and previous prescribing for sore throat increase reattendance . To avoid medicalising a self limiting illness doctors should avoid antibiotics or offer a delayed prescription for most patients with sore throat . Key messages Sore throat is one of the commonest presentations of upper respiratory illness in primary care and attendence is increasing Complications are rare with no , or delayed , antibiotic prescription Prescribing antibiotics increases reattendance for future episodes Unless patients are very ill general practitioners should consider exploring concerns , explain the natural history , and avoid or delay prescribing CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition A r and omised controlled trial involving 54 general practitioners ( GPs ) was conducted in Canberra , Australian Capital Territory from September 1997 to November 1999 . In the first year of the study , 24 GPs , who constituted the active arm of the intervention group , were involved in the consideration of evidence and the development and implementation of a set of clinical guidelines for the treatment of acute respiratory infections . These guidelines were then endorsed in a meeting together with specialist colleagues . In the second year of the study the group of GPs who had been acting as controls , received a moderate intervention consisting of a brief educational event and distribution of the locally developed guidelines . We obtained data from January 1997 to December 1999 from the Health Insurance Commission on prescribing rates for 40 of the doctors in the study . The rate of prescribing was calculated as the number of antibiotic prescriptions per 100 Medicare services . The average yearly prescribing decreased significantly in the intensive intervention group and increased in the moderate intervention group , ( p=0.026 ) . A mixed effects longitudinal time series model was fitted to the data to account for seasonal variation of antibiotic prescribing and trends over time . The intensive intervention group significantly reduced their antibiotic prescribing over time compared to the moderate intervention group , ( p<0.001 ) . This study has shown that an intensive intervention in which general practitioners were actively engaged in development and consideration of the evidence base for the guidelines result ed in a significant fall in general antibiotic prescribing Objective To assess the effect of general practitioner testing for C reactive protein ( disease approach ) and receiving training in enhanced communication skills ( illness approach ) on antibiotic prescribing for lower respiratory tract infection . Design Pragmatic , 2 × 2 factorial , cluster r and omised controlled trial . Setting 20 general practice s in the Netherl and s. Participants 40 general practitioners from 20 practice s recruited 431 patients with lower respiratory tract infection . Main outcome measures The primary outcome was antibiotic prescribing at the index consultation . Secondary outcomes were antibiotic prescribing during 28 days ’ follow-up , reconsultation , clinical recovery , and patients ’ satisfaction and enablement . Interventions General practitioners ’ use of C reactive protein point of care testing and training in enhanced communication skills separately and combined , and usual care . Results General practitioners in the C reactive protein test group prescribed antibiotics to 31 % of patients compared with 53 % in the no test group ( P=0.02 ) . General practitioners trained in enhanced communication skills prescribed antibiotics to 27 % of patients compared with 54 % in the no training group ( P<0.01 ) . Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days ’ follow-up . Clinicians in the combined intervention group prescribed antibiotics to 23 % of patients ( interaction term was non-significant ) . Patients ’ recovery and satisfaction were similar in all study groups . Conclusion Both general practitioners ’ use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients ’ recovery and satisfaction with care . A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care . Trial registration Current Controlled Trials IS RCT N85154857 BACKGROUND Antibiotic overuse is of great public health concern . This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use , specifically in classes known to promote antibiotic resistance among children in a community setting . METHODS We performed a cluster r and omized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practice s. The intervention was led by local leaders and engaged the participating physicians . It included physician focus group meetings , workshops , seminars , and practice campaigns . These activities focused on self-developed guidelines , improving parent and physician knowledge , diagnostic skills , and parent-physician communication skills that promoted awareness of antibiotic resistance . The main outcome measure was the change in annual antibiotic prescription rates ( APRs ) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians . The study comprised a 2-year pre-intervention period , a 3-year intervention period , and a 1-year follow-up period . Mixed-effect models were used to assess risk ratios to account for the clustered study design . RESULTS A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year ( APR decrease among control physicians , 40 % ; APR decrease among intervention physicians , 22 % ; relative risk [ RR ] , .76 ; 95 % confidence interval [ CI ] , .75-.78 ) . This reduction crossed over all antibiotic classes but was most prominent for macrolides ( macrolide prescription rate among control physicians , 58 % ; macrolide prescription rate among intervention physicians , 27 % ; RR , .58 ; 95 % CI , .55-.62 ) . The effect was sustained during the 4 following years . CONCLUSIONS . Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained . CLINICAL TRIALS REGISTRATION NCT01187758 INTRODUCTION Antibiotic overuse promotes resistant strains of bacteria and puts patients at risk for adverse reactions . Given the use of educational posters in government-sponsored public health campaigns , this study examined the effectiveness of a waiting room poster in reducing excessive antibiotic use in clinical practice . METHODS Investigators conducted a 1-month trial of an educational poster with historical controls using three private pediatric group practice s in Westchester County , New York . Children between the ages of 6 months and 10 years at the time of a visit to diagnose and treat symptoms of respiratory illness were enrolled as subjects . Antibiotic prescriptions for children with respiratory illnesses seen during the poster month were compared with prescriptions written during three 1-month historical control periods . The proportion of visits that result ed in a prescription for an antibiotic served as the outcome measure . RESULTS Overall , 326 of the 720 patients ( 45.2 % ) enrolled in the study were treated with an antibiotic . Multiple logistic regression analysis revealed no statistically significant difference in the proportion of visits result ing in an antibiotic prescription among the 4 study months ( P = .79 ) , indicating that the educational poster had no effect on antibiotic use . DISCUSSION Public education in the form of a waiting room poster was not sufficient to decrease antibiotic prescriptions . This finding has implication s for current large-scale programs and for health care providers as they continue to attempt to educate patients on the appropriate use of antibiotics BACKGROUND The rapid increase of antibiotic resistance poses a significant threat to human health . Overuse of antibiotics has been linked to rates of antibiotic resistance . This study assessed the utility of two common interventions --1 ) practice profiling and feedback and 2 ) patient education material s -- implemented to decrease antibiotic prescribing for pediatric upper respiratory infections ( URIs ) . METHODS Based on Medicaid regions in Kentucky , primary care physicians managing pediatric respiratory infections in Medicaid were r and omized into four groups . Groups received either 1 ) performance feedback only , 2 ) patient education material s only , 3 ) both feedback and education material s , or 4 ) no intervention . Participating physicians had their antibiotic prescribing assessed for the period of July 1 , 1996 , to November 30 , 1997 , with an intervention in June 1997 . The study included 216 physicians and 124,092 episodes of care . RESULTS All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods . Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group . Physicians did not change their coding of illness to justify antibiotics after the intervention , and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs . CONCLUSIONS These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing . Antibiotic prescribing for viral respiratory infections continues to increase , suggesting concomitant increases in antibiotic resistance Abstract BACKGROUND : Inappropriate use of antimicrobials to treat acute upper respiratory tract infections ( URIs ) , which usually have a viral etiology , contributes to emergence and spread of antimicrobial resistance in Streptococcus pneumoniae and other human bacterial pathogens . OBJECTIVE : To reduce antimicrobial use for management of acute URIs in adult and pediatric patients . DESIGN : Prospect i ve , nonr and omized , controlled trial . SETTING : Four primary care clinics within a staff model HMO in Detroit , Mich. PARTICIPANTS : Twenty-one primary care physicians at clinics where the educational intervention was implemented , and 9 primary care physicians at control clinics where no educational programs were implemented . MEASUREMENTS : Antibiotic prescribing for acute URIs during the baseline and study years among the intervention and control groups . RESULTS : A generalized linear mixed-effects model was used and showed that antimicrobial prescribing among the intervention group physicians decreased 24.6 % from the baseline to the postintervention period ( P<.0001 ) for both pediatric and adult medicine physicians . From the baseline to the study period , there was no significant decline in rates of antimicrobial prescribing by the control group of physicians ( pediatricians , P=.35 ; internists , P=.42 ) . The rates of decline in antimicrobial prescribing differed significantly between the intervention and control groups ( P<.0003 for pediatricians and P<.01 for Internists ) . CONCLUSIONS : An interactive , case-based educational program for physicians and their staff proved effective for reducing unwarranted prescribing of antibiotics in the treatment of URIs by primary care physicians in a Medicaid HMO setting Objective : To determine whether an educational intervention aim ed at parents leads to fewer antibiotic prescriptions for their children . Design : Placebo-controlled , r and omized controlled trial . Setting : Offices of primary care pediatricians who are members of a regional practice -based research network . Participants : Healthy children younger than 24 months old enrolled at the time of an office visit . Interventions : Parents of study children were r and omized to receive either a pamphlet and videotape ( featuring one of their child 's pediatricians ) promoting the judicious use of antibiotics ( intervention group ) or brochures about injury prevention ( control group ) . A total of 499 eligible children were enrolled , and data on outpatient visits during a 12-month observation period were collected . Main Outcome Measures : We compared the number of visits for upper respiratory tract infections ( URIs ) , number of diagnoses and antibiotic prescriptions for otitis media and /or sinusitis and total number of antibiotics per patient among children in the intervention and control groups using Poisson regression analysis , adjusted for clustering into different practice s. Results : Data on 4924 visits were review ed ; 28.8 % of these visits were because of URI symptoms . The mean number of visits per study patient for URI symptoms was 2.8 . Including all visits , the mean number of diagnoses of otitis media in study children was 2.1 , mean number of diagnoses of otitis media and /or sinusitis was 2.3 and mean number of antibiotic prescriptions was 2.4 ; there were no significant differences between children in the intervention and control groups for any of these outcomes . Overall physicians prescribed 1 or more antibiotics during 45.9 % of visits for a chief complaint of URI symptoms ; 92 % of antibiotic usage in children presenting with URI symptoms was for a diagnosis of otitis media and /or sinusitis . Conclusions : An educational intervention aim ed at parents did not result in a decrease in the number of antibiotic prescriptions in their children . The use of antibiotics among children with URI symptoms was common ; other interventions promoting the judicious use of these medications are needed BACKGROUND Excessive and inappropriate use of antibiotics has been identified as a leading cause of the emergence of multiply resistant strains of pneumococci . OBJECTIVE To examine the effects of academic detailing and a parental education program on community pediatricians ' prescription of antibiotics for young children . METHODS Physician leaders in study practice s prepared educational modules and presented the modules to their practice s. The control groups received only practice -specific report cards . Using a time-series analysis , we collected data on office visits and antibiotic prescriptions filled between May 1 , 2000 , and April 30 , 2001 ( baseline period ) , and between May 1 , 2001 , and April 30 , 2002 ( intervention period ) . Antibiotic prescription rate was defined as the ratio of antibiotic prescriptions filled to the number of office visits . RESULTS The antibiotic prescription rate decreased to 0.82 ( 95 % confidence interval , 0.71 - 0.95 ) of the baseline rate for the study group ( 6 practice s ) and to 0.86 ( 95 % confidence interval , 0.77 - 0.95 ) of the baseline for the control group ( 5 practice s ) . Similar patterns for antibiotic prescription rates were seen for study and control groups both before and after the intervention . Wide variations in prescription rates were observed among the practice s , but , in general , the control practice s had lower antibiotic prescribing rates during both the baseline and the intervention periods . Use of amoxicillin increased slightly in the study group and decreased slightly in the control group . The use of cephalosporins increased slightly in both groups . CONCLUSION Overall , academic detailing appeared to be no more effective in reducing antibiotic use than the practice -specific report cards alone OBJECTIVE To test whether an educational outreach intervention for families and physicians , based on the Centers for Disease Control and Prevention ( CDC ) principles of judicious antibiotic use , decreases antimicrobial drug prescribing for children younger than 6 years old . Setting . Twelve practice s affiliated with 2 managed care organizations ( MCOs ) in eastern Massachusetts and northwest Washington State . Patients . All enrolled children younger than 6 years old . METHODS Practice s stratified by MCO and size were r and omized to intervention or control groups . The intervention included 2 meetings of the practice with a physician peer leader , using CDC-endorsed summaries of judicious prescribing recommendations ; feedback on previous prescribing rates were also provided . Parents were mailed a CDC brochure on antibiotic use , and supporting material s were displayed in waiting rooms . Automated enrollment , ambulatory visit , and pharmacy cl aims were used to determine rates of antibiotic courses dispensed ( antibiotics/person-year ) during baseline ( 1996 - 1997 ) and intervention ( 1997 - 1998 ) years . The primary analysis ( for children 3 to < 36 months and 36 to < 72 months ) assessed the impact of the intervention among children during the intervention year , controlling for covariates including patient age and baseline prescription rate . Confirmatory analyses at the practice level were also performed . RESULTS The practice s cared for 14 468 and 13 460 children in the 2 study years , respectively ; 8815 children contributed data in both years . Sixty-two percent of antibiotic courses were dispensed for otitis media , 6.5 % for pharyngitis , 6.3 % for sinusitis , and 9.2 % for colds and bronchitis . Antibiotic dispensing for children 3 to < 36 months old decreased 0.41 antibiotics per person-year ( 18.6 % ) in intervention compared with 0.33 ( 11.5 % ) in control practice s. Among children 36 to < 72 months old , the rate decreased by 0.21 antibiotics per person-year ( 15 % ) in intervention and 0.17 ( 9.8 % ) in control practice s. Multivariate analysis showed an adjusted intervention effect of 16 % in the younger and 12 % in the older age groups . The direction and approximate magnitude of effect were confirmed in practice -level analyses . CONCLUSIONS A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practice s , even in the setting of substantial secular trends toward decreased prescribing . Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse Background . Computerized decision support ( CDS ) can potentially improve patient safety and guideline adherence . The authors developed an acute respiratory illness interactive template ( ARI-IT ) within an electronic health record ( EHR ) to manage pediatric ARIs and assessed the impact on antibiotic prescribing . Methods . They r and omized 12 practice s either to receive the ARI-IT or to the control group . Antibiotic rates among all eligible ARI diagnoses were compared among control and intervention ARI visits , controlling for clustering by clinician . Results . There was no difference in total antibiotic prescriptions between control and intervention clinics . Use of the ARI-IT significantly reduced antibiotic prescriptions ( 31.7 % vs 39.9 % ; P = .02 ) and use of macrolides ( 6.2 % vs 9.5 % ; P = .02 ) among visits compared with those eligible visits where it was not used . Conclusion . Use of the CDS reduced antibiotic prescribing and macrolide prescriptions among children with an ARI . Nonetheless , the low overall use result ed in an ineffective intervention Objective To evaluate the effectiveness and costs of a multifaceted flexible educational programme aim ed at reducing antibiotic dispensing at the practice level in primary care . Design R and omised controlled trial with general practice s as the unit of r and omisation and analysis . Clinicians and research ers were blinded to group allocation until after r and omisation . Setting 68 general practice s with about 480 000 patients in Wales , United Kingdom . Participants 34 practice s were r and omised to receive the educational programme and 34 practice s to be controls . 139 clinicians from the intervention practice s and 124 from control practice s had agreed to participate before r and omisation . Practice level data covering all the clinicians in the 68 practice s were analysed . Interventions Intervention practice s followed the Stemming the Tide of Antibiotic Resistance ( STAR ) educational programme , which included a practice based seminar reflecting on the practice s ’ own dispensing and resistance data , online educational elements , and practising consulting skills in routine care . Control practice s provided usual care . Main outcome measures Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention , adjusted for the previous year ’s dispensing . Secondary outcomes included reconsultations , admissions to hospital for selected causes , and costs . Results The rate of oral antibiotic dispensing ( items per 1000 registered patients ) decreased by 14.1 in the intervention group but increased by 12.1 in the control group , a net difference of 26.1 . After adjustment for baseline dispensing rate , this amounted to a 4.2 % ( 95 % confidence interval 0.6 % to 7.7 % ) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group ( P=0.02 ) . Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins ( penicillin V ) ( 7.3 % , 0.4 % to 13.7 % ) and macrolides ( 7.7 % , 1.1 % to 13.8 % ) . There were no significant differences between intervention and control practice s in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation . The mean cost of the programme was £ 2923 ( € 3491 , $ 4572 ) per practice ( SD £ 1187 ) . There was a 5.5 % reduction in the cost of dispensed antibiotics in the intervention group compared with the control group ( −0.4 % to 11.4 % ) , equivalent to a reduction of about £ 830 a year for an average intervention practice . Conclusion The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital , reconsultations , or costs . Trial registration IS RCT No 63355948 PURPOSE In an environment of multiple campaigns promoting judicious antibiotic use in children , identification of effective strategies is important . We assessed physician responses to a community-level intervention with respect to antibiotic prescribing , related practice s , and perceived effectiveness . METHODS This study was a mixed qualitative and quantitative evaluation of a r and omized controlled community-wide educational intervention in 16 Massachusetts communities . Physicians in intervention communities received locally endorsed guidelines , group educational sessions , and biweekly newsletters . Parents simultaneously received material s in physicians ’ offices and by mail . After the intervention , we conducted a mailed physician survey and individual interviews to assess the impact of the intervention . We compared survey responses for intervention and control physicians , and we analyzed interview transcripts to provide in-depth information about selected topics . RESULTS Among survey respondents ( n = 168 ) , 91 % of intervention and 4 % of control physicians reported receiving intervention material s. Physicians received information from multiple other sources . More intervention than control physicians reported decreased antibiotic prescribing from 2000–2003 ( 75 % vs 58 % , P = .03 ) , but there were no differences between groups in knowledge , attitudes , or behaviors favoring judicious antibiotic use . Both groups were concerned about antibiotic resistance and reported room to reduce their own prescribing . Interviewed physicians suggested frequent repetition of messages , brief written material s on specific topics for themselves and patients , and promotion in the mass media as the most effective strategies to reduce prescribing . CONCLUSIONS In multiple communities an intervention in physician offices to promote judicious antibiotic prescribing reached its intended audience , but physicians ’ self-reported attitudes and practice s were similar in intervention and control communities . Campaigns that repeat brief , consistent reminders to multiple stakeholder groups may be most effective at assuring judicious antibiotic use |
12,653 | 20,061,926 | Proteinuria decreased significantly in group A patients only .
Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism , plasma aldosterone , and ammonia excretion .
Patients with more than or equal to 30 % reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene .
The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year .
Lisinopril significantly reduced proteinuria , renal proximal tubular polypeptide catabolism , plasma aldosterone , and ammonia excretion suggesting relative preservation of graft function .
Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors | BACKGROUND Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure .
Data in renal transplantation remain limited .
A negative effect on glomerular filtration rate was concluded in a recent systematic review . | A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome . Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome . With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan ( RENAAL ) study data base as an example , the influence of baseline proteinuria on the primary composite endpoint , ESRD , and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined . Increasing baseline proteinuria was associated with increased risk for renal events , confirming that proteinuria is an important covariate for renal outcomes . When the r and omization was stratified according proteinuria < 2000 mg/g or > /=2000 mg/g , within the higher proteinuria stratum ( > /=2000 mg/g ) , patients in the losartan group had a higher baseline mean proteinuria value . When the imbalance was adjusted , an increase in the magnitude and the significance of the risk reduction with losartan for each outcome was observed . No apparent interaction between treatment effect and baseline proteinuria was found , and there was no heterogeneity in the treatment response in patients with different baseline proteinuria levels . After proteinuria was adjusted as a continuous variable , greater treatment effects were observed in the RENAAL study . This effect was due solely to the imbalance in baseline proteinuria . Considering the importance of proteinuria as a risk factor , adjustment for baseline proteinuria as a continuous covariate should be prespecified in the design and analysis of clinical trials involving renal outcomes , even when patients are stratified on the basis of level of proteinuria BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes BACKGROUND Chronic allograft nephropathy ( CAN ) is the leading cause of late allograft failure , with only limited treatment options . Blockade of the renin-angiotensin system ( RAS ) decreases progression in diabetic and non-diabetic renal disease , but the effect on CAN is as yet unclear . Therefore , we have studied retrospectively the effect of RAS blockade on renal survival in patients with biopsy-proven CAN . METHODS The medical records of 72 patients with biopsy-proven CAN were evaluated with regard to time course of graft function , proteinuria , blood pressure , and antihypertensive and immunosuppressive treatment . Cox 's proportional hazards model was used for analysing renal graft survival after the index biopsy . RESULTS On univariate analysis , histological determinants influencing renal survival were the chronic interstitial and chronic tubular score , and clinical parameters were the serum creatinine level at the time of the biopsy , the relative change in serum creatinine level between 12 months post-transplantation and at the time of the biopsy , mean systolic and diastolic blood pressure after the biopsy , and RAS blockade by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker . On multivariate analysis , graft outcome was influenced by the relative change in serum creatinine level between 12 months post-transplantation and the time of the index biopsy , the urinary protein excretion , the mean diastolic blood pressure after the index biopsy , and RAS blockade . Renal graft survival after treatment with RAS blockade was 6.3 ( 0.9 - 10.9 ) years as opposed to 1.8 ( 0.1 - 6.7 ) years in untreated patients ( P = 0.003 ) . CONCLUSION RAS blockade increases graft survival in CAN . In view of the limited treatment options for CAN , this finding is of importance and needs confirmation by a prospect i ve r and omized trial A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and analysis ) . The revised diagram explicitly includes the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers lets the reader know whether the authors have performed an intention-to-treat analysis ( 21 - 23 ) . Because some of the information may not always be known and to accommo date other information , the structure of the flow diagram may need to be modified for a particular trial . Inclusion of the participant flow diagram in the report is strongly recommended but may be unnecessary for simple trials , such as those without any participant withdrawals or dropouts . Discussion Specifically developed to guide authors about how to improve the quality of reporting of simple two-group , parallel RCTs , CONSORT encourages transparency with reporting of the methods and results so that reports of RCTs can be interpreted both readily and accurately . However , CONSORT does not address other facets of reporting that also require attention , such as scientific content and readability of RCT reports . Some authors , in their enthusiasm to use CONSORT , have modified the checklist ( 24 ) . We recommend against such modifications because they may be based on a different process than the one used by the CONSORT group . The use of CONSORT seems to reduce ( if not eliminate ) inadequate reporting of RCTs ( 14 , 15 ) . Potentially , the use of CONSORT should positively influence the manner in which RCTs are conducted . Granting agencies have noted this potential relationship and , in at least in one case ( 25 ) , have encouraged grantees to consider in their application how they have dealt with the CONSORT items . The evidence -based approach used to develop CONSORT has also been used 424 BMJ | 24 FEBRUARY 2007 | VOLUME 334 Almost all studies have some missing observations . Yet textbooks and software commonly assume that data are complete , and the topic of how to h and le missing data is not often discussed outside statistics journals . There are many types of missing data and different reasons for data being missing . Both issues affect the analysis . Some examples are : ( 1 ) In a postal question naire survey not all the selected individuals respond ; ( 2 ) In a r and omised trial some patients are lost to follow-up before the end of the study ; ( 3 ) In a multicentre study some centres do not measure a particular variable ; ( 4 ) In a study in which patients are assessed frequently some data are missing at some time points for unknown reasons ; ( 5 ) Occasional data values for a variable are missing because some equipment failed ; ( 6 ) Some laboratory sample s are lost in transit or technically unsatisfactory ; ( 7 ) In a magnetic resonance imaging study some very obese patients are excluded as they are too large for the machine ; ( 8) In a study assessing quality of life some patients die during the follow-up period Studies conducted over the last decade demonstrated variable therapeutic efficacy of angiotensin converting enzyme ( ACE ) inhibitor on the progression of glomerular diseases , including IgA nephropathy . In this study , among patients with biopsy-proven IgA nephropathy , 53 patients in whom creatinine clearance had been monitored over 5 yr were recruited for study . These patients were classified into two groups according to whether or not renal function had declined as determined by the slope of creatinine clearance against time : group 1 had stable renal function ; group 2 had declining renal function ( average : -6.7 + /- 1.3 ml/min/yr ) . 21 of 53 patients were treated with ACE inhibitor and followed for 48 wk . Gene polymorphism consisting of insertion ( I ) or deletion ( D ) of a 287-bp DNA fragment ( presumed to be a silencer element ) of the ACE gene was determined by PCR . 46 age-matched individuals without history of proteinuria were analyzed as controls . The DD genotype was significantly more frequent in group 2 ( 43 % ) than in controls ( 7 % ) or group 1 patients with stable renal function ( 16 % ) . 48 wk after ACE inhibitor administration , proteinuria significantly decreased in patients with DD genotype but not in those with ID or II genotypes . The results indicate that deletion polymorphism in the ACE gene , particularly the homozygote DD , is a risk factor for progression to chronic renal failure in IgA nephropathy . Moreover , this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and , potentially , on progressive deterioration of renal function OBJECTIVE This paper compares six missing data methods that can be used for carrying out statistical tests on repeated measures data : listwise deletion , last value carried forward ( LVCF ) , st and ardized score imputation , regression and two versions of a closest match method . METHOD The efficacy of each was investigated under a variety of sample sizes and with differing levels of missingness . R and omly selected sample s from a data set ( n = 804 ) were used to compare the methods using t-tests . Efficacy was defined as the closeness of the estimated t-values to the true t-values from the complete data set . RESULTS The results suggest a reliable and efficacious basis for imputation method for repeated measures data is to substitute a missing datum with a value from another individual who has the closest scores on the same variable measured at other timepoints , or the average value of four individuals who have the closest scores on the same variable at other timepoints . The LVCF and st and ardized score methods performed relatively poorly , which is of concern since these are often recommended . Listwise deletion was also an inefficient missing data method . CONCLUSIONS Research ers should consider using closest match missing data imputation . Since listwise deletion performed poorly , is widely reported and is the default method in many statistical software packages , the findings have broad implication BACKGROUND In diabetic nephropathy , angiotensin-converting-enzyme ( ACE ) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate ( GFR ) . Whether this difference applies to progression of nondiabetic proteinuric nephropathies is not clear . The Ramipril Efficacy in Nephropathy study of chronic nondiabetic nephropathies aim ed to address whether glomerular protein traffic influences renal-disease progression , and whether an ACE inhibitor was superior to conventional treatment , with the same blood-pressure control , in reducing proteinuria , limiting GFR decline , and preventing endstage renal disease . METHODS In this prospect i ve double-blind trial , 352 patients were classified according to baseline proteinuria ( stratum 1 : 1 - 3 g/24 h ; stratum 2 : > or = 3 g/24 h ) , and r and omly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg . The primary endpoint was the rate of GFR decline . Analysis was by intention to treat . FINDINGS At the second planned interim analysis , the difference in decline in GFR between the ramipril and placebo groups in stratum 2 was highly significant ( p = 0.001 ) . The Independent Adjudicating Panel therefore decided to open the r and omisation code and do the final analysis in this stratum ( stratum 1 continued in the trial ) . Data ( at least three GFR measurements including baseline ) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients . The decline in GFR per month was significantly lower in the ramipril group than the placebo group ( 0.53 [ 0.08 ] vs 0.88 [ 0.13 ] mL/min , p = 0.03 ) . Among the ramipril-assigned patients , percentage reduction in proteinuria was inversely correlated with decline in GFR ( p = 0.035 ) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure ( 18 ramipril vs 40 placebo , p = 0.04 ) . The risk of progression was still significantly reduced after adjustment for changes in systolic ( p = 0.04 ) and diastolic ( p = 0.04 ) blood pressure , but not after adjustment for changes in proteinuria . Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups . INTERPRETATION In chronic nephropathies with proteinuria of 3 g or more per 24 h , ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients . Although not accurate in renal transplantation , GFR is often estimated using creatinine-based equations . Cystatin C is a marker of GFR that seems to be more accurate than creatinine . Equations to predict GFR based on the serum cystatin C concentration have been developed , but their accuracy in transplantation is unknown . GFR was estimated using four equations ( Filler , Le Bricon , Larsson , and Hoek ) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients . GFR was measured using radiolabeled diethylenetriaminepentaacetic acid ( 99mTc-DTPA ) , and the bias , precision , and accuracy of each equation were determined . The mean (99m)Tc-DTPA GFR was 58 + /- 23 ml/min per 1.73 m(2 ) . The cystatin C-based equations of Filler and Le Bricon had the lowest bias ( -1.7 and -3.8 ml/min per 1.73 m2 ) , greatest precision ( 11.4 and 11.8 ml/min per 1.73 m2 ) , and highest accuracy ( 87 and 89 % within 30 % of measured GFR , respectively ) . The cystatin C equations remained accurate even when the measured GFR was > 60 ml/min per 1.73 m2 . The creatinine-based equations were not as accurate , with only 53 to 80 % of estimates within 30 % of measured GFR . Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations . Further prospect i ve studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme ( ACE ) in the renin‐angiotensin system . We hypothesized that ACE2 polymorphisms could confer a high risk of hypertension and have an impact on the antihypertensive response to ACE inhibitors . The hypothesis was tested in two case‐control studies and a clinical trial of 3,408 untreated hypertensive patients r and omized to Atenolol , Hydrochlorothiazide , Captopril , or Nifedipine treatments for 4 weeks . ACE2 rs2106809 T allele was found to confer a 1.6‐fold risk for hypertension in women ( 95 % confidence interval ( CI ) , 1.13–2.06 ) , whereas when combined with the effect of the ACE DD genotype , the risk was 2.34‐fold ( 95 % CI , 1.75–4.85 ) in two independent sample s. The adjusted diastolic blood pressure response to Captopril was 3.3 mm Hg lower in ACE2 T allele carriers than in CC genotype carriers ( P=0.019 ) in women . We conclude that the ACE2 T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors Context Guidelines recommend that laboratories estimate glomerular filtration rate ( GFR ) with equations that use serum creatinine level , age , sex , and ethnicity . St and ardizing creatinine measurements across clinical laboratories should reduce variability in estimated GFR . Contribution Using st and ardized creatinine assays , the authors calibrated serum creatinine levels in 1628 patients whose GFR had been measured by urinary clearance of 125I-iothalamate . They used these data to derive new equations for estimating GFR and to measure their accuracy . The equations were inaccurate only when kidney function was near-normal . Caution s There was no independent sample of patients for measuring accuracy . Implication s By using this equation and a st and ardized creatinine assay , different laboratories can report estimated GFR more uniformly and accurately . The Editors Chronic kidney disease is a recently recognized public health problem . Current guidelines define chronic kidney disease as kidney damage or a glomerular filtration rate ( GFR ) less than 60 mL/min per 1.73 m2 for 3 months or more , regardless of cause ( 13 ) . Kidney damage is usually ascertained from markers , such as albuminuria . The GFR can be estimated from serum creatinine concentration and demographic and clinical variables , such as age , sex , ethnicity , and body size . The normal mean value for GFR in healthy young men and women is approximately 130 mL/min per 1.73 m2 and 120 mL/min per 1.73 m2 , respectively , and declines by approximately 1 mL/min per 1.73 m2 per year after 40 years of age ( 4 ) . To facilitate detection of chronic kidney disease , guidelines recommend that clinical laboratories compute and report estimated GFR by using estimating equations , such as equations derived from the Modification of Diet in Renal Disease ( MDRD ) Study ( 13 , 510 ) . The original MDRD Study equation was developed by using 1628 patients with predominantly nondiabetic kidney disease . It was based on 6 variables : age ; sex ; ethnicity ; and serum levels of creatinine , urea , and albumin ( 11 ) . Subsequently , a 4-variable equation consisting of age , sex , ethnicity , and serum creatinine levels was proposed to simplify clinical use ( 3 , 12 ) . This equation is now widely accepted , and many clinical laboratories are using it to report GFR estimates . Extensive evaluation of the MDRD Study equation shows good performance in population s with lower levels of GFR but variable performance in those with higher levels ( 1332 ) . Variability among clinical laboratories in calibration of serum creatinine assays ( 33 , 34 ) introduces error in GFR estimates , especially at high levels of GFR ( 35 ) , and may account in part for the poorer performance in this range ( 13 , 14 , 16 , 1821 , 27 , 30 ) . The National Kidney Disease Education Program ( NKDEP ) has initiated a creatinine st and ardization program to improve and normalize serum creatinine results used in estimating equations ( 36 ) . The MDRD Study equation has now been reexpressed for use with a st and ardized serum creatinine assay ( 37 ) , allowing GFR estimates to be reported in clinical practice by using st and ardized serum creatinine and overcoming this limitation to the current use of GFR estimating equations . The purpose of this report is to describe the performance of the reexpressed 4-variable MDRD Study equation and compare it with the performance of the reexpressed 6-variable MDRD equation and the CockcroftGault equation ( 38 ) , with particular attention to the level of GFR . This information should facilitate implementation of reporting and interpreting estimated GFR in clinical practice . Methods Laboratory Methods Urinary clearances of 125I-iothalamate after subcutaneous infusion were determined at clinical centers participating in the MDRD Study . Serum and urine 125I-iothalamate were assayed in a central laboratory . All serum creatinine values reported in this study are traceable to primary reference material at the National Institute of St and ards and Technology ( NIST ) , with assigned values based on isotope-dilution mass spectrometry . The serum creatinine sample s from the MDRD Study were originally assayed from 1988 to 1994 in a central laboratory with the Beckman Synchron CX3 ( Global Medical Instrumentation , Inc. , Ramsey , Minnesota ) by using a kinetic alkaline picrate method . Sample s were reassayed in 2004 with the same instrument . The Beckman assay was calibrated to the Roche/Hitachi P module Creatinase Plus enzymatic assay ( Roche Diagnostics , Basel , Switzerl and ) , traceable to an isotope-dilution mass spectrometry assay at NIST ( 37 , 39 ) . On the basis of these results , the 4-variable and 6-variable MDRD Study equations were reexpressed for use with st and ardized serum creatinine assay . The CockcroftGault equation was not reexpressed because the original serum creatinine sample s were not available for calibration to st and ardized serum creatinine assay . Derivation and Validation of the MDRD Study Equation The MDRD Study was a multicenter , r and omized clinical trial of the effects of reduced dietary protein intake and strict blood pressure control on the progression of chronic kidney disease ( 40 ) . The derivation of the MDRD Study equation has been described previously ( 11 ) . Briefly , the equation was developed from data from 1628 patients enrolled during the baseline period . The GFR was computed as urinary clearance of 125I-iothalamate . Creatinine clearance was computed from creatinine excretion in a 24-hour urine collection and a single measurement of serum creatinine . Glomerular filtration rate and creatinine clearance were expressed per 1.73 m2 of body surface area . Ethnicity was assigned by study personnel , without explicit criteria , probably by examination of skin color . The MDRD Study equation was developed by using multiple linear regression to determine a set of variables that jointly estimated GFR in a r and om sample of 1070 patients ( development data set ) . The regressions were performed on log-transformed data to reduce variability in differences between estimated and measured GFR at higher levels . Several equations were developed , and the performance of these equations was compared in the remaining sample of 558 patients ( validation data set ) . To improve the accuracy of the final equations , the regression coefficients derived from the development data set were up date d on the basis of data from all 1628 patients ( 11 ) . Estimation of GFR Glomerular filtration rate was estimated by using the following 4 equations : the reexpressed 4-variable MDRD Study equation ( GFR= 175st and ardized Scr 1.154age0.2031.212 [ if black]0.742 [ if female ] ) , the reexpressed 6-variable MDRD Study equation ( GFR= 161.5st and ardized Scr 0.999age0.176SUN0.17albumin0.3181.18 [ if black]0.762 [ if female ] ) , the CockcroftGault equation adjusted for body surface area ( Ccr= [140age]weight0.85 [ if female]1.73/72 st and ardized ScrBSA ) , and the CockcroftGault equation adjusted for body surface area and corrected for the bias in the MDRD Study sample ( Ccr= 0.8[140age]weight0.85 [ if female]1.73/72 st and ardized ScrBSA ) . In these equations , GFR and creatinine clearance ( Ccr ) are expressed as mL/min per 1.73 m2 , serum creatinine and urea nitrogen ( SUN ) are expressed as mg/dL , albumin is expressed as g/dL , weight is expressed as kg , age is expressed as years , and body surface area ( BSA ) is expressed as m2 . Correction for bias improves performance of the CockcroftGault equation because it adjusts for systematic differences between studies , such as differences in the measures of kidney function ( GFR in the MDRD Study and creatinine clearance in the study by Cockcroft and Gault ) , the serum creatinine assays , and the study sample s. Hence , the bias correction for the CockcroftGault equation provided here reexpresses that equation for the estimation of GFR for use with st and ardized creatinine in study sample s similar to that in the MDRD Study . Measures of Performance Measures of performance include bias ( median difference of measured minus estimated GFR and measured GFR ) and percentage bias ( percentage of bias divided by measured GFR ) , precision ( interquartile range of the difference between estimated and measured GFR , and percentage of variance in log-measured GFR explained by the regression model [ R2 values ] ) , and accuracy ( percentage of estimates within 30 % of the measured values ) . In the overall data set , bias is expected to be close to 0 for equations derived in the MDRD Study data base , including the 4-variable and 6-variable equations and the CockcroftGault equation adjusted for bias . The bootstrap method ( based on percentiles , with 2000 bootstrap sample s ) was used to estimate 95 % CIs for interquartile ranges and R2 values . Confidence intervals for the percentage of estimates within 30 % of measured values were computed by using the normal approximation to the binomial or exact binomial probabilities , as appropriate . We also computed sensitivity , specificity , positive and negative predictive value of estimated GFR less than 60 mL/min per 1.73 m2 , and receiver-operating characteristic ( ROC ) curves by using measured GFR less than 60 mL/min per 1.73 m2 as the criterion st and ard . Areas under the ROC curves were compared by using the method of DeLong and colleagues ( 41 ) . R , version 2 ( Free Software Foundation , Inc. , Boston , Massachusetts ) , and SAS , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) , were used for statistical analysis . We used the lowess function in R to plot smoothed functions in the figures . Role of the Funding Source The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) as part of a cooperative agreement that gives the NIDDK substantial involvement in the design of the study and in the collection , analysis , and interpretation of the data . The NIDDK was not required to approve publication of the finished manuscript . The institutional review boards of all participating institutions approved the study . Results Clinical characteristics Objectives To investigate the relationship between polymorphisms in the angiotensin converting enzyme ( ACE ) , angiotensinogen ( AGT ) and type 1 angiotensin-II ( AT1R ) genes and ( 1 ) quantitative variations in blood pressure and ( 2 ) the blood pressure response to ACE inhibition in a hypertensive cohort . Design and methods We administered monotherapy with ACE inhibitors to 125 previously untreated essential hypertensives . Genotypes for ACE insertion and deletion , AGT M235 T and AT1R A1166±C polymorphisms were determined in DNA extracted from peripheral blood leucocytes . The influence of genotype on pretreatment blood pressure and the ACE inhibitor-induced decrease in blood pressure was tested by analysis of variance and multiple regression analysis , adjusting for age , sex , body mass index , alcohol intake and , where appropriate , pretreatment blood pressure . Results ACE and AT1R genotypes were independent predictors of pretreatment systolic and diastolic blood pressure , with an apparent interaction between these two gene loci . Although it did not influence pretreatment blood pressure in this population , AGT genotype was an independent predictor of the blood pressure response to ACE inhibition . Conclusions The ACE and AT1R gene loci ( chromosomes 17q and 3q , respectively ) may carry alleles influencing blood pressure variation in this hypertensive population , with a possible epistatic interaction between the two loci . The AGT T235 allele does not appear to be a marker for blood pressure variation in this group , but variants on chromosome 1q lying in or near the AGT gene may contribute to individual differences in the blood pressure response to ACE inhibition . Among essential hypertensives , differences in the ACE inhibitor response appear , in part , to be genetically determined Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy . Transforming growth factor-beta(1 ) ( TGF-beta(1 ) ) is the main cytokine involved in the fibrotic process that is involved in chronic rejection . Angiotensin II upregulates TGF-beta(1 ) production . Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-beta(1 ) production in renal transplant patients . The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics , as well as TGF-beta(1 ) and endothelin-1 ( ET-1 ) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine . Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a r and om 2 x 2 crossover trial with amlodipine and losartan ( 6 wk with each therapy ) . Three studies were performed ( at baseline and at the end of both treatment periods ) to determine renal hemodynamics , TGF-beta(1 ) , and ET-1 . Both treatments controlled BP to a similar degree , but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction . In contrast , losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly . Losartan and amlodipine had opposite effects on TGF-beta(1 ) . Amlodipine did not affect TGF-beta(1 ) concentrations . In contrast , losartan reduced the plasma levels of TGF-beta(1 ) by approximately by 50 % ( from baseline , 5.2 to 2.6 ng/ml ; P : = 0.01 ) ; the majority of the patients reached normal levels of TGF-beta(1 ) . ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment . The present study documents that with similar control of BP , losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-beta1 concentrations . These differences could be important for the management of chronic allograft nephropathy The renal benefits of agents inhibiting the renin‐angiotensin‐aldosterone system in renal transplant recipients , i.e. preventing the development of chronic graft nephropathy , are supposed but not finally proven . In a double‐blind , placebo‐controlled , cross‐over study , we evaluated the influence of losartan on surrogate markers of tubular injury , urine excretion of transforming growth factor β‐1 ( TGF‐β1 ) and amino‐terminal propeptide of type III procollagen ( PIIINP ) in 16 patients after transplantation . The patients received r and omly either losartan ( 50–100 mg daily ) or the β‐blocker carvedilol ( 12.5–25 mg ) for 8 weeks , allowing a placebo washout between treatments . The target office through blood pressure ( BP ) was below 130/85 mmHg . The BP did not differ in the treatment periods . Losartan significantly decreased N‐acetyl‐β‐d‐glucosaminidase and alfa‐1 microglobulin excretion relative to placebo and carvedilol . Urine excretion of TGF‐β1 and PIIINP was significantly lower after losartan . In conclusion , losartan reduces urine excretion of proteins associated with tubular damage and graft fibrosis BACKGROUND Allograft nephropathy , regardless of aetiology , leads to progressive renal injury and eventual graft loss . In native kidney disease , treatment of hypertension , in particular with angiotensin-converting enzyme inhibitors ( ACEi ) or angiotensin receptor blockers ( ARB ) , has proven beneficial in retarding renal function decline . In the present study , we review ed the clinical course of a renal transplant recipient cohort that was prescribed either an ACEi or ARB for biopsy-proven allograft nephropathy . METHODS Patients were followed from the time of post-biopsy initiation of ACEi/ARB and were stratified based on biopsy findings . Outcomes of interest included safety , allograft survival , renal function and change in slope of renal function pre- and post-ACEi/ARB . RESULTS The 5 year allograft survival after biopsy diagnosis of allograft nephropathy was 83 % . Serum creatinine was 191+/-97 ( 86 - 377 ) micromol/l at the time of biopsy and 228+/-102 ( 102 - 575 ) micromol/l at last follow-up . The slopes of reciprocal creatinine vs time were used to calculate the decline in renal function and were compared pre- and post-ACEi/ARB . The mean slope+/-SD was -0.06+/-0.21 l/micromol x 10(-3 ) per month in the 12 months prior to therapy and -0.03+/-0.09 l/micromol x 10(-3 ) per month following therapy . The absolute difference in slopes was 0.03 ( P = < 0.0001 ) . CONCLUSIONS Treatment with ACEi/ARB may be beneficial in the management of allograft nephropathy Several studies have shown that long-term therapy with angiotensin-converting enzyme inhibitors may reduce urinary protein excretion and decrease the rate of progression of renal disease in patients with insulin-dependent diabetes mellitus more effectively than conventional antihypertensive drugs . Only few studies , however , have been performed in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease , we conducted a prospect i ve , 18-month study in 42 proteinuric ( > 500 mg/day ) NIDDM and , for comparison , in 31 nondiabetic patients with a variety of renal diseases ( NDRD ) . Twenty-four NIDDM patients were treated with captopril and 18 with conventional drugs . Eighteen NDRD patients received captopril , and 13 received conventional drugs . Baseline proteinuria and glomerular filtration rate ( GFR ) were not different among groups . The blood pressure decreased equally in all group of patients , irrespective of whether they received captopril or conventional drugs . Urinary protein excretion , however , decreased significantly only in NIDDM and NDRD patients treated with captopril . The GFR decreased only in patients treated with conventional drugs , but not in those treated with captopril . The rate of decline in GFR in NIDDM patients treated with captopril was significantly lower than in patients treated with conventional drugs . However , in NDRD patients treated with captopril , the rate of decline in GFR was not different from that in patients treated with conventional drugs . The reduction of urinary protein excretion was poorly correlated with changes in blood pressure or with changes in renal function and renal hemodynamics . Serum potassium increased significantly in patients treated with captopril . 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12,654 | 29,987,564 | Conclusions TEP and TAPP have their own advantages .
TEP repair reduces short-term postoperative pain more effectively than TAPP repair and results in shorter hospital stay of primary cases .
In contrast , TAPP repair is correlated with shorter surgery duration . | Background Compared with open herniorrhaphy , laparoscopic herniorrhaphy can yield more favorable clinical outcomes .
However , previous studies failed to give definite answer for comparison between laparoscopic inguinal hernia repair approaches .
This study aim ed to systematic ally determine the differences in recurrence rate , duration of return to work , pain , surgery duration , and duration of hospital stay between transabdominal preperitoneal ( TAPP ) and totally extraperitoneal ( TEP ) approach for inguinal hernia . | Background The open tension-free mesh-plug hernia technique , transabdominal preperitoneal ( TAPP ) technique , and totally extraperitoneal ( TEP ) laparoscopic technique all are common surgical procedures for primary unilateral inguinal hernia repair . However , the choice of the right surgical procedure still is controversial in China . This study aim ed to compare open tension-free hernioplasty with two laparoscopic hernia repairs . Methods In this study , 164 male patients with primary unilateral inguinal hernia were r and omized to undergo an open operation with mesh-plug and patch , TAPP , or TEP . Results Completion of the study required 3 years , from February 2006 to February 2009 . Of the 164 patients , 62 underwent open repair , 50 had TAPP , and 52 had TEP . The patients then were followed up for 15.6 ± 8.5 months . The average operating time for the open repair group was significantly shorter than for the other two groups ( p < 0.001 ) . The cost for the open repair group also was significantly less than for the other two groups ( p < 0.001 ) . By contrast , the pain scores in the open mesh group were significantly higher than in the other two groups ( p < 0.001 ) . The hospital stay and the recovery time both were significantly longer in open repair group than in the other two groups ( p < 0.001 ) . No major complications or recurrence was found in any of the groups . Conclusions The findings show that open tension-free mesh-plug hernia repair , TAPP , and TEP are safe and effective for patients with primary unilateral inguinal hernia . Both TAPP and TEP are superior to open repair in terms of less postoperative pain and faster recovery time . The authors therefore recommend laparoscopic repair techniques as the preferable choice of surgical procedure . However , they think open repair will remain a practical solution in China because of its lower cost , short learning period , and need for no special equipment Background Data are insufficient to compare transabdominal preperitoneal repair ( TAPP ) and total extraperitoneal ( TEP ) techniques of laparoscopic inguinal hernia repair . There is very scant data comparing the two techniques in terms of long-term outcomes , which include chronic groin pain , quality of life , and time to return to normal activity . This prospect i ve , r and omized , controlled trial compared TEP versus TAPP techniques of laparoscopic inguinal hernia repair in terms of these long-term outcomes . Methods This study was conducted from May 1 , 2007 to March 30 , 2012 . Patients with uncomplicated groin hernia were r and omized to transabdominal preperitoneal ( TAPP ) or totally extraperitoneal ( TEP ) techniques . A total of 160 patients were r and omized to group I ( TEP ) and 154 patients to group II ( TAPP ) . Pain was assessed with Visual Analogue Scale ( VAS ) preoperatively and postoperatively at 24 h , 1 week , 6 weeks , 3 , 6 , and 12 months , and yearly thereafter . Quality of life was assessed with Short Form–36 version 2 ( SF 36v2 ) preoperatively and postoperatively at 3 months follow-up . Results Demographic , clinical profiles , intraoperative , and early postoperative parameters were well matched . There was significantly higher acute pain following TAPP repair ; however , the chronic groin pain was comparable in both TEP and TAPP . Preoperative pain and immediate postoperative pain had significant correlation with chronic groin pain . Significant improvement from preoperative to postoperative quality of life was seen in both TEP and TAPP repairs , but there was no difference between TEP and TAPP in postoperative period . Time to return to normal activity also was similar between the two groups . Conclusions The TEP and TAPP techniques of laparoscopic repair of inguinal hernia have comparable long-term outcomes in terms of incidence of chronic groin pain , quality of life , and resumption of normal activities . Chronic groin pain had a significant correlation with preoperative pain and early postoperative pain . However , TAPP was associated with significantly higher incidence of early postoperative pain , longer operative time , and cord edema , whereas TEP was associated with a significant higher incidence of seroma formation . The cost was comparable between the two AIM To compare four approaches in primary repair of inguinal hernia as regards operative and postoperative outcome . METHODS One hundred consecutive patients with primary inguinal hernia Nyhus I-III were r and omized into four groups . Group I had open pro-peritoneal repair , group II had Lichtenstein tension-free mesh repair , group III had Transabdominal pro-peritoneal ( TAPP ) repair while group IV had laparoscopic totally extraperitoneal ( TEP ) hernia repair . RESULTS Operative time ranged from 10.71 to 120.61 min . Laparoscopic operations were significantly longer than open operations ( 54.5 + 13.2 , 34.21 + 23.5 versus 96.12 + 22.5 , 77.4 + 43.21 ; t=3.891 , p<0.001 ) . Open pro-peritoneal approach had significantly longer operative time compared to Lichtenstein approach ( 54.5 + 13.2 versus 34.21 + 23.5 ) . Postoperative pain was significantly higher in patients who had open repairs ( 7.067 + 1.831 , 6.5 + 3.5 versus 5.8 + 1.568 , 4.8 + 2.33 ; t=3.424 , p=0.002 ) . There was one case of conversion in each of the two laparoscopic groups . Laparoscopic operations were associated with significantly faster return to normal domestic activities and to work . CONCLUSION Laparoscopic hernia repair offers less postoperative pain and faster recovery on the expense of longer operative time . TEP and TAPP laparoscopic techniques gave similar results Background There is very scant literature on the impact of inguinal hernia mesh repair on testicular functions and sexual functions following open and laparoscopic repair . The present r and omized study compares TAPP and TEP repairs in terms of testicular functions , sexual functions , quality of life and chronic groin pain . Methods This study was conducted from April 2012 to October 2014 . A total of 160 patients with uncomplicated groin hernia were r and omized to either trans-abdominal pre-peritoneal ( TAPP ) repair or totally extra-peritoneal ( TEP ) repair . Testicular functions were assessed by measuring testicular volume , testicular hormone levels preoperatively and at 3 months postoperatively . Sexual functions were assessed using BMSFI , and quality of life was assessed using WHO-QOL BREF scale preoperatively and at 3 and 6 months postoperatively . Chronic groin pain was evaluated using the VAS scale at 3 months , 6 months and at 1 year . Results The median duration of follow-up was 13 months ( range 6–18 months ) . The mean preoperative pain scores ( p value 0.35 ) as well as the chronic groin pain were similar between TEP and TAPP repairs at 3 months ( p value 0.06 ) and 6 months ( p value 0.86 ) . The testicular resistive index and testicular volume did not show any significant change at follow-up of 3 months ( p value 0.9 ) in the study population . No significant difference was observed in testicular resistive index and testicular volume when comparing TEP and TAPP groups at at follow-up of 3 months ( p value > 0.05 ) . There was a statistically significant improvement in the sexual drive score , erectile function and overall satisfaction over the follow-up period following laparoscopic inguinal hernia repair . However , sexual function improvement was similar in patients undergoing both TEP and TAPP repairs . All the domains of quality of life in the study population showed a significant improvement at a follow-up of 3 and 6 months . Subgroup analysis of all the domains of quality of life in both TAPP and TEP groups showed a similar increment as in the study population ( p value < 0.001 ) ; however , the mean scores of all the domains were comparable between the two subgroups ( p value > 0.05 ) , preoperatively and 3 and 6 months follow-up . Conclusions Laparoscopic groin hernia repair improves the testicular functions , sexual functions and quality of life , but TEP and TAPP repairs are comparable in terms of these long-term outcomes Background The current prospect i ve r and omized controlled clinical study aim ed to assess the short- and long-term results of recurrent inguinal hernia repair , and to compare the results for transabdominal preperitoneal ( TAPP ) and totally extraperitoneal ( TEP ) procedures with those for open tension-free repair . Methods For this study , 82 patients were r and omly assigned to undergo TAPP ( group A , n = 24 ) , TEP ( group B , n = 26 ) , or open Lichtenstein hernioplasty ( group C , n = 32 ) . All the patients with recurrent inguinal hernias had undergone previous repair using conventional open procedures . Physical examination showed Nyhus type II hernia in the vast majority of the patients ( 59 % ) . High-risk patients ( American Society of Anesthesiology [ ASA ] III or IV ) ; coagulation disorders ; previous abdominal or pelvic surgery ; and irreducible , congenital , and massive scrotal or sliding hernias were excluded from the study . Results There was a statistically significant difference ( p = 0.001 ) in operating time favoring the open procedure . The intensity of postoperative pain was greater in the open hernia repair group 24 h , 48 h , and 7 days after surgery ( p = 0.001 ) , with a greater consumption of pain medication among these patients ( p < 0.004 ) . The median time until return to work was 14 days for group A , 13 days for Group g , and 20 days for group C. The comparison was in favor of laparoscopically treated patients . Nine recurrences ( 4 in the laparoscopic groups and 5 in the open group ) were documented within 3 years of follow-up evaluation . Conclusion Laparoscopic inguinal hernia repair ( TAPP or TEP ) is the method of choice for dealing with recurrent inguinal hernia Background The aim of this prospect i ve r and omized multicenter trial was to evaluate the recurrence rates and complications of open versus laparoscopic repairs of inguinal hernias . Methods Patients with primary unilateral inguinal hernias were r and omized to Shouldice repair , Bassini operation , tension-free hernioplasty ( Lichtenstein repair ) , laparoscopic transabdominal extraperitoneal hernioplasty ( TEP ) , or laparoscopic transabdominal preperitoneal hernioplasty ( TAPP ) . The primary outcome parameter was the rate of recurrence at 3 years . The secondary outcome was the rate of intraoperative , perioperative , and long-term complications . Follow-up comprised of clinical examination after 1 , 2 , and 3 years . Results Three hundred and sixty-five patients were r and omly assigned to one of the five procedures . The intention-to-treat analysis showed that the cumulative 3-year recurrence rate was 3.4 % in the Bassini group , 4.7 % in the Shouldice group , 0 % in the Lichtenstein group , 4.7 % in the TAPP group , and 5.9 % in the TEP group ( p = 0.48 ) . Comparing open ( Bassini , Shouldice , Lichtenstein ) versus laparoscopic ( TAPP , TEP ) techniques ( p = 0.29 ) and comparing the use of mesh prostheses ( Lichtenstein , TAPP , TEP ) versus suturing techniques ( Bassini , Shouldice ) ( p = 0.74 ) showed no significance in the rate of recurrence . The rates of intraoperative ( p = 0.15 ) , perioperative ( p = 0.09 ) , and long-term complications ( p = 0.13 ) were without significance between the five groups . Comparing mesh techniques ( Lichtenstein , TAPP , TEP ) versus suturing techniques ( Bassini , Shouldice ) showed no significance in the rate of complications . The per- protocol analysis for the comparison of mesh ( Lichtenstein , TAPP , TEP ) versus suturing ( Bassini , Shouldice ) techniques revealed that recurrences ( p = 0.74 ) , intraoperative ( p = 0.64 ) , perioperative ( p = 0.27 ) , and long-term complications ( p = 0.91 ) were evenly distributed . Conclusions In this multicenter study , no significant difference in the recurrence rate and complications between laparoscopic and open methods of hernia repair was revealed OBJECTIVE To compare the effects of laparoscopic inguinal hernia repair ( LIHR ) and Lichtenstein tension-free inguinal hernia repair and to explore the safety and feasibility of LIHR as well as the advantages and disadvantages of these procedures . SUBJECTS AND METHODS In total , 252 patients with inguinal hernia were equally r and omized into the transabdominal preperitoneal ( TAPP ) repair , totally extraperitoneal ( TEP ) repair , and Lichtenstein tension-free hernia repair groups ( n=84 each ) . Operating time , postoperative pain scores , postoperative scrotal seroma , postoperative local esthesiodermia , postoperative chronic pains , postoperative long-term hernia relapse , and costs of hospitalization were compared among the three groups . RESULTS All laparoscopic operations were performed smoothly without intraoperative conversion to open surgery . The LIHR groups showed significantly better effects on postoperative pains and hernia recurrence than the Lichtenstein tension-free herniorrhaphy group ( P<.05 ) , but with a significantly higher hospitalization cost ( P<.05 ) . The occurrence rate of postoperative scrotal seroma or hydrops in the TAPP , TEP , and Lichtenstein groups was 11 ( 13.10 % ) , 13 ( 15.48 % ) , and 6 ( 7.14 % ) , respectively . No significant differences among the operating time , postoperative local esthesiodermia , or postoperative chronic pains of the groups were observed ( P>.05 ) . CONCLUSIONS LIHR is a safe and feasible procedure . It has significantly better effects on postoperative pains and hernia relapse than Lichtenstein tension-free hernia repair Purpose An inguinal hernia is a common pathology that can be treated using several different surgical procedures . Although there have been many studies comparing the clinical results of these techniques , there has so far been no digital analysis of the alterations developing secondary to pain with regard to the muscle functions of the lower extremities . This prospect i ve r and omized trial was design ed to compare this aspect for subjects treated using the laparoscopic techniques and those treated using the conventional method . Methods A total of 75 patients , 25 of whom who had undergone hernia repair using the total extraperitoneal technique , 25 of whom who had undergone repair using the transabdominal preperitoneal technique , and 25 who had undergone repair using the Prolene mesh graft technique , were evaluated preoperatively and on the third postoperative day by isometric and isokinetic measurements , the visual analog score ( VAS ) , the necessity of postoperative analgesia , complications , and the time that had elapsed before returning to work , and these results were recorded . Results Hernia repair using the conventional method led to an average of 3 times more muscle function loss compared with the laparoscopic techniques , and this difference was shown to be statistically significant . The VAS , postoperative complications , and time elapsed before returning to work were lower for laparoscopic surgeries and also were compatible with the findings described in the previous literature . Conclusions Use of a digital environment with numerical parameters and measurements recorded using a dynamometer demonstrated that in the early postoperative period and on the third postoperative day , open surgery causes more functional loss in the lower extremities than laparoscopic methods . Therefore , surgeons should use laparoscopic methods whenever possible to reduce both pain and loss of muscle function OBJECTIVE The aims of this study were to investigate the effects of carbon-dioxide ( CO(2 ) ) insufflation on hemodynamic and respiratory function during laparoscopic inguinal hernioplasty and to evaluate the safety of transabdominal preperitoneal hernia repair ( TAPP ) and extraperitoneal hernia repair ( TEP ) . MATERIAL S AND METHODS Forty patients with inguinal hernia were admitted for laparoscopic inguinal hernia repair in our study . The patients were r and omly assigned to undergo TAPP ( TAPP group , n = 20 ) or TEP ( TEP group , n = 20 ) . Hemodynamic and respiratory parameters , including heart rate , blood pressure , end-tidal CO(2 ) ( EtCO(2 ) ) , and blood-gas parameters , were observed and compared between the two groups . RESULTS There was no significant difference between the two groups in terms of sex , age , American Society of Anesthesiology degree , body-mass index , type of hernia , operation time , hospital stay , and postoperative pain score . In both groups , 5 minutes into the operation , blood pressure , EtCO(2 ) , PaCO(2 ) , and HCO(3)(- ) increased significantly , whereas heart rate and pH decreased significantly ( P < 0.05 ) . The above tendency became significant with the operation prolonged . All parameters recovered to normal levels at the end of surgery . No significant difference was found between the TAPP and TEP groups . CONCLUSIONS Both TAPP and TEP procedures can result in CO(2 ) accumulation , acidosis , increased blood pressure , and decreased heart rate . But , these effects were transient and could be well controlled by appropriate treatments during the operation . The laparoscopic TAPP and TEP techniques are safe for patients by proper perioperative management For this study , 66 patients with a preoperative diagnosis of unilateral primary inguinal hernia were r and omized to undergo laparoscopic totally extra peritoneal ( TEP ) , laparoscopic transabdominal ( TAPP ) , or open inguinal hernia repair with polypropylene mesh ( Lichtenstein type ) . Both the operative team caring for the patient postoperatively and the patient were blinded to the operative approach by placement of a large dressing covering the abdomen , which was not removed until postoperative day 3 . The patients recorded their pain level on a visual analog pain scale daily . Medication usage also was recorded . All patients were seen at 7-day intervals until they returned to work . The patients were interviewed during their postoperative visits by an investigator blinded to the operative approach and question ed regarding their ability to return to work and their pain levels . The average number of lost work days in all the groups was 12 , and there was no significant difference between the three groups ( p = 0.074 ) . The average operating time for the TAPP procedure was 59 min , less than the time required to complete either the TEP or the Lichtenstein approach , which had equivalent operative times ( p = 0.027 ) . The material cost was significantly lower for the Lichtenstein repair ( $ 1,200 less ) than for either of the laparoscopic approaches , a saving primarily related to consumable operating room supplies . The TEP repair costs were minimally higher than those for the TAPP repair ( $ 125 more ) . No significant differences were noted in the postoperative pain scales , and the use of postoperative oral analgesics was equivalent . The higher operative costs noted for the laparoscopic hernia repairs were not offset by a shortened convalescence . Postoperative pain appears to be equivalent regardless of the operative approach chosen and is easily managed with oral analgesics Background Minimal access approaches to inguinal hernia repair have added to the ongoing debate over the “ best groin hernia repair . ” The present prospect i ve r and omized controlled trial was done to compare the totally extraperitoneal ( TEP ) and transabdominal preperitoneal ( TAPP ) techniques of laparoscopic inguinal hernia repair . Methods The present prospect i ve r and omized study was conducted between May 2007 and March , 2009 and included 100 patients suffering from uncomplicated primary groin hernia . Patients were r and omized into group I ( TEP ) and group II ( TAPP ) . Intraoperative variables and postoperative pain scores were recorded in a prestructured form . Results One hundred patients were included in the study ( TEP , 53 ; TAPP , 47 ) . Both groups were comparable in terms of demographic profile and hernia characteristics . The average operative time was higher in the TAPP group ( p = 0.209 ) . The pain scores at 1 h and 24 h after surgery and at 3-month follow-up were significantly higher in the TAPP group ( p < 0.05 ) . The average follow-up was 30.5 months . In the TEP group , 37.8 % of patients had seroma compared to 18.3 % in the TAPP group ( p = 0.021 ) . However , there was a higher incidence of scrotal edema in the TAPP group ( 16 vs. 9 , p = 0.009 ) . The wound infection rates were equal ( 2 % vs. 3 % ) . There has been no recurrence in either group during the follow-up period of 44 months . Overall , the patients were more satisfied with TEP rather than TAPP ( p < 0.05 ) . Conclusions In the present study , TEP had a significant advantage over TAPP for significantly reduced postoperative pain up to 3 months , which result ed in a better patient satisfaction score . The other intraoperative complications , postoperative complications , and cost were similar in both groups . In terms of results , both repair techniques seemed equally effective , but TEP had an edge over TAPP Laser laparoscopic inguinal herniorraphy represents an extension of current technology . Based on the principles of preperitoneal inguinal herniorraphy , it is performed by internal incision of the peritoneum and identification of the musculofascial defect through a laparoscope . Polypropylene mesh is then passed down the laparoscope , placed into the defect to obliterate the space , and the edges of the peritoneum are then reapproximated . Results in 20 patients with an 11 month followup indicates success in nineteen exhibiting early resumption of activity ( 3.3 days ) and minimal pain ( 2.1 Tylenol # 3 tablets per patient ) . One early recurrence suggests that anatomic identification of a direct space hernia may be difficult and that routine support of this area with additional mesh may be a requirement of a complete inguinal hernia repair AIM To compare the effects of laparoscopic versus conventional inguinal hernia repair techniques on patients physical activity . MATERIAL S AND METHODS Ninety-three patients ( between 20 and 59 years old ) who presented with a need for inguinal hernia repair at the private Safa Hospital , General Surgery Clinic , were evaluated prospect ively between November 2011 and March 2013 . The patients mean age was 46.1 ( + -12.9 ) years . They were divided into three groups according to hernia repair technique . Thirty underwent total extraperitoneal repair ( TEP ) , 31 had transabdominalpreperitoneal repair ( TAPP ) and 32 had modified Bassiniprolene mesh grafting ( MBPMG ) . All patients were examined in the physical therapy and rehabilitation unit just before and after the operation . Lower extremity muscles isokinetic and isometric functions were measured with the Cybex isokinetic testing device . Patients length of stay in hospital , need for analgesics in the postoperative period , visual analogue scale ( VAS ) scores , time of return to work and postoperative complications were also compared . RESULTS Patients need for postoperative analgesics , the use of VAS scoring system ( between 0 and 10 ) , complication rates and the patients VAS scores on movement results were similar to those in the literature . On the postoperative third day , measurements recorded by the Cybex isokinetic testing device showed that the loss of strength in the lower extremities after the MBPMG procedure was greater than with TAPP and TEP . The isokinetic and isometric assessment of all cases revealed that postoperative mean muscle strength loss was two-thirds less in association with the laparoscopic procedure . Within a 95 % confidence interval ( CI ) , the significance of findings was accepted at P-values of less than 0.05 ( p 0.05 ) . CONCLUSION The quantitative data showed that there is a more favourable impact from laparoscopic hernia repair versus open surgery on patients physical activity and return to active work Background Laparoscopic and open preperitoneal hernia repair techniques both use the preperitoneal space . This study investigated whether the surgical approach to the inguinal canal affects outcome measures . Methods One hundred sixty patients with inguinal hernia were assigned r and omly into open anterior ( 42 ) , open preperitoneal ( 39 ) , laparoscopic transabdominal preperitoneal ( 39 ) , and laparoscopic total extraperitoneal ( 40 ) groups according to the surgical method . The peroperative serum tumor necrosis factor-α ( TNF-α ) levels , interleukin-6 ( IL-6 ) levels , VAS scores at 6 and 48 h , per- and postoperative complications , and recurrence rates were determined as main variables . Results The serum IL-6 levels were 335 ± 1.8 , 283 ± 1.8 , 283 ± 1.4 , and 269.3 ± 1.6 pg/ml in the open anterior , posterior , transabdominal preperitoneal , and total extraperitoneal groups , respectively ( P < 0.01 ) . The TNF-α levels were highest in the open anterior group . The pain scores were lower in groups undergoing the posterior approach than in the open anterior approach group . Conclusion The approach to the inguinal canal through the preperitoneal space appears to be less invasive than the transinguinal anterior approach INTRODUCTION Bilateral inguinal hernias form a part of the complex spectrum of weakness in the region of the myopectineal orifice . Laparoscopic surgery is one of the st and ard approaches for bilateral hernias . We describe the results of a r and omized trial that was undertaken to compare and evaluate TAPP and TEP repair for bilateral inguinal hernias . METHODS Sixty patients were r and omized into two groups . Group I ( TAPP ) and Group II ( TEP ) were compared in terms of procedure related variables , conversion , post-operative recovery and complications . Analysis was done using SPSS software version 17 . RESULTS Seventy-seven patients were assessed for fitness to include in the study . Seventeen patients had to be excluded due to either not meeting the inclusion criteria 's or for not giving consent . The median age ( 52 yrs ) was comparable in both groups . In Group II ( TEP ) mean operating time was 120.89 ± 29.28 min compared to 108.16 ± 16.10 min in Group I ( TAPP ) . Post-operative pain scores were less in Group I(TAPP ) at all levels of recording ( 8 h-48 h ) , though most patients required injectable analgesic for 32 h in both groups ( p-value 0.029 ) . Subcutaneous emphysema was more commonly noted in the Group II ( TEP ) ( p-value 0.038 ) . In Group I ( TAPP ) mean hospital stay was 52.0 ± 14.21 h while in Group II ( TEP ) it was 52.29 ± 9.36 h ( p-value 0.427 ) . Mean time for return to work was 11.8 ± 2.35 days in Group I ( TAPP ) and 12.41 ± 2.22 days in Group II ( TEP ) ( p-value 0.339 ) . CONCLUSION The procedures though different in approach were quite similar in outcome . Mean operating time was increased in the TEP repairs along with immediate post-operative pain scores . The pattern of some complications like subcutaneous emphysema was significantly more in the TEP group while minor vascular injury though not significant was different in both groups . The indirect cost incurred from consumables did not vary other than need for more tacks in the TAPP group |
12,655 | 30,274,963 | Results support the effectiveness of web-based mindfulness interventions in reducing depression and anxiety and in enhancing quality of life and mindfulness skills , particularly in those with clinical anxiety . | BACKGROUND Web-based mindfulness interventions are increasingly delivered through the internet to treat mental health conditions .
OBJECTIVE The objective of this study was to determine the effectiveness of web-based mindfulness interventions in clinical mental health population s. Secondary aims were to explore the impact of study variables on the effectiveness of web-based mindfulness interventions . | Comm and hallucinations represent a special problem for the clinical management of psychosis . While compliance with both non-harmful and harmful comm and s can be problematic , sometimes in the extreme , active efforts to resist comm and s may also contribute to their malignancy . Previous research suggests Cognitive Behaviour Therapy ( CBT ) to be a useful treatment for reducing compliance with harmful comm and hallucinations . The purpose of this trial was to evaluate whether CBT augmented with acceptance-based strategies from Acceptance and Commitment Therapy could more broadly reduce the negative impact of comm and hallucinations . Forty-three participants with problematic comm and hallucinations were r and omized to receive 15 sessions of the intervention " TORCH " ( Treatment of Resistant Comm and Hallucinations ) or the control , Befriending , then followed up for 6 months . A sub- sample of 17 participants was r and omized to a waitlist control before being allocated to TORCH or Befriending . Participants engaged equally well with both treatments . Despite TORCH participants subjectively reporting greater improvement in comm and hallucinations compared to Befriending participants , the study found no significant group differences in primary and secondary outcome measures based on blinded assessment data . Within-group analyses and comparisons between the combined treatments and waitlist suggested , however , that both treatments were beneficial with a differential pattern of outcomes observed across the two conditions Background . Psychodynamic psychotherapy is a psychological treatment approach that has a growing empirical base . Research has indicated an association between therapist-facilitated affective experience and outcome in psychodynamic therapy . Affect-phobia therapy ( APT ) , as outlined by McCullough et al. , is a psychodynamic treatment that emphasizes a strong focus on expression and experience of affect . This model has neither been evaluated for depression nor anxiety disorders in a r and omized controlled trial . While Internet-delivered psychodynamic treatments for depression and generalized anxiety disorder exist , they have not been based on APT . The aim of this r and omized controlled trial was to investigate the efficacy of an Internet-based , psychodynamic , guided self-help treatment based on APT for depression and anxiety disorders . Methods . One hundred participants with diagnoses of mood and anxiety disorders participated in a r and omized ( 1:1 ratio ) controlled trial of an active group versus a control condition . The treatment group received a 10-week , psychodynamic , guided self-help treatment based on APT that was delivered through the Internet . The treatment consisted of eight text-based treatment modules and included therapist contact ( 9.5 min per client and week , on average ) in a secure online environment . Participants in the control group also received online therapist support and clinical monitoring of symptoms , but received no treatment modules . Outcome measures were the 9-item Patient Health Question naire Depression Scale ( PHQ-9 ) and the 7-item Generalized Anxiety Disorder Scale ( GAD-7 ) . Process measures were also included . All measures were administered weekly during the treatment period and at a 7-month follow-up . Results . Mixed models analyses using the full intention-to-treat sample revealed significant interaction effects of group and time on all outcome measures , when comparing treatment to the control group . A large between-group effect size of Cohen ’s d = 0.77 ( 95 % CI : 0.37–1.18 ) was found on the PHQ-9 and a moderately large between-group effect size d = 0.48 ( 95 % CI : 0.08–0.87 ) was found on the GAD-7 . The number of patients who recovered ( had no diagnoses of depression and anxiety , and had less than 10 on both the PHQ-9 and the GAD-7 ) were at post-treatment 52 % in the treatment group and 24 % in the control group . This difference was significant , χ2(N = 100 , d f = 1 ) = 8.3 , p < .01 . From post-treatment to follow-up , treatment gains were maintained on the PHQ-9 , and significant improvements were seen on the GAD-7 . Conclusion . This study provides initial support for the efficacy of Internet-delivered psychodynamic therapy based on the affect-phobia model in the treatment of depression and anxiety disorders . The results support the conclusion that psychodynamic treatment approaches may be transferred to the guided self-help format and delivered via the Internet Background Adults with attention deficit hyperactivity disorder ( ADHD ) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life . This has a substantial personal and economic impact . In clinical practice there is a high need for additional or alternative interventions for existing treatments , usually consisting of pharmacotherapy and /or psycho-education . Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning , these studies have method ological limitations . This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy ( MBCT ) in further detail . Methods / design A multi-centre , parallel-group , r and omised controlled trial will be conducted in N = 120 adults with ADHD . Patients will be r and omised to MBCT in addition to treatment as usual ( TAU ) or TAU alone . Assessment s will take place at baseline and at three , six and nine months after baseline . Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician . Secondary outcome measures will be self-reported ADHD symptoms , executive functioning , mindfulness skills , self-compassion , positive mental health and general functioning . In addition , a cost-effectiveness analysis will be conducted . Discussion This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD.Trial registration Clinical Trials.gov NCT02463396 . Registered 8 June 2015 Objectives Evaluating and comparing the effectiveness of two smartphone-delivered treatments : one based on behavioural activation ( BA ) and other on mindfulness . Design Parallel r and omised controlled , open , trial . Participants were allocated using an online r and omisation tool , h and led by an independent person who was separate from the staff conducting the study . Setting General community , with recruitment nationally through mass media and advertisements . Participants 40 participants diagnosed with major depressive disorder received a BA treatment , and 41 participants received a mindfulness treatment . 9 participants were lost at the post-treatment . Intervention BA : An 8-week long behaviour programme administered via a smartphone application . Mindfulness : An 8-week long mindfulness programme , administered via a smartphone application . Main outcome measures The Beck Depression Inventory-II ( BDI-II ) and the nine-item Patient Health Question naire Depression Scale ( PHQ-9 ) . Results 81 participants were r and omised ( mean age 36.0 years ( SD=10.8 ) ) and analysed . Results showed no significant interaction effects of group and time on any of the outcome measures either from pretreatment to post-treatment or from pretreatment to the 6-month follow-up . Subgroup analyses showed that the BA treatment was more effective than the mindfulness treatment among participants with higher initial severity of depression from pretreatment to the 6-month follow-up ( PHQ-9 : F ( 1 , 362.1)=5.2 , p<0.05 ) . In contrast , the mindfulness treatment worked better than the BA treatment among participants with lower initial severity from pretreatment to the 6-month follow-up ( PHQ-9 : F ( 1 , 69.3)=7.7 , p<0.01 ) ; BDI-II : ( F(1 , 53.60)=6.25 , p<0.05 ) . Conclusions The two interventions did not differ significantly from one another . For participants with higher severity of depression , the treatment based on BA was superior to the treatment based on mindfulness . For participants with lower initial severity , the treatment based on mindfulness worked significantly better than the treatment based on BA . Trial registration Clinical Trials NCT01463020 BACKGROUND There appears to be consensus that patients with only one or two prior depressive episodes do not benefit from treatment with mindfulness-based cognitive therapy ( MBCT ) . AIMS To investigate whether the effect of MBCT on residual depressive symptoms is contingent on the number of previous depressive episodes ( trial number NTR1084 ) . METHOD Currently non-depressed adults with residual depressive symptoms and a history of depression ( ≤2 prior episodes : n = 71 ; ≥3 episodes : n = 59 ) were r and omised to MBCT ( n = 64 ) or a waiting list ( control : n = 66 ) in an open-label , r and omised controlled trial . The main outcome measured was the reduction in residual depressive symptoms ( Hamilton Rating Scale for Depression , HRSD-17 ) . RESULTS Mindfulness-based cognitive therapy was superior to the control condition across subgroups ( β = -0.56 , P<0.001 ) . The interaction between treatment and subgroup was not significant ( β = 0.45 , P = 0.16 ) . CONCLUSIONS Mindfulness-based cognitive therapy reduces residual depressive symptoms irrespective of the number of previous episodes of major depression Depression presents a serious condition for the individual and a major challenge to health care and society . Internet-based cognitive behavior therapy ( ICBT ) is a treatment option supported in several trials , but there is as yet a lack of effective studies of ICBT in “ real world ” primary care setting s. We examined whether ICBT differed from treatment-as-usual ( TAU ) in reducing depressive symptoms after 3 months . TAU comprised of visits to general practitioner , registered nurse , antidepressant drugs , waiting list for , or psychotherapy , or combinations of these alternatives . Patients , aged ≥ 18 years , who tentatively met criteria for mild to moderate depression at 16 primary care centers in the south-western region of Sweden were recruited and then assessed in a diagnostic interview . A total of 90 patients were r and omized to either TAU or ICBT . The ICBT treatment included interactive elements online , a workbook , a CD with mindfulness and acceptance exercises , and minimal therapist contact . The treatment period lasted for 12 weeks after which both groups were assessed . The main outcome measure was Beck Depression Inventory-II ( BDI-II ) . Additional measures were Montgomery Åsberg Depression Rating Scale – self rating version ( MADRS-S ) and Beck Anxiety Inventory ( BAI ) . The analyses revealed no significant difference between the two groups at post treatment , neither on BDI-II , MADRS-S , nor BAI . Twenty patients ( 56 % ) in the ICBT treatment completed all seven modules . Our findings suggest that ICBT may be successfully delivered in primary care and that the effectiveness , after 3 months , is at par with TAU Mindfulness-based cognitive therapy ( MBCT ) showed efficacy for currently depressed patients . However , most of the available studies suffer from important method ological shortcomings , including the lack of adequate control groups . The present study aims to compare MBCT with a psycho-educational control group design ed to be structurally equivalent to the MBCT program but excluding the main putative " active ingredient " of MBCT ( i.e. , mindfulness meditation practice ) for the treatment of patients with major depression ( MD ) who did not achieve remission following at least 8 weeks of antidepressant treatment . Out of 106 screened subjects , 43 were r and omized to receive MBCT or psycho-education and were prospect ively followed for 26 weeks . MD severity was assessed with the Hamilton Rating Scale for Depression ( HAM-D ) and the Beck Depression Inventory-II ( BDI-II ) . Measures of anxiety , mindfulness , and quality of life were also included . All assessment s were performed at baseline , 4 , 8 , 17 and 26-weeks . Both HAM-D and BDI scores , as well as quality of life and mindfulness scores , showed higher improvements , which were particularly evident over the long-term period , in the MBCT group than in the psycho-education group . Although limited by a small sample size , the results of this study suggest the superiority of MBCT over psycho-education for non-remitted MD subjects OBJECTIVES People in the late stage of bipolar disorder ( BD ) experience elevated relapse rates and poorer quality of life ( QoL ) compared with those in the early stages . Existing psychological interventions also appear less effective in this group . To address this need , we developed a new online mindfulness-based intervention targeting quality of life ( QoL ) in late stage BD . Here , we report on an open pilot trial of ORBIT ( online , recovery-focused , bipolar individual therapy ) . METHODS Inclusion criteria were : self-reported primary diagnosis of BD , six or more episodes of BD , under the care of a medical practitioner , access to the internet , proficient in English , 18 - 65 years of age . Primary outcome was change ( baseline - post-treatment ) on the Brief QoL.BD ( Michalak and Murray , 2010 ) . Secondary outcomes were depression , anxiety , and stress measured on the DASS scales ( Lovibond and Lovibond , 1993 ) . RESULTS Twenty-six people consented to participate ( Age M=46.6 years , SD=12.9 , and 75 % female ) . Ten participants were lost to follow-up ( 38.5 % attrition ) . Statistically significant improvement in QoL was found for the completers , t(15)=2.88 , 95 % CI:.89 - 5.98 , p=.011 , ( Cohen׳s dz=.72 , partial η(2)=.36 ) , and the intent-to-treat sample t(25)=2.65 , 95 % CI:.47 - 3.76 , ( Cohen׳s dz=.52 ; partial η(2)=.22 ) . A non-significant trend towards improvement was found on the DASS anxiety scale ( p=.06 ) in both completer and intent-to-treat sample s , but change on depression and stress did not approach significance . LIMITATIONS This was an open trial with no comparison group , so measured improvements may not be due to specific elements of the intervention . Structured diagnostic assessment s were not conducted , and interpretation of effectiveness was limited by substantial attrition . CONCLUSION Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective , and ORBIT warrants full development . Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention , adding caution s about the impact of extended meditations , and addition of coaching support/monitoring to optimise engagement This study evaluated mindfulness-based cognitive therapy ( MBCT ) , a group intervention design ed to train recovered recurrently depressed patients to disengage from dysphoria-activated depressogenic thinking that may mediate relapse/recurrence . Recovered recurrently depressed patients ( n = 145 ) were r and omized to continue with treatment as usual or , in addition , to receive MBCT . Relapse/recurrence to major depression was assessed over a 60-week study period . For patients with 3 or more previous episodes of depression ( 77 % of the sample ) , MBCT significantly reduced risk of relapse/recurrence . For patients with only 2 previous episodes , MBCT did not reduce relapse/recurrence . MBCT offers a promising cost-efficient psychological approach to preventing relapse/recurrence in recovered recurrently depressed patients This is the first trial to investigate the outcome of tailored and ACT-influenced , cognitive behavioral Internet treatment for eating disorder psychopathology , and the relation between knowledge acquisition and outcome . This study utilized a r and omized controlled design , with computer-based allocation to treatment or waiting list control group . Participants were recruited via advertisements in social media and newspapers in Sweden . Participants fulfilling the criteria for bulimia nervosa ( BN ) , or Eating Disorder Not Otherwise Specified ( EDNOS ) , with a BMI above 17.5 , were enrolled in the study ( N = 92 ) . The treatment group received an Internet-based , ACT-influenced CBT intervention , developed by the authors , for eating disorders . The treatment lasted 8 weeks , and was adapted to the participant 's individual needs . A clinician provided support . The main outcome measures were eating disorder symptoms and body shape dissatisfaction . Intent-to-treat analysis showed that the treatment group ( n = 46 ) improved significantly on eating disorder symptoms and body dissatisfaction , compared with the waiting list control group ( n = 46 ) , with small to moderate effect sizes ( between group effects , d = 0.35 - 0.64 ) . More than a third of the participants in the treatment group ( 36.6 % ) , compared to 7.1 % in the waiting list control condition , made clinical ly significant improvements . Results showed a significant increase in knowledge in the treatment group compared to the waiting list control group ( between group effect , d = 1.12 ) , but we found no significant correlations between knowledge acquisition and outcome ( r= -0.27 to -r = 0.23 ) . The results provide preliminary support for Internet-based , tailored , and ACT-influenced treatment , based on CBT for participants with eating disorder psychopathology The National Institute of Clinical Excellence ( NICE ) in the UK is responsible for producing evidence based guidelines for the treatment of most common illnesses , both physical and psychological . NICE uses a hierarchy of evidence , ranging from data from meta-analyses of r and omised controlled trials ( RCT 's ) at the apex , to the opinions of acknowledged experts at the bottom . The task of preparing guideline for depression involved us in performing clean meta-analyses of around 8,000 published RCTs of the treatment of this disorder . Where drug treatments were concerned we used three indicators of efficacy , as well as considering toxicity , tolerability and cost . We also distinguished between studies carried out in primary care , and studies in patients treated by the mental health services . We found it helpful to arrange our report in terms of a " stepped care " model , addressing the indications for patients being referred on for more specialised , and expensive , treatments . In the full guideline we included our doubts that depression was a homogenous clinical entity , and our awareness of the limitations of relying on r and omised controlled trials ( RCT 's ) as the only source of evidence . This Editorial summarises the content of the guideline on the treatment of depression and discusses how it was received and also what it did not say Acceptance and Commitment Therapy ( ACT ) can be effective in treating anxiety disorders , yet there has been no study on Internet-delivered ACT for social anxiety disorder ( SAD ) and panic disorder ( PD ) , nor any study investigating whether therapist guidance is superior to unguided self-help when supplemented with a smartphone application . In the current trial , n=152 participants diagnosed with SAD and /or PD were r and omized to therapist-guided or unguided treatment , or a waiting-list control group . Both treatment groups used an Internet-delivered ACT-based treatment program and a smartphone application . Outcome measures were self-rated general and social anxiety and panic symptoms . Treatment groups saw reduced general ( d=0.39 ) and social anxiety ( d=0.70 ) , but not panic symptoms ( d=0.05 ) compared to the waiting-list group , yet no differences in outcomes were observed between guided and unguided interventions . We conclude that Internet-delivered ACT is appropriate for treating SAD and potentially PD . Smartphone applications may partially compensate for lack of therapist support Mindfulness-based interventions have proven effective for the transdiagnostic treatment of heterogeneous anxiety disorders . So far , no study has investigated the potential of mindfulness-based treatments when delivered remotely via the Internet . The current trial aims at evaluating the efficacy of a st and -alone , unguided , Internet-based mindfulness treatment program for anxiety . Ninety-one participants diagnosed with social anxiety disorder , generalized anxiety disorder , panic disorder , or anxiety disorder not otherwise specified were r and omly assigned to a mindfulness treatment group ( MTG ) or to an online discussion forum control group ( CG ) . Mindfulness treatment consisted of 96 audio files with instructions for various mindfulness meditation exercises . Primary and secondary outcome measures were assessed at pre- , posttreatment , and at 6-months follow-up . Participants of the MTG showed a larger decrease of symptoms of anxiety , depression , and insomnia from pre- to post assessment than participants of the CG ( Cohen 's d(between)=0.36 - 0.99 ) . Within effect sizes were large in the MTG ( d=0.82 - 1.58 ) and small to moderate in the CG ( d=0.45 - 0.76 ) . In contrast to participants of the CG , participants of the MTG also achieved a moderate improvement in their quality of life . The study provided encouraging results for an Internet-based mindfulness protocol in the treatment of primary anxiety disorders . Future replications of these results will show whether Web-based mindfulness meditation can constitute a valid alternative to existing , evidence -based cognitive-behavioural Internet treatments . The trial was registered at Clinical Trials.gov ( NCT01577290 ) Depression is characterized by a large risk of relapse/recurrence . Mindfulness-based cognitive therapy ( MBCT ) is a recent non-drug psychotherapeutic intervention to prevent future depressive relapse/recurrence in remitted/recovered depressed patients . In this r and omized controlled trial , the authors investigated the effects of MBCT on the relapse in depression and the time to first relapse since study participation , as well as on several mood states and the quality of life of the patients . 106 recovered depressed patients with a history of at least 3 depressive episodes continued either with their treatment as usual ( TAU ) or received MBCT in addition to TAU . The efficacy of MBCT was assessed over a study period of 56 weeks . At the end of the study period relapse/recurrence was significantly reduced and the time until first relapse increased in the MBCT plus TAU condition in comparison with TAU alone . The MBCT plus TAU group also showed a significant reduction in both short and longer-term depressive mood and better mood states and quality of the life . For patients with a history of at least three depressive episodes who are not acutely depressed , MBCT , added to TAU , may play an important role in the domain of relapse prevention in depression OBJECTIVES There is growing evidence that mindfulness has positive consequences for both psychological and physical health in both clinical and non- clinical population s. The potential benefits of mindfulness underpin a range of therapeutic intervention approaches design ed to increase mindfulness in both clinical and community context s. Self-guided mindfulness-based interventions may be a way to increase access to the benefits of mindfulness . This study explored whether a brief , online , mindfulness-based intervention can increase mindfulness and reduce perceived stress and anxiety/depression symptoms within a student population . METHOD One hundred and four students were r and omly allocated to either immediately start a two-week , self-guided , online , mindfulness-based intervention or a wait-list control . Measures of mindfulness , perceived stress and anxiety/depression were administered before and after the intervention period . RESULTS Intention to treat analysis identified significant group by time interactions for mindfulness skills , perceived stress and anxiety/depression symptoms . Participation in the intervention was associated with significant improvements in all measured domains , where no significant changes on these measures were found for the control group . CONCLUSIONS This provides evidence in support of the feasibility and effectiveness of shorter self-guided mindfulness-based interventions . The limitations and implication s of this study for clinical practice are discussed BACKGROUND Internet-based cognitive behavior therapy for depression has been tested in several trials but there are no internet studies on behavioral activation ( BA ) , and no studies on BA over the internet including components of acceptance and commitment therapy ( ACT ) . The aim of this study was to develop and test the effects of internet-delivered BA combined with ACT against a waiting list control condition as a first test of the effects of treatment . METHODS Selection took place with a computerized screening interview and a subsequent semi-structured telephone interview . A total of 80 individuals from the general public were r and omized to one of two conditions . The treatment lasted for 8 weeks after which both groups were assessed . We also included a 3 month follow-up . The treatment included interactive elements online and a CD-ROM for mindfulness and acceptance exercises . In addition , written support and feedback was given by a therapist every week . RESULTS Results at posttreatment showed a large between group effect size on the Beck Depression inventory II d=0.98 ( 95%CI=0.51 - 1.44 ) . In the treated group 25 % ( 10/40 ) reached remission defined as a BDI score ≤ 10 vs. 5 % ( 2/40 ) in the control group . Results on secondary measures were smaller . While few dropped out from the study ( N=2 ) at posttreatment , the average number of completed modules was M=5.1 out of the seven modules . LIMITATIONS The study only included a waiting-list comparison and it is not possible to determine which treatment components were the most effective . CONCLUSIONS We conclude that there is initial evidence that BA with components of ACT can be effective in reducing symptoms of depression Generalized anxiety disorder ( GAD ) is a disabling condition which can be treated with cognitive behaviour therapy ( CBT ) . The present study tested the effects of therapist-guided internet-delivered acceptance-based behaviour therapy on symptoms of GAD and quality of life . An audio CD with acceptance and mindfulness exercises and a separate workbook were also included in the treatment . Participants diagnosed with GAD ( N = 103 ) were r and omly allocated to immediate therapist-guided internet-delivered acceptance-based behaviour therapy or to a waiting-list control condition . A six month follow-up was also included . Results using hierarchical linear modelling showed moderate to large effects on symptoms of GAD ( Cohen 's d = 0.70 to 0.98 ) , moderate effects on depressive symptoms ( Cohen 's d = 0.51 to 0.56 ) , and no effect on quality of life . Follow-up data showed maintained effects . While there was a 20 % dropout rate , sensitivity analyses showed that dropouts did not differ in their degree of change during treatment . To conclude , our study suggests that internet-delivered acceptance-based behaviour therapy can be effective in reducing the symptoms of GAD OBJECTIVE Our aim in this r and omized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments , acceptance and commitment therapy ( ACT ) and cognitive behavior therapy ( CBT ) , in guided self-help format . METHOD Ninety-nine participants ( mean age = 48.5 years ; 43 % female ) who were significantly distressed by tinnitus were recruited from the community . Participants were r and omly assigned to CBT ( n = 32 ) , ACT ( n = 35 ) , or a control condition ( monitored Internet discussion forum ; n = 32 ) , and they were assessed with st and ardized self-report measures ( Tinnitus H and icap Inventory ; Hospital Anxiety and Depression Scale ; Quality of Life Inventory ; Perceived Stress Scale ; Tinnitus Acceptance Question naire ) at pre- , posttreatment ( 8 weeks ) , and 1-year follow-up . RESULTS Mixed-effects linear regression analysis of all r and omized participants showed significant effects on the primary outcome ( Tinnitus H and icap Inventory ) for CBT and for ACT compared with control at posttreatment ( 95 % CI [ -17.03 , -2.94 ] , d = 0.70 , and 95 % CI [ -16.29 , -2.53 ] , d = 0.68 , respectively ) . Within-group effects were substantial from pretreatment through 1-year-follow-up for both treatments ( 95 % CI [ -44.65 , -20.45 ] , d = 1.34 ) , with no significant difference between treatments ( 95 % CI [ -14.87 , 11.21 ] , d = 0.16 ) . CONCLUSIONS Acceptance-based procedures may be a viable alternative to traditional CBT techniques in the management of tinnitus . The Internet can improve access to psychological interventions for tinnitus |
12,656 | 30,319,077 | This meta- analysis provides evidence that chronic , but not acute , ingestion of NaHCO3 increases both Wingate test peak and mean power | ABSTRACT The aim of this study was to perform a systematic review and meta- analysis on the acute and chronic effects of sodium bicarbonate ( NaHCO3 ) ingestion on Wingate performance . | The purpose of the study was to assess the effect of sodium bicarbonate ingestion upon repeated bouts of intensive short duration exercise . Twenty-three subjects participated in the investigation ( 8 females and 15 males , age 21.4 + /- 2.3 , mean + /- sd ) . Subjects completed six trials ; three following the ingestion of sodium bicarbonate ( 300 mg/kg body weight ) and three following the ingestion of a placebo ( 8 g sodium chloride ) . Each trial consisted of ten ten-second sprints on a cycle ergometer with 50 seconds recovery between each sprint . ' Peak power ' and ' average power output ' during each ten second sprint was measured from the flywheel of the ergometer using a light-sensitive monitor ( Cranlea ) linked to a BBC microcomputer . The power outputs recorded during each ten-second sprint of the bicarbonate trials were then compared with those recorded during the corresponding sprint of the placebo trials . The bicarbonate trials produced higher mean ' average power ' outputs in all ten of the ten-second sprints , with the difference in ' average power ' output being statistically significant in eight of these ( p less than 0.05 ) . The results also revealed that the difference in the ' average power ' outputs attained during the bicarbonate and placebo trials increased as the number of sprint repetitions increased ( p less than 0.01 ) . ' Peak power ' output was also greater in the bicarbonate trials with it being significantly higher ( p less than 0.001 ) during the final ten-second sprint . It was concluded that during exercise consisting of repeated , short- duration sprints , power output was enhanced following the ingestion of sodium bicarbonate , ( 300 mg/kg body weight ) ABSTRACT The aim of this study was to investigate the effects of sodium bicarbonate ( NaHCO3 ) on 4 km cycling time trial ( TT ) performance when individualised to a predetermined time to peak blood bicarbonate ( HCO3− ) . Eleven male trained cyclists volunteered for this study ( height 1.82 ± 0.80 m , body mass ( BM ) 86.4 ± 12.9 kg , age 32 ± 9 years , peak power output ( PPO ) 382 ± 22 W ) . Two trials were initially conducted to identify time to peak HCO3− following both 0.2 g.kg−1 BM ( SBC2 ) and 0.3 g.kg−1 BM ( SBC3 ) NaHCO3 . Thereafter , on three separate occasions using a r and omised , double-blind , crossover design , participants completed a 4 km TT following ingestion of either SBC2 , SBC3 , or a taste-matched placebo ( PLA ) containing 0.07 g.kg−1 BM sodium chloride ( NaCl ) at the predetermined individual time to peak HCO3−. Both SBC2 ( −8.3 ± 3.5 s ; p < 0.001 , d = 0.64 ) and SBC3 ( −8.6 ± 5.4 s ; p = 0.003 , d = 0.66 ) reduced the time to complete the 4 km TT , with no difference between SBC conditions ( mean difference = 0.2 ± 0.2 s ; p = 0.87 , d = 0.02 ) . These findings suggest trained cyclists may benefit from individualising NaHCO3 ingestion to time to peak HCO3− to enhance 4 km TT performance Zabala , M , Requena , B , Sánchez-Muñoz , C , González-Badillo , JJ , García , I , Ööpik , V , and Pääsuke , M. Effects of sodium bicarbonate ingestion on performance and perceptual responses in a laboratory-simulated BMX cycling qualification series . J Strength Cond Res 22(5 ) : 1645 - 1653 , 2008-The objective of this study was to examine the effect of sodium bicarbonate ( NaHCO3− ) ingestion on performance and perceptual responses in a laboratory-simulated bicycle motocross ( BMX ) qualification series . Nine elite BMX riders volunteered to participate in this study . After familiarization , subjects undertook two trials involving repeated sprints ( 3 × Wingate tests [ WTs ] separated by 30 minutes of recovery ; WT1 , WT2 , WT3 ) . Ninety minutes before each trial , subjects ingested either NaHCO3− or placebo in a counterbalanced , r and omly assigned , double-blind manner . Each trial was separated by 4 days . Performance variables of peak power , mean power , time to peak power , and fatigue index were calculated for each sprint . Ratings of perceived exertion were obtained after each sprint , and ratings of perceived readiness were obtained before each sprint . No significant differences were observed in performance variables between successive sprints or between trials . For the NaHCO3− trial , peak blood lactate during recovery was greater after WT2 ( p < 0.05 ) and tended to be greater after WT3 ( p = 0.07 ) , and ratings of perceived exertion were not influenced . However , improved ratings of perceived readiness were observed before WT2 and WT3 ( p < 0.05 ) . In conclusion , NaHCO3− ingestion had no effect on performance and RPE during a series of three WT simulating a BMX qualification series , possibly because of the short duration of each effort and the long recovery time used between the three WTs . On the contrary , NaHCO3− ingestion improved perceived readiness before each WT PURPOSE The aim of this study was to determine the effects of sodium bicarbonate ingestion on prolonged intermittent exercise and performance . METHODS Eight healthy male subjects ( mean + /- SD : age 25.4 + /- 6.4 yr , mass 70.9 + /- 5.1 kg , height 179 + /- 7 cm , VO(2max ) 4.21 + /- 0.51 L.min-1 ) volunteered for the study , which had received ethical approval . Subjects undertook two 30-min intermittent cycling trials ( repeated 3-min blocks ; 90 s at 40 % VO(2max ) , 60 s at 60 % VO(2max ) , 14-s maximal sprint , 16-s rest ) after ingestion of either sodium bicarbonate ( NaHCO(3 ) ; 0.3 g.kg-1 ) or sodium chloride ( NaCl ; 0.045 g x kg(-1 ) . Expired air , blood lactate ( BLa ) , bicarbonate ( HCO(3)- ) , and pH were measured at rest , 30 and 60 min postingestion , and during the 40 % VO(2max ) component of exercise ( 4 , 10 , 16 , and 29 min ) . RESULTS After ingestion , pH increased from rest to 7.46 + /- 0.03 and 7.40 + /- 0.01 for NaHCO(3 ) and NaCl , respectively ( main effect for time and trial ; P < 0.05 ) . Values decreased at 15 min of exercise to 7.30 + /- 0.07 and 7.21 + /- 0.06 , respectively , remaining at similar levels until the end of exercise . BLa peaked at 15 min ( 12.03 + /- 4.31 and 10.00 + /- 2.58 mmol . L-1 , for NaHCO(3 ) and NaCl , respectively ; P > 0.05 ) remaining elevated until the end of exercise ( P < 0.05 ) . Peak power expressed relative to sprint 1 demonstrated a significant main effect between trials ( P < 0.05 ) . Sprint 2 increased by 11.5 + /- 5 % and 1.8 + /- 9.5 % for NaHCO(3 ) and NaCl , respectively . During NaHCO(3 ) , sprint 8 remained similar to sprint 1 ( 0.2 + /- 17 % ) , whereas a decrease was observed during NaCl ( -10.0 + /- 16.0 % ) . CONCLUSION The results of this study suggest that ingestion of NaHCO(3 ) improves sprint performance during prolonged intermittent cycling Siegler , JC and Gleadall-Siddall , D0 . Sodium bicarbonate ingestion and repeated swim sprint performance . J Strength Cond Res 24(11 ) : 3105 - 3111 , 2010-The purpose of the present investigation was to observe the ergogenic potential of 0.3 g·kg−1 of sodium bicarbonate ( NaHCO3 ) in competitive , nonelite swimmers using a repeated swim sprint design that eliminated the technical component of turning . Six male ( 181.2 ± 7.2 cm ; 80.3 ± 11.9 kg ; 50.8 ± 5.5 ml·kg−1·min−1 & OV0312;O2max ) and 8 female ( 168.8 ± 5.6 cm ; 75.3 ± 10.1 kg ; 38.8 ± 2.6 ml·kg−1·min−1 & OV0312;O2max ) swimmers completed 2 trial conditions ( NaHCO3 [ BICARB ] and NaCl placebo [ PLAC ] ) implemented in a r and omized ( counterbalanced ) , single blind manner , each separated by 1 week . Swimmers were paired according to ability and completed 8 , 25-m front crawl maximal effort sprints each separated by 5 seconds . Blood acid-base status was assessed preingestion , pre , and postswim via capillary finger sticks , and total swim time was calculated as a performance measure . Total swim time was significantly decreased in the BICARB compared to PLAC condition ( p = 0.04 ) , with the BICARB condition result ing in a 2 % decrease in total swim time compared to the PLAC condition ( 159.4 ± 25.4 vs. 163.2 ± 25.6 seconds ; mean difference = 4.4 seconds ; 95 % confidence interval = 8.7 - 0.1 ) . Blood analysis revealed significantly elevated blood buffering potential preswim ( pH : BICARB = 7.48 ± 0.01 , PLAC = 7.41 ± 0.01 ) along with a significant decrease in extracellular K+ ( BICARB = 4.0 ± 0.1 mmol·L−1 , PLAC = 4.6 ± 0.1 mmol·L−1 ) . The findings suggest that 0.3 g·kg−1 NaHCO3 ingested 2.5 hours before exercise enhances the blood buffering potential and may positively influence swim performance Abstract We have evaluated whether sodium bicarbonate , taken chronically ( 0.5 g · kg−1 body mass ) for a period of 5 days would improve the performance of eight subjects during 60 s of high-intensity exercise on an electrically braked cycle ergometer . The first test was performed prior to chronic supplementation ( pre-ingestion ) while the post-ingestion test took place 6 days later . A control test took place approximately 1 month after the cessation of all testing . Acid-base and metabolite data ( n = 7 ) were measured from arterialised blood both pre- and post-exercise , as well as daily throughout the exercise period . The work completed by the subjects in the control and pre-ingestion test [ 21.1 ( 0.9 ) and 21.1 ( 0.9 ) MJ , respectively ] was less than ( P < 0.05 ) that completed in the post-ingestion test [ 24.1 ( 0.9 ) MJ ; F(2,21 ) = 3.4 , P < 0.05 , power = 0.57 ] . Peak power was higher after the 5-day supplementation period ( P < 0.05 ) . Ingestion of the sodium bicarbonate for a period of 5 days result ed in an increase in pH ( F(5,36 ) = 12.5 , P < 0.0001 , power = 1.0 ) over the 5-day period . The blood bicarbonate levels also rose during the trial ( P < 0.05 ) from a resting level of 22.8 ( 0.4 ) to 28.4 ( 1.1 ) mmol · l−1 after 24 h of ingestion . In conclusion , the addition of sodium bicarbonate to a normal diet proved to be of ergogenic benefit in the performance of short-term , high-intensity work PURPOSE Sodium bicarbonate ( NaHCO3 ) ingestion may prevent exercise-induced perturbations in acid-base balance , thus result ing in performance enhancement . This study aim ed to determine whether different levels of NaHCO3 intake influences acid-base balance and performance during high-intensity exercise after 5 d of supplementation . METHODS Twenty-four men ( 22 + /- 1.7 yr ) were r and omly assigned to one of three groups ( eight subjects per group ) : control ( C , placebo ) , moderate NaHCO3 intake ( MI , 0.3 g x kg(-1 ) x d(-1 ) ) , and high NaHCO3 intake ( HI , 0.5 g x kg(-1 ) x d(-1 ) ) . Arterial pH , HCO3(- ) , PO2 , PCO2 , K+ , Na , base excess ( BE ) , lactate , and mean power ( MP ) were measured before and after a Wingate test pre- and postsupplementation . RESULTS HCO3(- ) increased proportionately to the dosage level . No differences were detected in C. Supplementation increased MP ( W x kg(- ) ) in MI ( 7.36 + /- 0.7 vs 6.73 + /- 1.0 ) and HI ( 7.72 + /- 0.9 vs 6.69 + /- 0.6 ) , with HI being more effective than MI . NaHCO3 ingestion result ed postexercise in increased lactate ( mmol x L(-1 ) ) ( 12.3 + /- 1.8 vs 10.3 + /- 1.9 and 12.4 + /- 1.2 vs 10.4 + /- 1.5 in MI and HI , respectively ) , reduced exercise-induced drop of pH ( 7.305 + /- 0.04 vs 7.198 + /- 0.02 and 7.343 + /- 0.05 vs 7.2 + /- 0.01 in MI and HI , respectively ) and HCO3(- ) ( mmol x L(-1 ) ) ( 13.1 + /- 2.4 vs 17.5 + /- 2.8 and 13.2 + /- 2.7 vs 19.8 + /- 3.2 for HCO3 in MI and HI , respectively ) , and reduced K ( 3.875 + /- 0.2 vs 3.625 + /- 0.3 mmol x L(-1 ) in MI and HI , respectively ) . CONCLUSION NaHCO3 administration for 5 d may prevent acid-base balance disturbances and improve performance during anaerobic exercise in a dose-dependent manner BACKGROUND The aim of this study was to compare and contrast the effects of acute versus chronic sodium bicarbonate ingestion . METHODS PARTICIPANTS Eight male , ( mean+/-SE ) : age , 20.8+/-0.4 yrs ; height , 179.6+/-0.6 cm ; body mass , 79.4+/-0.85 kg , Sigma7skf , 48.6+/-4.8 mm , VO2max=55.9+/-0.8 ml x kg(-1 ) x min(-1 ) ) volunteer subjects , ingested NaHCO3 in either a dose of 0.5 g x kg(-1 ) body mass acutely or the same dose daily over a period of six days in order to determine whether there were any differences in performance of 90 sec maximal cycling ergometry . INTERVENTION After subjects undertook an initial control ( C ) test session , all were then r and omly assigned to one of two groups , acute or chronic NaHCO3 ingestion . Subjects in the acute ingestion ( AI ) group completed their supplemented test on day one , and then on the following day . Chronic ingestion ( CI ) subjects completed the test after one day of chronic ingestion as well as following six days of bicarbonate ingestion . Following ten days rest , subjects repeated the protocol in the opposite group . MEASURES Blood sample s were taken pre- and postingestion , daily , and pre- and postexercise and were analysed for , pH , Base excess ( BE ) , HCO3- , PO2 , PCO2 , Na+ , K+ , Cl- , and lactate . RESULTS Both the chronic ( CI ) and acute ingestion ( AI ) groups were significantly different to the control ( C ) value ( p<0.001 and p<0.05 , respectively ) . CONCLUSIONS We would suggest using chronic ingestion as a means to improve high intensity work rather than the acute ingestion of sodium bicarbonate . The ingestion of sodium bicarbonate , over a period of six days , significantly improved work output two days after bicarbonate ingestion ceased 1 . Five males were studied on three occasions , after oral administration of CaCO3 ( control ) , NH4Cl ( acidosis ) and NaHCO3 ( alkalosis ) , in a dose of 0.3 g/kg , taken over a 3 h period at rest . The subjects then exercised on a cycle ergometer for 20 min at 33 % maximal oxygen uptake ( VO2 max . ) , followed by 20 min at 66 % and at 95 % VO2 max . until exhaustion . 2 . Endurance at 95 % VO2 max . was longest with alkalosis ( 5.44 + /- 1.05 min ) , shortest with acidosis ( 3.13 + /- 0.97 min ) and intermediate in the control study ( 4.56 + /- 1.31 min ) ; venous blood pH at exhaustion was 7.33 + /- 0.02 ( mean + /- 1 SEM ) , 7.13 + /- 0.02 and 7.26 + /- 0.02 respectively . 3 . Concentrations of plasma lactate at exhaustion were 7.10 + /- 0.8 mmol/1 4.0 + /- 0.5 and 7.9 + /- 0.9 mmol/l in the control , acidosis and alkalosis studies respectively . 4 . Muscle lactate increased most from rest to exhaustion with alkalosis to 17.1 + /- 2.5 mumol/g and least with acidosis to 12.2 + /- 1.4 mumol/g . Muscle glycogen depletion was comparable in control and alkalosis studies . 5 . The lower plasma lactate concentration during exercise in acidosis compared with control and alkalosis appears to be due to an inhibition of muscle glycolysis combined with a reduction in lactate efflux from muscle Four groups of male subjects participated in anaerobic testing on a Repco EX10 cycle ergometer to determine the effectiveness of sodium bicarbonate ( 0.3 g kg-1 body mass ) as an ergogenic aid during exercise of 10 , 30 , 120 and 240 s duration . Blood was collected 90 min prior to ingestion of sodium bicarbonate ( NaHCO3 ) , after ingestion of NaHCO3 and immediately post-exercise from a heated ( 43 - 46 degrees C ) fingertip and analysed immediately post- collection for pH , base excess , bicarbonate and lactate . The total work undertaken ( kJ ) and peak power achieved during the tests were also obtained via a Repco Work Monitor Unit . Blood bicarbonate levels were again increased above the control and placebo conditions ( P < 0.001 ) and blood lactate levels were also increased following the bicarbonate trials . The pH levels fell significantly ( P < 0.05 ) below the control and placebo conditions in all trials . The results indicate that NaHCO3 at this dosage has no ergogenic benefit for work of either 10 or 30 s duration , even though blood bicarbonate levels were significantly increased ( P < 0.05 ) following ingestion of NaHCO3 . For work periods of 120 and 240 s , performance was significantly increased ( P < 0.05 ) above the control and placebo conditions following NaHCO3 ingestion Background Current evidence suggests sodium bicarbonate ( NaHCO3 ) should be ingested based upon the individualised alkalotic peak of either blood pH or bicarbonate ( HCO3− ) because of large inter-individual variations ( 10–180 min ) . If such a strategy is to be practical , the blood analyte response needs to be reproducible . Objective This study aim ed to evaluate the degree of reproducibility of both time to peak ( TTP ) and absolute change in blood pH , HCO3− and sodium ( Na+ ) following acute NaHCO3 ingestion . Methods Male participants ( n = 15 ) with background s in rugby , football or sprinting completed six r and omised treatments entailing ingestion of two doses of 0.2 g·kg−1 body mass ( BM ) NaHCO3 ( SBC2a and b ) , two doses of 0.3 g·kg−1 BM NaHCO3 ( SBC3a and b ) or two control treatments ( CON1a and b ) on separate days . Blood analysis included pH , HCO3− and Na+ prior to and at regular time points following NaHCO3 ingestion over a 3-h period . Results HCO3− displayed greater reproducibility than pH in intraclass correlation coefficient ( ICC ) analysis for both TTP ( HCO3− SBC2 r = 0.77 , P = 0.003 ; SBC3 r = 0.94 , P < 0.001 ; pH SBC2 r = 0.62 , P = 0.044 ; SBC3 r = 0.71 , P = 0.016 ) and absolute change ( HCO3− SBC2 r = 0.89 , P < 0.001 ; SBC3 r = 0.76 , P = 0.008 ; pH SBC2 r = 0.84 , P = 0.001 ; SBC3 r = 0.62 , P = 0.041 ) . Conclusion Our results indicate that both TTP and absolute change in HCO3− is more reliable than pH. As such , these data provide support for an individualised NaHCO3 ingestion strategy to consistently elicit peak alkalosis before exercise . Future work should utilise an individualised NaHCO3 ingestion strategy based on HCO3− responses and evaluate effects on exercise performance |
12,657 | 19,730,398 | RESULTS We found strong evidence that ergonomic and other musculoskeletal injury prevention interventions in manufacturing and warehousing are worth undertaking in terms of their financial merits .
We also found strong evidence that multisector disability management interventions are worth undertaking .
While the economic evaluation of interventions in this literature warrants further expansion , we found a sufficient number of studies to identify strong , moderate , and limited evidence in certain industry-intervention clusters . | OBJECTIVE We review ed the occupational health and safety intervention literature to synthesize evidence on financial merits of such interventions . | BACKGROUND Occupational low back pain ( OLBP ) is widespread in industrialized societies . We present a model to estimate the net economic costs of investments in ergonomic interventions at the company level to reduce work-related low back pain . METHODS Costs of interventions are defined by incorporating not only the costs of investment of equipment and labor , but also by taking into account the avoided costs of lost work time , medical care costs , and productivity improvements . In the net-cost model , all costs are annualized and are calculated at the level of an individual organization . Three case studies have been performed based on data from three companies in the manufacturing sector of the United States using the above approach . RESULTS The net-cost estimates for the three case studies consistently show that ergonomic interventions applied appropriately can result in substantial cost savings for the companies . CONCLUSIONS Although generalizing on the basis of three case studies is not ideal , our analyses show that it might be in the economic interest of management to play a more active role to prevent back pain . Gathering useful retrospective cost data , even on interventions deemed effective by corporate innovators , proved to be extremely difficult . We conclude that it is essential to incorporate a protocol for collecting cost and effectiveness data in the st and ard operating procedures of ergonomists and companies introducing such innovation . We intend to vali date the net-cost model for the monitoring and reporting of such data through prospect i ve studies in a variety of industrial setting s and in countries at various stages of economic development BACKGROUND High rates of work-related injuries are seen among health care workers involved in lifting and transferring patients . We studied the effects of a participatory worker-management ergonomics team among hospital orderlies . METHODS This prospect i ve intervention trial examined work injuries and other outcomes before and after the intervention , with other hospital employees used as a concurrent control . All orderlies in a 1,200-bed urban hospital were studied using passively collected data ( mean employment during study period 100 - 110 orderlies ) ; 67 orderlies ( preintervention ) and 88 orderlies ( postintervention ) also completed a question naire . The intervention was the formation of a participatory ergonomics team with three orderlies , one supervisor , and technical advisors . This team design ed and implemented changes in training and work practice s. RESULTS The 2-year postintervention period was marked by decreased risks of work injury ( RR = 0.50 , 95 % CI 0.35 - 0.72 ) , lost time injury ( RR = 0.26 , 95 % CI 0.14 - 0.48 ) , and injury with three or more days of time loss ( RR = 0.19 , 95 % CI 0.07 - 0.53 ) . Total lost days declined from 136.2 to 23.0 annually per 100 full-time worker equivalents ( FTE ) . Annual workers ' compensation costs declined from $ 237/FTE to $ 139/FTE . The proportion of workers with musculoskeletal symptoms declined and there were statistically significant improvements in job satisfaction , perceived psychosocial stressors , and social support among the orderlies . CONCLUSION Substantial improvements in health and safety were seen following implementation of a participatory ergonomics program Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness Background : Call centre work with computers is associated with increased rates of upper body pain and musculoskeletal disorders . Methods : This one year , r and omised controlled intervention trial evaluated the effects of a wide forearm support surface and a trackball on upper body pain severity and incident musculoskeletal disorders among 182 call centre operators at a large healthcare company . Participants were r and omised to receive ( 1 ) ergonomics training only , ( 2 ) training plus a trackball , ( 3 ) training plus a forearm support , or ( 4 ) training plus a trackball and forearm support . Outcome measures were weekly pain severity scores and diagnosis of incident musculoskeletal disorder in the upper extremities or the neck/shoulder region based on physical examination performed by a physician blinded to intervention . Analyses using Cox proportional hazard models and linear regression models adjusted for demographic factors , baseline pain levels , and psychosocial job factors . Results : Post-intervention , 63 participants were diagnosed with one or more incident musculoskeletal disorders . Hazard rate ratios showed a protective effect of the armboard for neck/shoulder disorders ( HR = 0.49 , 95 % CI 0.24 to 0.97 ) after adjusting for baseline pain levels and demographic and psychosocial factors . The armboard also significantly reduced neck/shoulder pain ( p = 0.01 ) and right upper extremity pain ( p = 0.002 ) in comparison to the control group . A return-on-investment model predicted a full return of armboard and installation costs within 10.6 months . Conclusion : Providing a large forearm support combined with ergonomic training is an effective intervention to prevent upper body musculoskeletal disorders and reduce upper body pain associated with computer work among call centre employees Musculoskeletal injuries in the workplace are recognized as a major health and economic problem ; however , little has been done to develop strategies that emphasize both quality and cost control . The purpose of this ten-year perspective investigation was to evaluate the use of quality -based st and ardized diagnostic and treatment protocol s as part of an unbiased injury surveillance system . The program was evaluated in a public utility company with more than 5300 employees , and result ed in a measurable and long-term improvement in all outcome parameters measured : ( 1 ) The number of days lost from work and the number of new injuries reported fell by 55 and 51 % , respectively . ( 2 ) The average time lost per injury dropped by 40 % . ( 3 ) The number of surgeries performed decreased by 67 % , and the operative success rate increased dramatically . ( 4 ) Finally , as an added benefit , there was a 60 % reduction in expenditures for lost time and replacement wages , result ing in a cumulative ten-year savings of more than 4.1 million dollars . The program accomplished the goal of ensuring quality care in a prospect i ve concurrent fashion . As an additional benefit , the program also reduced unjustified lost time and compensation costs through early functional return , efficient use of diagnostic studies , and avoidance of surgery whenever possible . Future emphasis on health-care delivery in the workers ' compensation setting should concentrate on high- quality medical care , which will , in turn , lead to secondary cost savings Study Design . A retrospective and prospect i ve cohort . Objectives . To compare the effectiveness of occupational intervention , early intervention , and st and ard care in the management of Worker ’s Compensation injury cl aims . Summary of Background Data . The current management of occupational back pain and work-related upper extremity disorders with either st and ard care or early intervention appears to be ineffective . Methods . A retrospective cohort compared injury cl aim incidence , duration , and costs between one company with access to st and ard care and another similar company with access to early intervention . A prospect i ve cohort looked at the effect of one company changing from st and ard care to occupational management in comparison with the control group with early intervention . Survival analysis was used to attempt to explain differences in injury cl aim duration . Results . St and ard care result ed in lower injury cl aim incidence , duration , and costs than early intervention , whereas occupational management result ed in lower injury cl aim incidence , duration , and costs than st and ard care . The covariates of physical therapist involvement , chiropractor involvement , injury severity , and relationship between Worker ’s Compensation and the employer were associated with delayed time to cl aim closure in the company with access to early intervention with the most important covariate being physical therapist involvement ( hazard rate ratio 19.88 , 95 % confidence interval 7.95–39.77 ) . Only the covariate of injury severity was associated with delayed time to cl aim closure in the company with access to occupational management ( hazard rate ratio 1.67 , 95 % confidence interval 1.05–27.20 ) . Conclusions . It is recommended that an occupational management approach , in comparison with st and ard care or early intervention , be considered for management of occupational injuries Aims : To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain , combining an occupational and a clinical rehabilitation intervention . Methods : A r and omised trial design with four arms was used : st and ard care , occupational arm , clinical arm , and Sherbrooke model arm ( combined occupational and clinical interventions ) . From the Quebec WCB perspective , a cost-benefit ( amount of consequence of disease costs saved ) and cost-effectiveness analysis ( amount of dollars spent for each saved day on full benefits ) were calculated for each experimental arm of the study , compared to st and ard care . Results : At the mean follow up of 6.4 years , all experimental study arms showed a trend towards cost benefit and cost effectiveness . These results were owing to a small number of very costly cases . The largest number of days saved from benefits was in the Sherbrooke model arm . Conclusions : A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers ’ compensation board and to save more days on benefits than usual care or partial interventions . A limited number of cases were responsible for most of the long term disability costs , in accordance with occupational back pain epidemiology . However , further studies with larger sample s will be necessary to confirm these results OBJECTIVES To determine the effectiveness and direct of two protective devices-a shielded 3 ml safety syringe ( Safety-Lok ; Becton Dickinson and Co. , Becton Dickinson Division , Franklin Lakes , N.J. ) and the components of a needleless IV system ( InterLink ; Baxter Healthcare Corp. , Deerfield , Ill.)--in preventing needlestick injuries to health care workers . DESIGN Twelve-month prospect i ve , controlled , before- and -after trial with a st and ardized question naire to monitor needlestick injury rates . SETTING Six hospital inpatient units , consisting of three medical units , two surgical units ( all of which were similar in patient census , acuity , and frequency of needlesticks ) , and a surgical-trauma intensive care unit , at a 900-bed urban university medical center . PARTICIPANTS All nursing personnel , including registered nurses , licensed practical nurses , nursing aides , and students , as well as medical teams consisting of an attending physician , resident physician , interns , and medical students on the study units . INTERVENTION After a 6-month prospect i ve surveillance period , the protective devices were r and omly introduced to four of the chosen study units and to the surgical-trauma intensive care unit . RESULTS Forty-seven needlesticks were reported throughout the entire study period , 33 in the 6 months before and 14 in the 6 months after the introduction of the protective devices . Nursing staff members who were using hollow-bore needles and manipulating intravenous lines accounted for the greatest number of needlestick injuries in the pre-intervention period . The overall rate of needlestick injury was reduced by 61 % , from 0.785 to 0.303 needlestick injuries per 1000 health care worker-days after the introduction of the protective devices ( relative risk = 1.958 ; 95 % confidence interval , 1.012 to 3.790 ; p = 0.046 ) . Needlestick injury rates associated with intravenous line manipulation , procedures with 3 ml syringes , and sharps disposal were reduced by 50 % ; however , reductions in these subcategories were not statistically significant . No seroconversions to HIV-1 or hepatitis B virus seropositivity occurred among those with needlestick injuries . The direct cost for each needlestick prevented was $ 789 . CONCLUSIONS Despite an overall reduction in needlestick injury rates , no statistically significant reductions could be directly attributed to the protective devices . These devices are associated with a significant increase in cost compared with conventional devices . Further studies must be concurrently controlled to establish the effectiveness of these devices BACKGROUND Low back injuries are common and costly , accounting for 15 to 25 percent of injuries covered by workers ' compensation and 30 to 40 percent of the payments made under that program . The high costs of injury , the lack of effective treatment . and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and h and ling . The effectiveness of those programs , however , has received little rigorous evaluation . METHODS We evaluated an educational program design ed to prevent low back injury in a r and omized , controlled trial involving about 4000 postal workers . The program , similar to that in wide use in so-called back schools , was taught by experienced physical therapists . Work units of workers and supervisors were trained in a two-session back school ( three hours of training ) , followed by three to four reinforcement sessions over the succeeding few years . Injured subjects ( from both the intervention and the control groups ) were r and omized a second time to receive either training or no training after their return to work . RESULTS Physical therapists trained 2534 postal workers and 134 supervisors . Over 5.5 years of follow-up , 360 workers reported low back injuries , for a rate of 21.2 injuries per 1000 worker-years of risk . The median time off from work per injury was 14 days ( range , 0 to 1717 ) ; the median cost was $ 204 ( range , zero to $ 190,380 ) . After their return to work , 75 workers were injured again . Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury , the median cost per injury , the time off from work per injury , the rate of related musculoskeletal injuries , or the rate of repeated injury after return to work ; only the subjects ' knowledge of safe behavior was increased by the training . CONCLUSIONS A large-scale , r and omized , controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P<0.004 ) . The back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10 & NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain To define the cost-effectiveness of a back school program in industry , a controlled longitudinal field study was carried out in a Dutch bus company . The experimental group received a program consisting of information on back care , physical fitness , nutrition , stress , and relaxation . Objective data on absenteeism were collected and compared during a 6-year period for the control and experimental groups . Results showed that a tailor-made back school program reduced absenteeism by at least 5 days per year per employee , therefore being cost-effective to industry . A reduction was not observed in incidence , but in mean length of absenteeism . This effect turned out to be persistent during a 2-year period following the program Sickness absenteeism caused by musculoskeletal disorders ( MSDs ) is a persistent and costly occupational health challenge . In a prospect i ve controlled trial , we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management . Patients with physician-diagnosed MSDs were r and omized either to the intervention group or the reference group offered the traditional case management routines . Participants filled out a comprehensive question naire at the initiation of the study and after 6 months . In addition , administrative data were collected at 0 , 6 , and 12 months after the initiation of the project . For the entire 12-month period , the total mean number of sick days for the intervention group was 144.9 ( SEM 11.8 ) days/person as compared to 197.9 ( 14.0 ) days in the reference group ( P < 0.01 ) . Compared with the reference group , employees in the intervention group significantly more often received a complete rehabilitation investigation ( 84 % versus 27 % ) . The time for doing this was reduced by half ( 59.4 ( 5.2 ) days versus 126.8 ( 19.2 ) , P < .01 ) . The odds ratio for returning to work in the intervention group was 2.5 ( 95 % confidence interval 1.2–5.1 ) as compared with the reference group . The direct cost savings were USD 1195 per case , yielding a direct benefit-to-cost ratio of 6.8 . It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability . Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial & NA ; The aim of the present study was to evaluate the outcome of a behavioral medicine ( BM ) rehabilitation program and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group ( CG ) . The study employed a 4 × 4 repeated‐ measures design with four groups and four assessment periods ( pre‐treatment , post‐treatment , 6‐month follow‐up , and 18‐month follow‐up ) . The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omized to one of four conditions , which were : ( 1 ) behavior‐oriented physical therapy ( PT ) ; ( 2 ) cognitive behavioral therapy ( CBT ) ; ( 3 ) BM rehabilitation consisting of PT+CBT ( BM ) ; ( 4 ) a ‘ treatment‐as‐usual ’ CG . The treatments were given over a period of 4 weeks , PT and CBT on a part‐time basis and BM on a full‐time basis . Outcome variables were sick leave , early retirement , and health‐related quality of life ( measured using the Short Form Health Survey , SF‐36 ) . The results showed that the risk of being granted full‐time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18‐month follow‐up period . However , the total absence from work ( sick listing plus early retirement ) in days over the 18‐month follow‐up period was not significantly different in the CG compared to the treatments . On the SF‐36 , women in CBT and BM reported a significantly better health‐related quality of life than women in the CG at the 18‐month follow‐up . No significant differences for men were found on the SF‐36 scales . In conclusion , the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program The study had two primary aims . The first aim was to combine a human re sources costing and accounting approach ( HRCA ) with a quantitative statistical approach in order to get an integrated model . The second aim was to apply this integrated model in a quasi-experimental study in order to investigate whether preventive intervention affected sickness absence costs at the company level . The intervention studied contained occupational organizational measures , competence development , physical and psychosocial working environmental measures and individual and rehabilitation measures on both an individual and a group basis . The study is a quasi-experimental design with a non-r and omized control group . Both groups involved cleaning jobs at predominantly female workplaces . The study plan involved carrying out before and after studies on both groups . The study included only those who were at the same workplace during the whole of the study period . In the HRCA model used here , the cost of sickness absence is the net difference between the costs , in the form of the value of the loss of production and the administrative cost , and the benefits in the form of lower labour costs . According to the HRCA model , the intervention used counteracted a rise in sickness absence costs at the company level , giving an average net effect of 266.5 Euros per person ( full-time working ) during an 8-month period . Using an analogue statistical analysis on the whole of the material , the contribution of the intervention counteracted a rise in sickness absence costs at the company level giving an average net effect of 283.2 Euros . Using a statistical method it was possible to study the regression coefficients in sub-groups and calculate the p-values for these coefficients ; in the younger group the intervention gave a calculated net contribution of 605.6 Euros with a p-value of 0.073 , while the intervention net contribution in the older group had a very high p-value . Using the statistical model it was also possible to study contributions of other variables and interactions . This study established that the HRCA model and the integrated model produced approximately the same monetary outcomes . The integrated model , however , allowed a deeper underst and ing of the various possible relationships and quantified the results with confidence intervals PROBLEM Few methods exist for comprehensively examining the costs and benefits of ergonomic interventions applicable to a variety of economic sectors and setting s. METHODS An instrument for data collection and data analysis at the facility level is presented . In this net-cost model intervention costs are defined by equipment and labor costs for the interventions as well as the avoided costs of lost work time , medical care , and productivity improvements . RESULTS Net-cost estimates for three case studies show that ergonomic interventions applied appropriately can result in substantial cost savings for the companies . DISCUSSION It would be prudent to incorporate a protocol for collecting cost and effectiveness data in the st and ard operating procedures of companies introducing ergonomic interventions . Validation of the net-cost model through prospect i ve studies is necessary . IMPACT ON INDUSTRY This model may be used to determine the net-cost of implemented or proposed ergonomic interventions in industrial facilities |
12,658 | 24,218,174 | Conclusion The findings of this study showed that totally implantable ports are superior to external catheters in terms of catheter-associated complications . | Purpose This systematic review and meta- analysis aim ed to evaluate the risks of complications ( infectious and non-infectious ) including the need for device removal associated with central ly inserted external catheters compared with totally implantable ports in patients undergoing chemotherapy . | This is an interval analysis of the 2-year prospect i ve multicenter Childrens Cancer Study Group study of 1,141 chronic venous access devices in 1,019 children with cancer . Device type was external catheter ( EC ) 72 % , totally implantable ( TID ) 28 % , and did not differ for diagnosis or age except more double-lumen devices in bone marrow transplant protocol s ( 77 % ) and more TIDs in children less than 1 year old ( 17.7 % ) . Insertion characteristics evaluated in 1,078 ( 95 % ) were : operating room placement 99 % ; general anesthesia 98 % ; cutdown 67 % ; percutaneous 33 % ; atrial position 50 % , caval position 50 % ; and perioperative antibiotics 48 % . Vein entry was the external jugular 33 % , internal jugular 22 % , subclavian 35 % , cephalic 7 % , and saphenous 3 % . Insertion was difficult or very difficult in only 10 % and operative complications occurred in only 0.7 % . Degree of difficulty bore no relationship to device type or patient age . The reasons for removal in 736 devices ( 67 % ) were due to complications in 39 % , of which infections were the most frequent . There was some variance between centers ranging from 8.5 % to 31 % for infection ; 2.8 % to 24 % for dislodgment ; and 0 % to 13 % for occlusion . ECs had a higher risk of dislodgment ; elective removals were more frequent in TIDs ; there was no difference in infection as a cause for removal between ECs and TIDs . Dislodgment was associated with the shortest distance of the cuff to the skin exit ( mean , 4 cm ) : less than or equal to 2 cm , 49 % ; greater than 2 cm , 28 % ( P = .009 ) and occurred most frequently in the younger patient ( 18.9 % , 0 to 1 years ; 0.5 % , greater than 8 years A group of 43 adult patients with acute leukaemia ( AL ) were r and omized to receive a double-lumen totally implantable subcutaneous port system ( PORT , n=19 ) or a double-lumen central venous catheter ( CVC , n=24 ) before induction chemotherapy . Six patients were excluded due to protocol violation ( n=4 , CVC ) and technical difficulties ( n=2 , PORT ) . A st and ardized catheter record form was used for recording of catheter function , local infection and bleeding . The study was prematurely closed due to extensive subcutaneous bleeding after placement in five patients with a PORT . Intention to treat ( n=43 ) or per protocol ( PP ) analysis ( n=37 ) did not reveal a significant difference between the two groups with regard to catheter survival time ( PP PORT , median 113 days , range 2–634 days ; CVC , 55 days , 11–223 days ) . The number of positive blood cultures per 100 central venous access device days was significantly higher in the CVC group ( median 3.6 per 100 days ) than in the PORT group ( 0.9 per 100 days ; P=0.02 ) . In addition , the time to the first blood culture positive for coagulase-negative staphylococcus was shorter in the CVC group ( median 14 days ) than in the PORT group ( 52 days ; P=0.02 ) . Despite fewer infectious complications in the PORT group the use of a double-lumen CVC is advocated in patients with AL undergoing induction treatment due to the risk of extensive local bleeding after placement of the PORT BACKGROUND The incidence of Hickman catheter sepsis is 10 % to 40 % , with result ant catheter loss in one third of infections . Urokinase causes dissolution of colonized intracatheter fibrin thrombi and may improve salvage . STUDY AIMS To evaluate the efficacy of 12-hour-interval slow-push urokinase infusion in addition to st and ard antibiotic therapy in the treatment of catheter sepsis in a pediatric oncology population . METHODS A two-arm r and omized double-blind trial was undertaken , with catheter salvage rate as the end point . Patients with Hickman catheter sepsis were r and omized after culture data confirmed the diagnosis . The study drug was administered by a slow intravenous push and given at 12-hour intervals for a total of four doses . The catheters were aspirated after 1 hour . RESULTS AND CONCLUSIONS The trial was stopped after 41 patients were entered into the study ; 18 patients received a placebo , and 23 received the urokinase . In the placebo group , six catheters were lost ; in the urokinase group , eight were lost . The rate of bacterial clearance was equivalent for both . After administration of the study drug , each group had three episodes of fever and chills ; two of these result ed in hypotension ( one in each group ) . The authors conclude that slow-push urokinase infusion during established Hickman catheter sepsis does not result in improved catheter salvage or bacterial clearance . Slow intravenous push infusions in this setting may provoke hemodynamic instability even after initiation of antibiotics From June 1982 until December 1989 , 93 permanent central venous catheters [ 59 external catheters ( ECs ) and 34 implanted catheters ( ICs ) ] were placed in 69 patients . The median age of these patients at placement was 5.6 years for ECs and 8.8 years for ICs ( P less than 0.05 ) . Follow-up evaluation was possible on 86 catheters ( 58 ECs and 28 ICs ) . The median time of insertion was 236 days and 316 days for ECs and ICs , respectively ( P less than 0.05 ) . The median number of open days was 58 for ECs and 66 for ICs ( not significant ) . 17 catheters ( 6 ECs and 11 ICs ) were transiently obstructed ( P less than 0.005 ) . 30 episodes of bacteraemia were documented in 20 patients . The incidence of catheter sepsis and bacteraemia of unknown source was one in 278 and 283 open days for ECs and ICs , respectively ( not significant ) . In this retrospective study , ECs appeared to be as safe as ICs when infection was correlated with use of the catheter , but this finding should be confirmed in a r and omised design Since 1984 , 316 subcutaneous ports ( SP ) and 339 external venous catheters ( EC ) [ Roko Catheter , The Hospital for Sick Children ( HSC ) ] have been inserted in hematology/ oncology patients at HSC . During a 22-month period ( July 1987 to April 1989 ) , a committed central line nurse ( J.I. ) prospect ively collected clinical and microbiologic data on 144 consecutive SPs and 130 consecutive ECs . Children with the SP had 0.6 infected lines and 0.7 infectious episodes per 1,000 patient days compared to 2.9 infected lines and 4.3 infectious episodes per 1,000 patient days with the EC ( p < 0.001 ) . This lower infectious complication rate with SP was demonstrated in the entire group of unselected patients and in a cohort of children with acute lymphoblastic leukemia ( ALL ) receiving intensive chemotherapy , and it was evident in all age groups . In view of the other advantages of SP – normal activity , absence of the need for home maintenance , improved body image , less expense – these data suggest that SPs are the preferred device in pediatric patients and provide effective venous access with acceptable complication rates PURPOSE To compare the frequency of infectious episodes or other problems occurring with an externalized catheter ( Hickman ) versus a subcutaneously implanted device ( Port-a-Cath , Pharmacia , Piscataway , NJ ) in cancer patients , we performed a prospect i ve , r and omized study in 100 cancer patients ( age range , 5 to 74 years ) . PATIENTS AND METHODS Patients who were chemotherapy c and i date s and required an indwelling catheter were monitored prospect ively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure . The frequency of catheter use , reason for access , and any problems that might have been related to catheter use were noted . All data were collected prospect ively and included the patient 's age , sex , underlying malignancy , temperature , and leukocyte and absolute granulocyte counts at the time of catheter insertion and when complications occurred . The time to and reason for removal of the catheter , as well as any intercurrent infectious or mechanical problems , were also determined . RESULTS Most of the infections that occurred were caused by gram-positive organisms , especially staphylococci or streptococci . A total of 22 complications ( 11 in each group ) result ed in removal of the central line . Only one infection in the Hickman catheter group and four in the Port-a-Cath group led to removal of the central line . All other infectious episodes were successfully treated without removal of the catheters . The mean device life was 230 days for the Hickman catheter and 318 days for the Port-a-Cath ( not significant ) . CONCLUSION There were no differences between the two study groups regarding incidence of documented infections or mechanical or thrombotic complications PURPOSE Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy . Since routine fibrinolytic therapy may decrease these complications , the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with st and ard heparin flushes in reducing the incidence of device-related infections and occlusions . MATERIAL S AND METHODS This study was a prospect i ve , r and omized phase III multicenter trial conducted by the Children 's Cancer Group , in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months . Study end points were time to first occlusion or time to first device-related infection . RESULTS Five hundred seventy-seven patients from 29 institutions were enrolled , of whom 51 % had external catheters and 49 % had ports . Urokinase administration result ed in fewer occlusive events than heparin ( 23 % v 31 % ; P = .02 ) , a longer time to first occlusive event ( log-rank analysis , P = .006 ) , and a 1.6-fold difference in the rate of occlusive events ( Poisson regression , P = .003 ) . Similar results were noted when comparing ports and tunneled catheters . The urokinase group also had a 1.4-fold difference in the rate of infection ( Poisson regression , P = .05 ) and longer time to first infection ( log-rank , P = .07 ) , but the difference was significant only in tunneled catheters . CONCLUSION Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration Long-term therapy of oncology patients has been facilitated by permanent indwelling central venous catheters , but catheter-related infections remain a serious complication of their use . Using a retrospective matched cohort design , we compared the risk of catheter-related infection in 47 adult solid tumor patients with right atrial Hickman catheters and 94 patients with totally implanted port catheters . Patients were matched for primary solid tumor , presence of metastases , age , gender , and date of catheter insertion . Seven of 47 patients with Hickman catheters developed catheter-related infection ( 1.8 infections/1,000 catheter days at risk ) compared with 10 of 94 patients with implanted port catheters ( 0.4/1000 catheter days , P less than 0.0002 ) . Hickman catheters were used more often for terminally ill patients than were port catheters which was a potential source of bias , but results were unchanged after stratifying patients on lifespan . Our study suggests that there are fewer infections in port than in Hickman catheters in adult patients with solid tumors , but prospect i ve r and omized studies are needed One hundred and forty-eight Hickman-Broviac ( HB ) catheters and 299 Port-a-Cath R ( PAC ) were inserted over the past 5 years at the Institut Jules Bordet . The HB catheter was associated with a complication rate of 4.1/1000 days of access , of which infections were the most common , leading to catheter removal in 22 % of patients . The average PAC remained in situ for 232.9 ( range 1 - 1298 ) days ; the complication rate was only 0.45/1000 days of access . The Hickman-Broviac catheter and the totally implanted port Port-a-Cath achieve safe and reliable venous access in cancer patients We prospect ively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period ( median follow-up , 376 days ) . Externalized catheters ( 91 Hickman [ H ] , 113 Broviac [ B ] ) and implantable ports ( n = 82 ) were compared for complications , including infection and thrombosis . The most frequent major complication of all catheters was infection , although the rates of infection varied with the duration of catheter use and were generally lower than reported by others . Overall , when catheter failures ( removal ) for infection , obstruction , or dislodgement were considered , ports had a significantly longer failure-free duration of use ( P = .0024 ) than did externalized catheters . Likewise , ports had a significantly longer infection-free ( P less than .01 ) duration of use than H and B catheters . However , differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome . In analysis of pairs matched for diagnosis , therapy , and age , ports had lower infection rates than did B catheters after 100 days ( P = .053 ) . This difference became significant at 400 days of catheter use ( P = .029 ) . Although there was a trend toward lower rates of infections for ports v H catheters , this difference was not significant . In view of our results in matched pairs , selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports . The superiority of ports for long-term use ( greater than 100 days ) needs to be confirmed in a large r and omized clinical trial Forty‐three evaluable patients with hematologic malignancies , mainly acute leukemia , were prospect ively r and omized to receive a double lumen central venous catheter or a totally implantable venous access system . The mean catheter stay was 166 days ( median , 104 days ) for the 23 double lumen catheters and 164 days ( median , 65 days ) for implanted systems . Exit site infections were not encountered in double lumen catheters , but there were two proven infections around the injection port of implanted devices . Tunnel infections did not occur . Seven double lumen catheters and four implanted systems were removed because of infection . Staphylococcus epidermidis was the predominant microorganism cultured from these catheters . Five of nine patients with double lumen catheters and catheter‐related S. epidermidis infection and the two patients with implanted systems in whom S. epidermidis was cultured were on selective gut decontamination . The pattern of infection did not seem to be influenced by this regimen . Totally implantable systems proved to be as safe as double lumen central venous lines BACKGROUND Catheter-associated blood stream infections ( CABSI ) are frequent complications encountered with cancer treatment . In order to underst and which factors might predispose to CABSIs in children and young adults , we evaluated risk for infection in association with tumor type , catheter type , and setting of occurrence . METHODS All pediatric oncology patients having a central venous catheter ( CVC ) with a tunneled external ( TE ) or totally implantable design ( TID ) were prospect ively followed for the occurrence of a CABSI for 12 months . CABSIs were defined in accordance with the guidelines published by the Centers for Disease Control , and were quantified as the number of occurrences per 1,000 device days . Rates of CABSIs were stratified by tumor histology , type of catheter design , and setting of occurrence . Statistical comparisons were made using the Mantel-Haenzel statistic and the Cox proportional hazard model . RESULTS A total of 58 CABSIs were identified in 139 patients over a period of 35,935 CVC days . The overall CABSI rate was 1.6 infections per 1,000 CVC days ( 95 % CI 1.2 , 2.1 ) . Stratified analysis demonstrated increased risk for CABSIs in hospitalized patients having TEs , and while patients with solid tumors were also at higher risk ; this association was not supported by the Cox proportional hazard model . CONCLUSION While our baseline CABSI rate was comparatively lower than for other institutions , subset analyses identified that hospitalized cancer patients having TEs are at the highest risk for developing CABSIs . Our findings may help to guide improved methods of anticipating and controlling infections in immunocompromised patients We retrospectively identified and prospect ively followed up 62 patients with 78 venous-access catheters over a 30-month period ( 15773 catheter-days ) to compare infectious complications of Broviac-Hickman catheters ( n = 33 ) and totally implantable . venous devices ( n = 45 ) in pediatric oncology patients . Demographic data and characteristics of catheter use were comparable for both groups . Significantly associated with the risk of a catheter-associated infection were ( 1 ) the percentage of time the patient was neutropenic and ( 2 ) a patient age of younger than 2 years . In the Broviac-Hickman catheter group , 14 catheter-associated infections occurred in 27 % of patients using catheters for an infection rate of 0.21/100 catheter-days . In the implantable venous device group , 13 infections occurred in 24 % of patients using catheters for an infection rate of 0.14/100 catheter-days . The relative risk of infection from Broviac-Hickman catheters compared with implantable venous devices was 1.5 , which was not significant ( 95 % confidence interval , 0.7 to 3.2 ) . Thus , the incidence of infectious complications was comparable for both catheter types A prospect i ve r and omized trial was organized at the Institut Gustave-Roussy to assess the reliability of classical external catheters ( CE ) versus totally implanted access systems ( TI ) for delivering intravenous chemotherapy for a duration of at least 6 months . The analysis was performed on the 96 patients whose implantation succeeded ( CE 46 , TI 50 ) . Failure was defined as loss of ability to function ( followed by removal ) within the 6-month period of the survey . Patients dying with functional catheters were considered as censored ( 15 cases ) at the time of death . Twenty-four access systems were removed . The removal-free curves differ significantly ( P less than 0.001 ) , favoring the TI access systems . The main reasons for removal were : catheter fall ( CE6 , ( TI 0 ) , migration ( CE 1 , TI 1 ) , infection ( CE 5 , TI 1 ) , thrombotic occlusion ( CE 1 , TI 0 ) and venous complications ( CE 1 thrombosis plus 1 pulmonary embolism , TI 1 thrombosis ) . In addition , a survey by question naire demonstrated a significantly better patient activity rate ( P = 0.02 ) and hygiene ( P less than 0.001 ) in the TI group . This prospect i ve r and omized study demonstrates that totally implanted access systems are more reliable , safer and better tolerated than classical external catheters for solid tumor patients undergoing intravenous chemotherapy for longer than 6 months |
12,659 | 26,224,582 | This systematic review found impaired knee-related QOL in ACL-deficient individuals ≥5 years after ACL rupture , compared to population norms .
Meta- analysis revealed similar knee-related QOL in ACL-deficient and ACL-reconstructed groups , and no difference in health-related QOL scores for seven of the eight SF-36 domains | BACKGROUND Physical and psychological impairments impacting quality of life ( QOL ) are common following ACL reconstruction .
Rehabilitation alone is an effective alternative to reconstruction for some patients , warranting the investigation of QOL in ACL-deficient individuals .
PURPOSE To report and compare QOL in ACL-deficient individuals with population norms and ACL-reconstructed groups , and investigate relationships between participant characteristics and QOL . | Background The additional effect of anterior cruciate ligament ( ACL ) reconstruction on muscle strength and physical performance after a structured exercise programme is not well understood . Objectives To investigate and compare muscle strength and physical performance test results after a structured exercise programme , in young active adults with acute ACL injury , between those treated with and without ACL reconstruction ( ACLR ) and to evaluate these test results as predictors of clinical outcomes 2 and 5 years after injury . Study design Prospect i ve cohort study . Methods In a treatment r and omised controlled trial of acute ACL injury ( the KANON- study ) , 87/121 young active adults underwent two muscle strength tests and five physical performance tests after a structured exercise programme ( median 37 ( IQR 24 ) weeks after injury ) . Results were presented and compared as limb symmetry indices ( LSI ) ; endpoints in predictive analyses were having a delayed ACLR over the first 5 years and self-reported knee function ( Knee injury and Osteoarthritis Outcome Score ; KOOS4 ) at 2 and 5 years . Results Overall , 74–95 % of patients had LSI≥90 % in the individual tests , with no difference between treatment groups ( p=0.08–0.92 ) . Results of the one-leg rise tests predicted KOOS4 at 2 and 5 years ( R2=0.25 and 0.24 , p=0.001 and 0.002 ) and vertical hop results predicted having a delayed ACLR over a 5-year course after injury ( p=0.048 ) in those starting with exercise alone ( n=21 ) . Conclusions After an acute ACL tear , the majority of young active adults regain physical performance and muscle strength after a structured exercise programme , with or without surgical reconstruction . Poor physical performance at the end of rehabilitation predicted worse patient-reported outcomes at 2 and 5 years regardless of treatment . Registration number : IS RCT N84752559 OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Purpose Several studies compare the short- and long-term results of anterior cruciate ligament ( ACL ) reconstruction using bone-patellar tendon-bone ( BPTB ) graft or double-looped semitendinosus and gracilis ( DLSG ) graft . However , no studies evaluate the long-term results of BPTB grafts fixed with metal interference screws and DLSG grafts fixed with the Bone Mulch Screw and the Washer Loc . This prospect i ve r and omized multicentre study has the null hypothesis that there is no difference in long-term outcome between the two procedures . Methods A total of 114 patients with a symptomatic ACL rupture were r and omized to reconstruction with either a BPTB graft ( N = 58 ) or a DLSG graft ( N = 56 ) . Follow-up was conducted after one , two and seven years . At the seven-year follow-up , 102 of the 114 patients ( 89 % ) were available for evaluation ; however , 16 of these by telephone-interview only . Results Ten patients in the BPTB group and 19 patients in the DLSG group underwent additional knee surgery ( P = 0.048 ) , two and three , respectively , of these were ACL revisions ( n.s . ) . The total flexion work was lower in the DLSG group ( P = 0.001 ) . The mean peak flexion torque and extension work , however , showed no difference between the groups . No significant differences were found between the groups regarding the Tegner activity score , the Lysholm functional score , the Knee injury and osteoarthritis outcome score ( KOOS ) , subjective knee function , anterior knee pain or mobility . There was no significant difference in laxity between the groups on the Lachman test or the KT-1,000 maximum manual force test . Conclusions Both grafts and fixation methods result ed in satisfactory subjective outcome and objective stability . Both these methods can therefore be considered as suitable alternatives for ACL reconstructions . Level of evidence II We investigated the long-term outcome of 100 patients 15 years after having been r and omly allocated to primary repair ( augmented or non-augmented ) or non-surgical treatment of an anterior cruciate ligament ( ACL ) rupture . The subjective outcome was similar between the groups , with no difference regarding activity level and knee-injury and osteoarthritis outcome score but with a slightly lower Lysholm score for the non-surgically treated group . This difference was attributed to more instability symptoms . The radiological osteoarthritis ( OA ) frequency did not differ between surgically or non-surgically treated patients , but if a meniscectomy was performed , two-thirds of the patients showed OA changes regardless of initial treatment of the ACL . There were significantly more meniscus injuries in patients initially treated non-surgically . One-third of the patients in the non-surgically treated group underwent secondary ACL reconstruction due to instability problems . In this study , ACL repair itself could not reduce the risk of OA nor increase the subjective outcome scores . However , one-third of the non-surgical treated patients were later ACL reconstructed due to instability . The status of the menisci was found to be the most important predictor of developing OA . Early ACL repair and also ACL reconstruction can reduce the risk of secondary meniscus tears . Indirectly this supports the hypothesis that early stabilization of the knee after ACL injury is advantageous for the long-term outcome Background There are conflicting results in the literature regarding the association between radiographic knee osteoarthritis ( OA ) and symptoms and function in subjects with previous anterior cruciate ligament ( ACL ) reconstruction . Aim To investigate the associations between radiographic tibiofemoral knee OA and knee pain , symptoms , function and knee-related quality of life ( QOL ) 10–15 years after ACL reconstruction . Study design Cross-sectional study . Material and methods 258 subjects were consecutively included at the time of ACL reconstruction and followed up prospect ively . The authors included the Knee Injury and Osteoarthritis Outcome Score to evaluate knee pain , other symptoms ( symptoms ) , activities of daily living and sport and recreation ( Sport/Rec ) and QOL . The subjects underwent st and ing radiographs 10–15 years after the ACL reconstruction . The radiographs were grade d with the Kellgren and Lawrence ( K&L ) classification ( grade 0–4 ) . Results 210 subjects ( 81 % ) consented to participate in the 10–15-year follow-up . Radiographic knee OA ( K&L ≥ grade 2 ) was detected in 71 % , and 24 % showed moderate or severe radiographic knee OA ( K&L grade s 3 and 4 ) . No significant associations were detected between radiographic knee OA ( K&L grade ≥2 ) and pain , function or QOL , respectively , but subjects with radiographic knee OA showed significantly increased symptoms . Severe radiographic knee OA ( K&L grade 4 ) was significantly associated with more pain , symptoms , impaired Sport/Rec and reduced QOL . Conclusion Subjects with radiographic knee OA showed significantly more symptoms than those without OA , and subjects with severe radiographic knee OA had significantly more pain , impaired function and reduced quality of life than those without radiographic knee OA 10–15 years after ACL reconstruction Background Specific guidelines for operative versus nonoperative management of anterior cruciate ligament injuries do not yet exist . Hypothesis Surgical risk factors can be used to indicate whether reconstruction or conservative management is best for an individual patient . Study Design Prospect i ve nonr and omized controlled clinical trial ; Level of evidence , 2 . Methods Patients were classified as high , moderate , or low risk using preinjury sports participation and knee laxity measurements . Early anterior cruciate ligament reconstruction ( within 3 months of injury ) was recommended to high-risk patients and conservative care to low-risk patients . It was recommended that moderate-risk patients have either early reconstruction or conservative care , according to the day of presentation . Assessment of subjective outcomes , activity , physical measurements , and radiographs was performed at mean follow-up of 6.6 years . Results Early phase conservative management result ed in more late phase meniscus surgery than did early phase reconstruction at all risk levels ( high risk , 25 % vs 6.5 % ; moderate risk , 37 % vs 7.7 % , P = . 01 ; low risk , 16 % vs 0 % ) . Early- and late-reconstruction patients ’ Tegner scores increased from presurgery to follow-up ( P < . 001 ) but did not return to preinjury levels . Early-reconstruction patients had higher rates of degenerative change on radiographs than did nonreconstruction patients ( P < . 05 ) . Conclusions Early phase reconstruction reduced late phase knee laxity , risk of symptomatic instability , and the risk of late meniscus tear and surgery . Moderate- and high-risk patients had similar rates of late phase injury and surgery . Reconstruction did not prevent the appearance of late degenerative changes on radiographs . Relationship between bone contusion on initial magnetic resonance images and the finding of degenerative changes on follow-up radiographs were not detected . The treatment algorithm used in this study was effective in predicting risk of late phase knee surgery Background Anterior cruciate ligament injuries are common in athletes , but there are few studies of long-term outcomes . Hypothesis Long-term knee function of anterior cruciate ligament-injured athletes is inferior to that of their uninjured teammates . Study Design Retrospective cohort study . Methods Thirty-three Division I-A athletes who had sustained an anterior cruciate ligament injury during their college career completed a series of question naires that assessed knee function and quality of life 2 to 14 years after injury . Their responses were compared with those of a matched cohort of their uninjured teammates . Results There were no differences in the mean Tegner scores , modified Lysholm scores , or in the scores of the SF-36 between groups . Sixteen anterior cruciate ligament-injured athletes scored A or B in the subjective portion of the International Knee Documentation Committee score and 17 scored C or D , whereas 24 control subjects scored A or B and 9 scored C or D , a statistically significant difference between groups . Five injured and 14 control athletes had participated at a professional or national team level after college . Conclusions Quality of life of elite collegiate athletes who sustained an anterior cruciate ligament injury was not significantly different from that of their uninjured teammates , but knee function differed between groups PURPOSE The purpose of the study was to quantify the amount of agreement among orthopaedic surgeons regarding the natural history of the anterior cruciate ligament (ACL)-deficient knee , surgery , and rehabilitation , and the treatment of these patients . TYPE OF STUDY Physician mail survey . METHODS Orthopaedic surgeons were r and omly selected from the American Academy of Orthopaedic Surgeons ( AAOS ) directory . Only individuals who treated or referred ACL-insufficient patients for treatment within the past year were asked to complete the 3-page survey . The survey included 25 questions regarding clinical opinion . Clinical agreement was present when 80 % or more of the surgeons agreed on the same response option . RESULTS The total number of surgeons who responded to the survey was 397 ( response rate , 54.8 % ) and the number who had treated or referred ACL-insufficient patients in the past year was 261 . Among surgeons who completed the question naire , the response rates to the individual questions ranged from 92 % to 100 % . The mean response rate for all questions was 97.4 % . The mean age of the surgeons was 48.4 years , and 35.8 % considered their practice to be a subspecialty in sports medicine or knee surgery . For 12 questions ( 48 % ) , there was clinical disagreement among the surgeons . Surgical volume was associated with clinical opinion for 16 of 25 questions ( P < or = .05 ) . CONCLUSIONS Significant variation is seen in clinical opinion and decision-making regarding ACL injuries among members of the AAOS , particularly regarding whether ACL-deficient patients can participate in all recreational sports activities , that ACL reconstruction reduces the rate of arthrosis , and on the use of braces in the postoperative period . Additionally , surgeons disagreed on the effect of 4 patient characteristics ( age over 40 , presence of pain , irreparable meniscal tear , injury involving Workers ' Compensation ) on the decision to perform surgery . Areas of significant clinical uncertainty should be the focus of future research and medical education for orthopaedic surgeons who treat ACL injuries Background Few prospect i ve long-term studies of more than 10 years have reported changes in knee function and radiologic outcomes after anterior cruciate ligament ( ACL ) reconstruction . Purpose To examine changes in knee function from 6 months to 10 to 15 years after ACL reconstruction and to compare knee function outcomes over time for subjects with isolated ACL injury with those with combined ACL and meniscal injury and /or chondral lesion . Furthermore , the aim was to compare the prevalence of radiographic and symptomatic radiographic knee osteoarthritis between subjects with isolated ACL injuries and those with combined ACL and meniscal and /or chondral lesions 10 to 15 years after ACL reconstruction . Study Design Cohort study ; Level of evidence , 2 . Methods Follow-up evaluations were performed on 221 subjects at 6 months , 1 year , 2 years , and 10 to 15 years after ACL reconstruction with bone-patellar tendon-bone autograft . Outcome measurements were KT-1000 arthrometer , Lachman and pivot shift tests , Cincinnati knee score , isokinetic muscle strength tests , hop tests , visual analog scale for pain , Tegner activity scale , and the Kellgren and Lawrence classification . Results One hundred eighty-one subjects ( 82 % ) were evaluated at the 10- to 15-year follow-up . A significant improvement over time was revealed for all prospect i ve outcomes of knee function . No significant differences in knee function over time were detected between the isolated and combined injury groups . Subjects with combined injury had significantly higher prevalence of radiographic knee osteoarthritis compared with those with isolated injury ( 80 % and 62 % , P = .008 ) , but no significant group differences were shown for symptomatic radiographic knee osteoarthritis ( 46 % and 32 % , P = .053 ) . Conclusion An overall improvement in knee function outcomes was detected from 6 months to 10 to 15 years after ACL reconstruction for both those with isolated and combined ACL injury , but significantly higher prevalence of radiographic knee osteoarthritis was found for those with combined injuries |
12,660 | 24,927,670 | Current data suggests that exercise is a feasible , safe , and promising supportive measure for neuropathic patients .
This is best documented for patients with diabetic peripheral neuropathy ( DPN ) , suggesting that endurance training has the potential to prevent the onset of and reduce the progression of DPN .
In general , balance exercises showed the highest effect on the motor as well as sensory symptoms in all types of PNP .
Conclusion Overall , balance training appears to be the most effective exercise intervention .
Studies focusing exclusively on strength , or a combination of endurance and strength , appear to have a lower impact .
For metabolically-induced neuropathies , endurance training also plays an important role . | Introduction Peripheral neuropathies ( PNPs ) encompass a large group of disorders of heterogeneous origin which can manifest themselves with sensory and /or motor deficits depending on the predominantly affected nerve fiber modality .
It represents a highly prevalent disease group which can be associated with significant disability and poor recovery .
Exercise has the potential to improve side effects of PNP .
Objective Our objective in this systematic review was to analyze exercise interventions for neuropathic patients in order to evaluate the possible benefits of exercise . | Aims /hypothesisGait characteristics and balance are altered in diabetic patients . Little is known about possible treatment strategies . This study evaluates the effect of a specific training programme on gait and balance of diabetic patients . Methods This was a r and omised controlled trial ( n = 71 ) with an intervention ( n = 35 ) and control group ( n = 36 ) . The intervention consisted of physiotherapeutic group training including gait and balance exercises with function-orientated strengthening ( twice weekly over 12 weeks ) . Controls received no treatment . Individuals were allocated to the groups in a central office . Gait , balance , fear of falls , muscle strength and joint mobility were measured at baseline , after intervention and at 6-month follow-up . Results The trial is closed to recruitment and follow-up . After training , the intervention group increased habitual walking speed by 0.149 m/s ( p < 0.001 ) compared with the control group . Patients in the intervention group also significantly improved their balance ( time to walk over a beam , balance index recorded on Biodex balance system ) , their performance-oriented mobility , their degree of concern about falling , their hip and ankle plantar flexor strength , and their hip flexion mobility compared with the control group . After 6 months , all these variables remained significant except for the Biodex sway index and ankle plantar flexor strength . Two patients developed pain in their Achilles tendon : the progression for two related exercises was slowed down . Conclusions /interpretationSpecific training can improve gait speed , balance , muscle strength and joint mobility in diabetic patients . Further studies are needed to explore the influence of these improvements on the number of reported falls , patients ’ physical activity levels and quality of life . Trial registration : Clinical Trials.gov NCT00637546 Funding : This work was supported by the Swiss National Foundation ( SNF ) : OBJECTIVE To determine the effect of a specific exercise regimen on clinical measures of postural stability and confidence in a population with peripheral neuropathy ( PN ) . DESIGN Prospect i ve , controlled , single blind study . SETTING Outpatient clinic of a university hospital . PARTICIPANTS Twenty subjects with diabetes mellitus and electrodiagnostically confirmed PN . INTERVENTION Ten subjects underwent a 3-week intervention exercise regimen design ed to increase rapidly available distal strength and balance . The other 10 subjects performed a control exercise regimen . MAIN OUTCOME MEASURES Unipedal stance time , functional reach , t and em stance time , and score on the activities-specific balance and confidence ( ABC ) scale . RESULTS The intervention subjects , but not the control subjects , showed significant improvement in all 3 clinical measures of balance and nonsignificant improvement on the ABC scale . CONCLUSION A brief , specific exercise regimen improved clinical measures of balance in patients with diabetic PN . Further studies are needed to determine if this result translates into a lower fall frequency in this high-risk population There is insufficient evidence to support the use of exercise in the management of chronic disablement in people with inflammatory peripheral neuropathy . Therefore , our study aim ed to determine the feasibility and effectiveness of a physiotherapist prescribed community based exercise programme for reducing chronic disablement in patients with stable motor neuropathy . We assessed the effects of a 12 week unsupervised , community based strengthening , aerobic and functional exercise programme on activity limitation and other measures of functioning in 16 people with stable motor neuropathy and 10 healthy control subjects . Fourteen of 16 patients and 8 out of 10 healthy control subjects completed the study and exercised safely in the community with no adverse events . Significant improvements were seen in all measures of activity limitation and in wider measures of health including anxiety , depression and fatigue in the patient group . Improvements were sustained at six months after completion of the exercise programme , except for depression . Ten patients continued to exercise regularly at six months . These findings demonstrate that individually prescribed community based exercise is feasible and acceptable for people with stable motor neuropathy and participation in exercise may be successful in reducing chronic disablement . Future r and omised controlled trials are needed to examine the efficacy of this complex community based intervention BACKGROUND Lymphoma patients undergoing therapy must cope with the side-effects of the disease itself , therapy and associated immobility . Peripheral neuropathy ( PNP ) , loss of balance control and weakness not only diminishes patients ' quality of life ( QOL ) , it can also affect planning and the dosage of therapy . Exercise may enable patients to reverse these declines , improving their performance level and QOL . PATIENTS AND METHODS We carried out a r and omized , controlled trial , assigning 61 lymphoma patients either to a control group ( CG ; N=31 ) or to a 36-week intervention ( IG ; N=30 ) , consisting of sensorimotor- , endurance- and strength training twice a week . Primary end point was QOL ; secondary end points included movement coordination , endurance , strength and therapy-induced side-effects . RESULTS Intergroup comparison revealed improved QOL- ( ΔT1-T0 ; P=0.03 ) and PNP-related deep sensitivity in the IG : 87.5 % were able to reduce the symptom , compared with 0 % in the CG ( P<0.001 ) . Significant differences in the change of balance control could be found between the groups , with the IG improving while the CG steadily declined ( monopedal static ΔT3-T0 ; P=0.03 ; dynamic ΔT3-T0 ; P=0.007 ; perturbed mono-ΔT3-T0 ; P=0.009 and bipedal ΔT3-T0 ; P=0.006 ) , failed attempts ( monopedal static ΔT3-T0 ; P=0.02 , dynamic ΔT3-T0 ; P<0.001 and perturbed ΔT3-T0 ; P=0.006 ) and improved time to regain balance ( ΔT3-T0 ; P=0.04 ) . Moreover , the change in the aerobic performance level ( ΔT3-T0 ; P=0.05 ) and additional amount of exercise carried out per week [ metabolic equivalent ( MET ) ; P=0.02 ] differed significantly across groups . CONCLUSIONS Exercise , especially sensorimotor training , is a feasible and promising method to support cancer patients during therapy . It improves patients QOL , reduces restrictions from side-effects such as PNP and improves patients ' balance control , physical performance level and mobility . GERMAN CLINICAL TRIALS REGISTER NUMBER DRKS00003894 This study was design ed to determine whether a 6-month Tai Chi exercise program can improve self-reported physical functioning limitations among healthy , physically inactive older individuals . Ninety-four community residents ages 65 to 96 ( M age = 72.8 years , SD = 5.1 ) volunteered to participate in the study . Participants were r and omly assigned to either a 6-month experimental ( Tai Chi ) group ( n = 49 ) , which exercised twice per week for 60 min , or a wait-list control group ( n = 45 ) . A 6-item self-report physical functioning scale , assessing the extent of behavioral dysfunction caused by health problems , was used to evaluate change in physical functioning limitations as a result of Tai Chi intervention . Results indicated that compared to the control group , participants in the Tai Chi group experienced significant improvements in all aspects of physical functioning over the course of the 6-month intervention . Overall , the experimental group had 65 % improvement across all 6 functional status measures ranging from daily activities such as walking and lifting to moderate-vigorous activities such as running . It was concluded that the 6-month Tai Chi exercise program was effective for improving functional status in healthy , physically inactive older adults . A self-paced and self-controlled activity such as Tai Chi has the potential to be an effective , low-cost means of improving functional status in older persons OBJECTIVE To assess the efficacy of a balance rehabilitation treatment by using both a powered platform on which subjects st and and specific physical exercises ( EXs ) . DESIGN Crossover trial . SETTING Physical and rehabilitation medicine department in Italy . PARTICIPANTS Patients ( N=33 ) with balance disorders ( 14 vestibular origin , 19 peripheral neuropathy origin ) . INTERVENTIONS Patients underwent powered platform then EX treatment ( n=17 ) ; the other 16 received the same treatments in reverse order . powered platform consisted of balancing on a sinusoidally oscillating powered platform ( in anteroposterior and laterolateral directions in separate trials ) with eyes open and closed . A physical therapist administered Cawthorne-Cooksey EXs for patients with vestibular disorders and modified Frenkel EXs for patients with neuropathy . Treatment lasted 1 hour a day for 10 consecutive days , except for the weekend . MAIN OUTCOME MEASURES Body sway area , subjective score of stability , balance and gait scores , and amplitude of head displacement while balancing on the oscillating powered platform were recorded before , ( t0 ) after the first ( t1 ) , and after the second treatment ( t2 ) , regardless of the powered platform or EX order . RESULTS On average , all participants improved balance regardless of the order of treatments , and more so at t2 than t1 . Improvement was observed by using instrumental evaluations and balance and gait scales . In both patient groups , powered platform treatment proved to be as effective as EX in improving balance . This effect was stronger in patients with vestibular disorders , independently of order of treatment . CONCLUSIONS Balance rehabilitation with either EX or powered platform is effective in patients with balance disorders of vestibular or neuropathic origin . These findings point to the value of either or both physical EXs and powered platform in increasing stability and potentially decrease the risk of falling in patients with neuropathy , for whom few results are documented in the literature BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001 , for both ) . The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P<.05 , and 29.8 % vs. 6.45 % , P<.05 , respectively ) . In addition , the percentage of diabetic patients who developed increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P<.05 ) . Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05 ) ; no significant change in Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN Background : Pain is a common symptom in peripheral neuropathies . The factors determining why some peripheral neuropathies are painful and others are not are incompletely understood . Pro-inflammatory cytokines have been implicated to play a crucial role in the generation of pain . Objective : To investigate whether cytokine profiles differ between patients with painful or painless neuropathy . Methods : In this prospect i ve study , we analyzed blood mRNA and protein levels of the pro-inflammatory cytokines interleukin-2 ( IL-2 ) and tumor necrosis factor-α ( TNF ) and the anti-inflammatory cytokines IL-4 and IL-10 in 32 patients with painful neuropathy , 20 patients with painless neuropathy , and 38 healthy control subjects , using quantitative real-time PCR and ELISA . Results : Patients with a painful neuropathy had about twofold higher IL-2 mRNA ( p = 0.001 ) and TNF mRNA ( p < 0.0001 ) and protein levels ( p = 0.009 ) than healthy control subjects and about twofold higher IL-2 and TNF mRNA ( p = 0.03 ; p = 0.001 ) and protein levels ( p = 0.04 ; p = 0.04 ) than patients with painless neuropathy . In contrast , mRNA levels of the anti-inflammatory cytokine IL-10 were about twofold higher in patients with painless neuropathy than in patients with painful neuropathy ( p = 0.001 ) and controls ( p = 0.004 ) . IL-4 protein levels were 20-fold higher in patients with painless neuropathy ( p < 0.0001 ) and 17-fold higher in patients with painful neuropathy ( p < 0.0001 ) than in healthy control subjects . Conclusions : A pro-inflammatory cytokine profile seems to be associated with pain in the setting of a peripheral neuropathy , corroborating findings in animal models with experimental painful neuropathies . This may have implication s for future treatment strategies PURPOSE The aim of this study was to determine the effects of Tai Chi exercise on glucose control , neuropathy scores , balance , and quality of life in patients with type 2 diabetes and neuropathy . METHODS A pretest-posttest design with a nonequivalent control group was utilized to recruit 59 diabetic patients with neuropathy from an outpatient clinic of a university hospital . A st and ardized Tai Chi for diabetes program was provided , which comprised 1 hour of Tai Chi per session , twice a week for 12 weeks . Outcome variables were fasting blood glucose and glycosylated hemoglobin for glucose control , the Semmes-Weinstein 10-g monofilament examination scores and total symptom scores for neuropathy , single leg stance for balance , and the Korean version of the SF-36v2 for quality of life . Thirty-nine patients completed the posttest measures after the 12-week Tai Chi intervention , giving a 34 % dropout rate . RESULTS The mean age of the participants was 64 years , and they had been diagnosed with type 2 diabetes for more than 12 years . The status was significantly better for the participants in the Tai Chi group ( n=20 ) than for their control ( i.e. , nonintervention ) counterparts ( n=19 ) in terms of total symptom scores , glucose control , balance , and quality of life . CONCLUSION Tai Chi improved glucose control , balance , neuropathic symptoms , and some dimensions of quality of life in diabetic patients with neuropathy . Further studies with larger sample s and long-term follow-up are needed to confirm the effects of Tai Chi on the management of diabetic neuropathy , which may have an impact on fall prevention in this population OBJECTIVE The prevalence of type 2 diabetes , especially in developing countries , has grown over the past decades . We performed a controlled clinical study to determine whether a community-based , group-centered public health intervention addressing nutrition and exercise can ameliorate glycemic control and associated cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica . RESEARCH DESIGN AND METHODS A total of 75 adults with type 2 diabetes , mean age 59 years , were r and omly assigned to the intervention group or the control group . All participants received basic diabetes education . The subjects in the intervention group participated in 11 weekly nutrition classes ( 90 min each session ) . Subjects for whom exercise was deemed safe also participated in triweekly walking groups ( 60 min each session ) . Glycosylated hemoglobin , fasting plasma glucose , total cholesterol , triglycerides , HDL and LDL cholesterol , height , weight , BMI , and blood pressure were measured at baseline and the end of the study ( after 12 weeks ) . RESULTS The intervention group lost 1.0 + /- 2.2 kg compared with a weight gain in the control group of 0.4 + /- 2.3 kg ( P = 0.028 ) . Fasting plasma glucose decreased 19 + /- 55 mg/dl in the intervention group and increased 16 + /- 78 mg/dl in the control group ( P = 0.048 ) . Glycosylated hemoglobin decreased 1.8 + /- 2.3 % in the intervention group and 0.4 + /- 2.3 % in the control group ( P = 0.028 ) . CONCLUSIONS Glycemic control of type 2 diabetic patients can be improved through community-based , group-centered public health interventions addressing nutrition and exercise . This pilot study provides an economically feasible model for programs that aim to improve the health status of people with type 2 diabetes Peripheral neuropathy is a common complaint of diabetes . Peripheral neural damage in turn will cause balance impairments in diabetic patients . The purpose of this study was to investigate the effects of balance exercises on sway indices in diabetic patients with neuropathy . In this clinical trial study , 10 diabetic patients with peripheral neuropathy were recruited through simple nonprobability sampling along with 10 nondisabled aged-matched subjects . Participants in both groups were examined for balance abilities with the Biodex Balance System before intervention . The experimental group was tested again after intervention . Intervention consisted of progressive Biodex stability and rocker and wobble-board training for 10 sessions . All tests were done in eyes open and closed conditions with bilateral st and ing . After intervention , the experimental group was re-examined in the same way . Student and paired t-tests were used for data analysis . The overall stability index and anterior-posterior stability index were significantly decreased after treatment in the experimental group during different conditions . Balance indices in the experimental group were significantly higher than the control group before treatment . There was no significant difference in indices between the two groups after treatment . The results show that balance training can improve stability indices in diabetic patients with neuropathy BACKGROUND Aging adversely affects balance and increases the propensity to slip and fall . Loss of plantar sensation due to diabetic peripheral neuropathy and other diseases has been shown to further increase this propensity to fall . The ancient Chinese art of Tai Chi has been previously shown as a method to improve balance in healthy elderly adults . METHODS The aim of this study was to determine if Tai Chi intervention improved both balance and plantar sensory perception in healthy elderly adults and elderly adults with diabetes and plantar sensory loss . Elderly subjects ( mean + /- SD age = 73.1 + /- 5.9 years , n = 18 ) were tested for plantar sensory ability and several balance metrics before Tai Chi training and again after 6 months of weekly sessions . Participants were grouped by initial sensory perception scores ( as measured by a vibrometer ) in order to make inferences on the effects of Tai Chi on sensory perception . RESULTS Plantar sensation results show all participants showed significant improvement in sensory ability with the 6 months of Tai Chi training . All groups also had a general improvement in all balance measures , with the greatest improvement seen in those subjects with large sensory losses . Hemoglobin A1C measurements also decreased as a result of the intervention . CONCLUSION This study demonstrates the effectiveness of Tai Chi training as a method of improving plantar sensation and balance in elderly adults and elderly adults with diabetes with a large plantar sensation loss OBJECTIVE To evaluate the effect of moderate intensity aerobic exercise ( 40%-60 % of Heart Rate Reserve ( HRR ) ) on diabetic peripheral neuropathy . METHODS A parallel-group , r and omized controlled trial was carried out in a tertiary health care setting , India . The study comprised of experimental ( moderate intensity aerobic exercise and st and ard care ) and control groups ( st and ard care ) . Population with type 2 diabetes with clinical neuropathy , defined as a minimum score of seven on the Michigan Diabetic Neuropathy Score ( MDNS ) , was r and omly assigned to experimental and control groups by computer generated r and om number tables . RANOVA was used for data analysis ( p<0.05 was significant ) . RESULTS A total of 87 patients with DPN were evaluated in the study . After r and omization there were 47 patients in the control group and 40 patients in the experimental group . A comparison of two groups using RANOVA for anthropometric measures showed an insignificant change at eight weeks . For distal peroneal nerve 's conduction velocity there was a significant difference in two groups at eight weeks ( p<0.05 ) , Degrees of freedom (Df)=1 , 62 , F=5.14 , and p=0.03 . Sural sensory nerve at eight weeks showed a significant difference in two groups for conduction velocity , Df = 1 , 60 , F=10.16 , and p=0.00 . Significant differences in mean scores of MDNS were also observed in the two groups at eight weeks ( p value significant<0.05 ) . CONCLUSION Moderate intensity aerobic exercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes OBJECTIVE To determine the effect on balance and strength of 3 months of intensive balance and /or weight training followed by 6 months of low intensity Tai Chi training for maintenance of gains . DESIGN R and omized control intervention . Four groups in 2 x 2 design : Control , Balance , Strength , Balance + Strength , using blinded testers . SETTING Exercise and balance laboratory at University of Connecticut Health Center . PARTICIPANTS Subjects were 110 healthy community dwellers ( mean age 80 ) who were free of dementia , neurological disease , and serious cardiovascular or musculoskeletal conditions . INTERVENTIONS Short-term training ( 3 months ) occurred 3 times/week ( 45 minutes Balance and Strength , 90 minutes Balance + Strength ) . Balance training included equilibrium control exercises of firm and foam surfaces and center-of-pressure biofeedback . Strengthening consisted of lower extremity weight-lifting . All subjects than received long-term group Tai Chi instruction ( 6 months , 1 hour , 1 time/week ) . MEASUREMENTS Losses of balance during Sensory Organization Testing ( LOB ) , single stance time ( SST ) , voluntary limits of stability ( FBOS ) , summed isokinetic torque of eight lower extremity movements ( ISOK ) , and usual gait velocity ( GVU ) . RESULTS AND CONCLUSIONS Balance training meaningfully improved all balance measures by restoring performance to a level analogous to an individual 3 to 10 years younger : LOB = -2.0 + /- 0.3 ( adjusted paired differences , P < .005 ANOVA ) ; SST = 7.0 + /- 1.2 sec ; and FBOS = 9.0 + /- 2.0 % of foot length ( P < .05 ) . Strengthening increased ISOK by 1.1 + /- 0.1 Nm kg-1 ( P < .005 ) . There was no interaction between balance and strength training . Significant gains persisted after 6 months of Tai Chi , although there was some decrement BACKGROUND AND PURPOSE The effects of a home exercise program for persons with chronic peripheral neuropathies ( CPN ) have not been documented . We compared changes in impairment and health-related quality of life ( HRQL ) between exercise and control groups , investigated the relationship between HRQL and measures of impairment , and contrasted the HRQL of individuals with CPN to that previously described for the general population . SUBJECTS Twenty-eight subjects with CPN , aged 23 to 84 years ( mean = 56.2 , SD = 14.9 ) , completed the study . METHODS Impairment measures included average muscle score ( AMS ) , h and grip force , walking time , and forced vital capacity . The HRQL instrument measured the eight scales of the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the component scales . The exercise group ( n = 14 ) completed a 6-week home exercise program . The control group ( n = 14 ) did not participate in a home exercise program . RESULTS There was an increase in the AMS in the exercise group compared with the control group . No other between-group differences were found . The exercise group improved in scores on the role limitation scales of the SF-36 . The AMS and walking time were moderately correlated with the physical function scale of the SF-36 ( r = .55 and -.62 , respectively ) . The SF-36 scores of individuals with CPN were lower than scores previously described for the general population . CONCLUSION AND DISCUSSION The home exercise program appears to be an important component of the treatment of persons with CPN . Compared with the general population , patients with CPN appear to have a lower HRQL , but some areas appear to improve following a home exercise program Bed rest is a recognized model for muscle atrophy and bone loss in space flight and in clinical medicine . We hypothesized that whole body vibration in combination with resistive exercise ( RVE ) would be an effective countermeasure . Twenty healthy male volunteers underwent horizontal bed rest for 56 days and were r and omly assigned either to a group that performed RVE 11 times per week or to a group that underwent bed rest only ( Ctrl ) . Bone mineral content ( BMC ) was assessed by peripheral quantitative computed tomography ( pQCT ) in the tibia and the radius and by dual x-ray absorptiometry ( DXA ) in the hip and lumbar spine at baseline and at regular intervals during bed rest and a 12-month follow-up . RVE appeared to protect muscle size and function , and it also prevented bone loss ( p-values between < 0.001 and 0.01 ) . Bone losses were largest in the distal tibia epiphysis , where BMC declined from 421.8 mg/mm ( SD 51.3 ) to 406.6 mg/mm ( SD 52.7 ) in Ctrl , but only from 411.1 mg/mm ( SD 56.6 ) to 409.6 mg/mm ( SD 66.7 ) in RVE . Most of the BMC losses were recovered by 12-month follow-up . Analyses showed that the epiphyseal cortex , rather than spongiosa , depicted the most pronounced changes during bed rest and recovery . These results suggest that the combined countermeasure applied in this study is effective to prevent bone losses from the tibia . This underlines the importance of mechanical usage for the maintenance of the human skeleton Background Ankle sprains are the most common injuries in a variety of sports . Hypothesis A proprioceptive balance board program is effective for prevention of ankle sprains in volleyball players . Study Design Prospect i ve controlled study . Methods There were 116 male and female volleyball teams followed prospect ively during the 2001 - 2002 season . Teams were r and omized by 4 geographical regions to an intervention group ( 66 teams , 641 players ) and control group ( 50 teams , 486 players ) . Intervention teams followed a prescribed balance board training program ; control teams followed their normal training routine . The coaches recorded exposure on a weekly basis for each player . Injuries were registered by the players within 1 week after onset . Results Significantly fewer ankle sprains in the intervention group were found compared to the control group ( risk difference = 0.4/1000 playing hours ; 95 % confidence interval , 0.1 - 0.7 ) . A significant reduction in ankle sprain risk was found only for players with a history of ankle sprains . The incidence of overuse knee injuries for players with history of knee injury was increased in the intervention group . History of knee injury may be a contraindication for proprioceptive balance board training . Conclusions Use of proprioceptive balance board program is effective for prevention of ankle sprain recurrences Background Polyneuropathy is a complication of diabetes mellitus that has been very challenging for clinicians . It results in high public health costs and has a huge impact on patients ' quality of life . Preventive interventions are still the most important approach to avoid plantar ulceration and amputation , which is the most devastating endpoint of the disease . Some therapeutic interventions improve gait quality , confidence , and quality of life ; however , there is no evidence yet of an effective physical therapy treatment for recovering musculoskeletal function and foot rollover during gait that could potentially redistribute plantar pressure and reduce the risk of ulcer formation . Methods / Design A r and omised , controlled trial , with blind assessment , was design ed to study the effect of a physiotherapy intervention on foot rollover during gait , range of motion , muscle strength and function of the foot and ankle , and balance confidence . The main outcome is plantar pressure during foot rollover , and the secondary outcomes are kinetic and kinematic parameters of gait , neuropathy signs and symptoms , foot and ankle range of motion and function , muscle strength , and balance confidence . The intervention is carried out for 12 weeks , twice a week , for 40 - 60 min each session . The follow-up period is 24 weeks from the baseline condition . Discussion Herein , we present a more comprehensive and specific physiotherapy approach for foot and ankle function , by choosing simple tasks , focusing on recovering range of motion , strength , and functionality of the joints most impaired by diabetic polyneuropathy . In addition , this intervention aims to transfer these peripheral gains to the functional and more complex task of foot rollover during gait , in order to reduce risk of ulceration . If it shows any benefit , this protocol can be used in clinical practice and can be indicated as complementary treatment for this disease . Trial Registration Clinical Trials.gov Identifier : OBJECTIVE To examine the effect of tai chi chuan exercise on peripheral nerve modulation in patients with type 2 diabetes mellitus . DESIGN Parallel group comparative study with a pre- and post- design . SUBJECTS Twenty-eight participants with diabetes mellitus and 32 healthy adult controls from communities in Kaohsiung , Taiwan . METHODS Cheng 's tai chi chuan , 3 times a week for 12 weeks . Fasting blood glucose levels , insulin resistance index and nerve conduction studies were measured . RESULTS A 12-week tai chi chuan programme significantly improved fasting blood glucose ( p = 0.035 ) and increased nerve conduction velocities in all nerves tested ( p = 0.046 , right ; p = 0.041 , left ) in diabetic patients . Tai chi chuan exercise did not advance the nerve conduction velocities of normal adults ; however , it significantly improved the motor nerve conduction velocities of bilateral median and tibial nerves , and distal sensory latencies of bilateral ulnar nerves in diabetic patients . Tai chi chuan exercise had no significant effect on amplitudes of all nerves tested in diabetic patients . CONCLUSIONS Results from this study suggest that fasting blood glucose and peripheral nerve conduction velocities in diabetic patients can be improved by 12 weeks tai chi chuan exercise . A further larger r and omized controlled clinical trial with longer follow-up time is needed A r and omized clinical trial on the effects of strength training was performed in myotonic dystrophy ( MyD ) patients and patients with hereditary motor and sensory neuropathy ( HMSN ) . Training and most measurement tools involved the proximal lower extremity muscles . The participants trained 3 times a week for 24 weeks with weights adapted to their force . Strength was evaluated by isokinetically measured knee torque . Fatiguability was assessed by the time an isometric contraction could be sustained . Functional performance was measured by timed motor performance and by question naires on functional performance . Serum myoglobin ( Mb ) levels were determined to detect changes in muscle fiber membrane permeability . The MyD group included 33 participants , and the HMSN group included 29 participants . Within each diagnostic group , patients were individually matched and subsequently r and omized for treatment allocation . In the MyD patients , none of the measurement techniques showed any training effect . Neither were there signs of deterioration caused by the training . In the HMSN group , knee torques increased . Timed motor performance did not change , although the question naires showed an improvement on items related to upper-leg function . Mb levels did not change significantly as a result of the training . In conclusion , the MyD group showed neither positive nor negative effects of the training protocol , whereas the training produced a moderate increase in strength and leg-related functional performance in the HMSN group The purpose of this study was to determine the effects of Tai Chi exercise among older women . Multiple regression analysis revealed statistically significant improvements in scores for balance ( p < .001 ) , functional mobility ( p < .05 ) , and fear of falling ( p < .001 ) and associated demographic factors . Three months of twice weekly , 30-minute Tai Chi classes was associated with statistically significant improvements in balance and functional mobility and a reduction in the fear of falling in this sample of older women living in retirement communities . T'ai Chi exercises may be an age-appropriate and acceptable form of exercise for older women Falls in the elderly constitute a growing public health problem . This r and omized controlled trial investigated the potential benefit of 6 months of whole body vibration ( WBV ) training and /or vitamin D supplementation on balance , functionality and estimated fall risk in institutionalized elderly women . A total of 113 women ( mean age : 79.6 ) were r and omly assigned to either a WBV or a no-training group , receiving either a conventional dose ( 880 IU/d ) or a high dose ( 1600 IU/d ) of vitamin D3 . The WBV group performed exercises on a vibration platform 3 × /week . Balance was evaluated by computerized posturography . Functionality was assessed by 10 m walk test , Timed up and Go ( TUG ) performance and endurance capacity ( Shuttle Walk ) . Fall risk was determined with the Physiological Profile Assessment . Performance on the 10 m walk test and on TUG improved over time in all groups . For none of the parameters , high-dose vitamin D result ed in a better performance than conventional dosing . The improvements in the WBV group in endurance capacity , walking at preferred speed , and TUG were significantly larger than the changes with supplementation alone . No additional benefit of WBV training could be detected on fall risk and postural control , although sway velocity and maximal isometric knee extension strength improved only in the WBV group . This trial showed that a high-dose vitamin D supplementation is not more efficient than conventional dosing in improving functionality in institutionalized elderly . WBV training on top of vitamin D supplementation provided an added benefit with regard to walking , TUG performance , and endurance capacity Background Weight-bearing exercise has been discouraged for people with diabetes mellitus and peripheral neuropathy ( DM+PN ) . However , people with diabetes mellitus and insensate feet have an increased risk of falling . Lower-extremity exercise and balance training reduce fall risk in some older adults . It is unknown whether those with neuropathy experience similar benefits . Objective As part of a study of the effects of weight-bearing exercise on foot ulceration in people with DM+PN , the effects of a lower-extremity exercise and walking intervention on balance , lower-extremity strength ( force-generating capacity ) , and fall incidence were determined . Design The study was an observer-masked , 12-month r and omized controlled trial . Setting Part 1 of the intervention took place in physical therapy offices , and part 2 took place in the community . Patients The participants were 79 people who were mostly sedentary , who had DM+PN , and who were r and omly assigned to either a control group ( n=38 ) or an intervention group ( n=41 ) . Intervention Part 1 included leg strengthening and balance exercises and a graduated , self-monitored walking program ; part 2 included motivational telephone calls . Both groups received regular foot care , foot care education , and 8 sessions with a physical therapist . Measurements The measurements collected were strength , balance , and participant-reported falls for the year after enrollment . Results There were no statistically significant differences between the groups for falls during follow-up . At 12 months , there was a small increase in the amount of time that participants in the intervention group could st and on 1 leg with their eyes closed . No other strength or balance measurements differed between the groups . Limitations The study was design ed to detect differences in physical activity , not falls . The intensity of the intervention was insufficient to improve strength and balance in this population . Conclusions The training program had a minimal effect on participants ' balance and lower-extremity strength . Increasing weight-bearing activity did not alter the rate of falling for participants in the intervention group relative to that for participants in the control group . People who are sedentary and who have DM+PN appear to be able to increase activity without increasing their rate of falling BACKGROUND Diabetes is the most common cause of peripheral neuropathies . No definitive treatment for diabetic neuropathies has been reported , and very few studies have been published on the role of exercise in reducing either the symptoms or incidence of diabetic neuropathies . METHODS This study assessed the effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies . Thirty-eight patients with diabetes having peripheral neuropathies were enrolled , r and omized , and subdivided in two groups : an experimental group of 19 participants with diabetes ( 72.9 ± 5.6 years old ) and a control group of 19 participants with diabetes ( 73.2 ± 5.4 years old ) . Both groups received health education on diabetes for 50 min/week for 8 weeks . The experimental group practice d an additional balance exercise program for 60 min , two times a week . The exercise training was performed two times per week for 8 weeks . Results were evaluated by both static and dynamic balance and trunk proprioception . RESULTS Postural sway significantly decreased ( P < 0.05 ) , the one-leg stance test significantly increased ( P < 0.05 ) , and dynamic balance from the Berg Balance Scale , Functional Reach Test , Timed Up and Go test , and 10-m walking time improved significantly after balance exercise ( P < 0.05 ) . Trunk repositioning errors also decreased with training ( P < 0.05 ) . CONCLUSION The balance exercise program improved balance and trunk proprioception . These results suggested that a balance exercise is suitable for individuals with diabetic neuropathy Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls . However , the information available on how such falls can be prevented is scarce . We investigated the effects of whole-body vibration ( WBV ) combined with a balance exercise program on balance , muscle strength , and glycosylated hemoglobin ( HbA1c ) in elderly patients with diabetic peripheral neuropathy . Fifty-five elderly patients with diabetic neuropathy were r and omly assigned to WBV with balance exercise group , balance exercise ( BE ) group , and control group . The WBV and BE groups performed the balance exercise program for 60 min per day , 2 times per week , for 6 weeks . Further , the WBV group performed WBV training ( up to 3 × 3 min , 3 times per week , for 6 weeks ) . The control group did not participate in any training . The main outcome measures were assessed at baseline and after 6 weeks of training ; namely , we assessed the postural sway and one leg stance ( OLS ) for static balance ; Berg balance scale ( BBS ) , timed up- and -go ( TUG ) test , and functional reach test ( FRT ) for dynamic balance ; five-times-sit-to-st and ( FTSTS ) test for muscle strength ; and HbA1c for predicting the progression of diabetes . Significant improvements were noted in the static balance , dynamic balance , muscle strength , and HbA1c in the WBV group , compared to the BE and control groups ( P < 0.05 ) . Thus , in combination with the balance exercise program , the short-term WBV therapy is beneficial in improving balance , muscle strength and HbA1c , in elderly patients with diabetic neuropathy who are at high risk for suffering falls Background : Assessment of chemotherapy-induced peripheral neuropathy signs and symptoms has been hampered because of the lack of simple , reliable , and valid measures . Objective : The study objective was to examine the internal consistency and interrater reliability as well as the structural validity of a 5-component total neuropathy score-reduced ( TNSr ) variant and a chemotherapy-induced neuropathy-specific Neuropathic Pain Scale . Methods : One hundred seventeen out patients receiving taxanes or platinums were assessed by a consistent nurse practitioner using the 2 instruments . Ten subjects participated in interrater reliability testing . Results : Mean scores and SDs for individual items were low . The strength item was deleted because of low interitem correlations and a floor effect . The reflex item was deleted because of low interitem correlations and its negative influence on Cronbach & agr;. Pin sensibility was deleted because of low factor loadings . The TNSr-short form and the chemotherapy-induced neuropathy-specific Neuropathic Pain Scale formed 2 distinct factors , providing evidence of structural validity . Cronbach & agr ; 's for the 2 instruments were .80 and .96 , respectively . The TNSr interrater reliability results suggested acceptable rater concordance , but minor revisions could further improve scoring precision . Conclusion : Clinimetric evidence supports the use of 2 new instruments when monitoring taxane- and platinum-related neuropathy and pain . Further instrument modifications are recommended , followed by additional testing in diverse population s. Implication s for Practice : With these new instruments , nurses can more easily incorporate prospect i ve neuropathy assessment into daily clinical practice . The outcome will be improved symptom awareness by oncology clinicians and patients , leading to fewer chemotherapy-induced peripheral neuropathy-related devastating effects on functionality and quality of life Previous studies revealed that adaptations following sensorimotor training , performed to improve functional joint or postural stability , were characterized by improvements in the rate of force development during maximum voluntary isometric contraction . In classical strength training studies using intense loads it has been shown that improvements in rate of force development is mainly due to adaptations in the intramuscular coordination . The purpose of the present study was to compare possible neuromuscular adaptations in two training groups following either sensorimotor or classical strength training over a period of four weeks . Additionally a control group was investigated to contrast the adaptations seen after training . Postural stability , maximum voluntary isometric contraction and performance in squat-jump and in drop-jump were measured before and after training . The results confirmed the positive effects of both training regimen on rate of force development and on maximum strength during maximum voluntary contraction as well as on jump performance , while only the improvements after the strength training were significant . Strength training reduced iMEG , while it was enhanced after sensorimotor training in most testing situations . Strength training had positive effects also on concentric contractions like squat-jump . The sensorimotor training improved performance in reactive drop-jump by enhanced neuromuscular activity immediately after ground contact . It is concluded that classical strength training with high loads basically improves the mechanical efficiency of the efferent drive on the motoneurons , whereas sensorimotor training alters the afferent input on the central nervous system . Both adaptations yield to specific effects during force development The unsatisfactory results associated with conventional treatments for symptoms of diabetic peripheral neuropathy ( DPN ) demonstrate a need for research into alternative therapies . The purpose of this study was to determine the efficacy of whole body vibration therapy ( WBV ) as a treatment for pain associated with DPN . Participants ( n = 8) with painful DPN received three treatment sessions per week for four weeks . Each session consisted of four bouts of 3 min of vibration ( frequency 25 Hz , amplitude 5 mm ) . The primary outcome measures were changes in the visual analog pain scale ( VAS ) and changes in the neuropathic pain scale ( NPS ) . WBV demonstrated a significant ( p < 0.05 ) acute pain reduction in the VAS , and a significant chronic reduction in both the VAS and NPS scales . No side-effects were observed during this study . WBV appears to be an effective , non-invasive treatment for pain associated with DPN The purpose of this study was to investigate the effects of a vibration training protocol and a conventional strength training program consisting of similar exercises on knee extensors and flexors strength and postural sway in middle-aged women . 38 women were r and omly assigned into a Vibration Group ( n=12 , static and dynamic exercises on a vibration plate , frequency : 15 - 25 Hz , amplitude : 2 - 12.8 cm ) , a Strength Group ( n=16 , same exercises without vibration ) and a Control Group ( n=10 ) . Both experimental groups trained for 12 weeks ( 3 sessions/w ) . Static balance was assessed in 3 tasks of increasing difficulty : Normal Quiet Stance , Sharpened T and em , and One-Legged Stance . Postural sway was evaluated using the Centre of Pressure variations in the Anterior/Posterior and Medio/Lateral direction . Eccentric and concentric strength of knee extensors and flexors was recorded using a Cybex dynamometer . After vibration training , postural sway significantly decreased in both directions for the vibration group in all tasks ( p<0.05 ) , whereas no significant differences were observed for the other groups . Isokinetic strength significantly ( p<0.05 ) increased for both experimental groups at selected angular velocities . It was concluded that side-alternating vibration could have beneficial effects on static balance control for middle-aged women . Gains in isokinetic strength were quite similar for both experimental groups Purpose . To quantitatively evaluate the effects of dynamic balance training in patients with hereditary sensory motor neuropathy ( HSMN ) . Methods . Sixteen patients with HSMN were r and omly assigned to either an experimental or control group . The intervention session consisted of passive stretching , muscle strengthening and dynamic balance training during st and ing and stepping , which differed in that the experimental group used commercially available balance training mechanical apparatus while the patients from the control group were physically managed by a physiotherapist . The intervention period was 12 days . Balance and mobility functions were assessed by means of Berg Balance Scale , Up&go test and 10-m walk test before and after the intervention period . Results . The within-group comparison ( 1-way repeated measures ANOVA ) for the experimental group showed statistically significant improvement ( p < 0.05 ) in Berg Balance Scale , Up&go test and 10-m walk test , while within-group comparison for the control group showed statistically significant improvement only in Berg Balance Scale ( p < 0.05 ) . The between-group comparison ( 2-way ANOVA ) showed larger improvement in the experimental group , however , these differences were not statistically significant . Conclusion . Dynamic balance training is useful training modality for patients with HSMN . When exercised in the balance training mechanical apparatus used in this study enables efficient balance and mobility training without requiring physical assistance from a physiotherapist or a caregiver , which opens new possibilities for continuing and more frequent physical exercise and mobility training of patients with HSMN also at their homes In young elite athletes the influence of a sensorimotor training ( SMT = balance training ) on strength , jump height and spinal reflex excitability was compared with adaptations induced by strength training ( ST ) . Seventeen athletes were r and omly assigned to either a SMT or a ST group . Before and after 6 weeks of training , maximal isometric strength ( MVC ) and rate of force development ( RFD ( max ) ) were determined . Changes in jump height and EMG activity were assessed during squat- ( SJ ) , countermovement- ( CMJ ) and drop-jump ( DJ ) . To evaluate neural adaptations , H-reflex recruitment was recorded at rest and during dynamic activation of the plantarflexors following stance perturbation . MVC was enhanced after ST but not influenced by SMT . RFD ( max ) was not affected by any training . Both SMT and ST significantly improved jump performance in SJ , CMJ , and DJ . Maximum H-reflex to maximum M-wave ratios ( H (max)/M (max)-ratios ) at rest remained unchanged . During stance perturbation , H (max)/M (max)-ratios were significantly reduced following SMT whereas ST augmented H (max)/M (max)-ratios ( p < 0.05 ) . In contrast to other studies , no changes in RFD were found . This may be explained by method ological and /or training specific differences . However , both SMT and ST improved jump performance in well trained young athletes but induced opposing adaptations of the H (max)/M (max)-ratio when measured during dynamic contractions . These adaptations were task-specific as indicated by the unchanged reflexes at rest . Decreased spinal excitability following SMT was interpreted as the attempt to improve movement control , whereas augmented excitability following ST accounts for the effort to enhance motoneuron output . Functionally , our results emphasise that SMT is not only beneficial for prevention and rehabilitation but also improves athletic performance Background Liver transplantation is nowadays the only effective answer to adjourn the outcome of functional limitations associated with familial amyloidotic polyneuropathy ( FAP ) , a neurodegenerative disease characterized by sensory and motor polyneuropathies . Nevertheless , there is a detrimental impact associated with the after-surgery period on the fragile physical condition of these patients . Exercise training has been proven to be effective on reconditioning patients after transplantation . However , the effects of exercise training in liver transplanted FAP patients have not been scrutinized yet . Methods The study aim ed to evaluate the effects of a 24-week exercise training program ( supervised or home-based ) on body composition , muscle strength , and walking capacity of liver transplanted FAP patients . To fulfill this goal , a sample corresponding to 33 % of all FAP patients who undergone a liver transplantation in the area of Lisbon between January 2006 and December 2008 were followed over time . Three evaluation periods were accomplished : M1 ( pre-exercise training period ) , M2 ( immediate post-exercise training period ) , and M3 ( 24 weeks after M2 ) . The former allowed an assessment of the impact of detraining in these patients . Results The exercise training program improved body composition ( lean mass and total body skeletal muscle mass ) , weight , and walking capacity . The improvements were more pronounced within the patients with supervised exercise training compared with the patients on the home-based program . In general , the benefits of the exercise training perdure even after a 24-week detraining period . Conclusions Exercise training results in significant improvements on the physical condition of liver transplanted FAP patients OBJECTIVE To determine the effects of weight-bearing ( WB ) versus nonweight-bearing ( NWB ) exercise for persons with diabetes mellitus ( DM ) and peripheral neuropathy ( PN ) . DESIGN R and omized controlled trial with evaluations at baseline and after intervention . SETTING University-based physical therapy research clinic . PARTICIPANTS Participants with DM and PN ( N=29 ) ( mean age ± SD , 64.5±12.5y ; mean body mass index [ kg/m(2 ) ] ± SD , 35.5±7.3 ) were r and omly assigned to WB ( n=15 ) and NWB ( n=14 ) exercise groups . All participants ( 100 % ) completed the intervention and follow-up evaluations . INTERVENTIONS Group-specific progressive balance , flexibility , strengthening , and aerobic exercise conducted sitting or lying ( NWB ) or st and ing and walking ( WB ) occurred 3 times a week for 12 weeks . MAIN OUTCOME MEASURES Measures included the 6-minute walk distance ( 6MWD ) and daily step counts . Secondary outcome measures represented domains across the International Classification of Functioning , Disability and Health . RESULTS The WB group showed greater gains than the NWB group over time on the 6MWD and average daily step count ( P<.05 ) . The mean and 95 % confidence intervals ( CIs ) between-group difference over time was 29 m ( 95 % CI , 6 - 51 ) for the 6MWD and 1178 ( 95 % CI , 150 - 2205 ) steps for the average daily step count . The NWB group showed greater improvements than the WB group over time in hemoglobin A1c values ( P<.05 ) . CONCLUSIONS The results of this study indicate the ability of this population with chronic disease to increase 6MWD and daily step count with a WB exercise program compared with an NWB exercise program PURPOSE Radiotherapy for prostate cancer ( PCa ) may cause unfavorable changes in fatigue , quality of life ( QOL ) , and physical fitness . We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue , QOL , physical fitness , body composition , prostate-specific antigen , testosterone , hemoglobin , and lipid levels in men with PCa receiving radiotherapy . PATIENTS AND METHODS Between 2003 and 2006 , we conducted a r and omized controlled trial in Ottawa , Canada , where 121 PCa patients initiating radiotherapy with or without and rogen deprivation therapy were r and omly assigned to usual care ( n = 41 ) , resistance ( n = 40 ) , or aerobic exercise ( n = 40 ) for 24 weeks . Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale . RESULTS The follow-up assessment rate for our primary end point of fatigue was 92.6 % . Median adherence to prescribed exercise was 85.5 % . Mixed-model repeated measures analyses indicated both resistance ( P = .010 ) and aerobic exercise ( P = .004 ) mitigated fatigue over the short term . Resistance exercise also produced longer-term improvements ( P = .002 ) . Compared with usual care , resistance training improved QOL ( P = .015 ) , aerobic fitness ( P = .041 ) , upper- ( P < .001 ) and lower-body ( P < .001 ) strength , and triglycerides ( P = .036 ) , while preventing an increase in body fat ( P = .049 ) . Aerobic training also improved fitness ( P = .052 ) . One serious adverse event occurred in the group that performed aerobic exercise . CONCLUSION In the short term , both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy . Resistance exercise generated longer-term improvements and additional benefits for QOL , strength , triglycerides , and body fat |
12,661 | 12,947,138 | The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination .
Frequent chest radiography might be harmful . | BACKGROUND Lung cancer is a substantial public health problem in western countries . | Three parallel studies on screening for lung cancer , supported by the National Cancer Institute , were carried out by the Mayo Clinic , Johns Hopkins Medical Institutions , and Memorial Sloan-Kettering Center from 1971 to 1982 . No significant mortality improvement was established that could be attributed to cytologic screening examinations . Many stage I lung cancers were detected by radiographic screening , with excellent changes for long-term survival . Patients with stage I cancers who were operated on had significantly better survival rates than those who failed to undergo surgery . Statistical modeling , however , indicates that long-term annual screening of a high-risk population would decrease lung cancer mortality by no more than 18 % Background . Ovarian cancer is the fifth most common cause of cancer‐related death in American women . The median age at diagnosis is about 62 years ; incidence rises rapidly after age 60 . Pelvic examination has been the primary method for detection of ovarian carcinoma . It is insensitive for the detection of early disease , however : most women present with disease beyond the pelvis ( Stages III and IV ) and are not curable with existing techniques . Two new technologies may be useful as screening tools for earlier detection of ovarian cancer . CA 125 is an antigenic determinant expressed on an ovarian cancer cell line . Transvaginal ultrasound ( TVUS ) images the ovaries from within the vagina and can be performed by a technician in about 10 minutes . In small preoperative studies of women with ovarian masses , serum CA 125 levels have been elevated ( typically above 35 U/ml ) in over two‐thirds of cases and in up to 50 % of Stage I cases . The test is not absolutely specific : elevations have been reported with pregnancy , endometriosis , menstruation , benign ovarian tumors , and with cancers of the breast , colon , pancreas , lung , stomach , and liver . Nevertheless , the specificity of CA 125 in postmenopausal women has been reported at about 95 % or more . TVUS provides higher resolving power for ovarian abnormalities than transabdominal ultrasound or physical examination ; however , experience with it is limited . CA 125 and TVUS may be complementary In a controlled investigation the survival prospect s of lung cancer in a population of men aged 40 and over who had been offered six-monthly chest radiographs over a period of three years were compared with lung cancer in a similar population without such x-ray facilities . The five-year survival rate of lung cancer in the study series was 15 % , and in cases discovered by six-monthly examination 23 % , compared with 6 % in the control series . The average expectation of life after diagnosis was 2·5 years for the test cases and 1·2 for the control cases . Survival declined with age . Of resected lung cancer , 32 % survived five years in the test series and 23 % in the control series . The five-year survival rate for squamous carcinoma and adenocarcinoma in the test series was 28 % and 25 % respectively , compared with 15 % and nil in the control series . On the basis of these results it is concluded that through earlier radiological detection a modest improvement in the prognosis of lung cancer can be achieved The Memorial Sloan-Kettering lung cancer screening program was begun in 1974 to evaluate sputum cytology as a supplement to the annual chest x-ray examination for early detection and diagnosis . The 10,040 adult , male cigarette smokers who enrolled were r and omly assigned to receive annual chest x-ray examinations only or a dual screen with annual chest x-ray examination and four monthly sputum cytology evaluation . Over 40 percent of the 288 who developed lung cancer were diagnosed in stage I , and their survival was 76 percent at five years ; overall survival was 35 percent . Nearly one third of the lung cancers detected on first examination on the dual screen , and 14 percent of those on subsequent examinations were found by cytologic examination . The same number of cancers developed in the x-ray screen only group , and were diagnosed at a later date . Despite the delay , survival and mortality were the same , suggesting that the squamous carcinomas detected by cytologic examination alone are very slow growing and tend to remain localized until detectable by x-ray examination BACKGROUND The Mayo Lung Project ( MLP ) was a r and omized , controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983 . The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years ; the usual-care arm was advised at trial entry to receive the same tests annually . No lung cancer mortality benefit was evident at the end of the study . We have extended follow-up through 1996 . METHODS A National Death Index-PLUS search was used to assign vital status and date and cause of death for 6523 participants with unknown information . The median survival for lung cancer patients diagnosed before July 1 , 1983 , was calculated by use of Kaplan-Meier estimates . Survival curves were compared with the log-rank test . RESULTS The median follow-up time was 20.5 years . Lung cancer mortality was 4.4 ( 95 % confidence interval [ CI ] = 3.9 - 4.9 ) deaths per 1000 person-years in the intervention arm and 3.9 ( 95 % CI = 3.5 - 4.4 ) in the usual-care arm ( two-sided P : for difference = .09 ) . For participants diagnosed with lung cancer before July 1 , 1983 , survival was better in the intervention arm ( two-sided P : = .0039 ) . The median survival for patients with resected early-stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm . CONCLUSIONS Extended follow-up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm . Similar mortality but better survival for individuals in the intervention arm indicates that some lesions with limited clinical relevance may have been identified in the intervention arm The Multiphasic Health Checkup Evaluation Study , a long-term clinical trial , has been completed . A study group of 5156 men and women age 35 - 54 at entry was urged to have annual multiphasic health checkups ( MHCs ) for 16 years . A control group of 5557 comparable subjects was not so urged but was followed up in a comparable fashion . The mean and median number of MHCs per person were 6.8 and 6 , respectively , in the study group and 2.8 and 1 , respectively , in the control group . During 16 years the study group experienced a 30 % reduction ( p less than 0.05 ) in deaths from pre-specified " potentially postponable " causes , largely associated with lower death rates from colorectal cancer and hypertension . This reduction was most pronounced in the early years of the study . The two groups did not differ to a statistically significant degree in mortality from all other causes ( 84 % of total mortality ) or in total mortality . There was no difference in self-reported disability in the overall groups . In the setting of our prepaid health care plan where MHCs were already available on a voluntary basis , a program of urging middle-aged persons to undergo regular MHCs brought about a substantial reduction in mortality from preselected diseases Cigarette‐smoking males ( 6,364 ) , aged 40–64 , were r and omized into an intervention group which received 6‐monthly screening by chest X‐ray and sputum cytology , and a control group which received no asymptomatic investigation . After 3 years , both groups entered a follow‐up period during which they received annual chest X‐rays . Lung cancer cases detected by screening were identified at an earlier stage , more often resectable , and had a significantly better survival than “ interval ” cases diagnosed mainly because of symptoms . Comparison of the 2 groups showed a higher incidence of lung cancer in the intervention group , despite the follow‐up period when both groups received annual examinations . There was no significant difference in mortality between the 2 groups The study was launched in the mid‐1970s to explore the capability of screening by chest X‐ray and sputum cytology to be used as an effective component of the lung cancer control program in the Czech Republic , a Central European country with a high and increasing occurrence of lung cancer in men at that time . A complementary objective of this report is to ascertain whether the cumulative numbers of lung cancer deaths would equalize in the two r and omized groups during a prolonged follow‐up period A prospect i ve and controlled study for early detection of lung cancer in the county of Erfurt with a follow-up of 10 years is presented . A collective of 41,532 males born between 1907 and 1932 was screened by chest fluorography at 6 month intervals and compared with a control group consisting of 102,348 males of the same age , who were screened at intervals of about 18 months . No significant reduction of overall mortality and of lung cancer mortality was achieved . Semi-annual screening brought about a higher detection rate ( 9%/6.5 % ) , an increase in the resection rate ( 28%/19 % ) and higher 5 and 10 year survival rates ( 52 % ; 27%/39 % ; 19 % ) of resected patients than screening in 18 month intervals . Among those patients who refused resection or were surgically untreatable , the difference in survival rates between the two investigation groups lasted only up to the 12 months barrier . This is regarded as the effect of the lead-time bias . Fluorographic screening is effective only in patients with peripheral cancers . Patients resected for central lung cancers did not show differences in the survival rates . In both investigation groups considered together surgical therapy was possible mainly in those patients who had been detected by screening ( resection rate : 48 % ; 5 yr survival rate : 26.9 % ) . The resection rate of all the others amounted to 9 % , the 5 yr survival rate to 1.4 % . Therefore we consider fluorography to time as the only chance for lung cancer control of high risk groups in spite of the absence of reduction of lung cancer mortality The Early Lung Cancer Action Project ( ELCAP ) is design ed to evaluate baseline and annual repeat screening by low radiation dose computed tomography ( low‐dose CT ) in persons at high‐risk for lung cancer . The authors report on the baseline screening experience . For full evaluation of screening , they await the results of annual repeat screening Objectives To examine whether age at entry , history of cigarette smoking , exposure to non-tobacco lung carcinogens , or previous pulmonary illnesses were confounders or effect modifiers of the relation between screening and lung cancer mortality in the Mayo Lung Project . Setting —The Mayo Lung Project was a r and omised , controlled , clinical trial conducted between 1971 and 1986 in 9211 male smokers over the age of 45 in Minnesota ( USA ) . The group screened received chest x ray examination and sputum cytology every four months for six years . The unscreened group were recommended to obtain usual care ( annual chest x ray examination and sputum cytology ) . After follow up , lung cancer mortality was similar in both groups . Methods —Proportional hazard models were used to analyse data . A variable was considered a confounder if its inclusion in a model changed the rate ratio for screening by more than 15 % ; a variable was considered an effect modifier if its stratum-specific rate ratio for screening differed by a factor of two . Results None of the four aforementioned variables changed the rate ratio associated with screening ( 1.07 ) by more than 2 % . The effect of screening may have differed by years smoked ( rate ratio for smoking fewer than 30 years 2.4 ; rate ratio for smoking 30 or more years 1.0 ) , though we suspect that this result occurred by chance . Conclusion Adjustment for or stratification by four established lung cancer risk factors did not alter the original findings of the Mayo Lung Project |
12,662 | 15,879,439 | The clinical implication of these results is that there are important differences in anti-fracture efficacy among currently available agents . | A major aim of evidence -based medicine is to assist clinical decision-making by providing the most current and reliable medical information .
Systematic review s and meta-analyses are important tools in this process .
Systematic review s identify and compile relevant evidence , while meta-analyses summarize and quantify the results of such review s. Results from meta-analyses are , at present , the main source of summary evidence for the efficacy of treatments for a specific condition .
They are important tools for helping to choose among treatment options , although they can not be used to directly compare the magnitude of the effect of various therapies .
However , the methods used and the consequent clinical value of the results , may be poorly understood by clinicians , who may therefore not take full advantage of the evidence . | Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity Abstract : To examine the risk of mortality following all clinical fractures , we followed 6459 women age 55–81 years participating in the Fracture Intervention Trial for an average of 3.8 years . All fractures and deaths were confirmed by medical record or death certificate . Clinical fractures were fractures that came to medical attention . Fracture status was used as a time-dependent covariate in proportional hazards models . The 907 women who experienced a fracture were older , had lower bone mineral density and were more likely to report a positive fracture history . A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture . The age-adjusted relative risk ( 95 % confidence intervals ) of dying following a clinical fracture was 2.15 ( 1.36 , 3.42 ) . This primarily reflected the higher mortality following a hip fracture , 6.68 ( 3.08 , 14.52 ) ; and clinical vertebral fracture , 8.64 ( 4.45 , 16.74 ) . Results were similar after adjusting for treatment assignment , health status and specific common comorbidities . There was no increase in mortality following a forearm or other fracture ( non-hip , non-wrist , non-vertebral fracture ) . In conclusion , clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women SUMMARY Objective : To compare the effects of alendronate ( ALN ) 70 mg once weekly ( OW ) and risedronate ( RIS ) 5 mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density ( BMD ) in postmenopausal women with osteoporosis . Research design and methods : This was a 3-month , r and omised , double-blind , placebo-controlled study with a double-blind extension to 12 months . The study enrolled 549 postmenopausal women ( ALN 219 , RIS 222 and placebo ( PBO ) 108 ) who were > 60 years of age at outpatient centres . Main outcome measures : The primary endpoint was reduction in urine N-telopeptides of type 1 collagen ( NTx ) corrected for creatinine level at 3 months . Secondary parameters included change in BMD at the spine and hip at 6 and 12 months , NTx at 1,6 and 12 months , and serum bone-specific alkaline phosphatase ( BSAP ) at 1 , 3 , 6 and 12 months . Adverse experiences ( AEs ) were recorded throughout the study for an assessment of treatment safety profiles and tolerability . Results : Over 3 months , ALN produced a significantly greater mean reduction in urine NTx than did RIS ( −52 % vs −32 % , p < 0.001 ) , which was maintained at 12 months . ALN produced a significantly greater mean BMD increase than did RIS at 6 months , and it was maintained at 12 months at the lumbar spine ( 4.8 % vs 2.8 % , p < 0.001 ) and total hip ( 2.7 % vs 0.9 % , p < 0.001 ) , as well as at the trochanter and femoral neck . Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment . Study size did not allow for meaningful assessment of differences in fracture rates . Tolerability was generally similar between ALN , RIS and PBO , and the incidence of upper GIAEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups . Conclusion : In this study , ALN 70 mg OW produced a 50 % greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily . The treatments had similar safety profiles and were generally well-tolerated . Additional studies are needed comparing OW ALN with OW RIS , which became available after the commencement of the present study Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction Both raloxifene ( RLX ) and alendronate ( ALN ) can treat and prevent new vertebral fractures , increase bone mineral density ( BMD ) , and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis . This phase 3 , r and omized , double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis ( femoral neck BMD T-score , less than -2 ) . Women ( aged < or = 75 yr ; > or = 2 yr since their last menstrual period ) received placebo , RLX 60 mg/d , ALN 10 mg/d , or RLX 60 mg/d and ALN 10 mg/d combined . At baseline , 6 and 12 months , BMD was measured by dual x-ray absorptiometry . The bone turnover markers serum osteocalcin , bone-specific alkaline phosphatase , and urinary N- and C-telopeptide corrected for creatinine were measured . The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant ( P > 0.10 ) in a two-way ANOVA model . All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups , and between the RLX and RLX+ALN groups ( P < 0.05 ) . On average , lumbar spine BMD increased by 2.1 , 4.3 , and 5.3 % from baseline with RLX , ALN , and RLX+ALN , respectively . The increase in femoral neck BMD in the RLX+ALN group ( 3.7 % ) was greater than the 2.7 and 1.7 % increases in the ALN ( P = 0.02 ) and RLX ( P < 0.001 ) groups , respectively . The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0 % with placebo , -23.8 to -46.5 % with RLX , -42.3 to -74.2 % with ALN , and -54.1 to -81.0 % in the RLX+ALN group . RLX and ALN increased lumbar spine and femoral neck BMD , and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner , because the interaction effects were not significant . Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group , it is not known how well these changes correlate to the clinical outcome of fracture . RLX+ALN reduced bone turnover more than either drug alone , result ing in greater BMD increment , but whether this difference reflects better fracture risk reduction was not assessed in this study BACKGROUND Up to 3 years of treatment with alendronate , 5 mg/d , prevents postmenopausal bone loss . OBJECTIVE To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued . DESIGN R and omized , controlled trial . SETTING United States and Europe . PARTICIPANTS 1609 postmenopausal women 45 to 59 years of age . INTERVENTION Participants were r and omly assigned to receive oral alendronate , 5 mg/d or 2.5 mg/d ; placebo ; or open-label estrogen-progestin . Women in the alendronate groups received alendronate for the first 2 years of the study . Treatment was then continued without change or replaced with placebo for the last 2 years of the study . MEASUREMENTS Annual measurement of bone mineral density . RESULTS By year 4 , the bone mineral density of participants in the placebo group had decreased by 1 % to 6 % ( P < 0.001 ) . Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine ( mean change [ + /-SE ] , 3.8%+/-0.3 % ) , hip ( mean , 2.9%+/-0.2 % ) , and total body ( mean , 0.9%+/-0.2 % ) ( P < 0.001 overall ) . By year 4 , bone mineral density at most skeletal sites was greater in participants who switched from alendronate to placebo than in those who continuously received placebo . In years 3 and 4 , bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo . Compared with 5 mg of alendronate per day , estrogen-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater . CONCLUSIONS Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss . A residual effect was seen 2 years after alendronate therapy was stopped ; however , continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo OBJECTIVE To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density ( BMD ) during alendronate treatment . METHODS Women in this study were age 55 - 81 years ( n = 2,984 ) . While participating in the Fracture Intervention Trial , they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12 - 30 months of the study . Their BMD was measured at baseline and at 12 and 24 months , and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures . RESULTS After 12 months of alendronate treatment , 35 % of participants had increases of > or =3 % in total hip BMD , and 21 % had either decreased total hip BMD or no change . Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period . Only 3.2 % of women with increases of > or =3 % in total hip BMD experienced new vertebral fractures , whereas twice as many women ( 6.3 % ) whose BMD declined or stayed the same experienced new fractures ( adjusted odds ratio 0.45 , 95 % confidence interval 0.27 - 0.72 ) . Similar patterns were observed for spine BMD at 12 months , and for both sites using change in BMD at 24 months . CONCLUSION Women with increases of > or =3 % in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures . These findings suggest that , among women taking antiresorptive agents , greater increases in BMD are associated with lower risk of new vertebral fractures The main objective of this study was to determine the effect of daily oral alendronate treatment on bone mass in postmenopausal women affected by osteoporosis . The efficacy of intranasal salmon calcitonin was also examined . Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48 and 76 with spinal bone mineral density > or = 2 SD below adult mean peak in the two-year , double-blind , r and omized , placebo-controlled trial . Patients were r and omized to one of four treatment arms : double-blind placebo , alendronate 10 mg/day , alendronate 20 mg/day , or open-label intranasal salmon calcitonin 100 IU/day ; all patients received 500 mg Ca++ supplements . Bone mass was measured by dual-energy x-ray absorptiometry every six months for two years . Patients who received alendronate 10 or 20 mg experienced significant increases in bone mass at all sites measured . At the end of the second year , the mean percent changes , for alendronate 10 and 20 mg relative to placebo , were 5.2 % and 7.3 % at the lumbar spine , 3.8 % and 4.6 % at the femoral neck , and 7.1 % and 7.5 % at the trochanter , respectively . In contrast , intranasal salmon calcitonin failed to increase bone mineral mass significantly at any site . Both alendronate doses significantly decreased serum alkaline phosphatase , serum osteocalcin , and urinary pyridinolines , markers of bone turnover , whereas placebo and intranasal calcitonin did not . Alendronate was generally well tolerated and no serious adverse events were attributed to its use . ( ABSTRACT TRUNCATED AT 250 WORDS The r and omized controlled trial has been used in medical research for a little over half a century . This manuscript provides an overview of some of the history and evolution of the r and omized controlled trial during this period . There exists hierarchies of evidence for therapeutic , diagnostic and prognostic questions , and the r and omized controlled trial is at the top of the therapeutic hierarchy . Despite being at the top of the therapeutic hierarchy r and omization in itself does not guarantee the trial results approximate the true effect . Issues that result in systematic and non systematic deviations from the truth in r and omized controlled trials must also be considered . We present a model for evidence -based decision making that includes the following components : the clinical state , patient preferences , research evidence from a range of studies and clinical expertise . We discuss the role of the r and omized controlled trial within evidence -based decision making OBJECTIVES To determine the relationship between prevalent vertebral deformities and the risk of mortality and hospitalization in older women with low bone mass . DESIGN A prospect i ve cohort study . SETTING Eleven clinical centers in the United States . PARTICIPANTS A total of 6459 community-dwelling women with low bone mass aged 55 to 81 participated in the Fracture Intervention Trial ( FIT ) , a multicenter clinical trial of alendronate that enrolled women into one of two study arms based solely on the presence or absence of existing radiographic vertebral deformities . There were 2027 women with at least one vertebral deformity enrolled in the vertebral fracture arm of FIT and followed prospect ively for an average of 2.9 years , whereas 4432 women with no vertebral deformity were enrolled in the clinical fracture arm of FIT and followed prospect ively for an average of 4.2 years . MEASUREMENTS Determination of prevalent vertebral deformities on baseline lateral thoracic and lumbar spine radiographs was made at the coordinating center using a combination of radiographic morphometry by digitization and semiquantitative radiologic interpretation . Deaths were confirmed by obtaining copies of original death certificates of all participants who died . Episodes of hospitalization were captured through adverse event reporting ; hospitalizations result ing solely from adverse events containing the words " fracture " or " trauma " were excluded from the analyses . RESULTS During the follow-up period , 122 women died , and 1676 women were hospitalized on at least one occasion for reasons not related solely to fracture . Compared with women without prevalent vertebral deformities , those women with prevalent deformities had higher risks of mortality ( age- and treatment assignment-adjusted relative risk 1.60 , 95 % confidence interval ( CI ) , 1.10 - 2.32 ) and hospitalization ( age- and treatment assignment-adjusted relative risk 1.18 , 95 % CI , 1.06 - 1.31 ) . In addition , further adjustment for other factors , including smoking status , physical activity , hypertension , coronary heart disease , obstructive lung disease , any fracture since the age of 50 , health status , total hip BMD , and body mass index did not alter the association between prevalent vertebral deformities and risk of mortality substantially ( multivariate relative risk 1.49 , 95 % CI , 1.05 - 2.21 ) . Adjustment for all these factors and diabetes also did not change the relationship between prevalent vertebral deformities and hospitalization ( multivariate relative risk 1.14 , 95 % CI , 1.02 - 1.27 ) . Rates of mortality and hospitalization increased with increasing number of prevalent vertebral deformities ( tests for trend P < .01 ) . CONCLUSIONS Prevalent vertebral deformities in older women with low bone mass are associated with increased risks of mortality and hospitalization . Only a portion of this increased risk was explained by other known predictors of these outcomes This paper aims to explore the potential usefulness and limitations of indirect comparisons in evaluating the relative efficacy of interventions . From a systematic review of antimicrobial prophylaxis in colorectal surgery , we identified 11 sets of r and omized trials that can be used to compare antibiotics both directly and indirectly . The discrepancy between the direct and the indirect comparison is defined as the absolute value of difference in log odds ratio . The adjusted indirect comparison has the advantages that the prognostic factors of participants in different trials can be partially taken into account and more uncertainty be incorporated into its result by providing a wider confidence interval . However , considerable discrepancies exist between the direct and the adjusted indirect comparisons . When there is no direct comparison , the adjusted indirect method may be used to obtain some evidence about the relative efficacy of competing interventions , although such indirect results should be interpreted with great caution . Further empirical and method ologic research is needed to explore the validity and generalizability of the adjusted indirect comparison for evaluating different interventions UNLABELLED Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis . These two agents were compared in a 12-month head-to-head trial . Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability . INTRODUCTION The nitrogen-containing bisphosphonates , alendronate and risedronate , are available in once-weekly ( OW ) formulations for the treatment of postmenopausal osteoporosis . A 12-month , head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD . MATERIAL S AND METHODS A total of 1053 patients from 78 U.S. sites were r and omized to OW alendronate 70 mg ( N = 520 ) or risedronate 35 mg ( N = 533 ) , taken in the morning after fasting . Endpoints included BMD changes over 6 and 12 months at the hip trochanter , total hip , femoral neck , and lumbar spine ( LS ) ; percent of patients with predefined levels of change in trochanter and LS BMD at 12 months ; and change in biochemical markers of bone turnover at 3 , 6 , and 12 months . Tolerability was evaluated by adverse experience ( AE ) reporting . RESULTS Significantly greater increases in hip trochanter BMD were seen with alendronate ( 3.4 % ) than risedronate ( 2.1 % ) at 12 months ( treatment difference , 1.4 % ; p < 0.001 ) as well as 6 months ( treatment difference , 1.3 % ; p < 0.001 ) . Significantly greater gains in BMD were seen with alendronate at all BMD sites measured ( 12-month difference : total hip , 1.0 % ; femoral neck , 0.7 % ; LS , 1.2 % ) . Significant differences were seen as early as 6 months at all sites . A greater percentage of patients had > or = 0 % ( p < 0.001 ) and > or =3 % ( p < 0.01 ) gain in trochanter and spine BMD at 12 months with alendronate than risedronate . Significantly greater ( p < 0.001 ) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months . No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation . CONCLUSIONS In this 12-month , head-to-head trial of alendronate and risedronate , given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women , alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate . The greater antiresorptive effect of alendronate was seen as early as 3 months , and the tolerability profiles were similar Context Alendronate and conjugated estrogen therapy both increase bone mineral density in postmenopausal women , but is the rate of bone loss greater when alendronate or estrogen therapy is discontinued ? Contribution The discontinuation phase of this double-blind , placebo-controlled trial showed loss of spine and trochanter bone mass in postmenopausal women 1 year after withdrawal of estrogen and no such loss after withdrawal of either alendronate or combination therapy with alendronate and estrogen therapy . Caution s The study was not large or long enough to show whether discontinuation of estrogen therapy is associated with more fractures than discontinuation of either alendronate or combination therapy . The Editors Several antiresorptive agents have been shown to increase bone mass and reduce osteoporotic fractures ( 1 - 3 ) . Because greater improvements in bone mass in women using therapy are associated with greater reductions in fracture ( 4 , 5 ) , investigators have begun to examine combinations of antiresorptive therapies to achieve more substantial gains in bone mass . Lindsay and colleagues demonstrated that addition of alendronate to hormone replacement therapy in postmenopausal women result ed in greater increases in bone mass than did maintenance of estrogen therapy alone ( 6 ) . We previously showed that administration of alendronate and estrogen for 2 years in postmenopausal women with low bone mass result ed in statistically significantly greater increases in bone mass at the lumbar spine and femoral neck than those seen in women taking either agent alone ( 7 ) . Furthermore , combination therapy was safe and result ed in normal findings on histologic examination of bone . In clinical practice , a key concern is the potential for accelerated bone loss when antiresorptive therapy is discontinued . Approximately one third of women discontinue hormone replacement therapy within 1 year of initiation ( 8) . Older studies have demonstrated significant losses in bone mass after discontinuation of hormone replacement therapy ( 9 - 11 ) . In contrast , when therapy with oral alendronate , 10 mg/d , is discontinued after osteoporosis treatment , bone mass at the hip and spine are maintained for 1 year ( 12 ) . However , no head-to-head comparison of hormone replacement therapy and alendronate or the combination of antiresorptive therapy after discontinuation has been done . In addition , future losses in bone mass when patients discontinue therapy must be considered in management of osteoporosis in postmenopausal women . We therefore sought to examine the rate of bone loss after discontinuation of 2 years of alendronate therapy , hormone replacement therapy , or combination therapy . A subset of participants continued to take combination therapy for a third year to determine whether prolonged therapy remained beneficial . Methods Study Participants Four hundred twenty-five postmenopausal women 42 to 82 years of age who had low bone mass were enrolled in a 2-year r and omized , double-blind , placebo-controlled clinical trial conducted at 18 centers in the United States ( 7 ) . Participants were recruited from clinics , private practice s , newspaper advertisements , and targeted mailings . All participants who completed the initial study were asked to enroll in the 1-year extension . Participants were told that if they were taking active treatment , they might be r and omly allocated to receive placebo or treatment for the third year and that if they were taking placebo , they would continue to do so . Entry criteria for the initial study are described elsewhere ( 7 ) . All women had had hysterectomy and had a bone mineral density at the lumbar spine that was less than or equal to a T score of 2.0 SDs below the peak bone mass in young adults . Data on presence or absence of ovaries were not collected . Exclusion criteria were metabolic bone disease , a low serum 25-hydroxyvitamin D level , use of medications known to affect bone turnover , renal insufficiency , severe cardiac disease , and recent major upper gastrointestinal disease . The institutional review board at each clinical site approved the extension protocol . After signing the extension consent form and undergoing baseline evaluation for the extension , participants were allocated to blinded treatment on the basis of their original treatment in the first 2 years of the study . The r and omization process was central ly determined by a statistician ; as in the initial study , treatment allocation was concealed . Design As described for the initial study at each center , patients were r and omly allocated to one of four treatment groups : placebo ( n = 50 ) ; alendronate , 10 mg/d ( n = 92 ) ; conjugated estrogen , 0.625 mg/d ( n = 143 ) ; or alendronate , 10 mg/d , plus conjugated estrogen , 0.625 mg/d ( n = 140 ) ( Figure 1 ) . The conjugated estrogen used was Premarin ( Wyeth-Ayerst , Philadelphia , Pennsylvania ) . All women received calcium carbonate to provide 500 mg of elemental calcium daily . Figure 1 . Design of original 2-year study and reallocation to extension phase for year 3 . At the end of the second year , 244 of the 425 women ( 57 % ) continued in a 1-year extension of the study ( Figure 1 ) . Of these women , 28 who previously received placebo continued to do so . Women who were taking combination therapy were reallocated to continue taking combination therapy ( n = 44 ) or switch to placebo ( n = 41 ) . In addition , 50 participants taking alendronate alone and 81 participants taking conjugated estrogen alone for the first 2 years were assigned to placebo for the third year . All patients and investigators remained blinded to medication allocation . Patients continued to receive calcium supplementation during the third year . Outcome Measures Women were examined at month 24 ( baseline of the 1-year extension ) , month 30 , and month 36 . Bone mineral density of the lumbar spine , hip ( femoral neck , trochanter , total hip ) , and total body were assessed by using dual-energy x-ray absorptiometry with QDR-1000W , QDR-1500 , or QDR-2000 series bone densitometers ( Hologic , Inc. , Bedford , Massachusetts ) . A st and ard phantom was used for cross-calibration at all sites . Serum and urine sample s were also obtained at months 24 , 30 , and 36 for assessment of biochemical markers of bone turnover , namely bone-specific alkaline phosphatase and urinary N-telopeptide cross-links of collagen type I , corrected for creatinine . Statistical Analysis We used SAS software , version 6.12 , TSLevel 0060 , PROCedureGLM ( SAS Institute , Inc. , Cary , North Carolina ) to analyze the data . The primary efficacy end point was the mean difference between groups in the percentage change in bone mineral density at the lumbar spine from month 24 to month 36 . Secondary efficacy end points were the mean percentage changes in bone mineral density of the hip and total body and biochemical markers of bone turnover . Overall percentage changes from month 0 to 36 in spine , hip , and total-body bone mineral density were also analyzed . The prespecified analysis was based on an intention-to-treat approach . At study design , we prespecified that all patients who had a baseline measurement and at least one measurement during treatment would be included in the analysis according to the group to which they were r and omly allocated . The missing data were approximated by carrying forward the last available value on treatment forward to the missing time point . No data from the original 2-year study were carried forward to the extension period for any assessment of change . Women who violated the protocol were excluded from analysis of biochemical markers , as previously reported ( 7 ) . Between-group comparisons of bone mineral density and biochemical measures were made by using analysis of variance techniques , with treatment , center , and treatment-by-center as factors . The assumption of homoscedasticity for the analysis of variance model was assessed by using the Levene test , and the normality assumption was assessed by using the ShapiroWilk test ( 13 ) . If the assumptions were violated , a nonparametric method was used to corroborate the parametric results . The Fisher exact test was used to compare treatment groups for the proportion of participants who exceeded predefined limits of change in laboratory safety variables ( 13 ) . Power calculations based on estimated sample sizes of 56 and 84 participants in the alendronate/placebo and estrogen/placebo treatment groups , respectively , yielded an estimate of 92 % power to detect a 1.5 % difference between mean percentage changes from month 24 to month 36 in bone mineral density at the lumbar spine ( = 0.05 , two-tailed test ) . As requested by the journal editors , data on bone mineral density were also analyzed by using a mixed-model analysis , and results of this analysis are presented . An appropriate curvilinear function was fitted to the actual data , and the function was estimated by using all data available across time points for each participant . A model that regressed bone mineral density versus log ( month + 1 ) provided the appropriate fit for the 3-year data and was used to analyze these data . The variable log ( month + 1 ) was used because log ( month ) is undefined when month is 0 , and log ( month + 1 ) yields the value 0 at baseline . The fitted values from the model were used to obtain the percentage change during the period of interest . Data on bone mineral density from the mixed-model analyses are presented unless otherwise specified . Role of the Funding Source Data were collected by investigators at each study site with the support of Merck Research Laboratories , Rahway , New Jersey . Analyses were performed by statisticians at Merck & Co. , Inc. Data were interpreted by the authors , who su bmi tted the manuscript for publication . Results Patient Characteristics and Retention Baseline r and omization characteristics did not differ between participants who entered the extension phase and those who did not . Baseline demographic characteristics of the 244 women who entered the extension phase were |
12,663 | 27,609,013 | CONCLUSION From the literature review ed the efficacy aPDT as adjunct to SRP in downregulating GCF cytokines remains debatable . | BACKGROUND The aim of the present review was to study the efficacy of scaling and root planing ( SRP ) with and without adjunct antibacterial photodynamic therapy ( aPDT ) on the expression of cytokines in the gingival crevicular fluid ( GCF ) of patients with periodontitis . | INTRODUCTION Clinical studies have shown the usefulness of antimicrobial photodynamic therapy ( aPDT ) as an adjunctive in periodontal therapy . These studies did not utilize indocyanine green ( ICG ) as a recently introduced photosensitizer . The aim of this study was to perform a full-mouth double-blind r and omized controlled clinical study to test the efficacy of adjunctive aPDT with ICG compared with scaling and root planing ( SRP ) alone in chronic periodontitis treatment . MATERIAL S AND METHODS Fifty patients were selected for this study . All patients received SRP . Then , each patient was r and omly assigned to either the test group ( aPDT+SRP ) or the control group ( SRP ) . aPDT was performed with a diode laser ( wavelength : 810 nm , power : 200mW ) and ICG as photosensitizer . The adjunctive procedure was repeated after 7 , 17 and 27 days . The clinical parameters including bleeding on probing ( BOP ) , clinical attachment loss ( CAL ) , plaque index ( PI ) , probing pocket depth ( PPD ) , full mouth plaque score ( FMPS ) and full mouth bleeding score ( FMBS ) were measured at baseline and after 1 and 3 months . RESULTS There were no significant differences between two groups at baseline . BOP , PPD and FMBS showed significant improvements in the test group ( P≤0.001 ) . In terms of PI , FMPS and CAL , no significant differences were observed between both groups ( P≥0.05 ) . CONCLUSION aPDT as an adjunctive approach yielded complete resolution of inflammation and significant reduction in periodontal pocket depth . However , aPDT had no additional advantages in clinical attachment gain and plaque score Background : There are limited clinical experiments addressing the effects of photodynamic therapy ( PDT ) and low-level laser therapy ( LLLT ) as an adjunct to conventional scaling and root planing ( SRP ) alone . Aim : The aim of this clinical trial was to evaluate the clinical effects of adjunctive use of PDT , combination of PDT with LLLT as adjunct to conventional SRP alone in the treatment of chronic periodontitis . Material s and Methods : In a single-centered r and omized and controlled clinical trial , 24 patients ( 15 males and 9 females ) with untreated chronic periodontitis were r and omly assigned in a split-mouth design into three treatment groups which included Group I : SRP only , Group II : SRP and PDT ( 1 % methylene blue [ MB ] solution ) , and Group III : SRP , PDT , and LLLT . Clinical parameters such as plaque index , gingival index , modified sulcular bleeding index , probing depth ( PD ) , and clinical attachment level ( CAL ) were measured at baseline , 1 , 3 , and 6 months after therapy . Results : Within each group , significant improvements ( P < 0.001 ) were found for all variables in 6-month follow-up compared with baseline . The improvement in clinical parameters was significantly greater in Group III compared to Group I and Group II . The mean PD ( mm ) reduction from baseline to 6 months in Group I was 2.50 ± 0.54 , Group II was 2.57 ± 0.53 , and Group III was 3.14 ± 0.50 . The mean CAL ( mm ) gain from baseline to 6 months in Group I was 2.63 ± 0.47 , Group II was 2.55 ± 0.44 , and Group III was 3.07 ± 0.55 . Conclusion : In patients with chronic periodontitis , a combination of a single application of PDT ( using a 980 nm laser and MB ) and LLLT provide additional benefit to SRP in terms of clinical parameters 6 months following the intervention AIM This split-mouth double-masked r and omized controlled clinical study evaluated the effectiveness of photoactivated disinfection ( PAD ) using light-emitting diode ( LED ) as an adjunct in the management of patients affected by moderate to severe chronic periodontitis . MATERIAL S AND METHODS Sixteen patients affected by moderate to severe chronic periodontitis were enrolled . After scaling and root planing ( SRP ) , each quadrant was assigned to one of the following groups : LED group ( 625 - 635 nm , maximum power density : 2000 mW/cm(2 ) ) , photosensitizer group ( tolouidine blue O , 0.1 mg/ml ) , PAD group ( photosensitizer and LED ) and control group ( no adjunctive treatment ) . The adjunctive treatments were repeated after 7 and 14 days . The clinical parameters of bleeding on probing , probing pocket depth and clinical attachment level were measured at baseline and 1 and 3 months after SRP . RESULTS At 1 and 3 months , all groups showed significant improvements with regard to all clinical parameters compared to baseline ( all p : < 0.001 ) . There were no significant differences among groups in terms of changes of clinical parameters in any time interval ( all p > 0.05 ) . CONCLUSION The application of PAD using LED with the current setting did not have additional effects on clinical parameters in patients diagnosed with moderate to severe chronic periodontitis compared with SRP alone OBJECTIVE To compare photodynamic therapy ( PDT ) as an adjunctive treatment of chronic periodontitis with scaling and root planing ( Sc/Rp ) in smokers . METHODS This is a split-mouth , single-masked r and omized controlled clinical trial conducted at the Faculty of Dentistry , King Abdulaziz University , Jeddah , Saudi Arabia between May 2010 and March 2011 . Fifty-four teeth with probing depth of ≥5 mm at one or more periodontal sites in 20 smokers diagnosed with moderate to severe chronic periodontitis were selected . In each patient , at least one tooth was r and omly assigned to Sc/Rp plus PDT ( test group ) and the contra-lateral tooth was assigned to Sc/Rp only ( control ) . Plaque index ( PI ) , bleeding on probing ( BOP ) , probing depth ( PD ) , recession and clinical attachment level ( CAL ) were recorded at baseline and 3 months after the periodontal treatment . Descriptive statistics and Wilcoxon signed ranked test were used for data analysis . RESULTS There was a statistically significant improvement in PD , CAL , BOP , and PI after periodontal treatment in both groups . No statistically significant differences between the 2 groups in any of the periodontal parameters were found at baseline ( p>0.05 ) , but a statistically significant greater reduction in PD ( p=0.028 ) and CAL ( p=0.044 ) in the test compared to the control group was found at the 3-month follow up . CONCLUSION Photodynamic therapy might have an additional benefit to scaling and root planing when treating smokers affected with periodontitis AIM To investigate the effect of photodynamic therapy ( PDT ) as adjunct to mechanical therapy in furcations . MATERIAL S AND METHODS A double-blind , parallel , r and omized controlled clinical trial was conducted in subjects presenting class II furcations . The subjects were r and omly allocated to a test ( PDT ; n = 16 ) or control group ( non-activated laser/only photosensitizer ; n = 21 ) . At baseline , 3 and 6 months , clinical , microbiological and cytokine pattern evaluation was performed . Clinical attachment level was defined as the primary outcome variable . RESULTS Clinical parameters improved after both therapies ( p < 0.05 ) with no differences between groups at any time point ( p > 0.05 ) . At 6 months , real-time PCR evaluation showed a decrease in Porphyromonas gingivalis and Tannerella forsythia only in the PDT group ( p < 0.05 ) with no inter-group differences . Regarding cytokines , IL-4 and IL-10 levels increased in both groups at 6 months . GM-CSF , IL-8 , IL-1β and IL-6 levels decreased only in the PDT group after 3 months ( p < 0.05 ) . At 3 months , inter-group analyses showed that GM-CSF , IFN-γ , IL-6 and IL-8 levels were lower in the PDT group . At 6 months , lower IL-1β levels were also observed in the PDT group ( p < 0.05 ) . CONCLUSION Photodynamic therapy did not promote clinical benefits for class II furcations ; however , advantages in local levels of cytokines and a reduction in periodontopathogens were demonstrated BACKGROUND There is an ongoing controversy on the benefits of treatment protocol s , including dental lasers and photodynamic therapy ( PDT ) . The purpose of this study is to compare the local biologic effects of PDT , diode soft laser ( DSL ) therapy , and conventional deep scaling and root planing ( SRP ) in residual pockets . METHODS Thirty-two individuals were included based on a history of previous treatment for periodontitis and the persistence of sites with probing depths > 4 mm and bleeding on probing . Residual pockets were debrided with an ultrasonic device and then r and omly assigned either to PDT , DSL , or SRP . Gingival crevicular fluid was collected before treatment , after 14 days , and at 2 and 6 months . Levels of 13 cytokines and nine acute-phase proteins were measured using a bead-based multiplexing analysis system . RESULTS Treatment with PDT , DSL , or SRP led to significant changes in several cytokines and acute-phase proteins : Compared with baseline , levels of interleukin-17 , basic fibroblast growth factor , granulocyte colony-stimulating factor , granulocyte macrophage colony-stimulating factor , and macrophage inflammatory protein 1-α were lower 14 days and 2 months after treatment . Except for granulocyte colony-stimulating factor , these differences remained significant throughout the observation period . The levels of five acute-phase proteins ( α-2 macroglobulin , haptoglobin , serum amyloid P , procalcitonin , and tissue plasminogen activator ) were significantly higher at 6 months than at baseline . No significant differences were observed among the three treatment modalities at any time point for any biochemical parameter . CONCLUSIONS Levels of several cytokines and acute-phase proteins significantly changed after treatment regardless of treatment modality . There was no evidence for a specific DSL- or PDT-enhanced expression of inflammatory mediators BACKGROUND AND OBJECTIVE In recent years , there has been a growing interest in the use of dental lasers for treatment of periodontal diseases . The purpose of this short-term clinical trial was to evaluate the effects of a combination of photodynamic therapy with low-level laser therapy as an adjunct to nonsurgical treatment of chronic periodontitis . MATERIAL AND METHODS Twenty-four nonsmoking adults with untreated chronic periodontitis were r and omly assigned in a split-mouth design to receive scaling and root debridement with or without one course of adjunctive photodynamic therapy and low-level laser therapy within 5 d. Plaque , bleeding on probing , probing depth and gingival recession were recorded at baseline , 1 and 3 mo after the treatment . Gingival crevicular fluid was collected for assay of interleukin-1β levels at baseline , 1 wk and 1 mo . RESULTS The test teeth achieved greater reductions in the percentage of sites with bleeding on probing and in mean probing depth at 1 mo compared with the control teeth ( p < 0.05 ) . A significant decrease in gingival crevicular fluid volume was observed in both groups at 1 wk ( p < 0.001 ) , with a further decrease at 1 mo in the test sites ( p < 0.05 ) . The test sites showed a greater reduction of interleukin-1β levels in gingival crevicular fluid at 1 wk than the control sites ( p < 0.05 ) . No significant differences in periodontal parameters were found between the test and control teeth at 3 mo . CONCLUSIONS The present study suggests that a combined course of photodynamic therapy with low-level laser therapy could be a beneficial adjunct to nonsurgical treatment of chronic periodontitis on a short-term basis . Further studies are required to assess the long-term effectiveness of the combination of photodynamic therapy with low-level laser therapy as an adjunct in nonsurgical treatment of periodontitis BACKGROUND The management of aggressive periodontitis ( AgP ) represents a challenge for clinicians because there are no st and ardized protocol s for an efficient control of the disease . This r and omized controlled clinical trial evaluated the effects of repeated applications of antimicrobial photodynamic therapy ( aPDT ) adjunctive to scaling and root planing ( SRP ) in patients with AgP. METHODS Using a split-mouth design , 20 patients with generalized AgP were treated with aPDT + SRP ( test group ) or SRP only ( control group ) . aPDT was applied at four periods . All patients were monitored for 90 days . Clinical , microbiologic , and immunologic parameters were statistically analyzed . RESULTS In deep periodontal pocket analysis ( probing depth [ PD ] ≥ 7 mm at baseline ) , the test group presented a decrease in PD and a clinical attachment gain significantly higher than the control group at 90 days ( P < 0.05 ) . The test group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower interleukin-1β/interleukin-10 ratio than the control group ( P < 0.05 ) . CONCLUSION The application of four sessions of aPDT , adjunctive to SRP , promotes additional clinical , microbiologic , and immunologic benefits in the treatment of deep periodontal pockets in single-rooted teeth in patients with The aim of this study was to investigate the adjunctive effect of antimicrobial photodynamic therapy ( aPDT ) to scaling and root planing ( SRP ) in smokers with chronic periodontitis . Twenty subjects had two contralateral teeth r and omly assigned to receive SRP ( SRP group ) or SRP + a single episode of aPDT ( SRP + aPDT group ) , with a diode laser and a phenothiazine photosensitizer . Plaque index , bleeding on probing , probing depth ( PD ) , clinical attachment level ( CAL ) , and gingival recession were recorded , and gingival crevicular fluid was collected for assay of IL-1β and matrix metalloproteinase (MMP)-8 levels . There was a significant PD reduction ( SRP 1.81 ± 0.52 mm/SRP + aPDT 1.58 ± 1.28 mm ; p < 0.001 ) and a significant CAL gain ( SRP 1.60 ± 0.92 mm/SRP + aPDT 1.41 ± 1.58 mm ; p < 0.001 ) for both groups . Significant differences were not observed in between-group comparisons . IL-1β level in gingival crevicular fluid was higher in SRP group after 1 week ( SRP 24.65 ± 18.85 pg/μL/SRP + aPDT 34.07 ± 24.81 pg/μL ; p = 0.048 ) , and MMP-8 level was higher in SRP group after 12 weeks ( SRP 303.31 ± 331.62 pg/μL/SRP + aPDT 534.23 ± 647.37 pg/μL ; p = 0.024 ) . There were no statistically significant differences in intragroup comparisons . The adjunctive effect of aPDT did not warrant improvements on clinical parameters in smokers . However , it result ed in a suppression of IL-1β and MMP-8 when compared with SRP alone BACKGROUND There are limited clinical experiments addressing the effects of photodynamic therapy ( PDT ) as an adjunct to conventional scaling and root planing ( SRP ) on clinical and biologic features of periodontitis . This trial compares the clinical parameters and cytokine profiles in gingival crevicular fluid of patients with moderate-to-severe chronic periodontitis ( CP ) who have been treated using SRP alone or SRP + PDT . METHODS Twenty-two patients with two contralateral teeth affected with moderate-to-severe CP were selected . After SRP , the participants ' teeth were r and omized to receive either no further treatment or a single application of PDT using a 638-nm laser and toluidine blue . Although the change in probing depth was the primary outcome , bleeding on probing , clinical attachment level , gingival recession , interleukin-1β , tumor necrosis factor (TNF)-α , and matrix metalloproteinase 8 and 9 were also evaluated at baseline and 3 months postintervention . An oral rinse assay was also performed to determine the total levels of oral polymorphonuclear cells ( PMNs ) before and 3 months after the treatments . RESULTS Within each group , significant improvements ( P < 0.001 ) were found for all variables in 3-month follow-up compared with baseline . Only TNF-α was significantly improved in the PDT + SRP versus SRP group . Total levels of PMNs were reduced for all patients compared with baseline levels ( P < 0.001 ) . CONCLUSION In patients with CP , a single application of PDT ( using a 638-nm laser and toluidine blue ) did not provide any additional benefit to SRP in terms of clinical parameters or inflammatory markers 3 months following the intervention INTRODUCTION Aggressive periodontitis comprises a group of rare , severe , rapidly progressive form of periodontitis . Conventional treatment includes mechanical debridement augmented with adjunctive antimicrobial therapy . Development of antibiotic resistance has led to use of lasers . Photodynamic therapy ( PDT ) is a novel non-invasive therapeutic approach with increased site and pathogen specificity . This study compares PDT and Lasers as an adjunct to conventional Scaling in the treatment of patients with aggressive periodontitis . MATERIAL S AND METHODS Fifteen untreated aggressive periodo-ntitis patients were r and omly assigned in a split mouth design for one of the following treatment modalities : 1 ) SRP alone ; ( 2 ) SRP + Diode Laser irradiation with 810 nm at 1W , continuous mode for 30 sec per tooth ; ( 3 ) SRP + PDT on " 0 " day ; ( 4 ) SRP + PDT on " 0 " , 7(th ) and 21(st ) day . The clinical parameters included PI , BOP , PPD , CAL recorded at the baseline & 3(rd ) month . The site with greatest probing pocket depth ( PPD ) was selected from each quadrant for bacterial sampling and cultured for Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis & Prevotella intermedia . RESULTS Statistically significant reduction in clinical & microbial parameters was seen . Sites 4 showed a greater reduction compared to other groups . CONCLUSION Photodynamic therapy is a valuable treatment modality adjunctive to conventional scaling and root planing BACKGROUND The current study was devised with the objective of using a split-mouth , controlled clinical trial to compare conventional mechanical debridement ( scaling and root planing ) treatment ( T1 ) with conventional mechanical treatment followed by photodynamic therapy ( PDT ) ( T2 ) in patients with severe periodontitis . METHODS Four PDT sessions were completed , and clinical parameters such as bleeding upon probing ( BOP positive ) , plaque index ( PI ) , probing pocket depth ( PPD ) and clinical attachment loss ( CAL ) were evaluated before and after the treatment series . In addition , gingival biopsies were collected at the start and finish of treatment , and were used for qPCR gene expression analysis of TNFA , IL1B , IL8 , IL10 , IL17 , MMP13 , FGF2 , RANK , RANKL and OPG . RESULTS The clinical results showed a significant improvement in BOP with treatment T2 ( p=0.03 ) . The molecular data showed an up-regulation of FGF2 , RANK and OPG gene expression after T2 . The expression levels of the other genes were not significantly different between T1 and T2 . PDT increased the expression of RANK and OPG , which could indicate a reduction in osteoclastogenesis . Furthermore , the use of PDT in conjunction with conventional treatment significantly increased the expression of FGF2 , which has an important role in the periodontal repair process . CONCLUSIONS PDT technology could be a means to improve conventional periodontitis treatment . Our results suggest that PDT acts in part by controlling bone resorption and increasing the expression of genes important for tissue repair BACKGROUND AND OBJECTIVE Antimicrobial photodynamic therapy ( aPDT ) has been proposed as an adjunctive therapy to scaling and root planing ( SRP ) . The transforming growth factor-β1 ( TGF-β ) has been considered as an anti-inflammatory cytokine , and its levels in the gingival crevicular fluid ( GCF ) could monitor the periodontal repair . This study evaluated the adjunct effect of aPDT compared with SRP , analyzing the TGF-β levels in GCF after nonsurgical and surgical therapy in chronic periodontitis patients . METHODS Fifteen patients , presenting bilaterally lower molars with class III furcation lesions , were selected . Each pair of teeth was r and omly assigned to a control group ( CG ) or test group ( TG ) . Initially , SRP was performed in the CG , and SRP + aPDT in the TG . Forty-five days later , flap surgery plus SRP , and flap surgery plus SRP + aPDT were performed in CG and TG , respectively . GCF was collected and an enzyme-linked immunosorbent assay ( ELISA ) test was conducted to determine the amount and concentration of TGF-β in the GCF at baseline , 45 days post-initial therapy , and 21 days after surgery . RESULTS Statistically significant differences between groups were found in relation to GCF volume 21 days after the surgical procedures ( p=0.03 ) and TGF-β concentration in GCF 45 days post-initial therapy ( p=0.04 ) , favoring the TG . CONCLUSIONS There was an additional effect of the aPDT protocol compared with SRP for the TGF-β concentration in GCF 45 days after nonsurgical therapy , and for the GCF volume 21 days after surgical therapy BACKGROUND / OBJECTIVE We hypothesized that nonsurgical-periodontal-therapy ( NSPT ) with adjunct Nd : YAG laser therapy is more effective in reducing periodontal inflammatory parameters ( plaque index [ PI ] , bleeding-on-probing [ BOP ] , and probing-pocket-depth [ PPD ] ) and serum interleukin-1beta ( IL-1β ) and matrix metalloproteinase-9 ( MMP-9 ) levels in patients with and without coronary artery disease ( CAD ) than NSPT alone . The aim of this short-term pilot study was to assess the effect of NSPT + Nd : YAG laser therapy on periodontal parameters and serum IL-1β and MMP-9 levels in patients with and without CAD . STUDY DESIGN A prospect i ve r and omized clinical study was conducted on 87 patients who were divided into two groups : Group-1 : 44 patients with CAD and periodontal disease ( PD ) and Group-2 : 43 patients with PD alone . Treatment-wise , these individuals were r and omly divided into two subgroups : ( i ) NSPT alone and ( ii ) NSPT + Nd : YAG laser therapy . Demographic information was collected using a self-completed question naire . Periodontal parameters ( PI , BOP , and PPD ) and serum IL-1β and MMP-9 levels were measured at baseline and after 3 months of treatment . P-values < 0.05 were considered statistically significant . RESULTS At 3 months follow-up , PI ( P < 0.01 ) , BOP ( P < 0.01 ) , PPD ≥ 4 mm ( P < 0.01 ) , and serum IL-1β ( P < 0.01 ) and MMP-9 ( P < 0.01 ) levels were significantly higher in patients treated with NSPT alone than those treated with NSPT + Nd : YAG laser therapy . Among patients that underwent NSPT + laser therapy in both groups , periodontal parameters and serum IL-1β , and MMP-9 levels were comparable at 3-months follow-up . CONCLUSION NSPT + Nd : YAG laser therapy may be more effective in reducing periodontal inflammation and serum IL-1β and MMP-9 levels in patients with and without CAD than NSPT alone . Lasers Surg . Med . 48:929 - 935 , 2016 . © 2016 Wiley Periodicals , |
12,664 | 16,043,674 | RESULTS The recommendations specify that all care setting s formulate structured , multilevel systems approaches ( sensitive to the type of pain , population served , and setting of care ) that ensure prompt recognition and treatment of pain , involvement of patients and families in the pain management plan , improved treatment patterns , regular re assessment and adjustment of the pain management plan as needed , and measurement of processes and outcomes of pain management . | null | null |
12,665 | 29,144,549 | Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine , risperidone or perphenazine , but there was no difference in EPSEs when compared to placebo or chlorpromazine .
Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride , and similar numbers of reported side-effects were found when its isomers were compared .
The other comparisons did not report adverse-effect data .Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo , chlorpromazine , chlorprothixene , clozapine , haloperidol , perphenazine , sulpiride , thiothixene , trifluoperazine , depot and isomers .
Zuclopenthixol dihydrochloride , when compared with risperidone , is favoured when assessed using the PANSS in the short term , but not in the medium term .
Prescribing practice is unlikely to change based on this meta- analysis .
Recommending any particular course of action about side-effect medication other than monitoring , using rating scales and clinical assessment , and prescriptions on a case-by-case basis , is also not possible . | BACKGROUND Oral zuclopenthixol dihydrochloride ( Clopixol ) is an anti-psychotic treatment for people with psychotic symptoms , especially those with schizophrenia .
It is associated with neuroleptic malignant syndrome , a prolongation of the QTc interval , extra-pyramidal reactions , venous thromboembolism and may modify insulin and glucose responses .
OBJECTIVES To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia . | Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect . This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia ( TD ) and less rebound aggravation after withdrawal than pure D2 antagonists . In this study the effect of zuclopenthixol ( mixed D1/D2 antagonist ) and haloperidol ( D2 antagonist ) was evaluated in chronic psychotic patients with TD . Fifteen patients completed a r and omized crossover study with blind evaluation of TD and parkinsonism . The test medications , haloperidol and zuclopenthixol , caused a significant suppression of TD and a significant increase of parkinsonism . No significant differences between haloperidol and zuclopenthixol were observed . No TD aggravation was seen . The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD 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 Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS . Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients 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 PURPOSE The aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in out patients with schizophrenia as compared to oral administration of the same antipsychotic . METHODS Forty-six previously violent patients with schizophrenia were r and omised to receive treatment with oral or depot zuclopenthixol for 1 year . Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence . An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month . RESULTS Violence during the follow-up year was inversely proportional to treatment adherence , better compliance , and greater reduction of positive symptoms . Lower frequency of violent acts was observed in the depot group . The level of insight at baseline was not significantly associated with violence recidivism . Regardless of route of administration , treatment non-adherence was the best predictor of violence . CONCLUSIONS Some patients with schizophrenia and prior violent behaviour may benefit from the depot formulation of antipsychotic medication Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly . However , patients view intramuscular administration as coercive , and conventional antipsychotics are often associated with adverse events . In this open study , consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2 - 6 mg/day ( n = 48 ) or oral zuclopenthixol 20 - 50 mg/day ( n = 27 ) for 7 - 14 days . Lorazepam ( either oral or intramuscular ) was administered to both groups as needed . Patients were assessed regularly until day 14 or discharge . Mean Positive And Negative Syndrome Scale ( PANSS ) aggression scores ( sum of item scores on excitement , poor impulse control , hostility and uncooperativeness ) decreased steadily and similarly in both groups ; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point . The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group , but not in the zuclopenthixol group . Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups . Overall , 18.7 % of patients showed minor extrapyramidal symptoms during the study , but only 16.7 % of risperidone-treated patients , compared to 59.3 % of zuclopenthixol-treated patients , received anti-parkinsonian medication ( p < 0.001 ) . Lorazepam was administered to all of the patients assigned to risperidone and to 89 % of those assigned to zuclopenthixol . Oral risperidone plus lorazepam is a convenient , effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry 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 on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds , although findings are inconsistent and effect sizes small . Several method ological issues , such as heterogeneous patient sample s , incomparable drug doses , effects of prior medication , construct validity , and retest effects on neuropsychological tasks , confound most results and the comparability between studies . Consequently , the conclusion concerning effects of antipsychotics on cognition is still equivocal . OBJECTIVE The present r and omized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic ( zuclopenthixol ) and an atypical antipsychotic ( risperidone ) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting . METHODS First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment ( N=25 ) were r and omly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design . Cognitive functions were examined both when patients were drug-naive , and after 13 weeks of treatment . A comprehensive neuropsychological battery was used in order to optimize construct validity , and principal components of cognitive functions were extrapolated in order to reduce type I errors . A healthy control group was tested at baseline and after 13 weeks , in order to examine retest effects . The cognitive domains studied were executive functions , selective attention , and reaction time . RESULTS The patients showed considerable cognitive deficits when drug-naive . There were few differential effects of risperidone and zuclopenthixol on cognitive deficits , except for a differential significance , respectively , tendency towards improved reaction and movement times in the risperidone group , and a lack of such in the zuclopenthixol group . These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls . CONCLUSION The study underscores the importance of examining impact of factors , such as clinical improvement , extrapyramidal side effects , anticholinergic medication and retest effects in longitudinal efficacy studies . This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication , because neither could be distinguished from retest effects of the healthy control group The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient . Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were r and omised to receive either zuclopenthixol acetate or haloperidol . They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) and UKU Side Effects Scale . Apart from repeat injections of the same medication , no other anti-psychotic was given for the duration of the study . 50 subjects entered the study of which 44 completed . 23 were given zuclopenthixol acetate and 21 haloperidol . Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating ( p < 0.001 ) . There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days ( p > 0.05 ) . More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study . Both groups had minimal side effects . Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic One hundred mentally retarded patients from five Finnish institutions took part in a double‐blind , double‐dummy 12‐week trial assessing the therapeutic effect of cis(Z)‐clopenthixol and haloperidol . Assessment s including CGI by psychiatrists and ward personnel as well as a 4‐item target symptom scale were done at weeks 0 , 4 , 8 , and 12 . Improvement was registered by the psychiatrists in 16 , 21 , and 24 cis(Z)‐clopenthixol patients and in 11 , 6 , and 7 haloperidol patients at weeks 4 , 8 , and 12 , respectively ‐ the difference between the two drugs being significant at weeks 8 and 12 . The ratings of CGI by the personnel and the 4‐item scale by the psychiatrists showed less improvements and no significant differences between the two drugs . While the overall impression of interference of patients ’ functioning by side‐effects were in the favour of haloperidol the number of single side effects increased more with haloperidol than with cis(Z)‐clopenthixol during the 12 weeks . Average doses administered at week 12 were 34 mg cis(Z)‐clopenthixol and 5 mg haloperidol Zuclopenthixol decanoate ( ZPT‐D ) and haloperidol decanoate ( HAL‐D ) were compared in the maintenance treatment of chronic schizophrenic patients . All patients were treated with either ZPT‐D or HAL‐D for at least 3 months and were then r and omly allocated to treatment with either ZPT‐D ( 100–600 mg every 4 weeks ) or HAL‐D ( 38–200 mg every 4 weeks ) for 9 months . Sixty‐four patients entered the study . Three patients were only assessed at baseline . Four patients in the HAL‐D group were withdrawn because of deterioration . One patient in the ZPT‐D group committed suicide . Fifty‐six patients completed the trial . The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses , the Brief Psychiatric Rating Scale ( BPRS ) , Montgomery‐Åsberg Depression Rating Scale ( MADRS ) , UKU Side Effect Scale and Simpson‐Angus Scale . Ratings were made at baseline and after 12 , 24 and 36 weeks of treatment . The severity of illness scores remained almost constant . The only between‐group difference was recorded at month 6 in favour of ZPT‐D. The BPRS total scores were reduced significantly in both groups with no between‐group differences . The depression scores on the MADRS were very low . Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson‐Angus scale , and there were no significant differences between the groups . Both ZPT‐D and HAL‐D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects . The injections of ZPT‐D and HAL‐D can be given at 4‐week intervals OBJECTIVES To study the effectiveness , frequency of administration and side effects of zuclopenthixol acetate ( ZPTA ) and haloperidol ( HAL ) in the treatment of acute psychotic disturbance with aggression . METHOD Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital , they were r and omly divided into 2 groups : ZPTA group and HAL group . All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression Scale ( CGI ) . Statistical analysis was performed by using the Student t-test and Linear regression . RESULTS There were 70 patients with diagnosis of schizophrenia , mania and acute psychosis . Thirty-eight patients were r and omly assigned to the ZPTA group and were given 50 - 100 mg of the drug , while 32 patients received HAL 5 - 10 mg . The result showed a significant reduction in BPRS or CGI scores in both groups . Patients treated with ZPTA required less frequent administration than did those on HAL ( p < 0.05 ) . There was no statistically significant difference in the reduction in scores between the two groups . Nor was there a statistical difference in reduction of aggression based on BPRS rating . Each group of patients showed a few side effects of mild degree . CONCLUSION Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression , but frequency of administration was lower in the ZPTA The clinical effect of cis(Z)‐clopenthixol has been compared with that of clopenthixol , which is a mixture of the pharmacologically active cis(Z)‐isomer and the inactive trans(E)‐isomer . In the 4‐week double‐blind trial were included 20 patients with acute psychoses and exacerbations of chronic psychoses , mainly schizophrenics . Ratings evaluating severity of illness , therapeutic effect , possible interference of side effects with the patient 's functioning were done at weeks 0 , 2 , and 4 , at which occassions also the BPRS was filled in 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 Fifty-four hospitalized chronic schizophrenics were included in a double-blind controlled trial to assess the value of clopenthixol in treating [ See Table 4 in Source Pdf . ] such cases and compare its effects with those of chlorpromazine . Two rating scales were used to assess the patients clinical ly : a behavioural scale with items fairly objective and concrete , and an inferential one with items more " speculative " or " interpretative " . The patients were rated without medication and four weeks later with medication . Clopenthixol result ed in a change at the behavioural level . Chlorpromazine result ed in changes at the behavioural and inferential levels . No changes occurred with the placebo . Side-effects were not severe at therapeutically effective levels The clinical properties of clopenthixol decaonate has been investigated versus perphenazine enanthate in a double‐blind clinical multicentre trial including 14 psychiatric hospitals in Finl and , Sweden , Norway , and Denmark A double‐blind , r and omized , multi‐center , parallel‐group study was conducted in Finl and to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder . Ninety‐eight patients were r and omly assigned to treatment with risperidone ( n= 48 ) or zuclopenthixol ( n= 50 ) , in variable doses , for 6 weeks . The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively . Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression . Safety assessment s included the Extrapyramidal Symptom Rating Scale , UKU Side‐Effect Rating Scale , vital signs , body weight and laboratory screening . The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes , with a trend towards greater improvement in the overall severity of symptoms . The onset of action was significantly shorter with risperidone than with zuclopenthixol . Although the general tolerability of the two drugs was comparable , fewer patients experienced extrapyramidal symptoms with risperidone , so that significantly fewer risperidone‐treated patients required antiparkinsonian medication Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram ( 40 mg/day ) to their treatment regimen . Plasma concentrations of citalopram and its main metabolite , desmethylcitalopram , were also measured . In addition , patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase ( CYP2D6 ) genotype , an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors . There were no significant changes in plasma concentrations of haloperidol , chlorpromazine , zuclopenthixol , levomepromazine , thioridazine or perphenazine during the study . Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy , and remained stable throughout the study . None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer . It is concluded that clinical ly important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients Sixty‐three chronic schizophrenic in‐ patients were included in the double‐blind , double‐dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)‐clopenthixol and haloperidol . Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS , NOSIE‐30 , CGI and single side effects done at weeks 0 , 2 , 4 , 8 , and 12 . The average end‐of‐trial doses were 40 mg cis(Z)‐clopenthixol and 10 mg haloperidol . Statistically significant improvements of total BPRS‐score and Thinking disturbance were registered with both drugs from week 2 onwards . At week 12 when 36 patients were receiving test treatment total BPRS‐score was reduced by 31 % in the cis(Z)‐clopenthixol group and by 17 % in the haloperidol group . At week 4 Thinking disturbance was reduced by 32 % in the cis(Z)‐clopenthixol group and by 16 % in the haloperidol group ‐ these findings constituted the only significant difference between test drugs . Compared to the BPRS‐ results less improvements and no differences between test drugs were registered with NOSIE‐30 and CGI . Any trends towards different frequency and severity of side effects were in the favour of cis(Z)‐clopenthixol Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally . Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol , and were excluded . The remaining 40 patients received the test preparations for 3 to 12 weeks , with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine . Clinical evaluations were done at baseline and at weeks 1 , 2 , 4 , 6 , 8 , and 12 including the CGI , a CPRS subscale for schizophrenia , and the UKU Side Effects Rating Scale . The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily . Statistically , significant reductions on the CGI , severity of illness , and on the CPRS ( total score ) were found for both drugs when comparing baseline with later scores . No significant differences between the drugs were found . It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS . Although small differences between the two drugs were found , as regards number and type of side effects , it is concluded that the pattern of side effects was almost identical in the two treatment groups BACKGROUND We compared the efficacy of two neuroleptics with different receptor profiles ( zuclopenthixol and haloperidol ) in learning disabled patients with behavioural disturbance . METHOD A double-blind crossover study ( 2 x 8 weeks ; n = 34 ) , interrupted by a two-week single-blind washout period , was employed . Assessment s included the Schedule for H and icaps , Behaviour , and Skills ( SHBS ) and Clinical Global Impression ( CGI ) . RESULTS The SHBS score was significantly reduced for the zuclopenthixol cohort only . End-point analysis between the two drugs also showed an enhanced effect for zuclopenthixol over haloperidol . CGI scores did not reveal significant differences between the two drugs . CONCLUSION Zuclopenthixol may be superior to haloperidol for the treatment of behavioural disturbances in mentally retarded subjects We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation . A parallel-group design was used with stratification by sex . Zuclopenthixol acetate ( 50 to 150 mg ) was given intramuscularly every 3 days , whereas liquid haloperidol ( 10 to 30 mg daily ) was given orally three times a day , with supplementary doses of each medication given under double-blind conditions when needed for agitation . No other sedative drugs , including benzodiazepines , were administered . The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol . The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale . Both drugs induced similar extrapyramidal side effects . However , more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval . Sedation was higher with zuclopenthixol acetate than with haloperidol . Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections . The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia The therapeutic effect of the neuroleptic cis(Z)‐clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double‐blind 8‐week trial . Forty‐nine of the 54 patients in the trial received clopenthixol in the pre‐trial period . Ratings with CGI and a single side effects form were done at weeks 0 , 2 , 4 , 6 , and 8 . The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)‐clopenthixol with patient 's functioning than by clopenthixol . The ratio of therapeutically equipotent cis(Z)‐clopenthixol/clopenthixol doses was found to be 1:2 . It is suggested that long‐term treatment with clopenthixol advantageously may be replaced by cis(Z)‐clopenthixol Objective : Antisaccade errors are consistently increased in schizophrenia . As they have been demonstrated only in cross sectional studies , it is unclear how they vary longitudinally or with different medications . In a previous cross sectional study , we reported a trend towards a reduction in error rates in a patient group treated with risperidone , compared with clozapine and sulpiride treated groups . Methods : Gap r and om and antisaccade paradigms were performed on two occasions in the same sample of DSM-IV schizophrenic patients ( n=12 ) in transition between conventional antipsychotic drugs and risperidone . A cross over design was used with six patients switching from risperidone to conventional ( group I ) and six in the opposite direction ( group II ) . A control sample ( n=12 ) was also tested on two occasions and their performance compared . The effects of practice between first and second testing and of switching between conventional antipsychotic drugs and risperidone and vice versa was also evaluated . Results : A significant reduction in error rate was demonstrated during risperidone treatment ( n=12 ) , compared with conventional APD treatment . Switching from conventional to risperidone produced a reduction in errors , and vice versa . Conclusions : Treatment with risperidone was associated with improvement in antisaccade errors In a double-blind placebo controlled clinical trial in chronic schizophrenic patients , haloperidol and clopenthixol were found to be effective antipsychotic agents , favorably altering behavior as observed by the psychiatrist , the nurse , and ward attendants . In this respect they appeared to compare adequately to the st and ard drug , chlorpromazine . In this experiment , neither the st and ard drug nor the investigational drugs affected psychological test performance . The expected side effects such as extrapyramidal signs and sedation did occur and in some instances required dose reduction for alleviation . One case of possible hepatoxicity in the CX group occurred at the end of the study and was considered of serious import requiring cessation of medication . It was concluded that these chemically unrelated antipsychotics could be used in practice as therapeutic alternatives , the particular choice depending on side effects and possibly symptomatology Fifty-two mentally-h and icapped in- patients with associated behavioural disorders were entered into this double-blind trial comparing zuclopenthixol dihydrochloride tablets ( 10 mg ) with placebo . The study consisted of a 6-week open phase , in which all patients were treated with zuclopenthixol tablets , followed by a 12-week double-blind phase where approximately half of the patients were transferred to placebo tablets . Demographic data was obtained from the patients at entry to the study . Clinical assessment s were performed at weeks 6 , 7 , 8 , 10 , 14 and 18 using the Clinical Global Assessment ( CGA ) , a Behavioural Disorder Assessment prepared specially for this study , and a side-effect check list . Analyses of the rating scales showed significant differences in favour of zuclopenthixol at end-point on the item ' improvement in behaviour disorder ' from the CGA and at week 14 and end-point on the Assessment of Behavioural Disorder . All other results demonstrated a favourable trend towards the zuclopenthixol treatment . Side-effects were reported slightly more frequently in the zuclopenthixol group , but generally , they were not a problem 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 BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias The clinical effect of clopenthixol decanoate has been assessed in a 5‐month controlled study including 21 hospitalized chronic schizophrenic patients . The ratings were done with BPRS , NOSIE‐30 , the two psychological tests of WAIS and Grünbaum , and the rating scale of Simpson & Angus to assess extrapyramidal side effects . Clopenthixol decanoate was found an effective and longacting antipsychotic compound with few autonomic and neurological side effects . Compared with previous maintenance treatment it also showed a positive influence on depression and facilitation of the social adaptation of the patients The clinical effect of cis(Z)‐clopenthixol has been compared with that of clopenthixol , which is a mixture of the pharmacologically month double‐blind trial were included 57 psychotic patients , mainly schizophrenics . Ratings evaluating severity of illness , therapeutic effect , possible interference of side effects with the patient 's functioning , as well as any individual side effects were done at months 0 , 1 , and 2 A double-blind , multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics , zuclopenthixol and haloperidol . Patients were allocated at r and om to receive treatment with one or other of the trial drugs for 8 weeks or until discharge . Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks ' treatment . Dosage was chosen and adjusted to the individual patient 's condition and response . The average daily doses in Week 4 were 33.5 mg and 10.3 mg , respectively . Clinical assessment s , including CGI , BPRS and the UKU side-effect scale , were done at baseline , and after 1 , 2 , 4 , 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8 . Both treatments caused a significant reduction in scores with no between-group differences . More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action . Zuclopenthixol caused a significantly greater improvement in ' anxious-depression ' factor score than haloperidol . The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups . The extrapyramidal symptoms tended to be transient in the zuclopenthixol group , but not in the haloperidol group . The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute , psychotic patients . There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol |
12,666 | 29,929,739 | For acute general medical and surgical hospital wards , it was unclear whether the weekend allied health service model provided in the two identified r and omised trials led to significant changes in measured outcomes .
The benefit of providing additional allied health services is clearer in subacute rehabilitation setting s than for acute general medical and surgical wards in hospitals . | QUESTION Are additional weekend allied health services effective and cost-effective for acute general medical and surgical wards , and subacute rehabilitation hospital wards ? | Background and Purpose — The optimum model of physiotherapy service delivery for maximizing active task practice during rehabilitation after stroke is unknown . The purpose of the study was to examine the relative effectiveness of 2 alternative models of physiotherapy service delivery against a usual care control with regard to increasing patient activity . Methods — Sub study within a large 3-armed r and omized controlled trial , which compared 3 different models of physiotherapy service delivery , was provided for 4 weeks during subacute , inpatient rehabilitation ( n=283 ) . The duration of all physiotherapy sessions was recorded . In addition , 32 participants were observed at 10-minute intervals for 1 weekday and 1 weekend day between 8:00 AM and 4:30 PM . At each observation , we recorded physical activity , location , and people present . Results — Participants receiving 7-day-week and circuit class therapy received an additional 3 hours and 22 hours of physiotherapy time , respectively , when compared with usual care . Participants were st and ing or walking for a median of 8.2 % of observations . On weekdays , circuit class therapy participants spent more time in therapy-related activity ( 10.2 % of observations ) when compared with usual care participants ( 6.1 % of observations ) . On weekends , 7-day therapy participants spent more time in therapy-related activity ( 4.2 % of observations ) when compared with both usual care and circuit class therapy participants ( 0 % of observations for both groups ) . Activity levels outside of therapy sessions did not differ between groups . Conclusions — A greater dosage of physiotherapy time did not translate into meaningful increases in physical activity across the day . Clinical Trial Registration — URL : http://www.anzctr.org.au/. Unique identifier : ACTRN12610000096055 Background Increased therapy has been linked to improvements in functional ability of people with stroke . Aim To determine the effectiveness of two alternative models of increased physiotherapy service delivery ( seven-day week therapy or group circuit class therapy five days a week ) to usual care . Method Three-armed r and omized controlled trial with blinded assessment of outcome . People admitted with a diagnosis of stroke , previously independently ambulant and with a moderate level of disability were recruited . ‘ Usual care ’ was individual physiotherapy provided five-days a week . Seven-day week therapy was usual care physiotherapy provided seven-days a week . Participants in the circuit class therapy arm of the trial received physiotherapy in group circuit classes in two 90-min sessions , five-days a week . Primary outcome was distance walked on the six-minute walk test at four-weeks post-r and omization . Results Two hundred eighty-three participants were r and omized ; primary outcome data were available for 259 ( 92 % ) . In the seven-day arm participants received an additional three hours of physiotherapy and thosein the circuit class armanadditional 22 h. There were no significant between-group differences at four-weeks in walking distance ( P = 0·72 ) . Length of stay was shorter for seven-day ( mean difference −2·9 days , 95 % confidence interval −17·9 to 12·0 ) and circuit class participants ( mean difference −9·2 days , 95 % confidence interval −24·2 to 5·8 ) compared to usual care , but this was not significant . Conclusions Both seven-day therapy and group circuit class therapy increased physiotherapy time , but walking outcomes were equivalent to usual care Abstract Purpose : This study determined the impact of a pragmatic 6-day physiotherapy service on length of stay , functional independence , gait and balance in people undergoing inpatient rehabilitation , compared to a 5-day service . Method : A prospect i ve cohort study with historical comparison was undertaken in a mixed inpatient rehabilitation unit . Intervention period participants ( 2011 ) meeting inclusion criteria were eligible for a 6-day physiotherapy service . All other participants , including the historical cohort ( 2010 ) received usual care ( 5-day physiotherapy ) . Length of stay , functional independence , gait and balance performance were measured . Results : A total of 536 individuals participated in this study ; 270 in 2011 ( 60 % received 6-day physiotherapy ) and 266 in 2010 . Participants in 2011 showed a trend for reduced length of stay ( 1.7 days , 95%CI −0.53 to 3.92 ) compared to 2010 . Other measures showed no significant differences between cohorts . In 2011 , those receiving 6-day physiotherapy were more dependent , but showed significantly improved functional independence and balance compared to those receiving 5-day physiotherapy ( p < 0.040 ) without impacting length of stay . Conclusion : Implementing a 6-day physiotherapy service in a “ real-world ” rehabilitation setting demonstrated a trend towards reduced length of stay , and improved functional gains . This service could lead to cost-savings for hospitals and improved patient flow . Implication s for Rehabilitation “ Real-world ” implementation of a 6-day physiotherapy service in rehabilitation shows a trend for reducing length of stay . This reduction in length of stay may lead to cost-savings for the hospital system , and improve patient flow into rehabilitation . Patients receiving 6-day physiotherapy made significant gains in balance and functional independence compared to patients receiving 5-day physiotherapy services in the rehabilitation setting Background The cause of adverse weekend clinical outcomes remains unknown . In 2013 , the “ NHS Services , Seven Days a Week ” project was initiated to improve access to services across the seven-day week . Three years on , we sought to analyse the impact of such changes across the English NHS . Methods Aggregated trust-level data on crude mortality rates , Summary Hospital-Level Mortality Indicator ( SHMI ) , mean length of stay ( LOS ) , A&E admission and four-hour breach rates were obtained from national Hospital Episode Statistics and A&E data sets across the English NHS , excluding mental and community health trusts . Trust annual reports were analysed to determine the presence of any seven-day service reorganisation in 2013–2014 . Funnel plots were generated to compare institutional performance and a difference in differences analysis was performed to determine the impact of seven-day changes on clinical outcomes between 2013 and 2014 , 2014–2015 and 2015–2016 . Data was summarised as mean ( SD ) . Results Of 159 NHS trusts , 79 ( 49.7 % ) instituted seven-day changes in 2013–2014 . Crude mortality rates , A&E admission rates and mean LOS remained relatively stable between 2013 and 2016 , whilst A&E four-hour breach rates nearly doubled from 5.3 to 9.7 % . From 2013 to 2014 to 2014–2015 and 2015–2016 , there were no significant differences in the change in crude mortality ( 2014–2015 p = 0.8 , 2015–2016 p = 0.9 ) , SHMI ( 2014–2015 p = 0.5 , 2015–2016 p = 0.5 ) , mean LOS ( 2014–2015 p = 0.5 , 2015–2016 p = 0.4 ) , A&E admission ( 2014–2015 p = 0.6 , 2015–2016 p = 1.0 ) or four-hour breach rates ( 2014–2015 p = 0.06 , 2015–2016 p = 0.6 ) between trusts that had implemented seven-day changes compared to those which had not . Conclusions Adverse weekend clinical outcomes may not be ameliorated by large scale reorganisations aim ed at improving access to health services across the week . Such changes may negatively impact care quality without additional financial investment , as demonstrated by worsening of some outcomes . Detailed prospect i ve research is required to determine whether such reallocation of finite re sources is clinical ly effective Background Providing additional Saturday rehabilitation can improve functional independence and health related quality of life at discharge and it may reduce patient length of stay , yet the economic implication s are not known . The aim of this study was to determine from a health service perspective if the provision of rehabilitation to in patients on a Saturday in addition to Monday to Friday was cost effective compared to Monday to Friday rehabilitation alone . Methods Cost utility and cost effectiveness analyses were undertaken alongside a multi-center , single-blind r and omized controlled trial with a 30-day follow up after discharge . Participants were adults admitted for inpatient rehabilitation in two publicly funded metropolitan rehabilitation facilities . The control group received usual care rehabilitation services from Monday to Friday and the intervention group received usual care plus an additional rehabilitation service on Saturday . Incremental cost utility ratio was reported as cost per quality adjusted life year ( QALY ) gained and an incremental cost effectiveness ratio ( ICER ) was reported as cost for a minimal clinical ly important difference ( MCID ) in functional independence . Results 996 patients ( mean age 74 ( st and ard deviation 13 ) years ) were r and omly assigned to the intervention ( n = 496 ) or the control group ( n = 500 ) . Mean difference in cost of AUD$1,673 ( 95 % confidence interval ( CI ) -271 to 3,618 ) was a saving in favor of the intervention group . The incremental cost utility ratio found a saving of AUD$41,825 ( 95 % CI -2,817 to 74,620 ) per QALY gained for the intervention group . The ICER found a saving of AUD$16,003 ( 95 % CI -3,074 to 87,361 ) in achieving a MCID in functional independence for the intervention group . If the willingness to pay per QALY gained or for a MCID in functional independence was zero dollars the probability of the intervention being cost effective was 96 % and 95 % , respectively . A sensitivity analysis removing Saturday penalty rates did not significantly alter the outcome . Conclusions From a health service perspective , the provision of rehabilitation to in patients on a Saturday in addition to Monday to Friday , compared to Monday to Friday rehabilitation alone , is likely to be cost saving per QALY gained and for a MCID in functional independence . Trial registration Australian and New Zeal and Clinical Trials Registry November 2009 Background Disinvestment from inefficient or ineffective health services is a growing priority for health care systems . Provision of allied health services over the weekend is now commonplace despite a relative paucity of evidence supporting their provision . The relatively high cost of providing this service combined with the paucity of evidence supporting its provision makes this a potential c and i date for disinvestment so that re sources consumed can be used in other areas .This study aims to determine the effectiveness , cost-effectiveness and safety of the current model of weekend allied health service and a new stakeholder-driven model of weekend allied health service delivery on acute medical and surgical wards compared to having no weekend allied health service . Methods / Design Two stepped wedge , cluster r and omised trials of weekend allied health services will be conducted in six acute medical/surgical wards across two public metropolitan hospitals in Melbourne ( Australia ) . Wards have been chosen to participate by management teams at each hospital . The allied health services to be investigated will include physiotherapy , occupational therapy , speech therapy , dietetics , social work and allied health assistants . At baseline , all wards will be receiving weekend allied health services . Study 1 intervention will be the sequential disinvestment ( roll-in ) of the current weekend allied health service model from each participating ward in monthly intervals and study 2 will be the roll-out of a new stakeholder-driven model of weekend allied health service delivery . The order in which weekend allied health services will be rolled in and out amongst participating wards will be determined r and omly . This trial will be conducted in each of the two participating hospitals at a different time interval . Primary outcomes will be length of stay , rate of unplanned hospital readmission within 28 days and rate of adverse events . Secondary outcomes will be number of complaints and compliments , staff absenteeism , and patient discharge destination , satisfaction , and functional independence at discharge . Discussion This is the world ’s first application of the recently described non-inferiority ( roll-in ) stepped wedge trial design , and the largest investigation of the effectiveness of weekend allied health services on acute medical surgical wards to date .Trial registration Australian New Zeal and Clinical Trials Registry . Registration number : ACTRN12613001231730 ( first study ) and ACTRN12613001361796 ( second study ) .Was this trial prospect ively registered ? : Yes . Date registered : 8 November 2013 ( first study ) , 12 December 2013 ( second study ) .Anticipated completion : June 2015 . Protocol version : 1.Role of trial sponsor : KP and DL are directly employed by one of the trial sponsors , their roles were : KP assisted with overall development of research design and assisted with overall project management ; DL contributed to project management , administration and communications strategy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES To identify factors relating to the intensity of rehabilitation services received and to ascertain the relation between injury outcomes , demographics , types of therapy , and the intensity of rehabilitation services provided . DESIGN A multicenter , prospect i ve , nonr and omized study with inpatient rehabilitation data collected between 1989 and 1996 . SETTING Three medical centers in the federally sponsored Traumatic Brain Injury Model Systems . In each setting , the continuum of care includes emergency medical services , intensive and acute medical care , and inpatient rehabilitation . PARTICIPANTS A total of 491 consecutively enrolled patients with a mean age + /- st and ard deviation of 34.3+/-15.88 years recruited from 3 medical centers . To be included in the study , patients must have been at least 16 years of age , have presented to the emergency department within 24 hours of injury , and have received acute care and inpatient rehabilitation . INTERVENTIONS Patients received comprehensive medical care along with a combination of rehabilitative therapies , including physical , occupational , psychologic , and speech therapy . MAIN OUTCOME MEASURES Therapy intensity ; levels of functional independence , cognitive function , functional gain , and treatment efficiency , as indicated by the FIM instrument ; rehabilitation length of stay ( LOS ) ; and charges . RESULTS Age predicted the intensity of both psychologic ( P<.001 ) and total therapy ( P<.01 ) services . Acute care LOS was also a significant predictor of psychologic services ( P<.01 ) . Only admission motor FIM was relevant in predicting speech services intensity ( P<.01 ) . Therapy intensity was predictive of motor functioning at discharge ( P<.001 ) . However , therapy intensity did not predict cognitive gain ( P<.05 ) . CONCLUSIONS This study is among the first multicenter efforts to examine the potential benefits of individual therapy services . Findings support assertions that increased therapy intensity , particularly physical and psychologic therapies , enhances functional outcomes Abstract Background Many in patients receive little or no rehabilitation on weekends . Our aim was to determine what effect providing additional Saturday rehabilitation during inpatient rehabilitation had on functional independence , quality of life and length of stay compared to 5 days per week of rehabilitation . Methods This was a multicenter , single-blind ( assessors ) r and omized controlled trial with concealed allocation and 12-month follow-up conducted in two publically funded metropolitan inpatient rehabilitation facilities in Melbourne , Australia . Patients were eligible if they were adults ( aged ≥18 years ) admitted for rehabilitation for any orthopedic , neurological or other disabling conditions excluding those admitted for slow stream rehabilitation/geriatric evaluation and management . Participants were r and omly allocated to usual care Monday to Friday rehabilitation ( control ) or to Monday to Saturday rehabilitation ( intervention ) . The additional Saturday rehabilitation comprised physiotherapy and occupational therapy . The primary outcomes were functional independence ( functional independence measure ( FIM ) ; measured on an 18 to 126 point scale ) , health-related quality of life ( EQ-5D utility index ; measured on a 0 to 1 scale , and EQ-5D visual analog scale ; measured on a 0 to 100 scale ) , and patient length of stay . Outcome measures were assessed on admission , discharge ( primary endpoint ) , and at 6 and 12 months post discharge . Results We r and omly assigned 996 adults ( mean ( SD ) age 74 ( 13 ) years ) to Monday to Saturday rehabilitation ( n = 496 ) or usual care Monday to Friday rehabilitation ( n = 500 ) . Relative to admission scores , intervention group participants had higher functional independence ( mean difference ( MD ) 2.3 , 95 % confidence interval ( CI ) 0.5 to 4.1 , P = 0.01 ) and health-related quality of life ( MD 0.04 , 95 % CI 0.01 to 0.07 , P = 0.009 ) on discharge and may have had a shorter length of stay by 2 days ( 95 % CI 0 to 4 , P = 0.1 ) when compared to control group participants . Intervention group participants were 17 % more likely to have achieved a clinical ly significant change in functional independence of 22 FIM points or more ( risk ratio ( RR ) 1.17 , 95 % CI 1.03 to 1.34 ) and 18 % more likely to have achieved a clinical ly significant change in health-related quality of life ( RR 1.18 , 95 % CI 1.04 to 1.34 ) on discharge compared to the control group . There was some maintenance of effect for functional independence and health-related quality of life at 6-month follow-up but not at 12-month follow-up . There was no difference in the number of adverse events between the groups ( incidence rate ratio = 0.81 , 95 % CI 0.61 to 1.08 ) . Conclusions Providing an additional day of rehabilitation improved functional independence and health-related quality of life at discharge and may have reduced length of stay for patients receiving inpatient rehabilitation . Trial registration Australian and New Zeal and Clinical Trials Registry ACTRN12609000973213 Please see related commentary : http://www.biomed central .com/10.1186/1741 - 7015 - 11 - 199 We performed a prospect i ve correlational study to evaluate the efficiency and cost effectiveness of weekend physiotherapy in accelerating rehabilitation , reducing hospital stay as well as hospital costs for joint arthroplasty patients in a busy Scottish district general hospital . Patients that underwent elective hip ( 470 ) and knee ( 321 ) arthroplasty were analysed over a 12 month period . A four month period with weekend physiotherapy provision was arranged to ascertain its effectiveness on the length of stay and the achievement of set physiotherapy milestones . Data collected included length of stay and progression in a defined set of physiotherapy milestones . The relationship between time to discharge , mobilisation with sticks , straight leg raise , 90º knee flexion and cost effectiveness of service were used to determine the correlation , and analysis of the interactions of these factors separately . Our Outcome data demonstrate a statistical significance for the time to mobilisation with two sticks for hip ( p=0.0030 ) and knee ( p= 0.0037 ) arthroplasty patients . There was a trend towards earlier discharge times for all patients receiving weekend physiotherapy , but this was not statistically significant . We conclude that the provision of a continuous programme of weekend physiotherapy for all arthroplasty patients has the potential benefit of a quicker rehabilitation that would results in a cost saving Background Our previous work showed that providing additional rehabilitation on a Saturday was cost effective in the short term from the perspective of the health service provider . This study aim ed to evaluate if providing additional rehabilitation on a Saturday was cost effective at 12 months , from a health system perspective inclusive of private costs . Methods Cost effectiveness analyses alongside a single-blinded r and omized controlled trial with 12 months follow up inclusive of informal care . Participants were adults admitted to two publicly funded inpatient rehabilitation facilities . The control group received usual care rehabilitation services from Monday to Friday and the intervention group received usual care plus additional Saturday rehabilitation . Incremental cost effectiveness ratios were reported as cost per quality adjusted life year ( QALY ) gained and for a minimal clinical important difference ( MCID ) in functional independence . Results A total of 996 patients [ mean age 74 years ( SD 13 ) ] were r and omly assigned to the intervention ( n = 496 ) or control group ( n = 500 ) . The intervention was associated with improvements in QALY and MCID in function , as well as a non-significant reduction in cost from admission to 12 months ( mean difference ( MD ) AUD$6,325 ; 95 % CI −4,081 to 16,730 ; t test p = 0.23 and MWU p = 0.06 ) , and a significant reduction in cost from admission to 6 months ( MD AUD$6,445 ; 95 % CI 3,368 to 9,522 ; t test p = 0.04 and MWU p = 0.01 ) . There is a high degree of certainty that providing additional rehabilitation services on Saturday is cost effective . Sensitivity analyses varying the cost of informal carers and self-reported health service utilization , favored the intervention . Conclusions From a health system perspective inclusive of private costs the provision of additional Saturday rehabilitation for in patients is likely to have sustained cost savings per QALY gained and for a MCID in functional independence , for the inpatient stay and 12 months following discharge , without a cost shift into the community . Trial registration Australian and New Zeal and Clinical Trials Registry November 2009 ACTRN12609000973213 Background Older adults receiving inpatient rehabilitation have low activity levels and poor mobility outcomes . Increased physical activity may improve mobility . The objective of this Phase II study was to evaluate the feasibility of a r and omized controlled trial ( RCT ) of enhanced physical activity in older adults receiving rehabilitation . Methods Patients admitted to aged care rehabilitation with reduced mobility were r and omized to receive usual care or usual care plus additional physical activity , which was delivered by a physiotherapist or physiotherapy assistant . The feasibility and safety of the proposed RCT protocol was evaluated . The primary clinical outcome was mobility , which was assessed on hospital admission and discharge by an assessor blinded to group assignment . To determine the most appropriate measure of mobility , three measures were trialled ; the Timed Up and Go , the Elderly Mobility Scale and the de Morton Mobility Index . Results The protocol was feasible . Thirty-four percent of people admitted to the ward were recruited , with 47 participants r and omised to a control ( n = 25 ) or intervention group ( n = 22 ) . The rates of adverse events ( death , falls and readmission to an acute service ) did not differ between the groups . Usual care therapists remained blind to group allocation , with no change in usual practice . Physical activity targets were met on weekdays but not weekends and the intervention was acceptable to participants . The de Morton Mobility Index was the most appropriate measure of mobility . Conclusions The proposed RCT of enhanced physical activity in older adults receiving rehabilitation was feasible . A larger multi-centre RCT to establish whether this intervention is cost effective and improves mobility is warranted . Trial registration The trial was registered with the ANZTCR ( ACTRN12608000427370 ) Background Health services that operate 7 days per week are under pressure to show the increased cost of providing weekend services can be measured in improved patient outcomes . The evidence for weekend allied health services in acute medical and surgical wards is weak and there is wide variation between the services offered at different hospitals . Methods This qualitative study was undertaken during a multi-site stepped wedge r and omised controlled trial involving twelve acute medical and surgical wards from two Australian hospitals , in which weekend allied health services were removed before being reinstated with a stakeholder driven model . In-depth interviews were conducted with twenty-two staff responsible for managing weekend services at the involved hospitals . Participants were asked about their perceptions of the advantages and disadvantages of providing a weekend allied health service . Results Managers perceive the services improve patient flow and quality of care and reduce adverse incidents , such as falls and intensive care admissions . They also highlighted the challenges involved in planning , staffing and managing these services and the uncertainties about how to provide it most effectively . Conclusions Rising healthcare costs provide opportunity for public and professional debate about the most effective way of providing weekend allied health care services , particularly when health services provide limited other weekend services . Some managers perceived weekend allied health services to improve patient quality of care , but without studies which show these services on acute medical and surgical wards clearly change patient outcomes or provide health economic gains , these re sources may need to be redirected . The re sources may be better spent in areas with clear evidence to show the addition of weekend allied health services improves patient outcomes , such as on acute assess units and rehabilitation wards QUESTION Is additional Saturday physiotherapy intervention beneficial for in patients undergoing rehabilitation ? DESIGN R and omised controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS Two hundred and sixty-two in patients undergoing rehabilitation in an Australian metropolitan hospital . INTERVENTION The experimental group received physiotherapy intervention from Monday to Saturday and the control group from Monday to Friday . OUTCOME MEASURES Primary outcomes were hospital and physiotherapy length of stay . Secondary measures were collected to reflect patient outcomes ( health state , independence , activity , flexibility and strength ) and burden of care ( discharge destination , adverse events , and follow-up physiotherapy intervention ) . RESULTS There was a 3.2 day reduction for the experimental group ( 95 % CI -0.5 to 6.9 ) in hospital length of stay and a 2.5 day reduction ( 95 % CI -0.9 to 5.9 ) in physiotherapy length of stay . There was no significant between-group difference in change from admission to discharge for most of the secondary patient outcomes ( health state , independence , activity , flexibility ) . The risk of the experimental group being categorised as strong relative to the control group was 1.2 ( 95 % CI 0.99 to 1.50 ) . The risk of not being discharged home , of having an adverse event , or requiring follow-up physiotherapy intervention was no greater for the experimental group than the control group . CONCLUSION The provision of additional Saturday physiotherapy intervention result ed in a trend to shorter hospital and physiotherapy length of stay without affecting patient outcome unfavourably or increasing burden of care , suggesting that a larger multicentre trial is warranted Background : Early discharge after myocardial infa rct ion is safe and feasible . Factors that delay discharge need to be identified in order to improve care and reduce bed occupancy . Objective : To investigate the potential of the restricted weekend service that operates in most hospitals to delay patient discharge . Design : Prospect i ve cohort study . Subjects and setting : 2541 consecutive patients with acute myocardial infa rct ion admitted to the coronary care unit of three local district hospitals over a 12 year period . Results : Clinical factors affecting the duration of stay were age , sex , and severity of infa rct ion . Thus older patients and women stayed significantly longer , as did patients with enzymatically large infa rcts . Day of week also had an important influence on duration of stay . Discharge occurred most often on a Friday ( p = 0.006 ) and least often over the weekend ( p = 0.0001 ) . Patients were preferentially discharged on a Friday if the length of stay was more than 72 hours . Thus patients admitted on a Sunday or Monday were usually discharged the following Friday , corresponding to a median duration of stay of five or four days , respectively . For patients admitted on Tuesday to Saturday , weekend discharge was avoided and the median duration of stay was six to eight days . Conclusions : For patients with acute myocardial infa rct ion , discharge decisions were influenced appropriately by clinical indicators of risk , but inappropriately by the day of the week . Thus weekend discharge was generally avoided , leading to variations in length of stay that were largely determined by the day of the week on which admission occurred rather than clinical need Objective : To investigate if a Saturday rehabilitation service in addition to usual care improved return to work outcomes 12 months post discharge and to report predictors of return to work . Design : Subgroup analysis of a single-blind r and omized controlled trial . Setting : General inpatient rehabilitation service . Subjects : A mixed cohort of 137 adults previously engaged in work , who were admitted for inpatient rehabilitation and allocated to a control group ( n=63 ) or an intervention group ( n=74 ) . Intervention : The control group received usual care rehabilitation from Monday to Friday and the intervention group received usual care plus an additional rehabilitation service on Saturdays ( physiotherapy and occupational therapy ) . Main outcome : Return to paid or unpaid work . Results : After 12 months , 36 participants ( 57 % ) in the control group and 38 participants ( 51 % ) in the intervention group had returned to work . There was no difference between groups ( mean difference -1.06 hours per week , 95 % CI -8.70 to 6.57 ) in return to work outcomes . Functional status on discharge ( OR 1.05 , 95%CI 1.00 to 1.10 ) , an orthopaedic diagnosis ( OR 4.92 , 95%CI 2.01 to 12.03 ) and engagement in unpaid work prior to rehabilitation ( OR 5.08 , 95%CI 1.39 to 18.58 ) were predictive of return to work at 12 months . Conclusion : A Saturday rehabilitation service in addition to usual care showed no improvement in return to work outcomes at 12 months . Predictors of return to work may help identify those at risk of not returning to work and who require follow-up vocational rehabilitation services PURPOSE To describe the provision of weekend physiotherapy ( PT ) services in tertiary-care hospitals in Canada . METHODS A prospect i ve cross-sectional survey was conducted across tertiary-care hospitals , defined as those with university affiliation and at least one intensive care unit ( ICU ) . Data were collected via telephone-administered question naires addressing hospital demographics , weekend staffing , workload , and weekend referral criteria . RESULTS A response rate of 84 % ( n=36 ) was obtained . Of facilities providing weekend PT services ( 97 % ) , 35 ( 100 % ) provided care on Saturdays , 32 ( 91 % ) on Sundays , and 33 ( 94 % ) on statutory holidays . Weekend services were staffed using permanent full-time ( n=35 ; 100 % ) or part-time ( n=28 ; 80 % ) in-patient staff or out source d staff ( n=1 ; 3 % ) . The number of physiotherapists available on the weekend was smaller than the number available during the week ( p<0.001 ) . Common weekend referral criteria included cardiorespiratory problems ( n=35 ; 100 % ) , postoperative assessment of patients at risk for deterioration ( n=32 ; 91 % ) , and patients scheduled for discharge pending PT assessment ( n=30 ; 86 % ) . CONCLUSION Both the scope and the number of staff available to provide PT services were less on the weekend than during the week . Despite the use of common criteria for weekend referral , variability in this service exists . Knowledge pertaining to current weekend PT services provides opportunities for harmonization of service delivery Background Disinvestment ( removal , reduction , or reallocation ) of routinely provided health services can be difficult when there is little published evidence examining whether the services are effective or not . Evidence is required to underst and if removing these services produces outcomes that are inferior to keeping such services in place . However , organisational imperatives , such as budget cuts , may force healthcare providers to disinvest from these services before the required evidence becomes available . There are presently no experimental studies examining the effectiveness of allied health services ( e.g. , physical therapy , occupational therapy , and social work ) provided on weekends across acute medical and surgical hospital wards , despite these services being routinely provided internationally . The aim of this study was to underst and the impact of removing weekend allied health services from acute medical and surgical wards using a disinvestment-specific non-inferiority research design . Methods and findings We conducted 2 stepped-wedge cluster r and omised controlled trials between 1 February 2014 and 30 April 2015 among patients on 12 acute medical or surgical hospital wards spread across 2 hospitals . The hospitals involved were 2 metropolitan teaching hospitals in Melbourne , Australia . Data from n = 14,834 patients were collected for inclusion in Trial 1 , and n = 12,674 in Trial 2 . Trial 1 was a disinvestment-specific non-inferiority stepped-wedge trial where the ‘ current ’ weekend allied health service was incrementally removed from participating wards each calendar month , in a r and om order , while Trial 2 used a conventional non-inferiority stepped-wedge design , where a ‘ newly developed ’ service was incrementally reinstated on the same wards as in Trial 1 . Primary outcome measures were patient length of stay ( proportion staying longer than expected and mean length of stay ) , the proportion of patients experiencing any adverse event , and the proportion with an unplanned readmission within 28 days of discharge . The ‘ no weekend allied health service ’ condition was considered to be not inferior if the 95 % CIs of the differences between this condition and the condition with weekend allied health service delivery were below a 2 % increase in the proportion of patients who stayed in hospital longer than expected , a 2 % increase in the proportion who had an unplanned readmission within 28 days , a 2 % increase in the proportion who had any adverse event , and a 1-day increase in the mean length of stay . The current weekend allied health service included physical therapy , occupational therapy , speech therapy , dietetics , social work , and allied health assistant services in line with usual care at the participating sites . The newly developed weekend allied health service allowed managers at each site to reprioritise tasks being performed and the balance of hours provided by each professional group and on which days they were provided . Analyses conducted on an intention-to-treat basis demonstrated that there was no estimated effect size difference between groups in the proportion of patients staying longer than expected ( weekend versus no weekend ; estimated effect size difference [ 95 % CI ] , p-value ) in Trial 1 ( 0.40 versus 0.38 ; estimated effect size difference 0.01 [ −0.01 to 0.04 ] , p = 0.31 , CI was both above and below non-inferiority margin ) , but the proportion staying longer than expected was greater with the newly developed service compared to its no weekend service control condition ( 0.39 versus 0.40 ; estimated effect size difference 0.02 [ 0.01 to 0.04 ] , p = 0.04 , CI was completely below non-inferiority margin ) in Trial 2 . Trial 1 and 2 findings were discordant for the mean length of stay outcome ( Trial 1 : 5.5 versus 6.3 days ; estimated effect size difference 1.3 days [ 0.9 to 1.8 ] , p < 0.001 , CI was both above and below non-inferiority margin ; Trial 2 : 5.9 versus 5.0 days ; estimated effect size difference −1.6 days [ −2.0 to −1.1 ] , p < 0.001 , CI was completely below non-inferiority margin ) . There was no difference between conditions for the proportion who had an unplanned readmission within 28 days in either trial ( Trial 1 : 0.01 [ −0.01 to 0.03 ] , p = 0.18 , CI was both above and below non-inferiority margin ; Trial 2 : −0.01 [ −0.02 to 0.01 ] , p = 0.62 , CI completely below non-inferiority margin ) . There was no difference between conditions in the proportion of patients who experienced any adverse event in Trial 1 ( 0.01 [ −0.01 to 0.03 ] , p = 0.33 , CI was both above and below non-inferiority margin ) , but a lower proportion of patients had an adverse event in Trial 2 when exposed to the no weekend allied health condition ( −0.03 [ −0.05 to −0.004 ] , p = 0.02 , CI completely below non-inferiority margin ) . Limitations of this research were that 1 of the trial wards was closed by the healthcare provider after Trial 1 and could not be included in Trial 2 , and that both withdrawing the current weekend allied health service model and installing a new one may have led to an accommodation period for staff to adapt to the new service setting s. Stepped-wedge trials are potentially susceptible to bias from naturally occurring change over time at the service level ; however , this was adjusted for in our analyses . Conclusions In Trial 1 , criteria to say that the no weekend allied health condition was non-inferior to current weekend allied health condition were not met , while neither the no weekend nor current weekend allied health condition demonstrated superiority . In Trial 2 , the no weekend allied health condition was non-inferior to the newly developed weekend allied health condition across all primary outcomes , and superior for the outcomes proportion of patients staying longer than expected , proportion experiencing any adverse event , and mean length of stay . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12613001231730 and Objective : To examine whether additional therapy provided by nurses at the weekend improved the physical outcome for people with stroke on a stroke rehabilitation unit . Design : A single blind r and omized controlled trial . Setting : A 16-bed stroke rehabilitation unit in the north of Engl and . Subjects : Forty-one people with stroke were r and omized by means of minimization to intervention and control groups . Interventions : The intervention group received additional exercise at the weekend provided by the nursing staff and the control group received their usual care . Both groups received usual care during weekdays . Main outcome measures : The Motor Assessment Scale ( MAS ) , the Barthel Index ( BI ) and length of stay in hospital . Results : No significant differences were found between the groups in terms of MAS and BI at discharge but there was a borderline significant difference between the groups on unconditional testing in terms of length of stay in hospital and on the stroke unit ( p = 0.05 and p = 0.07 respectively ) . However , these findings were in favour of the control group . On conditional testing ( adjusting for BI on admission and age ) these differences disappeared ( p = 0.14 and p = 0.15 ) for length of stay in hospital and on the stroke unit respectively . Conclusions : The present study indicates that an increase in one-to-one input by nurses for people with stroke did not lead to a measurable difference in outcome in this small study Objective : To assess the effectiveness of an on-call physical therapy programme in the management of acute exacerbations of chronic obstructive pulmonary diseases . Design : R and omized controlled trial . Setting : Secondary care level , rural hospital . Subjects : Thirty-eight patients with acute exacerbations of chronic obstructive pulmonary disease . Interventions : Regular physical therapy and on-call physical therapy was given to two groups of patients with 19 in each arm . On-call physical therapy included providing respiratory physical therapy as required by the patient out of business hours . Main measures : Peak expiratory flow rate , sustained maximal inspiration , six-minute walk distance and rating of perceived exertion post six-minute walk test . Results : In the group receiving on-call physical therapy , peak expiratory flow rate and six-minute walk test showed a significant difference ( 52.1 L/min and 98.16 m , respectively ) when compared with the control group ( 211.57 ± 51.12 L/min and 159.47 ± 67.78 L/min ; P = 0.01 and 387.89 ± 110.1 m and 289.73 ± 103.2 m ; P=0.004 respectively ) . The difference in peak expiratory flow rate ( Δ peak expiratory flow rate ) was seen to be more in the on-call group ( 120 L/min ) when compared to the control group ( 50 L/min ) , P = 0.002 . Improvements in sustained maximal inspiration and Borg ’s rating of perceived exertion after the six-minute walk test were also observed ( P>0.05 ) . Conclusion : On-call physical therapy brings about a significant increase in peak expiratory flow rates , six-minute walk distance and sustained maximal inspiration BACKGROUND AND PURPOSE Physiotherapy services provided outside of business hours may improve patient and hospital outcomes , but there is limited underst and ing of what services are provided . This study described current services provided outside of business hours across Australian hospitals . METHODS Design Descriptive , cross-sectional , Web-based survey . Participants A r and om sample of Australian hospitals from the public or private sector located in either metropolitan or rural/regional areas . RESULTS A total of 112 completed surveys were su bmi tted . The most common service outside of business hours was a Saturday service , provided by 61 % of participating hospitals with a median ( interquartile range [ IQR ] ) of 1.0 hour ( 0.0 and 3.4 ) of physiotherapy per 30 beds . Sunday services were provided by 43 % of hospitals , and services provided outside of business hours from Monday to Friday were provided by 14 % of hospitals . More private hospitals provided some form of physiotherapy service outside of business hours ( 91 % ) than public hospitals ( 48 % ) . More metropolitan hospitals provided some form of physiotherapy service outside of business hours ( 90 % ) than rural/regional hospitals ( 28 % ) . Few of the hospitals providing sub-acute services had weekend physiotherapy ( 30 % ) , but the majority of highly acute wards provided weekend physiotherapy ( 81 % ) . Highly acute wards also provided more hours of service on a Saturday ( median 8.1 hours per 30 beds , IQR 0.6 - 22.5 ) compared with acute wards ( median 0.8 hours per 30 beds , IQR 0.0 - 2.8 ) . CONCLUSION There is limited availability of physiotherapy services in Australian hospitals outside of business hours . There are inequalities in physiotherapy services provided outside of business hours , with public , rural/regional and sub-acute facilities receiving fewer services outside of business hours than private , metropolitan and highly acute facilities Objective The present study evaluated the effect of an initiative to fund increased allied health ( AH ) services , enabling increased days and both volume and scope of AH services , for general medical in- patients in the Central Adelaide Local Health Network for a 6-month trial period . Methods A quasi-experimental mixed- methods study was undertaken involving general medical in- patients at two acute tertiary-referral public hospitals with a prospect i ve ( December 2015-May 2016 ) and historical comparison ( December 2014-May 2015 ) cohort . Outcome measures compared between the two cohorts included hospital length of stay ( LOS ) , occupied bed-days , adverse events and AH service data . Results After implementation of increased AH services , there were significant decreases in the median ( interquartile range ) of both hospital LOS ( from 7.2 ( 7.0 - 8.0 ) to 6.5 ( 6.1 - 6.7 ) days ; P=0.006 ) and occupied bed-days ( from 5295.0 ( 5200.0 - 5622.3 ) to 4662.5 ( 4335.8 - 4744.3 ) bed-days per month ; P=0.004 ) . There was no significant change in weekend discharges or adverse events . AH services increased , with the median number of referrals seen by AH professionals per month , occasions of AH service and AH intervention time per month increasing by 17 % , 45 % and 43 % respectively after implementation , along with a faster response time to referrals . Conclusions Increased levels of AH staffing to general medical in- patients were associated with a significant reduction in hospital LOS and occupied bed-days . What is known about the topic ? AH services are an important component in the delivery of safe , effective and efficient health care to hospitalised patients . There is little evidence specifically investigating the effect of increased AH services for general medical patients in an acute hospital setting . What does this paper add ? This study provides new evidence demonstrating that increasing AH services to general medical in- patients within two acute tertiary-referral public hospitals decreased hospital LOS and occupied bed-days , without an increase in adverse events . What are the implication s for practitioners ? A funding initiative to enable increased AH services to general medical in- patients significantly reduced hospital LOS and occupied bed-days . These findings will be of considerable interest to other healthcare centres , particularly those where AH levels are below benchmark figures OBJECTIVE To determine whether adults with lower limb orthopedic conditions who received additional weekend physical therapy ( PT ) and occupational therapy ( OT ) demonstrated increased habitual physical activity . DESIGN R and omized controlled trial . SETTING Inpatient rehabilitation center . PARTICIPANTS Adults ( N=105 , 72 women ; mean age ± SD , 74±12y ) admitted with a lower limb orthopedic condition , cognitively alert and able to walk . INTERVENTION The control group received PT and OT Monday to Friday ; in addition , the experimental group also received a full Saturday PT and OT service . Participants wore an activity monitor for 7 days . MAIN OUTCOME MEASURES Daily steps and daily upright time ( hours ) . RESULTS Overall , participants took a mean of 589±640 steps per day and spent a mean of 1.2±0.9 hours upright per day . Experimental group participants took more than twice as many steps ( mean difference , 428 steps ; 95 % confidence interval [ CI ] , 184 - 673 ) and spent 50%±20 % more time upright ( mean difference , 0.5h ; 95 % CI , 0.1 - 0.9 ) than control group participants on Saturdays . In the days after additional therapy , experimental group participants took 63%±28 % more steps ( mean difference , 283 steps ; 95 % CI , 34 - 532 ) and spent 40%±17 % more time upright ( mean difference , 0.4h ; 95 % CI , 0.1 - 0.8 ) per day than participants in the control group . CONCLUSIONS Providing additional rehabilitation services on the weekend increased habitual activity , but patients with lower limb orthopedic conditions admitted to rehabilitation remained relatively inactive even with additional therapy |
12,667 | 30,092,609 | Pooling of six studies ( 94 participants ) suggests that exercise training also improves basal hepatic insulin sensitivity ( mean change in hepatic insulin sensitivity index : 0.13 [ 0.05 to 0.21 ] mg m-2 min-1 per μU mL-1 ) , but available evidence is limited , and the impact of exercise on insulin-stimulated hepatic insulin sensitivity remains unclear | This systematic review and meta- analysis determined the impact of structured exercise training , and the influence of associated weight loss , on intrahepatic triglyceride ( IHTG ) in individuals with non-alcoholic fatty liver disease ( NAFLD ) . | Aims /hypothesisCardiac disease remains the leading cause of mortality in type 2 diabetes , yet few strategies to target cardiac dysfunction have been developed . This r and omised controlled trial aim ed to investigate high intensity intermittent training ( HIIT ) as a potential therapy to improve cardiac structure and function in type 2 diabetes . The impact of HIIT on liver fat and metabolic control was also investigated . Methods Using an online r and om allocation sequence , 28 patients with type 2 diabetes ( metformin and diet controlled ) were r and omised to 12 weeks of HIIT ( n = 14 ) or st and ard care ( n = 14 ) . Cardiac structure and function were measured by 3.0 T MRI and tagging . Liver fat was determined by 1H-magnetic resonance spectroscopy and glucose control by an OGTT . MRI analysis was performed by an observer blinded to group allocation . All study procedures took place in Newcastle upon Tyne , UK . Results Five patients did not complete the study and were therefore excluded from analysis : this left 12 HIIT and 11 control patients for the intention-to-treat analysis . Compared with controls , HIIT improved cardiac structure ( left ventricular wall mass 104 ± 17 g to 116 ± 20 g vs 107 ± 25 g to 105 ± 25 g , p < 0.05 ) and systolic function ( stroke volume 76 ± 16 ml to 87 ± 19 ml vs 79 ± 14 ml to 75 ± 15 ml , p < 0.01 ) . Early diastolic filling rates increased ( 241 ± 84 ml/s to 299 ± 89 ml/s vs 250 ± 44 ml/s to 251 ± 47 ml/s , p < 0.05 ) and peak torsion decreased ( 8.1 ± 1.8 ° to 6.9 ± 1.6 ° vs 7.1 ± 2.2 ° to 7.6 ± 1.9 ° , p < 0.05 ) in the treatment group . Following HIIT , there was a 39 % relative reduction in liver fat ( p < 0.05 ) and a reduction in HbA1c ( 7.1 ± 1.0 % [ 54.5 mmol/mol ] to 6.8 ± 0.9 % [ 51.3 mmol/mol ] vs 7.2 ± 0.5 % [ 54.9 mmol/mol ] to 7.4 ± 0.7 % [ 57.0 mmol/mol ] , p < 0.05 ) . Changes in liver fat correlated with changes in HbA1c ( r = 0.70 , p < 0.000 ) and 2 h glucose ( r = 0.57 , p < 0.004 ) . No adverse events were recorded . Conclusions /interpretationThis is the first study to demonstrate improvements in cardiac structure and function , along with the greatest reduction in liver fat , to be recorded following an exercise intervention in type 2 diabetes . HIIT should be considered by clinical care teams as a therapy to improve cardiometabolic risk in patients with type 2 diabetes . Trial registration : www.is rct n.com 78698481 Funding : Medical Research Council BACKGROUND & AIMS We determined the effects of acute and chronic calorie restriction with either a low-fat , high-carbohydrate ( HC ) diet or a low-carbohydrate ( LC ) diet on hepatic and skeletal muscle insulin sensitivity . METHODS Twenty-two obese subjects ( body mass index , 36.5 + /- 0.8 kg/m2 ) were r and omized to an HC ( > 180 g/day ) or LC ( < 50 g/day ) energy-deficit diet . A euglycemic-hyperinsulinemic clamp , muscle biopsy specimens , and magnetic resonance spectroscopy were used to determine insulin action , cellular insulin signaling , and intrahepatic triglyceride ( IHTG ) content before , after 48 hours , and after approximately 11 weeks ( 7 % weight loss ) of diet therapy . RESULTS At 48 hours , IHTG content decreased more in the LC than the HC diet group ( 29.6 % + /- 4.8 % vs 8.9 % + /- 1.4 % ; P < .05 ) but was similar in both groups after 7 % weight loss ( LC diet , 38.0 % + /- 4.5 % ; HC diet , 44.5 % + /- 13.5 % ) . Basal glucose production rate decreased more in the LC than the HC diet group at 48 hours ( 23.4 % + /- 2.2 % vs 7.2 % + /- 1.4 % ; P < .05 ) and after 7 % weight loss ( 20.0 % + /- 2.4 % vs 7.9 % + /- 1.2 % ; P < .05 ) . Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7 % weight loss ( 48.4 % + /- 14.3 % ; P < .05 ) . In both groups , insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29 % + /- 13 % and phosphorylation of Akt and insulin receptor substrate 1 increased by 35 % + /- 9 % and 36 % + /- 9 % , respectively , after 7 % weight loss ( all P < .05 ) . CONCLUSIONS Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism ; 48 hours of calorie restriction affects the liver ( IHTG content , hepatic insulin sensitivity , and glucose production ) , whereas moderate weight loss affects muscle ( insulin-mediated glucose uptake and insulin signaling ) IMPORTANCE Nonalcoholic fatty liver disease ( NAFLD ) is a prevalent risk factor for chronic liver disease and cardiovascular disease . OBJECTIVE To compare the effects of moderate and vigorous exercise on intrahepatic triglyceride content and metabolic risk factors among patients with NAFLD . DESIGN , SETTING , AND PARTICIPANTS In this r and omized clinical trial , participants with central obesity and NAFLD were recruited from community-based screening in Xiamen , China , from December 1 , 2011 , through December 25 , 2013 . Data analysis was performed from August 28 , 2015 , through December 15 , 2015 . INTERVENTIONS Participants were r and omly assigned to vigorous-moderate exercise ( jogging 150 minutes per week at 65%-80 % of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55 % of maximum heart rate for another 6 months ) , moderate exercise ( brisk walking 150 minutes per week for 12 months ) , or no exercise . MAIN OUTCOMES AND MEASURES Primary outcome , change in intrahepatic triglyceride content measured by proton magnetic resonance spectroscopy at 6 and 12 months ; secondary outcomes , changes in body weight , waist circumference , body fat , and metabolic risk factors . RESULTS A total of 220 individuals ( mean [ SD ] age , 53.9 [ 7.1 ] years ; 149 woman [ 67.7 % ] ) were r and omly assigned to control ( n = 74 ) , moderate exercise ( n = 73 ) , and vigorous-moderate exercise ( n = 73 ) groups . Of them , 211 ( 95.9 % ) completed the 6-month follow-up visit ; 208 ( 94.5 % ) completed the 12-month follow-up visit . Intrahepatic triglyceride content was reduced by 5.0 % ( 95 % CI , -7.2 % to 2.8 % ; P < .001 ) in the vigorous-moderate exercise group and 4.2 % ( 95 % CI , -6.3 % to -2.0 % ; P < .001 ) in the moderate exercise group compared with the control group at the 6-month assessment . It was reduced by 3.9 % ( 95 % CI , -6.0 % to -1.7 % ; P < .001 ) in the vigorous-moderate exercise group and 3.5 % ( 95 % CI , -5.6 % to -1.3 % ; P = .002 ) in the moderate exercise group compared with the control group at the 12-month assessment . Changes in intrahepatic triglyceride content were not significantly different between vigorous-moderate and moderate exercise at the 6- or 12-month assessment . Body weight , waist circumference , and blood pressure were significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 6-month assessment and in the vigorous-moderate and moderate exercise groups compared with the control group at the 12-month assessment . In addition , body fat was significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 12-month assessment . After adjusting for weight loss , the net changes in intrahepatic triglyceride content were diminished and became nonsignificant between the exercise and control groups ( except for the moderate exercise group at the 6-month assessment ) . CONCLUSIONS AND RELEVANCE Vigorous and moderate exercise were equally effective in reducing intrahepatic triglyceride content ; the effect appeared to be largely mediated by weight loss . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01418027 BACKGROUND & AIMS Little is known about how weight loss affects magnetic resonance imaging ( MRI ) of liver fat and volume or liver histology in patients with nonalcoholic steatohepatitis ( NASH ) . We measured changes in liver fat and liver volume associated with weight loss by using an advanced MRI method . METHODS We analyzed data collected from a previous r and omized controlled trial in which 43 adult patients with biopsy-proven NASH underwent clinical evaluation , biochemical tests , and MRI and liver biopsy analyses at the start of the study and after 24 weeks . We compared data between patients who did and did not have at least 5 % decrease in body mass index ( BMI ) during the study period . RESULTS Ten of 43 patients had at least a 5 % decrease in BMI during the study period . These patients had a significant decrease in liver fat , which was based on MRI proton density fat fraction estimates ( 18.3 % ± 7.6 % to 13.6 % ± 13.6 % , P = .03 ) , a relative 25.5 % reduction . They also had a significant decrease in liver volume ( 5.3 % ) . However , no significant changes in levels of alanine aminotransferase or aspartate aminotransferase were observed with weight loss . Thirty-three patients without at least 5 % decrease in BMI had insignificant increases in estimated liver fat fraction and liver volume . CONCLUSIONS A reduction in BMI of at least 5 % is associated with significant decrease in liver fat and volume in patients with biopsy-proven NASH . These data should be considered in assessing effect size in studies of patients with nonalcoholic fatty liver disease or obesity that use MRI-estimated liver fat and volume as end points BACKGROUND & AIMS Aerobic exercise reduces liver fat and visceral adipose tissue ( VAT ) . However , there is limited data from r and omized trials to inform exercise programming recommendations . This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a r and omized placebo-controlled design . METHODS Inactive and overweight/obese adults received 8 weeks of either ; i ) low to moderate intensity , high volume aerobic exercise ( LO : HI , 50 % VO 2peak , 60 min , 4d/week ) ; ii ) high intensity , low volume aerobic exercise ( HI : LO , 70 % VO 2peak , 45 min , 3d/week ) ; iii ) low to moderate intensity , low volume aerobic exercise ( LO : LO , 50 % VO 2peak , 45 min , 3d/week ) ; or iv ) placebo ( PLA ) . Liver fat ( spectroscopy ) and VAT ( magnetic resonance imaging ) were measured before and after intervention . RESULTS Forty-seven of the 48 ( n = 12 in each group ) participants completed the trial . There were no serious adverse events . There was a significant change in group × time interaction in liver fat , which reduced in HI : LO by 2.38 ± 0.73 % , in LO : HI by 2.62 ± 1.00 % , and in LO : LO by 0.84 ± 0.47 % but not in PLA ( increase of 1.10 ± 0.62 % ) ( p = 0.04 ) . There was a significant reduction in VAT in HI : LO ( -258.38 ± 87.78 cm(3 ) ) , in LO : HI ( -386.80 ± 119.5 cm(3 ) ) , and in LO : LO ( -212.96 ± 105.54 cm(3 ) ) , but not in PLA ( 92.64 ± 83.46 cm(3 ) ) ( p = 0.03 ) . There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT ( p > 0.05 ) . CONCLUSION The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity . All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinical ly significant weight loss Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant . Healthy older ( 73 + /- 10 yr ) women ( N = 25 ) who were inactive , but not obese , were r and omized into one of three training programs ( 9-mo duration ): 1 ) high-intensity [ 80 % peak aerobic capacity ( V(O2)peak ) ; T(H ) ] aerobic training ; 2 ) moderate-intensity ( 65 % V(O2)peak ; T(M ) ) aerobic training ; or 3 ) low-intensity ( stretching ) placebo control ( 50 % V(O2)peak ) ; C(TB ) ) . Importantly , exercise volume ( 300 kcal/session ) was held constant for subjects in both the T(H ) and the T(M ) groups . V(O2)peak was determined by using a grade d exercise challenge on a treadmill . Total body fat and lean mass were determined with dual-energy X-ray absorptiometry . The rate of insulin-stimulated glucose utilization as well as the suppression of lipolysis were determined approximately 72 h after the final exercise bout by using a two-step euglycemic-hyperinsulinemic clamp . We observed improved glucose utilization at the higher insulin dose with training , but these improvements were statistically significant only in the T(H ) ( 21 % ; P = 0.02 ) compared with the T(M ) ( 16 % ; P = 0.17 ) and C(TB ) ( 8 % ; P = 0.37 ) groups and were observed without changes in either body composition or V(O2)peak . Likewise in the T(H ) group , we detected a significant improvement in insulin-stimulated suppression ( % ) of adipose tissue lipolysis at the low-insulin dose ( 38 - 55 % , P < 0.05 ) . Our findings suggest that long-term higher intensity exercise training provides more enduring benefits to insulin action compared with moderate- or low-intensity exercise , likely due to greater transient effects It is unclear whether regular exercise alone ( no caloric restriction ) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls . We examined the effects of aerobic ( AE ) vs. resistance exercise ( RE ) alone on visceral adipose tissue ( VAT ) , intrahepatic lipid , and insulin sensitivity in obese girls . Forty-four obese adolescent girls ( BMI ≥95th percentile , 12 - 18 yr ) with abdominal obesity ( waist circumference 106.5 ± 11.1 cm ) were r and omized to 3 mo of 180 min/wk AE ( n = 16 ) or RE ( n = 16 ) or a nonexercising control group ( n = 12 ) . Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy . Intermuscular AT ( IMAT ) was measured by CT . Insulin sensitivity was evaluated by a 3-h hyperinsulinemic ( 80 mU·m(2)·min(-1 ) ) euglycemic clamp . Compared with controls ( 0.13 ± 1.10 kg ) , body weight did not change ( P > 0.1 ) in the AE ( -1.31 ± 1.43 kg ) and RE ( -0.31 ± 1.38 kg ) groups . Despite the absence of weight loss , total body fat ( % ) and IMAT decreased ( P < 0.05 ) in both exercise groups compared with control . Compared with control , significant ( P < 0.05 ) reductions in VAT ( Δ-15.68 ± 7.64 cm(2 ) ) and intrahepatic lipid ( Δ-1.70 ± 0.74 % ) and improvement in insulin sensitivity ( Δ0.92 ± 0.27 mg·kg(-1)·min(-1 ) per μU/ml ) were observed in the AE group but not the RE group . Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass ( r = -0.65 , P = 0.02 ) . In obese adolescent girls , AE but not RE is effective in reducing liver fat and visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction BACKGROUND & AIMS : Pharmacologic treatments for nonalcoholic steatohepatitis ( NASH ) are limited . Lifestyle interventions are believed to be effective in reducing features of NASH , although the effect of regular exercise , independent of dietary change , is unclear . We performed a r and omized controlled trial to study the effect of exercise on hepatic triglyceride content ( HTGC ) and biomarkers of fibrosis in patients with NASH . METHODS : Twenty‐four patients ( mean age , 52 ± 14 y ; body mass index , 33 ± 6 kg/m2 ) with sedentary lifestyles ( < 60 min/wk of moderate – vigorous activity ) and biopsy‐proven NASH were assigned r and omly to groups that exercised ( n = 12 ) or continued st and ard care ( controls , n = 12 ) for 12 weeks while maintaining their weight . The exercise ( cycling and resistance training ) was supervised at an accredited sports center and supervised by a certified exercise specialist and recorded 3 times per week on nonconsecutive days . We measured HTGC , body composition , circulating markers of inflammation , fibrosis , and glucose tolerance at baseline and at 12 weeks . RESULTS : Compared with baseline , exercise significantly reduced HTGC ( reduction of 16 % ± 24 % vs an increase of 9 % ± 15 % for controls ; P < .05 ) , visceral fat ( reduction of 22 ± 33 cm2 vs an increase of 14 ± 48 cm2 for controls ; P < .05 ) , plasma triglycerides ( reduction of 0.5 ± 1.0 mmol/L vs an increase of 0.3 ± 0.4 mmol/L for controls ; P < .05 ) , and & ggr;‐glutamyltransferase ( reduction of 10 ± 28 U/L–1 vs a reduction of 17 ± 38 U/L−1 for controls ; P < .05 ) . There were no effects of exercise on liver enzyme levels , metabolic parameters , circulatory markers of inflammation ( levels of interleukin 6 , tumor necrosis factor‐&agr ; , or C‐reactive protein ) and fibrosis . CONCLUSIONS : In a r and omized controlled trial , 12 weeks of exercise significantly reduced HTGC , visceral fat , and plasma triglyceride levels in patients with NASH , but did not affect circulating markers of inflammation or fibrosis . Exercise without weight loss therefore affects some but not all factors associated with NASH . Clinical care teams should consider exercise as part of a management strategy of NASH , but weight management strategies should be included . Larger and longer‐term studies are required to determine the effects of exercise in patients with NASH . IS RCT N registry.com : IS RCT N16070927 The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies . Currently , only limited data are available on the effects of exercise programs on insulin resistance , and visceral , hepatic , and intramyocellular fat accumulation . We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral , hepatic , and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents . Twenty-nine postpubertal ( Tanner stage IV and V ) , Hispanic adolescents , 15 obese ( 7 boys , 8 girls ; 15.6 + /- 0.4 years ; 33.7 + /- 1.1 kg/m(2 ) ; 38.3 + /- 1.5 % body fat ) and 14 lean ( 10 boys , 4 girls ; 15.1 + /- 0.3 years ; 20.6 + /- 0.8 kg/m(2 ) ; 18.9 + /- 1.5 % body fat ) , completed a 12-week aerobic exercise program ( 4 x 30 min/week at > or = 70 % of peak oxygen consumption ( VO(2)peak ) ) . Measurements of cardiovascular fitness , visceral , hepatic , and intramyocellular fat content ( magnetic resonance imaging (MRI)/magnetic resonance spectroscopy ( MRS ) ) , and insulin resistance were obtained at baseline and postexercise . In both groups , fitness increased ( obese : 13 + /- 2 % , lean : 16 + /- 4 % ; both P < 0.01 ) . In obese participants , intramyocellular fat remained unchanged , whereas hepatic fat content decreased from 8.9 + /- 3.2 to 5.6 + /- 1.8 % ; P < 0.05 and visceral fat content from 54.7 + /- 6.0 to 49.6 + /- 5.5 cm(2 ) ; P < 0.05 . Insulin resistance decreased indicated by decreased fasting insulin ( 21.8 + /- 2.7 to 18.2 + /- 2.4 microU/ml ; P < 0.01 ) and homeostasis model assessment of insulin resistance ( HOMA(IR ) ) ( 4.9 + /- 0.7 to 4.1 + /- 0.6 ; P < 0.01 ) . The decrease in visceral fat correlated with the decrease in fasting insulin ( R(2 ) = 0.40 ; P < 0.05 ) . No significant changes were observed in any parameter in lean participants except a small increase in lean body mass ( LBM ) . Thus , a controlled aerobic exercise program , without weight loss , reduced hepatic and visceral fat accumulation , and decreased insulin resistance in obese adolescents OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity UNLABELLED Nonalcoholic fatty liver disease ( NAFLD ) and alterations in hepatic lipoprotein kinetics are common metabolic complications associated with obesity . Lifestyle modification involving diet-induced weight loss and regular exercise decreases intrahepatic triglyceride ( IHTG ) content and very low density lipoprotein ( VLDL ) triglyceride ( TG ) secretion rate . The aim of this study was to evaluate the weight loss-independent effect of following the physical activity guidelines recommended by the Department of Health and Human Services on IHTG content and VLDL kinetics in obese persons with NAFLD . Eighteen obese people ( body mass index [ BMI ] : 38.1 ± 4.6 kg/m(2 ) ) with NAFLD were r and omized to 16 weeks of exercise training ( 45%-55 % VO(2peak ) , 30 - 60 minutes × 5 days/week ; n = 12 ) or observation ( control ; n = 6 ) . Magnetic resonance spectroscopy and stable isotope tracer infusions in conjunction with compartmental modeling were used to evaluate IHTG content and hepatic VLDL-TG and apolipoprotein B-100 ( apoB-100 ) secretion rates . Exercise training result ed in a 10.3 % ± 4.6 % decrease in IHTG content ( P < 0.05 ) , but did not change total body weight ( 103.1 ± 4.2 kg before and 102.9 ± 4.2 kg after training ) or percent body fat ( 38.9 % ± 2.1 % before and 39.2 % ± 2.1 % after training ) . Exercise training did not change the hepatic VLDL-TG secretion rate ( 17.7 ± 3.9 μmol/min before and 16.8 ± 5.4 μmol/min after training ) or VLDL-apoB-100 secretion rate ( 1.5 ± 0.5 nmol/min before and 1.6 ± 0.6 nmol/min after training ) . CONCLUSION Following the Department of Health and Human Services recommended physical activity guidelines has small but beneficial effects on IHTG content , but does not improve hepatic lipoprotein kinetics in obese persons with NAFLD OBJECTIVE Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test ( OGTT ) . However , the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique . In this study , we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique . RESEARCH DESIGN AND METHODS In this study , 153 subjects ( 66 men and 87 women , aged 18 - 71 years , BMI 20 - 65 kg/m2 ) with varying degrees of glucose tolerance ( 62 subjects with normal glucose tolerance , 31 subjects with impaired glucose tolerance , and 60 subjects with type 2 diabetes ) were studied . After a 10-h overnight fast , all subjects underwent , in r and om order , a 75-g OGTT and a euglycemic insulin clamp , which was performed with the infusion of [3 - 3H]glucose . The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis . RESULTS The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp ( r = -0.02 , NS ) . From the OGTT , we developed an index of whole-body insulin sensitivity ( 10,000/square root of [ fasting glucose x fasting insulin ] x [ mean glucose x mean insulin during OGTT ] ) , which is highly correlated ( r = 0.73 , P < 0.0001 ) with the rate of whole-body glucose disposal during the euglycemic insulin clamp . CONCLUSIONS Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT . Our results demonstrate the limitations of such an approach . We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT BACKGROUND & AIMS Healthy lifestyle is the most important management of non-alcoholic fatty liver disease ( NAFLD ) . This study aim ed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD . METHODS This was a parallel group , superiority , r and omized controlled trial . 154 adults with NAFLD identified during population screening were r and omized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months . The primary outcome was remission of NAFLD at month 12 as evidence d by intrahepatic triglyceride content ( IHTG ) of less than 5 % by proton-magnetic resonance spectroscopy . RESULTS 74 patients in the intervention group and 71 patients in the control group completed all study assessment s. In an intention-to-treat analysis of all 154 patients , 64 % of the patients in the intervention group and 20 % in the control group achieved remission of NAFLD ( difference between groups 44 % ; 95 % CI 30 - 58 % ; p<0.001 ) . The mean ( SD ) changes in IHTG from baseline to month 12 were -6.7 % ( 6.1 % ) in the intervention group and -2.1 % ( 6.4 % ) in the control group ( p<0.001 ) . Body weight decreased by 5.6 ( 4.4 ) kg and 0.6 ( 2.5 ) kg in the two groups , respectively ( p<0.001 ) . While 97 % of patients with weight loss of more than 10 % had remission of NAFLD , 41 % of those with weight loss of 3.0 - 4.9 % could also achieve the primary outcome . CONCLUSIONS The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients Non-alcoholic fatty liver disease ( NAFLD ) is associated with multi-organ ( hepatic , skeletal muscle , adipose tissue ) insulin resistance ( IR ) . Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown . We aim ed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral ( skeletal muscle and adipose tissue ) insulin sensitivity . Sixty nine NAFLD patients were r and omized to 16 weeks exercise supervision ( n=38 ) or counselling ( n=31 ) without dietary modification . All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride , before and following exercise/counselling . To quantify changes in hepatic and peripheral insulin sensitivity , a pre-determined subset ( n=12 per group ) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention . Results are shown as mean [ 95 % confidence interval ( CI ) ] . Fifty participants ( 30 exercise , 20 counselling ) , 51 years ( IQR 40 , 56 ) , body mass index ( BMI ) 31 kg/m(2 ) ( IQR 29 , 35 ) with baseline liver fat/water % of 18.8 % ( IQR 10.7 , 34.6 ) completed the study ( 12/12 exercise and 7/12 counselling completed the clamp studies ) . Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [ Δ mean change 4.7 % ( 0.01 , 9.4 ) ; P<0.05 ] , which correlated with the change in cardiorespiratory fitness ( r=-0.34 , P=0.0173 ) . With exercise , peripheral insulin sensitivity significantly increased ( following high-dose insulin ) despite no significant change in hepatic glucose production ( HGP ; following low-dose insulin ) ; no changes were observed in the control group . Although supervised exercise effectively reduced liver fat , improving peripheral IR in NAFLD , the reduction in liver fat was insufficient to improve hepatic IR CONTEXT It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance . OBJECTIVE Utilizing metabolic feeding and supervised exercise training , we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance . DESIGN , PARTICIPANTS , AND INTERVENTION Thirty-four obese , older subjects were r and omized to : caloric restriction with weight loss ( CR ) , exercise training with weight loss ( EWL ) , exercise training without weight loss ( EX ) , or controls . Based on an equivalent caloric deficit in EWL and CR , we induced matched weight loss . Subjects in the EX group received caloric compensation . Combined with [6,6(2)H(2)]glucose , an octreotide , glucagon , multistage insulin infusion was performed to determine suppression of glucose production ( SGP ) and insulin-stimulated glucose disposal ( ISGD ) . Computed tomography scans were performed to assess changes in fat distribution . RESULTS Body weight decreased similarly in EWL and CR , and did not change in EX and controls . The reduction in visceral fat was significantly greater in EWL ( -71 + /- 15 cm(2 ) ) compared to CR and EX . The increase in SGP was also almost 3-fold greater ( 27 + /- 2 % ) in EWL . EWL and CR promoted similar improvements in ISGD [ + 2.5 + /- 0.4 and 2.4 + /- 0.9 mg x kg fat-free mass (FFM)(-1 ) x min(-1 ) ] , respectively . CONCLUSIONS EWL promoted the most significant reduction in visceral fat and the greatest improvement in SGP . Equivalent increases in ISGD were noted in EWL and CR , whereas EX provided a modest improvement . Based on our results , EWL promoted the optimal intervention-based changes in body fat distribution and systemic insulin resistance |
12,668 | 30,347,499 | Conclusion These results are consistent with a lack of improvement in calcium dietary intake during pregnancy and confirm the gap between HICs and LMICs , with alarmingly low intakes recorded for pregnant women in LMICs . | Background Evidence shows that adequate calcium intake during pregnancy reduces the risk of hypertensive disorders of pregnancy .
In most low‐ and middle‐income countries ( LMICs ) the daily calcium intake is well below recommendations .
Mapping calcium intake during pregnancy worldwide and identifying population s with low calcium intake will provide the evidence base for more targeted actions to improve calcium intake .
Objective To assess dietary calcium intake during pregnancy worldwide . | Background Behavior Change Communications ( BCC ) play a decisive role in modifying socio-cultural norms affecting the perception and nutritional practice s during pregnancy . Objective To examine the effectiveness of ‘ Trials of Improved Practice s ’ ( TIPs ) on dietary and iron-folate intake during pregnancy . Design Community based quasi experimental study with a control group Setting Four villages of Chiraigaon Community Development Block of Varanasi , India from May 2010 and recruited from August 2010 . End line assessment , after 12 weeks of intervention , was completed in April 2011 . Participants Pregnant women in 13–28 weeks of gestation Intervention TIPs was implemented in addition to ongoing essential obstetric care services in two villages through 3 home ( assessment , negotiation and evaluation ) visits and only assessment and evaluation visits in the other two control villages . Interpersonal communication , endorsing the active participation of family members and home based reminder material s were the TIPs based strategies . The effect of TIPs was assessed by comparing key outcome variables at baseline and after 12 weeks of intervention . Outcome Measures Hemoglobin% , anemia prevalence , weight gain , compliance for iron-folate supplementation and dietary intake of calorie , protein , calcium and iron . Results A total of 86 participants completed the study . At the end , mean hemoglobin levels were 11.5±1.24 g/dl and 10.37±1.38 g/dl in the TIPs and control groups , respectively . The prevalence of anemia reduced by half in TIPs group and increased by 2.4 % in the control group . Weight gain ( grams/week ) was significantly ( p<0.01 ) higher in TIPs group ( 326.9±91.8 vs. 244.6±97.4 ) . More than 85 % of the PW in TIPs group were compliant for Iron-folate and only 38 % were compliant among controls . The mean intake of protein increased by 1.78gm in intervention group and decreased by 1.81 gm in controls ( p<0.05 ) . More than two thirds of PW in TIPs group were taking one extra meal and only one third of controls were doing the same . Conclusion TIPs found to be an effective approach to improve the nutritional status of pregnant women in the study area . TIPs strategy could be further explored on larger sample representing different socio-cultural and geographical areas . Trial Registration Clinical Trial Registry of India BACKGROUND Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human population s is lacking , despite robust evidence in animal models . OBJECTIVE We sought to evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition , including fat mass and fat-free mass . STUDY DESIGN The analysis was conducted among 1040 mother-offspring pairs enrolled in the prospect i ve prebirth observational cohort : the Healthy Start Study . Diet during pregnancy was collected using repeated 24-hour dietary recalls ( up to 8) . Direct measures of body composition were obtained using air displacement plethysmography . The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy . Multivariable partition ( nonisocaloric ) and nutrient density ( isocaloric ) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition . RESULTS The median macronutrient composition during pregnancy was 32.2 % from fat , 15.0 % from protein , and 47.8 % from carbohydrates . In the partition multivariate regression model , individual macronutrient intake values were not associated with birthweight or fat-free mass , but were associated with fat mass . Respectively , 418 kJ increases in total fat , saturated fat , unsaturated fat , and total carbohydrates were associated with 4.2-g ( P = .03 ) , 11.1-g ( P = .003 ) , 5.9-g ( P = .04 ) , and 2.9-g ( P = .02 ) increases in neonatal fat mass , independent of prepregnancy body mass index . In the nutrient density multivariate regression model , macronutrient balance was not associated with fat mass , fat-free mass , or birthweight after adjustment for prepregnancy body mass index . CONCLUSION Neonatal adiposity , but not birthweight , is independently associated with increased maternal intake of total fat , saturated fat , unsaturated fat , and total carbohydrates , but not protein , suggesting that most forms of increased caloric intake contribute to fetal fat accretion Background Although it is known that lifestyle behaviors of pregnant women are closely related to maternal and fetal health , number of data concerning efficacy of intervention on lifestyle during pregnancy is limited . The purpose of this study is to determine the effect of lifestyle interventions on improving dietary habits and lifestyle behaviors , ensuring gestational weight gain ( GWG ) within recommended levels and limiting postpartum weight retention ( PWR ) . Methods The study was conducted as a r and omized controlled trial in a family health center located in Istanbul , Turkey , between June 2011 and July 2012 . The primary outcomes were GWG , and the proportion of pregnant women whose GWG was within the Institute of Medicine ( IOM ) guidelines . One hundred two pregnant women with gestation ≤12 weeks , age ≥18 years , gravidity ≤2 , and who did not intend to lose weight in prepregnancy period were r and omly included in this study as intervention ( n = 51 ) and control ( n = 51 ) groups . The study was completed with 45 women for each group . The control group received routine antenatal care . The intervention group was received an individualized lifestyle intervention focusing on healthy lifestyle , diet , exercise , and weight monitoring as four sessions at 12–15 , 16–18 , 20–24 , and 37 weeks gestation . Lifestyle behaviors were evaluated with Health-Promoting Lifestyle Profile-II . Dietary habits were assessed by 3-day dietary recalls , and weight was followed from pregnancy until 6 weeks postpartum . Results The lifestyle interventions had a significant effect on improving lifestyle behaviors , protein intake , percentage of energy from protein , calcium , magnesium , iron , zinc , and vegetable intakes when adjusted for confounders ( p < 0.05 ) . The proportion of women who were within the IOM recommendations was higher in the intervention group ( 51.1 % ) than in the control group ( 28.9 % ) The odds ratio for GWG within IOM was statistically significant between the groups ( OR = 0.59 , 95 % CI , 0.45–0.72 ) . There were no difference between groups in terms of the other dietary intakes , total GWG , and PWR ( p > 0.05 ) . Conclusions Lifestyle intervention improves the lifestyle behaviors during pregnancy and increases the appropriate GWG for prepregnancy body mass index ( BMI ) , but it has a limited effect in terms of improving dietary habits and has no effect on PWR BACKGROUND The role played by dairy product intake during pregnancy on neonatal outcomes has raised interest in the last few years . However , studies on this association remain scarce . Thus , the aim of this study was to determine the association between dairy product consumption during pregnancy and neonatal and maternal outcomes . METHODS A prospect i ve study was conducted with 98 pregnant women , aged 18 - 40 , from the city of Porto , Portugal . Socio-demographic and lifestyle characteristics were assessed through a question naire . Dairy product consumption was assessed with a three-day food diary completed during the first and second trimesters . Postpartum medical records were examined for neonatal and maternal outcomes . Multivariate linear regression analyses were performed to assess the association between dairy intake and neonatal and maternal outcomes , adjusting for dietary variables and maternal characteristics . RESULTS Compared to the first trimester pregnant women had higher energy intake and lower calcium , iodine and yogurt intake in the second trimester ( P<0.05 ) . Total dairy and yogurt intake in the first trimester were positively associated with head circumference and placental weight ( respectively β=0.002 , P=0.014 , β=0.333 , P=0.012 ) . Change in total dairy intake between the second and first trimester was negatively associated with maternal weight gain during pregnancy ( β=-0.007 , P=0.020 ) . CONCLUSION The findings of this study suggest that dairy product intake during pregnancy may have an effect on neonatal head circumference , placental weight , and gestational weight gain Previous studies revealed associations of urinary Cd ( U-Cd ) , a chronic Cd exposure biomarker , with blood pressure ( BP ) in non-pregnant adults . However , the evidence regarding trimester-specific blood pressure in pregnancy and U-Cd and effect modification by dietary intake of micronutrients is scarce . We r and omly selected 653 women from the Omega Study cohort . U-Cd was quantified by inductively coupled plasma mass spectrometry . Trimester-specific , systolic ( SBP ) and diastolic blood pressure ( DBP ) were determined employing st and ard protocol s and mean arterial pressure ( MAP ) was also calculated . Associations of SBP , DBP , and MAP with U-Cd tertiles ( ≤0.21 ; 0.22–0.41 ; ≥0.42 μg/g Cr ) were assessed using multivariable linear regression models . We also explored effect modification by pre-pregnancy BMI ( ≤25 or > 25 kg/m2 ) or low/high micronutrients intake . After adjusting confounders in women with elevated ( upper tertile ) as compared with those with low ( lowest tertile ) U-Cd ( ≥0.42 vs. ≤0.21 μg/g Cr , respectively ) had reduced third trimester MAP ( −1.8 ; 95 % confidence interval ( CI ) = −3.1 , −0.5 mmHg ) and second trimester MAP ( −1.1 ; 95 % CI = −2.3 , −0.03 mmHg ) . A significant decrease in third-trimester MAP associated with increased U-Cd was observed only among normal/underweight women ( BMI ≤ 25 kg/m2 ) and women with high dietary intake of micronutrients ( calcium , magnesium , zinc , and selenium ) . Notably , U-Cd concentrations increased with the increased consumption of zinc and non-heme iron food sources . No significant differences in U-Cd concentrations were found in preeclamptic women compared with non-preeclamptic women . Our study provides evidence that dietary intake of micronutrients should be taken into account when assessing the health effects of Cd in pregnant women BACKGROUND Maternal diet during pregnancy has been suggested to influence bone health in later life . OBJECTIVE We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass . DESIGN In a prospect i ve cohort study in 2819 mothers and their children , we measured first-trimester daily energy , protein , fat , carbohydrate , calcium , phosphorus , and magnesium intakes by using a food-frequency question naire and homocysteine , folate , and vitamin B-12 concentrations in venous blood . We measured childhood total body bone mass by using dual-energy X-ray absorptiometry at the median age of 6.0 y. RESULTS Higher first-trimester maternal protein , calcium , and phosphorus intakes and vitamin B-12 concentrations were associated with higher childhood bone mass , whereas carbohydrate intake and homocysteine concentrations were associated with lower childhood bone mass ( all P-trend < 0.01 ) . Maternal fat , magnesium intake , and folate concentrations were not associated with childhood bone mass . In the fully adjusted regression model that included all dietary factors significantly associated with childhood bone mass , maternal phosphorus intake and homocysteine concentrations most-strongly predicted childhood bone mineral content ( BMC ) [ β = 2.8 ( 95 % CI : 1.1 , 4.5 ) and β = -1.8 ( 95 % CI : -3.6 , 0.1 ) g per SD increase , respectively ] , whereas maternal protein intake and vitamin B-12 concentrations most strongly predicted BMC adjusted for bone area [ β = 2.1 ( 95 % CI : 0.7 , 3.5 ) and β = 1.8 ( 95 % CI : 0.4 , 3.2 ) g per SD increase , respectively ] . CONCLUSION Maternal first-trimester dietary factors are associated with childhood bone mass , suggesting that fetal nutritional exposures may permanently influence bone development Obese pregnant women are the focus of numerous dietary and lifestyle intervention studies , however there is a paucity of literature examining the habitual dietary and lifestyle habits of this population . This paper aims to assess maternal dietary and lifestyle habits in an obese cohort , in order to identify priority areas to be addressed in future studies and in clinical practice . This prospect i ve observational study recruited 100 pregnant women with a body mass index 30.0–39.9 kg/m2 from routine antenatal clinics . Dietary intakes were assessed using a 3-day food diary and a structured lifestyle question naire assessed physical activity levels , smoking and alcohol habits and wellbeing . Macronutrient intakes as a percentage of total energy were not compliant to healthy eating guidelines with an inadequate intake of carbohydrate and excess intake of saturated fat . Compliance to recommended intakes of calcium , iron , folate and vitamin D was poor from diet alone . The consumption of energy dense food groups high in fat and sugar was greater than for published pregnant population s and the general female non-pregnant population . One-third of women reported engaging in weekly physical activity that would comply with recommendations for pregnant women while 25 % reported low mood status indicating potential depression . High intakes of energy-dense processed foods and poor compliance to micronutrient recommendations are critical dietary issues of concern among obese pregnant women . Low mood is a barrier to motivation for changing behaviour which would also need to be addressed in future lifestyle intervention studies OBJECTIVE To study the effect of calcium supplementation during pregnancy on blood pressure and maternal and neonatal outcomes . METHOD A total of 524 healthy primigravidas with a blood pressure less than 140/90 mm Hg were r and omly assigned between the 12th and 25th weeks to receive 2 g of elemental calcium or placebo and were followed-up until delivery . RESULTS The incidence of pre-eclampsia was significantly less in the calcium than in the placebo group ( 4.0 % vs 12.0 % ; odds ratio [ OR ] , 0.31 ; 95 % confidence interval [ CI ] , 0.15 - 0.63 ) ; the mean systolic and diastolic blood pressures at study completion were different in the calcium and placebo group ( P=0.007 and P=0.02 ) . The risk for preterm delivery was less in the calcium ( 7.0 % ) than in the placebo ( 12.7 % ) group ( OR , 0.51 ; 95 % CI , 0.28 - 0.93 ) . The mean baseline calcium intake was 313.83+/-203.25 mg/day ( range , 85.71 - 910.71 mg/day ) , which is lower than the recommended dietary intake of 1000 mg , and the 24-hour urinary calcium excretion was 130.82+/-67.44 mg/dL ( range , 40.5 - 387 mg/dL ) . CONCLUSION Calcium supplementation appears to reduce the occurrence of pre-eclampsia and preterm delivery in primigravidas who have a daily dietary calcium intake less than the recommended dietary allowances Background : Since preterm premature rupture of membranes ( PPROM ) is one of the most important complications of pregnancy and its relationship with nutrition status have not been surveyed comprehensively , we decided to study the relationship of maternal received nutrients ( 36 macro- and micro-nutrients ) in three trimesters and PPROM which could be considered as a unique study . Material s and Methods : In this prospect i ve cohort study , data was collected by filling a question naire through interviews with 620 pregnant women who had no parameters to affect pregnancy outcome . 48-hr dietary recalls were completed for eligible women at 11th–15th , 26th , 34th–37th weeks of gestation . Physical activity was also assessed using a st and ard question naire . Also pregnant mother 's reproductive and demographic characteristic and supplementation are considered . Results : The mean value of received saturated fatty acids , polyunsaturated fatty acids and energy , in the first trimester ( P < 0.001 , P= 0.007 , and P < 0.001 respectively ) , the mean values of calcium , sodium intake in the second trimester ( P = 0.045 , P= 0.006 , and P= 0.004 respectively ) , Vitamins C , A ( mg ) , β-carotene , cartenoids intake in the second trimester ( P = 0.03 , P= 0.001 , P= 0.007 , and P= 0.01 respectively ) , and higher Vitamin C intake during the first trimester ( P = 0.02 ) was significantly greater among subjects with PPROM compared to the others . Conclusions : The mean value of mentioned received nutrients in subjects who experienced PPROM later in pregnancy was higher than the others , which is independent of demographic and reproductive characteristic , estimated physical activity , and supplementation . Therefore , these findings could be considered in the nutritional programming for pregnant women to manage the risk of PPROM Objective : The purpose of this trial is to investigate the relationship between dietary calcium content and incidence of preeclampsia , comparing diet calcium content in normotensive and preeclampsia patients . Dietary calcium was measured by a dietary interview conducted at the day after delivery . Methods : This is a prospect i ve cross-sectional study involving 1092 patients who delivered at Hospital de Clínicas de Porto Alegre – Brazil . Results : The average diet calcium content in the studied population was 1038 mg . The average calcium intake in the normotensive group was 1057 mg , in chronic hypertension group was 962 mg , in transient hypertension group was 963 mg , in mild preeclampsia was 902 mg and in severe preeclampsia group was 755 mg . The results of this study show that pregnant women who develop severe preeclampsia have a significant lower diet calcium intake when compared to normotensive women ( P = 0.018 ) . Conclusion : The results of the present study can provide the foundations for prospect i ve trials , including r and omised clinical trials involving only patients with a low content of calcium in their diet Micronutrient deficiencies and imbalanced dietary intake tend to occur during the reproductive period among women in China . In accordance with traditional Chinese culture , pregnant women are commonly advised to follow a specific set of dietary pre caution s. The purpose of this study was to assess dietary intake data and identify risk factors for nutritional inadequacy in pregnant women from urban and rural areas of Deyang region , Sichuan province of China . Cross-sectional sampling was applied in two urban hospitals and five rural clinics ( r and omly selected ) in Deyang region . Between July and October 2010 , a total of 203 pregnant women in the third trimester , aged 19–42 years , were recruited on the basis of informed consent during antenatal clinic sessions . Semi-structured interviews on background information and 24-h dietary recalls were conducted . On the basis of self-reported height and pre-pregnancy weight , 68.7 % of the women had a pre-pregnancy body mass index ( BMI ) within the normal range ( 18.5 ≤ BMI < 25 ) , 26.3 % were found to be underweight with a BMI < 18.5 ( 20.8 % in urban vs. 35.6 % in rural areas ) , while only 5.1 % were overweight with a BMI ≥30 . In view of acceptable macronutrient distribution ranges ( AMDRs ) the women ’s overall dietary energy originated excessively from fat ( 39 % ) , was low in carbohydrates ( 49.6 % ) , and reached the lower limits for protein ( 12.1 % ) . Compared to rural areas , women living in urban areas had significantly higher reference nutrient intake ( RNI ) fulfillment levels for energy ( 106.1 % vs. 93.4 % ) , fat ( 146.6 % vs. 119.7 % ) , protein ( 86.9 % vs. 71.6 % ) , vitamin A ( 94.3 % vs. 65.2 % ) , Zn ( 70.9 % vs. 61.8 % ) , Fe ( 56.3 % vs. 48 % ) , Ca ( 55.1 % vs. 41 % ) and riboflavin ( 74.7 % vs. 60 % ) . The likelihood of pregnant women following traditional food recommendations , such as avoiding rabbit meat , beef and lamb , was higher in rural ( 80 % ) than in urban ( 65.1 % ) areas . In conclusion , culturally sensitive nutrition education sessions are necessary for both urban and rural women . The prevalence of underweight before conception and an insufficient supply of important micronutrients were more pronounced in rural areas . Therefore , attention must be given to the nutritional status , especially of rural women before , or at the latest , during pregnancy Background : During the last 3 decades , China has dramatic changes of the dietary pattern among its citizens , particularly in urban cities . This study aim ed to determine the nutrient intake status and factors associated with nutrient intakes of urban Chinese pregnant women now-a-day . Methods : The multistage stratified r and om sampling method was applied in the cross-sectional study . 479 women in three trimesters of pregnancy from eight cities of China were recruited . Nutrient intakes were evaluated with one 24 h dietary recall , and compared with the Chinese Dietary Reference Intakes ( DRIs ) 2013 for available nutrients . Results : Most pregnant women had imbalanced macronutrient distribution with excessive energy derived from fat . Intakes of Vitamin A , B6 , calcium , magnesium , and selenium were below Chinese Recommended Nutrient Intake ( RNI ) and Estimated Average Requirements ( EARs ) in all trimesters . Most pregnant women took more folic acid in the first trimester with a significant decrease in the second and third trimester ( P < 0.05 ) . Shortfall in iron intake was found in the third trimester whereas some women may be at the risk of excessive iron intake . Intakes of thiamin met RNI in the first trimester but were below EAR in all trimesters . Trimester phasing was positively associated with most nutrients ( P < 0.05 ) . Prepregnancy body mass index was inversely associated with energy , fat , Vitamin C , and calcium intake ( P < 0.05 ) . Educational level and household income were positively associated with folic acid intake ( P < 0.05 ) . Conclusions : Current prenatal dietary choices of urban pregnant women in China are imbalanced in the nutrient intake when compared with national DRIs 2013 , particularly in intakes of energy derived from fat and micronutrients . Appropriate dietary advice to pregnant women should promote a balanced diet with emphasis on avoidance of foods of high fat content and incorporation of foods that are good sources of the key micronutrients that are usually lacking in a regular pregnancy diet . Further research is needed to underst and the eating habits and food patterns that contribute to this imbalanced diet in order to be able to effectively improve prenatal women 's nutrient intake status BACKGROUND Maternal obesity and excessive gestational weight gain ( GWG ) are major short- and long-term risk factors for maternal and fetal complications . OBJECTIVE The objective was to study whether a lifestyle intervention based on a brochure or on active education can improve dietary habits , increase physical activity ( PA ) , and reduce GWG in obese pregnant women . DESIGN In this r and omized controlled trial , 195 white , obese pregnant women [ age : 29 + or - 4 y ; body mass index ( in kg/m(2 ) ) ; 33.6 + or - 4.2 ] were r and omly assigned into 3 groups : a group that received nutritional advice from a brochure , a group that received the brochure and lifestyle education by a nutritionist , and a control group . Nutritional habits were evaluated every trimester through 7-d food records . PA was evaluated with the Baecke question naire . RESULTS Energy intake did not change during pregnancy and was comparable in all groups . Fat intake , specifically saturated fat intake , decreased and protein intake increased from the first to the third trimester in the passive and active groups compared with an opposite change in the control group . Calcium intake and vegetable consumption increased during pregnancy in all groups . PA decreased in all groups , especially in the third trimester . No significant differences in GWG and obstetrical or neonatal outcome could be observed between the groups . CONCLUSIONS Both lifestyle interventions improved the nutritional habits of obese women during pregnancy . Neither PA nor GWG was affected Objective : This study was carried out to evaluate the dietary nutrient intake of pregnant women . The relationship between dietary intake and pregnancy outcome was also studied . Method : A total of 114 pregnant women were studied , using systematic r and om sampling . Results : The percentages of the mean nutrient intake below the recommended dietary allowances ( RDA ) for pregnant women were as the follows : 51.8 % , 93.9 % , 82.5 % and 98.2 % for energy , vitamin B1 , calcium and iron , respectively . Moreover , 13.2 % of the women experienced some form of pica . Using height and mid-arm circumferences , about 2.8 % and 4.4 % were seen to be undernourished respectively . Conclusion : Saudi pregnant women need guidance in selecting nutrient dense foods to reduce maternal and outcome health hazards Abstract Although pregnant women are required to increase food and nutrient intake to accommo date for the increased nutritional dem and s , information on dietary behaviour and nutrient intake is limited . This study aim ed to identify the adequacy and differences in intake between pregnant and non‐pregnant women in a rural community of Butajira district , Southern Ethiopia . Simple r and om sampling was used to recruit 159 pregnant and 164 non‐pregnant women . An interactive multiple pass 24‐h recall survey was used to evaluate the food and nutrient intake of the study participants . Except for iron , vitamin A and C , intakes of macro and micronutrient were below the recommendations . Almost all study participants were deficient in energy , protein , calcium , folate and niacin intakes . There was no significant difference in the mean dietary intake of all nutrients between pregnant and non‐pregnant women ( p > 0.05 ) . The prevalence of inadequacy was comparable between pregnant and non‐pregnant women in all of the nutrient intakes except for Zn , where the prevalence of inadequacy was much higher among the pregnant women . Nearly all ( 99.0 % ) of the pregnant women were deficient in niacin , folate and calcium . Although all pregnant women considered it important to increase food intake during pregnancy , only a quarter of women reported to do so . In conclusion , pregnant women in the rural community of Butajira district do not make significant dietary intake adjustments to account for increased nutrient needs during pregnancy . In food insecure areas , such as ours , nutritional counselling complemented with supplementary feeding programmes could be key to ensure adequate dietary intake . © 2016 John Wiley & Sons OBJECTIVE : To evaluate the effects of dietary calcium ( Ca ) intervention on adolescent pregnant mothers and their newborns . METHODS : Seventy-two pregnant adolescent mothers were r and omized into one of 3 groups : control , orange juice fortified with calcium , and dairy . The orange juice and dairy groups were required to take more than 1,200 mg Ca . Calcium tablets were added for those not able to meet required Ca . Maternal and infant weight , length , and blood pressure ( BP ) were recorded . Maternal dietary records were evaluated . Mother ’s blood was drawn for serum Ca , phosphate ( P ) , magnesium ( Mg ) , and vitamin 25-hydroxyvitamin D ( D ) . Cord blood was collected for serum Ca and D. Newborn total body Ca was determined . RESULTS : All mothers were similar in weight , height , and BP . Mothers in the orange juice plus calcium and dairy groups had higher intakes of Ca ( 1,472 mg and 1,771 mg ) than controls ( 862 mg ) . One half of the mothers in the orange juice plus calcium group required Ca tablets . Mothers in the dairy group had higher intakes of P , D , and Mg , higher serum folate and D , and higher cord D levels . Mothers in the orange juice plus calcium group had higher serum P but lower serum folate and D. Infants ( 3,517±273 g ) in the dairy group were heavier than infants in the control ( 3,277±177 g ) and orange juice plus calcium ( 3,292±165 g ) groups . Infants in the dairy group had higher total body calcium than control infants . CONCLUSION : Calcium diet supplemented with dairy products during adolescent pregnancy result ed in higher maternal vitamin D and folate serum levels and higher newborn weight and bone mineralization compared with controls . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00320125 LEVEL OF EVIDENCE : INTRODUCTION The purpose of this study was to evaluate the relationships between first-trimester dietary factors and biochemical measures and subsequent risk of gestational hypertension . METHODS This pilot study used a prospect i ve design utilizing a convenience sample of nulliparous women enrolled at their first prenatal visit . A total of 57 women completed the study . Participants were divided into 2 groups for data analysis : normotensive pregnancy and gestational hypertension . RESULTS Nearly one-quarter of study participants ( 22.8 % ) developed gestational hypertension , of whom 84.6 % had significant proteinuria meeting the criteria for preeclampsia . There were no significant differences in micronutrient or macronutrient dietary intakes between groups . Serum iron and zinc levels were lower for the gestational hypertension group compared with the normotensive pregnancy group ( P ≤ .01 ) . Low serum zinc levels were related to a risk of developing gestational hypertension ( adjusted odds ratio , 0.930 ; 95 % confidence interval , 0.872 - 0.992 ) . DISCUSSION Ensuring adequate intake of zinc and monitoring serum zinc levels in nulliparous pregnant women may help to prevent or contribute to early detection of gestational hypertension Objective Calcium dem and is increased during pregnancy . However , few r and omized controlled trials examined the effects of calcium supplementation on bone mass during pregnancy . This study determined effects of calcium and milk supplementation on maternal bone mineral density ( BMD ) and bone turnover in pregnant Chinese women with habitual low calcium intake . Methods In this r and omized controlled trial , 36 Chinese pregnant women ( 24–31 years , 18 gestational weeks ) were r and omly assigned to the following three arms ( 12 each ) : I , usual diet ; II , “ I ” + 45 g milk powder ( containing 350 mg calcium ) ; or III , “ II ” + 600 mg calcium/day from gestational age of 20 weeks to 6 weeks post-partum ( PP ) . BMD was measured post-treatment using dual-energy X-ray absorptiometry . Dietary intakes , 24-h urinary calcium , bone resorption ( urinary hydroxyproline ) and formation ( serum osteocalcin ) biomarkers were examined at the gestational age of 20 and 34 weeks , and 6 weeks PP . Results A dose-dependent relationship was observed between calcium intake and BMDs . The BMD values were significantly higher in subjects with calcium and milk supplementation than those in the controls at the whole body and spine ( p < 0.05 ) but not at the hip sites . We found significant decreases in changes of urinary hydroxyproline , and significant increases in serum osteocalcin during the intervention period in the calcium/milk intervention groups than those in the control group ( all p < 0.05 ) . Conclusion Calcium/milk supplementation during pregnancy is associated with greater BMD at the spine and whole body and suppresses bone resorption in Chinese women with habitual low calcium intake Background : The objective of this study was to determine the favorable effects of multi mineral-Vitamin D supplementation on pregnancy outcomes among women at risk for pre-eclampsia . Methods : This r and omized double-blind controlled clinical trial was conducted among 46 women at risk for pre-eclampsia at 27 weeks ’ gestation with positive roll-over test . Pregnant women were r and omly assigned to receive either the multi mineral-Vitamin D supplements ( n = 23 ) or the placebo ( n = 23 ) for 9-week . Multi mineral-Vitamin D supplements were containing 800 mg calcium , 200 mg magnesium , 8 mg zinc , and 400 IU Vitamin D3 . Fasting blood sample s were taken at baseline and after 9-week intervention to measure related factors . Newborn 's outcomes were determined . Results : Although no significant difference was seen in newborn 's weight and head circumference between the two groups , mean newborns ’ length ( 51.3 ± 1.7 vs. 50.3 ± 1.2 cm , P = 0.03 ) was significantly higher in multi mineral-Vitamin D group than that in the placebo group . Compared to the placebo , consumption of multi mineral-Vitamin D supplements result ed in increased levels of serum calcium ( + 0.19 vs. −0.08 mg/dL , P = 0.03 ) , magnesium ( + 0.15 vs. −0.08 mg/dL , P = 0.03 ) , zinc ( + 8.25 vs. −21.38 mg/dL , P = 0.001 ) and Vitamin D ( + 3.79 vs. −1.37 ng/ml , P = 0.01 ) . In addition , taking multi mineral-Vitamin D supplements favorably influenced systolic blood pressure ( SBP ) ( −1.08 vs. 6.08 mmHg , P = 0.001 ) and diastolic blood pressure ( DBP ) ( −0.44 vs. 3.05 mmHg , P = 0.02 ) . Conclusions : Multi mineral-Vitamin D supplementation for 9-week in pregnant women at risk for pre-eclampsia result ed in increased newborn 's length , increased circulating levels of maternal serum calcium , magnesium , zinc and Vitamin D , and led to decreased maternal SBP and DBP BACKGROUND Despite normal gestational weight gain , dietary studies in pregnant women show intakes below the recommendations for energy and micronutrients . OBJECTIVE This study compared changes in dietary intake from the second to third trimester with emphasis on energy intake and carbohydrate quality . DESIGN These post hoc analyses were based on 566 women participating in the Pregnancy and Glycemic Index Outcomes study , a r and omized controlled trial comparing the effect of low-glycemic index ( GI ) dietary advice with healthy eating advice on selected pregnancy outcomes . With the use of multilevel mixed-regression analysis , changes in total energy intake , starch , sugar , fiber intake , GI , and glycemic load ( GL ) were correlated with intake of different micronutrients . RESULTS Energy intake decreased in the third trimester , and most women did not meet the national recommended amounts for iron , folate , and dietary fiber from food sources alone . After adjustment for age , ethnicity , prepregnancy body mass index , and intervention group , change in energy intake was positively related to change in intake of all micronutrients ( P < 0.001 ) . GI , GL , and starch intake were inversely related to micronutrient intake ( P < 0.001 ) , whereas higher total sugars predicted higher intake ( P < 0.001 ) . Associations with dietary fiber were inconsistent . CONCLUSIONS Normal pregnancy can be associated with a decline in energy and micronutrient intake from diet . Low dietary GI and GL were the best predictors of a favorable micronutrient profile . This trial was registered at www.anzctr.org.au as ACTRN12610000174088 This cross-sectional study assessed the influence of duration of residence in the United States on periconception dietary intake of pregnant Mexican immigrant women , using baseline data from Healthy Mothers on the Move , a r and omized control trial conducted with 234 women from 2004 to 2006 in Detroit , MI . Average maternal age was 27.3±5.2 years ( range=18 to 41 years ) with 5.99±4.76 years of US residence ( range=0 to 36 years ) . Women 's usual dietary intake during the past 12 months was recorded on a vali date d food frequency question naire ( 17.3 weeks average gestation ) . Intakes of selected micronutrients , macronutrients , and food groups were compared by US residence categories ( ≤5 , 6 to 10 , or ≥11 years ) using analysis of covariance . The percent of women with intakes below the Estimated Average Requirement and the percent not meeting US dietary guidelines were calculated . There was no association between dietary intake and duration of US residence in this population . Percentages of women with dietary intake below the Estimated Average Requirement were : 12.0 % for folate , 7.7 % for vitamin C , 23.9 % for calcium , 11.2 % for protein , and 5.1 % for carbohydrates . US dietary guidelines were not met for fruit by 17.5 % and for vegetables by 74.8 % of women . Typical diets were high in saturated fat and cholesterol . Of the 2,195 kcal average daily energy intake , > 25 % came from saturated fats , trans fats , and added sugars that may replace nutrients important for healthy fetal growth and development and women 's health . Interventions to improve intake before , during , and after pregnancy are important in this population , regardless of duration of US residence In a study population that comprised 34 normal black pregnant women , biochemical changes are compared between a group of women who received 1.5 gm of calcium supplementation a day and a group of women who received placebos . The blood pressure-lowering effect of calcium supplementation appears to involve a mechanism that relates parathyroid hormone and plasma renin activity . Other alterations in calcium and magnesium metabolism , as reflected by increased urinary calcium excretion and serum magnesium levels , may also contribute to this effect . Subgroups of study participants with initial ( less than 26 weeks ' gestation ) low levels of serum calcium and plasma renin activity are the ones with the largest reductions in blood pressure . Whether these alterations can produce a reduction in the incidence of pregnancy-induced hypertension is the next question to be answered in this area Purpose Pregnancy is characterised by increased bone turnover , but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling . Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy . The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D ( 25OHD ) and dietary calcium on a marker of bone resorption . Methods This was prospect i ve study of 205 pregnant women [ two cohorts ; early pregnancy at 13 weeks ( n = 96 ) , and late pregnancy at 28 weeks ( n = 109 ) ] . Serum 25OHD and urine cross-linked N-telopeptides of type I collagen ( uNTX ) were measured at both time points . Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester . Results Compared to summer pregnancies , winter pregnancies had significantly lower 25OHD and significantly higher uNTX . Higher calcium intakes were negatively correlated with uNTX in winter , but not summer . In late pregnancy , compared to those reporting calcium intakes ≥1000 mg/day , intakes of < 1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer ( 41.8 vs. 0.9 % ) . Increasing calcium intake in winter by 200 mg/day predicted a 13.3 % reduction in late pregnancy uNTX . Conclusions In late pregnancy , during winter months when 25OHD is inadequate , intakes of dietary calcium < 1000 mg/day were associated with significantly increased bone resorption ( uNTX ) . Additional dietary calcium is associated with reduced bone resorption in late pregnancy , with greater effect observed in winter . Further research regarding optimal dietary calcium and 25OHD in pregnancy is required , particularly for women gestating through winter BACKGROUND Excessive gestational weight gain ( GWG ) is associated with adverse maternal-child health outcomes . Managing energy intake and GWG versus optimising nutrient intake can be challenging . The present study aim ed to examine the relationships between dietary portion size , GWG and nutrient intakes during pregnancy . It is hypothesised that , after adjustment for potential confounders , portion size would be positively associated with both GWG and nutrient intakes during pregnancy . METHODS Prospect i ve data were obtained for 179 Australian women from the Women and Their Children 's Health Study . A vali date d food frequency question naire was used at 18 - 24 and 36 - 40 weeks of gestation to quantify diet and portion size during the previous 3 months of pregnancy . Nutrient intakes were compared with Australian Nutrient Reference Values ( NRVs ) . GWG was measured up to 36 weeks and compared with the Institute of Medicine weight gain recommendations ( WtAdh ) . RESULTS In multivariate regression models , portion size factor ( PSF ) was positively associated with GWG in women with high socio-economic status ( SES ; β = 0.20 , P = 0.04 ) and those with an overweight/obese pre-pregnancy body mass index ( BMI ) ( β = 0.28 , P = 0.04 ) . PSF uniquely accounted for 8.2 % and 3.7 % of the variability in GWG for women with high SES and overweight/obese pre-pregnancy BMI s , respectively . Nutrient intakes and PSF were similar regardless of WtAdh . Women achieved NRVs for calcium and zinc in all PSF categories . Most of the women with large PSF still failed to achieve the NRVs for folate ( 95.7 % ) , iron ( 89.6 % ) and fibre ( 85.5 % ) . CONCLUSIONS All women require advice on quality food choices during pregnancy to optimise health outcomes . Targeting portion size alone is insufficient to manage GWG but may prove to be a valuable tool in pregnant women of high SES and /or those who are overweight/obese pre-pregnancy Purpose : Activity restriction ( AR ) , one of the most common interventions used in high-risk pregnancies , may exacerbate loss of bone mass . The purpose of this study was to determine changes over time in bone resorption in hospitalized AR women during late pregnancy . Methods : This was a short-term prospect i ve study conducted in two tertiary-care obstetric hospitals . We measured urinary deoxypyridinoline ( Dpd ) excretion , a marker of bone resorption , once per week in a convenience sample of 14 hospitalized AR women in the third trimester and compared values at 28–31 and 34–36 weeks ’ gestation to those of 11 ambulatory control women . Both groups completed a bone-loading question naire , 3-day food intake record , and pedometer step counts at the same gestational age . Results : Urinary Dpd excretion increased from Days 1–7 ( 2.60 ± 0.32 nmol/mmol creatinine ) to Days 22–28 ( 5.36 ± 0.83 nmol/mmol creatinine ; p ≤ .05 ) . Dpd excretion was higher in AR women ( 4.51 ± 0.31 nmol/mmol creatinine ) than ambulatory women ( 2.72 ± 0.39 nmol/mmol creatinine ) at 34–36 weeks ’ gestation ( p ≤ .05 ) . Energy intake between ambulatory and AR women was not different ( p ≥ .05 ) . All women met the daily requirements for calcium and vitamin D intake during pregnancy . Average daily pedometer steps for the AR women were significantly less compared to controls ( 1,329 ± 936 and 8,024 ± 1,890 steps/day , respectively ; p ≤ .05 ) . Conclusions : AR leads to increased bone resorption in hospitalized pregnant women , which may impact future risk of developing osteopenia and osteoporosis |
12,669 | 31,215,788 | This Systematic Review concludes that omega-3 supplementation might have a positive effect on cognitive function .
Thus , n-3 LCPUFAs could be used as a preventive or therapeutic tool for cognitive decline in aged or elder adults | In a growing elderly population , Mild Cognitive Impairment ( MCI ) and Age Related Cognitive Decline ( ARCD ) are increasing in prevalence worldwide .
In the search for food compounds able to ameliorate this condition , it has been postulated that n-3 Long Chain Polyunsaturated Fatty Acids ( n-3 LCPUFA ) , also known as omega-3 , consumption could have a positive effect in the prevention or therapy of these cognitive declines .
This current systematic review studies the relationship between n-3 LCPUFAs and cognitive status in aged adult and elder population s to determine whether there is or not a positive effect of n-3 LCPUFAs supplementation on cognitive decline . | BACKGROUND Dietary intake of fish and the omega-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke . OBJECTIVE To examine whether intakes of fish and the omega-3 fatty acids protect against age-related cognitive decline . DESIGN Prospect i ve cohort study . SETTING Geographically defined Chicago , Ill , community . PARTICIPANTS Residents , 65 years and older , who participated in the Chicago Health and Aging Project . MAIN OUTCOME MEASURE Change in a global cognitive score estimated from mixed models . The global score was computed by summing scores of 4 st and ardized tests . In-home cognitive assessment s were performed 3 times over 6 years of follow-up . RESULTS Cognitive scores declined on average at a rate of 0.04 st and ardized units per year ( SU/y ) . Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age , sex , race , education , cognitive activity , physical activity , alcohol consumption , and total energy intake . Compared with a decline rate in score of -0.100 SU/y among persons who consumed fish less than weekly , the rate was 10 % slower ( -0.090 SU/y ) among persons who consumed 1 fish meal per week and 13 % slower ( -0.088 SU/y ) among persons who consumed 2 or more fish meals per week . The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated , polyunsaturated , and trans fats . There was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change . CONCLUSIONS Fish consumption may be associated with slower cognitive decline with age . Further study is needed to determine whether fat composition is the relevant dietary constituent Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids ( n-3 LC PUFAs ) and better cognitive outcomes in older adults . To date , only two r and omised , controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy population s. Of these trials only one found a benefit , in the subgroup carrying the ApoE-ε4 allele . The benefits of n-3 LC PUFA supplementation on cognitive function in older normal population s thus still remain unclear . The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people , and included ApoE-ε4 allele carriage as a potential moderating factor . The detailed methodology of the trial is reported herein . Methods The study was a parallel , 18-month , r and omised , double-blind , placebo-controlled intervention with assessment at baseline and repeated 6-monthly . Participants ( N = 391 , 53.7 % female ) aged 65 - 90 years , English-speaking and with normal cognitive function , were recruited from metropolitan Adelaide , South Australia . Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules . The primary outcome is rate of change in cognitive performance , as measured by latent variables for the cognitive constructs ( encompassing Reasoning , Working Memory , Short-term Memory , Retrieval Fluency , Inhibition , Simple and Choice-Reaction Time , Perceptual Speed , Odd-man-out Reaction Time , Speed of Memory Scanning , and Psychomotor Speed ) and assessed by latent growth curve modeling . Secondary outcomes are change in the Mini-mental State Examination , functional capacity and well-being ( including health status , depression , mood , and self-report cognitive functioning ) , blood pressure , and biomarkers of n-3 LC PUFA status , glucose , lipid metabolism , inflammation , oxidative stress , and DNA damage . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Given evidence that eicosapentaenoic acid ( EPA ) , docosahexaenoic acid ( DHA ) , and anthocyanin-rich blueberries provide neurocognitive benefit , we investigated long-term supplementation in older adults with cognitive complaints . In a 24-week r and omized , double-blind , placebo-controlled trial , elderly men and women received daily fish oil ( FO ) or blueberry ( BB ) or both . Diet records confirmed that participants reduced background consumption of EPA , DHA , and anthocyanins as prescribed . Erythrocyte EPA + DHA composition increased in the FO groups ( p = 0.0001 ) . Total urinary anthocyanins did not differ between the groups after supplementation but glycoside and native ( food ) forms increased only in the BB-supplemented groups . The FO ( p = 0.03 ) and BB ( p = 0.05 ) groups reported fewer cognitive symptoms , and the BB group showed improved memory discrimination ( p = 0.04 ) , indicating that supplementation improved cognition . Cognitive benefit in the BB group was associated with the presence of urinary anthocyanins reflecting recent BB intake but not with anthocyanin metabolites . However , combined FO + BB treatment was not associated with cognitive enhancement as expected Docosahexaenoic acid ( DHA ) is important for brain function , and higher DHA intake is inversely correlated with relative risk of Alzheimer 's disease . The potential benefits of DHA supplementation in people with mild cognitive impairment ( MCI ) have not been fully examined . Our study aim ed to determine the effect of DHA supplementation on cognitive function and hippocampal atrophy in elderly subjects with MCI . This was a r and omized , double-blind , placebo-controlled trial in Tianjin , China . 240 individuals with MCI aged 65 years and over were recruited and equalized r and omly allocated to the DHA or the placebo group . Participants received 12-month DHA supplementation ( 2 g/day ) or corn oil as placebo . Both global and specific subdomains of cognitive function and hippocampal volume were measured at baseline , 6 months , and 12 months . Both changes were analyzed by repeated-measure analysis of variance ( ANOVA ) . This trial has been registered : ChiCTR-IOR-15006058 . A total of 219 participants ( DHA : 110 , Placebo : 109 ) completed the trial . The change in mean serum DHA levels was greater in the intervention group ( + 3.85 % ) compared to the control group ( + 1.06 % ) . Repeated- measures analyses of covariance showed that , over 12 months , there was a significant difference in the Full-Scale Intelligence Quotient ( ηp2 = 0.084 ; p = 0.039 ) , Information ( ηp2 = 0.439 ; p = 0.000 ) , and Digit Span ( ηp2 = 0.375 ; p = 0.000 ) between DHA-treated versus the placebo group . In addition , there were significant differences in volumes of left hippocampus ( ηp2 = 0.121 , p = 0.016 ) , right hippocampus ( ηp2 = 0.757 , p = 0.008 ) , total hippocampus ( ηp2 = 0.124 , p = 0.023 ) , and global cerebrum ( ηp2 = 0.145 , p = 0.032 ) between the two groups . These findings suggest that DHA supplementation ( 2 g/day ) for 12 months in MCI subjects can significantly improve cognitive function and slow the progression of hippocampal atrophy . Larger , longer-term confirmatory studies are warranted BACKGROUND Plasma fatty acids may affect the risk of cognitive decline in older adults . OBJECTIVES We prospect ively studied the association between plasma fatty acids and cognitive decline in adults aged 50 - 65 y at baseline and conducted a subgroup analysis . DESIGN From 1987 through 1989 , the Atherosclerosis Risk in Communities ( ARIC ) Study analyzed plasma fatty acids in cholesteryl esters and phospholipids in whites residing in Minneapolis , MN . From 1990 through 1992 and from 1996 through 1998 , 3 neuropsychological tests in the domains of delayed word recall , psychomotor speed , and verbal fluency were administered . We selected cutoffs for statistically reliable cognitive decline in each of these domains and a measure of global cognitive change computed by principal-components analysis . Multivariate logistic regression was conducted . Focusing on n-3 highly unsaturated fatty acids ( HUFAs ) , a subgroup analysis assessed differential association across potential effect modifiers implicated in oxidative stress and increased risk of neurodegenerative disease . RESULTS In the 2251 study subjects , the risk of global cognitive decline increased with elevated palmitic acid in both fractions and with high arachidonic acid and low linoleic acid in cholesteryl esters . Higher n-3 HUFAs reduced the risk of decline in verbal fluency , particularly in hypertensive and dyslipidemic subjects . No significant findings were shown for psychomotor speed or delayed word recall . CONCLUSIONS Promoting higher intakes of n-3 HUFAs in the diet of hypertensive and dyslipidemic persons may have substantial benefits in reducing their risk of cognitive decline in the area of verbal fluency . However , clinical trials are needed to confirm this finding BACKGROUND Very-long-chain n-3 polyunsaturated fatty acids ( n-3 PUFAs ) are suggested to be related to cognitive performance in older adults . However , limited data exist on the association between n-3 PUFAs and performance in specific cognitive domains . OBJECTIVE We evaluated the association between plasma n-3 PUFA proportions and cognitive performance in 5 cognitive domains and determined whether plasma n-3 PUFA proportions predict cognitive change over 3 y. DESIGN We used data from the FACIT trial , in which participants received folic acid or placebo capsules for 3 y. Fatty acid proportions in plasma cholesteryl esters at baseline were measured in 807 men and women aged 50 - 70 y. Cognitive performance for memory , sensorimotor speed , complex speed , information-processing speed , and word fluency was assessed at baseline and after 3 y. The cross-sectional analyses were based on all 807 participants ; the longitudinal analyses were based only on 404 participants in the placebo group . RESULTS Higher plasma n-3 PUFA proportions predicted less decline in sensorimotor speed ( multiple linear regression coefficient , z score = 0.31 ; 95 % CI : 0.06 , 0.57 ) and complex speed ( 0.40 ; 95 % CI : 0.10 , 0.70 ) over 3 y. Plasma n-3 PUFA proportions did not predict 3-y changes in memory , information-processing speed , or word fluency . The cross-sectional analyses showed no association between plasma n-3 PUFA proportions and performance in any of the 5 cognitive domains . CONCLUSIONS In this population , plasma n-3 PUFA proportions were associated with less decline in the speed-related cognitive domains over 3 y. These results need to be confirmed in r and omized controlled trials Depressive symptoms may increase the risk of progressing from mild cognitive impairment ( MCI ) to dementia . Consumption of n-3 PUFA may alleviate both cognitive decline and depression . The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA , DHA and EPA , for depressive symptoms , quality of life ( QOL ) and cognition in elderly people with MCI . We conducted a 6-month double-blind , r and omised controlled trial . A total of fifty people aged > 65 years with MCI were allocated to receive a supplement rich in EPA ( 1·67 g EPA + 0·16 g DHA/d ; n 17 ) , DHA ( 1·55 g DHA + 0·40 g EPA/d ; n 18 ) or the n-6 PUFA linoleic acid ( LA ; 2·2 g/d ; n 15 ) . Treatment allocation was by minimisation based on age , sex and depressive symptoms ( Geriatric Depression Scale , GDS ) . Physiological and cognitive assessment s , question naires and fatty acid composition of erythrocytes were obtained at baseline and 6 months ( completers : n 40 ; EPA n 13 , DHA n 16 , LA n 11 ) . Compared with the LA group , GDS scores improved in the EPA ( P=0·04 ) and DHA ( P=0·01 ) groups and verbal fluency ( Initial Letter Fluency ) in the DHA group ( P=0·04 ) . Improved GDS scores were correlated with increased DHA plus EPA ( r 0·39 , P=0·02 ) . Improved self-reported physical health was associated with increased DHA . There were no treatment effects on other cognitive or QOL parameters . Increased intakes of DHA and EPA benefited mental health in older people with MCI . Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia . This needs to be investigated in larger , depressed sample s with MCI BACKGROUND Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids , for example , docosahexaenoic acid and eicosapentaenoic acid , may prevent Alzheimer disease ( AD ) . OBJECTIVE To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD . DESIGN R and omized , double-blind , placebo-controlled clinical trial . PARTICIPANTS Two hundred four patients with AD ( age range [ mean + /- SD ] , 74 + /- 9 years ) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination ( MMSE ) score of 15 points or more were r and omized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid ( omega-3 fatty acid-treated group ) or placebo for 6 months , after which all received omega-3 fatty acid supplementation for 6 months more . MAIN OUTCOME MEASURES The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale . The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale ; safety and tolerability of omega-3 fatty acid supplementation ; and blood pressure determinations . RESULTS One hundred seventy-four patients fulfilled the trial . At baseline , mean values for the Clinical Dementia Rating Scale , MMSE , and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 r and omized groups were similar . At 6 months , the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups . However , in a subgroup ( n = 32 ) with very mild cognitive dysfunction ( MMSE > 27 points ) , a significant ( P<.05 ) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group . A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation . The omega-3 fatty acid treatment was safe and well tolerated . CONCLUSIONS Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale . However , positive effects were observed in a small group of patients with very mild AD ( MMSE > 27 points ) Objective : Intake of n-3 polyunsaturated fatty acids ( n-3 PUFAs ) may protect against mild cognitive impairment ( MCI ) . However , there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China . The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI . Methods : Eighty six MCI individuals aged 60 years or older were r and omly assigned to receive either n-3 PUFAs ( 480 mg DHA and 720 mg EPA per day , n = 44 ) or placebo ( olive oil , n = 42 ) capsules . The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests ( BCAT ) . Results : The mean age of participants was 71 years old , and 59 % of the participants were men . n-3 PUFA supplementation was associated with improved total BCAT scores , perceptual speed , space imagery efficiency , and working memory ( p < 0.01 ) , but not with mental arithmetic efficiency or recognition memory ( p > 0.05 ) . Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed ( p = 0.001 ) , space imagery efficiency ( p = 0.013 ) , working memory ( p = 0.018 ) , and total BCAT scores ( p = 0.000 ) in males . However , in females , the significant beneficial effects can only be observed in perceptual speed ( p = 0.027 ) , space imagery efficiency ( p = 0.006 ) , and total BCAT scores ( p = 0.015)—not working memory ( p = 0.113 ) . Conclusion : n-3 PUFAs can improve cognitive function in people with MCI . Further studies with different fish oil dosages , longer intervention periods , and larger sample sizes should be investigated before definite recommendations can be made Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids ( PUFAs ) such as docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) may reduce the risk of cognitive decline and Alzheimer ’s disease ( AD ) . To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia ( CIND ) or Alzheimer ’s disease ( AD ) a four month , r and omised , double-blind , placebo controlled study was conducted . Fifty-seven participants with CIND and nineteen with AD were r and omised to receive either omega-3 PUFAs ( 600 mg EPA and 625 mg DHA per day ) or placebo ( olive oil ) over a four month period . Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood . These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia . More intervention studies need to be undertaken with longer study duration s and larger sample sizes . It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes A 24-week , r and omized , double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids ( PUFAs ) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants . Twenty three participants with mild or moderate Alzheimer 's disease and twenty three with mild cognitive impairment were r and omized to receive omega-3 PUFAs 1.8 g/day or placebo ( olive oil ) . The data of 35 ( 76 % ) participants with at least one post-treatment visit was analyzed . There were no severe adverse effects in either group and it suggests that omega-3 PUFAs were well tolerable in this population . The treatment group showed better improvement on the Clinician 's Interview-Based Impression of Change Scale ( CIBIC-plus ) than those in the placebo group over the 24 week follow-up ( p=0.008 ) . There was no significant difference in the cognitive portion of the Alzheimer 's Disease Assessment Scale ( ADAS-cog ) change during follow-up in these two groups . However , the omega-3 fatty acids group showed significant improvement in ADAS-cog compared to the placebo group in participants with mild cognitive impairment ( p=0.03 ) , which was not observed in those with Alzheimer 's disease . Higher proportions of eicosapentaenoic acid on RBC membranes were also associated with better cognitive outcome ( p=0.003 ) . Further studies should be considered with a larger- sample size , diet registration , higher dosages , comparisons between different combinations of PUFAs , and greater homogeneity of participants , especially those with mild Alzheimer 's disease and mild cognitive impairment Background Krill oil , rich in n-3 ( omega-3 ) polyunsaturated fatty acids ( PUFAs ) incorporated in phosphatidylcholine , has been reported to have many effects on physiological function . However , there are few studies using psychophysiological methods published that describe the effects of krill oil on brain function . We investigated the influence of ingestion of krill oil on cognitive function in elderly subjects by using near-infrared spectroscopy and electroencephalography . Methods A r and omized , double-blind , parallel-group comparative study design was adopted . Forty-five healthy elderly males aged 61–72 years were assigned to receive 12 weeks of treatment with : medium-chain triglycerides as placebo ; krill oil , which is rich in n-3 PUFAs incorporated in phosphatidylcholine ; or sardine oil , which is abundant in n-3 PUFAs incorporated in triglycerides . Changes in oxyhemoglobin concentrations in the cerebral cortex during memory and calculation tasks were measured . The P300 component of event-related potentials was also measured during a working memory task . Results During the working memory task , changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups were significantly greater than those in the medium-chain triglyceride group at week 12 . The differential value for P300 latency in the krill oil group was significantly lower than that in the medium-chain triglyceride group at week 12 . With regard to the calculation task , changes in oxyhemoglobin concentrations in the krill oil group were significantly greater than those in the medium-chain triglyceride group at week 12 . Conclusion This study provides evidence that n-3 PUFAs activate cognitive function in the elderly . This is especially the case with krill oil , in which the majority of n-3 PUFAs are incorporated into phosphatidylcholine , causing it to be more effective than sardine oil , in which n-3 PUFAs are present as triglycerides DHA and arachidonic acid ( AA ) are important for neurodevelopment . A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants . Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition . We investigated whether supplementation of DHA during pregnancy and lactation influences the infant 's brain development and whether additional AA modulates this effect . Healthy women were r and omly assigned to DHA ( 220 mg/d , n 42 ) , DHA+AA ( 220 mg each/d , n 41 ) or control ( n 36 ) , from about week 17 ( range 14 - 20 weeks ) of pregnancy until 12 weeks postpartum . The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios . The st and ardised neonatal neurological examination was carried out at 2 weeks . General movement quality was assessed at 2 and 12 weeks . Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination . General movement quality of infants in the DHA group was lower than that of infants in the other two groups , especially at 12 weeks : 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group ( P = 0.008 ) and 34 % in the DHA+AA group ( P = 0.015 ) . We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids ( LC-n3-FA ) may be beneficial for the aging brain . We tested in a prospect i ve interventional design whether high levels of supplementary LC-n3-FA would improve cognition , and addressed potential mechanisms underlying the effects . Sixty-five healthy subjects ( 50 - 75 years , 30 females ) successfully completed 26 weeks of either fish oil ( 2.2 g/day LC-n3-FA ) or placebo intake . Before and after the intervention period , cognitive performance , structural neuroimaging , vascular markers , and blood parameters were assayed . We found a significant increase in executive functions after LC-n3-FA compared with placebo ( P = 0.023 ) . In parallel , LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal , temporal , parietal , and limbic areas primarily of the left hemisphere , and on carotid intima media thickness and diastolic blood pressure . Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor , and negatively with changes in peripheral fasting insulin . This double-blind r and omized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults , and eluci date s underlying mechanisms . Our findings suggest novel strategies to maintain cognitive functions into old age Rationale Epidemiological studies have suggested a beneficial effect of fish oil supplementation in halting the initial progression of Alzheimer ’s disease . However , it remains unclear whether fish oil affects cognitive function in older people with mild cognitive impairment ( MCI ) . Objectives This study investigated the effects of fish oil supplementation on cognitive function in elderly person with MCI . Methods This was a 12-month , r and omised , double-blind , placebo-controlled study using fish oil supplementation with concentrated docosahexaenoic acid ( DHA ) . Thirty six low-socioeconomic-status elderly subjects with MCI were r and omly assigned to receive either concentrated DHA fish oil ( n = 18 ) or placebo ( n = 18 ) capsules . The changes of memory , psychomotor speed , executive function and attention , and visual-constructive skills were assessed using cognitive tests . Secondary outcomes were safety and tolerability of the DHA concentrate . Results The fish oil group showed significant improvement in short-term and working memory ( F = 9.890 ; ηp2 = 0.254 ; p < 0.0001 ) , immediate verbal memory ( F = 3.715 ; ηp2 = 0.114 ; p < 0.05 ) and delayed recall capability ( F = 3.986 ; ηp2 = 0.121 ; p < 0.05 ) . The 12-month change in memory ( p < 0.01 ) was significantly better in the fish oil group . Fish oil consumption was well tolerated , and the side effects were minimal and self-limiting . Conclusions This study suggested the potential role of fish oil to improve memory function in MCI subjects . Studies with larger sample sizes , longer intervention periods , different fish oil dosages and genetic determinations should be investigated before definite recommendations can be made The omega-3 fatty acid docosahexaenoic acid ( DHA ) is essential for nervous system and retinal development and there is evidence to suggest that DHA deficiencies increase with normal aging . A triple-blind placebo-controlled r and omized repeated- measures trial was conducted with 74 healthy participants , aged 45 - 77 years . Cognitive and visual acuity measures and plasma levels of DHA were determined at baseline and after 90 days of administration of either HiDHA ( ® ) ( Clover Corp. , Sydney , NSW , Australia : 1000 mg of tuna oil ; comprising 252 mg DHA , 60 mg EPA and 10 mg vitamin E ) or placebo ( 1000 mg soybean oil ) . Ninety days of DHA supplementation was found to significantly raise both plasma DHA and total ω-3 plasma levels in the treatment group , as well as significantly lower total ω-6 levels . However , no significant effects of DHA supplementation on cognitive functioning were found . For participants with corrected vision , the group receiving DHA were found to have significantly better right eye visual acuity posttreatment in comparison with the placebo group ( F(1,22 ) = 7.651 ; p = 0.011 ; partial η(2 ) = 0.258 ) Objective To determine the effects of long-chain omega-3 ( LCn-3 ) fatty acids found in fish oil , including eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , on cortical blood oxygen level-dependent ( BOLD ) activity during a working memory task in older adults with subjective memory impairment . Design R and omized , double-blind , placebo-controlled study . Setting Academic medical center . Participants Healthy older adults ( 62–80 years ) with subjective memory impairment , but not meeting criteria for mild cognitive impairment or dementia . InterventionFish oil ( EPA+DHA : 2.4 g/d , n=11 ) or placebo ( corn oil , n=10 ) for 24 weeks . Measurements Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging ( fMRI ) . Results At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil ( + 31 % , p≤0.0001 ) but not placebo ( −17 % , p=0.06 ) . Multivariate modeling of fMRI data identified a significant interaction among treatment , visit , and memory loading in the right cingulate ( BA 23/24 ) , and in the right sensorimotor area ( BA 3/4 ) . In the fish oil group , BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading . A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back ( p=0.0003 ) and 2-back ( p=0.0005 ) conditions . Among all participants , the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task ( p = 0.01 ) , and with cingulate BOLD signal during the 1-back ( p = 0.005 ) with a trend during the 2-back ( p = 0.09 ) . Further , cingulate BOLD activity was related to performance in the 2-back condition . Conclusions Dietary fish oil supplementation increases red blood cell omega-3 content , working memory performance , and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge Several studies have reported that the supplementation of long-chain polyunsaturated fatty acids ( LCPUFA ) , such as docosahexaenoic acid ( DHA ) , eicosapentaenoic acid ( EPA ) , and arachidonic acid ( ARA ) improve cognitive function in the elderly . However , the doses used in these studies were higher than general dietary LCPUFA intake levels . This r and omized , double-blind , placebo-controlled trial evaluated the effects of low doses of LCPUFA supplementation corresponding to general dietary intake on cognitive function in non-demented elderly Japanese participants . Japanese men aged 55 - 64 years were enrolled and r and omly allocated to the placebo or LCPUFA group . Participants received 4 weeks of supplementation with LCPUFA-containing oil ( DHA , 300 mg/day ; EPA , 100 mg/day ; and ARA , 120 mg/day ) or purified olive oil as placebo . Event-related potential P300 , reflecting cognitive processes , was measured before and after supplementation . A total of 113 participants completed the supplementation period , and the per- protocol analysis included 69 participants . Changes in P300 latency were significantly different between the placebo group ( + 13.6 msec ) and the LCPUFA group ( -1.8 msec ) after supplementation . Significant increases in DHA ( + 0.9 % ) and ARA ( + 0.6 % ) contents in plasma phospholipids were observed in the LCPUFA group ; no changes were observed in the placebo group . Dietary DHA , EPA , and ARA intake were in the normal range for Japan participants and remained unchanged during the study . These results suggest that low doses of LCPUFA supplementation have the potential to improve cognitive function in elderly Japanese men Abstract Despite the reported benefits associated with ω3 fatty acids for cardiovascular disease , there remains concern that increased intake may lead to increased lipid peroxidation . To date , however , the data , particularly in vivo , are inconclusive . This report describes two interventions , one providing daily fish meals and the other eicosapentaenoic acid ( EPA , 20:5 ω3 ) or docosahexaenoic acid ( DHA , 22:6 ω3 ) , the two principal ω3 fatty acids in marine oils , in which in vivo lipid peroxidation was assessed by measurement of urinary excretion of F2-isoprostanes . In both trials , urinary F2-isoprostanes were significantly reduced by 20–27 % . Therefore , in contrast with previous reports in the literature , these results demonstrate that ω3 fatty acids reduce in vivo oxidant stress in humans Age-dependent increase of peroxidation of membrane fatty acids such as arachidonic acid ( ARA ) and docosahexaenoic acid ( DHA ) in neurons was reported to cause a decline of the hippocampal long-term potentiation ( LTP ) and cognitive dysfunction in rodents . Although supplementation of ARA and DHA can improve LTP and cognitive function in rodents , their effects in humans are unknown . The present work was undertaken to study whether ARA and DHA have beneficial effects in human amnesic patients . The subjects were 21 mild cognitive dysfunction ( 12 MCI-A with supplementation and 9 MIC-P with placebo ) , 10 organic brain lesions ( organic ) , and 8 Alzheimer 's disease ( AD ) . The cognitive functions were evaluated using Japanese version of repeatable battery for assessment of neuropsychological status ( RBANS ) at two time points : before and 90 days after the supplementation of 240 mg/day ARA and DHA , or 240 mg/day of olive oil , respectively . MCI-A group showed a significant improvement of the immediate memory and attention score . In addition , organic group showed a significant improvement of immediate and delayed memories . However , there were no significant improvements of each score in AD and MCI-P groups . It is suggested from these data that ARA and DHA supplementation can improve the cognitive dysfunction due to organic brain damages or aging AIM We examined the effects of the administration of docosahexaenoic acid (DHA)-enriched meals on cognitive function in the oldest elderly with cognitive impairment , such as dementia , living in nursing homes , and on the improvement in caregiver burden at aging agencies . METHODS Participants in elderly care facilities and nursing homes ( n = 75 ; 88.5 ± 0.6 years ) were r and omized in active and placebo groups . The active group had family-style meals containing an additional 1720 mg of docosahexaenoic acid per day for 12 months . At baseline , and after 6 and 12 months of intervention , cognitive function was assessed using Hasegawa 's Dementia Scale-Revised and the Mini-Mental State Examination ; mental health condition was assessed with the Apathy scale and the Zung Self-Rating Depression Scale ; caregiver burden was evaluated using Zarit Burden Interview scores ; and participants ' serum biochemical factors were measured . RESULTS The participants were suggested to have dementia . After 12 months , the mean change in Mini-Mental State Examination subitem " Registration " score from baseline to month 12 showed a tendency to be greater in the active group than that in the placebo group . Mean changes in the Apathy scale from baseline to month 12 were less , and the changes in the Zung Self-Rating Depression Scale and the total Zarit Burden Interview scores showed a tendency to be lower in the active group than in the placebo group , respectively . CONCLUSION These results suggest that docosahexaenoic acid-enriched meals protect against age-related cognitive decline , and also improve apathy and caregiver burden for the oldest-elderly Japanese with cognitive impairment , such as dementia . Geriatr Gerontol Int 2017 ; 17 : 330 - 337 Objective : Fish oils and multivitamins are two of the most commonly used dietary supplements . Fish oil use may reduce vascular risk factors associated with cognitive decline , thus providing benefits to both heart and brain health . Multivitamins may also have direct effects on brain function . The present study investigated the effects of fish oil , with and without the addition of a multivitamin , on cognitive and cardiovascular function . Methods : In a r and omized , placebo-controlled , double-blind fashion , 160 healthy adults aged 50–70 years were r and omized to receive either 3 g of fish oil ( 240 mg eicosapentaenoic acid [ EPA ] + 240 mg docosahexaenoic acid [ DHA ] ) with a multivitamin , 6 g of fish oil ( 480 mg EPA + 480 mg DHA ) with a multivitamin , or 6 g of fish oil without a multivitamin or a placebo . Cognitive performance , brachial blood pressure , and aortic ( central ) blood pressure were measured at baseline , 6 weeks , and 16 weeks . Results : Treatment allocation had no effect on the primary cognitive outcomes at endpoint . Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory . The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure , two measures of aortic blood pressure and aortic stiffness . Conclusions : Fish oil decreased aortic pulse pressure and augmentation pressure . Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition |
12,670 | 31,425,629 | Several confounding factors , most notably the differences in design of the trials with respect to blinding , were likely to have impacted on the results of the primary outcome ' time to treatment failure ' , and in turn , the treatment failure rates may have impacted on the secondary efficacy outcomes of time to first seizure and time to 12-month and six-month remission .
AUTHORS ' CONCLUSIONS Low-certainty evidence from this review suggests that phenytoin may be a more effective drug than phenobarbitone in terms of treatment retention ( treatment failures due to lack of efficacy or adverse events or both ) .
Moderate-certainty evidence from this review also indicates no differences between the drugs in terms of time to seizure recurrence and seizure remission . | BACKGROUND This is an up date of a Cochrane Review first published in 2001 , and last up date d in 2013 .
This review is one in a series of Cochrane Review s investigating pair-wise monotherapy comparisons .
Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures .
It is believed that with effective drug treatment , up to 70 % of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy .
Worldwide , particularly in the developing world , phenytoin and phenobarbitone are commonly used antiepileptic drugs , primarily because they are inexpensive .
The aim of this review is to summarise data from existing trials comparing phenytoin and phenobarbitone .
OBJECTIVES To review the time to treatment failure , remission and first seizure with phenobarbitone compared with phenytoin when used as monotherapy in people with focal onset seizures ( simple or complex focal and secondarily generalised ) , or generalised onset tonic-clonic seizures ( with or without other generalised seizure types ) . | The Fifth Commission on Antiepileptic Drugs of the International League Against Epilepsy was asked to advise the ILAE Executive on the place of new drugs in the treatment of patients with newly diagnosed or chronic epilepsy . With the licensing of a significant number of new antiepileptic drugs ( AEDs ) in the last 5 - 10 years , there is an obvious need for these new treatments to be introduced efficiently and effectively to benefit the care and management of people with epilepsy . Implicit in this will be a determination of the comparative efficacy , tolerability , and overall effectiveness against st and ard ( existing ) AEDs and against other new drugs . Although many of the issues relating to comparative studies were addressed in Guidelines for the Clinical Evaluation of Antiepileptic Drugs , produced by the Fourth Commission , several complex ethical and method ological problems remain that would benefit from further discussion aim ed at the establishment of some form of consensus . Although determination of the relative risks of rare but potentially serious idiosyncratic adverse reactions and teratogenicity can be determined only by adequate postmarketing surveillance , other issues concerning the efficacy , tolerability , and effectiveness of new drugs can best be determined within the context of well- design ed r and omized ( or otherwise controlled ) clinical trials ( RCTs ) . It is the design , structure , and outcomes of such comparative RCTs that dem and further consideration . Many of the difficulties arise because the most meaningful and satisfactory comparative studies will essentially be those that compare monotherapy with a new agent with monotherapy with alternative agents . The Commission recognizes that several different parties have interests in comparative studies . First and foremost patients and their doctors require adequate information to guide daily practice in an “ evidence -based ” way so that patients can make fully informed decisions about their drug treatment . Individual pharmaceutical manufacturers need to know how their drug compares with other products so that a drug can be appropriately positioned in the market . Licensing authorities have traditionally ignored issues of comparative Background The choice of antiepileptic drug for an individual should be based upon the highest quality evidence regarding potential benefits and harms of the available treatments . Systematic review s and meta- analysis of r and omised controlled trials should be a major source of evidence supporting this decision making process . We summarise all available individual patient data evidence from r and omised controlled trials that compared at least two out of eight antiepileptic drugs given as monotherapy . Methods Multiple treatment comparisons from epilepsy monotherapy trials were synthesized in a single stratified Cox regression model adjusted for treatment by epilepsy type interactions and making use of direct and indirect evidence . Primary outcomes were time to treatment failure and time to 12 month remission from seizures . A secondary outcome was time to first seizure . Results Individual patient data for 6418 patients from 20 r and omised trials comparing eight antiepileptic drugs were synthesized . For partial onset seizures ( 4628 ( 72 % ) patients ) , lamotrigine , carbamazepine and oxcarbazepine provide the best combination of seizure control and treatment failure . Lamotrigine is clinical ly superior to all other drugs for treatment failure but estimates suggest a disadvantage compared to carbamazepine for time to 12 month remission [ Hazard Ratio ( 95 % Confidence Interval ) = 0.87(0.73 to 1.04 ) ] and time to first seizure [ 1.29(1.13 to 1.48 ) ] . Phenobarbitone may delay time to first seizure [ 0.77(0.61 to 0.96 ) ] but at the expense of increased treatment failure [ 1.60(1.22 to 2.10 ) ] . For generalized onset tonic clonic seizures ( 1790 ( 28 % ) patients ) estimates suggest valproate or phenytoin may provide the best combination of seizure control and treatment failure but some uncertainty remains about the relative effectiveness of other drugs . Conclusion For patients with partial onset seizures , results favour carbamazepine , oxcarbazepine and lamotrigine . For generalized onset tonic clonic seizures , results favour valproate and phenytoin Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged BACKGROUND The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects ; however , whether this research can validly be extrapolated to developing countries is not clear . We undertook a r and omised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India . METHODS Between August , 1995 , and February , 1996 , 109 unselected children aged 2 - 18 years with partial and generalised tonic-clonic epilepsy were identified by population screening . 15 families declined to take part . 94 children were r and omly allocated treatment with phenobarbital ( 1.5 mg/kg daily for 2 weeks ; maintenance dose 3.0 mg/kg daily ; n = 47 ) or phenytoin ( 2.5 mg/kg daily then 5.0 mg/kg daily ; n = 47 ) . Children were followed up for 12 months . The primary outcome measure was the frequency of behavioural side-effects ; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older , and by the preschool behaviour screening question naire ( BSQ ) for those aged 2 - 5 years , at 12 months or at withdrawal from treatment . Analysis was by intention to treat . FINDINGS The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups ( Conners 2.64 [ SD 0.71 ] vs 2.65 [ 0.89 ] , p = 0.97 ; n = 32 in each group : BSQ 2.12 [ 1.31 ] vs 2.18 [ 1.02 ] , p = 0.94 ; n = 4 vs 3 ) . The odds ratio for behavioural problems ( phenobarbital vs phenytoin ) was 0.51 ( 95 % CI 0.16 - 1.59 ) . There was no excess in parental reports of side-effects for phenobarbital . We found no difference in efficacy between the study drugs ( adjusted hazard ratio for time to first seizure from r and omisation 0.97 [ 0.28 - 3.30 ] ) . INTERPRETATION This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural setting s in developing countries PRIMIDONE ( Mysoline ) has been shown to be an effective anticonvulsant drug . 1 - 6 It has been stated that primidone is exceptionally valuable in the control of focal seizures and the " drug of choice " for the treatment of psychomotor seizures . 7 - 9 Previous clinical comparative studies have not contradicted this cl aim . 4,5 One study found that phenobarbital and primidone were equally effective as anticonvulsants with 50 mg of phenobarbital being equivalent to 250 mg of primidone . Another similar study 5 revealed that primidone and phenobarbital are about equally effective as anticonvulsants but more effective than diphenylhydantoin ( Dilantin ) . However , as the authors of that study point out , the five day medication trial was not sufficient for maximal anticonvulsant effect of diphenylhydantoin to occur . Their data revealed a sharp increase in effectiveness of diphenylhydantoin on the fifth treatment day , while primidone and phenobarbital were relatively more effective on the first and second days . Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug . We therefore undertook a prospect i ve r and omised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs , utilised as monotherapy in newly diagnosed epileptic patients . Between 1981 and 1987 243 adult patients aged 16 years or over , newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were r and omly allocated to treatment with phenobarbitone , phenytoin , carbamazepine , or sodium valproate . The protocol was design ed to conform with st and ard clinical practice . Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission . The overall outcome with all of the four drugs was good with 27 % remaining seizure free and 75 % entering one year of remission by three years of follow up . No significant differences between the four drugs were found for either measure of efficacy at one , two , or three years of follow up . The overall incidence of unacceptable side effects , necessitating withdrawal of the r and omised drug , was 10 % . For the individual drugs phenobarbitone ( 22 % ) was more likely to be withdrawn than phenytoin ( 3 % ) , carbamazepine ( 11 % ) , and sodium valproate ( 5 % ) . In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures , the choice of drug will be more influenced by considerations of toxicity and costs Objective : To assess the relative risk of major congenital malformation ( MCM ) from in utero exposure to antiepileptic drug ( AEDs ) . Methods : Prospect i ve data collected by the UK Epilepsy and Pregnancy Register were analysed . The presence of MCMs recorded within the first three months of life was the main outcome measure . Results : Full outcome data were collected on 3607 cases . The overall MCM rate for all AED exposed cases was 4.2 % ( 95 % confidence interval ( CI ) , 3.6 % to 5.0 % ) . The MCM rate was higher for polytherapy ( 6.0 % ) ( n = 770 ) than for monotherapy ( 3.7 % ) ( n = 2598 ) ( crude odds ratio ( OR ) = 1.63 ( p = 0.010 ) , adjusted OR = 1.83 ( p = 0.002 ) ) . The MCM rate for women with epilepsy who had not taken AEDs during pregnancy ( n = 239 ) was 3.5 % ( 1.8 % to 6.8 % ) . The MCM rate was greater for pregnancies exposed only to valproate ( 6.2 % ( 95 % CI , 4.6 % to 8.2 % ) than only to carbamazepine ( 2.2 % ( 1.4 % to 3.4 % ) ( OR = 2.78 ( p<0.001 ) ; adjusted OR = 2.97 ( p<0.001 ) ) . There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate . A positive dose response for MCMs was found for lamotrigine ( p = 0.006 ) . Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate ( OR = 2.49 ( 1.31 to 4.70 ) ) . Conclusions : Only 4.2 % of live births to women with epilepsy had an MCM . The MCM rate for polytherapy exposure was greater than for monotherapy exposure . Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate . For monotherapy exposures , carbamazepine was associated with the lowest risk of MCM Objective To compare the behavioural side effects associated with two commonly used antiepilepsy drugs — phenobarbital and carbamazepine — in children in Bangladesh . Design Prospect i ve r and omised controlled single centre trial . Setting Specialist children 's hospital in Dhaka , Bangladesh . Participants 108 children aged 2 - 15 with generalised tonic-clonic ( n=51 ) or partial and secondary generalised seizures ( n=57 ) . Main outcome measures Seizure control and behavioural side effects . Results 91 children were followed up for 12 months . Six required a change of antiepilepsy drug . Side effects were compared in 85 children . In the last quarter of the 12 month follow-up , 71 children were seizure free after one year 's treatment . Thirty two in the phenobarbital group and 39 in the carbamazepine group had no seizures in 74 and 102 days after r and omisation , respectively . Ten children had increased behavioural problems , which were unacceptable in four ( one in the phenobarbital group and three in the carbamazepine group ) . Independent t tests , however , showed no difference between the two trial drugs . Conclusion There was no excess in behavioural side effects with phenobarbital in children with epilepsy in a country with limited re sources . Trial registration NCT00381537 The objective of this study was to identify the factors , at the time of diagnosis , that determine the prognosis for remission of epilepsy . A prospect i ve community‐based cohort study of 792 patients recruited at the time of their first diagnosis of epileptic seizures was undertaken ; in those classified 6 months after presentation , the median follow‐up period was 7.2 years ( quartiles at 6.2 and 8.2 years ) after presentation . We analyzed data from 6 months after the first identified seizure , which prompted the dianosis of epilepsy , to allow us to factor in those aspects contingent on a diagnostic assessment . Baseline clinical and demographic data were analyzed using the Cox proportional hazards regression model with remission of epilepsy for 1 , 2 , 3 , and 5 years as outcome measures . The dominant clinical feature predicting remission was the number of seizures in the 6‐month diagnostic assessment period . Thus , the chance of entering 1 year of remission by 6 years for a patient who had 2 seizures during this initial 6 months was 95 % ; for 5 years of remission , it was 47 % as opposed to 75 % for 1 year of remission and 24 % for 5 years of remission if there had been 10 or more seizures during this period . The number of seizures in the early phase of epilepsy ( here , taken as the first 6 months after presentation ) is the single most important predictive factor for both early and long‐term remission of seizures . Ann Neurol This prospect i ve study followed the pregnancy course of epileptic women at the Motherisk Program of The Hospital for Sick Children , Toronto . We compared fetal outcome of women treated with carbamazepine ( CBZ ) , those treated with diphenylhydantoin ( phenytoin , DPH ) , and a drug-free control group . Seizures were reported in 15 pregnancies ; in a subgroup of 9 women without change in drug or schedule , an increase in seizure frequency was evident in 6 , a decrease in 1 , and no change in 2 , regardless of the drug taken . Of 23 children exposed to CBZ in utero , one was born with a lumbar myelomeningocele and multiple congenital anomalies . Of 21 children exposed to DPH , there was one case of severe developmental delay and four with minor features of fetal hydantoin syndromes ( FHS ) . The three groups did not differ in birth weights or gestational ages of the babies . Although much more experience is needed , as a result of this study and other similar reports , Motherisk now offers women treated with CBZ diagnostic tests to detect neural tube defects during the second trimester of pregnancy OBJECTIVE To compare the efficacy and side effects of phenobarbitone ( PB ) , phenytoin ( PHT ) and sodium valproate ( SVP ) in controlling generalized tonic-clonic convulsions ( GTC ) . DESIGN R and omized , double blind clinical trial . SETTING Out- Patients in a tertiary care hospital . PATIENTS 151 children with GTC , aged 4 - 12 yrs , from Madras city were enrolled . At the end of 2 yrs , 127 children remained in the study . INTERVENTION Each child was given one active drug and 2 placebo tablets . Clinical , hematological and biochemical evaluations were done every month . Serum drug levels were assessed periodically . MAIN OUTCOME MEASURES Recurrence of convulsion and side effects . RESULTS The proportion of children with recurrence did not differ among the 3 groups . More than one side effect was observed in 16 ( 32 % ) children on PB , 20 ( 40 % ) children on PHT and 9 ( 19 % ) children on SVP and this difference was statistically significant ( p < 0.05 ) . Hyperactivity was the major side effect of PB , observed in 22 % of children . CONCLUSION All 3 drugs were equally effective in controlling seizures . Side effects were minimal with SVP followed by PB . Though side effects were more frequent with PHT , most of them disappeared on adjusting drug dosage . Least expensive phenobarbitone may be preferred as the first drug of choice but , only for pre-school children . SVP is advised for school going children We investigated the neuropsychological effects of carbamazepine , phenobarbital , and phenytoin in 15 partial complex epilepsy patients treated with each drug for 3 months , using a r and omized double-blind , triple crossover design . Neuropsychological evaluation at the end of each treatment period included Digit Span , Selective Reminding Test , Digit Symbol , Finger Tapping , Grooved Pegboard , Choice Reaction Time , P3 evoked potential , and Profile of Mood States . Employing anticonvulsant blood levels and seizure frequencies as covariates , the only significant difference was for Digit Symbol . Performance with phenobarbital was significantly worse than with the other 2 anticonvulsants despite phenobarbital 's having had the lowest overall blood levels . Our data show that patients receiving carbamazepine , phenobarbital , and phenytoin have comparable neuropsychological performance on most measures . The results suggest that the differential cognitive effects of anticonvulsants may be subtle Our objective was to evaluate the patterns of malformations in children exposed in utero to phenytoin ( DPH ) and carbamazepine ( CBZ ) monotherapy , and to compare them prospect ively with matched mother-child pairs exposed to nonteratogens , and to separate the effects of antiepileptic drugs ( AEDs ) from those of epilepsy by collecting groups of untreated epileptics and those treated with DPH and CBZ for conditions other than epilepsy . This was a prospect i ve , controlled , and blinded observational study . Thirty-six mother-child pairs exposed to CBZ monotherapy , 34 pairs exposed to DPH monotherapy , and 9 nonmedicated epileptic women and their children were compared with matched mother-child pairs exposed to nonteratogens . The control mothers were matched for maternal age , time of consultation , obstetric history , and socioeconomic status ( SES ) . One main outcome measures a " blinded " morphological assessment of the offspring . We found that minor anomalies were significantly more common among children of epileptics on either drug ( P = 0.01 ) and among DPH-treated nonepileptic offspring ( P = 0.03 ) . Among epileptics , the relative risk for minor anomalies following DPH ( 2.1 ) was similar to that after exposure to either DPH ( P = 0.006 ) or CBZ ( P = 0.01 ) . Increased rates of hypertelorism were detected among DPH-exposed offspring . High forehead , frontal bossing , malar hypoplasia , epicanthus and micrognathia were associated with untreated epilepsy , as well as with DPH and CBZ treatment Remission of seizures is a crucial measure of outcome in epilepsy . The National General Practice Study of Epilepsy ( NGPSE ) aim ed to investigate the remission of patients with epilepsy and the effect of various factors on the likelihood of remission . The NGPSE is a prospect i ve population -based study free from major selection bias . We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practice s throughout the UK between 1984 and 1987 . Remission was analysed in those patients who were classified after 6 months as having definite epilepsy ( n = 564 ) or possible epilepsy ( n = 228 ) . After 9 years from the index seizure , 86 % ( 95 % CI 81 - 90 ) of patients with definite epilepsy had achieved a remission of 3 years and 68 % ( 61 - 75 ) a remission of 5 years . For the complete cohort , including those with possible epilepsy , the remission rates at 9 years were 87 % ( 83 - 91 ) for 3-year remission and 71 % ( 65 - 77 ) for 5-year remission . The proportion of patients with definite epilepsy who were still in remission at 9 years ' follow-up ( terminal remission ) was 68 % ( 62 - 74 ) for 3-year and 54 % ( 48 - 60 ) for 5-year remission . 61 % ( 56 - 68 ) of patients with idiopathic seizures and 61 % ( 46 - 75 ) of those with remote symptomatic epilepsy had achieved 5-year remission by 9 years . Overall , age and seizure type had little effect on the chances of achieving remission . This study confirms the good outcome for seizure control in the majority of patients We conducted a 10-center , double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults . Patients were r and omly assigned to treatment with carbamazepine , phenobarbital , phenytoin , or primidone and were followed for two years or until the drug failed to control seizures or caused unacceptable side effects . Overall treatment success was highest with carbamazepine or phenytoin , intermediate with phenobarbital , and lowest with primidone ( P less than 0.002 ) . Differences in failure rates of the drugs were explained primarily by the fact that primidone caused more intolerable acute toxic effects , such as nausea , vomiting , dizziness , and sedation . Decreased libido and impotence were more common in patients given primidone . Phenytoin caused more dysmorphic effects and hypersensitivity . Control of tonic-clonic seizures did not differ significantly with the various drugs . Carbamazepine provided complete control of partial seizures more often than primidone or phenobarbital ( P less than 0.03 ) . Overall , carbamazepine and phenytoin are recommended drugs of first choice for single-drug therapy of adults with partial or generalized tonic-clonic seizures or with both BACKGROUND No population -based incidence studies of epilepsy have studied syndrome classification from the outset . We prospect ively studied the incidence of a single unprovoked seizure and epilepsy in the population of Icel and , and applied the syndrome classification endorsed by the International League Against Epilepsy to this population . METHODS We used a nationwide surveillance system to prospect ively identify all residents of Icel and who presented with a first diagnosis of a single unprovoked seizure or epilepsy between December 1995 and February 1999 . All cases were classified by seizure type , cause or risk factors , and epilepsy syndrome . RESULTS The mean annual incidence of first unprovoked seizures was 56.8 per 100,000 person-years , 23.5 per 100,000 person-years for single unprovoked seizures , and 33.3 per 100,000 person-years for epilepsy ( recurrent unprovoked seizures ) . Incidence was similar in males and females . Partial seizures occurred in 40 % and a putative cause was identified in 33 % . Age-specific incidence was highest in the first year of life ( 130 per 100,000 person-years ) and in those 65 years and older ( 110.5 per 100,000 person-years ) . Using strict diagnostic criteria for epilepsy syndromes , 58 % of cases fell into non-informative categories . Idiopathic epilepsy syndromes were identified in 14 % of all cases . INTERPRETATION Findings are consistent with incidence studies from developed countries . Although the epilepsy syndrome classification might be useful in tertiary epilepsy centers , it has limited practicality in population studies and for use by general neurologists The efficacy , bioavailability , and tolerance of carbamazepine in epilepsy were evaluated in a prospect i ve , double-blind study . The study was made in 45 institutionalized patients whose seizures were not controlled completely by combinations of currently available an-tiepileptic drugs in adequate dosages as determined by serum concentrations . In this population , carbamazepine was equal in efficacy to phenobarbital or diphenylhydantoin in controlling seizure frequency , and side effects were minimal . Serum concentrations of carbamazepine were measured up to 13.7 rncg per milliliter , with 70 percent of the values ranging from 5 to 10 mcg per milliliter . Individual episodes of transient leukopenia occurred during the 21-day lest period , but a statistically significant incidence of leukopenia was not observed The efficacy and bioavailability , and tolerance to carbamazepine when administered with phenobarbital or phenytoin or with both drugs were evaluated in a prospect i ve , double‐blind study of patients whose seizures were not completely controlled by currently available antiepileptic drugs in usually therapeutic dosages as determined by serum levels . During each of four 21‐day treatment periods , one fourth of the patients received daily doses of : ( 1 ) carbamazepine ( 1,200 mg ) and phenytoin ( 300 mg ) ; ( 2 ) carbamazepine ( 1,200 mg ) and phenobarbital ( 300 mg ) ; ( 3 ) phenytoin ( 300 mg ) and phenobarbital ( 300 mg ) ; or ( 4 ) carbamazepine ( 1,200 mg ) , with phenytoin ( 300 mg ) and phenobarbital ( 300 mg ) . The treatment periods were separated by 2 wk of each patient 's usual pre study medication . Treatment with all three drugs was the most efficacious for seizure control . Serum carbamazepine concentration was significantly decreased when the drug was administered with either phenytoin or phenobarbital or both BACKGROUND More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy , but why this happens and whether it can be predicted are unknown . We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures . METHODS We prospect ively studied 525 patients ( age , 9 to 93 years ) who were given a diagnosis , treated , and followed up at a single center between 1984 and 1997 . Epilepsy was classified as idiopathic ( with a presumed genetic basis ) , symptomatic ( result ing from a structural abnormality ) , or cryptogenic ( result ing from an unknown underlying cause ) . Patients were considered to be seizure-free if they had not had any seizures for at least one year . RESULTS Among the 525 patients , 333 ( 63 percent ) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped . The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy ( 40 percent vs. 26 percent , P=0.004 ) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer ( 51 percent vs. 29 percent , P<0.001 ) . The seizure-free rate was similar in patients who were treated with a single established drug ( 67 percent ) and patients who were treated with a single new drug ( 69 percent ) . Among 470 previously untreated patients , 222 ( 47 percent ) became seizure-free during treatment with their first antiepileptic drug and 67 ( 14 percent ) became seizure-free during treatment with a second or third drug . In 12 patients ( 3 percent ) epilepsy was controlled by treatment with two drugs . Among patients who had no response to the first drug , the percentage who subsequently became seizure-free was smaller ( 11 percent ) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects ( 41 percent ) or an idiosyncratic reaction ( 55 percent ) . CONCLUSIONS Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy BACKGROUND The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients . We know of only one r and omised comparative trial ( of two drugs ) in newly diagnosed childhood epilepsy . We have undertaken a long-term , prospect i ve , r and omised , unmasked , pragmatic trial of the comparative efficacy and toxicity of four st and ard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy . METHODS Between 1981 and 1987 , 167 children aged 3 - 16 years , who had had at least two previously untreated tonic-clonic or partial seizures , with or without secondary generalisation , were r and omly allocated treatment with phenobarbitone , phenytoin , carbamazepine , or sodium valproate . The protocol was design ed to conform to st and ard clinical practice . Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission . FINDINGS The overall outcome with all four drugs was good . 20 % of children remained free of seizures and 73 % had achieved 1-year remission by 3 years of follow-up . We found no significant differences between the drugs for either measure of efficacy at 1 , 2 , or 3 years of follow-up . The overall frequency of unacceptable side-effects necessitating withdrawal of the r and omised drug was 9 % . This total included six of the first ten children assigned phenobarbitone ; no further children were allocated this drug . Of the other three drugs , phenytoin ( 9 % ) was more likely to be withdrawn than carbamazepine ( 4 % ) or sodium valproate ( 4 % ) . INTERPRETATION Our data will inform choice of drug and outcome with four of the st and ard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children |
12,671 | 20,091,519 | The results still need to be interpreted with caution as Marcoux 1997 reported a large positive effect of surgery whereas Gruppo Italiano reported a small negative effect .
When considering fetal losses , meta- analysis did not demonstrate an effect of laparoscopic surgery when compared to diagnostic laparoscopy only .
The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility | BACKGROUND Endometriosis is the presence of endometrial gl and s or stroma in sites other than the uterine cavity .
It is variable in both its surgical appearance and clinical manifestation , often with poor correlation between the two .
Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by the division of adhesions .
OBJECTIVES To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis .
The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility . | STUDY OBJECTIVE To assess the efficacy of 13CO2 laser laparoscopy in treating infertile women with minimal to mild endometriosis according the American Fertility Society classification in terms of pregnancy rates . DESIGN Prospect i ve study . SETTING Medical school-affiliated hospital . PATIENTS One hundred seventy-six women whose infertility was associated with minimal or mild endometriosis diagnosed by laparoscopy . INTERVENTIONS The patients were treated with one of four methods : 49 underwent operative laparoscopy with newly developed 13CO2 laser vaporization and /or resection ; 45 were treated by operative laparoscopy with simple monopolar electrocoagulation ; 43 who had undergone only diagnostic laparoscopy did not receive any treatment ; and 39 received danazol 800 mg/day for 3 months after diagnostic laparoscopy . MEASUREMENTS AND MAIN RESULTS Estimated cumulative pregnancy rates using life table analyses were indicators of treatment of success and compared among the treatments . A subgroup of 111 patients considered to have endometriosis as the only major infertility factor were also evaluated and compared among treatment options . Pregnancy rates in the CO2 laser laparoscopy group were significantly higher than in the other three groups and in endometriosis-only subset . CONCLUSIONS Advanced laparoscopic surgery with the CO2 laser can be more efficient than other modalities in treating infertile women with minimal to mild endometriosis in terms of pregnancy rates . It appears that in experienced h and s , laser laparoscopy has more favorable results than the other treatments OBJECTIVE To determine pregnancy rates ( PR ) after fimbrioplasty and salpingostomy in nonocclusive distal tubal disease . To evaluate the relative impact of various factors using contemporary statistical analysis . DESIGN Prospect i ve cohort . SETTING Tertiary institutional infertility clinic . PATIENTS ( S ) Infertility patients . INTERVENTION(S ) Fimbrioplasty and salpingostomy . MAIN OUTCOME MEASURE(S ) Cumulative PR , monthly fecundity rates , monthly probability of pregnancy , crude PR , and cure rates . RESULTS ( S ) Thirty-five percent of patients conceived with a cure rate of 72.2 % , monthly probability of pregnancy of 3.9 % , and monthly fecundity rate of 3.9 % . Cumulative PRs were 22 % , 35 % , and 58 % at 6 , 12 , and 24 months , respectively . Pairwise comparisons ( unilateral , bilateral , or either ) failed to detect any statistical difference between the salpingostomy and fimbrioplasty groups . Salpingostomy patients initially may have a higher tendency to become pregnant but appear to lose that advantage after the first few months . When patients with tubo-ovarian adhesions are excluded from the analysis , patients who underwent a bilateral salpingostomy as their sole procedure had better outcome compared with those who only underwent bilateral fimbrioplasty . There was no significant association between pregnancy outcome and the presence of endometriosis , other infertility factors , or tubo-ovarian adhesions . The staging of adnexal adhesions and endometriosis did not predict pregnancy outcome . CONCLUSION ( S ) Laparoscopic fimbrioplasty and salpingostomy are clinical ly efficacious for the treatment of nonocclusive distal tubal disease . After accounting for statistical interactions of various factors among them , no particular association with pregnancy outcome could be identified . This illustrates the need for a revision of the classification of patients with distal tubal disease Minor degrees of endometriosis have often been regarded as being of no import and hence remain untreated , but a study of the natural history of endometriosis has demonstrated that 47 % ( 95 % confidence limits , 23–71 % ) of patients ( n=35 ) given placebo in a double‐blind , r and omized controlled trial showed progression of the disease when assessed before and after treatment by laparoscopy . The active agent , the progestogen gestrinone , was given at a dose of 2.5 mg twice weekly and result ed in an improvement of the disease ( p < 0.004 ) . Furthermore , follow‐up over 12 months showed no significant difference between those patients treated with active agent or placebo , and none between those with persistent disease and those in whom it had been obliterated . These data suggest that a diagnosis of mild endometriosis should be followed by treatment to prevent progressive disease , but that the treatment does not influence subsequent fertility . They indicate that expectant treatment has no place and that even if fertility is not an immediate requirement , active treatment should be instituted , and that the new gestogen , gestrinone is efficacious . Other treatments , such as danazol or luteinizing hormone releasing hormone ( LHRH ) agonists , or the older contraceptive or pseudopregnancy regimens , must be set against spontaneous improvement ( in 5 of 17 patients i.e. 29 % ) or elimination ( in 4 of 17 patients i.e. 24 % ) in the placebo group . Infertile patients with mild endometriosis have disorders of follicular and luteal function , and in vitro fertilization suggests a reduced fertilization rate . Nevertheless , these patients require active treatment if these problems are not to be compounded by adhesions , possibly leading to ovarian enclosure , that would further reduce the untreated cumulative conception rate Minimal pelvic endometriosis can be the only pathology found in infertility patients undergoing an infertility work-up . Although the mechanism by which endometriosis causes infertility is not known , it is well established that pregnancy can be attained in many patients when this disease is treated . Three different modes of treatment were used in 167 infertility patients who had minimal pelvic endometriosis without other pelvic pathology . Group I ( danazol ) achieved 48.9 % pregnancy rates ( 23/47 ) , group II ( CO2 laser ) had 44.6 % pregnancy rates ( 37/83 ) , and group III ( CO2 laser and danazol ) achieved 51.4 % pregnancy rates ( 19/37 ) . Although the pregnancy rates in groups I and III were higher , they were not statistically significant when compared with group II Ninety infertility patients with moderate endometriosis were r and omized between laparoscopic electrocautery and 6 months of danazol therapy and studied for 7 months after treatment . Twenty of the 45 patients undergoing electrocautery conceived ( 44 % ) during the follow-up interval . Forty-one of the 45 patients in the danazol group completed the course of therapy , and 16 of those conceived ( 39 % ) during the same follow-up interval . There was no statistical difference between the two groups ( P less than 0.53 ) . No patients in the electrocautery group experienced complications . This demonstrates that electrocautery is safe and effective in the treatment of moderate endometriosis OBJECTIVE To assess the efficacy of laser laparoscopic surgery in the treatment of pain associated with minimal , mild , and moderate endometriosis . DESIGN A prospect i ve , r and omized , double-blind , and controlled clinical study . SETTING Royal Surrey County Hospital , Guildford , United Kingdom , a referral center for the laser laparoscopic treatment of endometriosis . PATIENTS Sixty-three patients with pain ( dysmenorrhoea , pelvic pain , or dyspareunia ) and minimal to moderate endometriosis . INTERVENTIONS The patients were r and omized at the time of laparoscopy to laser ablation of endometriotic deposits and laparoscopic uterine nerve ablation or expectant management . Pain symptoms were recorded subjectively and by visual analogue scale . The women were unaware of the treatment allocated as was the nurse who assessed them at 3 and 6 months after surgery . MAIN OUTCOME MEASURE Improvement or resolution of pain symptoms assessed subjectively and by visual analogue score . RESULTS Laser laparoscopy results in statistically significant pain relief compared with expectant management at 6 months after surgery . Sixty-two and a half percent of the lasered patients reported improvement or resolution of symptoms compared with 22.6 % in the expectant group . Results were poorest for minimal disease and , if patients with mild and moderate disease only are included , 73.7 % of patients achieved pain relief . There were no operative or laser complications . CONCLUSIONS Laser laparoscopy is a safe , simple , and effective treatment in alleviating pain symptoms in women with stages I , II , and III endometriosis OBJECTIVE To determine the efficacy of the endoscopic treatment of complete distal tubal occlusion or moderate to severe tubal phimosis and to analyze outcome using contemporary statistical method ologies . DESIGN Prospect i ve cohort analysis . SETTING Tertiary-care institution . PATIENTS One hundred thirteen consecutive patients undergoing a neosalpingostomy or salpingostomy . INTERVENTIONS KTP/532 laser ( Laserscope , Santa Clara , CA ) laparoscopy . Additional infertility factors were treated postoperatively . MAIN OUTCOME MEASURES Crude pregnancy rate ( PR ) , monthly fecundity rate , monthly probability of pregnancy , cure rate , and cumulative PRs . Outcome was compared on the basis of the surgical procedure performed . The impact of endometriosis as well as other fertility factors was analyzed . RESULTS Twenty-three patients conceived yielding a crude PR of 20.4 % , a monthly fecundity rate of 2.6 % , a monthly probability of pregnancy of 6.4 % , and a cure rate of 52.4 % . There were six ectopic pregnancies ( 5.3 % ) . A significant difference was found among the cumulative pregnancy curves . The cumulative pregnancy curve for unilateral salpingostomy differed significantly from that of unilateral neosalpingostomy . Patients with endometriosis and no other infertility factors had a significantly better cumulative pregnancy curve compared with patients without endometriosis or other factors as well as compared with patients with no endometriosis but with other infertility factors . Patients undergoing bilateral neosalpingostomy had a cure rate of 9.0 % whereas patients undergoing bilateral salpingostomy had a cure rate of 34.2 % . CONCLUSIONS Operative endoscopy yields PRs that are comparable to those reported in the literature for laparotomy . The presence of complete bilateral distal tubal occlusion has a negative impact on outcome In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility , we conducted a r and omized clinical trial . Eligible patients were women aged < /=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis ( stage I or II of the revised American Fertility Society classification ) and otherwise unexplained infertility for > /=2 years . Eligible women were r and omly assigned to resection or ablation of visible endometriosis ( 54 patients ) or diagnostic laparoscopy only ( 47 patients ) . After laparoscopy women tried to conceive spontaneously for 1 year ( follow-up period ) . A total of five women withdrew from the study : three for personal reasons , and two were lost to follow-up . Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period , 12 ( 24 % ) in the resection/ablation group and 13 ( 29 % ) in the no treatment group conceived ; the difference was not significant . Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one . Thus the 1 year birth rate was 10 out of 51 women ( 19.6 % ) in the resection/ablation group and 10 out of 45 women ( 22.2 % ) in the no-treatment group . In conclusion , the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates BACKGROUND Minimal or mild endometriosis is frequently diagnosed in infertile women . It is often treated by resection or ablation of the lesions , but whether this improves fertility has not been established . We carried out a r and omized , controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis . METHODS We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis . During diagnostic laparoscopy the women were r and omly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only . They were followed for 36 weeks after the laparoscopy or , for those who became pregnant during that interval , for up to 20 weeks of pregnancy . RESULTS Among the 172 women who had resection or ablation of endometriosis , 50 became pregnant and had pregnancies that continued for 20 weeks or longer , as compared with 29 of the 169 women in the diagnostic-laparoscopy group ( cumulative probabilities , 30.7 percent and 17.7 percent , respectively ; P=0.006 by the log-rank test ) . The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months ( rate ratio , 1.9 ; 95 percent confidence interval , 1.2 to 3.1 ) . Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group ( P=0.91 ) . Four minor operative complications ( intestinal contusion , slight tear of the tubal serosa , difficult pneumoperitoneum , and vascular trauma ) were reported ( three in the surgery group and one in the control group ) . CONCLUSIONS Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women OBJECTIVE To assess whether infertile women with minimal or mild endometriosis have lower fecundity than women with unexplained infertility . DESIGN Prospect i ve cohort study . SETTING Twenty-three infertility clinics across Canada . PATIENT(S ) Three hundred thirty-one infertile women aged 20 - 39 years . INTERVENTION(S ) Diagnostic laparoscopy for infertility . Infertile women with minimal or mild endometriosis ( n = 168 ) were compared with women with unexplained infertility ( n = 263 ) . Both groups were managed expectantly . The women were followed up for 36 weeks after the laparoscopy or , for those who became pregnant , for up to 20 weeks of the pregnancy . MAIN OUTCOME MEASURE(S ) Fecundity refers to the probability of becoming pregnant in the first 36 weeks after laparoscopy and carrying the pregnancy for > or = 20 weeks . The fecundity rate is the number of pregnancies per 100 person-months . RESULT ( S ) Fecundity was 18.2 % in infertile women with minimal or mild endometriosis and 23.7 % in women without endometriosis ( log-rank test ) . The fecundity rate was 2.52 per 100 person-months in women with endometriosis and 3.48 per 100 person-months in women with unexplained infertility . The crude and adjusted fecundity rate ratios were 0.72 and 0.83 ( 95 % confidence interval = 0.53 - 1.32 ) , respectively . CONCLUSION ( S ) The fecundity of infertile women with minimal or mild endometriosis is not significantly lower than that of women with unexplained infertility OBJECTIVE To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief , pregnancy rate , and disease recurrence . DESIGN Prospect i ve , r and omized clinical trial . SETTING Tertiary care hospital . PATIENT(S ) Sixty-four patients with advanced stages of endometriosis . INTERVENTION(S ) Patients were r and omly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma ( group 1 ) or drainage of the endometrioma and bipolar coagulation of the inner lining ( group 2 ) . MAIN OUTCOME MEASURE(S ) Pain relief and pregnancy rate . RESULT ( S ) Thirty-two patients were enrolled in each group . The 24-month cumulative recurrence rates of dysmenorrhea , deep dyspareunia , and nonmenstrual pelvic pain were lower in group 1 than in group 2 ( dysmenorrhea : 15.8 % versus 52.9 % ; deep dyspareunia : 20 % versus 75 % ; nonmenstrual pelvic pain : 10 % versus 52.9 % ) . The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 ( 19 months [ range , 13.5 - 24 months ] versus 9.5 months [ range , 3 - 20 months ] ) . The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 ( 66.7 % versus 23.5 % ) . CONCLUSION ( S ) For the treatment of ovarian endometriomas , a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation We have evaluated the prevalence of endometriosis in selected gynaecological conditions requiring surgery . Eligible for the study were women with primary or secondary sterility , chronic pelvic pain , fibroids or benign ovarian cysts requiring laparoscopy or laparotomy consecutively observed during the study period in 23 obstetrics and gynaecology departments in Italy between May 1991 and July 1992 . Women with a previous diagnosis of endometriosis were specifically excluded . A total of 3684 subjects entered the study . Of these , 660 ( mean age 31 years ) were included for sterility , 409 ( mean age 32 ) for chronic pelvic pain , 1880 ( mean age 42 ) for fibroids and 735 ( mean age 33 ) for benign ovarian cysts . During the surgical procedure surgeons were asked to examine the pelvis carefully to identify endometriosis . Out of the 660 women included for sterility , 195 [ 30 % , 95 % confidence interval ( CI ) 26 - 35 ] had endometriosis ; the corresponding figures were 185 out of 409 ( 45 % , 95 % CI 39 - 52 ) for pelvic pain , 219 out of 1880 ( 12 % , 95 % CI 10 - 14 ) for fibroids and 257 out of 735 ( 35 % , 95 % CI 31 - 40 ) for ovarian cysts ; these differences were significant ( chi2(3 ) heterogeneity , absence versus presence = 323.9 , P < 0.001 ) . Among women with endometriosis who entered the study for sterility , 51 % were at stage 1 , 22 % at stage 2 , 20 % at stage 3 and 7 % at stage 4 . The corresponding figures for pelvic pain and fibroids were largely similar : 37 % , 24 % , 30 % , 10 % for women with pelvic pain , 36 % , 11 % , 45 % and 8 % for those with fibroids , but among cases with ovarian cysts stage 3 was over-represented ( 62 % of cases ) . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study conducted between March 1996 and December 1999 was to identify the differences in the perioperative outcome of women undergoing definitive surgery for severe endometriosis either as laparoscopic assisted vaginal hysterectomy and salpingo-oophorectomy ( LAVH+BSO ) or as total abdominal hysterectomy and bilateral salpingo-oophorectomy ( TAH+BSO ) . Study participants included 147 patients with known or suspected endometriosis causing pelvic pain and /or mass with no interest in further childbearing . Among these 90 of them were prospect ively r and omized to have the procedure either as LAVH+BSO ( n = 45 ) or as TAH+BSO ( n = 45 ) . Results showed that laparoscopically-assisted definitive treatment took longer and result ed in a more significant fall in hemoglobin values . However those who underwent this procedure experienced less pain postoperatively during a vigorous cough both after 24 hours and 6 days required less narcotics were discharged earlier and experienced a quicker return to daily activities . With regards to tissue injury in terms of early postoperative C-reactive protein both techniques have the same results OBJECTIVE To determine the outcome of laparoscopy compared with laparotomy in conservative surgical treatment for severe endometriosis . DESIGN Comparison of nonr and omized historical surgical series . SETTING Two teaching hospitals and referral centers specializing in reparative and reconstructive surgery . PATIENT(S ) A total of 216 patients operated for severe endometriosis during a 5-year period . INTERVENTION(S ) Conservative surgical treatment at laparoscopy ( n = 67 ) or laparotomy ( n = 149 ) with median follow-up of 24 months . MAIN OUTCOME MEASURE(S ) Cumulative probability of pregnancy in previously infertile patients ( 22 in the laparoscopy group and 70 in the laparotomy group ) and cumulative probability of pain recurrence in subjects with moderate or severe symptoms before surgery ( 47 in the laparoscopy group and 108 in the laparotomy group ) . RESULT ( S ) The 24-month cumulative probability of pregnancy according to the Kaplan-Meier method was 44.9 % after laparoscopy and 62.7 % after laparotomy . The 24-month cumulative probability of symptoms recurrence evaluated with a 0 to 3 point verbal rating scale was , respectively , 16.4 % versus 20.3 % for dysmenorrhea , 33.3 % versus 15.4 % for deep dyspareunia , and 25.0 % versus 15.9 % for nonmenstrual pain . The corresponding figures obtained with a 10-point linear analogue scale were 20.3 % versus 24.7 % , 28.6 % versus 10.4 % , and 17.5 % versus 20.1 % . No difference is statistically significant . CONCLUSION ( S ) Laparoscopy and laparotomy seem equally effective in the treatment of infertility and chronic pelvic pain associated with severe endometriosis . However , a trend was observed toward a higher pregnancy rate and lower dyspareunia recurrence rate after surgery for severe endometriosis performed at laparotomy compared with laparoscopy |
12,672 | 25,840,776 | No phase III trial has been published using proton beam therapy in comparison with the best photon therapy , but numerous retrospective and dosimetric studies have revealed an advantage of proton beam therapy compared to photons , above all in tumours next to parallel organs at risk ( thoracic and abdominal tumours ) .
Use of proton beam therapy is growing for common cancers within clinical trials but some indications could be applied sooner since in silico analysis showed major advantages with this technique | Proton beam therapy is indicated as a treatment for some rare tumours and paediatric tumours because the technique allows a good local control with minimal toxicity ; the growing number of centres that use proton beam therapy is associated with an increase of dosimetric and clinical data for other malignant tumours as well .
This paper review s potential indications of proton beam therapy . | PURPOSE To evaluate the safety , efficacy and biomarkers of short-course proton beam radiation and capecitabine , followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma ( PDAC ) patients . METHODS AND MATERIAL S Patients with radiographically resectable , biopsy-proven PDAC were treated with neoadjuvant short-course ( 2-week ) proton-based radiation with capecitabine , followed by surgery and adjuvant gemcitabine . The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of < 20 % . Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood . RESULTS The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled , of whom 35 patients were treated in the phase 2 portion . There were no grade 4 or 5 toxicities , and only 2 of 35 patients ( 4.1 % ) experienced a grade 3 toxicity event ( chest wall pain grade 1 , colitis grade 1 ) . Of 48 patients eligible for analysis , 37 underwent pancreaticoduodenectomy . Thirty of 37 ( 81 % ) had positive nodes . Locoregional failure occurred in 6 of 37 resected patients ( 16.2 % ) , and distant recurrence occurred in 35 of 48 patients ( 72.9 % ) . With median follow-up of 38 months , the median progression-free survival for the entire group was 10 months , and overall survival was 17 months . Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12 , stromal CXCR7 expression , and circulating biomarkers CEA , CA19 - 9 , and HGF ( all , P<.05 ) . CONCLUSIONS This study met the primary endpoint by showing a rate of 4.1 % grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation . Treatment was associated with favorable local control . In exploratory analyses , KRAS(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Context . Hadrontherapy is an innovative form of radiotherapy using beams of protons or carbon ions able to destroy some radio-resistant tumours . Because these tumours are highly specific amongst all cancerous tumours , it is impossible to determine the incidence of these diseases from surveillance registries . Goal . To assess , within the Rhône-Alpes region , the incidence of cancers being hadrontherapy indications . Method . Prospect i ve , multicentre continuous data collection during 1 year , by practitioners participating to multidisciplinary tumor board . Tumours are inoperable , radio resistant , at primary stage of development , or locally recurrent , with low metastatic potential . Results . Study involved 27 healthcare centres , 52 groups of specialist practitioners . The estimated incidence of cancers eligible for hadrontherapy in the Rhône-Alpes region in 2010 , that is , for 34 locations in all , is of 8.5/100 000 inhabitants . Appraisal of the low potential of metastatic progression is impeded , because these are rare diseases , whose outcome is unfamiliar to investigators . Conclusion . Future epidemiological studies will need to focus on prognosis and on the metastatic progression rate of these diseases . Indeed , there are few information available on this subject in the literature that could be used to improve preventive measures , medical care , and the surveillance of these rare cancers PURPOSE This study describes the early clinical outcomes of a prospect i ve phase 2 study of consolidative involved-node proton therapy ( INPT ) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma ( HL ) with mediastinal involvement . METHODS AND MATERIAL S Between September 2009 and June 2013 , 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy ( 3DCRT ) and intensity modulated RT . Based on (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ( (18)F-FDG PET/CT ) response , 5 children received 15 to 25.5 cobalt Gy equivalent ( CGE ) of INPT after receiving 4 cycles of Adriamycin , Bleomycin , Vincristine , Etoposide , Prednisone , Cyclophosphamide or Vincristine , adriamycin , methotrexate , Prednisone chemotherapy , and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin , Bleomycine , Vinblastine , Dacarbazine . Patients were routinely evaluated for toxicity during and after treatment , using Common Terminology Criteria for Adverse Events , version 3.0 , and for relapse by physical examination and routine imaging . Relapse-free survival ( RFS ) and event-free survival ( EFS ) rates were calculated using the Kaplan-Meier method from the time of diagnosis . RESULTS The median follow-up was 37 months ( range , 26 - 55 ) . Two events occurred during follow-up : 1 relapse ( inside and outside the targeted field ) and 1 transformation into a primary mediastinal large B cell lymphoma . The 3-year RFS rate was 93 % , and the 3-year EFS rate was 87 % . No acute or late grade 3 nonhematologic toxicities were observed . CONCLUSIONS Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects , PT following chemotherapy in patients with HL is well-tolerated , and disease outcomes were similar to those of conventional photon therapy Background and purpose Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue . The goal of the study was to evaluate the efficacy and feasibility of reirradiation for patients with recurrent malignant brain tumors . Patients and methods The subjects comprised 26 patients with recurrent malignant brain tumors treated with conventional radiotherapy ( RT , n = 8) , stereotactic radiotherapy ( SRT , n = 10 ) , and proton beam therapy ( PBT , n = 8) at our institute . Fifteen patients had glioblastoma , 6 had WHO grade 3 glioma , and 5 had other tumors . The dose of initial radiotherapy was 34.5–94.4 Gy . Different radiation schedules were compared using the equivalent dose in 2-Gy fractions . Results Reirradiation was completed in all patients without a severe acute reaction . The reirradiation doses were 30–60 Gy ( median , 42.3 Gy ) and the total doses for the initial and second treatments were 64.5–150.4 Gy ( median , 100.0 Gy ) . Currently , 11 patients are alive ( median follow-up period , 19.4 months ) and 15 are dead . The median survival and local control periods after reirradiation of the 26 patients were 18.3 and 9.3 months , respectively . For the 15 patients with glioblastoma , these periods were 13.1 and 11.0 months , respectively . Two patients showed radiation necrosis that was treated by surgery or conservative therapy . Conclusion Reirradiation for recurrent malignant brain tumor using conventional RT , SRT , or PBT was feasible and effective in selected cases . Further investigation is needed for treatment optimization for a given patient and tumor condition . ZusammenfassungHintergrund und ZielsetzungBei bösartigen Hirntumoren ist eine operative Beh and lung schwierig und bei rezidivierenden Tumoren schränkt die Dosistoleranz des normalen Hirngewebes eine Strahlentherapie häufig ein . Ziel der Studie war es , die Durchführbarkeit und Wirksamkeit einer erneuten Bestrahlung ( Rebestrahlung ) bei Patienten mit einem rezidivierenden bösartigen intrakraniellen Tumor zu bewerten . Patienten und Method enBei den Prob and en h and elte es sich um 26 Patienten , die mit konventioneller Strahlentherapie ( RT , n = 8) , stereotaktischer Strahlentherapie ( SRT , n = 10 ) und Protonentherapie ( PBT , n = 8) in unserer Einrichtung beh and elt wurden . Die Beh and lung wurde in Abhängigkeit vom Tumorzust and ausgewählt . Ein Glioblastom hatten 15 Patienten , darunter 6 Patienten mit einem Gliom vom WHO-Grad III . Die Dosis der anfänglichen Strahlentherapie lag bei 34,5–94,4 Gy . Es wurden verschiedene Bestrahlungspläne anh and der Äquivalentdosis in 2-Gy-Fraktionen verglichen . ErgebnisseBei allen Patienten wurde die Rebestrahlung ohne schwere akute Reaktion abgeschlossen . Die Rebestrahlungsdosen betrugen 30–60 Gy ( Median 42,3 Gy ) und die Gesamtdosen der ersten und zweiten Beh and lung 64,5–150,4 Gy ( Median 100,0 Gy ) . Gegenwärtig leben noch 11 Patienten ( medianer Nachuntersuchungszeitraum 19,4 Monate ) , 15 Patienten sind bereits verstorben . Die mediane Überlebenszeit betrug 18,3 Monate und der Zeitraum für die lokale Kontrolle 9,3 Monate bezogen auf alle Patienten sowie 13,1 bzw . 11,0 Monate bezogen auf die Glioblastompatienten . Eine beherrschbare Strahlennekrose hatten 2 der 26 Patienten . SchlussfolgerungenDie Rebestrahlung bei rezidivierendem bösartigem Hirntumor anh and konventioneller RT , SRT oder PBT war durchführbar und wirksam . Weitere Untersuchungen sind notwendig , um die optimale Beh and lung für einzelne Patienten bzw . einen bestimmten Tumorzust and herauszufinden Background While conventionally fractionated radiation therapy alone is an acceptable option for poor prognostic patients with unresectable stage III NSCLC , we hypothesized that accelerated hypofractionated radiotherapy will have similar efficacy without increasing toxicity . Methods This is a retrospective analysis of 300 patients diagnosed with stage III NSCLC treated between 1993 and 2009 . Patients included in the study were medically or surgically inoperable , were free of metastatic disease at initial workup and did not receive concurrent chemotherapy . Patients were categorized into three groups . Group 1 received 45 Gy in 15 fractions over 3 weeks ( Accelerated Radiotherapy ( ACRT ) ) while group 2 received 60 - 63 Gy ( St and ard Radiation Therapy 1 ( STRT1 ) ) and group 3 received > 63 Gy ( St and ard Radiation Therapy ( STRT2 ) ) . Results There were 119 ( 39.7 % ) patients in the ACRT group , 90 ( 30.0 % ) in STRT1 and 91 ( 30.3 % ) in STRT2 . More patients in the ACRT group had KPS ≤ 60 ( p < 0.001 ) , more commonly presented with weight loss > 5 % ( p = 0.002 ) , and had stage 3B disease ( p < 0.001 ) . After adjusting for clinical variables , there were no differences in the radiation groups in terms of the patterns of local or distant tumor control or overall survival . Some benefit in relapse free survival was seen in the STRT1 group as compared to ACRT ( HR = 0.65 , p = 0.011 ) . Acute toxicity profiles in the ACRT were significantly lower for grade ≥ 2 radiation dermatitis ( p = 0.002 ) , nausea/vomiting ( p = 0.022 ) , and weight loss during treatment ( p = 0.020 ) . Conclusions Despite the limitations of a retrospective analysis , our experience of accelerated hypofractionated radiation therapy with 45 Gy in 15 fractions appears to be an acceptable treatment option for poor performance status patients with stage III inoperable tumors . Such a treatment regimen ( or higher doses in 15 fractions ) should be prospect ively evaluated using modern radiation technologies with the addition of sequential high dose chemotherapy in stage III NSCLC PURPOSE Combined-modality treatment is st and ard treatment for patients with clinical stage I/II Hodgkin lymphoma ( HL ) . We hypothesized that an early positron emission tomography ( PET ) scan could be used to adapt treatment . Therefore , we started the r and omized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy ( IN-RT ) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD ( doxorubicin , bleomycin , vinblastine , and dacarbazine ) as compared with st and ard combined-modality treatment . PATIENTS AND METHODS Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible . Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET-negative group . Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference , a one-sided superiority test was conducted . RESULTS The analysis included 1,137 patients . In the favorable subgroup , 85.8 % had a negative early PET scan ( st and ard arm , one event v experimental arm , nine events ) . In the unfavorable subgroup , 74.8 % had a negative early PET scan ( st and ard arm , seven events v experimental arm , 16 events ) . The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping r and om assignment for early PET-negative patients . CONCLUSION On the basis of this analysis , combined-modality treatment result ed in fewer early progressions in clinical stage I/II HL , although early outcome was excellent in both arms . The final analysis will reveal whether this finding is maintained over time BACKGROUND Currently no prospect i ve r and omized trial has measured the efficacy of radiation therapy for resected retroperitoneal sarcomas ( RPS ) . Our objective was to determine the effect of radiation therapy on disease-specific and overall survival between propensity score-matched surgically resected RPS patients using the Surveillance , Epidemiology , and End Results ( SEER ) data base . PATIENTS AND METHODS The study population consisted of patients with histologically confirmed RPS who underwent surgical resection between 1988 and 2006 . Exclusion criteria included multiple malignancies , distant metastasis , and unknown grade or stage . Cox modeling was used to determine covariate associations with disease-specific survival . Propensity score methods were used to perform survival analysis in patients who received radiation matched with patients who underwent surgery alone . RESULTS Prior to matching , there were 762 patients ( 558 surgery only , 204 surgery with radiation ) . Factors independently associated with radiation therapy were age ( P = 0.037 ) , geographic region ( P = 0.041 ) , grade ( P = 0.047 ) , stage ( P = 0.003 ) , and surgery type ( P = 0.01 ) . Cox modeling demonstrated that age , sex , grade , and stage were independently associated with survival . Propensity scoring ( 309 matched pairs ) and survival analysis using Kaplan-Meier methods demonstrated no difference between propensity score-matched patients receiving radiation therapy and those who did not ( P = 0.35 ) . CONCLUSION At present , SEER patients with surgically resected RPS who received radiation therapy did not demonstrate survival benefit Introduction : We developed an innovative approach for malignant pleural mesothelioma ( MPM ) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy ( IMRT ) followed by extrapleural pneumonectomy ( EPP ) . This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy ( SMART ) . Methods : All resectable clinical T1 - 3N0M0 histologically proven , previously untreated MPMs were eligible . Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT . Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings . The primary end point was treatment-related mortality and secondary end points were overall survival , disease-free survival , treatment-related morbidity , and patterns of failure . Results : Targeted accrual of 25 patients was completed between November 2008 and October 2012 . All patients completed SMART . IMRT was well tolerated with no grade 3 + toxicities . EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality . Thirteen patients developed grade 3 + surgical complications . One patient ( 4 % ) died from treatment-related toxicity ( empyema ) during follow-up . All but one patient had stage III or IV disease on final pathologic findings . Five of 13 ypN2 patients received adjuvant chemotherapy . After a median follow-up of 23 months ( range , 6–51 ) , the cumulative 3-year survival reached 84 % in epithelial subtypes compared with 13 % in biphasic subtypes ( p = 0.0002 ) . Conclusions : SMART is feasible in resectable MPM patients . This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes Most new radiation techniques , have been introduced primarily to reduce the dose to normal tissues in order to prevent radiation-induced side effects . Radiotherapy with protons is such a radiation technique that due to its superior beam properties compared to photons enables better sparing of normal tissues . This paper describes a stepwise methodology to select patients for proton therapy when the primary aim is to reduce side effects . This method has been accepted by the Dutch health authorities to select patients for proton therapy . In addition , an alternative method is described in case r and omised controlled trials are considered not appropriate PURPOSE Dosimetric planning studies have described potential benefits for the use of proton radiation therapy ( RT ) for locally advanced breast cancer . We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction . METHODS AND MATERIAL S Twelve patients were enrolled in an institutional review board-approved prospect i ve clinical trial . The patients were assessed for skin toxicity , fatigue , and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy . All patients consented to have photographs taken for documentation of skin toxicity . RESULTS Eleven of 12 patients had left-sided breast cancer . One patient was treated for right-sided breast cancer with bilateral implants . Five women had permanent implants at the time of RT , and 7 did not have immediate reconstruction . All patients completed proton RT to a dose of 50.4 Gy ( relative biological effectiveness [ RBE ] ) to the chest wall and 45 to 50.4 Gy ( RBE ) to the regional lymphatics . No photon or electron component was used . The maximum skin toxicity during radiation was grade 2 , according to the Common Terminology Criteria for Adverse Events ( CTCAE ) . The maximum CTCAE fatigue was grade 3 . There have been no cases of RT pneumonitis to date . CONCLUSIONS Proton RT for postmastectomy RT is feasible and well tolerated . This treatment may be warranted for selected patients with unfavorable cardiac anatomy , immediate reconstruction , or both that otherwise limits optimal RT delivery using st and ard methods Purpose Intensity-modulated radiation therapy ( IMRT ) is the state-of-the-art treatment for patients with malignant pleural mesothelioma ( MPM ) . The goal of this work was to assess whether intensity-modulated proton therapy ( IMPT ) could further improve the dosimetric results allowed by IMRT . Patients and methods We re-planned 7 MPM cases using both photons and protons , by carrying out IMRT and IMPT plans . For both techniques , conventional dose comparisons and normal tissue complication probability ( NTCP ) analysis were performed . In 3 cases , additional IMPT plans were generated with different beam dimensions . Results IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity ( p < 0.001 ) and dose homogeneity ( p = 0.01 ) . Better organ at risk ( OAR ) sparing was obtained with IMPT , in particular for the liver ( Dmean reduction of 9.5 Gy , p = 0.001 ) and ipsilateral kidney ( V20 reduction of 58 % , p = 0.001 ) , together with a very large reduction of mean dose for the contralateral lung ( 0.2 Gy vs 6.1 Gy , p = 0.0001 ) . NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus ( average NTCP 14 % vs. 30.5 % ) and the ipsilateral kidney ( p = 0.001 ) . Concerning plans obtained with different spot dimensions , a slight loss of target coverage was observed along with sigma increase , while maintaining OAR irradiation always under planning constraints . Conclusion Results suggest that IMPT allows better OAR sparing with respect to IMRT , mainly for the liver , ipsilateral kidney , and contralateral lung . The use of a spot dimension larger than 3 × 3 mm ( up to 9 × 9 mm ) does not compromise dosimetric results and allows a shorter delivery time . ZusammenfassungZielDie intensitätsmodulierte Strahlentherapie ( IMRT ) erhöht die therapeutische Dosis auf die Pleurahöhle und reduziert die Dosis auf die Risikoorgane ( OAR ) bei Patienten mit malignem Pleuramesotheliom ( MPM ) . Ziel dieser Arbeit ist zu prüfen , ob Protonen , als intensitätsmodulierte Protonentherapie ( IMPT ) angewendet , die dosimetrischen Ergebnisse i m Vergleich zu einer IMRT weiter verbessern können . Patienten und Method enWir haben für 7 MPM-Fälle jeweils mit Photonen und Protonen , unter Verwendung von IMRT und IMPT , Bestrahlungspläne wiedererstellt . Für beide Verfahren haben wir eine Analyse der Normalgewebskomplikationen ( NTCP ) durchgeführt . In 3 Fällen wurden zusätzliche IMPT-Pläne mit geänderter Fokusgröße erstellt . ErgebnisseDie IMPT erlaubt eine leichte Verbesserung der Zielvolumenabdeckung und klare Vorteile in der Konformität ( p < 0,001 ) sowie in der Homogenität ( p = 0,01 ) . Durch IMPT wurde eine bessere Schonung der OAR erreicht , i m Einzelnen für die Leber mit einer Reduktion der Dmean auf 9,5 Gy , ( p = 0,001 ) , für die ipsilaterale Niere ( 58%-Reduktion von V20 ; p = 0,001 ) sowie eine starke Reduktion der mittleren Dosis der kontralateralen Lunge ( 0,2 Gy vs. 6,1 Gy ; p = 0,0001 ) . NTCP-Werte für die Leber zeigten eine systematische Überlegenheit der IMPT gegenüber der IMRT , Ähnliches für die Speiseröhre ( Durchschnitts-NTCP 14 % vs. 30,5 % ) und die ipsilaterale Niere ( p = 0,001 ) . Bezüglich der Pläne mit and erer Fokusgröße zeigt sich ein leichter Verlust der Zielvolumenabdeckung zusammen mit einer Sigma-Erhöhung . Die vorgegebenen Dosisbegrenzungen für die Risikoorgane wurden immer eingehalten . SchlussfolgerungenDie Ergebnisse zeigen , dass IMPT eine bessere Schonung der OAR ermöglicht , vor allem für Leber , ipsilaterale Niere und kontralaterale Lunge . Die Verwendung von Fokusgrößen größer als 3 × 3 mm ( bis 9 × 9 mm ) gefährdet nicht die dosimetrischen Ergebnisse und ermöglicht eine kürzere Bestrahlungszeit BACKGROUND We report the first clinical experience and toxicity of multifield optimization ( MFO ) intensity modulated proton therapy ( IMPT ) for patients with head and neck tumors . METHODS AND MATERIAL S Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy . Patients with squamous cell carcinoma ( SCC ) had comprehensive treatment extending from the base of the skull to the clavicle . The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy , respectively . The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients . Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target , and the scanning nozzle delivered the spot scanning treatment " spot by spot " and " layer by layer . " RESULTS Ten patients presented with SCC and 5 with adenoid cystic carcinoma . All 15 patients were able to complete treatment with MFO-IMPT , with no need for treatment breaks and no hospitalizations . There were no treatment-related deaths , and with a median follow-up time of 28 months ( range , 20 - 35 months ) , the overall clinical complete response rate was 93.3 % ( 95 % confidence interval , 68.1%-99.8 % ) . Xerostomia occurred in all 15 patients as follows : grade 1 in 10 patients , grade 2 in 4 patients , and grade 3 in 1 patient . Mucositis within the planning target volumes was seen during the treatment of all patients : grade 1 in 1 patient , grade 2 in 8 patients , and grade 3 in 6 patients . No patient experienced grade 2 or higher anterior oral mucositis . CONCLUSIONS To our knowledge , this is the first clinical report of MFO-IMPT for head and neck tumors . Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospect i ve clinical trials |
12,673 | 29,208,562 | CONTENT Meta-analyses and systematic review s have shown that CDI and rCDI risk factors are similar .
C. difficile spore germination can be influenced by gut environmental factors result ing from dysbiosis , and spore outgrowth may be affected stage by some antimicrobials ( e.g. fidaxomicin , ramoplanin , oritavancin ) . | BACKGROUND Recurrent Clostridium difficile infection ( rCDI ) places a huge economic and practical burden on healthcare facilities .
Furthermore , rCDI may affect quality of life , leaving patients in an rCDI cycle and dependant on antibiotic therapy .
AIMS To discuss the importance of microbiologic factors in the development of rCDI .
Development of rCDI is attendant on many factors , including immune status or function , comorbidities and concomitant treatments .
Studies suggest that poor bacterial diversity is correlated with clinical rCDI .
Narrow-spectrum gut microflora-sparing antimicrobials ( e.g. surotomycin , cadazolid , ridinilazole ) are in development for CDI treatment , while microbiota therapeutics ( faecal microbiota transplantation , nontoxigenic C. difficile , stool substitutes ) are increasingly being explored .
rCDI can only occur when viable C. difficile spores are present , either within the gut lumen after infection or when reacquired from the environment . | Abstract Background Although the incidence of Clostridium difficile infection ( CDI ) is increasing , available CDI treatment options are limited in terms of sustained response after treatment . This phase 3 trial assessed the efficacy and safety of surotomycin , a novel bactericidal cyclic lipopeptide , versus oral vancomycin in subjects with CDI . Methods In this r and omized , double-blind , active-controlled , multicenter , international trial , subjects with CDI confirmed by a positive toxin result were r and omized to receive surotomycin ( 250 mg twice daily ) or vancomycin ( 125 mg 4 times daily ) orally for 10 days . The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety . The key secondary endpoints were clinical response over time and sustained clinical response through a 30- to 40-day follow-up period . Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed . Results In total , 570 subjects were r and omized and had confirmed CDI ; 290 subjects received surotomycin and 280 subjects received vancomycin . Surotomycin clinical cure rates at end of treatment ( surotomycin/vancomycin : 79.0%/83.6 % ; difference of −4.6 % ; 95 % confidence interval , −11.0 to 1.9 ] ) , clinical response over time ( stratified log-rank test , P = .832 ) , and sustained clinical response at end of trial ( Day 40–50 ) ( 60.6%/61.4 % ; difference of −0.8 % ; 95 % CI , −8.8 to 7.1 ) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin . Both treatments were generally well tolerated . Conclusions Surotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial Background The available treatment options for Clostridium difficile infection ( CDI ) are limited by high recurrence rates . Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial . Objectives To assess surotomycin safety and clinical response ( non-inferiority versus vancomycin ) at the end of treatment ( EOT ) of CDI . Additionally , to assess surotomycin response over time and sustained response at 30 - 40 days post-EOT ( superiority versus vancomycin ) . Patients and methods Patients with CDI were r and omized ( 1:1 ) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3 , double-blind , multicentre , international trial . Clinical response over time and sustained clinical response were monitored until the end of the trial , through a follow-up period of 30 - 40 days . Clinical Trial Registration : NCT01598311 . Results A total of 285 and 292 patients with confirmed CDI were r and omized to receive surotomycin and vancomycin , respectively . Surotomycin-associated clinical response at EOT was non-inferior to vancomycin ( surotomycin/vancomycin : 83.4%/82.1 % ; difference 1.4 % , 95 % CI - 4.9 , 7.6 ) . Following treatment with surotomycin , both clinical response over time ( stratified log-rank test , P = 0.277 ) and sustained clinical response ( 63.3%/59.0 % ; difference 4.3 % , 95 % CI - 3.6 , 12.2 ) did not demonstrate superiority versus vancomycin at end of trial . Both treatments were generally well tolerated . Conclusions Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT . Surotomycin did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate IMPORTANCE Clostridium difficile infection ( CDI ) is a major burden in health care and community setting s. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues . Fecal microbiota transplantation ( FMT ) is a promising , but not readily available , intervention . OBJECTIVE To determine whether frozen- and -thawed ( frozen , experimental ) FMT is noninferior to fresh ( st and ard ) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , noninferiority trial enrolling 232 adults with recurrent or refractory CDI , conducted between July 2012 and September 2014 at 6 academic medical centers in Canada . INTERVENTIONS Patients were r and omly allocated to receive frozen ( n = 114 ) or fresh ( n = 118 ) FMT via enema . MAIN OUTCOMES AND MEASURES The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events . Noninferiority margin was set at 15 % . RESULTS A total of 219 patients ( n = 108 in the frozen FMT group and n = 111 in the fresh FMT group ) were included in the modified intention-to-treat ( mITT ) population and 178 ( frozen FMT : n = 91 , fresh FMT : n = 87 ) in the per- protocol population . In the per- protocol population , the proportion of patients with clinical resolution was 83.5 % for the frozen FMT group and 85.1 % for the fresh FMT group ( difference , -1.6 % [ 95 % CI , -10.5 % to ∞ ] ; P = .01 for noninferiority ) . In the mITT population the clinical resolution was 75.0 % for the frozen FMT group and 70.3 % for the fresh FMT group ( difference , 4.7 % [ 95 % CI , -5.2 % to ∞ ] ; P < .001 for noninferiority ) . There were no differences in the proportion of adverse or serious adverse events between the treatment groups . CONCLUSIONS AND RELEVANCE Among adults with recurrent or refractory CDI , the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea . Given the potential advantages of providing frozen FMT , its use is a reasonable option in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01398969 BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 . Recurrence of Clostridium difficile infection ( CDI ) occurs in approximately 25 % of successfully treated patients . Two phase 3 r and omized , double-blind trials were conducted at 154 sites in the United States , Canada , and Europe to compare fidaxomicin vs vancomycin in treating CDI . Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days . The primary end point was clinical cure of CDI at end of treatment , and a secondary end point was recurrence during the 28 days following clinical cure . In all , 1164 subjects were enrolled , of which a subgroup of 128 in the per- protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment . In the analysis of this subgroup , initial response to therapy was similar for both drugs ( > 90 % cure ) . However , recurrence within 28 days occurred in 35.5 % of patients treated with vancomycin and 19.7 % of patients treated with fidaxomicin ( −15.8 % difference ; 95 % confidence interval , −30.4 % to −0.3 % ; P = .045 ) . Early recurrence ( within 14 days ) was reported in 27 % of patients treated with vancomycin and 8 % of patients treated with fidaxomicin ( P = .003 ) . In patients with a first recurrence of CDI , fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days . Clinical Trials Registration . NCT00314951 and NCT00468728 Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection ( CDI ) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days . Strains originated from patients who had been entered into two phase 3 r and omized clinical trials of fidaxomicin versus vancomycin . Isolates of C. difficile from the initial and recurrent episodes within 28 ( ±2 ) days of cure of CDI were compared using restriction endonuclease analysis ( REA ) typing . Paired isolates were available from 90 of 194 ( 46 % ) patients with recurrent CDI . Patients with isolates available were significantly younger ( P = .008 ) and more likely to be from Canadian sites ( P = .0001 ) , compared with patients without isolates . In 75 of 90 subjects ( 83.3 % ) , the identical REA type strain was identified at recurrence and the initial episode ( putative relapse ) . Early recurrences ( 0–14 days after treatment completion ) were relapses in 86.7 % and a new strain ( reinfection ) in 13.3 % . Later recurrences ( 15–31 days after treatment ) were relapses in 76.7 % and reinfections in 23.3 % . Mean time ( ± st and ard deviation ) to recurrence was 12.2 ( ±6.4 ) days for relapses and 14.7 ( ±6.8 ) days for reinfections ( P = .177 ) . The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain ( relapse ) , compared with the other REA groups ( 39 of 42 [ 93 % ] vs 36 of 48 [ 75 % ] , respectively ; P = .023 ) . We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode , a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains , such as groups BI and J , for which relapse rates may be higher than for other REA groups . Caution in generalizing these observations is required , because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates . Clinical Trials Registration . NCT00314951 and NCT00468728 Background Clostridium difficile infection ( CDI ) is a leading cause of diarrhoea in health care setting s with symptoms ranging from mild and self-limiting to life threatening . SMT19969 is a novel , non-absorbable antibiotic currently under development for the treatment of CDI . Here we report the results from a Phase I study . Methods A double-blind , r and omized , placebo-controlled study assessing safety and tolerability of single and multiple oral doses of SMT19969 in healthy volunteers . Pharmacokinetic assessment s included blood and faecal sampling . The effect of food on systemic exposure and analysis of the gut microbiota were also included . Results Fifty-six healthy male subjects were enrolled . Following single oral doses of up to 2,000 mg in the fasted state , plasma concentrations of SMT19969 were generally below the lower limit of quantification . In the fed state levels ranged from 0.102 to 0.296 ng/mL after single dosing and after repeat dosing at Day 10 from 0.105 to 0.305 ng/mL. Following single and multiple oral doses of SMT19969 , mean daily faecal concentrations increased with increasing dose level and were significantly above the typical MIC range for C. difficile ( 0.06 - 0.5 μg/mL ) . At 200 mg BID , mean ( ± SD ) faecal concentrations of 1,466 ( ±547 ) μg/g and 1,364 ( ±446 ) μg/g were determined on days 5 and 10 of dosing respectively . No notable metabolites were detected in faeces . Overall , all doses of SMT19969 were well tolerated both as single oral doses or BID oral doses for 10 days . The majority ( 88 % ) of adverse events ( AEs ) were classified as gastrointestinal disorders and were mild in severity , resolving without treatment . The gut microbiota was analysed in the multiple dose groups with minimal changes observed in the bacterial groups analysed except for total clostridia which were reduced to below the limit of detection by day 4 of dosing . Conclusions Oral administration of SMT19969 was considered safe and well tolerated and was associated with negligible plasma concentrations after single and multiple doses . In addition , minimal disruption of normal gut microbiota was noted , confirming the highly selective spectrum of the compound . These results support the further clinical development of SMT19969 as an oral therapy for CDI.Trial registration Current Controlled Trials . IS RCT N10858225 BACKGROUND Previous studies comparing Clostridium difficile infection ( CDI ) due to different ribotypes have been conflicting , and many have only compared small numbers of cases or few ribotypes . AIM To compare patient and episode characteristics for CDI due to different ribotypes . METHODS The ribotyping results from 3333 toxin-producing isolates collected from 110 Belgian hospitals between October 2010 and December 2015 were matched to clinical data from the national CDI surveillance data base . Data for ribotypes with at least 100 occurrences were compared . In addition , the national reference laboratory quantitatively measured the level of toxin production in five r and omly chosen cultured isolates for each of the most common ribotypes . FINDINGS Ribotypes with more than 100 occurrences were R014 , R020 , R002 , R078 , R027 , R005 and R106 ( Brazier classification ) . The median age for all patients was 79 years [ patients with R027 , 83 years ( P<0.001 ) ; patients with R106 , 73 years ( P<0.001 ) ] . In total , 10 % of episodes were recurrences ; values were higher for R027 ( 22 % ) and R106 ( 18 % ) . CDI due to R078 was not significantly more likely to be community associated than healthcare associated ( 28 % vs 24 % ; P=0.1 ) . Complications occurred in 7 % of all episodes , and 12 % for those with R027 and R078 . However , after adjusting for age , onset outside the hospital and recurrence , R027 was no longer associated with complications [ odds ratio ( OR ) 1.3 , 95 % confidence interval ( CI ) 0.7 - 2.4 ] , unlike R078 ( OR 1.7 , 95 % CI 1.0 - 2.6 ; P=0.04 ) . A positive stool toxin test and greater levels of toxin production in the cultured isolates were more likely for R078 and R027 . CONCLUSION Out of the seven most common ribotypes in hospital patients , R078 and R027 were associated with higher rates of complications . Infections with R027 and R106 were more likely to be recurrent . The presence of toxin in stools was most likely with R078 , R027 and R106 , with highest levels of toxin production in vitro for R078 and R027 . R060 produced the lowest levels of toxin in vitro Clostridium difficile infection ( CDI ) is the most common identifiable cause of diarrhoea in hospitalized patients . Current therapies rely on the administration of metronidazole or vancomycin , which reduce vegetative population s of C. difficile in the bowel . Recurrence of the disease when treatment with these antibiotics ceases indicates that metronidazole and vancomycin affect not only C. difficile but also commensal population s that normally mediate competitive exclusion . Fidaxomicin is a new antibiotic that inhibits C. difficile . Our study shows that fidaxomicin had little effect on the composition of the faecal microbiota in terms of its major phylogenetic clusters . Notably , clostridial clusters XIVa and IV , and Bifidobacterium , were much less affected by fidaxomicin compared to vancomycin treatment . These findings help to explain the substantially reduced rates of relapse following treatment of CDI with fidaxomicin in recent clinical trials The microflora-sparing properties of fidaxomicin were examined during the conduct of a r and omized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of Clostridium difficile infection ( CDI ) . Fecal sample s were obtained from 89 patients ( 45 received fidaxomicin , and 44 received vancomycin ) at study entry and on days 4 , 10 , 14 , 21 , 28 , and 38 for quantitative cultures for C. difficile and cytotoxin B fecal filtrate concentrations . Additionally , sample s from 10 patients , each receiving vancomycin or fidaxomicin , and 10 sample s from healthy controls were analyzed by quantitative real-time polymerase chain reaction with multiple group-specific primers to evaluate the impact of antibiotic treatment on the microbiome . Compared with controls , patients with CDI at study entry had counts of major microbiome components that were 2–3-log10 colony-forming units (CFU)/g lower . In patients with CDI , fidaxomicin allowed the major components to persist , whereas vancomycin was associated with a further 2–4-log10 CFU reduction of Bacteroides/Prevotella group organisms , which persisted to day 28 of the study , and shorter term and temporary suppression of both Clostridium coccoides and Clostridium leptum group organisms . In the posttreatment period , C. difficile counts similarly persisted in both study population s , but reappearance of toxin in fecal filtrates was observed in 28 % of vancomycin-treated patient sample s ( 29 of 94 ) , compared with 14 % of fidaxomicin-treated patient sample s ( 13 of 91 ; P = .03 ) . Similarly , 23 % of vancomycin-treated patients ( 10 of 44 ) and 11 % of fidaxomicin-treated patients ( 5 of 44 ) had recurrence of CDI . Whereas vancomycin and fidaxomicin are equally effective in resolving CDI symptoms , preservation of the microflora by fidaxomicin is associated with a lower likelihood of CDI recurrence . Clinical Trials Registration . NTC00314951 BACKGROUND Recurrent Clostridium difficile infection is difficult to treat , and failure rates for antibiotic therapy are high . We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection . METHODS We r and omly assigned patients to receive one of three therapies : an initial vancomycin regimen ( 500 mg orally four times per day for 4 days ) , followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube ; a st and ard vancomycin regimen ( 500 mg orally four times per day for 14 days ) ; or a st and ard vancomycin regimen with bowel lavage . The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks . RESULTS The study was stopped after an interim analysis . Of 16 patients in the infusion group , 13 ( 81 % ) had resolution of C. difficile-associated diarrhea after the first infusion . The 3 remaining patients received a second infusion with feces from a different donor , with resolution in 2 patients . Resolution of C. difficile infection occurred in 4 of 13 patients ( 31 % ) receiving vancomycin alone and in 3 of 13 patients ( 23 % ) receiving vancomycin with bowel lavage ( P<0.001 for both comparisons with the infusion group ) . No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day . After donor-feces infusion , patients showed increased fecal bacterial diversity , similar to that in healthy donors , with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species . CONCLUSIONS The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin . ( Funded by the Netherl and s Organization for Health Research and Development and the Netherl and s Organization for Scientific Research ; Netherl and s Trial Register number , NTR1177 . ) We have fingerprinted Clostridium difficile isolates from patients with symptomatic recurrences of infection , using r and om amplified polymorphic DNA ( RAPD ) . The medical records of 55/79 patients were examined , from whom multiple C. difficile-positive faeces were received during hospitalization at least five days , but no more than two months , apart . In 20 of these cases symptoms either did not recur ( i.e. , absent for at least three days between episodes ) , or were explainable by other causes , such as laxative administration . Of the remaining 35 patients , 27 sets of C. difficile isolates ( 23 pairs and four triplicates ) were available for RAPD fingerprinting . Differing C. difficile DNA fingerprints ( at least three major b and s difference ) were obtained for 15/27 patients , and hence at least 56 % of the clinical recurrences of infection were in fact due to re-infection as opposed to relapse . Since we found that an endemic C. difficile clone was present in 18 out of 27 patients ( 67 % ) and accounted for 53 % ( 31/58 ) of all isolates , it is probable that the majority of symptomatic recurrences are in fact re-infections , with either a different or the same C. difficile strain . We conclude that more attention must be given to preventing the re-infection of C. difficile symptomatic patients . Isolation of symptomatic individuals is the preferred option for the protection of other patients , but measures must be taken to ensure that further strain acquisition by the index cases does not occur ABSTRACT Clostridium difficile-associated diarrhea has been associated with disruption of the normal intestinal microbiota , particularly the Bacteroides fragilis group and Prevotella species . Surotomycin is a bactericidal cyclic lipopeptide in development for treatment of Clostridium difficile-associated diarrhea that has selective and potent activity against C. difficile and other Gram-positive bacteria and a minimal impact on intestinal Gram-negative organisms . The impacts of ascending doses of surotomycin on major organism groups in the gut microbiota of healthy volunteers were evaluated during a r and omized , double-blind , placebo-controlled , multiple-dose phase 1 study . Thirty volunteers were r and omized into 3 cohorts , using a 4:1 ratio , to receive 250 mg , 500 mg , or 1,000 mg of surotomycin , or placebo , twice daily for 14 days . Stool sample s collected at baseline ( days 0 and 1 ) and at the end of treatment ( days 13 to 15 ) were cultured quantitatively . The B. fragilis group , the Bacteroides/Prevotella group , and Enterobacteriaceae were also quantified by quantitative real-time PCR . Baseline and end-of-treatment stool sample s showed 1- to 2-log10 CFU/g reductions in total bacterial counts for most volunteers . Various decreases in clostridial , Lactobacillus-Bifidobacterium group , and enterococcus-streptococcus group counts occurred while patients were receiving surotomycin , whereas the enterobacteria and the B. fragilis group persisted at the end of treatment . There was no change in enterococcus MICs of surotomycin , nor was vancomycin-resistant Enterococcus detected after exposure . Surotomycin at doses of up to 1,000 mg twice daily had only modest disruptive effects on the gut microbiota . The potential sparing of the gut microbiota by surotomycin may decrease the risk of disease recurrence BACKGROUND Few studies have investigated the additional healthcare costs of recurrent C. difficile infection ( CDI ) . AIM To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only , compared with CDI patients who experienced recurrent CDI . METHODS This was a prospect i ve , observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes . Total and CDI-attributable hospital length of stay ( LOS ) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode . FINDINGS In all , 540 hospitalized patients aged 62±17 years ( 42 % males ) with primary CDI were enrolled , of whom 95 patients ( 18 % ) experienced 101 recurrent CDI episodes . CDI-attributable median ( interquartile range ) LOS and costs ( in US$ ) increased from 7 ( 4 - 13 ) days and $ 13,168 ( 7,525 - 24,456 ) for patients with primary CDI only versus 15 ( 8 - 25 ) days and $ 28,218 ( 15,050 - 47,030 ) for patients with recurrent CDI ( P<0.0001 , each ) . Total hospital median LOS and costs increased from 11 ( 6 - 22 ) days and $ 20,693 ( 11,287 - 41,386 ) for patients with primary CDI only versus 24 ( 11 - 48 ) days and $ 45,148 ( 20,693 - 82,772 ) for patients with recurrent CDI ( P<0.0001 , each ) . The median cost of pharmacological treatment while hospitalized was $ 60 ( 23 - 200 ) for patients with primary CDI only ( N=445 ) and $ 140 ( 30 - 260 ) for patients with recurrent CDI ( P=0.0013 ) . CONCLUSION This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI . Economic costs and healthcare burden increased significantly for patients with recurrent CDI IMPORTANCE Clostridium difficile is the most common cause of health care-associated infection in US hospitals . Recurrence occurs in 25 % to 30 % of patients . OBJECTIVE To determine the safety , fecal colonization , recurrence rate , and optimal dosing schedule of nontoxigenic C. difficile strain M3 ( VP20621 ; NTCD-M3 ) for prevention of recurrent C. difficile infection ( CDI ) . DESIGN , SETTING , AND PARTICIPANTS Phase 2 , r and omized , double-blind , placebo-controlled , dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI ( first episode or first recurrence ) and had successfully completed treatment with metronidazole , oral vancomycin , or both at 44 study centers in the United States , Canada , and Europe . INTERVENTIONS Patients were r and omly assigned to receive 1 of 4 treatments : oral liquid formulation of NTCD-M3 , 10(4 ) spores/d for 7 days ( n = 43 ) , 10(7 ) spores/d for 7 days ( n = 44 ) , or 10(7 ) spores/d for 14 days ( n = 42 ) , or placebo for 14 days ( n = 44 ) . MAIN OUTCOMES AND MEASURES The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment . Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6 . RESULTS Among 168 patients who started treatment , 157 completed treatment . One or more treatment-emergent adverse events were reported in 78 % of patients receiving NTCD-M3 and 86 % of patients receiving placebo . Diarrhea and abdominal pain were reported in 46 % and 17 % of patients receiving NTCD-M3 and 60 % and 33 % of placebo patients , respectively . Serious treatment-emergent adverse events were reported in 7 % of patients receiving placebo and 3 % of all patients who received NTCD-M3 . Headache was reported in 10 % of patients receiving NTCD-M3 and 2 % of placebo patients . Fecal colonization occurred in 69 % of NTCD-M3 patients : 71 % with 10(7 ) spores/d and 63 % with 10(4 ) spores/d . Recurrence of CDI occurred in 13 ( 30 % ) of 43 placebo patients and 14 ( 11 % ) of 125 NTCD-M3 patients ( odds ratio [ OR ] , 0.28 ; 95 % CI , 0.11 - 0.69 ; P = .006 ) ; the lowest recurrence was in 2 ( 5 % ) of 43 patients receiving 10(7 ) spores/d for 7 days ( OR , 0.1 ; 95 % CI , 0.0 - 0.6 ; P = .01 vs placebo ] ) . Recurrence occurred in 2 ( 2 % ) of 86 patients who were colonized vs 12 ( 31 % ) of 39 patients who received NTCD-M3 and were not colonized ( OR , 0.01 ; 95 % CI , 0.00 - 0.05 ; P < .001 ) . CONCLUSIONS AND RELEVANCE Among patients with CDI who clinical ly recovered following treatment with metronidazole or vancomycin , oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe . Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01259726 BACKGROUND Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea . We aim ed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe , Canada , and the USA . METHODS In this multicentre , double-blind , r and omised , non-inferiority trial , we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19 , 2007 , and Dec 11 , 2009 . Eligible patients were aged 16 years or older with acute , toxin-positive C difficile infection . Patients were r and omly allocated ( 1:1 ) to receive oral fidaxomicin ( 200 mg every 12 h ) or oral vancomycin ( 125 mg every 6 h ) for 10 days . The primary endpoint was clinical cure , defined as resolution of diarrhoea and no further need for treatment . An interactive voice-response system and computer-generated r and omisation schedule gave a r and omisation number and medication kit number for each patient . Participants and investigators were masked to treatment allocation . Non-inferiority was prespecified with a margin of 10 % . Modified intention-to-treat and per- protocol population s were analysed . This study is registered with Clinical Trials.gov , number NCT00468728 . FINDINGS Of 535 patients enrolled , 270 were assigned fidaxomicin and 265 vancomycin . After 26 patients were excluded , 509 were included in the modified intention-to-treat ( mITT ) population . 198 ( 91·7 % ) of 216 patients in the per- protocol population given fidaxomicin achieved clinical cure , compared with 213 ( 90·6 % ) of 235 given vancomycin , meeting the criterion for non-inferiority ( one-sided 97·5 % CI -4·3 % ) . Non-inferiority was also shown for clinical cure in the mITT population , with 221 ( 87·7 % ) of 252 patients given fidaxomicin and 223 ( 86·8 % ) of 257 given vancomycin cured ( one-sided 97·5 % CI -4·9 % ) . In most subgroup analyses of the primary endpoint in the mITT population , outcomes in the two treatment groups did not differ significantly ; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin ( 46 [ 90·2 % ] of 51 ) than with vancomycin ( 33 [ 73·3 % ] of 45 ; p=0·031 ) . Occurrence of treatment-emergent adverse events did not differ between groups . 20 ( 7·6 % ) of 264 patients given at least one dose of fidaxomicin and 17 ( 6·5 % ) of 260 given vancomycin died . INTERPRETATION Fidaxomicin could be an alternative treatment for infection with C difficile , with similar efficacy and safety to vancomycin . FUNDING Optimer Pharmaceuticals ABSTRACT Cadazolid , a novel fluoroquinolone-oxazolidinone antibiotic , exhibits potent in vitro activity against Clostridium difficile , including the epidemic BI/NAP1/027 strain . This multicenter , r and omized , double-blind , active reference group , phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection ( CDI ) . Eligible patients with first occurrence/first recurrence of CDI were r and omized 1:1:1:1 to 250 , 500 , or 1,000 mg cadazolid twice daily ( BID ) or oral 125 mg vancomycin four times daily ( QID ) for 10 days . The primary endpoint was clinical cure at test of cure ( 48 ± 24 h after the end of treatment ; modified intent-to-treat population ) , defined as resolution of diarrhea with no further CDI treatment required . Secondary endpoints included recurrence rate , sustained clinical response ( clinical cure without recurrence ) , and time to diarrhea resolution . Of 84 patients enrolled , 20 , 22 , 20 , and 22 received 250 , 500 , or 1,000 mg cadazolid BID or 125 mg vancomycin QID , respectively . The primary endpoint was achieved in 76.5 % ( 80 % confidence interval [ CI ] , 58.4 , 89.3 ) , 80.0 % ( 63.9 , 91.0 ) , 68.4 % ( 51.1 , 82.5 ) , and 68.2 % ( 52.3 , 81.3 ) of patients , respectively . There was no evidence of a cadazolid dosage-dependent response . Each dosage of cadazolid result ed in a lower recurrence rate than with vancomycin ( 18.2 to 25.0 % versus 50 % ) . Consequently , higher sustained clinical response rates were observed with cadazolid ( 46.7 to 60.0 % ) than with vancomycin ( 33.3 % ) . The times to diarrhea resolution were similar for cadazolid and vancomycin . Cadazolid was well tolerated , with no safety signal observed . The results of this phase 2 study support further clinical development of cadazolid . ( This study has been registered in the United States at Clinical Trials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010 - 020941 - 29 . In 2009 the first European Society of Clinical Microbiology and Infection ( ESCMID ) treatment guidance document for Clostridium difficile infection ( CDI ) was published . The guideline has been applied widely in clinical practice . In this document an up date and review on the comparative effectiveness of the currently available treatment modalities of CDI is given , thereby providing evidence -based recommendations on this issue . A computerized literature search was carried out to investigate r and omized and non-r and omized trials investigating the effect of an intervention on the clinical outcome of CDI . The Grade s of Recommendation Assessment , Development and Evaluation ( GRADE ) system was used to grade the strength of our recommendations and the quality of the evidence . The ESCMID and an international team of experts from 11 European countries supported the process . To improve clinical guidance in the treatment of CDI , recommendations are specified for various patient groups , e.g. initial non-severe disease , severe CDI , first recurrence or risk for recurrent disease , multiple recurrences and treatment of CDI when oral administration is not possible . Treatment options that are review ed include : antibiotics , toxin-binding resins and polymers , immunotherapy , probiotics , and faecal or bacterial intestinal transplantation . Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised . The main antibiotics that are recommended are metronidazole , vancomycin and fidaxomicin . Faecal transplantation is strongly recommended for multiple recurrent CDI . In case of perforation of the colon and /or systemic inflammation and deteriorating clinical condition despite antibiotic therapy , total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended |
12,674 | 21,527,934 | There was no statistically significant difference in the risk of osteonecrosis , sepsis , fungal infection , diabetes or pancreatitis .
DEX in induction therapy for children with ALL is more efficacious than PRED .
However , DEX is also associated with more toxicity , and currently it remains unclear whether short-term superiority of DEX will also result in better overall survival | This systematic review and meta- analysis compared the efficacy and toxicity of dexamethasone ( DEX ) versus prednisone ( PRED ) for induction therapy in childhood acute lymphoblastic leukemia ( ALL ) . | We report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia ( Ph+ ALL ) treated on the UK Medical Research Council ( MRC ) trial for childhood ALL , MRC ALL 97 , between January 1997 and June 2002 . Forty‐two ( 2·3 % ) patients were Ph+ . Nineteen ( 45 % ) had < 25 % blasts in bone marrow ( BM ) within the first 2 weeks of treatment and were defined as a good response group ( GRG ) , the others as a poor response group ( PRG ) . Thirty‐six ( 86 % ) achieved first complete remission ( CR1 ) at the end of induction , of which 28 underwent BM transplantation ( BMT ) . The median follow‐up was 42 months ( range , 21–84 ) . The 3‐year event‐free survival ( EFS ; 52 % , 95 % CI , 36–66 % ) was a considerable improvement on the previous MRC UKALL XI trial ( 27 % ) . EFS for the GRG and PRG were 68 % ( 43–84 % ) and 39 % ( 18–59 % ) , respectively ( P = 0·03 ) ; presenting white cell count < 50 × 109/l ( P = 0·02 ) was predictive for overall survival . Changes in the MRC ALL97 trial within the study period result ed in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction . Though the use of daunorubicin during induction was not a prospect i ve study question , EFS was significantly better for those whose induction included this drug ( P = 0·02 ) . Steroid r and omization was not stratified for Ph+ ALL patients and was not predictive for EFS . BMT in CR1 appeared to reduce the risk of a subsequent BM relapse . These results show significant improvement on previous MRC trials ; future therapeutic strategies should include early intensive therapy and BMT in CR1 Despite a widespread belief that glucocorticoid therapy is associated with positive energy balance and excess weight gain there is a dearth of quantitative evidence about its effects and the underlying mechanisms of any effects . The primary aim of the present study was to quantify the effect of dexamethasone and prednisone treatment on energy intake in children treated for childhood acute lymphoblastic leukemia . A secondary aim was to test for differences in excess weight gain between patients treated using the 2 glucocorticoids . We measured energy intake in 26 patients ( mean + /- SD age , 6.3 + /- 2.3 yr ) during a 5-d period " on " steroids and again in the week before steroid treatment . Changes in body mass index from diagnosis to 1 and 2 yr postdiagnosis were expressed as SD scores . Steroid treatment was associated with a significant increase in energy intake of approximately 20 % ( mean paired difference , 1.7 MJ/d ; SD , 2.8 ; 95 % confidence interval , 0.7 - 2.8 MJ/d ) , with no significant difference between the 2 steroids . The mean change in body mass index SD score was + 0.38 ( SD , 1.10 ; P < 0.05 ) to 1 yr and + 0.68 ( SD , 1.38 ; P < 0.05 ) to 2 yr , with no significant difference between the 2 groups of patients . Glucocorticoid treatment in childhood acute lymphoblastic leukemia increases energy intake markedly , and this effect contributes to the excess weight gain and obesity characteristic of patients being treated for acute lymphoblastic leukemia In previous clinical trials of childhood acute lymphoblastic leukemia ( ALL ) , dexamethasone result ed in higher event-free survival rates than prednisone , presumably due to greater central nervous system penetration . Dexamethasone 's association with long-term neurocognitive toxicity is unknown . In this multisite study , we measured neurocognitive functioning in 92 children with st and ard-risk ALL , 1 to 9.99 years at diagnosis , at a mean of 9.8 years after r and omization to prednisone ( n = 41 ) or dexamethasone ( n = 51 ) on Children 's Cancer Group ( CCG ) 1922 . No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age , sex , and time since diagnosis . The exception was that patients receiving dexamethasone scored one-third of a st and ard deviation worse on word reading ( 98.8 + /- 1.7 vs 104.9 + /- 1.8 ; P = .02 ) . There were no group differences in the distribution of test scores or the parents ' report of neurologic complications , psychotropic drug use , and special education . Further analyses suggested for the dexamethasone group , older age of diagnosis was associated with worse neurocognitive functioning ; for the prednisone group , younger age at diagnosis was associated with worse functioning . In conclusion , our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid r and omization . This study is registered with http://www . clinical trials.gov under NCT00085176 objective Disturbances in body weight regulation are often encountered during glucocorticoid treatment and are associated with increased insulin resistance and truncal fat accumulation . Children were investigated who were receiving glucocorticoid treatment for acute lymphoblastic leukaemia ( ALL ) . They were r and omized to receive either prednisolone or dexamethasone as part of induction of remission . This r and omization process provided a suitable opportunity to compare the effects of these two administered steroid on surrogate markers of adipocyte activity ( leptin ) and hyperinsulinaemia/insulin resistance ( SHBG ) The 1997 acute lymphoblastic leukaemia ( ALL ) trial ( ALL97 ) was a r and omised comparison of prednisolone versus dexamethasone and of 6‐mercaptopurine versus 6‐thioguanine . During the first 2 years of the trial , review of survival data showed the preceding trial , UKALL XI , was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups . The therapy template was therefore altered to an American Children ’s Cancer Group ( CCG ) style regimen , including stratification by age , white cell count and early response to therapy by assessment of the bone marrow . This phase of the trial was design ated ALL97/99 . Comparison of the two phases showed that the event‐free survival ( EFS ) for both ALL97 and ALL97/99 was better than previous UKALL trials , as was overall survival ( OS ) for ALL97/99 . Both EFS and OS were significantly better in ALL97/99 than in ALL97 ( at five years , 80·0 % vs. 74·0 % , P = 0·002 ; and 88·0 % vs. 83·5 % , P = 0·005 , respectively ) . Isolated central nervous system ( CNS ) relapse for patients in ALL97/99 was half that in ALL97 ( 3·0 % vs. 4·9 % ) , P = 0·03 ) and the overall CNS relapse rate was halved in ALL97/99 ( 4·4 % vs. 9·6 % , P < 0·00005 ) . There were no significant differences for non‐CNS relapse , induction deaths or deaths in remission between the two phases of the trial Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia ( ALL ) receiving Escherichia coli asparaginase ( CASP ) combined with steroids . Moreover , hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocol s ( including CASP combined with prednisone during induction therapy ) . To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities ( prednisone or dexamethasone ) , the present analysis was performed . Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocol s ( PRED group , n = 280 , 60 mg/m(2 ) prednisone ; DEXA group , n = 56 , 10 mg/m(2 ) dexamethasone during induction therapy ) were studied . Study end point was the onset of symptomatic vascular accidents during induction therapy . Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group ( thrombosis frequency , 10.4 % ) compared with children in the DEXA group ( thrombosis frequency , 1.8 % ; P = .028 ) . Although no significant difference was found in the overall prevalence of prothrombotic risk factors , 46.5 % of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor , whereas no carrier in the DEXA group had a thromboembolism . At the time of maximum CASP activity , fibrinogen and activities of antithrombin , plasminogen , and protein S were significantly reduced in the PRED group . No significant correlation could be found between CASP activity and levels of coagulation factors . In conclusion , the use of dexamethasone instead of prednisone , administered with CASP , significantly reduced the onset of venous thromboembolism The Children 's Cancer Group enrolled 13 298 young people age < 21 years on 1 of 16 protocol s between 1983 and 2002 . Outcomes were examined in three time periods , 1983–1988 , 1989–1995 , 1996–2002 . Over the three intervals , 10-year event-free survival ( EFS ) for Rome/National Cancer Institute st and ard risk ( SR ) and higher risk ( HR ) B-precursor patients was 68 and 58 % , 77 and 63 % , and 78 and 67 % , respectively , whereas for SR and HR T-cell patients , EFS was 65 and 56 % , 78 and 68 % , and 70 and 72 % , respectively . Five-year EFS for infants was 36 , 38 , and 43 % , respectively . Seminal r and omized studies led to a number of important findings . Stronger post-induction intensification improved outcome for both SR and HR patients . With improved systemic therapy , additional intrathecal ( IT ) methotrexate effectively replaced cranial radiation . For SR patients receiving three-drug induction , iso-toxic substitution of dexamethasone for prednisone improved EFS . Pegylated asparaginase safely and effectively replaced native asparaginase . Thus , rational therapy modifications yielded better outcomes for both SR and HR patients . These trials provide the platforms for current Children 's Oncology Group trials Conventional therapy for childhood acute lymphoblastic leukemia ( ALL ) includes prednisone and oral 6-mercaptopurine . Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous ( IV ) over oral 6-mercaptopurine , which remain to be vali date d. We report the results of a r and omized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine . Children with National Cancer Institute st and ard-risk ALL were r and omly assigned in a 2 x 2 factorial design to receive dexamethasone ( 6 mg/m(2)/d ) for 28 days in induction , plus taper , compared with prednisone ( 40 mg/m(2)/d ) . The second r and omized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation . During maintenance , 5 days of the r and omized steroid was given monthly , at the same dose , and all patients received daily oral 6-mercaptopurine . During delayed intensification , all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days , with taper . Intrathecal ( IT ) methotrexate was the sole central nervous system-directed therapy . Patients r and omly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7 % + /- 0.8 % , compared with 7.1 % + /- 1.1 % for prednisone ( P = .01 ) . There was also a trend toward fewer isolated bone marrow relapses with dexamethasone . The 6-year event-free survival ( EFS ) was 85 % + /- 2 % for dexamethasone and 77 % + /- 2 % for prednisone ( P = .002 ) . EFS was similar with oral or IV 6-mercaptopurine ; however , patients assigned to IV 6-mercaptopurine had decreased survival after relapse PURPOSE To evaluate whether dexamethasone ( DEXA ) yields a better outcome than prednisolone ( PRED ) in a prospect i ve , r and omized , controlled trial for the treatment of childhood acute lymphoblastic leukemia ( ALL ) . PATIENTS AND METHODS Two hundred thirty-one st and ard-risk ( SR ) patients and 128 intermediate-risk ( IR ) non-B-cell ALL patients were registered from March 1995 to March 1999 . After r and om assignment in each group , the PRED arm patients received PRED 60 mg/m2 during induction followed by PRED 40 mg/m2 over four intensifications in the SR group and three intensifications in the IR group . DEXA arm patients received DEXA 8 mg/m2 during induction and DEXA 6 mg/m2 during the intensifications . The maintenance phase was continued until week 104 . RESULTS Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1 % + /- 3.9 % ( n = 117 ) and 84.4 % + /- 5.2 % ( n = 114 ) , respectively , in the SR group ( P = .217 ) and 84.9 % + /- 4.6 % ( n = 62 ) and 80.4 % + /- 5.1 % ( n = 66 ) , respectively , in the IR group ( P = .625 ) . The primary reason for treatment failure was marrow relapse . Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm . Although complications were more prevalent in the DEXA arm than in the PRED arm , fatal toxicity was rare both groups . CONCLUSION DEXA administered at 8 mg/m2 during induction and 6 mg/m2 during intensification showed no advantage over PRED administered at 60 mg/m2 during induction and 40 mg/m2 during intensification in both the SR and IR groups Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia ( ALL ) . Prednisolone is the most commonly used steroid , particularly in the maintenance phase of therapy . There is increasing evidence that , even in equipotent dosage for glucocorticoid effect , dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system ( CNS ) compared with prednisolone . Substitution of dexamethasone for prednisolone in the treatment of ALL might , therefore , result in improved event‐free and overall survival . Children with newly diagnosed ALL were r and omly assigned to receive either dexamethasone or prednisolone in the induction , consolidation ( all received dexamethasone in intensification ) and continuation phases of treatment . Among 1603 eligible r and omized patients , those receiving dexamethasone had half the risk of isolated CNS relapse ( P = 0·0007 ) . Event‐free survival was significantly improved with dexamethasone ( 84·2 % vs. 75·6 % at 5 years ; P = 0·01 ) , with no evidence of differing effects in any subgroup of patients . The use of 6·5 mg/m2 dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk‐groups of patients and , despite the increased toxicity , should now be regarded as part of st and ard therapy for childhood ALL Background Corticosteroids are a st and ard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma . Our aim was to determine whether dexamethasone results in a better outcome than prednisolone . Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were r and omized to receive , as part of their induction therapy on days 1–8 and 15–22 , either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2 . Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase . Subsequently patients younger than 50 years , with a suitable donor , were to undergo allogeneic stem cell transplantation , whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation . R and omization was done with a minimization technique . The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis . Results Between August 1995 and October 2003 , 325 patients between 15 to 72 years of age were r and omized to receive either dexamethasone ( 163 patients ) or prednisolone ( 162 patients ) . After induction and the course of first consolidation therapy , 131 ( 80.4 % ) patients in the dexamethasone group and 124 ( 76.5 % ) in the prednisolone group achieved complete remission . No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates ( ±SE ) which were 25.9 % ( 3.6 % ) and 28.7 % ( 3.5 % ) in the dexamethasone and prednisolone groups , respectively ( P=0.82 , hazard ratio 0.97 ; 95 % confidence interval , 0.75–1.25 ) . Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups , the 6-year rates being 32.3 % and 37.5 % , respectively ( hazard ratio 1.03 ; 95 % confidence interval 0.76–1.40 ) . The 6-year cumulative incidences of relapse were 49.8 % and 53.5 % ( Gray ’s test : P=0.30 ) while the 6-year cumulative incidences of death were 18 % and 9 % ( Gray ’s test : P=0.07 ) . Conclusions In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma , treatment with dexamethasone did not show any advantage over treatment with prednisolone aim To compare the relative potency of prednisolone ( Pred ) and dexamethasone ( Dex ) on short‐term growth and bone turnover PURPOSE We investigated whether there was a dose-response relationship for the use of corticosteroids in childhood acute lymphoblastic leukemia ( ALL ) . PATIENTS AND METHODS Three hundred sixty-nine patients , ages 1 to 18 years with ALL , were r and omly assigned to receive one of four different doses of corticosteroid ( prednisolone 40 mg/m(2)/d or dexamethasone 6 , 18 , or 150 mg/m(2)/d ) administered as a 3-day , single-drug window before initiation of st and ard , multidrug induction chemotherapy . Corticosteroid drug response was measured by reduction in bone marrow blast counts and absolute peripheral blast counts after 3 days . Glucocorticoid receptor ( GCR ) number and the effective concentration of dexamethasone result ing in a 50 % reduction of leukemic cell viability in vitro ( EC-50 ) were evaluated at days 0 and 3 . RESULTS Increasing dexamethasone doses result ed in greater marrow blast response ( P = .007 ) , with a similar trend in peripheral-blood blast response . High-dose corticosteroid regimens ( dexamethasone 18 or 150 mg/m(2)/d ) elicited better responses than st and ard doses of dexamethasone or prednisone ( bone marrow , P = .002 ; peripheral blasts , P = .05 ) . Among patients treated with st and ard-dose corticosteroids , 38 % with resistant ( EC-50 > 10(-7 ) ) peripheral blasts had a good response compared with 92 % with sensitive ( EC-50 < 10(-7 ) ) peripheral blasts ( P = .01 ) . In contrast , there was no differential response according to EC-50 group after high-dose corticosteroids . Similarly , an association between response and GCR on peripheral-blood blasts was noted after st and ard-dose corticosteroid regimens but not after high-dose corticosteroid regimens . CONCLUSION Response of ALL to glucocorticoid therapy increased with dose . Higher-dose corticosteroid treatment abrogated the effect of relative drug insensitivity and of low GCR on peripheral blasts In 1971 , Cancer and Leukemia Group B ( CALGB ) mounted a study of acute lymphocytic leukemia ( ALL ) that compared the effects of the two steroid hormones dexamethasone and prednisone . Six-hundred-forty-six children and adolescents with ALL were r and omized to receive either prednisone or dexamethasone as part of their remission induction therapy . The 493 evaluable patients who achieved complete remission received the same steroid as pulses throughout remission . Specific central nervous system ( CNS ) therapy was r and omized to either six injections of intrathecal methotrexate ( IT MTX ) alone or to six injections of IT MTX with cranial radiation ( 2,400 cGy ) . Both cranial radiation and dexamethasone offered increased protection against CNS relapse as the first site of failure over IT MTX alone . There were 30 CNS relapses among 238 patients ( 12.6 % ) receiving cranial radiation plus IT MTX , whereas there were 70 CNS relapses among 225 ( P less than 0.001 ) ( 22.5 % ) in those who received IT MTX alone . Similarly , there were 33 CNS relapses among 231 ( 14.3 % ) children treated with dexamethasone , whereas there were 67 CNS relapses among 262 ( 25.6 % ) treated with prednisone ( P = 0.017 ) . Both steroids appeared equal in protecting the bone marrow . Recent national studies have shown significant improvements in preventing CNS relapse over the results in the present report . However , this finding warrants further investigation and , with further documentation , could lead to the substitution of prednisone by dexamethasone to aid further in preventing CNS relapse . This may be particularly important in patients at higher risk for CNS relapse Children with acute lymphoblastic leukemia ( ALL ) receive as part of induction therapy a 4-week course of high-dose glucocorticoid , which is either abruptly discontinued or shortly tapered . The aim of this study was to evaluate the signs and symptoms of steroid withdrawal syndrome and performance status ( according to Lansky scale ) during the 9-day tapering period and 1 week after withdrawal of the steroid in 63 children r and omly allocated to receive prednisone or dexamethasone as part of induction treatment according the AIEOP ALL 2000 protocol . Twenty of 28 ( 75 % ) patients on dexamethasone versus 18 of 35 ( 51.4 % ) on prednisone ( P < 0.05 ) developed at least one steroid withdrawal symptom during the study period . Three or more symptoms were observed in 39.3 % ( 11/28 ) of the dexamethasone group and 8.6 % ( 3/35 ) of the prednisone group ( P < 0.05 ) . Dexamethasone patients developed clinical signs earlier ( within 3 days from the steroid tapering ) than symptomatic prednisone patients . In the prednisone group , the symptoms were less severe and the performance status was higher ( P < 0.05 ) . Steroid withdrawal morbidity in ALL children during induction is a frequent and clinical ly relevant complaint . A more gradual ( for dexamethasone ) or a more prolonged ( for prednisone ) tapering might be suggested BACKGROUND Dexamethasone is increasingly used as the steroid of choice in trials for st and ard risk children with acute lymphoblastic leukemia ( ALL ) . Improvements in event-free survival ( EFS ) have been attributed to lower CNS relapse rates , However , there are concerns that dexamethasone may be more toxic than previous conventional therapy with prednisone . Such toxicity raises questions about the implication s for child neuropsychological function and HRQOL . Patients participating in the UK ALL 99/01 trial were r and omized to receive dexamethasone or prednisone as their steroid in induction and maintenance chemotherapy . We compared the HRQOL and behavior in children r and omized to receive both these agents . PROCEDURE St and ardized question naires to assess parent and child HRQOL at 3 - 6 months after diagnosis ( T1 ) and 1 year later ( T2 ) completed by mothers in family homes . Forty-five mothers of a child with ALL ( 32 male , 13 female ; average age at T1 , 7 years 3 months ; at T2 , 8 years 3 months ) completed HRQOL question naires . RESULTS For the total group , child HRQOL scores improved and behavior problems decreased significantly from T1 to T2 . Comparison of HRQOL scores between the 17 children r and omized to dexamethasone and 28 children r and omized to prednisone showed no significant differences . The rate of improvement in HRQOL from T1 to T2 did not differ between children r and omized to dexamethasone or prednisone . CONCLUSIONS Dexamethasone is increasingly used in the treatment of ALL and has been linked with improved survival rates . Long-term use of dexamethasone raises questions about neuropsychologic toxicity . Although HRQOL increased significantly over the year for all children , the extent of this increase did not differ by chemotherapy . These results should contribute to lessened concerns about use of dexamethasone in the treatment of ALL BACKGROUND A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase . In this study , adrenal function and signs and symptoms of adrenal insufficiency were prospect ively assessed in children with acute lymphoblastic leukemia ( ALL ) after induction treatment including high-dose prednisone ( PDN ) or dexamethasone ( DXM ) . PROCEDURES Sixty-four children with ALL , treated according to the AIEOP ALL 2000 Study protocol , underwent low dose ACTH ( LD-ACTH ) stimulation 24 hr after the last tapered steroid dose . In those with impaired cortisol response , additional LD ACTH tests were performed every 1 - 2 weeks until cortisol levels normalized . Signs and symptoms of adrenal insufficiency were recorded during the observation period . RESULTS All patients had normal basal cortisol values at diagnosis . Twenty-four hours after last glucocorticoid dose , morning cortisol was reduced in 40/64 ( 62.5 % ) patients . LD-ACTH testing showed adrenal suppression in 52/64 ( 81.5 % ) patients . At the following ACTH test 7 - 14 days later , morning cortisol values were reduced in 8/52 ( 15.4 % ) patients and response to the test was impaired in 12/52 ( 23 % ) . Adrenal function completely recovered in all patients within 10 weeks . No difference was found between patients treated with PDN or DXM . Almost 35 % of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency . One child developed a severe adrenal crisis during adrenal suppression . CONCLUSIONS High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms . Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated |
12,675 | 23,328,935 | Conclusion The results of most studies of the studies review ed suggest that critical illness and ICU treatment are associated with long-term cognitive impairment . | Purpose There is increasing evidence that critical illness and treatment in an intensive care unit ( ICU ) may result in significant long-term morbidity .
The purpose of this systematic review was to summarize the current literature on long-term cognitive impairment in ICU survivors . | Background The purpose of this study was to identify predictors of 3-month mortality in critically ill older persons under medical care and to assess the clinical impact of an ICU stay on physical and cognitive dependence and subjective health status in survivors . Methods We conducted a prospect i ve observational cohort study including all older persons 75 years and older consecutively admitted into ICU during a one-year period , except those admitted after cardiac arrest , All patients were followed for 3 months or until death . Comorbidities were assessed using the Charlson index and physical dependence was evaluated using the Katz index of Activity of Daily Living ( ADL ) . Cognitive dependence was determined by a score based on the individual components of the Lawton index of Daily Living and subjective health status was evaluated using the Nottingham Health Profile ( NHP ) score . Results One hundred patients were included in the analysis . The mean age was 79.3 ± 3.4 years . The median Charlson index was 6 [ IQR , 4 to 7 ] and the mean ADL and cognitive scores were 5.4 ± 1.1 and 1.2 ± 1.4 , respectively , corresponding to a population with a high level of comorbidities but low physical and cognitive dependence . Mortality was 61/100 ( 61 % ) at 3 months . In multivariate analysis only comorbidities assessed by the Charlson index [ Adjusted Odds Ratio , 1.6 ; 95 % CI , 1.2 - 2.2 ; p < 0.003 ] and the number of organ failures assessed by the SOFA score [ Adjusted Odds Ratio , 2.5 ; 95 % CI , 1.1 - 5.2 ; p < 0.02 ] were independently associated with 3-month mortality . All 22 patients needing renal support after Day 3 died . Compared with pre-admission , physical ( p = 0.04 ) , and cognitive ( p = 0.62 ) dependence in survivors had changed very little at 3 months . In addition , the mean NHP score was 213.1 ± 132.8 at 3 months , suggesting an acceptable perception of their quality of life . Conclusions In a selected population of non surgical patients 75 years and older , admission into the ICU is associated with a 3-month survival rate of 38 % with little impact on physical and cognitive dependence and subjective health status . Nevertheless , a high comorbidity level ( ie , Charlson index ) , multi-organ failure , and the need for extra-renal support at the early phase of intensive care could be considered as predictors of death Objective : To examine the impact of delirium during intensive care unit stay on long-term health-related quality of life and cognitive function in intensive care unit survivors . Design : Prospect i ve 18-month follow-up study . Setting : Four intensive care units of a university hospital . Patients : A median of 18 months after intensive care discharge , question naires were sent to 1,292 intensive care survivors with ( n = 272 ) and without ( n = 1020 ) delirium during their intensive care stay . Measurements and Main Results : The Short Form-36v1 , checklist individual strength-fatigue , and cognitive failure question naire were used . Covariance analysis was performed to adjust for relevant covariates . Of the 915 responders , 171 patients were delirious during their intensive care stay ( median age 65 [ interquartile range 58–85 ] , Acute Physiology and Chronic Health Evaluation II score 17 [ interquartile range 14–20 ] ) , and 745 patients were not ( median age 65 [ interquartile range 57–72 ] , Acute Physiology and Chronic Health Evaluation II score 13 [ interquartile range 10–16 ] ) . After adjusting for covariates , no differences were found between delirium and nondelirium survivors on the Short Form-36 and checklist individual strength-fatigue . However , survivors who had suffered from delirium reported that they made significantly more social blunders , and their total cognitive failure question naire score was significantly higher , compared to survivors who had not been delirious . Survivors of a hypoactive delirium subtype performed significantly better on the domain mental health than mixed and hyperactive delirium patients . Duration of delirium was significantly correlated to problems with memory and names . Conclusions : Intensive care survivors with delirium during their intensive care unit stay had a similar adjusted health-related quality of life evaluation , but significantly more cognitive problems than those who did not suffer from delirium , even after adjusting for relevant covariates . In addition , the duration of delirium was related to long-term cognitive problems BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research Objective Recent studies have shown significant cognitive problems some months after critical illness . However there has been no research examining cognitive function within the intensive care unit ( ICU ) in non-delirious patients . Design and setting A prospect i ve study in an ICU . Patients and participants Using the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) , 30 long-stay , tracheal-intubated ICU patients were tested . Prior to testing on ICU the Confusion Assessment Measure ( CAM-ICU ) was administered and only those patients clearly not delirious and off sedation for several days were tested . The CANTAB tests were repeated a week after ICU discharge on the general ward and then again at 2 months . Sixteen patients completed the follow-up . Results While on ICU all 30 patients showed significant problems with strategic thinking and problem solving ; 20 patients had some problems with memory . The degree of difficulty with problem solving on ICU was correlated with length of ICU stay ( p = 0.011 ) , age ( p = 0.036 ) and length of hospital stay post ICU ( p = 0.044 ) . Problems with memory in ICU and on the general ward were correlated with admission APACHE II score ( p = 0.004 and p = 0.005 respectively ) . At the 2-month follow-up 5 of 16 patients ( 31 % ) scored below the 25 percentile for memory and 8 of 16 ( 50 % ) below the 25 percentile for problem solving ( Slater TA , Jones C , Griffiths RD , Wilson S , Benjamin K ( 2004 ) Cognitive impairment during and after intensive care : a pilot study . Intensive Care Med 30 [ Suppl 1]:S199 ) . Conclusions Difficulties with problem solving and poor memory remained a significant issue for 2 months after ICU discharge Objective To examine neuropsychological function , depression , and quality of life 6 months after discharge in patients who received mechanical ventilation in the intensive care unit . Design Prospect i ve cohort study . Setting Tertiary care , medical and coronary intensive care unit of a university-based medical center . Study Population A total of 275 consecutive , mechanically ventilated patients from a medical intensive care unit were prospect ively followed . At 6 months , 157 were alive , of whom 41 ( 26 % ) returned for extensive follow-up testing . Measurement and Main Results Neuropsychological testing and assessment of depression and quality of life were performed at 6-month follow-up . Seven of 41 patients were excluded from further analysis due to preexisting cognitive impairment determined via surrogate interviews using the Modified Blessed Dementia Rating Scale and a review of medical records . On the basis of strict criteria derived from normative data , we found that 11 of 34 patients ( 32 % ) were neuropsychologically impaired . Impairment was generally diffuse but occurred primarily in areas of psychomotor speed , visual and working memory , verbal fluency , and visuo-construction . The rate of neuropsychological deficits in the study population was markedly higher than population norms for mild dementia . Scores on the Geriatric Depression Scale – Short Form were significantly more abnormal in the neuropsychologically impaired group than in the nonimpaired group at hospital discharge ( p = .04 ) and at 6-month follow-up ( p = .02 ) , and clinical ly significant depression was found in 27 % of impaired subjects at hospital discharge and in 36 % at 6-month follow-up . No differences were observed between groups in quality of life as measured with the Short Form Health Survey-12 at discharge or 6-month follow-up . Conclusions Prolonged neuropsychological impairment is common among survivors of the medical intensive care unit and occurs with greater than anticipated frequency when compared with relevant normative data . Future investigations are warranted to eluci date the nature of the association between critical illness , neuropsychological impairment , depression , and decreased quality of life Introduction Long-term outcomes of elderly patients after medical ICU care are little known . The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU . Methods We prospect ively studied 112/230 healthy elderly patients ( ≥65 years surviving at least 12 months after ICU discharge ) with full functional autonomy without cognitive impairment prior to ICU entry . The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III ( APACHE III ) classification diagnosis and length of ICU stay and ICU scores ( APACHE II , Sepsis-related Organ Failure Assessment ( SOFA ) and OMEGA ) at admission and discharge were collected . Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton , Barthel , and Charlson Indexes and Informant Question naire on Cognitive Decline to evaluate functionality , comorbidity and cognitive status , respectively . The EuroQol-5D assessed quality of life . Data were collected at baseline , during ICU and ward stay and 3 , 6 and 12 months after hospital discharge . Paired or unpaired T-tests compared differences between groups ( continuous variables ) , whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables . For variables significant ( P ≤ 0.1 ) on univariate analysis , a forward multiple regression analysis was performed . Results Only 48.9 % of patients ( mean age : 73.4 ± 5.5 years ) were alive 12 months after discharge showing a significant decrease in functional autonomy ( Lawton and Barthel Indexes ) and quality of life ( EuroQol-5D ) compared to baseline status ( P < 0.001 , all ) . Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery ( P < 0.01 , both ) . Thus , in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥40 at discharge the hazard ratio for full functional recovery was 4.04 ( 95 % CI : 1.58 to 10.33 ; P = 0.005 ) and 6.1 ( 95 % CI : 1.9 to 19.9 ; P < 0.01 ) , respectively . Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up ( P < 0.001 ) . Conclusions The survival rate of elderly medical patients 12 months after discharge from the ICU is low ( 49 % ) , although functional status and quality of life remained similar to baseline in most of the survivors . However , there was a two-fold increase in the prevalence of geriatric syndromes Objective : To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation . Design : Prospect i ve cohort study . Setting : Medical intensive care unit in a large community hospital in the United States . Patients : Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessment s 3 and 12 mos after discharge . Measurements and Main Results : Of 126 eligible patients , 99 survived ≥3 months after critical illness ; long-term cognitive outcomes were obtained for 77 ( 78 % ) patients . Median age was 61 yrs , 51 % were admitted with sepsis/acute respiratory distress syndrome , and median duration of delirium was 2 days . At 3-mo and 12-mo follow-up , 79 % and 71 % of survivors had cognitive impairment , respectively ( with 62 % and 36 % being severely impaired ) . After adjusting for age , education , preexisting cognitive function , severity of illness , severe sepsis , and exposure to sedative medications in the intensive care unit , increasing duration of delirium was an independent predictor of worse cognitive performance — determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition — at 3-mo ( p = .02 ) and 12-mo follow-up ( p = .03 ) . Duration of mechanical ventilation , alternatively , was not associated with long-term cognitive impairment ( p = .20 and .58 ) . Conclusions : In this study of mechanically ventilated medical intensive care unit patients , duration of delirium ( which is potentially modifiable ) was independently associated with long-term cognitive impairment , a common public health problem among intensive care unit survivors . ( Crit Care Med 2010 ; Objective To evaluate the effectiveness of a rehabilitation program following critical illness to aid physical and psychological recovery . Design R and omized controlled trial , blind at follow-up with final assessment at 6 months . Setting Two district general hospitals and one teaching hospital . Patients Patients were 126 consecutively admitted intensive care patients meeting the inclusion criteria . Interventions Control patients received ward visits , three telephone calls at home , and clinic appointments at 8 wks and 6 months . Intervention patients received the same plus a 6-wk self-help rehabilitation manual . Measurements and Main Results We measured levels of depression and anxiety ( Hospital Anxiety and Depression Scale ) , phobic symptoms ( Fear Index ) , posttraumatic stress disorder (PTSD)-related symptoms ( Impact of Events Scale ) , and scores on the Short-Form Health Survey physical dimension 8 wks and 6 months after intensive care unit ( ICU ) treatment . Memory for ICU was assessed at 2 wks post-ICU discharge using the ICU Memory Tool . The intervention group improved , compared with the control patients , on the Short-Form Health Survey physical function scores at 8 wks and 6 months ( p = .006 ) , and there was a trend to a lower rate of depression at 8 wks ( 12 % vs. 25 % ) . However , there were no differences in levels of anxiety and PTSD-related symptoms between the groups . The presence of delusional memories was correlated significantly with both anxiety and Impact of Events Scale scores . Conclusions A self-help rehabilitation manual is effective in aiding physical recovery and reducing depression . However , in those patients recalling delusional memories from the ICU , further psychological care may be needed to reduce the incidence of anxiety and PTSD-related symptoms Acute Respiratory Distress Syndrome ( ARDS ) is characterized by lung injury and hypoxemia , has a high mortality rate , and is associated with significant morbidity including cognitive and emotional sequelae and decreased quality of life . There is limited information regarding which of these factors are associated with decreased quality of life . This study assessed the relationships between quality of life , cognitive and emotional function in ARDS survivors at 1-year post-hospital discharge . Sixty-six ARDS survivors were administered a battery of neuropsychological tests , measures of emotional function and quality of life 1 year post-hospital discharge . At 1 year 45 % of the ARDS patients had cognitive sequelae and 29 % had mild to moderate symptoms of depression and anxiety . Depression , anxiety , and intensive care unit length of stay were significantly correlated with decreased quality of life . Cognitive impairments did not correlate with decreased quality of life . Illness severity and emotional function , but not cognitive sequelae , are associated with decreased quality of life 1 year following ARDS . ARDS is common and may result in significant cognitive and emotional morbidity and decreased quality of life A prospect i ve study using neuropsychological testing explored cognitive performance , and specifically executive function , in survivors of critical illness during the first year of recovery . Fifty‐one patients who had survived 3 days or more in the intensive care unit were studied approximately 3 months after discharge ; 45 of them were studied again 6 months later . General health was assessed using the Short‐Form 36 . Cognitive and executive functions were measured using Raven 's Progressive Matrices , the Hayling Sentence completion test and the Six‐Element Test . Three months after discharge from intensive care , all eight domains of Short‐Form 36 were impaired among survivors ; by 9 months , four of the eight domains showed significant improvement . At 3 months , 35 % of patients scored at or below a level equivalent to the lowest performing 5 % of a normal population ( i.e. the fifth percentile ) on two or more tests of cognitive function ; by 9 months only 4 % of patients were impaired to this extent . Although cognitive performance improved with time , it remained below normal which originally used the 20 % decline on 20 % of the tests criterion in the analysis of cognitive change after conventional and off-pump CABG [ 4 ] . Because this was a r and omized trial , nonsurgical controls were not included . In their original analysis , 31 % of the CABG patients were classified as having decline at 3 months . In a follow-up to this study , they recruited healthy controls not undergoing surgery and applied the same criteria for decline , and it was found that an unexpected 28 % of these normal controls also met this criterion for decline [ 6 ] . Using a more conservative definition to define decline , they then compared their original CABG group with this control group and found at 3 months that 7.7 % of the CABG and 4.6 % of the controls were classified as having decline . These authors conclude that their previous use of the 20 % decline of 20 % of test criteria had thus greatly overestimated the incidence of cognitive decline after CABG . We exp and on the findings just mentioned by illustrating the effects of applying the arbitrary criterion of 20 % decline on one or more tests to previously published data from our prospect i ve study of cognitive outcomes comparing CABG and nonsurgical controls with coronary artery disease and heart-healthy controls ( without risk factors for coronary artery disease ) [ 7 ] . The results clearly demonstrate that there is considerable variability ( both improvement and decline ) in the follow-up test performance even for the control subjects without surgery . Therefore , in the absence of a control group , this normal variability associated with follow-up cognitive testing might have been OBJECTIVES To quantify the long-term ( > 6 years ) health-related quality of life ( HRQOL ) of a large cohort of patients admitted to a surgical intensive care unit ( ICU ) . In addition , we aim ed to explore the influence of different surgical classifications on long-term health status and to make comparisons with general population norms . DESIGN Prospect i ve observational cohort study . SETTING A Dutch teaching hospital . PATIENTS All surviving surgical ICU patients admitted to the Dutch teaching hospital between 1995 and 2000 . MAIN OUTCOME MEASURES Patient-reported data on HRQOL were collected with the EuroQol-6D ( EQ-6D ) after a mean follow-up of 8 years ( range , 6 - 11 years ) . Patient characteristics , surgical classification , length of ICU stay , and survival were prospect ively registered . The EQ utility scores ( measured with the EQ-5D US index tariff ) , EQ visual analog scale scores , and prevalences of domain-specific health problems were calculated . The effect of surgical classification on EQ utility scores and EQ visual analog scale scores was assessed by multivariable generalized linear regression analysis . Logistic regression was used to explore the influence of surgical classification on domain-specific health problems . Long-term HRQOL of surgical ICU patients was compared with an age- and sex-matched general Dutch population using t test analysis . RESULTS Eight hundred thirty-four patients survived the ICU and were available for follow-up . In 575 patients ( 69 % ) , the HRQOL was measured . For all surgical classifications combined , after 6 to 11 years , nearly half of all patients still had problems with mobility ( 52 % ) , usual activity ( 52 % ) , pain/discomfort ( 57 % ) , and cognition ( 43 % ) . Compared with the age- and sex-matched general population , HRQOL was worse , with a difference of 0.11 on the EQ utility score ( range , 0 - 1 ) . Oncological surgery patients had the best ( EQ utility score , 0.83 ) and vascular patients had the worst ( EQ utility score , 0.72 ) HRQOL . Trauma ( odds ratio between 2.47 - 3.47 ) and vascular surgery ( odds ratio between 2.27 - 5.37 ) patients showed significantly increased prevalences of problems in mobility , self-care , usual activities , and cognition . CONCLUSIONS More than 6 years after a surgical ICU admission , HRQOL of this patient population is largely reduced . Many patients still have a variety of health problems , including decreased cognitive functioning . Treatment advances should be made to reduce the current health deficit of surgical ICU survivors compared with the general population CONTEXT Studies suggest that many survivors of critical illness experience long-term cognitive impairment but have not included premorbid measures of cognitive functioning and have not evaluated risk for dementia associated with critical illness . OBJECTIVES To determine whether decline in cognitive function was greater among older individuals who experienced acute care or critical illness hospitalizations relative to those not hospitalized and to determine whether the risk for incident dementia differed by these exposures . DESIGN , SETTING , AND PARTICIPANTS Analysis of data from a prospect i ve cohort study from 1994 through 2007 comprising 2929 individuals 65 years old and older without dementia at baseline residing in the community in the Seattle area and belonging to the Group Health Cooperative . Participants with 2 or more study visits were included , and those who had a hospitalization for a diagnosis of primary brain injury were censored at the time of hospitalization . Individuals were screened with the Cognitive Abilities Screening Instrument ( CASI ) ( score range , 0 - 100 ) every 2 years at follow-up visits , and those with a score less than 86 underwent a clinical examination for dementia . MAIN OUTCOME MEASURES Score on the CASI at follow-up study visits and incident dementia diagnosed in study participants , adjusted for baseline cognitive scores , age , and other risk factors . RESULTS During a mean ( SD ) follow-up of 6.1 ( 3.2 ) years , 1601 participants had no hospitalization , 1287 had 1 or more noncritical illness hospitalizations , and 41 had 1 or more critical illness hospitalizations . The CASI score was assessed more than 45 days after discharge for 94.3 % of participants . Adjusted CASI scores averaged 1.01 points lower for visits following acute care illness hospitalization compared with follow-up visits not following any hospitalization ( 95 % confidence interval [ CI ] , -1.33 to -0.70 ; P < .001 ) and 2.14 points lower on average for visits following critical illness hospitalization ( 95 % CI , -4.24 to -0.03 ; P = .047 ) . There were 146 cases of dementia among those not hospitalized , 228 cases of dementia among those with 1 or more noncritical illness hospitalizations , and 5 cases of dementia among those with 1 or more critical illness hospitalizations . The adjusted hazard ratio for incident dementia was 1.4 following a noncritical illness hospitalization ( 95 % CI , 1.1 to 1.7 ; P = .001 ) and 2.3 following a critical illness hospitalization ( 95 % CI , 0.9 to 5.7 ; P = .09 ) . CONCLUSIONS Among a cohort of older adults without dementia at baseline , those who experienced acute care hospitalization and critical illness hospitalization had a greater likelihood of cognitive decline compared with those who had no hospitalization . Noncritical illness hospitalization was significantly associated with the development of dementia |
12,676 | 15,238,371 | Since these cutoff points are not absolute , there is no definite threshold of risk below which no further work-up is warranted .
The probabilities for nonanginal chest pain and atypical angina are larger in primary care practice .
For risk stratification in a patient with chronic stable angina who has a history of documented MI or Q waves on | It covers diagnosis and risk stratification for patients with symptomatic chronic stable angina who have not had an acute myocardial infa rct ion ( MI ) or revascularization procedure in the previous 6 months .
Angina is defined as a clinical syndrome characterized by discomfort in the chest , jaw , shoulder , back , or arm .
Clinical Classification of Chest Pain In 2002 , the ACC/AHA published an up date d guideline , which the ACP recognized as a scientifically valid review of the evidence and background paper ( 2 ) .
Methods The ACP has traditionally developed evidence -based guidelines .
However , more than 50 % of patients with chronic stable angina have normal results on resting ECG ( 2 ) .
Chest radiography is not useful for the diagnosis of CAD unless the patient also has signs and symptoms of congestive heart failure , valvular heart disease , or pericardial disease .
While severe coronary calcification on chest radiography increases the likelihood of clinical ly significant CAD , the sensitivity of this finding is only 40 % ( 2 ) .
The ACC/AHA does not recommend electron-beam computed tomography , also known as ultra-fast computed tomography , as a screening test for CAD ( 3 ) . | BACKGROUND Before any new diagnostic test is accepted in clinical practice , such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed . The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography ( two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours ) versus maximal symptom-limited bicycle exercise ECG test in patients with angina . METHODS AND RESULTS We studied 429 consecutive in-hospital patients who met the following inclusion criteria : history of chest pain , off antianginal therapy for at least 2 days ( 1 week for beta-blockers ) , no previous myocardial infa rct ion and /or obvious regional left ventricular dyssynergy of contraction ( akinesis or dyskinesis ) at baseline , and acceptable acoustic window under resting conditions . All patients underwent dipyridamole echocardiography and exercise ECG -- on different days and in r and om order -- within 1 week of coronary angiography ( which was performed independent of test results ) and were followed up for 37.8 + /- 14 months ( range , 1 to 73 months ) . Criteria of positivity were for dipyridamole echocardiography , a transient regional dyssynergy absent in the baseline examination ; for exercise ECG , an ST-segment shift of > or = 0.1 mV from baseline ; and for coronary angiography , a luminal reduction of > or = 75 % in at least one major coronary vessel ( 50 % for left main ) . There were 183 patients without and 246 with coronary artery disease ; 132 had one- , 70 had two- , and 44 had three- and /or left main vessel disease . The specificity was higher for dipyridamole echocardiography than for exercise ECG ( 90 % versus 51 % , P < .001 ) . The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG ( 75 % versus 74 % , P = NS ) , with no significant differences in the subset with one- ( 67 % versus 69 % , P = NS ) , two- ( 79 % versus 77 % , P = NS ) , or three- ( 93 % versus 86 % , P = NS ) vessel disease . During the follow-up , there were 20 deaths , 13 nonfatal myocardial infa rct ions , and 126 revascularization procedures . In the univariate analysis , dipyridamole result ed in higher chi 2 values than did exercise stress testing . A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death ( chi 2 = 19.4 , P < .0001 ) of all invasive and noninvasive parameters . The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age , diabetes , resting ECG , and exercise stress test according to a modified , interactive stepwise procedure . This is true when death only , death and myocardial infa rct ion , and death , myocardial infa rct ion , and revascularization procedures were considered end points . CONCLUSIONS In patients with no previous myocardial infa rct ion and good resting left ventricular function , compared with exercise ECG , dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease . Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death , infa rct ion , and all events when the presence as well as the timing , severity , and extension of dipyridamole-induced wall motion abnormalities are considered Because of numerous reports of false positive results with thallium-201 ( Tl-201 ) stress testing in patients with left bundle branch block , the authors decided to evaluate another mode of coronary vasodilatation , dipyridamole , for the diagnosis of coronary atheromatosis . Nine patients were prospect ively studied with stress and dipyridamole Tl-201 scintigraphy ; both tests were performed within three to 79 days of one another . Five of the patients also had coronary angiograms ( four within one year , one five years earlier ) . Four of the patients had normal results with both tests ( two normal angiograms , two not performed ) ; two had reversible septal defects with stress-induced coronary vasodilatation but normal dipyridamole studies ( only one had an angiogram , which was normal ) ; one patient had a fully reversible septal defect with stress and a fixed defect with dipyridamole ( normal angiogram ) ; one had a partially reversible septal stress defect which was fixed with dipyridamole ; and one had a normal stress study but a reversible septal defect with dipyridamole ( an angiogram performed five years earlier showed 30 to 40 % stenosis of the anterior descending artery ) . Because it seems that dipyridamole produces fewer false positive results , it should be used instead of stress testing to induce coronary vasodilatation in patients with left bundle branch block BACKGROUND The prognostic value of tomographic myocardial perfusion imaging with dipyridamole or adenosine in patients with left bundle-branch block has not been established . METHODS AND RESULTS The study group consisted of 245 patients with left bundle-branch block who underwent tomographic ( single photon emission tomography ) myocardial perfusion imaging with thallium-201 ( n=173 ) or technetium-99 m sestamibi ( n=72 ) and either dipyridamole ( n=153 ) or adenosine ( n=92 ) stress . Patients were prospect ively classified into two groups . Patients were classified as " high risk " if they had ( 1 ) a large severe fixed defect ( n=28 ) , ( 2 ) a large reversible defect ( n=36 ) , or ( 3 ) cardiac enlargement and either increased pulmonary uptake ( thallium ) or a decreased resting ejection fraction ( sestamibi ) ( n=20 ) . The remaining 161 patients ( 66 % of the study group ) were at " low risk . " Follow-up was 99 % complete at 3+/-1.4 years . Three-year overall survival was 57 % in the high-risk group compared with 87 % in the low-risk group ( P<.0001 ) . Survival free of cardiac death/nonfatal myocardial infa rct ion/cardiac transplantation was 55 % in the high-risk group and 93 % in the low-risk group ( P<.0001 ) . The presence of a high-risk scan had significant incremental prognostic value after adjustment for age , sex , diabetes , and previous myocardial infa rct ion ( P<.0001 ) . Patients with a low-risk scan had an overall survival that was not significantly different from that of a US age-matched population ( P=.86 ) . CONCLUSIONS Tomographic myocardial perfusion imaging with adenosine or dipyridamole stress provides important prognostic information in patients with left bundle-branch block , which is incremental to clinical assessment This article is the first of two papers about the care of patients with chronic stable angina . The second paper , which deals with the treatment of patients with chronic stable angina , will be published in a future issue . Both articles have been adapted from material s created by the Committee on Guidelines for Chronic Stable Angina sponsored by the American College of Cardiology ( ACC ) , the American Heart Association ( AHA ) , and the American College of PhysiciansAmerican Society of Internal Medicine ( ACPASIM ) ( 1 - 3 ) . The adaptations in these articles are intended to make the information more useful for clinicians who do not specialize in the care of patients with heart disease . The committee created the original material s after review ing published reports identified in part through MEDLINE search es of the English literature from 1975 through 1998 . The weight of the evidence was ranked high and given a grade of A if the data were derived from multiple r and omized clinical trials involving many patients . The weight of the evidence was ranked intermediate and given a grade of B if the data were derived from a few r and omized trials involving small numbers of patients , nonr and omized studies , or observational registries . A lower rank and a grade of C were given when an expert consensus was the primary basis for the recommendation . We used the following classification system for final recommendations . Class I referred to conditions for which there is evidence or general agreement that a given procedure or treatment is useful and effective ; class II referred to conditions for which there is conflicting evidence or a divergence of opinion about the usefulness or efficacy of a procedure or treatment ; class IIa referred to conditions for which the weight of evidence or opinion is in favor of usefulness or efficacy of a procedure or treatment ; class IIb referred to conditions for which usefulness or efficacy of a procedure or treatment is less well established by evidence or opinion ; and class III referred to conditions for which there is evidence or general agreement that the procedure or treatment is not useful or effective and in some cases may be harmful . For the sake of brevity , we have combined some original recommendations and omitted others , especially those that affect fewer patients , are based on weaker evidence , or recommend that interventions not be done . Scope of the Guidelines These recommendations are intended for adult patients with stable chest pain syndromes and known or suspected ischemic heart disease and patients who have ischemic equivalents , such as dyspnea or arm pain with exertion . Also , some recommendations about follow-up apply to patients who become asymptomatic during therapy . These guidelines are not intended for patients with acute ischemic syndromes , patients with chest pain after cardiac transplantation , patients with chest pain within 6 months of revascularization by percutaneous techniques or coronary artery bypass grafting ( CABG ) , patients with coronary artery disease ( CAD ) detected without symptoms , patients with nonanginal chest pain , or pediatric patients . The Initial Evaluation The initial evaluation of patients presenting with chest pain includes a detailed history , a focused physical examination , and performance of a few tests and procedures that are useful for estimating the probability of significant CAD ( Figure 1 ) . Significant CAD is defined as an obstruction of at least one major epicardial artery that occupies at least 70 % of the artery 's cross-sectional diameter or an obstruction of the left main coronary artery that occupies at least 50 % of its diameter . Figure 1 . Diagnosis of chest pain . Comorbid conditions and patient preferences . The history should elicit specific information about chest pain because accurate characterization helps determine whether CAD is the cause of angina . Angina usually occurs in patients with CAD , but it can occur in patients with unobstructed coronary arteries who have myocardial ischemia related to an arterial spasm or endothelial dysfunction . It also can occur in patients with other cardiovascular problems , such as aortic stenosis , hypertrophic cardiomyopathy , or uncontrolled hypertension . Symptoms that mimic angina can also occur in patients with noncardiac conditions involving the chest wall , esophagus , or lung . The following characteristics of chest pain should be determined : quality , location , duration , and the presence of factors that provoke and relieve the pain . Angina is characterized by a substernal pain or discomfort , although it may radiate to the neck , jaw , epigastrium , or arms . Patients often describe the quality of angina with characteristic terms , such as squeezing , grip-like , pressure-like , suffocating , or heavy . Angina usually lasts for minutes . Exertion or emotional stress provokes it , and rest or nitroglycerin relieves it , typically within 30 seconds to several minutes . After the history is obtained , the clinician should classify the chest pain . Typical angina has the following characteristics : 1 ) substernal chest discomfort with a characteristic quality and duration that is 2 ) provoked by exertion or emotional stress and 3 ) relieved by rest or nitroglycerin . Atypical angina has two of the three characteristics of typical angina , while noncardiac chest pain has one or none of the characteristics of typical angina . The term noncardiac chest pain means that the probability of CAD is low . The term nonspecific chest pain more accurately describes this situation , but tradition prevents its use . In patients with angina , the severity of pain should be grade d according to the Canadian Cardiovascular Society ( CCS ) classification system ( Table 1 ) ( 6 ) . Although grading chest pain is less useful for establishing a diagnosis or estimating risk , it is essential for evaluating the effects of therapy . Table 1 . Grading of Angina by the Canadian Cardiovascular Society Classification System In patients with angina , the stability of pain should be assessed . Patients have unstable angina if the pain started recently ; is more easily provoked ; or occurs with increased frequency , severity , or duration ( 7 ) . Some patients with unstable angina have a measurable risk for short-term death ( 8) . Those characterized as high risk have a 1.7 % probability of dying within 30 days , and those characterized as moderate risk have a 1.2 % probability . These patients have pain at rest , nocturnal pain , signs or symptoms of heart failure , or new or ischemic changes on resting electrocardiography ( ECG ) . They should be evaluated in the inpatient setting . However , patients with unstable angina whose pain has been present for at least 2 weeks and who lack any of angina 's more worrisome clinical features , including ECG changes , can be evaluated in an outpatient setting because their probability of death or myocardial infa rct ion within 30 days is indistinguishable from zero . The initial history should also include information about the risk factors for CAD , such as smoking , hyperlipidemia , diabetes , hypertension , and a family history of premature CAD . Findings on physical examination are often normal in patients with stable angina ( 9 ) . During an episode of pain , however , there uncommonly may be an S4 or S3 gallop , a mitral regurgitant murmur , a paradoxically split S2 , bibasilar rales , or a chest wall heave . Each of these findings makes CAD more likely , especially if the finding disappears when the pain goes away ( 10 ) . Evidence of noncoronary atherosclerotic disease , such as a carotid bruit , diminished pedal pulses , or an abdominal aneurysm , increases the likelihood of CAD . Elevated blood pressure , xanthomas , and retinal exu date s identify CAD risk factors . Table 2 lists recommendations for the tests and procedures that we believe should be used in the initial evaluation of patients with suspected chronic stable angina . Resting , 12-lead ECG should be performed , although the results will be normal in 50 % of patients with chronic stable angina ( 11 ) . Therefore , results on normal resting ECG do not exclude CAD . Evidence on ECG of left ventricular hypertrophy or ST T-wave changes consistent with myocardial ischemia favor the diagnosis of angina ( 12 ) . The presence of arrhythmias , such as atrial fibrillation or ventricular tachyarrhythmias , also increases the probability of CAD , but other types of cardiac disease frequently cause these arrhythmias . Q waves suggesting a previous myocardial infa rct ion make CAD very likely , although an isolated Q wave in lead III or a QS pattern in lead V1 and V2 is often nonspecific . Atrioventricular block may suggest multivessel CAD but is also nonspecific . Table 2 . Recommendations for Initial Laboratory Tests , Electrocardiography , and Chest Radiography for the Diagnosis of Chronic Stable Angina Results on ECG performed during chest pain are abnormal in approximately 50 % of patients with angina who have normal results on resting ECG . Sinus tachycardia occurs commonly ; bradyarrhythmias are less common . ST T-wave depression or inversion on resting ECG or pseudo-normalization of these abnormalities during pain is another indicator of CAD ( 13 ) . Tachyarrhythmias , atrioventricular blocks , left anterior fascicular block , or bundle-branch block occurring with chest pain also increases the probability of coronary heart disease . ST-segment elevation or depression also increases the probability of CAD , and it increases the risk for myocardial infa rct ion or death because there is ischemia at a low workload . Results of chest radiography are often normal in patients with stable angina , and its usefulness as a routine test is not well established . Ultra-fast electron-beam computed tomography is now frequently used to detect coronary artery calcification , which is a sensitive indicator of coronary stenosis ( 14 ) . However , the specificity of electron-beam computed tomography is in the range of 41 % to 76 % , which means that many results are false positive . Moreover , the BACKGROUND The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events . We devised a prognostic score , based on the results of treadmill exercise testing , that accurately predicts outcome among in patients referred for cardiac catheterization . This study was design ed to determine whether this score could also accurately predict prognosis in unselected out patients . METHODS We prospect ively studied 613 consecutive out patients with suspected coronary disease who were referred for exercise testing between 1983 and 1985 . Follow-up was 98 percent complete at four years . The treadmill score was calculated as follows : duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise , in millimeters)--(4 x the treadmill angina index ) . The numerical treadmill angina index was 0 for no angina , 1 for nonlimiting angina , and 2 for exercise-limiting angina . Treadmill scores ranged from -25 ( indicating the highest risk ) to + 15 ( indicating the lowest risk ) . RESULTS Predicted outcomes for the out patients , based on their treadmill scores , agreed closely with the observed outcomes . The score accurately separated patients who subsequently died from those who lived for four years ( area under the receiver-operating-characteristic curve = 0.849 ) . The treadmill score was a better discriminator than the clinical data and was even more useful for out patients than it had been for in patients . Approximately two thirds of the out patients had treadmill scores indicating low risk ( greater than or equal to + 5 ) , reflecting longer exercise times and little or no ST-segment deviation , and their four-year survival rate was 99 percent ( average annual mortality rate , 0.25 percent ) . Four percent of the out patients had scores indicating high risk ( less than -10 ) , reflecting shorter exercise times and more severe ST-segment deviation ; their four-year survival rate was 79 percent ( average annual mortality rate , 5 percent ) . CONCLUSIONS The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer out patients with suspected coronary disease for cardiac catheterization . In this study , it was a better predictor of outcome than the clinical assessment To determine the prognostic value of the treadmill exercise test , we evaluated 2842 consecutive patients with chest pain who had both treadmill testing cardiac catheterization . The population was r and omly divided into two equal-sized groups and the Cox regression model was used in one to form a treadmill score that was then vali date d in the other group . The final treadmill score was calculated as follows : exercise time--(5 X ST deviation)--(4 X treadmill angina index ) . Using this treadmill score , 13 % of the patients were found to be at high risk ; 53 % , at moderate risk ; and 34 % , at low risk . The treadmill score added independent prognostic information to that provided by clinical data , coronary anatomy , and left ventricular ejection fraction : patients with three-vessel disease with a score of -11 or less had a 5-year survival rate of 67 % , and those with a score of + 7 or more had a 5-year survival rate of 93 % . The treadmill score was useful for stratifying prognosis in patients with suspected coronary artery disease who were referred to us for catheterization , and may provide a useful adjunct to clinical decision making in the larger population of patients being evaluated for chest pain Background Reduced septal or anteroseptal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block ( LBBB ) even in the absence of left anterior descending ( LAD ) coronary artery disease . The purpose of this study was to evaluate prospect ively the accuracy of dipyridamole201TI single-photon emission computed tomography ( SPECT ) in detecting LAD coronary artery disease in patients with LBBB and septal or anteroseptal perfusion defects on exercise201TI SPECT . Methods and Results Twelve consecutive patients ( 10 men and two women ) with complete LBBB and septal or anteroseptal perfusion defects on exercise201TI SPECT underwent dipyridamole201TI SPECT . The delay between dipyridamole and exercise was 2 to 30 days . Coronary angiography was performed during this period in all patients . Six ( 50 % ) of 12 patients with exercise perfusion defects showed normal perfusion after dipyridamole ; all had normal coronary angiograms . The remaining six patients also had positive results of dipyridamole studies , two with moderate and four with severe septal or anteroseptal perfusion defects . Coronary angiography showed significant ( > 50 % ) LAD coronary artery stenosis in three patients ; three patients with severe septal or anteroseptal perfusion defects after dipyridamole had normal coronary angiograms . Neither the evaluation of apical involvement nor the presence of dilated ventricles , decreased left ventricular ejection fraction , or wall motion abnormalities could help to identify ( or explain ) false-positive results . Conclusion This study confirms that dipyridamole is more accurate than exercise in excluding LAD coronary artery disease . However , there are still false-positive results and the severity of the septal or anteroseptal perfusion defect does not add additional information to identify LAD coronary artery disease . Coronary angiography is thus necessary for positive dipyridamole study results to identify coronary artery disease as a major prognostic factor in patients with LBBB OBJECTIVES This study sought to establish the prognostic implication s of ischemic and viable myocardium identified by dobutamine echocardiography in patients with left ventricular dysfunction . BACKGROUND Recent studies have suggested that in patients with viable myocardium identified by positron emission tomography , medical treatment is associated with recurrent cardiac events . Dobutamine echocardiography has been used to identify viable myocardium in patients with left ventricular dysfunction , but the prognostic significance of this test is undefined . METHODS One hundred thirty-six consecutive patients ( mean [ + /- SD ] age 67 + /- 7.9 years ; 104 men ) with moderate or severe left ventricular dysfunction ( left ventricular ejection fraction 30 + /- 5 % ) undergoing dobutamine echocardiography were included in the study . Dobutamine was administered using a st and ard incremental protocol ( 5 to 40 micrograms/kg body weight per min intravenously in 3-min stages ) with additional atropine ( 1 mg intravenously ) as required . St and ard body weight echocardiographic views were digitized on-line and compared using a side-by-side display . Viable myocardium was identified by enhancement of regional function at low dose ( < 10 micrograms ) ; scar was diagnosed by akinesia at rest or dyskinesia without change and ischemia as new or worsening dysfunction . One hundred thirty patients ( 95 % ) were followed up for 16 + /- 8 months after the original study for major cardiac events ( cardiac death , myocardial infa rct ion or severe unstable angina requiring late myocardial revascularization ) . RESULTS No significant complications occurred during dobutamine echocardiography . Viable myocardium was detected in 26 patients ( 19 % ) , ischemia in 23 ( 17 % ) , both viability and ischemia in 13 ( 10 % ) and scar in 74 ( 54 % ) . Of 108 patients treated medically , 46 had viable or ischemic myocardium , and 62 had scar only . There were no significant differences in age or other clinical characteristics , stress response , left ventricular dimensions and ejection fraction between the two groups . Cardiac events occurred in 26 medically treated patients ( 24 % ) : 18 died of cardiac-related causes ; 4 had a nonfatal myocardial infa rct ion ; and 4 had late revascularization because of unstable angina . The event rate was greater in patients with viable or ischemic myocardium than those with scar ( 43 % vs. 8 % , p = 0.01 by log-rank test ) . In a Cox regression model , the presence of viable or ischemic myocardium was found to predict subsequent events ( relative risk 3.51 , p = 0.02 ) independently of ejection fraction and age . CONCLUSIONS Viable or ischemic myocardium detected at dobutamine echocardiography in patients with left ventricular dysfunction is associated with an adverse prognosis , independent of age and ejection fraction |
12,677 | 25,609,141 | This meta- analysis supports that low thyrotropin level is significantly associated with an increased risk of Alzheimer ’s disease in the elderly | Although several epidemiological studies assessed the relationship between thyrotropin and risk of Alzheimer ’s disease in the elderly , the results were inconsistent . | We investigated the prospect i ve relationship between thyroid status and the risk of dementia and Alzheimer 's disease among a r and om sample of 1843 participants , aged 55 years and over , from the population ‐based prospect i ve Rotterdam Study OBJECTIVE Sub clinical thyroid disorders are common in older individuals . Health risks associated with sub clinical hypothyroidism in older adults are unclear . The aim of the study is to evaluate whether thyroid status in elderly subjects correlates with physical and cognitive function at baseline and with 3-year mortality . DESIGN A population -based , prospect i ve cohort of the OCTABAIX study ( 307 inhabitants aged 85 years at baseline ) . METHODS Chronic drug prescription , functional status ( Barthel and Lawton indices ) and cognitive status according to the Spanish version of the Mini-Mental State Examination were recorded . Quality of life was assessed using the visual analogue scale of the quality of life test . Concentrations of TSH and thyroxine were measured . Participants were classified in accordance with clinical categories of thyroid function . RESULTS Twenty ( 6.5 % ) individuals had sub clinical hypothyroidism and five ( 1.6 % ) had sub clinical hyperthyroidism . Compared with euthyroid subjects ( n=280 ; 91.8 % ) , sub clinical hypo- and hyperthyroidism subjects were not significantly associated with poor physical or cognitive function at baseline . Fifty-one ( 15.1 % ) subjects died during the 36 months of follow-up . TSH values and sub clinical hypo- and hyperthyroidism were not associated with an increased overall mortality risk ( hazard ratio ( HR ) 1.086 , 95 % CI 0.987 - 1.196 and HR 0.905 , 95 % CI 0.902 - 1.053 respectively ) . CONCLUSIONS This study does not support the association of TSH or thyroid disorders with physical or cognitive function at baseline or with 3-year mortality in the oldest old subjects OBJECTIVE To what extent endogenous sub clinical thyroid disorders contribute to impaired physical and cognitive function , depression , and mortality in older individuals remains a matter of debate . DESIGN A population -based , prospect i ve cohort of the Longitudinal Aging Study Amsterdam . METHODS TSH and , if necessary , thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older . Participants were classified according to clinical categories of thyroid function . Participants with overt thyroid disease or use of thyroid medication were excluded , leaving 1219 participants for analyses . Outcome measures were physical and cognitive function , depressive symptoms ( cross-sectional ) , and mortality ( longitudinal ) RESULTS Sixty-four ( 5.3 % ) individuals had sub clinical hypothyroidism and 34 ( 2.8 % ) individuals had sub clinical hyperthyroidism . Compared with euthyroidism ( n=1121 ) , sub clinical hypo- , and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function , or depression . On the contrary , participants with sub clinical hypothyroidism did less often report more than one activity limitation ( odds ratio 0.44 , 95 % confidence interval ( CI ) 0.22 - 0.86 ) . After a median follow-up of 10.7 years , 601 participants were deceased . Sub clinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk ( hazard ratio 0.89 , 95 % CI 0.59 - 1.35 and 0.69 , 95 % CI 0.40 - 1.20 respectively ) . CONCLUSIONS This study does not support disadvantageous effects of sub clinical thyroid disorders on physical or cognitive function , depression , or mortality in an older population Background : It is unclear whether in late life serum thyroid-stimulating hormone ( TSH ) predicts risk of developing cognitive impairment . Objective : This study investigated the prospect i ve relationship of serum TSH with the risk of developing mild cognitive impairment ( MCI ) , Alzheimer ’s disease ( AD ) and vascular dementia ( VaD ) in an elderly cohort with a 4-year follow-up . Methods : Data are for 660 subjects aged 65 years and older from an Italian population -based cohort who were cognitively normal at an extensive assessment in 1999/2000 and underwent follow-up assessment in 2003/2004 . Serum TSH was measured at baseline . Multinomial logistic models adjusted for sociodemographic and cardiovascular risk factors were used to investigate the association of serum TSH ( both as a tertile and continuous log-transformed variable ) with risk of incident MCI , AD and VaD diagnosed according to international criteria . Results : Over 3.8 ± 0.7 years of follow-up , there were 149 incident MCI cases ( 77 with impairment of memory and 72 with impairment of nonmemory domains ) and 86 incident dementia cases ( 53 with AD , 28 with VaD ) . No association between baseline TSH and risk of developing any MCI subtype or AD was found . The highest TSH tertile had a threefold higher increased risk of VaD ( OR : 3.25 , 95 % CI : 1.01–10.77 , p = 0.048 ) compared to the lowest tertile . Risk of VaD increased about 60 % for each 1 SD increase in log-transformed TSH ( OR : 1.61 , 95 % CI : 1.06–2.44 , p = 0.025 ) . Conclusions : In this elderly cohort , baseline TSH was not related to the risk of developing MCI or AD , but high TSH was associated with an increased risk of VaD. These results suggest further need for research using larger sample s to examine the role of TSH as a predictor of VaD and the role of thyroid autoimmunity in vascular cognitive impairment Neuroanatomical connections point to possible interactions between areas influencing energy homeostasis and those influencing cognition . We assessed whether serum leptin , thyroxine , and thyroid stimulating hormone ( TSH ) levels are associated with and interact to influence cognitive performance among US adults . Data from the National Health and Nutrition Examination Survey III ( 1988 - 1994 ) were used . Measures included a battery of neuropsychological tests and serum leptin , thyroxine , and TSH levels ( 20 - 59-year-old : n = 1114 - 2665 ; 60 - 90-year-old : n = 1365 - 5519 ) . Among those 20 - 59-year-old , the middle tertile of leptin ( vs. first tertile ) was inversely related to the number of errors on the symbol digits substitution test . Increased thyroxine level was associated with a poorer performance on the serial digits test in the 20 - 59-year-old , but a better performance on the math test in 60 - 90-year-old group . TSH was associated with poor performance on various tests in the 20 - 59-year-old , but better performance in the 60 - 90-year-old group . Significant antagonistic interactions were found in both age groups between thyroxine , TSH , and leptin for a number of tests , including between leptin and thyroxine in the 60 - 90-year-old group in their association with word recall-correct score . We found significant associations of our main exposures with cognitive function among US adults , going in opposite directions between age groups in the cases of thyroid hormonal levels , as well as some interactive effects between exposures . It is important to conduct prospect i ve cohort studies to provide further insight into potential interventions that would assess interactive effects of various hormonal replacement regimens Thyroid dysfunction is associated with cognitive impairment and dementia , including Alzheimer 's disease ( AD ) . It remains unclear whether thyroid dysfunction results from , or contributes to , Alzheimer pathology . We determined whether thyroid function is associated with dementia , specifically AD , and Alzheimer-type neuropathology in a prospect i ve population -based cohort of Japanese-American men . Thyrotropin , total and free thyroxine were available in 665 men aged 71 - 93 years and dementia-free at baseline ( 1991 ) , including 143 men who participated in an autopsy sub- study . During a mean follow-up of 4.7 ( S.D. : 1.8 ) years , 106 men developed dementia of whom 74 had AD . Higher total and free thyroxine levels were associated with an increased risk of dementia and AD ( age and sex adjusted hazard ratio ( 95 % confidence interval ) per S.D. increase in free thyroxine : 1.21 ( 1.04 ; 1.40 ) and 1.31 ( 1.14 ; 1.51 ) , respectively ) . In the autopsied sub- sample , higher total thyroxine was associated with higher number of neocortical neuritic plaques and neurofibrillary tangles . No associations were found for thyrotropin . Our findings suggest that higher thyroxine levels are present with Alzheimer clinical disease and neuropathology Background Sub clinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age , but results are inconsistent . We investigated the association between sub clinical thyroid dysfunction and cognitive decline in the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Methods Prospect i ve longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition ( N = 5,154 ) . Participants taking antithyroid medications , thyroid hormone supplementation and /or amiodarone were excluded . Thyroid function was measured at baseline : sub clinical hyper- and hypothyroidism were defined as thyroid stimulating hormones ( TSH ) < 0.45 mU/L or > 4.50 mU/L respectively , with normal levels of free thyroxine ( FT4 ) . Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years , using five neuropsychological performance tests . Results Sub clinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants , respectively . We found no consistent association of sub clinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests . Similarly , there was no association with rate of cognitive decline during follow-up . Conclusion We found no consistent evidence that sub clinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age . Although our data are not in support of treatment of sub clinical thyroid dysfunction to prevent cognitive dysfunction in later life , only large r and omized controlled trials can provide definitive evidence IMPORTANCE An association of clinical and sub clinical hypothyroidism with mild cognitive impairment ( MCI ) has not been established . OBJECTIVE To evaluate the association of clinical and sub clinical hypothyroidism with MCI in a large population -based cohort . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional , population -based study was conducted in Olmsted County , Minnesota . R and omly selected participants were aged 70 to 89 years on October 1 , 2004 , and were without documented prevalent dementia [ CORRECTED ] . A total of 2050 participants were evaluated and underwent in-person interview , neurologic evaluation , and neuropsychological testing to assess performance in memory , attention/executive function , and visuospatial and language domains . Participants were categorized by consensus as being cognitively normal , having MCI , or having dementia according to published criteria . Clinical and sub clinical hypothyroidism were ascertained from a medical records linkage system . MAIN OUTCOMES AND MEASURES Association of clinical and sub clinical hypothyroidism with MCI . RESULTS Among 1904 eligible participants , the frequency of MCI was 16 % in 1450 individuals with normal thyroid function , 17 % in 313 persons with clinical hypothyroidism , and 18 % in 141 individuals with sub clinical hypothyroidism . After adjusting for covariates ( age , educational level , sex , apolipoprotein E ε4 , depression , diabetes mellitus , hypertension , stroke , body mass index , and coronary artery disease ) we found no significant association between clinical or sub clinical hypothyroidism and MCI ( odds ratio [ OR ] , 0.99 [ 95 % CI , 0.66 - 1.48 ] and 0.88 [ 0.38 - 2.03 ] , respectively ) . No effect of sex interaction was seen on these effects . In stratified analysis , the odds of MCI with clinical and sub clinical hypothyroidism among men was 1.02 ( 95 % CI , 0.57 - 1.82 ) and 1.29 ( 0.68 - 2.44 ) and , among women , was 1.04 ( 0.66 - 1.66 ) and 0.86 ( 0.37 - 2.02 ) , respectively . CONCLUSIONS AND RELEVANCE In this population -based cohort of elderly people , neither clinical nor sub clinical hypothyroidism was associated with MCI . Our findings need to be vali date d in a separate setting using the published criteria for MCI and confirmed in a longitudinal study CONTEXT The association between sub clinical hyperthyroidism and the risk of dementia has been vali date d in several studies . However , the effect of thyroid function within reference range on the risk of cognitive dysfunction including mild cognitive impairment ( MCI ) and dementia is still unclear . OBJECTIVE Our aim was to investigate the association between thyroid function and the risk of MCI and dementia in euthyroid elderly subjects . DESIGN , SETTING , AND PARTICIPANTS We conducted a population -based prospect i ve study as a part of the Korean Longitudinal Study on Health and Aging . A total of 313 participants who were euthyroid and nondemented at baseline and completed cognitive function tests at a 5-year follow-up evaluation ( mean age 72.5 ± 6.9 y ) were analyzed in the present study . MAIN OUTCOME MEASURE Baseline thyroid function was compared according to the development of MCI or dementia during the study period . Binary logistic regression analysis was performed to investigate the independent association between thyroid function and cognitive impairment . RESULTS At baseline evaluation , 237 subjects were cognitively normal , and 76 subjects had MCI . Diagnoses of cognitive function in 259 subjects remained unchanged or improved during the study period ( nonprogression group ) , whereas 54 subjects showed progression of cognitive impairment to MCI or dementia ( progression group ) . In the progression group , baseline serum TSH levels were lower than those in nonprogression group . Baseline serum free T₄ levels were not significantly different between these two groups . The association between lower baseline serum TSH levels and the development of MCI or dementia was maintained after adjustment for conventional baseline risk factors . CONCLUSIONS Lower serum TSH level within the reference range was independently associated with the risk of cognitive impairment including MCI and dementia in elderly subjects Background / Aim : The combination of elevated total homocysteine ( tHcy ) levels and low levels of thyroid-stimulating hormone ( TSH ) are linked to Alzheimer ’s disease ( AD ) in some studies , although the evidence is mixed . Our objective was to prospect ively investigate the association between tHcy and TSH and the subsequent development of AD . Methods : A sub sample of 200 nondemented subjects was taken from the Kungsholmen Project , a population -based study among people ≥75 years . Information about tHcy and TSH levels were taken from the baseline investigation of the Kungsholmen Project study . Results : Increased tHcy levels were related to an elevated risk of AD ( n = 61 ) after a mean follow-up time of 6.7 years . People with high tHcy ( the 3rd tertile ) had more than twice as high a risk of developing AD than those with low tHcy , even after adjusting for age , sex , education , ApoE status , MMSE score and laboratory parameters . tHcy was negatively correlated with TSH ( p = 0.02 ) . There was neither an influence of TSH nor an interaction between tHcy and TSH in the development of AD . Conclusions : These results suggest that homocysteine , but not TSH , is involved in the development of AD . The connection between elevated tHcy and low TSH levels needs to be studied further CONTEXT Despite the equivocal outcomes of r and omized controlled trials , general clinical opinion favors screening and treatment of elderly individuals with sub clinical thyroid disorders . OBJECTIVES To determine whether sub clinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , observational , population -based follow-up study within the Leiden 85-Plus Study of 87 % of a 2-year birth cohort ( 1912 - 1914 ) in the municipality of Leiden , the Netherl and s. A total of 599 participants were followed up from age 85 years through age 89 years ( mean [ SD ] follow-up , 3.7 [ 1.4 ] years ) . MAIN OUTCOME MEASURES Complete thyroid status at baseline ; disability in daily life , depressive symptoms , cognitive function , and mortality from age 85 years through 89 years . RESULTS Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life , depressive symptoms , and cognitive impairment at baseline or during follow-up . Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status . The hazard ratio ( HR ) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 ( 95 % confidence interval [ CI ] , 0.63 - 0.94 ; P = .009 ) . The HR for mortality per SD increase of 0.21 ng/dL ( 2.67 pmol/L ) of free thyroxine increased 1.16-fold ( 95 % CI , 1.04 - 1.30 ; P = .009 ) . CONCLUSIONS In the general population of the oldest old , elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span . However , evidence for not treating elderly individuals can only come from a well- design ed , r and omized placebo-controlled clinical trial CONTEXT Both hypothyroidism and sub clinical hyperthyroidism hinder cognitive function . OBJECTIVE We aim ed to determine whether more subtle alterations of thyroid hormone levels predict increased incidence of dementia in aging men . PARTICIPANTS AND DESIGN Community-dwelling men aged 70 - 89 yr participated in this prospect i ve longitudinal study . MAIN OUTCOME MEASURES The St and ardized Mini-Mental State Examination was performed at baseline ( 2001 - 2004 ) , and circulating TSH and free T(4 ) ( FT(4 ) ) were assayed . Men with known thyroid disease or dementia , or St and ardized Mini-Mental State Examination scores below 24 were excluded from follow-up . New-onset dementia , defined by International Classification of Disease ( ICD ) codes , was ascertained using data linkage ( 2001 - 2009 ) . RESULTS During follow-up , 145 of 3401 men ( 4.3 % ) were diagnosed for the first time with dementia . Men who developed dementia had higher baseline FT(4 ) ( 16.5 ± 2.2 vs. 15.9 ± 2.2 pmol/liter , P = 0.004 ) but similar TSH ( 2.2 ± 1.4 vs. 2.3 ± 1.6 mU/liter , P = 0.23 ) compared with men who did not receive this diagnosis . After adjusting for covariates , higher FT(4 ) predicted new-onset dementia ( 11 % increased risk per 1 pmol/liter increase in FT(4 ) , P = 0.005 ; quartiles Q2 - 4 vs. Q1 : adjusted hazard ratio = 1.76 , 95 % confidence interval = 1.03 - 3.00 , P = 0.04 ) . There was no association between TSH quartiles and incident dementia . When the analysis was restricted to euthyroid men ( excluding those with sub clinical hyper- or hypothyroidism ) , higher FT(4 ) remained associated with incident dementia ( 11 % increase per unit increment , P = 0.03 ; Q2 - 4 vs. Q1 : adjusted hazard ratio = 2.02 , 95 % confidence interval = 1.10 - 3.71 , P = 0.024 ) . CONCLUSIONS Higher FT(4 ) levels predict new-onset dementia in older men , independently of conventional risk factors for cognitive decline . Additional studies are needed to explore potential underlying mechanisms and to clarify the utility of thyroid function testing in older men at risk of dementia |
12,678 | 17,761,616 | We addressed the questions in one of three ways , based on available evidence : ( 1 ) commissioned systematic review , ( 2 ) modified systematic review , or ( 3 ) summary of existing Cochrane review s. CONCLUSIONS It is hoped that the guidelines provided in this article will facilitate the appropriate application of these treatments to improve and extend the lives of all individuals with cystic fibrosis | RATIONALE Cystic fibrosis is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance .
As a result , individuals with the disease have difficulty clearing pathogens from the lung and experience chronic pulmonary infections and inflammation .
Death is usually a result of respiratory failure .
Newly introduced therapies and aggressive management of the lung disease have result ed in great improvements in length and quality of life , with the result that the median expected survival age has reached 36 years .
However , as the number of treatments exp and s , the medical regimen becomes increasingly burdensome in time , money , and health re sources .
Hence , it is important that treatments should be recommended on the basis of available evidence of efficacy and safety .
OBJECTIVES The Cystic Fibrosis Foundation therefore established a committee to examine the clinical evidence for each therapy and to provide guidance for the prescription of these therapies . | ABSTRACT . A double blind controlled trial of Becotide ® ( beclomethasone diproprionate ) inhalations was carried out for treating cystic fibrosis patients with chronic P. aeruginosa lung infection to determine its efficacy and safety . The aim of the treatment was to diminish the inflammatory response in the lungs of these patients , a response which is initiated by an allergic type III reaction . Pulmonary inflammation was evaluated by measurements of proteolytic activity , albumin concentration and immune complex activity in the sputum solphase before , during , and after the 16 weeks the trial lasted . 26 cystic fibrosis patients participated ( 13 received Becotide ® and 13 placebo ) and the results showed that local steroids have no effect on the inflammatory response in the lungs of cystic fibrosis patients with chronic P. aeruginosa lung infection . No adverse effects were demonstrated . There was , however , a significant increase in the inflammatory parameters for all 26 cystic fibrosis patients when the trial period was over , compared to the insidious pulmonary destruction which takes place in the lungs of these patients , and it corresponded to a significant decrease ( p<0.05 ) in forced vital capacity which took place at the same time . Therefore , chronic P. aeruginosa lung infection in these patients should be treated as efficiently as possible Long-term treatment with ibuprofen twice daily , at doses that achieve peak plasma concentration ( Cmax ) > 50 μg/ml , slows progression of lung disease in patients with cystic fibrosis ( CF ) . Previous data suggest that Cmax > 50 μg/ml is associated with a reduction in neutrophil ( PMN ) migration into the lung and that lower concentrations are associated with an increase in PMN migration . To estimate the threshold concentration at which ibuprofen is associated with a decrease in PMN migration in vivo , we measured the PMN content of oral mucosal washes in 35 healthy ( age 19 - 40 years ) and 16 CF ( age 18 - 32 years ) subjects who took ibuprofen twice daily for 10 days in doses that achieved Cmax 8 to 90 μg/ml . Cmax > 50 μg/ml was associated with a 31 ± 7 % ( mean ± S.E.M. ) reduction in PMNs in CF ( n = 11 , p < 0.001 ) and 25 ± 6 % reduction in PMNs in healthy subjects ( n = 16 , p < 0.001 ) . Increasing concentrations above 50 μg/ml was not associated with a greater decrease in PMNs . The reduction in PMN migration was consistently present 12 h after a dose , but not after 24 h. Cmax < 50 μg/ml was associated with an increase in PMNs of approximately 40 % . These results suggest that Cmax > 50 μg/ml and twice daily dosing of ibuprofen are required to decrease PMN migration , and reinforce the current recommendation that pharmacokinetics should be performed in CF patients prescribed ibuprofen Abstract A double-blind r and omised cross-over trial of aerosol carbenicillin and gentamicin treatment in young adult cystic-fibrosis patients chronically infected with Pseudomonas aeruginosa has shown that aerosol antibiotic treatment produces both subjective and objective improvement . This treatment therefore appears to be useful in selected patients BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . A r and omized cross-over study was undertaken to compare nebulized ( 1 ) ceftazidime with ( 2 ) a combination of gentamicin and carbenicillin , and ( 3 ) saline , each given for 4 months , in patients with cystic fibrosis infected with Pseudomonas aeruginosa . Mean peak expiratory flow on ceftazidime , 299 litres/min , and on gentamicin and carbenicillin , 297 litres/min , were greater than on saline , 278 litres/min ( P less than 0.02 and P less than 0.05 respectively ) . Similarly mean forced expiratory volume in 1 second on ceftazidime , 1.70 litres , and on gentamicin and carbenicillin , 1.70 litres , were greater than on saline , 1.48 litres ( P less than 0.02 and P less than 0.01 respectively ) . Mean forced vital capacity on gentamicin and carbenicillin , 2.93 litres , was also greater than on saline ( P less than 0.05 ) . We were unable to demonstrate any difference in efficacy between the antibiotic regimens . The patients were admitted to hospital less frequently during the study year compared with the previous year ( P less than 0.05 ) . Sixty-nine per cent of patients had a clinical ly significant ( 20 % ) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study , but a minority of patients appear not to respond to this form of treatment BACKGROUND Aztreonam lysine for inhalation ( AZLI ) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection . METHODS This double-blind , r and omized , placebo-controlled Phase 2 study evaluated the safety , tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow Electronic Nebulizer ( Pari Innovative Manufacturers , Inc. , Midlothian , VA ) . Patients were 13 years and older with FEV1>or=40 % predicted , chronic P. aeruginosa infection , and had used no anti-pseudomonal antibiotics for 56 days . RESULTS Of 131 patients screened , 105 received AZLI or placebo . Mean age was 26 years and mean FEV1 percent predicted was 77 % at baseline . There was a statistically significant reduction , compared to placebo , in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 ( P<0.001 ) . The planned primary analysis , percent change in FEV1 at Day 14 , demonstrated no statistically significant difference . Post hoc analysis demonstrated significant increase in FEV1 at Day 7 for the subset of patients with baseline FEV1<75 % predicted in the 225 mg AZLI group . Bronchodilator use was associated with greater improvement in FEV1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group . Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group . CONCLUSION These data support the further development of AZLI and provide information for the design of subsequent studies BACKGROUND Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis . OBJECTIVE To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis . DESIGN Double blind placebo controlled r and omised sequence crossover trial . Fluticasone propionate ( 400 μg/day ) was given as a dry powder inhaler for six weeks with a four week washout period before crossover . OUTCOME MEASURES Sputum inflammatory markers ( interleukin-8 , tumour necrosis factor-α ( TNF-α ) and neutrophil elastase — both free and bound to α1-antiprotease ) , sputum interleukin-10 , lung function , and symptomatology . SUBJECTS Twenty three children from a regional cystic fibrosis centre were enrolled into the study , with mean age 10.3 years ( range 7 to 17 years ) and mean baseline forced expiratory volume in one second ( FEV1 ) of 64 % ( range 21 % to 102 % ) predicted for sex and height . One patient was excluded for non-compliance to the study protocol . RESULTS No significant benefit was shown for the use of fluticasone propionate in any of the outcomes . For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml ( 95 % confidence interval ( CI ) 8 to 2866 pg/ml ) in favour of placebo ; while for maximal expiratory flow at 25 % ( MEF25 % ) remaining forced vital capacity predicted for sex and height there was a 15 percentage points ( pp ) ( 95 % CI 4 to 26 pp ) mean treatment difference in favour of placebo . Sputum interleukin-10 was undetected in any sample s and unaffected by fluticasone propionate . Neither atopic status , baseline FEV1 , nor concomitant DNase therapy had any effect on response to treatment . CONCLUSIONS Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways . It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy Background : Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases . The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis . Methods : A multicentre , r and omised , double blind , placebo controlled trial was conducted from October 2001 to June 2003 . The criteria for enrolment were age older than 6 years and forced expiratory volume in 1 second ( FEV1 ) of 40 % or more . The active group received either 250 mg or 500 mg ( body weight < or ⩾40 kg ) of oral azithromycin three times a week for 12 months . The primary end point was change in FEV1 . Results : Eighty two patients of mean ( SD ) age 11.0 ( 3.3 ) years and mean ( SD ) FEV1 85 (22)% predicted were r and omised : 40 in the azithromycin group and 42 in the placebo group . Nineteen patients were infected with Pseudomonas aeruginosa . The relative change in FEV1 at month 12 did not differ significantly between the two groups . The number of pulmonary exacerbations ( count ratio 0.50 ( 95 % CI 0.32 to 0.79 ) , p<0.005 ) , the time elapsed before the first pulmonary exacerbation ( hazard ratio 0.37 ( 95 % CI 0.22 to 0.63 ) , p<0.0001 ) , and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status ( count ratio 0.55 ( 95 % CI 0.36 to 0.85 ) , p<0.01 ) . No severe adverse events were reported . Conclusion : Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression , even before infection with Pseudomonas aeruginosa BACKGROUND Persistent endobronchial inflammation is in part responsible for the attrition of lung function seen in cystic fibrosis . Leukotrienes act as pro-inflammatory mediators . The aim of this study was to assess the efficacy of the leukotriene receptor antagonist zafirlukast as a potential anti-inflammatory agent in the treatment of adult patients with cystic fibrosis . METHODS Clinical ly stable patients were enrolled in the study if they had no history or clinical evidence of asthma , bronchial hyper-reactivity , or aspergillosis . They were r and omised to receive zafirlukast 20 mg twice daily with all routine treatment for four months or routine treatment alone in an open cross-over design . Primary endpoints were changes in respiratory function tests and a modified NIH clinical score . RESULTS Thirty patients were enrolled and 25 completed . There was a significant improvement in the modified NIH clinical score but no significant increase in respiratory function with zafirlukast . CONCLUSIONS Patients receiving a leukotriene receptor antagonist in addition to routine treatments showed significant improvement in a clinical score which is a composite of clinical wellbeing , chest radiograph appearance , and physical examination . Respiratory function showed a non-significant trend towards improvement with treatment . Zafirlukast may benefit patients with CF . An adequately powered study is justified on the basis of these results STUDY OBJECTIVE The 12-week efficacy and safety of aerosolized recombinant human DNase ( dornase alfa ) were evaluated in previously untreated patients with cystic fibrosis ( CF ) with advanced lung disease . DESIGN In this multicenter , double-blind , placebo-controlled study , CF patients with advanced lung disease were r and omized to receive either dornase alfa or placebo once a day for 12 weeks . PATIENTS A total of 320 patients in clinical ly stable condition with documented CF and an FVC less than 40 % of predicted were recruited from 65 CF Foundation care centers in the United States . The dornase alfa and placebo groups were comparable with respect to age ( range , 7 to 57 years ) , height , and weight . Male subjects outnumbered female subjects ( 55 % vs 45 % ) and few subjects were younger than 17 years of age ( 15 % ) . The percentages of predicted FEV1 and FVC were significantly lower in the dornase alfa group at baseline ( p < or = 0.05 ) . INTERVENTIONS Patients were r and omly assigned to receive either 2.5 mg dornase alfa once daily ( n = 158 ) or placebo once daily ( n = 162 ) . All patients continued to receive st and ard medications and treatments administered for CF . MEASUREMENTS AND RESULTS Dornase alfa improved the mean percent change in FEV1 from baseline by 9.4 % compared with 2.1 % for placebo ( p < 0.001 ) . The actively treated group showed a 12.4 % improvement in FVC compared with 7.3 % for placebo ( p < 0.01 ) . There were no differences between the treatment groups in dyspnea score number of days receiving i.v . antibiotics , or length of hospital stay ; the overall incidence of adverse events was comparable between treatment groups . Fifteen patients died : 9 in the dornase alfa group and 6 in the placebo group ; no differentiating clinical characteristics were demonstrated . CONCLUSIONS Pulmonary function as measured by FEV1 and FVC improved significantly in the dornase alfa-treated patients . Dornase alfa was found to be safe and well tolerated over the 12-week study period OBJECTIVE To assess the feasibility of measuring short-term effects of inhaled recombinant human deoxyribonuclease ( rhDNase , Pulmozyme on lung function , pulse oximetry and symptom scores in infants and toddlers with stable cystic fibrosis . DESIGN open-label r and omized placebo controlled cross-over pilot study . PATIENTS AND METHODS We treated nine CF patients ( 0.7 - 1.9 years ) with nebulised rhDNase ( 2.5 mg ) and NaCl 0.9 % ( 10 ml ) via jet nebulizer cross-over once daily during 2-week treatment blocks . Measurements were performed at baseline and after treatment blocks and consisted of lung function tests ( plethysmography and tidal rapid thoraco-abdominal compression technique ) , overnight pulse oximetry , and daily symptom scores . RESULTS DNase treatment and the different assessment s were well tolerated by all children and their parents . Lung function showed increased airway patency after treatment with rhDNase ( P < 0.001 ) , but not after NaCl 0.9 % . Overnight pulse oximetry and daily symptom scores did not change during the study period . CONCLUSIONS This pilot study indicates that objective assessment of the effects of rhDNase is feasible in infants with CF who have little or no respiratory symptoms . Our results warrant a larger r and omized placebo-controlled trial Background : Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis ( CF ) . While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial , their use is limited by side effects . Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis , a condition with features in common with the lung disease of CF . Methods : To determine if azithromycin ( AZM ) improves clinical parameters and reduces inflammation in patients with CF , a 3 month prospect i ve r and omised double blind , placebo controlled study of AZM ( 250 mg/day ) was undertaken in adults with CF . Monthly assessment included lung function , weight , and quality of life ( QOL ) . Blood and sputum collection assessed systemic inflammation and changes in bacterial flora . Respiratory exacerbations were treated according to the policy of the CF Unit . Results : Sixty patients were recruited ( 29 men ) of mean ( SD ) age 27.9 ( 6.5 ) years and initial forced expiratory volume in 1 second ( FEV1 ) 56.6 (22.3)% predicted . FEV1 % and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean ( SE ) decline of –3.62 (1.78)% ( p=0.047 ) and –5.73 (1.66)% ( p=0.001 ) , respectively . Fewer courses of intravenous antibiotics were used in patients on AZM ( 0.37 v 1.13 , p=0.016 ) . Median C reactive protein ( CRP ) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group ( p<0.001 ) . QOL improved over time in patients on AZM and remained unchanged in those on placebo ( p=0.035 ) . Conclusion : AZM in adults with CF significantly improved QOL , reduced CRP levels and the number of respiratory exacerbations , and reduced the rate of decline in lung function . Long term AZM may have a significant impact on morbidity and mortality in patients with CF . Further studies are required to define frequency of dosing and duration of benefit Despite absence of clear proof of efficacy , the use of inhaled corticosteroids ( ICS ) is widespread in cystic fibrosis ( CF ) patients . Therefore , the effect of ICS on lung function and other clinical variables was studied in 27 prepubertal CF children with mild to moderate lung disease . In a prospect i ve double-blind case-controlled study , fluticasone propionate 500 μg or placebo were administered twice daily during 12 months . The mean ( st and ard error of the mean , SEM ) patient age was 8.2 ( 0.6 ) years in the placebo group and 9.0 ( 0.5 ) years in the fluticasone group . The mean ( SEM ) forced expiratory volume in 1 s ( FEV1 ) was 91 % ( 4 % ) in the placebo group and 86 % ( 4 % ) in the fluticasone group . There was no statistically significant difference in the evolution of lung function and the number of respiratory exacerbations between groups . However , longitudinal growth in fluticasone patients was significantly slower than in placebo patients : 3.96 ( 0.29 ) cm versus 5.49 ( 0.38 ) cm [ p<0.005 , analysis of variance ( ANOVA ) ] over the 12-month study duration . This result ed in a significant change in height st and ard deviation score ( SDS ) of –0.38 ( 0.09 ) in the fluticasone group versus –0.01 ( 0.07 ) in the placebo group ( p<0.003 , ANOVA ) . No catch-up growth was noted 1–2 years after discontinuation of inhaled steroids . The use of high-dose ICS in CF patients with mild lung disease may lead to persistent growth impairment Abstract Autoantibodies against bactericidal/permeability- increasing protein ( BPI-ANCA ) were found in patients with cystic fibrosis ( CF ) . It is speculated that they represent a marker of the chronic endobronchial infection and sustained inflammatory response in CF . Our aim was to evaluate whether azithromycin ( AZM ) , through its antiinflammatory effect , could affect the level of BPI – ANCA in CF patients . Eighteen patients with CF aged 5.5–36.3 years ( median 15.1 ) were enrolled in a r and omised , double– blind , placebo – controlled trial of AZM ( 250 mg twice a week to 10 patients ) or placebo ( 8 patients ) for 12 weeks . BPI – ANCA levels were recorded pre– and post – treatment and compared to a group of 18 matched healthy controls . Chi – square analysis , Kruskal – Wallis and Mann – Whitney tests were used to compare between the groups . Pre– and post – treatment values were compared using the Wilcoxon Signed – Ranked test . BPI – ANCA was found in 12 CF patients ( 67 % ) and four ( 22 % ) healthy subjects ( P<0.001 ) . The mean BPI – ANCA level was 3.94±6.15 U/ml ( mean±SD ) in healthy subjects and 38.11±42.34 U/ml in CF patients ( P=0.023 ) . The mean BPI – ANCA level was higher in patients with Pseudomonas aeruginosa compared to those without ( 64±35 U/ml and 25±41 U/ml respectively , P=0.032 ) . No change in BPI – ANCA levels occurred in the AZM – treated patients [ 35 ( 0–127 ) U/ml ( median ( range ) and 30 ( 0–120 ) U/ml , respectively ] or in the placebo group [ 10 ( 0–66 ) U/ml and 13 ( 0–83 ) U/ml , respectively ] . BPI – ANCA levels are significantly higher in patients with CF compared to healthy controls . BPIANCA levels are higher among patients colonised with P. aeruginosa . Twelve weeks of AZM therapy did not lower the BPI – ANCA level in patients with CF Recombinant human deoxyribonuclease ( rhDNase ) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis ( CF ) , but its long-term effect on airway inflammation remains unknown . In this study , we used bronchoalveolar lavage ( BAL ) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease . A total of 105 patients with CF ( > or = 5 years of age ) having normal lung function were r and omized to receive rhDNase ( 2.5 mg/day ) or no rhDNase . Patients with a normal percentage of neutrophils in BAL fluid at baseline were not r and omized and served as the control group . The percentage of neutrophils in the pooled BAL sample was similar in both r and omized groups at baseline . A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects , whereas neutrophils remained unchanged in patients treated with rhDNase . Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase . We conclude that in patients with CF , an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment RATIONALE Lung inflammation and injury is critical in cystic fibrosis . An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence . OBJECTIVES To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations . METHODS Multicenter r and omized double-blind placebo-controlled trial in 18 pediatric and adult UK centers . Eligibility criteria included age>6.0 yr , FEV1>or=40 % predicted , and corticosteroid use>3 mo . During the 2-mo run-in period , all patients received fluticasone ; they then took either fluticasone or placebo for 6 mo . MEASUREMENTS AND MAIN RESULTS Fluticasone group : n=84 , median age 14.6 yr , mean ( SD ) FEV1 76 % ( 18 ) ; placebo group : n=87 , median age 15.8 yr , mean ( SD ) FEV1 76 % ( 18 ) . There was no difference in time to first exacerbation ( primary outcome ) with hazard ratio ( 95 % confidence interval ) of 1.07 ( 0.68 to 1.70 ) for fluticasone versus placebo . There was no effect of age , atopy , corticosteroid dose , FEV1 , or Pseudomonas aeruginosa status . There was no change in lung function or differences in antibiotic or rescue bronchodilator use . Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events ( 9 vs. 15 % ) ; with a relative risk ( 95 % confidence interval ) of 0.59 ( 0.23 - 1.48 ) fluticasone versus placebo . CONCLUSIONS In this study population ( applicable to 40 % of patients with cystic fibrosis in the UK ) , it appears safe to consider stopping inhaled corticosteroids . Potential advantages will be to reduce the drug burden on patients , reduce adverse effects , and make financial savings Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis ( CF ) patients . The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients chronically infected with P. aeruginosa . One-hundred and fifteen patients , aged ≥6 yrs , were r and omised to receive either TNS or colistin , twice daily for 4 weeks . The primary end point was an evaluation of the relative change in lung function from baseline , as measured by forced expiratory volume in one second % predicted . Secondary end points included changes in sputum P. aeruginosa density , tobramycin/colistin minimum inhibitory concentrations and safety assessment s. TNS produced a mean 6.7 % improvement in lung function ( p=0.006 ) , whilst there was no significant improvement in the colistin-treated patients ( mean change 0.37 % ) . Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density , and there was no development of highly resistant strains over the course of the study . The safety profile for both nebulised antibiotics was good . Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa , but colistin did not , in this study of 1-month 's duration . Both treatments reduced the bacterial load Inhaled corticosteroids have been proposed to decrease pulmonary inflammation in cystic fibrosis ( CF ) . In this study the effects of therapy with inhaled fluticasone on clinical and sputum outcomes ( leukocyte count , activity of myeloperoxidase , superoxide anion release ) in adult CF patients were investigated in an open label design . Twenty-six stable patients ( median+/-SD forced expiratory volume in one second ( FEV1 ) 58.1+/-19.9 % pred . ) were r and omly assigned to the study group ( 500 microg b.i.d . , for three weeks ) or the control group ( n=14 ; nonsteroid medication ) . Sputum sample s were obtained during inhalation of hypertonic saline ( 3 % , 20 min ) , which was found not to alter the investigated sputum parameters . No significant changes in clinical parameters , sputum leukocyte count , activity of myeloperoxidase , and baseline superoxide anion release where observed following therapy . Surprisingly , stimulated superoxide anion release increased significantly after therapy ( 34.1+/-17.7 versus 25.2+/-17.4 nmol x hr(-1 ) x 10(6 ) cells , p<0.03 ) and exceeded spontaneous variability of this parameter ( p=0.02 versus control group ) . In conclusion , in adult cystic fibrosis patients short-term fluticasone therapy had no evident effect on clinical and sputum parameters . Further investigations are necessary to evaluate whether the observed up-regulation of oxidative capacity of inflammatory cells is of concern or benefit in these patients CONTEXT Treatment strategies for cystic fibrosis ( CF ) lung disease include antibiotics , mucolytics , and anti-inflammatory therapies . Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF . OBJECTIVE To determine if an association between azithromycin use and pulmonary function exists in patients with CF . DESIGN AND SETTING A multicenter , r and omized , double-blind , placebo-controlled trial conducted from December 15 , 2000 , to May 2 , 2002 , at 23 CF care centers in the United States . PARTICIPANTS Of the 251 screened participants with a diagnosis of CF , 185 ( 74 % ) were r and omized . Eligibility criteria included age 6 years or older , infection with Pseudomonas aeruginosa for 1 or more years , and a forced expiratory volume in 1 second ( FEV1 ) of 30 % or more . Participants were stratified by FEV1 ( > or = 60 % predicted vs < 60 % predicted ) , weight of less than 40 kg vs 40 kg or more , and CF center . INTERVENTION The active group ( n = 87 ) received 250 mg ( weight < 40 kg ) or 500 mg ( weight > or = 40 kg ) of oral azithromycin 3 days a week for 168 days ; placebo group ( n = 98 ) received identically packaged tablets . MAIN OUTCOME MEASURES Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety . Secondary outcomes included pulmonary exacerbations and weight gain . RESULTS The azithromycin group had a mean 0.097-L ( SD , 0.26 ) increase in FEV1 at day 168 compared with 0.003 L ( SD , 0.23 ) in the placebo group ( mean difference , 0.094 L ; 95 % confidence interval [ CI ] , 0.023 - 0.165 ; P = .009 ) . Nausea occurred in 17 % more participants in the azithromycin group ( P = .01 ) , diarrhea in 15 % more ( P = .009 ) , and wheezing in 13 % more ( P = .007 ) . Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group ( hazard ratio , 0.65 ; 95 % CI , 0.44 - 0.95 ; P = .03 ) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo ( 95 % CI , 0.1 - 1.4 kg ; P = .02 ) . CONCLUSION Azithromycin treatment was associated with improvement in clinical ly relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis ( CF ) , antibiotic therapy generally fails to eradicate the bacterial pathogen . The mucoid bacterial phenotype , high sputum production by the host , and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy . We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection . In a prospect i ve placebo-controlled , double-blind , r and omized multicenter study , 22 CF patients received either 80 mg b.i.d . of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization . Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period . Using life table analysis , the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group ( P < 0.05 , log rank test ) . Lung function parameters and markers of inflammation did not change in either group during treatment . The results of this study suggest that early tobramycin inhalation may prevent and /or delay P. aeruginosa pulmonary infection in CF patients OBJECTIVE Our objective was to determine whether long-term treatment of young patients with cystic fibrosis ( CF ) with dornase alfa maintains lung function and reduces respiratory tract exacerbations . STUDY DESIGN This was a 96-week , r and omized , double-blind , placebo-controlled trial involving 49 CF centers . Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85 % predicted . Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months . Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor . RESULTS Patients were r and omized , 239 to dornase alfa and 235 to placebo . At baseline the mean age was 8.4 years , the mean forced expiratory volume in 1 second 95 % predicted , the mean forced expiratory flow , midexpiratory phase 85 % predicted , and the mean forced vital capacity 102 % predicted . At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted ( mean + /- SE ) was 3.2 + /- 1.2 for forced expiratory volume in 1 second ( P = .006 ) , 7.9 + /- 2.3 for forced expiratory flow between 25 % and 75 % of vital capacity ( P = .0008 ) , and 0.7 + /- 1.0 for forced vital capacity ( P = .51 ) . The risk of respiratory tract exacerbation was reduced by 34 % in patients who received dornase alfa ( relative risk 0.66 , P = .048 ) . There was no statistically significant difference between the groups in changes in weight-for-age percentile . Adverse event profiles for the treatment groups were similar . CONCLUSIONS Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period Abstract Background and aim Progressive respiratory failure due to Pseudomonas aeruginosa colonization is the most significant morbidity in patients with cystic fibrosis ( CF ) . This trial was design ed to investigate the efficacy and safety of a highly concentrated ( 300mg/4mL ) tobramycin solution for inhalation ( TSI ) [ Bramitob ® ] in patients with CF and P. aeruginosa infection . Methods Fifty-nine patients were r and omized to receive a 4-week treatment with tobramycin or placebo administered twice daily via the Pari LC Plus ® nebulizer and Pari TurboBoy ™ compressor , followed by a 4-week run-out phase . Pulmonary function ( forced expiratory volume in 1 second [ FEV1 ] , forced vital capacity [ FVC ] , and forced expiratory flow at the midportion of vital capacity [ FEF25–75 % ] ) , P. aeruginosa susceptibility , microbiologic results , and in vitro minimum inhibitory concentration for 90 % of strains ( MIC90 ) were the efficacy outcome measures , while safety was monitored by the recording of adverse events , audiometry ( bone conduction at 250–8000Hz frequency ) , laboratory tests , physical examination and general health condition . The concentration of tobramycin attained in sputum was measured in a cohort of 21 patients . Results FEV1 significantly increased from baseline in the tobramycin group compared with no change in the placebo group : the absolute difference between groups ( intent-to-treat population ) of predicted normal was 13.2 % at week 2 ( p = 0.002 ) and 13.3 % at week 4 ( p = 0.003 ) . Significant differences in favor of the tobramycin group were also observed for FVC and FEF25–75 % . The microbiologic results at the end of the treatment period ( P. aeruginosa-negative culture , persistence , superinfection ) showed a significantly better outcome in the tobramycin group compared with placebo ( p = 0.033 ) . The effects of tobramycin on pulmonary function and microbiology were not maintained at the end of the run-out phase . Mean sputum concentrations of tobramycin after the first dose ( 695.6 ± 817.0 µg/mL ) were similar to those measured after the last dose ( 716.9 ± 799 µg/mL ) and were superior to the detected specific MIC90.The proportion of patients with drug-related adverse events was lower in the tobramycin group and no signs of renal or auditory toxicity were observed . Conclusions The 4-week administration of a highly concentrated TSI significantly improved pulmonary function and microbiologic outcome compared with placebo and was well tolerated . The results of this study should be confirmed in further long-term trials in larger population BACKGROUND AND METHODS We conducted two multicenter , double-blind , placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection . A total of 520 patients ( mean age , 21 years ) were r and omly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks , followed by four weeks with no study drug . Patients received treatment or placebo in three on-off cycles for a total of 24 weeks . The end points included pulmonary function , the density of P. aeruginosa in sputum , and hospitalization . RESULTS The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second ( FEV1 ) of 10 percent at week 20 as compared with week 0 , whereas the patients receiving placebo had a 2 percent decline in FEV1 ( P<0.001 ) . In the tobramycin group , the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units ( CFU ) per gram of expectorated sputum from week 0 to week 20 , as compared with an increase of 0.3 log10 CFU per gram in the placebo group ( P<0.001 ) . The patients in the tobramycin group were 26 percent ( 95 percent confidence interval , 2 to 43 percent ) less likely to be hospitalized than those in the placebo group . Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum . The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group , as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group . CONCLUSIONS In a 24-week study of patients with cystic fibrosis , intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function , decreased the density of P. aeruginosa in sputum , and decreased the risk of hospitalization BACKGROUND : Viscoelastic secretions in cystic fibrosis cause impaired mucus clearance and persistence of bacteria within the lung . The abnormal rheology is partly due to the presence of high molecular weight deoxyribonucleic acid ( DNA ) . Recombinant human DNase I ( rhDNase ) has been shown to depolymerise DNA and thereby reduce the in vitro viscoelasticity of sputum in patients with cystic fibrosis . A phase II double blind placebo controlled study showed that rhDNase improved pulmonary function in patients with cystic fibrosis . The object of the present study was to evaluate the in vivo effects of rhDNase on sputum rheology and to determine whether these were correlated with changes in pulmonary function . METHODS : Patients were r and omised to receive either placebo or rhDNase 2.5 mg twice daily for 10 days . Sputum sample s were collected in sterile containers during screening and during treatment with the study drug . Pulmonary function and rheological analysis were the primary outcomes evaluated . Other parameters assessed were quantitative sputum bacteriology , sputum DNA concentration , and change in molecular mass of DNA polymers . RESULTS : The viscoelasticity of the sputum in untreated patients with cystic fibrosis was high and treatment with rhDNase reduced all the rheological parameters measured : dynamic storage modulus ( a measure of elasticity ) , dynamic loss modulus ( a measure of viscosity ) , and log complex modulus ( a measure of mucus rigidity ) . The calculated cough clearance index was also improved following treatment with rhDNase . These rheological parameters showed a correlation with forced expiratory volume in one second ( FEV1 ) which was improved by a mean ( SE ) of 13.3 (5.6)% on day 10 of treatment with rhDNase compared with a change of 0.2 (3.1)% in the placebo group . There was no change in bacterial colony counts or sputum DNA concentrations following treatment with rhDNase , but a small decrease in high molecular weight DNA was observed . CONCLUSIONS : Patients with cystic fibrosis treated with rhDNase show an improvement in rheological properties and pulmonary function , one of the mechanisms being a reduction in the proportion of high molecular weight DNA Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospect i ve double-blind placebo-controlled study of colistin inhalation . Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline . Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group ( 18 versus 11 ) . Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score , maintenance of pulmonary function and inflammatory parameters . We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy BACKGROUND Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function , with low systemic toxicity . We conducted a r and omized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections . METHODS Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and r and omly assigned to one of two crossover regimens . Group 1 received 600 mg of aerosolized tobramycin for 28 days , followed by half-strength physiologic saline ( placebo ) for two 28-day period . Group 2 received placebo for 28 days , followed by tobramycin for two 28-day periods . Pulmonary function , the density of P. aeruginosa in sputum , ototoxicity , nephrotoxicity , and the emergence of tobramycin-resistant P. aeruginosa were monitored . RESULTS In the first 28-day period , treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second ( 9.7 percentage points higher than the value for placebo ; P < 0.001 ) , forced vital capacity ( 6.2 percentage points higher than the value for placebo ; P = 0.014 ) , and forced expiratory flow at the midportion of the vital capacity ( 13.0 percentage points higher than the value for placebo ; P < 0.001 ) . A decrease in the density of P. aeruginosa in sputum by a factor of 100 ( P < 0.001 ) was found during all periods of tobramycin administration . Neither ototoxicity nor nephrotoxicity was detected . The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration . CONCLUSIONS The short-term aerosol administration of a high dose of tobramycin in patients with clinical ly stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa BACKGROUND In cystic fibrosis ( CF ) , the inflammatory process contributes to progressive lung tissue damage . Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects . OBJECTIVE To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF . METHODS Twenty-six patients aged 6 to 18 years were recruited to this 20-week , r and omized , double-blind , placebo-controlled , crossover trial . Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment . Before and after treatment , findings from spirometry , whole-body plethysmography , and the clinical wheezing and cough scales were evaluated . At the same time , serum and sputum sample s were obtained for the measurement of eosinophil cationic protein , interleukin 10 ( IL-10 ) , IL-8 , and myeloperoxidase levels . RESULTS Twenty-three patients completed the study . Compared with placebo use , montelukast treatment significantly improved forced expiratory volume in I second , peak expiratory flow , and forced expiratory flow between 25 % and 75 % and significantly decreased cough and wheezing scale scores ( P < .001 for all ) . There were no significant changes in vital capacity , thoracic gas volume , airway resistance , and residual volume after treatment . Compared with placebo use , montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8 , decreased sputum levels of myeloperoxidase , and increased serum and sputum levels of IL-10 ( P < .001 for all ) . CONCLUSIONS Montelukast may have measurable anti-inflammatory properties in patients with CF Our objective was to study the effect of tobramycin solution for inhalation ( TSI ; TOBI , Chiron Corp. ) on lung function decline rate in 400 young persons with cystic fibrosis ( CF ) and mild lung disease . Effects on hospitalization , antibiotic use , school days missed , and nutritional status also were determined . This was an open-label , r and omized ( stratified by sex and age group , i.e. , 6 - 10 and 11 - 15 years ) , parallel-group , multicenter study . Routine subject management ( control group ) was compared to routine management plus 28 days of twice-daily TSI inhalation , followed by 28 days off the drug ( TSI group ) for 56 weeks . Primary efficacy endpoints included rate of lung function decline ( as measured by forced expiratory volume in 1 sec ; FEV(1 ) ) , hospitalization , and concomitant antibiotic use . Safety was assessed by analysis of treatment-emergent adverse events . Only 184 of 400 planned subjects were recruited and r and omized ( 93 to the TSI group , and 91 to the control group ) . Enrollment was ended after 2 years because of difficult recruitment . An interim safety review showed a 2.42-fold risk of respiratory hospitalization for control group subjects ( P = 0.020 ) , and the study was terminated . Sixty-three subjects ( 34.2 % ) completed the entire study ( 30 in the TSI group , or 32.3 % ; and 33 in the control group , or 36.3 % ) . Significantly fewer TSI subjects were hospitalized for worsening of respiratory symptoms ( 11.0 % vs. 25.6 % ; P = 0.011 ) , and fewer TSI subjects were hospitalized overall ( 16.5 % vs. 27.8 % ; P = 0.065 ) . Fewer TSI subjects received antibiotics other than the study drug ( 78.0 % vs. 95.6 % ) , and significantly fewer received oral antibiotics ( 76.9 % vs. 91.1 % ; P = 0.009 ) . No other safety or adverse event differences were observed . In conclusion , significant reductions in respiratory hospitalizations , concomitant antibiotic use , and a trend towards improvement in percent predicted forced expiratory flow ( FEF(25 - 75 ) ) provide evidence of a clinical benefit of TSI use in young persons with CF and mild lung disease . An effect on lung function decline rate could not be evaluated as planned , due to inadequate enrollment and early study termination The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis ( CF ) and complicating chronic Pseudomonas aeruginosa ( P.a . ) lung infection was studied in a placebo-controlled , parallel , double-blind single center trial . Active treatment consisted of budesonide dry powder , 800 microg twice daily , delivered from a Turbuhaler . The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics . Fifty-five patients entered the study , with a mean age of 20 yr and a mean FEV1 of 63 % of predicted . Analysis of all patients entered , irrespective of trial adherence ( " intention to treat " ) , showed a decrease in FEV1 in the first period of -0.032 L in patients on budesonide versus -0.187 L in patients on placebo ( p = 0.08 ) . The corresponding figures for the patients adhering to the protocol during the first period were -0.017 L versus -0.198 L ( p < 0.05 , confidence interval of the difference : -0.035 to + 0.327 L ) . For all patients entered , as well as for patients adhering to the trial , there was always a trend in favor of budesonide , as judged by changes in FEV1 and FVC in both 3-mo periods . None of the patients had asthma , but the patients on budesonide had a mean improvement in histamine reactivity of + 1.15 dose steps over the entire 6-mo period , as opposed to + 0.017 dose steps in patients on placebo ( p < 0.05 ) . There was also a significant ( p = 0.01 ) correlation between pre-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide . We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a . infection and that those patients most likely to benefit from this treatment are patients with hyperreactive airways . Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I ( rhDNase ) on ciliary and cough clearance in a group of cystic fibrosis patients , using a radioaerosol and gamma camera technique . Patients were initially r and omized to receive either rhDNase ( 2.5 mg qd ) or placebo . Following the measurement of baseline clearance , patients were given a 7-day course of either rhDNase or placebo . The patient then returned on the seventh day for follow-up clearance measurements . This was followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution . On each of the study days , mucociliary clearance was initially measured for a period of 60 min ( IC ) . This was followed by cough clearance ( CC ) measurements for 30 min , during which patients were requested to cough a total of 120 times . Post-cough clearance ( PCC ) was then measured for a further 60 min . Thirteen patients completed the study . Patients ' age ranged between 18 - 38 years , and they had baseline values of FEV(1 ) of 27 - 103 % of predicted values . Following completion of the course of rhDNase , there was a mean percent increase from baseline of 7.5 % for FEV(1 ) and 5.4 % for FVC% ( P = 0 . 03 ) . There was a small , nonsignificant increase in IC ( 6.2 + /- 3.6 % ) on the rhDNase arm compared with the placebo arm ( -2.3 + /- 2.9 % ) , P = 0.1 . No changes were seen in either CC ( 1.0 + /- 3.2 % [ rhDNase ] vs. 1.9 + /- 2.4 % [ placebo ] , P = 0.9 ) or PCC ( -0.7 + /- 1.5 % [ rhDNase ] vs. 0.9 + /- 1.7 % [ placebo ] , P = 0.3 ) . Patients who achieved a 10 % or greater improvement in FEV(1 ) ( n = 5 ) in response to rhDNase did not show any greater change in clearance than nonresponders . In conclusion , we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase . The mechanism of action of this drug in vivo remains uncertain PURPOSE S To evaluate quantitative air trapping measurements in children with mild cystic fibrosis ( CF ) lung disease during a 1-year , double-blind , placebo-controlled , recombinant human deoxyribonuclease ( rhDNase ) [ dornase alfa ] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT ( H RCT ) scans of the chest . MATERIAL S AND METHODS Twenty-five children with CF r and omized to either daily rhDNase or placebo aerosol were evaluated at baseline , and at 3 months and 12 months by spirometer-triggered H RCT and spirometry . Outcome variables were percentage of predicted FVC , FEV1 , and forced expiratory flow , midexpiratory phase ( FEF(25 - 75 % ) ) ; total and subcomponent visual H RCT scores ; and quantitative air trapping measurements derived from chest H RCT images . RESULTS At baseline , there were no statistical differences between groups in any of the variables used as an outcome . After 3 months of treatment , both groups had improvements in percentage of predicted FEV1 and FEF(25 - 75 % ) , and total H RCT visual scores . In contrast , the rhDNase group had a 13 % decrease in quantitative air trapping from baseline ( severe air trapping [ A3 ] ) , compared to an increase of 48 % in the placebo group ( p = 0.023 ) . After 12 months , both groups had declines in percentage of predicted FVC and FEV1 , but the rhDNase group retained improvements in percentage of predicted FEF(25 - 75 % ) and quantitative air trapping . The mucus plugging and total H RCT visual scores were also improved in the rhDNase group after 12 months of treatment , with and without significant differences between groups ( p = 0.026 and p = 0.676 ) . Quantitative air trapping ( A3 ) remained improved in the rhDNase group ( - 15.4 % ) and worsened in the placebo group ( + 61.3 % ) with nearly significant differences noted between groups ( p = 0.053 ) after 12 months of treatment . CONCLUSIONS Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total H RCT scores , and can discriminate differences in treatment effects in children with minimal CF lung disease BACKGROUND Since the inflammatory response to chronic infection contributes to lung destruction in patients with cystic fibrosis , we hypothesized that anti-inflammatory therapy might slow the progression of lung disease . METHODS In a double-blind trial , 85 patients , 5 to 39 years of age , with mild lung disease ( forced expiratory volume in one second [ FEV1 ] , > or = 60 percent of the predicted value ) were r and omly assigned to receive ibuprofen or placebo orally twice daily for four years . Doses were adjusted individually to achieve peak plasma concentrations of 50 to 100 micrograms per milliliter . Changes in pulmonary function , the percentage of ideal body weight , the chest-radiograph score , and the frequency of hospitalization were assessed . RESULTS Patients r and omly assigned to ibuprofen had a slower annual rate of change in FEV1 than the patients assigned to placebo ( mean [ + /- SE ] slope , -2.17 + /- 0.57 percent vs. -3.60 + /- 0.55 percent in the placebo group ; P = 0.02 ) , and weight ( as a percentage of ideal body weight ) was better maintained in the former group ( P = 0.02 ) . Among the patients who took ibuprofen for four years and had at least a 70 percent rate of compliance , the annual rate of change in FEV1 was even slower ( -1.48 + /- 0.69 percent vs. -3.57 + /- 0.65 percent in the placebo group , P = 0.03 ) , and this group of patients also had a significantly slower rate of decline in forced vital capacity , the percentage of ideal body weight , and the chest-radiograph score . There was no significant difference between the ibuprofen and placebo groups in the frequency of hospitalization . One patient was withdrawn from the study because of conjunctivitis , and one because of epistaxis related to ibuprofen . CONCLUSIONS In patients with cystic fibrosis and mild lung disease , high-dose ibuprofen , taken consistently for four years , significantly slows the progression of the lung disease without serious adverse effects BACKGROUND We assessed the short-term efficacy and safety of aztreonam lysine for inhalation ( AZLI [ an aerosolized monobactam antibiotic ] ) in patients with cystic fibrosis ( CF ) and Pseudomonas aeruginosa ( PA ) airway infection . METHODS In this r and omized , double-blind , placebo-controlled , international study ( AIR-CF1 trial ; June 2005 to April 2007 ) , patients ( n = 164 ; > or= 6 years of age ) with FEV(1 ) > or= 25 % and < or= 75 % predicted values , and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI ( three times daily for 28 days ) or placebo ( 1:1 r and omization ) , then were monitored for 14 days after study drug completion . The primary efficacy end point was change in patient-reported respiratory symptoms ( CF- Question naire-Revised [ CFQ-R ] Respiratory Scale ) . Secondary end points included changes in pulmonary function ( FEV(1 ) ) , sputum PA density , and nonrespiratory CFQ-R scales . Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored . RESULTS After 28 days of treatment , AZLI improved the mean CFQ-R respiratory score ( 9.7 points ; p < 0.001 ) , FEV(1 ) ( 10.3 % predicted ; p < 0.001 ) , and sputum PA density ( - 1.453 log(10 ) cfu/g ; p < 0.001 ) , compared with placebo . Significant improvements in Eating , Emotional Functioning , Health Perceptions , Physical Functioning , Role Limitation/School Performance , and Vitality CFQ-R scales were observed . Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of " productive cough " was reduced by half in AZLI-treated patients . PA aztreonam susceptibility at baseline and end of therapy were similar . CONCLUSIONS In patients with CF , PA airway infection , moderate-to-severe lung disease , and no recent use of antipseudomonal antibiotics or azithromycin , 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function , and was well tolerated . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00112359 OBJECTIVE To assess the effectiveness and safety of high-dose ibuprofen when used as part of routine therapy in patients with cystic fibrosis ( CF ) . STUDY DESIGN In this multicenter , double-blinded , placebo-controlled trial , a total of 142 patients age 6 to 18 years with mild lung disease ( forced expiratory volume in 1 minute [ FEV1 ] > 60 predicted ) were r and omized to receive either high-dose ibuprofen ( 70 subjects , 20 to 30 mg/kg/twice daily , adjusted to a peak serum concentration of 50 to 100 mug/mL ) or placebo ( 72 subjects ) for a 2-year period . The primary outcome was the annualized rate of change in FEV1 % predicted . RESULTS The patients in the high-dose ibuprofen group exhibited a significant reduction in the rate of decline of forced vital capacity percent predicted ( 0.07 + /- 0.51 vs -1.62 + /- 0.52 ; P = .03 ) , but not FEV1 % . The ibuprofen group also spent fewer days in hospital after adjusting for age ( 1.8 vs 4.1 days per year ; P = .07 ) . A total of 11 patients ( 4 in the ibuprofen group and 7 in the placebo group ) withdrew due to adverse events . CONCLUSIONS High-dose ibuprofen has a significant effect on slowing the progression of lung disease in CF and generally is well tolerated To evaluate the effect of long-term bronchodilator therapy in CF patients with demonstrated bronchial hyperresponsiveness , we first performed methacholine challenges to determine responsiveness , then entered 27 patients ( 16 methacholine responders and 11 nonresponders ) into a two-month double-blind crossover trial of albuterol , 90 micrograms by inhalation four times a day vs placebo . Among the responders , daily PEFR measures improved significantly more during treatment with albuterol ( 12 + /- 32 L/min ) than with placebo ( -0.4 + /- 19 L/min ; p less than 0.05 ) . In addition , a clinical ly important level of improvement in PEFR ( 15 percent increase ) was reached significantly more frequently in the responders . Methacholine nonresponders had no change in PEFR on either albuterol or placebo . Daily symptom scores as well as spirometry measurements at biweekly visits did not show significant changes . We conclude that long-term therapy with inhaled albuterol improves lung function in CF patients , but only in those with bronchial hyperresponsiveness as demonstrated by methacholine challenge OBJECTIVE To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis . STUDY DESIGN We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction ( forced expiratory volume in 1 second < or = 55 % of the predicted value ) ; 25 patients were given inhaled corticosteroids for 30 days ( 1500 micrograms of beclomethasone via spacer ) , and 24 patients had the same st and ard treatment but no inhaled corticosteroids . RESULTS Forced vital capacity , forced expiratory volume in 1 second , and airway resistance showed significant improvement in both study groups , but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids . When concomitant medications were taken into account , analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume . CONCLUSION Inhaled corticosteroids in combination with st and ard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction . Our preliminary data seem encouraging enough to warrant a multicenter , long-term , blind control study We conducted a double-blind , placebo-controlled , multicenter , r and omized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa ( Pa ) density from the lower airway of young children with cystic fibrosis . Ninety-eight subjects were to be r and omized ; however , the trial was stopped early because of evidence of a significant microbiological treatment effect . Twenty-one children under age 6 years were r and omized ( 8 active ; 13 placebo ) and underwent bronchoalveolar lavage at baseline and on Day 28 . There was a significant difference between treatment groups in the reduction in Pa density ; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients . We observed no differences between treatment groups for clinical indices , markers of inflammation , or incidence of adverse events . No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment . We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis The aim of this study was to evaluate the ability of high-resolution computerized tomography ( H RCT ) of the chest and chest x-rays ( CXR ) to determine efficacy of inhaled recombinant human DNase ( rhDNase ) in cystic fibrosis ( CF ) patients younger than 5 years of age . A r and omized , double-blind , placebo-controlled pilot study of 12 patients with CF younger than 5 years of age , attending the University of Michigan Cystic Fibrosis Center ( Ann Arbor , MI ) was conducted . The changes in the H RCT and CXR score from baseline to day 100 of therapy were assessed using a previously vali date d scoring system . The mean changes of H RCT scores between the rhDNase and placebo groups were found to be significant at the 95 % level , with mean change + /- SE mean of - 1.00 + /- 0.53 and 0.58 + /- 0.24 for rhDNase and placebo groups , respectively ( P = 0.02 ) . The difference in CXR score was not significant between the two groups . An analysis was performed to relate H RCT subscores to CXR score ; only thickening of the intra-interlobular septae was significantly correlated with the total CXR score ( r = - 0.7 , P < 0.01 ) . There was improvement in the parents ' assessment s of the patients ' well-being , with improvement in physical activity , decreased cough , sleep quality , and appetite in those subjects receiving rhDNase . We conclude that the administration of rhDNase was associated with improvement in the H RCT scan in CF patients younger than 5 years of age . Findings indicate that H RCT of the chest is useful and sensitive in study ing responses to therapy in patients with CF lung disease . To our knowledge , this is the first report of the use of H RCT to assess the effectiveness of a therapeutic modality in so young a CF patient population Bronchial hyperresponsiveness is present in 40 - 60 % of adult patients with cystic fibrosis ( CF ) . Drugs which alter airway hyperresponsiveness have not yet been studied in CF . In this r and omized placebo-controlled study , we investigated the effects of an inhaled corticosteroid , budesonide , on lung function and bronchial hyperresponsiveness in adult CF patients , with proven bronchial hyperresponsiveness to histamine . Twelve patients were treated with budesonide , 1600 micrograms day-1 , and with placebo during two periods of 6 weeks in a r and omized , double-blind , cross-over study . Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine , spirometry and clinical symptom scores . After treatment with budesonide , no significant differences in spirometry were seen , however , bronchial hyperresponsiveness to histamine significantly improved as compared to baseline . Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine . Daily symptom scores showed small , but statistically significant , improvements in dyspnoea and cough after budesonide treatment . There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF . Treatment with oral corticosteroids improved the clinical course of selected CF patients , but was associated with unacceptable adverse effects . We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small , but significant , improvement in bronchial hyperresponsiveness to histamine , and symptoms of cough and dyspnoea in adult CF patients . Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF Progressive lung disease in patients with cystic fibrosis ( CF ) is caused by thick secretions , which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms . Recently , recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function . Ultrasonically nebulized hypertonic saline ( HS ) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions , and may therefore provide a low cost alternative . We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease . The patients were evaluated following 2 weeks of treatment with HS in an open-label study . Subjects were r and omly allocated to receive 10 ml of either 0.9 % NaCl ( IS ) or 6 % NaCl ( HS ) . Twice daily , prior to physiotherapy , treatments were delivered by a portable ultrasonic nebulizer . To prevent bronchoconstriction , 600 mg of salbutamol was administered prior to the nebulized solutions . A symptom score was recorded and spirometry was performed on day 0 before therapy was started , on day 14 ( the last day of therapy ) , and on day 28 ( 14 days after the last treatment with either IS or HS ) . Fifty-two patients ( 32 males ) , with a mean age of 16.2 ( range 7 - 36 ) years completed the study . There was no difference in baseline characteristics between the two groups . Following 2 weeks of treatment , there was a significant improvement from baseline in FEV1 of 15.0 + /- 16.0 % ( mean + /- SD ) in patients treated with HS , compared with a change of 2.8 + /- 13 % in those on IS therapy ( P = 0.004 ) . Furthermore , there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS ( P = 0.02 ) . The treatment was well tolerated . We conclude that in patients with CF , ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period . Nebulized saline also enhances the perception of effectiveness of chest physiotherapy Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF . The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes . Recombinant human DNase I ( rhDNase ) reduces the viscosity of CF sputum in vitro . To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF , we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase ( 0.6 , 2.5 , or 10.0 mg twice daily ) in 181 out patients using a r and omized , placebo-controlled parallel design . Forced vital capacity ( FVC ) improved 10 to 12 % ( p < 0.05 to 0.001 ) , and forced expiratory volume in one second ( FEV1 ) improved 10 to 15 % ( p < 0.001 ) across all doses of rhDNase compared with placebo . The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 ( p < 0.001 ) . rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being . No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase . Some patients experienced mild upper airway irritation , but no major adverse events were reported . Administration for 10 days of aerosolized rhDNase to pediatric and adult out patients with CF improves lung function and is well tolerated . Although all three doses were efficacious , the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups The major goal of the U.S. Preventive Services Task Force ( USPSTF ) is to provide clinicians and policymakers with a reliable and accurate source of evidence -based recommendations on a wide range of preventive services . To accomplish this goal , the USPSTF systematic ally review s the evidence concerning both the benefits and harms of widespread implementation of a preventive service . It then assesses the certainty of the evidence and the magnitude of the benefits and harms . On the basis of this assessment , the USPSTF assigns a letter grade to each preventive service signifying its recommendation about provision of the service ( Table 1 ) . Table 1 . U.S. Preventive Services Task Force Recommendation Grid * An important , but often challenging , step is determining the balance between benefits and harms to estimate net benefit ( that is , benefits minus harms ) . In this issue , the Task Force reports an up date to its recommendation for carotid artery stenosis screening ( 1 , 2 ) . Because carotid artery stenosis screening has both known benefits and harms , estimating net benefit was critical in the final USPSTF recommendation that clinicians not provide carotid artery stenosis screening in asymptomatic people ( recommendation letter grade D ) . Release of this recommendation provides an opportunity for the Task Force to up date and explain to a clinical audience the process by which it evaluates evidence , determines the certainty and magnitude of net benefit , and gives a letter grade to the recommendation . We will do this by considering 3 questions : 1 ) What evidence does the Task Force consider to estimate net benefit ? 2 ) How does the Task Force estimate the certainty of net benefit ? and 3 ) How does the Task Force estimate the magnitude of net benefit ? What Evidence Does the Task Force Consider to Estimate Net Benefit ? The overarching question that the Task Force seeks to answer for every preventive service is whether evidence suggests that provision of the service would improve health outcomes if implemented in a general primary care population . For screening topics , this st and ard could be met by a large r and omized , controlled trial ( RCT ) in a representative asymptomatic population with follow-up of all members of both the group invited for screening and the group not invited for screening . For example , the Multicentre Aneurysm Screening Study ( 3 ) was a population -based RCT of screening for abdominal aortic aneurysm in which 67800 asymptomatic men age 65 to 74 years in the United Kingdom were r and omly assigned to be invited or not to be invited for screening . Both groups were followed for a mean of 4.1 years , and abdominal aortic aneurysmrelated mortality and all-cause mortality were compared . No RCTs of carotid artery stenosis screening have been published ; however , RCTs comparing carotid endarterectomy to medical management of asymptomatic carotid artery stenosis are available . The distinction between RCTs that r and omly assign people to undergo screening versus RCTs that r and omly assign people known to have a condition to an intervention is important . In contrast to the latter , RCTs of screening take into account the false-positive and false-negative rates of the screening test , the possibility of adverse events from the test , the accuracy and potential for adverse events of any subsequent confirmatory diagnostic tests , and the inevitable failure to follow through on the test or any subsequent steps needed before the therapeutic intervention is delivered . In addition , conditions detected by screening may have different biological characteristics than those detected in other ways . The benefits of treating screened individuals , therefore , can not be assumed to be the same as those of treating symptomatic individuals . Screening trials directly answer a simple question important to the primary care setting : Does screening for a certain condition improve health outcomes ? Direct RCT evidence about screening is often unavailable , so the Task Force considers indirect evidence . To guide its selection of indirect evidence , the Task Force constructs a chain of evidence within an analytic framework . Figure 1 of the evidence up date ( 2 ) in this issue ( page 861 ) shows the analytic framework for the Task Force assessment of carotid artery stenosis screening . Each arrow in the framework defines a key question , and each key question represents a link in the chain of evidence . Rectangles in the framework represent the intermediate outcomes ( rounded corners ) or the health outcomes ( square corners ) ; ovals represent harms . To form an unbroken chain , evidence must support each link in the chain , thereby connecting the target population ( far left side of the framework ) to the improved health outcome ( far right side of the framework ) . For each key question , the body of pertinent literature is critically appraised , focusing on 6 questions ( Table 2 ) . The USPSTF will now describe its judgment about the evidence for each key question as convincing , adequate , or inadequate . Evidence may be considered convincing when derived from several high- quality studies with consistent , logical results that are generalizable to the U.S. primary care population and setting . Evidence may be deemed adequate when , on the basis of judgment , most but not all of these 6 questions are answered favorably . When evidence is conflicting or the studies are of poor quality individually or in aggregate , the evidence for a key question is considered inadequate . Inadequate evidence may create a critical gap in the evidence chain . Table 2 . Questions Considered by the U.S. Preventive Services Task Force for Evaluating Evidence Related Both to Key Questions and to the Overall Certainty of the Evidence of Net Benefit for the Preventive Service How Does the Task Force Estimate the Certainty of Net Benefit ? The next step in the Task Force process is to use the evidence from the key questions to assess whether there would be net benefit if the service were implemented . In 2001 , the USPSTF published an article that documented its systematic processes of evidence evaluation and recommendation development ( 4 ) . At that time , the Task Force 's overall assessment of evidence was described as good , fair , or poor . The Task Force realized that this rating seemed to apply only to how well studies were conducted and did not fully capture all of the issues that go into an overall assessment of the evidence about net benefit . To avoid confusion , the USPSTF has changed its terminology . Whereas individual study quality will continue to be characterized as good , fair , or poor , the term certainty will now be used to describe the Task Force 's assessment of the overall body of evidence about net benefit of a preventive service and the likelihood that the assessment is correct . Certainty will be determined by considering all 6 questions in Table 2 ; the judgment about certainty will be described as high , moderate , or low . In making its assessment of certainty about net benefit , the evaluation of the evidence from each key question plays a primary role . It is important to note that the Task Force makes recommendations for real-world medical practice in the United States and must determine to what extent the evidence for each key question even evidence from screening RCTs or treatment RCTs can be applied to the general primary care population . Frequently , studies are conducted in highly selected population s under special conditions . The Task Force must consider differences between the general primary care population and the population s studied in RCTs and make judgments about the likelihood of observing the same effect in actual practice . For carotid artery stenosis screening , the Task Force search ed for evidence about the true prevalence of high- grade carotid artery stenosis in the general population , the generalizability of treatment effectiveness estimates based on RCTs conducted in selected population s , and the complication rate from carotid endarterectomy in asymptomatic individuals if performed in nontrial setting s ( for example , community hospitals ) . It is also important to note that 1 of the key questions in the analytic framework refers to the potential harms of the preventive service . The Task Force considers the evidence about the benefits and harms of preventive services separately and equally . Data about harms are often obtained from observational studies because harms observed in RCTs may not be representative of those found in usual practice and because some harms are not completely measured and reported in RCTs . For example , the surgeons who enrolled patients in RCTs of carotid artery stenosis were selected on the basis of their low postoperative stroke and mortality rates . Widespread screening for carotid artery stenosis would invariably lead to surgical treatment provided in hospitals ( or by surgeons ) with higher rates of complications . The harms of screening for carotid artery stenosis , including the harms from carotid angiography to confirm the diagnosis of carotid artery stenosis in patients screening positive by carotid ultrasonography , were not captured in some treatment RCTs . Putting the body of evidence for all key questions together as a chain , the Task Force assesses the certainty of net benefit of a preventive service by asking the 6 major questions in Table 2 . The Task Force would rate a body of convincing evidence about the benefits of a service that , for example , derives from several RCTs of screening in which the estimate of benefits can be generalized to the general primary care population as high certainty ( Table 3 ) . The Task Force would rate a body of evidence that was not clearly applicable to general practice or has other defects in quality , research design , or consistency of studies as moderate certainty . Certainty is low when , for example , there are gaps in the evidence linking parts of the analytic framework , when evidence to determine the harms of treatment is unavailable , or BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset . CONCLUSIONS In patients with cystic fibrosis , the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms , result ed in slight improvement in pulmonary function , and was well tolerated Twenty-seven patients with cystic fibrosis and endobronchial colonization with Pseudomonas aeruginosa were r and omly assigned to inhale either 2 mL saline ( 12 patients ) or 80 mg tobramycin solution ( 15 patients ) 3 times daily . One control patient died ; all others completed the study ( mean duration 32 months ) . No significant differences were found between the two groups at enrollment . The treatment group showed no change , while the control group had a significant decline in both pulmonary function and clinical status over the study period . Individually , 11 of 12 patients in the control group showed deterioration , while 9 of 15 in the treatment group with susceptible P. aeruginosa at enrollment acquired resistant organisms . There was no evidence of significant nephro- or ototoxicity . Although inhaled tobramycin appeared to arrest the decline in pulmonary status , further work is required to identify patients most likely to respond STUDY OBJECTIVES To assess the impact of inhaled , buffered reduced glutathione ( GSH ) on clinical indicators of cystic fibrosis ( CF ) pathophysiology . DESIGN AND PATIENTS A r and omized , double-blind , placebo-controlled pilot study was conducted over an 8-week period . Nineteen subjects , age 6 to 19 years , with CF status documented by positive sweat chloride test results ( > 60 mEq/L ) were recruited for the trial . After matching on age and sex , 10 patients were r and omly assigned to the treatment group and 9 patients to the placebo group . Primary outcomes were FEV1 , FVC , forced expiratory flow at 25 to 75 % of vital capacity , and peak flow ; secondary outcomes were body mass index , 6-min walk distance , and self-reported cough frequency , mucus production/viscosity/color , wellness , improvement , and stamina . INTERVENTIONS AND ANALYSIS : Treatment was buffered GSH , and placebo was sodium chloride with a hint of quinine . The total daily dose of buffered GSH was approximately 66 mg/kg of body weight , and the total daily dose of placebo was approximately 15 mg/kg of body weight ( quinine , 25 to 30 microg/kg ) . Doses were distributed across four inhalation sessions per day and spaced 3- to 4-h apart . General linear mixed models were used to analyze the data . The final sample size was nine subjects in the treatment group and seven subjects in the placebo group . RESULTS Mean change for peak flow was -6.5 L/min for the placebo group and + 33.7 L/min for the GSH group ( p = 0.04 ) , and self-reported average improvement on a scale from 1 to 5 ( 1 being much worse and 5 being much better ) was 2.8 for placebo and 4.7 for GSH ( p = 0.004 ) . Of the 13 primary and secondary outcomes examined , 11 outcomes favored the treatment group over the placebo group ( p = 0.002 ) , indicating a general tendency of improvement in the GSH group . No adverse events in the treatment group were noted . CONCLUSION This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease , and longer , larger , and improved studies of inhaled GSH are warranted The cytokines interleukin-1 and interleukin-2 participate in the inflammatory response , and may contribute to hypergammaglobulinaemia G and the development of lung injury in cystic fibrosis . Anti-inflammatory treatment with corticosteroids may attenuate this response . The effect of a 12 week course of oral prednisolone on spirometry and serum concentrations of interleukin-1 alpha ( IL-1 alpha ) , soluble interleukin-2 receptor ( sIL-2R ) , and IgG was investigated in 24 children with cystic fibrosis . Prednisolone was administered , in a double blind and placebo controlled manner , at an initial dose of 2 mg/kg daily for 14 days and tapered to 1 mg/kg on alternate days for 10 weeks . The treated group ( n = 12 ) experienced an increase in forced expiratory volume in one second and forced vital capacity at 14 days , however , these changes were smaller at 12 weeks . In the treated group , change in pulmonary function was associated with decreased serum IgG and cytokine concentrations . Prednisolone suppresses serum concentrations of these cytokines , which may participate in the inflammatory response , the excessive synthesis of IgG , and airflow obstruction observed in cystic fibrosis patients Antiinflammatory therapy with ibuprofen has been proposed to retard the progression of lund disease in cystic fibrosis ( CF ) . The pharmacokinetics and toxicity of ibuprofen were investigated in a r and omized , double-blind , placebo-controlled , 3-month dose-escalation study in 19 children with CF , 6 to 12 years of age . The subjects received orally and twice daily 300 mg of drug during the first month , 400 mg in the second month , and 600 mg in the third month . Ibuprofen pharmacokinetics and evaluation for adverse effects were performed at the beginning and end of each month . The dose of ibuprofen was increased if peak plasma concentration ( Cmax ) was less than 50 micrograms/ml . To preserve the blind nature of the study , the dose in matched subjects taking placebo was also increased . The subjects r and omly assigned to receive ibuprofen ( n = 13 ) completed 26 months of treatment ; placebo subjects ( n = 5 ) completed 12 months . With dose escalation , Cmax and the area under the concentration-time curve from zero to infinity significantly increased ( p less than 0.01 ) . The pharmacokinetics of ibuprofen in 13 children with CF who received 13.4 + /- 4.1 mg/kg ( mean + /- SD ) were compared with those in four healthy children who received a similar dose . Peak plasma concentration ( 48 + /- 17 micrograms/ml ) was decreased by 27 % ( p = 0.06 ) , the area under the concentration-time curve ( 6.1 + /- 1.7 mg.min/ml ) was decreased by 46 % ( p less than 0.001 ) , apparent total clearance ( 2.3 + /- 0.6 ml/min.kg-1 ) was increased by 77 % ( p less than 0.01 ) , and apparent volume of distribution during terminal phase ( 291 + /- 91 ml/kg ) was increased by 84 % ( p = 0.01 ) in the children with CF . Time to Cmax ( 66 + /- 20 minutes ) and elimination half-life ( 92 + /- 27 minutes ) were not significantly different . No subjects were withdrawn from the study because of side effects . No adverse effects could be attributed to ibuprofen . Thus ibuprofen administration has no significant toxic effects , but Cmax will need to be monitored for effective dosing in patients with CF The effects of oral administration of cephalexin were evaluated in a double-blind , placebo-controlled , crossover study in 17 patients with mild to moderate pulmonary disease due to cystic fibrosis . For two years , four-month periods with cephalexin were alternated with four-month placebo periods . Thus , patients served as their own control subjects . Fungal vulvovaginitis occurred in two patients and a cephalexin-resistant Enterobacter cloacae was acquired in the sputum of another patient during cephalexin therapy . During the 2 years of study , the rate of colonization with mucoid strains of Pseudomonas aeruginosa increased and disease severity deteriorated in patients initially colonized with P. aeruginosa . Short-term courses of sputum culture-specific antibiotics improved the course of some patients with mild to moderate pulmonary disease due to cystic fibrosis . Treatment with cephalexin decreased the frequency of respiratory illnesses , respiratory illnesses requiring antibiotics , and hospitalizations for respiratory illnesses in patients initially colonized with Staphylococcus aureus and /or Haemophilus influenzae , and also reduced colonization with these organisms . Improved weight gain in 16 of 17 patients was associated with periods of cephalexin therapy . Pulmonary function tests remained stable or improved in 10 of 14 patients . Disease severity improved in patients not colonized with P. aeruginosa OBJECTIVES To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis ( CF ) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease . STUDY DESIGN A 7-year , multicenter , double-blind , placebo-controlled study of continuous antistaphylococcal therapy . Otherwise healthy children < 2 years of age with CF were r and omly assigned to be treated with daily cephalexin ( 80 - 100 mg/kg/day ) or placebo . Clinical , microbiologic , laboratory , radiographic , and anthropometric outcomes were evaluated . RESULTS Of 209 children enrolled , 119 completed a 5- to 7-year course of therapy . Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups , respectively . Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus ( 6.0 % vs 30.4 % ; P < .001 ) . They were , however , much more likely to be positive for Pseudomonas aeruginosa ( 25.6 % vs 13.5 % ; P < .009 ) . These differences became apparent in the first year after enrollment and persisted over the duration of the study . In contrast to these microbiologic differences , there were no differences in clinical outcome measures , including radiographic ( Brasfield score , 23.4 vs 23.2 ) or anthropometric scores or pulmonary function . CONCLUSIONS Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus , it enhanced colonization with P aeruginosa and did not lead to clinical ly significant improvement in major health outcomes . These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF This placebo-controlled study was design ed to confirm a previously performed open label study that showed significant improvement in spirometry on maintenance therapy with albuterol for 1 year . In a double-blind , cross-over trial , albuterol ( by metered dose inhaler ) 180 microg b.i.d . or placebo were given for 6 months each . Spirometry was monitored at the start , and 3 and 6 months following initiation of each arm of the study . Peak expiratory flow rate ( PEFR ) was measured twice daily at home before and after study drug administration . Only patients with clinical ly detectable lung disease were enrolled . Twenty-one patients finished the study . All spirometric tests showed a significant improvement from start to end of the 6 month treatment with albuterol ; there was no significant change on placebo . Forced vital capacity improved by 8.2 % and forced expiratory volume in 1 s by 12.1 % on albuterol therapy . Nevertheless , there was no significant difference between change on albuterol and change on placebo . Home measurements of PEFR showed a significant improvement of 4.7 % on albuterol and a non-significant change of 2.0 % on placebo from the first to the last week of treatment . None of the long-term improvements ( spirometry or home PEFR ) correlated with mean daily bronchodilation . For albuterol , the number of days of hospitalization was less than half that for patients on placebo ( 1.0/patient on albuterol versus 2.6 on placebo ) , but this did not reach statistical significance . These results suggest a beneficial effect from maintenance therapy with albuterol . Bronchodilation alone probably can not explain the long-term benefits of albuterol , and other mechanisms may play a role . The lack of significant difference between change on albuterol and change on placebo is probably due to too small a number of patients in this study and lack of statistical power A r and omised , double-blind , placebo-controlled study examined the effects of alternate-day prednisone therapy on morbidity and progression of lung disease in cystic fibrosis ( CF ) . At baseline the patients ( aged 1 - 12 years ) had mild to moderate lung disease , and the prednisone group did not differ significantly from the placebo group for any values measured . After 4 years , the prednisone-treated group had significant advantages over the placebo group for height , weight , vital capacity , forced expiratory volume in 1 s , peak flow rate , erythrocyte sedimentation rate , and serum IgG. The prednisone-treated group required 9 admissions to hospital for CF-related pulmonary disease compared with 35 for the placebo group . There were no steroid-induced side-effects . To rule out bias in case selection , 69 CF clinic patients comparable in age and clinical status but not included in the study were compared with the placebo group at 4 years ; no significant differences between the groups were found The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period . In 15 North American cystic fibrosis centers , we screened 320 patients and enrolled 285 patients from April 1986 to December 1987 . Patients were r and omly assigned to take prednisone , 1 mg/kg per dose or 2 mg/kg per dose , or a matching placebo given on alternate days . Lung function , clinical status , hospitalizations , growth , and steroid side effects were monitored . During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group ( p < 0.0001 ) and the 2 mg/kg group ( p < 0.01 ) when each was compared with placebo . Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months ( p < 0.0025 ) , but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline . For 48 months , the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo ( p < 0.02 ) . The prednisone-treated groups had a reduction in serum IgG concentrations ( 1 mg/kg vs placebo , p < 0.007 ; 2 mg/kg vs placebo , p < 0.003 ) . From 6 months onward , height z scores fell in the 2 mg/kg group compared with those given placebo ( p < 0.001 ) . For the 1 mg/kg group , height z scores were lower from 24 months . An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group ( p < 0.005 ) . Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis . The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months In 31 adult patients with cystic fibrosis ( CF ) who were chronically infected with Pseudomonas aeruginosa we examined the effect of giving regular three monthly oral ciprofloxacin . Patients received ciprofloxacin or placebo for 10 days every 3 months for 1 yr in a r and omized , double-blind , placebo-controlled study . During each course of treatment patients receiving ciprofloxacin reported an improvement in cough , sputum production and peak expiratory flow ( PEF ) P = < 0.005 . During the year of study patients receiving ciprofloxacin showed an improvement in PEF when compared with those receiving placebo ( P = < 0.05 ) but the changes in FEV1 and FVC were not statistically different in either group . Regular oral ciprofloxacin was well tolerated but did not prevent hospital admissions or reduce the number of courses of intravenous antibiotics throughout the year . The median MIC to ciprofloxacin in the active treatment group rose from 0.5 mg l-1 to 0.75 mg l-1 during treatment . We conclude that CF patients are likely to benefit from oral ciprofloxacin for exacerbations of respiratory symptoms . However , regular treatment with ciprofloxacin over 1 yr improves PEF but does not reduce the rate of hospital admissions with acute exacerbations of respiratory symptoms Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis . High levels of DNA in the sputum make the sputum viscous and difficult to expectorate . Recombinant human deoxyribonuclease ( rhDNase ) in vitro has been shown to reduce the viscoelasticity of the sputum from CF patients . We have done a phase II double-blind r and omised placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for 10 days . All patients had forced vital capacity ( FVC ) above 40 % predicted and were clinical ly stable . Patients were followed up for 42 days from the start of drug/placebo administration . All 71 r and omised patients , aged 16 - 55 , completed every aspect of the study and baseline characteristics were similar in the two groups . Baseline forced expiratory volume in one second ( FEV1 ) was 46 % of predicted for patients r and omised to rhDNase , and 48 % for those r and omised to placebo ; and baseline FVC was 76 % of predicted for both groups . The mean percentage change in FEV1 from baseline was a 13.3 % rise on rhDNase and a 0.2 % fall on placebo ( p < 0.001 ) . FVC rose 7.2 % in the rhDNase group and 2.3 % in the placebo group ( not significant ) . There were no life-threatening adverse events and no anaphylactic reactions . There was no significant difference in side-effects between the groups . This study confirms that short-term administration of rhDNase in stable patients with cystic fibrosis is safe and improves lung function RATIONALE The effectiveness and safety of aztreonam lysine for inhalation ( AZLI ) in patients with cystic fibrosis ( CF ) on maintenance treatment for Pseudomonas aeruginosa ( PA ) airway infection was evaluated in this r and omized , double-blind , placebo-controlled study . OBJECTIVES To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF . METHODS After r and omization and a 28-day course of tobramycin inhalation solution ( TIS ) , patients ( n = 211 ; > or = 6 yr ; > or =3 TIS courses within previous year ; FEV(1 ) > or = 25 % and < or = 75 % predicted values ) were treated with 75 mg AZLI or placebo , twice or three times daily for 28 days , then monitored for 56 days . The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics . Secondary endpoints included changes in respiratory symptoms ( CF Question naire-Revised [ CFQ-R ] Respiratory Scale ) , pulmonary function ( FEV(1 ) ) , and sputum PA density . Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored . MEASUREMENTS AND MAIN RESULTS AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days , compared with placebo ( AZLI , 92 d ; placebo , 71 d ; P = 0.007 ) . AZLI improved mean CFQ-R respiratory scores ( 5.01 points , P = 0.02 ) , FEV(1 ) ( 6.3 % , P = 0.001 ) , and sputum PA density ( -0.66 log(10 ) cfu/g , P = 0.006 ) compared with placebo ; no AZLI dose-response was observed . Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease . Susceptibility of PA to aztreonam at baseline and end of therapy were similar . CONCLUSIONS AZLI was effective in patients with CF using frequent TIS therapy . AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics , improved respiratory symptoms and pulmonary function , and was well tolerated . Clinical trial registered with www . clinical trials.gov ( NCT 00104520 ) Abstract Background and aim Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis ( CF ) causes progressive deterioration in lung function . The purpose of this trial was to assess the efficacy and tolerability of a tobramycin highly concentrated solution for inhalation ( TSI ) [ 300mg/4mL ; Bramitob ® ] when added to other antipseudomonal therapies in CF patients with chronic P. aeruginosa infection . Methods In a multinational , double-blind , multicenter study , CF patients with chronic P. aeruginosa infection were r and omized to receive nebulized tobramycin or placebo over a 24-week study period in which 4-week treatment periods ( ‘ on ’ cycles ) were followed by 4-week periods without treatment ( ‘ off ’ cycles ) . Forced expiratory volume in 1 second ( FEV1 ) percentage of predicted normal was used as the primary efficacy outcome parameter . Forced vital capacity ( FVC ) , forced expiratory flow at 25–75 % of FVC ( FEF25–75 % ) , P. aeruginosa susceptibility , minimum concentration required to inhibit 90 % of strains ( MIC90 ) , rates of P. aeruginosa-negative culture , P. aeruginosa persistence and superinfection , need for hospitalization and parenteral antipseudomonal antibiotics , loss of school/working days due to the disease , and nutritional status ( bodyweight and body mass index ) were considered as secondary efficacy outcome parameters . Adverse events reporting , audiometry , and renal function were monitored to evaluate the tolerability and safety of TSI . Results A total of 247 patients were r and omized in the study . At endpoint time assessment ( week 20 ) , FEV1 was significantly increased in the tobramycin group and the adjusted mean difference between groups ( intention-to-treat population ) was statistically significant ( p < 0.001 ) . At the same time , clinical ly relevant improvements in FVC and FEF25–75 % were detected in the TSI group ( p = 0.022 and p = 0.001 , respectively ) . The microbiologic outcomes at the end of the last ‘ on ’ cycle period were significantly better in the TSI group than the placebo group ( p = 0.024 ) , although there was a concomitant trend toward an increase in the MIC of isolated P. aeruginosa strains . The percentage of patients hospitalized as well as the need for parenteral antipseudomonal antibiotics was significantly lower in the TSI group ( p = 0.002 and p = 0.009 , respectively ) . Patients treated with TSI had fewer lost school/working days due to the disease ( p < 0.001 ) . A favorable effect of tobramycin in terms of an increase in bodyweight and body mass index was also noted , when compared with placebo , at all timepoints ( p < 0.01 and p < 0.001 , respectively ) . No significant changes in serum creatinine and auditory function were detected . The proportion of patients with drug-related adverse events was 15 % in both treatment groups . Conclusions Long-term , intermittent administration of this aerosolized tobramycin formulation ( 300mg/4mL ) in CF patients with P. aeruginosa chronic infection significantly improved pulmonary function and microbiologic outcome , decreased hospitalizations , increased nutritional status , and was well tolerated Background : Aerosolized recombinant human deoxyribonuclease ( rhDNase I ( Pulmozyme ® ) ) has previously been shown to increase pulmonary function and reduce exacerbations of respiratory symptoms in cystic fibrosis ( CF ) patients with moderate to severe reduction in pulmonary function . Aim : To analyse whether aerosolized Pulmozyme ® could reduce the number of bacterial infections in the lower respiratory airways of CF patients without chronic pulmonary infection . Methods : Patients were r and omized either to aerosolized Pulmozyme ® 2½ mg once daily or to no rhDNase treatment . The study period was 1 y , and the study was blinded for the Department of Clinical Microbiology . Results : Overall , the number of positive cultures was significantly higher in the untreated group ( 82 % ) compared with the treated group ( 72 % ) ( p<0.05 ) . The most striking difference was found for Staphylococcus aureus , with a prevalence of 30 % in the untreated group compared with 16 % in the treated group ( χ2 test , p<0.0001 ) . Pulmonary function ( FEV1 ) in the treated group showed a significant increase of 7.3 % compared to 0.9 % in the untreated group ( p<0.05 ) BACKGROUND The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis . Since findings of open pilot studies seemed to show clinical benefit , we undertook a formal trial . METHODS 41 children with cystic fibrosis , aged 8 - 18 years , and with a median forced expiratory volume in 1 s ( FEV1 ) of 61 % ( range 33 - 80 % ) participated in a 15-month r and omised double-blind , placebo-controlled crossover trial . They received either azithromycin ( bodyweight < or = 40 kg : 250 mg daily , > 40 kg : 500 mg daily ) or placebo for 6 months . After 2 months of washout , the treatments were crossed over . The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods . Sputum cultures , sputum interleukin 8 and neutrophil elastase , exercise testing , quality of life , antibiotic use , and pulmonary exacerbation rates were secondary outcome measures . Side-effects were assessed by pure tone audiometry and liver function tests . Analysis was by intention-to-treat . FINDINGS Median relative difference in FEV1 between azithromycin and placebo was 5.4 % ( 95 % CI 0.8 - 10.5 ) . 13 of 41 patients improved by more than 13 % and five of 41 deteriorated by more than 13 % ( p=0.059 ) . Forced vital capacity and mid-expiratory flow did not significantly change overall . 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo , and five had six extra courses ( p=0.005 ) . Sputum bacterial densities , inflammatory markers , exercise tolerance , and subjective well-being did not change . There were no noticeable side-effects . INTERPRETATION A 4 - 6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment . The mechanism of action remains unknown |
12,679 | 24,826,920 | There was a medium to large positive effect on zinc status .
We found no clear evidence of benefit or harm of supplementation with regard to haemoglobin or iron status .
Supplementation had a negative effect on copper status .
AUTHORS ' CONCLUSIONS In our opinion , the benefits of preventive zinc supplementation outweigh the harms in areas where the risk of zinc deficiency is relatively high . | BACKGROUND Zinc deficiency is prevalent in low- and middle-income countries , and contributes to significant diarrhoea- , pneumonia- , and malaria-related morbidity and mortality among young children .
Zinc deficiency also impairs growth .
OBJECTIVES To assess the effects of zinc supplementation for preventing mortality and morbidity , and for promoting growth , in children aged six months to 12 years of age . | Abstract Objective : To evaluate the effect of simultaneous zinc and vitamin A supplementation on diarrhoea and acute lower respiratory infections in children . Study design : R and omised double blind placebo controlled trial . Setting : Urban slums of Dhaka , Bangladesh . Participants and methods : 800 children aged 12 - 35 months were r and omly assigned to one of four intervention groups : 20 mg zinc once daily for 14 days ; 200 000 IU vitamin A , single dose on day 14 ; both zinc and vitamin A ; placebo . The children were followed up once a week for six months , and morbidity information was collected . Results : The incidence and prevalence of diarrhoea were lower in the zinc and vitamin A groups than in the placebo group . Zinc and vitamin A interaction had a rate ratio ( 95 % confidence interval ) of 0.79 ( 0.66 to 0.94 ) for the prevalence of persistent diarrhoea and 0.80 ( 0.67 to 0.95 ) for dysentery . Incidence ( 1.62 ; 1.16 to 2.25 ) and prevalence ( 2.07 ; 1.76 to 2.44 ) of acute lower respiratory infection were significantly higher in the zinc group than in the placebo group . The interaction term had rate ratios of 0.75 ( 0.46 to 1.20 ) for incidence and 0.58 ( 0.46 to 0.73 ) for prevalence of acute lower respiratory infection . Conclusions : Combined zinc and vitamin A synergistically reduced the prevalence of persistent diarrhoea and dysentery . Zinc was associated with a significant increase in acute lower respiratory infection , but this adverse effect was reduced by the interaction between zinc and vitamin A. What is already known on this topic Trials of vitamin A supplementation have failed to show a beneficial effect on morbidity in children Experimental studies have shown that , in the presence of zinc deficiency , vitamin A supplementation fails to reverse vitamin A deficiency Coexistence of deficiencies of zinc and vitamin A could be a reason for the failure of vitamin A supplementation , but data in humans are limited What this paper adds Combined zinc and vitamin A supplementation is more effective in reducing persistent diarrhoea and dysentery than either vitamin A or zinc alone Zinc alone increased respiratory illnesses , but interaction between zinc and vitamin A reduced this adverse Poor micronutrient status is associated with diarrheal illness , but it is not known whether low folate and /or cobalamin status are independent risk factors for diarrhea . We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospect i ve cohort study of 2296 children aged 6 - 30 mo in New Delhi , India . Plasma concentrations of folate , cobalamin , total homocysteine ( tHcy ) , and methylmalonic acid were determined at baseline . Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial . Diarrhea episodes lasting < 7 , ≥7 , and ≥14 d were classified as acute , prolonged , and persistent , respectively . There was a total of 4596 child periods with acute , 633 with prolonged , and 117 with persistent diarrhea during follow-up . Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [ adjusted OR = 1.77 ( 95 % CI = 1.14 , 2.75 ) ; P = 0.01 ] . This effect differed between boys [ adjusted OR = 2.51 ( 95 % CI = 1.47 , 4.28 ) ] and girls [ adjusted OR = 1.03 ( 95 % CI = 0.53 , 2.01 ) ; P-interaction = 0.030 ] . We found a small but significant association between high plasma tHcy concentration and acute diarrhea [ adjusted OR = 1.14 ( 95 % CI = 1.04 , 1.24 ) ; P = 0.006 ] . Plasma cobalamin concentration was not a predictor of diarrheal morbidity . In conclusion , poor folate status was an independent predictor of persistent diarrhea in this population Background / Objectives : Zinc is an essential micronutrient and deficiency can lead to an increased risk for infectious diseases and growth retardation among children under 5 years of age . We aim ed to estimate disease-specific and all-cause mortality attributable to zinc deficiency . Subject/ Methods : We estimated the prevalence of zinc deficiency in Latin America , Africa and Asia , where based on zinc availability in the diet and childhood stunting rates , zinc deficiency is widespread . The relative risks of death among zinc-deficient children for diarrhea , malaria and pneumonia were estimated from r and omized controlled trials . We used the comparative risk assessment methods to calculate deaths and burden of disease ( measured in disability-adjusted life years , DALYs ) from each of these three diseases attributable to zinc deficiency in these regions . Results : Zinc deficiency was responsible for 453 207 deaths ( 4.4 % of childhood deaths ) , and 1.2 % of the burden of disease ( 3.8 % among children between 6 months and 5 years ) in these three regions in 2004 . Of these deaths , 260 502 were in Africa , 182 546 in Asia and 10 159 in Latin America . Zinc deficiency accounted for 14.4 % of diarrhea deaths , 10.4 % of malaria deaths and 6.7 % of pneumonia deaths among children between 6 months and 5 years of age . Conclusions : Zinc deficiency contributes to substantial morbidity and mortality , especially from diarrhea . Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency Background Vitamin A and zinc are crucial for normal immune function , and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum . Methods A r and omized , double-blind , placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village , Burkina Faso . Children aged from 6 to 72 months were r and omized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc , six days a week ( n = 74 ) or placebo ( n = 74 ) for a period of six months . Cross-sectional surveys were conducted at the beginning and the end of the study , and children were evaluated daily for fever . Microscopic examination of blood smear was done in the case of fever ( temperature ≥37.5 ° C ) for malaria parasite detection . Results At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group ( 34 % ) compared to the placebo group ( 3.5 % ) ( p < 0.001 ) . Malaria episodes were lower in the supplemented group ( p = 0.029 ) , with a 30.2 % reduction of malaria cases ( p = 0.025 ) . Time to first malaria episode was longer in the supplemented group ( p = 0.015 ) . The supplemented group also had 22 % fewer fever episodes than the placebo group ( p = 0.030 ) . Conclusion These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children , and thus may play a key role in malaria control strategies for children in Africa Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy , few studies have examined the effects of micronutrient supplementation on specific cognitive indicators . This study investigated , in 2002 , the effects of iron-folic acid and /or zinc supplementation on the results of Fagan Test of Infant Intelligence ( FTII ) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district . Infants were enrolled in a cluster-r and omized , placebo-controlled clinical trial of daily supplementation with 5 mg of zinc , 6.25 mg of iron with 25 µg of folic acid , or zinc-iron-folic acid , or placebo . These were tested on both the tasks using five indicators of information processing : preference for novelty ( FTII ) , fixation duration ( FTII ) , accelerated performance ( ≥85 % correct ; A-not-B ) , deteriorated performance ( < 75 % correct and > 1 error on repeat-following-correct trails ; A-not-B ) , and the A-not-B error ( A-not-B ) . At 39 and 52 weeks , 247 and 333 infants respectively attempted the cognitive tests ; 213 made an attempt to solve both the tests . The likelihood of females completing the A-not-B Task was lower compared to males when cluster r and omization was controlled [ odds ratio=0.67 ; 95 % confidence interval 0.46 - 0.97 ; p<0.05 ] . All of the five cognitive outcomes were modelled in linear and logistic regression . The results were not consistent across either the testing sessions or the information-processing indicators . Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task ( p>0.05 ) . These findings suggest that broader interventions ( both in terms of scope and duration ) are needed for infants who face many biological and social stressors Controversy exists about the effect of zinc on growth and the GH-IGF system . Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children . However the mechanism of this effect has not been well characterized . Furthermore , the effect of zinc supplementation on non-zinc-deficient short children is unknown . We investigated the effect of zinc supplementation on endogenous GH secretion , serum IGF-I and IGFBP-3 concentrations , IGF-I and IGFBP-3 generation in response to exogenous GH , bone formation markers , and linear growth of non-zinc-deficient children with idiopathic short stature . We analyzed prospect ively serum zinc , IGF-I , IGFBP-3 , alkaline phosphatase , osteocalcin , and GH response to clonidine test , and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 ( 16 M , 6 F ) prepubertal children with idiopathic short stature . Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml ( p < 0.001 ) , IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml ( p < 0.001 ) , alkaline phosphatase from 525+/-136 to 666+/-197 U/l ( p < 0.0001 ) , and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml ( p < 0.05 ) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation ( peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml , GH area under the curve during clonidine test 689+/-395 vs 761+/-468 , NS ) . Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation ( 118 % vs 136 % and 57 % vs 44 % , respectively ) . There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested . Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months ( 6 - 12 months ) ( -2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS , respectively ) . Zinc supplementation increased basal IGF-I , IGFBP-3 , alkaline phosphatase and osteocalcin without changing GH response to clonidine . Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test . These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3 , alkaline phosphatase and osteocalcin . Despite improvements in the above parameters , zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6 - 12 months follow-up Summary Background In north India , vitamin A deficiency ( retinol < 0·70 μmol/L ) is common in pre-school children and 2–3 % die at ages 1·0–6·0 years . We aim ed to assess whether periodic vitamin A supplementation could reduce this mortality . Methods Participants in this cluster-r and omised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres ( under-5 population 1 million ) in 72 administrative blocks . Groups of four neighbouring blocks ( clusters ) were cluster-r and omly allocated in Oxford , UK , between 6-monthly vitamin A ( retinol capsule of 200 000 IU retinyl acetate in oil , to be cut and dripped into the child 's mouth every 6 months ) , albendazole ( 400 mg tablet every 6 months ) , both , or neither ( open control ) . Analyses of retinol effects are by block ( 36 vs 36 clusters ) . The study spanned 5 calendar years , with 11 6-monthly mass-treatment days for all children then aged 6–72 months . Annually , one centre per block was r and omly selected and visited by a study team 1–5 months after any trial vitamin A to sample blood ( for retinol assay , technically reliable only after mid- study ) , examine eyes , and interview caregivers . Separately , all 8338 centres were visited every 6 months to monitor pre-school deaths ( 100 000 visits , 25 000 deaths at ages 1·0–6·0 years [ the primary outcome ] ) . This trial is registered at Clinical Trials.gov , NCT00222547 . Findings Estimated compliance with 6-monthly retinol supplements was 86 % . Among 2581 versus 2584 children surveyed during the second half of the study , mean plasma retinol was one-sixth higher ( 0·72 [ SE 0·01 ] vs 0·62 [ 0·01 ] μmol/L , increase 0·10 [ SE 0·01 ] μmol/L ) and the prevalence of severe deficiency was halved ( retinol < 0·35 μmol/L 6 % vs 13 % , decrease 7 % [ SE 1 % ] ) , as was that of Bitot 's spots ( 1·4 % vs 3·5 % , decrease 2·1 % [ SE 0·7 % ] ) . Comparing the 36 retinol-allocated versus 36 control blocks in analyses of the primary outcome , deaths per child-care centre at ages 1·0–6·0 years during the 5-year study were 3·01 retinol versus 3·15 control ( absolute reduction 0·14 [ SE 0·11 ] , mortality ratio 0·96 , 95 % CI 0·89–1·03 , p=0·22 ) , suggesting absolute risks of death between ages 1·0 and 6·0 years of approximately 2·5 % retinol versus 2·6 % control . No specific cause of death was significantly affected . Interpretation DEVTA contradicts the expectation from other trials that vitamin A supplementation would reduce child mortality by 20–30 % , but can not rule out some more modest effect . Meta- analysis of DEVTA plus eight previous r and omised trials of supplementation ( in various different population s ) yielded a weighted average mortality reduction of 11 % ( 95 % CI 5–16 , p=0·00015 ) , reliably contradicting the hypothesis of no effect . Funding UK Medical Research Council , USAID , World Bank ( vitamin A donated by Roche ) Abstract Objective . Many patients with nonerosive reflux disease ( NERD ) have insufficient relief on proton pump inhibitors ( PPIs ) . Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 ( TRPV1 ) antagonists . Aim . To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients . Material and methods . Enrolled patients had NERD and a partial PPI response ( moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks ' PPI therapy ) . Fourteen patients ( 21–69 years , 9 women ) were block-r and omized into this placebo-controlled , double-blinded , crossover study examining efficacy of a single dose ( 95 mg ) of AZD1386 . On treatment days , each participant 's esophagus was stimulated with heat , distension , and electrical current at teaching hospitals in Denmark and Sweden . Heat and pressure pain served as somatic control stimuli . Per protocol results were analyzed . Results . Of 14 r and omized patients , 12 were treated with AZD1386 . In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [ –3 % , 95 % confidence interval ( CI ) , –22;20 % ] , distension ( –11 % , 95 % CI , –28;10 % ) , or electrical current ( 6 % , 95 % CI , –10;25 % ) . Mean cutaneous heat tolerance increased by 4.9 ° C ( 95 % CI , 3.7;6.2 ° C ) . AZD1386 increased the maximum body temperature by a mean of 0.59 ° C ( 95 % CI , 0.40–0.79 ° C ) , normalizing within 4 h. Conclusions . AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response , whereas it increased cutaneous heat tolerance . TRPV1 does not play a major role in heat- , mechanically and electrically evoked esophageal pain in these patients . Clinical Trials.gov identifier : D9127C00002 Zn supplementation has shown inconsistent effects on respiratory morbidity in young children in developing countries . Few studies have focused on upper respiratory tract infection ( URTI ) , a frequent cause of morbidity in this group , and potential benefit from Zn supplementation or factors that influence its efficacy . We investigated the effects of Zn supplementation on URTI before and after vitamin A supplementation . This r and omised double-blinded controlled Zn supplementation study was conducted on 826 children aged 2 - 5 years . Placebo or Zn ( 10 mg/d ) was given in syrup daily for 4 months , with 200 000 IU vitamin A ( 60 mg retinol ) given to all children at 2 months . Health workers visited children every 3 d for compliance and morbidity information . We found that 84 % of children experienced URTI during the study . Zn supplementation reduced the percentage of days with URTI ( 12 % reduction ; P = 0·09 ) , with greater impact following vitamin A supplementation ( 20 % reduction ; P = 0·01 ) . Vitamin A supplementation was associated with a decreased number but an increased duration of URTI episodes . We conclude that Zn combined with vitamin A supplementation significantly reduced the percentage of days with URTI in a population of preschool Indonesian children with marginal nutritional status . The results suggest that vitamin A status modifies the efficacy of Zn supplementation on URTI This study is to clarify the impact of vitamin A or vitamin A combined with other micronutrients supplementation on anemia and growth in preschoolers . In the present study , a total of 290 preschoolers , aged 36 - 72 months old were r and omly assigned to 3 treatment groups : vitamin A ( A group ) , vitamin A plus zinc ( AZ group ) , and vitamin A combined with additional multiple-micronutrient ( AMM group ) . After 6-month supplementation , the height and height-for-age z-score gains of the AZ group were significantly higher than the other groups ; the weight gain of the AMM group was greater than the other groups . Compared with baseline values , the concentrations of hemoglobin , and zinc at the end significantly increased in all 3 groups . The incremental concentrations of hemoglobin in the AMM group were significant higher than in the other two groups . Furthermore , the incremental concentrations of serum retinol in the AMM group , and the increase in serum zinc concentrations in the AZ group were significantly higher , respectively , than in the other groups . These 3 kinds of supplements in the present study are effective in enhancing height gains and are effective in reducing the prevalence of anemia . Supplementation of zinc plus vitamin A is a better way for improving children 's height and height-for-age z-score . Vitamin A combined with multiple-micronutrient is more effective in improving the hemoglobin concentrations in preschool children OBJECTIVES : To assess the effect of zinc supplementation on susceptibility to S. mansoni reinfections among schoolchildren . DESIGN : R and omized , double-blind , placebo-controlled trial . SETTING AND SUBJECTS : 313 rural Zimbabwean schoolchildren ( 144 boys and 169 girls ) , 11–17 y ) . INTERVENTIONS : Supplementation with zinc ( 30 or 50 mg ) or placebo on schooldays for 12 months . Due to drought , a food programme was in operation during the last eight months of the study . OUTCOME MEASURES : S. mansoni and S. haematobium reinfection rates and intensities . RESULTS : There was no difference in reinfection rates between the zinc and placebo groups ( 25 vs 29 % , P=0.46 ) . However , the median intensity of S. mansoni reinfection , although low in both groups , was significantly lower in the zinc than in the placebo group ( 7 vs 13 eggs per gram of faeces , P=0.048 ) . No difference in either S. haematobium reinfection rates or intensities were seen . CONCLUSIONS : Zinc supplementation reduced the intensity of S. mansoni reinfections . Although the intensities of reinfection were very low , the finding probably reflects a biological effect of zinc that could be of public health importance in setting s with higher transmission . SPONSORSHIP : Danish International Development Assistance BACKGROUND : Zinc supplementation during diarrhea substantially reduces the incidence and severity of diarrhea . However , the effect of short-course zinc prophylaxis has been observed only in children > 12 months of age . Because the incidence of diarrhea is comparatively high in children aged 6 to 11 months , we assessed the prophylactic effect of zinc on incidence and duration of diarrhea in this age group . METHODS : In this r and omized , double-blind , placebo-controlled trial , we enrolled infants aged 6 to 11 months from an urban resettlement colony in Delhi , India , between January 1 , 2011 , and January 15 , 2012 . We r and omly assigned 272 infants to receive either 20 mg of zinc or a placebo suspension orally every day for 2 weeks . The primary outcome was the incidence of diarrhea per child-year . All analyses were done by intention-to-treat . RESULTS : A total of 134 infants in the zinc and 124 in the placebo groups were assessed for the incidence of diarrhea . There was a 39 % reduction ( crude incident rate ratio [ IRR ] 0.61 , 95 % confidence interval [ CI ] 0.53–0.71 ) in episodes of diarrhea , 39 % ( adjusted IRR 0.61 , 95 % CI 0.54–0.69 ) in the total number of days that a child suffered from diarrhea , and reduction of 36 % in duration per episode of diarrhea ( IRR 0.64 , 95 % CI 0.56–0.74 ) during the 5 months of follow-up . CONCLUSIONS : Short-course prophylactic zinc supplementation for 2 weeks may reduce diarrhea morbidity in infants of 6 to 11 months for up to 5 months , in population s with high prevalence of wasting and stunting Apparently healthy preschool children ( 46 boys , 52 girls ) aged 27 - 50 mo from low socioeconomic conditions who attended daycare centers in Santiago participated in a 14-mo long double-blind zinc supplementation trial . Unlike most previous studies , no additional inclusion criteria such as short stature or slow growth rate were considered . Subjects were pair matched according to sex and age and r and omly assigned to two experimental groups : the supplemented group , which received 10 mg Zn/d , and the placebo group . Selected anthropometric , clinical , dietary , biochemical , and functional indexes were determined at the beginning of the study and after 6 and 14 mo of intervention . Actual dietary zinc intake was 66 % of the recommended dietary allowance . Height gain after 14 mo was on average 0.5 cm higher in the supplemented group ( P = 0.10 ) . The response , however , was different between sexes . Boys from the supplemented group gained 0.9 cm more than those in the placebo group ( P = 0.045 ) . No effect was seen in girls . Although no significant differences were observed in the rest of the variables studied , trends ( 0.05 < P < 0.10 ) in the supplemented group compared with the placebo group for increased midarm muscle area in boys , improved response to tuberculin , and reduced rates of parasite reinfestation were noted . We conclude that in preschool children of low socioeconomic status , zinc is a limiting factor in the expression of growth potential BACKGROUND Despite ample food supplies , the incidence of childhood underweight and stunting remains high in Ug and a. Many factors contribute to this situation , but the role of low zinc intakes has not been adequately explored . OBJECTIVE Our objective was to study the effect of zinc supplementation on growth and body composition of preschool children by using the outcome measures of weight , height , and midupper arm circumference ( MUAC ) . DESIGN The study was r and omized , double-blind , placebo-controlled , parallel , and 8 mo long , and incorporated 6 mo of zinc supplementation . Children ( n = 153 ) aged 55.8 + /- 11.2 mo from 3 r and omly selected nursery schools of medium , low , and very low socioeconomic status in a suburb of Kampala took part . The intervention comprised 10 mg Zn ( as ZnSO4 ) or placebo daily in freshly prepared fruit juice , Monday to Friday inclusive . RESULTS Zinc supplementation increased MUAC by the end of the study ( P = 0.029 ) and led to greater weight gain in children from the school of medium socioeconomic status at 3 and 8 mo ( P = 0.019 and P = 0.038 , respectively ) . There was no effect on weight gain of the children from the other schools . Zinc supplementation had no influence on height . Infection rates ( of which 82 % were recorded as malaria ) were lower in the zinc-supplemented group than in control subjects ( P = 0.063 ) . CONCLUSIONS Zinc supplementation may counter the age-related decrease in MUAC often observed in preschool children in developing countries . The study provides evidence that zinc may not be the most limiting nutrient for weight gain in children of poor nutritional status , but may become so as nutritional status improves The effects of supplementation of the diets of 6- to 12-year-old children in a village near Shiraz in Iran with zinc plus iron or iron alone , together with the indispensable amino acids in the form of egg white protein , vitamins , minerals , and corn oil have been evaluated . Initially 48 of 59 children had zinc concentrations below the minimum found in well-nourished persons . Eight months of supplementation with zinc plus iron ( 20 mg daily of elemental zinc as carbonate and 20 mg ferrous iron as fumarate ) failed to stimulate growth or bone development or to bring about an increase in plasma zinc concentrations . However , supplementation with iron in the above amount was associated with an acceleration of growth in height and weight . The persistence of low concentrations of zinc in plasma and the failure of supplemental zinc to stimulate growth are attributed to the poor availability of both dietary and supplemental zinc result ing from sequestering action of fiber and phytate present in large amounts in the unleavened whole meal bread consumed by villagers . In addition , the results suggest that simultaneous administration of iron and zinc supplements may impair utilization of the metals BACKGROUND Several vitamin A supplementation trials have failed to improve the growth rate in children . Addition of zinc to vitamin A might result in enhanced growth . OBJECTIVE This study evaluated the effect on growth in children of simultaneous supplementation with zinc and vitamin A. DESIGN This was a r and omized , double-blind , placebo-controlled intervention trial . Six hundred fifty-three children aged 12 - 35 mo were r and omly assigned to 1 of 4 intervention groups : 20 mg Zn/d for 14 d ( Z group ) , 60000 retinol equivalents ( 200000 IU ) vitamin A on day 14 ( A group ) , zinc plus vitamin A ( ZA group ) , or placebo syrup and placebo capsule ( placebo group ) . Weight and length were measured at enrollment and again after 3 and 6 mo . RESULTS Gains in weight and length during the 6-mo follow-up period were not significantly different among the 4 groups by analysis of variance . Catch-up growth also did not differ significantly among the groups . The proportions of children whose weight-for-age z scores did not change or decreased were 57 % in the Z group , 46 % in the A group , 50 % in the ZA group , and 54 % in the placebo group ( NS ) . The proportions of children whose length-for-age z scores did not change or decreased were 42 % in the Z group , 48 % in the A group , 53 % in the ZA group , and 46 % in the placebo group ( NS ) . CONCLUSION Combined short-term zinc supplementation and a single dose of vitamin A has no significant effects on weight and length increments in children over a 6-mo period BACKGROUND Prebiotics are nondigestible food ingredients that stimulate the growth of Bifidobacterium and other bacteria in the gastrointestinal tract . Improved gastrointestinal and other health effects have been attributed to them . OBJECTIVE The objective of this study was to evaluate the effects of dietary supplementation with the prebiotic oligofructose with and without zinc on the prevalence of diarrhea in a community with a high burden of gastrointestinal and other infections . DESIGN Two consecutive r and omized , blinded , controlled clinical trials were performed in a shantytown community near Lima , Peru . The first trial compared an infant cereal supplemented with oligofructose ( 0.55 g/15 g cereal ) with nonsupplemented cereal . During the second trial , zinc ( 1 mg/15 g cereal ) was added to both oligofructose-supplemented and control cereals . RESULTS We enrolled 282 infants in the first trial and 349 in the second . In the first trial , mean ( + /- SD ) days of diarrhea were 10.3 + /- 9.6 in the nonsupplemented cereal group and 9.8 + /- 11.0 in the prebiotic-supplemented cereal group ( P = 0.66 ) . In the second trial , mean days of diarrhea were 10.3 + /- 8.9 in the group consuming cereal fortified only with zinc and 9.5 + /- 8.9 in the group consuming cereal containing both zinc and prebiotics ( P = 0.35 ) . Postimmunization titers of antibody to Haemophilus influenzae type B were similar in all groups , as were gains in height , visits to clinic , hospitalizations , and use of antibiotics . CONCLUSIONS Cereal supplemented with prebiotics was not associated with any change in diarrhea prevalence , use of health care re sources , or response to H. influenzae type B immunization . Infants and young children who continue to breast-feed may not benefit from prebiotic supplementation BACKGROUND In developing countries , incomplete resolution of anemia with iron supplementation is often attributed to poor compliance or inadequate duration of supplementation , but it could result from deficiencies of other micronutrients . OBJECTIVE Our objective was to assess children 's hematologic response to supervised , long-term iron supplementation and the relation of this response to other micronutrient deficiencies , anthropometry , morbidity , and usual dietary intake . DESIGN Rural Mexican children aged 18 - 36 mo ( n = 219 ) were supplemented for 12 mo with either 20 mg Fe , 20 mg Zn , both iron and zinc , or placebo . Children were categorized as iron-unsupplemented ( IUS ; n = 109 ) or iron supplemented ( IS ; n = 108 ) . Hemoglobin , hematocrit , mean corpuscular volume , mean cell hemoglobin , plasma concentrations of micronutrients that can affect hematopoiesis , anthropometry , and diet were assessed at 0 , 6 , and 12 mo ; morbidity was assessed biweekly . RESULTS At baseline , 70 % of children had low hemoglobin ( < /=115 g/L ) , 60 % had low hematocrit , 48 % were ferritin deficient , 10 % had deficient and 33 % had low plasma vitamin B-12 concentrations , 29 % had deficient vitamin A concentrations , and 70 % had deficient vitamin E concentrations . Iron supplementation increased ferritin from 11 + /- 14 microg/L at baseline to 31 + /- 18 microg/L after 6 mo ( P < 0.001 ) and 41 + /- 17 microg/L after 12 mo . However , anemia persisted in 30 % and 31 % of supplemented children at 6 and 12 mo , respectively , and was not significantly different between the IUS and IS groups at 12 mo . Initial plasma vitamin B-12 , height-for-age , and dietary quality predicted the hematopoietic response to iron . CONCLUSION Lack of hemoglobin response to iron was associated with indicators of chronic undernutrition and multiple micronutrient deficiencies The effects of zinc , 40 mg daily , given as zinc carbonate , in combination with a supplement of egg-white protein ( 10 g daily ) , corn oil , minerals , and vitamins to fulfill many requirements , were evaluated in 1 3-year-old prepubertal village schoolboys in southern Iran . Thirty-five of the 49 boys participating had subnormal plasma zinc concentrations . The boys continued their usual diets in which unleavened wholemeal wheat bread rich in phytate was the main staple . A similar group serving as controls received the same supplements without zinc . A second control group received only the protein supplement . Observations were continued for 18 months . Significantly increased heights , weights , and bone ages occurred in those receiving the supplementary zinc , despite zinc concentrations in plasma that remained subnormal throughout the study in most of the boys . These gains occurred mainly during the final 12 months of supplementation . Serum total protein and albumin concentrations were moderately decreased initially in approximately 757 of the boys . Concentrations of total protein became normal during the first 3 months of treatment . The results demonstrate a clearly defined stimulus to growth brought about by supplementation with zinc when adequate amounts are given . Contrary to findings in a previous study , no statistically significant stimulation of gonadal development was detected in the zinc-supplemented group compared with the controls . However , a tendency toward accelerated sexual development in the zinc supplemented boys was evident . Am . I Clin . Nutr . 27 : 112 - 121 , 1974 BACKGROUND The Third National Health and Nutrition Examination Survey suggested some Mexican American children are at risk of zinc deficiency . OBJECTIVE We measured the effects of zinc and micronutrients or of micronutrients alone on indexes of cell-mediated immunity and antiinflammatory plasma proteins . DESIGN Subjects ( n = 54 ) aged 6 - 7 y were r and omly assigned and treated in double-blind fashion in equal numbers with 20 mg Zn ( as sulfate ) and micronutrients or with micronutrients alone 5 d/wk for 10 wk . RESULTS Before treatment the mean + /- SD plasma zinc was 14.9 + /- 1.7 micromol/dL and the range was within the reference ; hair zinc was 1.78 + /- 0.52 micromol/g and 41.6 % were < or = 1.68 micromol/g ; serum ferritin was 25.7 + /- 18.6 microg/L and 50.0 % were < or = 20 microg/L. The zinc and micronutrients treatment increased the lymphocyte ratios of CD4(+ ) to CD8(+ ) and of CD4(+)CD45RA(+ ) to CD4(+)CD45RO(+ ) , increased the ex vivo generation of interleukin-2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) , decreased the generation of interleukin-10 ( IL-10 ) , and increased plasma interleukin-1 receptor antagonist ( sIL-1ra ) and soluble tumor necrosis factor receptor 1 ( sTNF-R1 ) . Micronutrients alone increased the ratio of CD4(+ ) to CD8(+ ) but not of CD4(+)CD45RA(+ ) to CD4(+)CD45RO(+ ) , increased IFN-gamma but had no effect on IL-2 or IL-10 , and increased sIL-1ra but not sTNF-R1 . Efficacy of zinc and micronutrients was greater than micronutrients alone for all indexes except the ratio of CD4(+ ) to CD8(+ ) , which was affected similarly . CONCLUSIONS Before treatment , concentrations of hair zinc in 41.6 % of subjects and serum ferritin in 50 % were consistent with the presence of zinc deficiency . The greater efficacy of the zinc and micronutrients treatment compared with micronutrients alone supports this interpretation Persistent diarrhea ( PD ) and dysentery ( DD ) account for most diarrhea-associated deaths among children in developing countries . Zinc deficiency can cause stunting and impaired immune function , both of which are risk factors for these diarrheal illnesses . We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based , double-blind r and omized trial in children 6 - 35 mo of age . Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group ( 3.61 vs. 0.009 mumol . L-1 ) , indicated successful supplementation . The overall reductions in the zinc supplemented group of 21 % in the incidence of PD ( 95 % CI -6 to 42 % ) and 14 % in the incidence of dysentery ( 95 % CI -15 to 36 % ) were not significant . There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD . In the zinc-supplemented group compared with the control group , the incidence of PD was reduced by 73 % ( P < 0.05 ; 95 % CI 34 to 91 % ) in children with a baseline zinc < 7.65 mumol . L-1 and by 49 % ( P < 0.05 ; 95%CI 24 to 66 % ) in children > 11 mo of age . Zinc supplementation result ed in a 38 % ( P < 0.05 95%CI 8 to 59 % ) reduction in the incidence of DD in boys . There was no effect on PD among children 6 - 11 mo old or on DD in girls . In conclusion , zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc , as well as on dysentery in boys . These findings may have important implication s for reducing diarrhea-related morbidity and mortality BACKGROUND Zinc deficiency limits the bioavailability of vitamin A. Because zinc and vitamin A deficiency often coexist in malnourished children , simultaneous zinc and vitamin A supplementation may improve the vitamin A deficiency in these children . OBJECTIVE A r and omized , double-blind , placebo-controlled intervention trial was conducted to evaluate whether combining zinc and vitamin A supplementation would improve the biochemical indexes of vitamin A nutriture . DESIGN Children aged 12 - 35 mo were r and omly assigned to 1 of 4 intervention groups : 20 mg Zn/d for 14 d ( Z group ) , 60000 retinol equivalents ( 200000 IU ) vitamin A on day 14 ( A group ) , zinc plus vitamin A ( ZA group ) , or placebo syrup and placebo capsule ( placebo group ) . Venous blood was drawn at enrollment and on day 21 . RESULTS Mean serum retinol concentrations were not significantly different between the A and ZA groups . Among vitamin A-deficient children , the proportion of children who remained vitamin A deficient ( serum retinol < 0.7 micromol/L ) after supplementation was 40.6 % in the Z group , 37.5 % in the A group , and 47.0 % in the placebo group ; only 13.3 % in the ZA group remained vitamin A deficient ( P < 0.05 compared with the placebo group ) . The proportion of children whose retinol binding protein concentrations remained low was significantly lower in the ZA group than in the other groups ( P < 0.05 ) . CONCLUSION Combined zinc and vitamin A supplementation improves vitamin A nutriture in vitamin A-deficient children BACKGROUND Undernourished children have poor levels of development that benefit from stimulation . Zinc deficiency is prevalent in undernourished children and may contribute to their poor development . OBJECTIVE We assessed the effects of zinc supplementation and psychosocial stimulation given together or separately on the psychomotor development of undernourished children . DESIGN This was a r and omized controlled trial with 4 groups : stimulation alone , zinc supplementation alone , both interventions , and control ( routine care only ) . Subjects were 114 children aged 9 - 30 mo and below -1.5 z scores of the National Center for Health Statistics weight-for-age references who were recruited from 18 health clinics . Clinics were r and omly assigned to receive stimulation or not ; individual children were r and omly assigned to receive zinc or placebo . The stimulation program comprised weekly home visits during which play was demonstrated and maternal-child interactions were encouraged . The supplementation was 10 mg Zn as sulfate daily or placebo . Development ( assessed by use of the Griffiths Mental Development Scales ) , length , and weight were measured at baseline and 6 mo later . Weekly morbidity histories were taken . RESULTS Significant interactions were found between zinc supplementation and stimulation . Zinc benefited the developmental quotient only in children who received stimulation , and benefits from zinc to h and and eye coordination were greater in stimulated children . Zinc supplementation alone improved h and and eye coordination , and stimulation alone benefited the developmental quotient , hearing and speech , and performance . Zinc supplementation also reduced diarrheal morbidity but did not significantly improve growth . CONCLUSION Zinc supplementation benefits development in undernourished children , and the benefits are enhanced if stimulation is also provided To determine whether zinc deficiency might be involved in the failure to thrive observed in undernourished Vietnamese children , we assessed growth , incidence of infections , and circulating insulin-like growth factor I ( IGF-I ) concentrations in a double-blind study of zinc supplementation . Growth-retarded children ( n=146 ) aged 4 - 36 mo were paired according to age , sex , commune , Z scores for weight ( WAZ ) and for height ( HAZ ) , and number of siblings , and were r and omly assigned to receive either 153 micromol ( 10 mg ) Zn/d or a placebo for 5 mo . Weight , height , and episodes of infection were recorded each month and plasma IGF-I was measured 1 and 5 mo after the start of zinc supplementation . Multiple-linear-regression analysis for paired data showed that zinc supplementation increased weight ( + 0.5 + /- 0.1 kg ; P<0.001 ) and height ( + 1.5+/-0.2 cm ; P<0.001 ) after 5 mo compared with placebo treatment . The relative risk of infectious episodes in the zinc-treated subjects was reduced 3-fold for diarrhea ( P=0.012 ) and 2.5-fold for respiratory infections ( p=0.057 ) . The probability of having at least two episodes of diarrhea or respiratory infection was 2.9- and 3.2-fold lower , respectively , in zinc-treated subjects between 1 and 5 mo ( P=0.018 ) , whereas they did not change in placebo-treated subjects ( P-0.584 ) . After 1 mo , IGF-I concentration ( -x+/-SD ) in zinc-treated subjects was 2.8+/-0.3 nmol/L compared with 1.9+/-0.2 nmol/L in placebo-treated subjects ( P=0.021 ) . After 5 mo , the values were 3.4+/-0.5 nmol/L ( zinc-treated ) and 2.0+/-0.3 nmol/L ( placebo-treated ; P=0.044 ) . Our study suggests that zinc deficiency may limit growth in nutritionally deprived children . Because the increase in growth velocity result ing from zinc supplementation was associated with increased plasma IGF-I concentrations , we suggest that the growth-stimulating effect of zinc might be mediated through changes in circulating BACKGROUND Iron and zinc deficiency are prevalent during infancy in low-income countries . OBJECTIVES The objectives were to examine whether a weekly supplement of iron , zinc , iron+zinc , or a micronutrient mix ( MM ) of 16 vitamins and minerals would alter infant development and behavior . DESIGN The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies . Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment ( HOME ) scale . In this double-blind trial , the infants were r and omly assigned to 1 of 5 treatment conditions : iron ( 20 mg ) , zinc ( 20 mg ) , iron+zinc , MM ( 16 vitamins and minerals , including iron and zinc ) , or riboflavin weekly from 6 to 12 mo . Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group , with control for maternal education , HOME score , months breastfed , anemia , growth at 6 mo , and change in growth from 6 to 12 mo . RESULTS Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development . Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement . Two-thirds of the infants were mildly anemic , no treatment effects on hemoglobin concentration were observed , and hemoglobin was not associated with measures of development or behavior . CONCLUSION The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together BACKGROUND Multiple studies have shown the benefits of zinc supplementation among young children in high-risk population s. However , the optimal dose and safe upper level of zinc have not been determined . OBJECTIVES The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration , morbidity , and growth of young children ; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status ; and to determine whether any adverse effects are alleviated by providing copper with zinc . DESIGN This r and omized , double-masked , community-based intervention trial was conducted in 631 Ecuadorian children who were 12 - 30 mo old at baseline and who had initial length-for-age z scores < -1.3 . Children received 1 of 5 daily supplements for 6 mo : 3 , 7 , or 10 mg Zn as zinc sulfate , 10 mg Zn + 0.5 mg Cu as copper sulfate , or placebo . RESULTS The change in plasma zinc concentration from baseline was positively related to the zinc dose ( P < 0.001 ) . Zinc supplementation , including doses as low as 3 mg/d , reduced the incidence of diarrhea by 21 - 42 % ( P < 0.01 ) . There were no other significant group-wise differences . CONCLUSIONS Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population . There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status . The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children BACKGROUND Zinc supplementation decreases morbidity from infections and increases growth of stunted children , but there is little information on functional responses to zinc delivered in fortified foods . OBJECTIVE The aim was to examine the effects of zinc fortification on the growth , morbidity from infections , and plasma zinc concentrations of young children . DESIGN We compared the physical growth , morbidity , and micronutrient status of 6 - 8-mo-old Peruvian children with initial length-for-age z score ( LAZ ) < -0.50 who were r and omly assigned to receive one of the following treatments daily for 6 mo : 1 ) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin ( MV ) supplement between meals ( control group ) , 2 ) the same porridge and MV with 3 mg Zn added to the supplement dose ( ZnSuppl group ) , or 3 ) the porridge with added zinc ( 150 mg/kg dry weight ) and MV without zinc ( ZnFort group ) . RESULTS The children consumed a mean of 22 - 26 g dry porridge/d and 96 % of the possible MV doses . After adjustment for small baseline differences in socioeconomic status and morbidity , no significant differences in weight or length increments were observed between the groups , even among the subset with an initial LAZ < -1.5 , and no significant differences in the rates of common illnesses were observed . Mean plasma zinc concentrations decreased in the control group ( -3.9 microg/dL ) , increased in the ZnSuppl group ( 4.3 microg/dL ) , and did not change significantly in the ZnFort group ( -1.5 microg/dL ; P < 0.001 for group-wise comparison ) . CONCLUSIONS Provision of additional zinc , either in an aqueous supplement or a fortified porridge , did not significantly affect the children 's physical growth or morbidity from infections , possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate . Additional studies of the functional effect of zinc-fortified foods are needed in population s that are known to respond to zinc supplements Zinc deficiency has been associated with growth deficits , reduced dietary intake and appetite , and has been hypothesized to result in reduced activity . This r and omized , double-blind , placebo-controlled study examined whether 10 mg of oral zinc as zinc sulfate , given daily for up to 7 mo , affected activity patterns of 85 Guatemalan infants recruited at 6 - 9 mo of age . Infant activity was assessed by time sampling-observation method at 10-min intervals during a 12-h data collection period , at base line , 3 and 7 mo follow-up . Motor development and the percentage of time infants were observed in various positions ( being carried , lying down , sitting , crawling , st and ing or walking ) and engaged in various activities ( eating , sleeping , resting , crying/whining or playing ) were compared by treatment group . No differences in motor development were observed by treatment group . However , at follow-up 2 ( after 7 mo of supplementation ) , zinc-supplemented infants were significantly more frequently observed sitting up compared with lying down , and were playing during 4.18 + /- 1.95 % ( P < 0.05 ) more observations than unsupplemented infants . They were also somewhat less likely to be observed crying or whining ( P < 0.10 ) compared with those receiving the placebo . These effects are independent of other factors including infant age , motor development , sex , maternal education , family socioeconomic status and nutritional status at base line . Further research must be conducted to determine the long-term developmental importance of these differences in activity patterns associated with zinc supplementation in this setting The exact mechanism whereby zinc influences growth is unknown , although it has been postulated that zinc may stimulate appetite and energy intake or enhance fat-free mass ( FFM ) accrual directly . We compared energy intake , reported appetite , and body composition of 6- to 8-mo-old Peruvian children with initial length-for-age Z-score ( LAZ ) < -0.5 SD who were r and omly assigned to receive daily for 6 mo : 1 ) 3 mg/d zinc in a liquid supplement ; 2 ) 3 mg/d zinc in a fortified porridge ; or 3 ) no extra zinc in either the supplement or porridge . There were no group-wise differences in changes in dietary energy intakes or body composition or in the prevalence of reported poor appetite . However , among children with an initial LAZ less than the median ( -1.1 SD ) , those who received zinc as a liquid supplement had a 0.41 kg greater increase in FFM than those who did not receive zinc ( P < 0.05 ) . We concluded that daily provision of 3 mg of supplemental zinc did not affect energy intake or reported appetite . Among children with initial mild-to-moderate stunting , those who received the zinc supplement had a greater increase in FFM than those who did not receive additional zinc . It is possible that the growth-restricted children were more likely to be zinc deficient and that FFM accrual may be an early growth response to supplemental zinc . Zinc supplements may be more efficacious than the same dose of zinc provided in fortified food ; therefore , further research is needed on the optimal level of zinc fortification that will result in improved health outcomes in population s with high rates of zinc deficiency The impact of zinc supplementation on the growth and body composition of Guatemalan infants was assessed in a community-based , double-blind intervention trial . Infants aged 6 - 9 mo were assigned r and omly to receive 4 mL of a beverage containing 10 mg of zinc as zinc sulfate ( n = 45 ) or a placebo ( n = 44 ) daily ( 7 d/wk ) for an average of 6.9 mo . The children 's weight , length , mid-upper arm and head circumferences , and triceps skinfolds were measured at baseline and at 1 - 2 mo intervals until the end of supplementation . Midarm muscle area ( MMA ) was derived from the mid-upper arm circumference and triceps skinfolds measurements . Maternal anthropometry and family socioeconomic and demographic characteristics also were obtained . Zinc supplementation was associated with an overall increase of 0.61 cm2 in MMA ( P = 0.02 ) . Children who received zinc supplements had a mean length increment that was 0.75 cm greater than those who did not ( P = 0.12 ) . However , there was a significant interaction between treatment group and initial length-for-age status ( P = 0.04 ) , such that supplemented children who were stunted at baseline ( length-for-age Z score less than -2 ) gained 1.40 cm more than stunted children who received the placebo . We conclude that zinc supplementation of these rural Guatemalan infants during 6 . 9 mo increased accretion of fat-free mass and enhanced the linear growth of those who were stunted at baseline . Further research is required to determine whether zinc supplementation during longer periods of time may achieve larger and more generalized effects on physical growth Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation . The impact of daily zinc supplementation administered with iron plus folic acid ( IFA ) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated . In a double blind cluster-r and omized controlled trial , 94,359 subjects aged 1 - 23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment . The intervention group tablet contained 10 mg of elemental zinc , 12.5 mg of iron , and 50 microg of folic acid . The control group tablets were similar except that they contained a placebo for zinc . Infants aged < 6 mo were administered half a tablet , and those older received 1 tablet dissolved in breast milk or water . Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals . Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo . The overall death rates did not differ significantly between the 2 groups when adjusted for cluster r and omization ( hazard ratio = 1.02 , 95 % CI 0.87 , 1.19 ) . Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates ( overall rate ratio = 1.08 , 95 % CI 0.98 , 1.19 ; diarrhea-specific rate ratio = 1.15 , 95 % CI 0.99 , 1.34 ; or pneumonia-specific rate ratio = 1.09 , 95 % CI 0.94 , 1.25 ) . The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron , where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity . Future research should address iron and zinc interaction effects on important functional outcomes INTRODUCTION Anemia is the most prevalent nutritional deficiency in the world . Attempts to improve iron indexes are affected by deficiency of and interaction between other micronutrients . OBJECTIVE Our goal was to assess whether zinc added to iron treatment alone or with vitamin A improves iron indexes and affects diarrheal episodes . DESIGN This was a r and omized , placebo-controlled , double-blind trial conducted in Peru . Anemic children aged 6 - 35 mo were assigned to 3 treatment groups : ferrous sulfate ( FS ; n = 104 ) , ferrous sulfate and zinc sulfate ( FSZn ; n = 109 ) , and ferrous sulfate , zinc sulfate , and vitamin A ( FSZnA ; n = 110 ) . Vitamin A or its placebo was supplied only once ; iron and zinc were provided under supervision > /=1 h apart 6 d/wk for 18 wk . RESULTS The prevalence of anemia was 42.97 % . The increase in hemoglobin in the FS group ( 19.5 g/L ) was significantly less than that in the other 2 groups ( 24.0 and 23.8 g/L in the FSZn and FSZnA groups , respectively ) . The increase in serum ferritin in the FS group ( 24.5 mug/L ) was significantly less than that in the other 2 groups ( 33.0 and 30.8 mug/L in the FSZn and FSZnA groups , respectively ) . The median duration of diarrhea and the mean number of stools per day was significantly higher in the FS group than in other 2 groups ( P < 0.005 ) . CONCLUSION Adding zinc to iron treatment increases hemoglobin response , improves iron indexes , and has positive effects on diarrhea . No additional effect of vitamin A was found BACKGROUND Evidence for an effect of zinc supplementation on growth and morbidity in very young infants in developing countries is scarce and inconsistent . OBJECTIVE We assessed the effect of zinc supplementation on growth and morbidity in poor Bangladeshi infants aged 4 - 24 wk . DESIGN Infants from Dhaka slums were enrolled at 4 wk of age and r and omly assigned to receive 5 mg elemental Zn/d ( n = 152 ) or placebo ( n = 149 ) until 24 wk of age . They were followed weekly for information on compliance and morbidity ; anthropometric measurements were performed monthly . Serum zinc was assessed at baseline and at 24 wk of age . RESULTS At 24 wk of age , serum zinc concentrations were higher in the zinc than in the placebo group ( 13.3 + /- 3.8 and 10.7 + /- 2.9 micro mol/L , respectively ; P < 0.001 ) . Significantly greater weight gains were observed in the zinc than in the placebo group for 43 infants who were zinc deficient ( < 9.18 micro mol/L ) at baseline ( 3.15 + /- 0.77 and 2.66 + /- 0.80 kg , respectively ; P < 0.04 ) . In the other infants , no significant differences were observed in mean weight and length gains during the study period . Zinc-deficient infants showed a reduced risk of incidence of acute lower respiratory infection after zinc supplementation ( relative risk : 0.30 ; 95 % CI : 0.10 , 0.92 ) ; among the non-zinc-deficient infants there were no significant differences between treatment groups . CONCLUSIONS Zinc-deficient Bangladeshi infants showed improvements in growth rate and a reduced incidence of acute lower respiratory infection after zinc supplementation . In infants with serum zinc concentrations > 9.18 micro mol/L , supplementation improved only biochemical zinc status BACKGROUND It has been documented that growth patterns differ between breastfed and formula-fed infants . Some investigators have suggested that these differences may be related to differences in zinc nutriture . OBJECTIVE The objective of this study was to examine the effect of zinc supplementation on growth , morbidity , and motor development in healthy , term , breastfed infants . DESIGN We conducted a r and omized double-blind intervention comparing zinc supplementation ( 5 mg/d as zinc sulfate ) with placebo in breastfed infants aged 4 - 10 mo . Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo . Morbidity data were collected weekly . RESULTS Eighty-five infants were enrolled , and 70 completed the study . The baseline characteristics , attained weight or length at 10 mo , growth velocity , gross motor development , and morbidity did not differ significantly between groups , even after control for potentially confounding variables . CONCLUSIONS The dietary zinc intake of these breastfed infants appeared to be adequate , given that zinc supplementation did not affect growth , development , or risk of infection ( although sample size for detection of differences in development or infection was limited ) . Previously described differences in growth between breastfed and formula-fed infants in such population s do not appear to be due to differences in zinc nutriture BACKGROUND The coexistence of multiple micronutrient deficiencies is a widespread public health problem in many regions of the world . Interactions between zinc deficiency and vitamin A metabolism have been reported but no longitudinal studies have evaluated the effect of iron deficiency on vitamin A. OBJECTIVE The objective of this study was to investigate the effect of supplementation with iron , zinc , or both on vitamin A and its metabolically related proteins retinol binding protein ( RBP ) and transthyretin . DESIGN The study was a longitudinal , double-blind , placebo-controlled trial in which 219 rural Mexican children aged 18 - 36 mo were r and omly assigned to receive 20 mg Zn/d , 20 mg Fe/d , 20 mg Zn/d plus 20 mg Fe/d , or placebo . RESULTS Six months after supplementation , plasma retinol increased in all supplemented groups . Compared with placebo , zinc supplementation was associated with significantly higher plasma retinol and transthyretin but the increase in RBP was not significant . Iron supplementation significantly increased plasma retinol , RBP , and transthyretin . Supplementation with zinc plus iron significantly increased plasma retinol but not RBP or transthyretin . Children deficient in zinc , iron , or vitamin A ( as indicated by nutrient plasma concentration ) at the beginning of the study had a significantly greater increase in retinol than did children with adequate nutrient status . CONCLUSIONS Supplementation with zinc , iron , or both improved indicators of vitamin A status . The results of this study agree with previous observations of a metabolic interaction between zinc and vitamin A and suggest an interaction between iron and vitamin A metabolism The effects of a zinc supplement on growth velocity were assessed in a double-blind , pair-matched controlled study in 40 children with low growth percentiles . Participants were low-income Spanish-American children , 2 to 6 yr of age with heights below the 10th percentile and nutritional or biochemical evidence of zinc deficiency . After 1 yr , the mean height velocity of the zinc-supplemented children was slightly , but significantly ( p less than 0.005 ) , greater than that of control children . This effect was primarily due to a greater height achievement of the zinc-supplemented boys . Increases in height-for-age z-scores were also significant for the supplemented males ( p less than 0.001 ) and for the combined sexes ( p less than 0.05 ) . This study indicates the existence of a growth-limiting syndrome of mild zinc deficiency in children Changes in growth , body composition , and zinc indexes were evaluated after 25 wk in a double-blind zinc-supplementation study of 162 periurban Guatemalan children aged 81.5 + /- 7.0 mo ( mean + /- SD ) . Children receiving the zinc supplement ( 10 mg Zn/d as amino acid chelate ) for 90.1 + /- 9.2 d had higher mean fasting plasma zinc ( 16.2 + /- 2.9 vs 14.9 + /- 2.1 mumol/L , P < 0.01 ) , a greater increase in median triceps skinfold Z score ( 0.50 vs 0.38 , P < 0.05 ) , and a smaller deficit in median midarm circumference ( MAC ) Z score ( -0.03 vs -0.20 , P < 0.05 ) compared with the placebo group . Initial hair zinc classified as < 1.68 and > 1.68 mumol/g was the only laboratory variable that explained some of the variance in final Z scores of midarm-muscle area ( P < 0.05 ) and MAC ( P < 0.01 ) . Children responded to the zinc supplement with changes in indexes of body composition rather than growth BACKGROUND Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients , but knowledge of their potential interactions when given together is insufficient . OBJECTIVE The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe + 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Venous blood sample s were collected at the start and end of the study . Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood sample s available for analysis . RESULTS Baseline prevalences of anemia , iron deficiency anemia ( anemia and low serum ferritin ) , and low serum zinc ( < 10.7 micromol/L ) were 41 % , 8 % , and 78 % , respectively . After supplementation , the Fe group had higher hemoglobin ( 119.4 compared with 115.3 g/L ; P < 0.05 ) and serum ferritin ( 46.5 compared with 32.3 microg/L ; P < 0.05 ) values than did the Fe+Zn group , indicating an effect of zinc on iron absorption . The Zn group had higher serum zinc ( 11.58 compared with 9.06 micromol/L ; P < 0.05 ) than did the placebo group . There was a dose effect on serum ferritin in the Fe and Fe+Zn groups , but at different levels . There was a significant dose effect on serum zinc in the Zn group , whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d . CONCLUSION Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status , with evidence of an interaction between iron and zinc when the combined supplement was given A community-based , double-blind , r and omized trial was conducted in a population of low socioeconomic status in urban India to determine whether daily zinc supplementation reduces the incidence and prevalence of acute diarrhea , especially in those with zinc deficiency . Children 6 - 35 mo of age were r and omly assigned to zinc ( n = 286 ) and control ( n = 293 ) groups and received a supplement daily for 6 mo . Zinc gluconate ( 10 mg elemental Zn ) was given , with both zinc and control groups also receiving multivitamins . The primary outcome measures determined by home visits every fifth day and physician examinations were the number of acute diarrheal episodes ( incidence ) and total diarrheal days ( prevalence ) . Zinc supplementation had no effect in children 6 - 11 mo old . In children aged > 11 mo there was significantly less diarrhea in the zinc group . In boys > 11 mo old , supplementation result ed in a 26 % ( 95 % CI : 13 % , 38 % ) lower diarrheal incidence and a 35 % ( 95 % CI : 20 % , 50 % ) lower prevalence . In zinc-supplemented girls > 11 mo of age , the incidence was 17 % ( 95 % CI : 2 % , 30 % ) lower and the prevalence was 19 % ( 95 % CI : 4 % , 47 % ) lower . Overall , zinc supplementation result ed in a 17 % ( 95 % CI : 1 % , 30 % ) lower diarrheal incidence in children with plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33 % ( 95 % CI : 6 % , 52 % ) lower incidence in children with concentrations < 50 mumol/L. In conclusion , zinc supplementation had a significant effect on acute diarrheal morbidity in children > 11 mo old and in children with low plasma zinc concentrations Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children , albeit inconsistently . In this community-based , r and omized double-blind trial , iron+folic acid ( FeFA ) ( 12.5 mg Fe + 50 mug folic acid ) , zinc ( Zn ) ( 10 mg ) , and iron+folic acid+zinc ( FeFA+Zn ) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba , Zanzibar . The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5 - 11 mo at the start of supplementation . Treatment effects on changes in hemoglobin ( Hb ) and zinc protoporphyrin ( ZPP ) and height-for-age ( HAZ ) and weight-for-age ( WAZ ) Z scores were evaluated using linear regression . Attained motor milestone was recorded every 2 wk for 1 y. Hb , ZPP , HAZ , and WAZ were measured at baseline and after 6 mo of treatment . FeFA with or without Zn reduced the time it took for children to walk assisted . Children who received any iron walked unassisted sooner than those who received no iron [ median difference approximately 15 d , P = 0.035 , risk ratio ( RR ) = 1.28 , 95 % CI = 1.02 , 1.61 ] and this effect was stronger in those who had iron deficiency anemia ( IDA ) at baseline ( median difference was approximately 30 d ; P = 0.002 ; RR = 1.68 ; 95 % CI = 1.21 , 2.32 ) . FeFA alone and Zn alone improved Hb and ZPP compared with placebo . There were no significant treatment effects on changes in HAZ or WAZ . The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin , but were not mediated through improvements in growth Because infants and young children in many developing countries are deficient in both iron and zinc , and zinc can affect iron metabolism , evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority . This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron , zinc , and copper status in Bangladeshi infants . In a double-blind , r and omized , controlled community trial , 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin ( control , n = 82 ) or 1 mg riboflavin + 20 mg iron ( n = 83 ) , 20 mg zinc ( n = 83 ) , or both ( n = 85 ) for 6 mo . Hemoglobin , serum ferritin , transferrin receptor , zinc , and copper concentrations were measured at baseline and at the end of intervention . Serum Zn increased in both groups receiving zinc ; the increase was greatest among children with low baseline serum zinc concentration . Iron status indicators did not differ among the groups before or after 6 mo of supplementation . Supplementation with either zinc or iron decreased serum copper after 6 mo . Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children . However , the dosing regimen may not have been adequate to achieve the desired biochemical effects Iron deficiency is prevalent in children and infants worldwide . Zinc deficiency may be prevalent , but data are lacking . Both iron and zinc deficiency negatively affect growth and psychomotor development . Combined iron and zinc supplementation might be beneficial , but the potential interactions need to be verified . In a r and omized , placebo-controlled trial using 2 x 2 factorial design , 609 Thai infants aged 4 - 6 mo were supplemented daily with 10 mg of iron and /or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth . Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined . Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined . Baseline iron deficiency was very low , and iron deficiency anemia was almost nil . After supplementation , prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc . Serum zinc was higher in infants receiving zinc ( 16.7 + /- 5.2 micromol/L ) , iron and zinc ( 12.1 + /- 3.8 micromol/L ) or iron alone ( 11.5 + /- 2.5 micromol/L ) than in the placebo group ( 9.8 + /- 1.9 micromol/L ) . Iron and zinc interacted to affect iron and zinc status , but not hemoglobin . Iron supplementation had a small but significant effect on ponderal growth , whereas zinc supplementation did not . To conclude , in Thai infants , iron supplementation improved hemoglobin , iron status , and ponderal growth , whereas zinc supplementation improved zinc status . Overall , for infants , combined iron and zinc supplementation is preferable to iron or zinc supplementation alone BACKGROUND Zinc supplements reduce childhood morbidity in population s in whom zinc deficiency is common . In such population s , deficiencies in other micronutrients may also occur . OBJECTIVE The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children 's morbidity and physical growth . DESIGN Two hundred forty-six children aged 6 - 35 mo with persistent diarrhea were r and omly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone ( Zn ; n = 81 ) , zinc plus vitamins and other minerals at 1 - 2 times recommended daily intakes ( Zn+VM ; n = 82 ) , or placebo ( n = 83 ) for approximately 6 mo after the diarrhea episode ended . Morbidity information was collected on weekdays . Weight , length , and other anthropometric indicators were measured monthly , and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo . RESULTS Supplement consumption was high ( approximately 90 % ) in all groups , although slightly more vomiting was reported in the Zn+VM group ( P < 0.0001 , analysis of variance ) . The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups ( 6.1 , 27.3 , and 16.2 micro g/dL in the placebo , Zn , and Zn+VM groups , respectively ; P < 0.0001 , analysis of variance ) . The Zn group had fewer episodes of diarrhea , dysentery , and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group ( P = 0.05 ) . No significant effects of supplementation on growth were observed . CONCLUSION Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone Previous surveys suggested that young children in Northeast Thail and may benefit from vitamin A and /or zinc supplementation . One hundred thirty-three children aged 6 - 13 y with marginal plasma retinol ( less than 1.05 mumol/L ) and Zn ( less than 12.2 mumol/L ) concentrations participated in a double-blind study . They were r and omly assigned and supplemented with either zinc ( 25 mg/d ) , vitamin A ( 1500 RE/d ) , zinc plus vitamin A , or placebo for 6 mo . Biochemical indices of vitamin A ( plasma vitamin A , retinol-binding protein ) and zinc status ( plasma zinc , alkaline phosphatase ) increased significantly . The children had adequate liver stores of vitamin A ( relative dose response less than 20 % ) . Zinc supplementation result ed in an improvement in vision restoration time ( VRT ) in dim light ( dark adaptometry ) . Vitamin A and zinc synergistically normalized conjunctival epithelium as measured by conjunctival impression cytology ( CIC ) . Both functional indices , VRT and CIC , showed significant correlations with plasma zinc and vitamin A , respectively . The data suggest that functional improvements in population s with suboptimal vitamin A and zinc nutriture can be accomplished by supplementation with less than two times the recommended dietary allowance of these nutrients BACKGROUND The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured . OBJECTIVE We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics . DESIGN A double-blind , r and omized , placebo-controlled trial was carried out in which 736 children aged 6 - 15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo , zinc daily , vitamin A and zinc together , or placebo . Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections . RESULTS Vitamin A supplementation was associated with a 27 % increase in diarrheal disease [ risk ratio ( RR ) : 1.27 ; 95 % CI : 1.10 , 1.45 ; P < 0.001 ] and a 23 % increase in cough with fever ( RR : 1.23 ; 95 % CI : 1.02 , 1.47 ; P = 0.02 ) , whereas zinc had no effect on these outcomes . Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors , piped water , and indoor bathrooms . Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated . Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers . CONCLUSIONS Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City . Vitamin A and zinc have more heterogeneous effects in different subgroups of children BACKGROUND Leptin , ghrelin , and insulin are hormonal regulators of energy balance and , therefore , may be related to growth during infancy . Zinc is essential for growth , and its growth effects may be mediated through these hormones . OBJECTIVE We examined the effects of supplemental zinc on plasma leptin , ghrelin , and insulin concentrations among young children at risk of zinc deficiency and examined the relations between these hormones and physical growth . DESIGN Children ( n = 142 ) aged 6 - 8 mo were r and omly assigned to receive 3 mg Zn/d as a supplement , in a fortified food , or as a placebo for 6 mo . Relations between hormones and anthropometric z scores , body composition , and growth rates were examined at baseline and 3 and 6 mo after the start of the intervention . RESULTS No treatment group-related differences were found in plasma leptin , ghrelin , or glucose concentrations or in anthropometric z scores at 3 or 6 mo after the start of the zinc intervention . Neither plasma leptin nor ghrelin concentrations at baseline or 3 mo were predictive of subsequent changes in growth . However , changes in weight-for-age z scores over the two 3-mo time intervals were positively associated with subsequent leptin concentrations and inversely associated with subsequent plasma ghrelin concentrations . CONCLUSIONS Supplemental zinc did not affect the children 's growth , anthropometric indexes , or plasma hormone concentrations in this study population . Our results suggest that plasma leptin and ghrelin concentrations in later infancy are a consequence of previous weight changes rather than predictors of short-term growth One hundred thirty children ( 65 - 95 mo old ) from a low-socioeconomic neighborhood of Guatemala City participated in a r and omized , double-blind , controlled trial of zinc supplementation . One group received 10 mg Zn/d ( n = 65 ) and the other group received a placebo ( n = 65 ) ; 90 + /- 9.2 doses were given over 120 - 150 d. Stools were examined for prevalence and intensity of helminths and prevalence of protozoa at the beginning and end of the study . The initial prevalence was 42 % for helminths and 18 % for protozoa , with no differences between groups . Mebendazole was administered to all children , and protozoal infections were treated specifically at the beginning of the study . The reinfection rates were 17 % ( 11 of 65 ) for helminths and 12.3 % ( 8 of 65 ) for protozoa in the zinc group and 15 % ( 10 of 65 ) and 10.7 % ( 7 of 65 ) , respectively , in the placebo group ( P > 0.05 ) . Analysis by specific parasites revealed no treatment effect . We conclude that neither plasma or hair zinc status nor oral zinc supplementation had an effect on parasite status in children Data from 4 r and omized , placebo-controlled , double-blind trials in Indonesia , Thail and , and Vietnam , the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants ( SEAMTIZI ) , were pooled to investigate the effects of iron and zinc supplementation infant growth . Infants ( n = 2451 ) aged 4 - 6 mo old were supplemented with iron ( 10 mg/d ) and /or zinc ( 10 mg/d ) for 6 mo . Overall , neither iron nor zinc supplementation prevented the progressive growth faltering during infancy , which is common in many developing countries . However , infants who received zinc were less likely to be stunted at the end of the supplementation period ( odds ratio 0.80 ; 95 % CI 0.64 - 1.0 ) . Boys had a 30 % higher risk of being stunted at the end of the study than girls ( P < 0.01 ) . Baseline factors modified the effect of supplementation , with infants anemic at baseline ( hemoglobin < 105 g/L ) benefiting from zinc supplementation , with an estimated increase in height-for-age Z-score ( HAZ ) score of 0.17 ( P < 0.01 ) , but with no effect of zinc supplementation on growth in infants not anemic at baseline . Iron supplementation negatively affected linear growth in infants with a birth weight of > 3500 g ( estimated effect size , -0 . 14 HAZ score ; P < 0.01 ) , but with no significant effect in infants with a lower birth weight . This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some . Hence , interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies BACKGROUND Deficiencies of iron and zinc are associated with delayed development , growth faltering , and increased infectious-disease morbidity during infancy and childhood . Combined iron and zinc supplementation may therefore be a logical preventive strategy . OBJECTIVE The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth , psychomotor development , and incidence of infectious disease . DESIGN Indonesian infants ( n = 680 ) were r and omly assigned to daily supplementation with 10 mg Fe ( Fe group ) , 10 mg Zn ( Zn group ) , 10 mg Fe and 10 mg Zn ( Fe+Zn group ) , or placebo from 6 to 12 mo of age . Anthropometric indexes , developmental indexes ( Bayley Scales of Infant Development ; BSID ) , and morbidity were recorded . RESULTS At 12 mo , two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score , knee-heel length , and BSID psychomotor development . Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups , knee-heel length was higher in the Zn and Fe groups than in the placebo group , and the BSID psychomotor development index was higher in the Fe group than in the placebo group . No significant effect on morbidity was found . CONCLUSIONS Single supplementation with zinc significantly improved growth , and single supplementation with iron significantly improved growth and psychomotor development , but combined supplementation with iron and zinc had no significant effect on growth or development . Combined , simultaneous supplementation with iron and zinc to infants can not be routinely recommended at the iron-to-zinc ratio used in this study Given the high prevalence of micronutrient deficiencies and infectious diseases in infants in developing countries , an evaluation of the efficacy of different micronutrient formulations on infant morbidity is a priority . The efficacy of weekly supplementation of four different micronutrient formulations on diarrhea and acute lower respiratory infection ( ALRI ) morbidity was evaluated in Bangladeshi infants . In a double-blind , r and omized , controlled community trial , 799 infants aged 6 mo were r and omly assigned to one of the following 5 groups : 1 ) 20 mg elemental iron with 1 mg riboflavin , 2 ) 20 mg elemental zinc with 1 mg riboflavin , 3 ) 20 mg iron and 20 mg zinc with 1 mg riboflavin , 4 ) a micronutrient mix ( MM ) containing 20 mg iron , 20 mg zinc , 1 mg riboflavin along with other minerals and vitamins and 5 ) a control treatment , 1 mg riboflavin only . Health workers visited each infant weekly until age 12 mo to feed the supplement and to collect data on diarrhea and ALRI morbidity . Hemoglobin , serum ferritin and serum zinc levels of a sample of infants were measured at 6 and 12 mo . Compared with the control group , at 12 mo , serum ferritin levels were higher in the iron + zinc group , and serum zinc levels were higher in the zinc and iron + zinc groups . Simultaneous supplementation with iron + zinc was associated with lower risk of severe diarrhea , 19 % lower in all infants and 30 % lower in less well-nourished infants with weight-for-age Z-score below -1 . Iron + zinc supplementation was also associated with 40 % lower risk of severe ALRI in less well-nourished infants . MM supplementation was associated with a 15 % higher risk of diarrhea in all infants and 22 % higher risk in less well-nourished infants . Intermittent simultaneous supplementation with iron + zinc seems promising ; it will be useful to determine whether higher doses would provide greater benefits Deficiencies of iron and zinc are prevalent worldwide . Interactions between these micronutrients therefore have important consequences , also for supplementation . To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants , data from 4 parallel , r and omized , placebo-controlled , double-blind trials in Indonesia , Thail and , and Vietnam were pooled . Infants ( n=2468 ) , aged 4 - 6 mo , were supplemented daily with iron ( 10 mg ) and /or zinc ( 10 mg ) for 6 mo . At 3 sites , infants were given vitamin A capsules ( VAC ) at recruitment . Combined supplementation reduced prevalences of anemia by 21 % ( P<0.01 ) and zinc deficiency by 10 % ( P<0.05 ) but was less effective ( P<0.05 ) than supplementation with either iron ( 28 % reduction in anemia ) or zinc alone ( 18 % reduction in zinc deficiency ) . Iron reduced the effect of zinc supplementation ( interaction P<0.01 ) , but had no separate effect on zinc status , whereas zinc supplementation had a negative effect on hemoglobin concentrations ( -2.5 g/L , P<0.001 ) , independent of iron supplementation ( Pinteraction=0.25 ) . The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls ( effect size 12.0 vs. 6.8 g/L , respectively ) . In infants not receiving iron , VAC administration tended to be associated with lower ( 3.2 % , P=0.07 ) hemoglobin concentrations . Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies . Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status . Furthermore , VAC administration in the absence of iron supplementation may increase the incidence of anemia BACKGROUND Rates of mental illness in children are increasing throughout the world . Observational studies of depression , anxiety , and attention-deficit hyperactivity disorder suggest that zinc is an alternative treatment . OBJECTIVE We examined the effect of zinc supplementation on the mental health of school-age children in Guatemala . DESIGN From January to October 2006 , we conducted a 6-mo r and omized , double-blind , controlled trial comparing zinc supplementation ( 10 mg ZnO/d for 5 d/wk ) with a placebo ( 10 mg glucose ) in 674 Guatemalan children in grade s 1 - 4 . Outcome measures included internalizing ( ie , depression and anxiety ) and externalizing ( ie , hyperactivity and conduct disorder ) problem behaviors , positive behaviors ( ie , socialization and leadership ) , and serum zinc concentrations . RESULTS Zinc and placebo groups did not differ significantly in any behavioral measures at baseline or at follow-up . At baseline , 21.4 % of children had serum zinc concentrations < 65 μg/dL. At follow-up , both groups improved significantly , and zinc concentrations were higher in the zinc group . Increases in serum zinc concentrations were inversely associated with decreases in depressive symptoms ( estimate : -0.01 points per μg Zn/dL ; P = 0.01 ) , anxiety ( estimate : -0.012 points per μg Zn/dL ; P = 0.02 ) , internalizing symptoms ( estimate : -0.021 points per μg Zn/dL ; P = 0.02 ) , and social skills ( estimate : -0.019 points per μg Zn/dL ; P = 0.01 ) in adjusted models that were controlled for child age , sex , socioeconomic status , household , and treatment group . CONCLUSIONS Six months of zinc supplementation did not induce differences in mental health outcomes between zinc and placebo groups . However , increases in serum zinc concentrations were associated with decreases in internalizing symptoms ( ie , depression and anxiety ) in a community-based sample of children at risk of zinc deficiency . This trial was registered at clinical trials.gov as NCT00283660 Hans Verhoef and colleagues report findings from a r and omized trial conducted among Tanzanian children at high risk for malaria . Children in the trial received either daily oral supplementation with either zinc alone , multi-nutrients without zinc , multi-nutrients with zinc , or placebo . The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes Background The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients . We aim ed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity . Methods and Findings Rural Tanzanian children ( n = 612 ) aged 6–60 months and with height-for-age z-score < –1.5 SD were r and omized to daily supplementation with zinc ( 10 mg ) alone , multi-nutrients without zinc , multi-nutrients with zinc , or placebo . Children were followed for an average of 45 weeks . During follow-up , we recorded morbidity episodes . We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea , respiratory illness , fever without localizing signs , or other illness ( guardian-reported illness with symptoms involving skin , ears , eyes and abscesses , but excluding trauma or burns ) . Zinc supplementation reduced the hazard rate of diarrhea by 24 % ( 4%–40 % ) . By contrast , multi-nutrients seemed to increase this rate ( HR ; 95 % CI : 1.19 ; 0.94–1.50 ) , particularly in children with asymptomatic Giardia infection at baseline ( 2.03 ; 1.24–3.32 ) . Zinc also protected against episodes of fever without localizing signs ( 0.75 ; 0.57–0.96 ) , but we found no evidence that it reduced the overall number of clinic visits . Conclusions We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients . By reducing rates of fever without localizing signs , supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics . Trial Registration Clinical Trials.gov This paper assessed gender bias within hospitalisation rates to ascertain whether differential care-seeking practice s significantly contribute to excess female mortality . It then examined the impact of socio-economic factors , particularly maternal education and economic status , on gender bias . The results find both the clear and significant impact of gender on hospitalisation rates , as well as the simultaneous inability of rising education and economic status to alleviate this bias . A secondary analysis was conducted within a uniquely large and ongoing r and omised control trial that sought to measure the impact of Zinc supplementation on hospitalisations and deaths in low-income communities in New Delhi , India . During the course of the study , 85,633 children were enrolled and monitored over one year of follow-up . Of the 430 deaths that occurred , 230 were female ( 0.57 % of total females ) , while 200 were male ( 0.43 % of all males ) . Despite this higher mortality amongst females ( p<0.02 ) , girls were hospitalised far less frequently than boys . Of the 4418 children who were hospitalised at least once , 2854 ( 64.6 % ) were males and only 1564 ( 35.4 % ) were females , indicating a significantly lower rate of care-seeking for females ( p<0.00 ) . Curiously , our results show that gender bias is highest amongst highly educated mothers , and decreases steadily for children of mothers with a middle school education , a primary school education , and is lowest amongst mothers with no formal education . Put differently , female children of mothers with no formal education were significantly more likely to be hospitalised than children of mothers with several years of formal education , even after adjusting for all other factors . Economic status was not found to affect the association of gender and hospitalisation , though overall odds of hospitalisation rose with increasing economic status . Paternal education was found not to be significantly related to hospitalisation Objectives : To determine the effect of low-dose weekly supplementation with iron , zinc or both on growth of infants from 6 to 12 months of age . Subjects/ Methods : A total of 645 breastfed infants age 6 months who were not severely anemic ( Hb⩾90 g l−1 ) or severely malnourished ( weight-for-age ⩾60 % median ) were r and omized to receive 20 mg iron and 1 mg riboflavin ; 20 mg zinc and 1 mg riboflavin ; 20 mg iron , 20 mg zinc and 1 mg riboflavin ; or riboflavin alone ( control ) weekly for 6 months . Results : Baseline characteristics were similar among the four supplementation groups . Weight , length and mid-upper arm circumference were assessed at baseline , 8 , 10 and 12 months of age . There was no interaction of iron and zinc when given in a combined supplement on either weight or length ( P>0.05 ) . There were no effects of either iron or zinc on the rate of length or weight gain for all infants or when stratified by baseline Hb concentration . Conclusions : Weekly supplementation of 20 mg Fe , 20 mg Zn , or both does not benefit growth among infants 6–12 months of age in rural Bangladesh , a region with high rates of anemia and zinc deficiency Background Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries , but its efficacy in children in Africa is uncertain . Objective To determine if zinc , or zinc plus multiple micronutrients , reduces diarrhea and respiratory disease prevalence . Design R and omized , double-blind , controlled trial . Setting Rural community in South Africa . Participants Three cohorts : 32 HIV-infected children ; 154 HIV-uninfected children born to HIV-infected mothers ; and 187 HIV-uninfected children born to HIV-uninfected mothers . Interventions Children received either 1250 IU of vitamin A ; vitamin A and 10 mg of zinc ; or vitamin A , zinc , vitamins B1 , B2 , B6 , B12 , C , D , E , and K and copper , iodine , iron , and niacin starting at 6 months and continuing to 24 months of age . Homes were visited weekly . Outcome Measures Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts . Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report , or confirmed by the field worker . Results Among HIV-uninfected children born to HIV-infected mothers , median percentage of days with diarrhea was 2.3 % for 49 children allocated to vitamin A ; 2.5 % in 47 children allocated to receive vitamin A and zinc ; and 2.2 % for 46 children allocated to multiple micronutrients ( P = 0.852 ) . Among HIV-uninfected children born to HIV-uninfected mothers , median percentage of days of diarrhea was 2.4 % in 56 children in the vitamin A group ; 1.8 % in 57 children in the vitamin A and zinc group ; and 2.7 % in 52 children in the multiple micronutrient group ( P = 0.857 ) . Only 32 HIV-infected children were enrolled , and there were no differences between treatment arms in the prevalence of diarrhea . The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts . Conclusion When compared with vitamin A alone , supplementation with zinc , or with zinc and multiple micronutrients , did not reduce diarrhea and respiratory morbidity in rural South African children . Trial Registration Clinical Trials.gov After age 6 mo , the combination of breast-feeding and unfortified plant-based complementary feeding provides inadequate zinc ( Zn ) . Additionally , high phytate intakes compromise the bioavailability of zinc . Our principal objective in this r and omized controlled , doubly masked trial was to determine the effect of substituting low-phytate maize , a daily 5-mg zinc supplement , or both , in infants between ages 6 - 12 mo on impaired linear growth velocity , a common feature of zinc deficiency . In the Western Highl and s of Guatemala , 412 infants were r and omized to receive low-phytate or control maize . Within each maize group , infants were further r and omized to receive a zinc supplement or placebo . Length , weight , and head circumference were measured at 6 , 9 , and 12 mo of age . There were no significant differences between the 2 maize groups or between the Zn supplement and placebo groups and no treatment interaction was observed for length-for-age ( LAZ ) , weight-for-length ( WLZ ) or head circumference Z-scores . Overall mean ( + /- SD ) Z-scores at 6 mo for combined treatment groups were : LAZ , -2.1 + /- 1.1 ; WLZ , 0.7 + /- 1.0 ; and head circumference Z-score , -0.7.0 + /- 1.0 . At 12 mo , these had declined further to : LAZ , -2.5 + /- 1.1 ; WLZ , -0.0 + /- 0.9 ; and head circumference Z-score , -0.9 + /- 1.1 ; 83.3 % were stunted and 2 % were wasted . Low linear growth in older Guatemalan infants was not improved with either low-phytate maize or a daily 5-mg zinc supplement . Low contribution of maize to the complementary food of the infants negated any potential advantage of feeding low-phytate maize In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVE To assess zinc absorption from dispersible tablets by investigating the effects of short-term zinc supplementation , provided either as zinc ( Zn ) sulfate dispersible tablets or solution , on changes in plasma Zn concentration in young children . STUDY DESIGN We conducted a r and omized , partially-masked , placebo-controlled trial in 451 children 6 to 23 months of age in Burkina Faso , r and omly assigned to receive a dispersible tablet containing 5 mg Zn , a Zn solution containing 5 mg Zn/5 mL , or a placebo solution , daily for 3 weeks . The main outcome measure was change in plasma zinc concentration after supplementation compared with baseline . RESULTS The mean plus or minus SD change in plasma Zn concentration ( μg/dL ) was significantly greater in both Zn supplemented groups ( tablets : 16.9±13.1μg/dL , liquid : 16.6±14.2 μg/dL ) , compared with the placebo group ( 0.2±10.9 μg/dL ; P<.001 , ANOVA ) . In both Zn supplemented groups , but not in the placebo group , change in plasma Zn concentration was progressively less with increasing age in months ( -0.79 μg/dL/mo and -1.15 μg/dL/mo , respectively ; P<.001 ) ; this effect did not differ in the Zn supplemented groups ( P=.18 ) . CONCLUSIONS Short-term supplementation results in a large increase in plasma Zn concentration , regardless of whether the additional Zn is provided as a dispersible tablet or solution BACKGROUND Stunting is highly prevalent in Ethiopia and many other developing countries but the reason for it is poorly understood . Zinc is essential for growth but diets in such countries often do not contain zinc in sufficient quantity or of sufficient bioavailability . Thus zinc deficiency may play a major role in stunting . The aim of the study was to investigate whether the low rate of linear growth of apparently healthy breastfed infants in a rural village in Ethiopia could be improved by zinc supplementation . METHODS A r and omised , double-blind , placebo-controlled trial was done on apparently healthy breastfed infants aged 6 - 12 months . 100 non-stunted ( length-for-age , Z score < -2 ) were matched for age and sex with 100 r and omly selected stunted ( > -2 ) infants . Infants , both stunted and non stunted , were matched by sex , age ( within 2 months ) and recumbent length ( within 3 cm ) for r and om assignment , to receive a zinc supplement ( 10 mg zinc per day , as zinc sulphate ) or placebo , 6 days a week for 6 months . Anthropometric measurements were taken monthly , data on illness and appetite were collected daily , and sample s of serum and hair were taken at the end of the intervention for the analysis of zinc . FINDINGS The length of stunted infants increased significantly more ( p<0.001 ) when supplemented with zinc ( 7.0 cm [ SE 1.1 ] ) than with placebo ( 2.8 cm [ 0.9 ] ) ; and the effect was greater ( p<0.01 ) than in non-stunted infants ( 6.6 [ 0.9 ] vs 5.0 [ 0.8 ] cm for the zinc and placebo groups respectively , p<0.01 ) . Zinc supplementation also increased the weight of stunted children ( 1.73 [ 0.39 ] vs 0.95 [ 0.39 ] kg for the corresponding placebo group , p<0.001 ) and of non-stunted children ( 1.19 [ 0.39 ] vs 1.02 [ 0.32 ] kg for the corresponding placebo group , p<0.05 ) . Zinc supplementation result ed in a markedly lower incidence of anorexia and morbidity from cough , diarrhoea , fever , and vomiting in the stunted children . The total number of these conditions per child was 1.56 and 1.11 in the stunted and non-stunted zinc supplemented children versus 3.38 and 1.64 in the stunted and non-stunted placebo-treated children , respectively . At the end of the intervention period , the concentrations of zinc in serum and hair of stunted infants , who had not been supplemented with zinc , were lower than the respective concentrations of zinc in serum and hair of their non-stunted counterparts . INTERPRETATION Combating zinc deficiency can increase the growth rate of stunted children to that of non-stunted infants in rural Ethiopia . This would appear to be due , at least in part , to reduction in morbidity from infection and increased appetite OBJECTIVE To examine intellectual and motor functioning of children who received micronutrient supplementation from 12 to 35 months of age . DESIGN Cohort follow-up of children 7 to 9 years of age who participated in a 2 × 2 factorial , placebo-controlled , r and omized trial from October 2001 through January 2006 . SETTING Rural Nepal . PARTICIPANTS A total of 734 children 12 to 35 months of age at supplementation and 7 to 9 years of age at testing . INTERVENTIONS Children received iron plus folic acid ( 12.5 mg of iron and 50 μg of folic acid ) ; zinc ( 10 mg ) ; iron plus folic acid and zinc ; or placebo . MAIN OUTCOME MEASURES Intellectual , motor , and executive function . RESULTS In both the unadjusted and adjusted analyses , iron plus folic acid supplementation had no effect overall or on any individual outcome measures being tested . In the unadjusted analysis , zinc supplementation had an overall effect , although none of the individual test score differences were significant . In the adjusted analysis , the overall difference was not significant . CONCLUSION In rural Nepal , we found that iron plus folic acid or zinc supplementation during the preschool years had no effect on aspects of intellectual , executive , and motor function at 7 to 9 years of age , suggesting no long-term developmental benefit of iron or zinc supplementation during 12 to 35 months of age The present study tested the hypothesis that inadequate Zn intake might be responsible for failure to thrive and impaired catch-up growth in young rural Gambian children , and that Zn supplements might be beneficial . Gambian children might be deprived of Zn because of its poor availability from their predominantly plant-based diet . Rural Gambian children ( 110 ; fifty boys , sixty girls ) aged between 0.57 and 2.30 years were divided into two matched groups , one to receive 70 mg Zn twice weekly for 1.25 years , and the other a placebo . Growth and mid-upper-arm circumference were measured at weekly intervals throughout the study and illnesses were monitored . Capillary blood and urine sample s were collected at 0 , 2 and 8 weeks . Body weights and arm circumferences showed a linear increase , plus a seasonal effect ( rainy season faltering ) . For body weight there was no significant overall effect of the supplement . For arm circumference , a very small ( 2 % ) but significant ( P < 0.01 ) difference favoured the supplemented group . Plasma thymulin was much lower at the first clinic than at the second and third clinics , and in vitro Zn stimulation was greater at the first clinic . There was , however , no effect of Zn in vivo . Likewise , Zn did not significantly benefit T-cell numbers or ratios , secretory IgA in urine , circulating hormone levels or biochemical indices of Zn status . One index of intestinal permeability , i.e. lactulose : creatinine , was improved ( P < 0.02 ) by the supplement , but the lactulose : mannitol value was not ; this requires further investigation . Dietary Zn deficiency is , thus , unlikely to be of major overall importance for rural Gambian children 's ability to thrive , and blanket Zn supplementation is not justified . There may , however , be vulnerable sub-groups who would benefit from Zn supplements BACKGROUND Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children , but evidence from malarious population s in Africa has been inconsistent . Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba , Zanzibar . METHODS We enrolled 42,546 children aged 1 - 36 months , contributing a total of 56,507 child-years in a r and omised , double-blind , placebo-controlled trial in Pemba , Zanzibar . R and omisation was by household . 21 274 children received daily supplementation with zinc 10 mg ( 5 mg in children younger than 12 months ) for mean 484.7 days ( SD 306.6 ) . 21,272 received placebo . The primary endpoint was overall mortality , and analysis was by intention to treat . This study is registered as an International St and ard R and omised Clinical Trial , number IS RCT N59549825 . FINDINGS Overall , there was a non-significant 7 % ( 95 % CI -6 % to 19 % ; p=0.29 ) reduction in the relative risk of all-cause mortality associated with zinc supplementation . INTERPRETATION We believe that a meta- analysis of all studies of mortality and morbidity , will help to make evidence -based recommendations for the role of zinc supplementation in public health policy to improve mortality , morbidity , growth , and development in young children To investigate whether micronutrient supplementation could improve the vibriocidal antibody response of children to a killed oral cholera vaccine , 2 - 5-year-old children were r and omly assigned to receive vitamin A and zinc ( AZ group ) , vitamin A and a placebo ( A group ) , zinc and a placebo ( Z group ) , or both placebos ( P group ) . All children received 2 doses of the vaccine . The number of children who had a > or = 4-fold increase in vibriocidal antibody was significantly greater in the AZ group than in the P group ( P = .025-.028 ) . Factorial analysis suggested that the proportion of children with a > or = 4-fold increase in vibriocidal antibody titer was significantly greater in the zinc-supplemented groups than in the groups that did not receive zinc ( P = .013-.048 ) and that vitamin A supplementation did not have a significant effect . Thus , supplementation with zinc improves seroconversion to vibriocidal antibody and , hence , has the potential to improve the efficacy of oral cholera vaccine in children Objective : To test the efficacy of zinc supplementation through diet or ayurvedic zinc tablet on cognitive function and taste acuity in adolescent girls . Methods : Using zinc-rich food items , snacks were prepared by adopting food-processing methods that enhance zinc bioavailability . Ayurvedic zinc tablet ( jasad bhasma ) was chosen as a natural elemental zinc supplement . Efficacy of snacks and the tablet was assessed in 180 schoolgirls ( 12.5 ± 0.85 years ) from Pune City , India , who were r and omly allocated to any of the 3 groups : ( 1 ) ayurvedic zinc tablet — J , ( 2 ) zinc-rich snacks — D , or ( 3 ) Control — C. Supplementation was given on every school day ( 6 days/wk ) for 10 weeks . All measurements were recorded at baseline and at the end of the study period . Food intake was recorded by 24-hour diet recall on 3 r and om days . Hemoglobin , serum ferritin , and plasma zinc were estimated on a fasting blood sample . Cognitive assessment was done on each participant using tests for simple reaction time ( SRT ) , recognition reaction time ( RRT ) , visual memory , and Raven 's Progressive Matrices ( RPM ) . Taste acuity was determined by recognition thresholds for salt ( RTS ) over a range of 10 different salt concentrations . Results : A higher increase in plasma zinc ( 61.3 % ) was observed in the J group than in the D group ( 9.9 % ) ( p < 0.01 ) , whereas plasma zinc declined in the control group ( −2.2 % ) over baseline ( p > 0.1 ) . Hemoglobin showed no change in all 3 groups ( p > 0.1 ) . Percent increment in scores for memory and RPM was significantly more in the D and J groups ( 24.5%–29.6 % ) than in the C group ( 6.5 % ) ( p < 0.05 ) . Mean SRT and RRT were reduced more in the D and J groups ( 5%–16 % ) than in the C group ( 1.6 % ) ( p < 0.05 ) . A significant fall in median RTS from 5 to 2.5 mmol/L was noted after both diet and zinc supplementation ( p < 0.01 ) ; however , it remained the same at 5 mmol/L in the Control group after 10 weeks . Conclusion : Supplementation of ayurvedic zinc and zinc-rich foods are effective in improving cognitive performance and the recognition threshold for salt of adolescent girls OBJECTIVES : To assess the effect of zinc supplementation on growth and body composition among schoolchildren . DESIGN : R and omized , double-blind , placebo-controlled trial . SETTING AND SUBJECTS : 313 rural Zimbabwean schoolchildren ( 144 boys and 169 girls ) , 11–17 y ) . INTERVENTIONS : Supplementation with zinc ( 30 or 50 mg ) or placebo on schooldays for 12 months . Due to drought , a food programme was in operation during the last eight months of the study .VARIABLES : Weight , height , upper arm circumference , triceps skinfold thickness , and weight-for-age , height-for-age , weight-for-height , arm muscle-area-for-age and arm fat-area-for-age Z-scores . RESULTS : Significant effects on weight gain ( 0.51 vs 0.14 kg , P=0.01 ) , weight-for-age Z ( −0.08 vs −0.14 , P=0.01 ) and arm muscle area-for-age Z-score ( 0.10 vs 0.01 , P=0.03 ) were seen over the first three months , whereas no effects were seen over the full 12 months . CONCLUSIONS : Zinc deficiency impairing lean body mass and weight gain was documented . However , the effect of zinc seen over the first three months vanished during the last nine months when the food programme was in operation . Zinc deficiency may have persisted , but another nutrient may have become growth limiting during the last nine months . SPONSORSHIP : Danish International Development Assistance Zinc is crucial for normal immune function and can reduce morbidity from multiple infectious diseases . To determine the influence of zinc on malaria morbidity we conducted a r and omized placebo-controlled trial of daily zinc supplementation in children residing in a malaria endemic region of Papua New Guinea . A total of 274 preschool children aged 6 to 60 months were given 10 mg elemental zinc ( n = 136 ) or placebo ( n = 138 ) for 6 days a week for 46 weeks . Slide-confirmed malaria episodes were detected by surveillance of cases self-reporting to a local health center . Cross-sectional surveys were conducted at the beginning , middle , and end of the study to assess infection rates , parasite density , spleen enlargement , and hemoglobin levels . Zinc supplementation result ed in a 38 % ( 95 % CI 3 - 60 , P = 0.037 ) reduction in Plasmodium falciparum health center-based episodes , defined as parasitemia > or = 9200 parasites/microl with axial temperature > or = 37.5 degreesC or reported fever . Episodes accompanied by any parasitemia were also reduced by 38 % ( 95 % CI 5 - 60 , P = 0.028 ) , and episodes with parasitemia > or = 100,000/microl were reduced by 69 % ( 95 % CI 25 - 87 , P = 0.009 ) . There was no evidence of the effects of zinc on Plasmodium vivax morbidity or on health center attendance for causes other than P. falciparum . Zinc had no consistent effect on cross-sectional malariometric indices . Although P. falciparum prevalence tended to be lower at the end of the study in children given the placebo , such changes were absent at the mid- study survey . These results suggest that improved dietary zinc intake may reduce morbidity due to P. falciparum OBJECTIVE To analyse the effects of zinc supplementation on growth parameters in a representative sample of young children in rural Burkina Faso . Design R and omized , double-blind , placebo-controlled efficacy trial . Setting Eighteen villages in rural northwestern Burkina Faso . Subjects In all , 709 children aged 6 - 31 months were enrolled ; 685 completed the trial . Intervention Supplementation with zinc ( 12.5 mg zinc sulphate ) or placebo daily for 6 days a week for 6 months . Outcomes Weight , length/height , mid-arm circumference , and serum zinc . RESULTS In a representative sub sample of study children , 72 % were zinc-deficient at baseline . After supplementation , serum zinc increased in zinc-supplemented but not in control children of the sub sample . No significant differences between groups were observed during follow-up regarding length/height , weight , mid-arm circumference , and z scores for height-for-age , weight-for-age , and weight-for-height . CONCLUSIONS We conclude that zinc supplementation does not have an effect of public health importance on growth in West African population s of young children with a high prevalence of malnutrition . Multinutrient interventions are likely to be more effective In a community-based double-blind r and omized trial in children aged 6–35 months , both intervention and control groups received a multi-vitamin syrup containing vitamin A , while the intervention group had zinc gluconate ( equivalent to 10 mg of elemental zinc ) additional in the syrup . There was a significant decrease in diarrhoea and pneumonia in the intervention group . This study was undertaken to investigate if addition of zinc to vitamin A had improved plasma retinol levels , which , in turn , was responsible for the effects observed in the intervention group . In a r and omly-selected sub sample of 200 children—100 each from the intervention and the control group , plasma retinol levels after 120 days of supplementation were measured . There was no difference in the mean plasma retinol levels [ the difference in the mean 0.46 μg/dL ( 95 % confidence interval -1.42–2.36 ) ] between the two groups following supplementation . No difference in plasma retinol levels was observed in the subgroups based on baseline nutritional status and plasma zinc levels . Addition of zinc to low-dose vitamin A in this study did not improve the vitamin A status of children and can not explain morbidity effects of the intervention Community-based data relating to factors influencing zinc deficiency among preschool children in India are inadequate . Data of a large , double-blinded , r and omized , controlled zinc-supplementation trial were used for assessing the descriptive epidemiology of zinc deficiency among children aged 6–35 months ( n=940 ) . In total , 609 children were followed up for 120 days for information on morbidity . Of these children , 116 from the control group belonging to the upper and the lower 25th quartile of plasma zinc status at baseline were selected for assessing the association of zinc deficiency with prospect i ve morbidity . At baseline , demographic , socioeconomic and dietary information was collected , and anthropometric measurements and levels of plasma zinc were assessed . At baseline , 73.3 % of the children were zinc-deficient ( plasma zinc < 70 µg/dL ) , of which 33.8 % had levels of plasma zinc below 60 µg/dL. A significantly higher risk of morbidity was prevalent among the subjects with lower plasma zinc compared to those with higher levels of plasma zinc Aim : The aim of the present study , which was undertaken as a sub‐ study within a r and omized controlled trial of zinc supplementation , was to evaluate the effect of prolonged zinc supplementation on copper status as assessed by hematological markers . Methods : Plasma copper and zinc were estimated at baseline and after 120 d of supplementation in a r and omly selected infant subset ( 115 ) of the children . Of these , 61 children were in a zinc group ( Z ) getting 10 mg of elemental zinc , and 54 were in a control group ( C ) getting supplement without zinc . Results : Baseline plasma zinc was comparable in the two groups ; post‐supplementation zinc was significantly higher ( Z 93.0 ± 3.6 vs C 60.6 ± 8.0 ) in the zinc supplementation group . There was no significant difference in the mean/median copper levels between the zinc and control groups . The percentage of children with plasma copper < 100 μg/dl was also not significantly different between groups ( baseline Z 14.8 % , C 11.1 % ; post‐supplementation Z 18.0 % , C 11.1 % ) . There were no differences between the zinc and control groups after 120 d of supplementation in hemoglobin ( Hgb ) , mean corpuscular volume ( MCV ) , mean corpuscular hemoglobin concentration ( MCHC ) , or number of lymphocytes or granulocytes The knowledge that zinc is essential for growth and neuropsychologic performance and a report of zinc-responsive stunting in Chinese children prompted this project . This article summarizes findings from a 10-wk , double-blind , controlled trial of zinc repletion in 740 urban , 6 - 9-y-old first grade rs from low-income families in Chongqing , Qingdao , and Shanghai , People 's Republic of China . Treatments were 20 mg Zn alone ( Z ) , 20 mg Zn with micronutrients ( ZM ) , and micronutrients alone ( M ) . The M mixture was based on National Research Council guidelines . Nutrients that might interfere with zinc retention were excluded or given in lower amounts . Main outcomes were changes in neuropsychologic performance and knee height . Hemoglobin , serum ferritin , plasma and hair zinc , and whole blood and hair lead were also measured . Anemia was not common , and serum ferritin concentrations were usually within the range of normal . Mean baseline plasma zinc concentrations were marginal in children from Chongqing and Qingdao and normal in children from Shanghai . After treatment with ZM or M plasma zinc increased . Hair zinc tended to decrease after all treatments . Mean baseline whole blood lead concentrations were slightly below the limit considered excessive for children by the US Centers for Disease Control and Prevention . Neuropsychologic performance and growth were most improved after treatment with ZM . These findings were consistent with the presence of zinc and other micronutrient deficiencies Abstract Objective : To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa . Design : R and omised , double blind , placebo controlled efficacy trial . Setting : 18 villages in rural northwestern Burkina Faso . Participants : 709 children were enrolled ; 685 completed the trial . Intervention : Supplementation with zinc ( 12.5 mg zinc sulphate ) or placebo daily for six days a week for six months . Main outcome measures : The primary outcome was the incidence of symptomatic falciparum malaria . Secondary outcomes were the severity of malaria episodes , prevalence of malaria parasite , mean parasite densities , mean packed cell volume , prevalence of other morbidity , and all cause mortality . Results : The mean number of malaria episodes per child ( defined as a temperature ≥37.5 ° C with ≥5000 parasites/μl ) was 1.7 , 99.7 % due to infection with Plasmodium falciparum . No difference was found between the zinc and placebo groups in the incidence of falciparum malaria ( relative risk 0.98 , 95 % confidence interval 0.86 to 1.11 ) , mean temperature , and mean parasite densities during malaria episodes , nor in malaria parasite rates , mean parasite densities , and mean packed cell volume during cross sectional surveys . Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea ( 0.87 , 0.79 to 0.95 ) . All cause mortality was non-significantly lower in children given zinc compared with those given placebo ( 5 v 12 , P=0.1 ) . Conclusions : Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa , but it does reduce morbidity associated with diarrhoea . What is already known on this topic Zinc deficiency is common in infants in developing countries Zinc supplementation has been shown to reduce morbidity from infectious disease in such population s , particularly through reductions in morbidity from diarrhoea and respiratory infections Limited evidence exists for zinc supplementation being effective in reducing morbidity from malaria What this study adds Zinc supplementation has no effect on falciparum malaria in children in rural west Africa It is effective in reducing morbidity from diarrhoea and may help to reduce mortality from all Background / Objective : The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of human immunodeficiency virus (HIV)-exposed children . Potential modifying factors , such as stunting , need to be addressed . The objective of this study was to determine whether adding zinc or zinc plus multiple micronutrients to vitamin A reduces diarrhoea incidence , and whether this differs between the strata of stunted or HIV-infected children . Methods : We analyzed data from a r and omized , controlled , double-blinded trial ( Clinical Trials.gov NCT00156832 ) of prophylactic micronutrient supplementation to children aged 6–24 months . Three cohorts of children : 32 HIV-infected children , 154 HIV-uninfected children born to HIV-infected mothers and 187 uninfected children born to HIV-uninfected mothers , received vitamin A , vitamin A plus zinc or multiple micronutrients , which included vitamin A and zinc . The main outcome was incidence of diarrhoea . Poisson regression was used in intent-to-treat analyses . Stratified analyses followed testing for statistical interaction between intervention and stunting . Results : We observed no significant differences in overall diarrhoea incidence among treatment arms . Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence when supplemented with zinc or multiple micronutrients compared with vitamin A alone ( 2.04 and 2.23 vs 3.92 episodes/year , respectively , P=0.024 ) . No meaningful subgroup analyses could be done in the cohort of HIV-infected children . Conclusions : Compared with vitamin A alone , supplementation with zinc and with zinc and multiple micronutrients , reduced diarrhoea morbidity in stunted rural South African children . Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups Background Asymptomatic carriage of Giardia intestinalis is highly prevalent among children in developing countries , and evidence regarding its role as a diarrhea-causing agent in these setting s is controversial . Impaired linear growth and cognition have been associated with giardiasis , presumably mediated by malabsorption of nutrients . In a prospect i ve cohort study , we aim to compare diarrhea rates in pre-school children with and without Giardia infection . Because the study was conducted in the context of an intervention trial assessing the effects of multi-nutrients on morbidity , we also assessed how supplementation influenced the relationship between Giardia and diarrhoea rates , and to what extent Giardia modifies the intervention effect on nutritional status . Methods and Findings Data were collected in the context of a r and omized placebo-controlled efficacy trial with 2 × 2 factorial design assessing the effects of zinc and /or multi-micronutrients on morbidity ( n = 612 ; height-for-age z-score < −1.5 SD ) . Outcomes measures were episodes of diarrhea ( any reported , or with ≥3 stools in the last 24 h ) and fever without localizing signs , as detected with health-facility based surveillance . Giardia was detected in stool by enzyme-linked immunosorbent assay . Among children who did not receive multi-nutrients , asymptomatic Giardia infection at baseline was associated with a substantial reduction in the rate of diarrhea ( HR 0.32 ; 0.15–0.66 ) and fever without localizing signs ( HR 0.56 ; 0.36–0.87 ) , whereas no such effect was observed among children who received multi-nutrients ( p-values for interaction 0.03 for both outcomes ) . This interaction was independent of age , HAZ-scores and distance to the research dispensary . There was no evidence that Giardia modified the intervention effect on nutritional status . Conclusion Although causality of the Giardia-associated reduction in morbidity can not be established , multi-nutrient supplementation results in a loss of this protection and thus seems to influence the proliferation or virulence of Giardia or associated intestinal pathogens Background The benefits of zinc or multiple micronutrient supplementations in African children are uncertain . African children may differ from other population s of children in developing countries because of differences in the prevalence of zinc deficiency , low birth weight and preterm delivery , recurrent or chronic infections such as HIV , or the quality of complementary diets and genetic polymorphisms affecting iron metabolism . The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6 - 24 months . Methods R and omized , controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6 - 24 months . Children in three cohorts - 32 HIV-infected children , 154 HIV-uninfected children born to HIV-infected mothers , and 187 uninfected children born to HIV-uninfected mothers - were separately r and omly assigned to receive daily vitamin A ( VA ) [ n = 124 ] , vitamin A plus zinc ( VAZ ) [ n = 123 ] , or multiple micronutrients that included vitamin A and zinc ( MM ) [ n = 126 ] . Results Among all children there were no significant differences between intervention arms in length-for-age Z scores ( LAZ ) changes over 18 months . Among stunted children ( LAZ below -2 ) [ n = 62 ] , those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA ( P = 0.029 when comparing effects of treatment over time ) . In the 154 HIV-uninfected children , MM ameliorated the effect of repeated diarrhea on growth . Among those experiencing more than six episodes , those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively ( P = 0.06 for treatment by time interaction ) . After 12 months , there was 24 % reduction in proportion of children with anemia ( hemoglobin below 11 g/dL ) in MM arm ( P = 0.001 ) , 11 % in VAZ ( P = 0.131 ) and 18 % in VA ( P = 0.019 ) . Although the within arm changes were significant ; the between-group differences were not significant . Conclusions Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting , compared to vitamin A alone or to vitamin A plus zinc . Effects on anemia require further study .Trial registration This study is registered with Clinical Trials.gov , number .NCT00156832 Objective : To determine the effect of zinc supplementation on diarrheal incidence and to discover any operational constraints of zinc supplementation at the community level . Methods : We included 1712 children aged between 6 and 48 months in a r and omized double blind study in rural area comprising of 11 villages . Children were r and omly divided into 2 groups . Zinc/placebo syrup supplementation was continued for 6 months in a weekly schedule from May 2003 . Children were followed up weekly for detection of diarrhea from May 2003 until April 2004 . Around 30 % of the study children were evaluated every 2 months during supplementation period . Results : During the period , 80,534 weekly visits were made giving 1548.73-child years of observation . We detected 1438 diarrheal episodes among 846 children . The incidence of diarrhea was significantly less during the supplemented period ( P < 0.001 ; RR 0.74 ( 0.64–0.87 ) ) in the zinc group . A significant difference was also noted during the follow up period ( P < 0.05 ) . In the zinc group , children < 2 years of age had significantly less diarrhea during supplementation and the follow up period . Multiple episodes of diarrhea ( ≥2 ) were significantly less in the zinc group . Approximately 85 % of the surveillance workers made weekly visits to the houses and 96 % of mothers administered syrup weekly to their children . Around 80 % of mother 's were aware of the possible benefits of zinc supplementation . Conclusion : Weekly zinc supplementation was effective in reducing diarrheal morbidity at the community level and it was operationally feasible OBJECTIVE In a zinc supplementation trial ( with a significant impact on diarrheal morbidity ) , to evaluate effect of zinc supplementation on cellular immune status before and after 120 days of supplementation . DESIGN A double blind , r and omized controlled trial with immune assessment at baseline and after 120 days on supplement . SETTING Community based study in an urban slum population . SUBJECTS R and omly selected children ( zinc 38 , control 48 ) , had a Multitest CMI skin test at both times . In 66 children ( zinc 22 , control 34 ) , proportions of CD3 , CD4 , CD8 , CD16 , CD20 cells and the CD/CD8 ratio were also estimated using a whole blood lysis method and flowcytometry . INTERVENTION Zinc gluconate to provide elemental zinc 10 mg daily and 20 mg during diarrhea . MAIN OUTCOME RESULTS Regarding CMI , the percentage of anergic or hypoergic children ( using in duration score ) decreased from 67 % to 47 % in the zinc group , while in the control group it remained unchanged ( 73 % vs 71 % ) ( p = 0.05 ) . The percentage of children deteriorating between first and second tests was significantly lower in the zinc group ( 13 % vs 33 % , p = 0.03 ) . Regarding lymphocyte subsets , the zinc group had a significantly higher rise in the geometric means of CD3 ( 25 % , p = 0.02 ) , CD4 ( 64 % p = 0.001 ) , and CD4/CD8 ratio ( 73 % p = 0.004 ) with no difference in CD8 and CD20 . The rise in CD4 was significantly higher in the zinc as compared to the control group ; the ratio of geometric means was 1.45 ( 95 % CI , 1.03 - 2.01 ) . CONCLUSION Zinc supplementation improves cellular immune status , which may have been one of the mechanisms for observed impact of zinc supplementation on diarrheal morbidity A sample of 471 pre-school children who frequented schools and crêches in a poor district of Manaus ( Amazonas ) , Brazil , were r and omly su bmi tted to faecal parasitological tests . Two-hundred- and -forty children from both sexes between the ages of 3 and 7 years with Ascaris lumbricoides and /or Giardia lamblia were selected . The objective of the study was to determine the possible influence of these two intestinal parasites and vitamin A and /or zinc supplementation on the serum retinol levels of primary school children . The children were su bmi tted to clinical and anthropometric examinations , dietary interviews and biochemical examinations of retinol and carotene in the serum and of zinc in the hair . The parasitic incidence was 85.0 % and about 54 % of the children were polyparasitic . During the pretreatment phase , the retinol and carotene serum levels were 36 % and 57 % , respectively , below the normal levels . Using the Waterlow classification , the anthropometric analyses revealed that 88 % of the children showed normal growth . A significant effect was observed of the anti-parasitic medicine on the serum retinol levels Background / objective : To assess the effects of micronutrient supplementation on head circumference of rural Nepali infants and children . Subjects/ methods : We used a r and omized controlled trial to assess the effects of micronutrient supplementation on head circumference in 569 rural Nepali infants and children aged 4–17 months . Children were r and omized to : ( 1 ) zinc , ( 2 ) iron – folic acid , ( 3 ) zinc plus iron – folic acid or ( 4 ) a placebo group . Data on head circumference were collected during five visits at ∼3 month intervals over the course of a year . We calculated change in head circumference in treatment groups receiving zinc and iron comparing the first and fifth visits as well as used generalized estimating equations ( GEE ) to take advantage of data from all points in time . Models were adjusted for covariates unbalanced in the r and omization and for baseline head circumference . Results : Estimating differences in head circumference between baseline and visit 5 , children in the zinc treatment group showed smaller decreases in head circumference z-score compared with placebo ( adjusted β=0.13 , 95 % confidence interval ( CI ) : 0.03 to 0.23 ) . Using GEE , zinc treatment was associated with 0.11 ( 95 % CI : 0.05 to 0.17 ) decrease in the rate of decline in head circumference z-score across visits as compared with placebo . Iron – folic acid supplementation was not associated with head circumference z-scores when comparing visits 1 with 5 or including data across all visits in adjusted models . Conclusion : Our results suggest that zinc supplementation confers a beneficial effect on the rate of head growth in Nepali infants A community-based , cluster-r and omized , placebo-controlled trial of daily zinc and /or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1 - 36 mo of age between 2001 and 2006 . Treatment groups included placebo , zinc ( 10 mg ) , iron+folic acid ( 12.5 mg iron + 50 microg folic acid ) , and zinc+iron+folic acid ( 10 mg zinc + 12.5 mg iron + 50 microg folic acid ) . Infants received half of these doses . The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board ; zinc and placebo continued until January 2006 . A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo . Mean age at first walking unassisted did not differ among groups and was 444 + /- 81 d ( mean + /- SD ) in the placebo group , 444 + /- 81 d in the zinc group , 464 + /- 85 d in the iron+folic acid group , and 446 + /- 87 d in the iron+folic acid+zinc group . Results were similar after adjustment for age at enrollment , asset ownership , maternal literacy , and prior child deaths in the household and in children who consumed at least 60 tablets . Compared with placebo , iron+folic acid was associated with an adjusted mean delay of 28.0 d ( 95 % CI : 11.3 , 44.7 ) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference ( MUAC ) < 9.5 cm [ 60.6 d , ( 95 % CI : 28.5 , 92.6 ) ] . Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration Objective : To evaluate the effect of combined iron – zinc supplementation on micronutrient status , growth and morbidity . Design : R and omized , double-masked , placebo-controlled supplementation trial . Setting : Rural district of Que Vo , in the Red River Delta in Vietnam . Subjects : A total of 915 breast-fed infants aged 4–7 months were included and 784 completed the study . Interventions : The Fe-group received daily and for a 6-month period 10 mg of iron , the Zn-group 10 mg zinc , the Fe – Zn group 10 mg iron+10 mg zinc and the placebo group a placebo . Hemoglobin ( Hb ) , serum ferritin ( SF ) and zinc ( SZn ) , and anthropometry were measured before and at the end of the intervention . Morbidity was recorded daily . Results : Changes of Hb and SF were higher in both Fe and Fe+Zn groups ( respectively 22.6 and 20.6 g/l for Hb ; 36.0 and 24.8 μg/l for SF ) compared to Zn and placebo groups ( Hb : 6.4 and 9.8 g/l ; SF : −18.2 and −16.9 μg/l , P<0.0001 ) . SZn increased more in Zn group ( 10.3 μmol/l ) than in Fe+Zn group ( 8.0 μmol/l , P=0.03 ) and more in these groups compared to Fe and placebo groups ( 1.6 and 1.2 μmol/l , P<0.0001 ) . Weight gain was higher in the Zn group . No significant effects of supplementations on growth in length or morbidity . Conclusions : Combined iron – zinc supplementation had a positive effect on iron and zinc status in infants . However , the positive effect of zinc alone on SZn and weight would indicate a negative interaction of iron when added to zinc supplements . Sponsorship : UNICEF New York Our objective in this trial was to assess the impact of daily zinc supplementation on growth in young children . A double-blind , r and omized , placebo-controlled trial was conducted in New Delhi , India . We enrolled 2482 children aged 6 - 30 mo who were supplemented daily with placebo or zinc ( 10 mg elemental zinc to infants and 20 mg to older children ) for 4 mo . At enrollment , all children also received a single dose of vitamin A ( 104.7 micromol for infants and 209.4 micromol for older children ) . Weight and length were measured at enrollment and 4 mo later . Weekly visits were conducted by field workers to ascertain morbidity in the previous 7 d. Change in length , weight , length-for-age Z-scores ( LAZ ) , and weight-for-length Z-scores ( WLZ ) after 4 mo of supplementation were assessed in the zinc and placebo groups . After 4 mo of supplementation , the weight and length gains in the 2 groups did not differ and there was no impact on LAZ , weight-for-age , and WLZ in the 2 groups . There was no substantial effect in any of the subgroups defined for age , income , gender , zinc levels in the crude analysis nor after adjusting for age , gender , income , breast-feeding status , and baseline anthropometric status . Despite successful zinc supplementation reflected in increased plasma zinc concentration and a substantially reduced incidence of diarrhea and pneumonia in zinc-supplemented children , the intervention did not have a beneficial effect on growth Physical growth retardation is an early and prominent feature of zinc deficiency , but the effect of zinc supplementation in children is still not completely clear . This study investigated the impact of zinc supplementation on linear growth , growth velocity , IGF-I levels , and skeletal maturation of short children during and after mineral supplementation . The study was design ed as a double-blind , r and omized , controlled trial of zinc supplementation during a 6-month period , with a subsequent 6-month follow-up . Anthropometric data were collected at 0 , 6 , and 12 months . Measurements included plasma Zn , IGF-I , height , weight , triceps skinfold thickness , and body mass index . Eighteen healthy pre-pubertal short children ( z-score -2.0 ) 7 to 10 years old with normal GH and IGF-I levels were r and omized to two groups , one with zinc supplementation ( 5 mg/kg/d of ZnSO4 ) and the other with placebo . In the first 6 months , only height velocity increased significantly , 5.99+/-0.80 cm/yr vs 5.05+/-0.85 cm/yr ( p=0.03 ) . After 12 months , height velocity returned to the initial values , 3.92+/-0.59 cm/yr vs 4.19+/-1.08 cm/yr ( p=0.29 ) . This study indicates that zinc supplementation increased growth velocity , but these effects did not persist after supplementation was discontinued Objective : To determine the effectiveness of combined iron and zinc over the iron or zinc-only supplementation in correcting deficiency and possible interactive effects in a group of adolescent school children . Subjects and methods : Schoolchildren ( n=821 ) of 12–16 years of age were r and omized into four groups and supplemented with iron ( 50 mg/day ) , zinc ( 14 mg/day ) , iron+zinc or placebo capsules 5 days per week for 24 weeks . Anthropometry , and haemoglobin ( Hb ) , serum zinc ( SZn ) and serum ferritin ( SF ) concentrations were determined before and after the intervention . Results : There were no significant effects between-groups in their weight , height and Hb concentrations with the intervention when compared with the placebo group . Iron-only and combination-supplemented groups had reached mean SF concentrations of 55.1 μg/l with no difference between them ( P=0.99 ) . The zinc-only group had a mean change of 4.3 μmol//l whereas the combine-supplemented group had a mean change of 4.0 μmol/l ( P=0.82 ) . The prevalence of anaemia was found to be 70.3 % in the iron group at baseline ; this was reduced to 14.5 % after the supplementation . In the combine-supplemented group anaemia , prevalence was reduced from 64.8 to 19.3 % . Conclusions : Zinc alone or in combination with iron has not shown a significant improvement in growth in adolescence . Severe and moderate forms of anaemia were successfully treated in children who received iron supplementation . Initial high prevalence of low SZn and iron stores was significantly improved with micronutrient supplementation BACKGROUND In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status , both factors that may be associated with zinc deficiency . In children with severe zinc deficiency , diarrhea is common and responds quickly to zinc supplementation . METHODS To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea , we conducted a double-blind , r and omized , controlled trial involving 937 children , 6 to 35 months of age , in New Delhi , India . All the children also received oral rehydration therapy and vitamin supplements . RESULTS Among the children who received zinc supplementation , there was a 23 percent reduction ( 95 percent confidence interval , 12 percent to 32 percent ) in the risk of continued diarrhea . Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent ( 95 percent confidence interval , -9 percent to + 22 percent ) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent ( 95 percent confidence interval , 27 percent to 48 percent ) after day 3 . When zinc supplementation was initiated within three days of the onset of diarrhea , there was a 39 percent reduction ( 95 percent confidence interval , 7 percent to 61 percent ) in the proportion of episodes lasting more than seven days . In the zinc-supplementation group there was a decrease of 39 percent ( 95 percent confidence interval , 6 percent to 70 percent ) in the mean number of watery stools per day ( P = 0.02 ) and a decrease of 21 percent ( 95 percent confidence interval , 10 percent to 31 percent ) in the number of days with watery diarrhea . The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth . CONCLUSION For infants and young children with acute diarrhea , zinc supplementation results in clinical ly important reductions in the duration and severity of diarrhea OBJECTIVE To evaluate the effect of zinc on the appetite for salt foods in children aged 8 months to 5 years . METHOD Double-blind , placebo-controlled study . Two groups of 20 children refusing to eat salt foods were followed during 6 months . The children in the first group received zinc chelate 1 mg/kg daily for 3 months . The second group received a placebo solution . The two groups were similar in terms of age , sex , weight , duration of breastfeeding , age at weaning , biochemical and hematological data . The response of children to treatment was informed by their mothers . RESULTS 17/20 ( 85 % ) of the children receiving zinc chelate and 10/20 ( 50 % ) of the children receiving placebo improved their appetite for salt foods . The difference was statistically significant ( p < 0.05 , chi-square test ) . CONCLUSION Zinc supplementation may improve the acceptance of salt foods by children INTRODUCTION Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent . Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient population s , but little is known about the risks of mortality and morbidity associated with supplementation . METHODS We did a community-based , cluster-r and omised , double-masked , placebo-controlled , 2x2 factorial trial in children aged 1 - 36 months and residing in southern Nepal . We r and omly assigned children daily oral supplementation to age 36 months with : iron ( 12.5 mg ) and folic acid ( 50 microg ; n=8337 ) , zinc alone ( 10 mg ) , iron , folic acid , and zinc ( n=9230 ) , or placebo ( n=8683 ) ; children aged 1 - 11 months received half the dose . Our primary outcome measure was all-cause mortality , and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea , dysentery , and acute respiratory illness . Analyses were by intention to treat . This study is registered at , number NCT00109551 . FINDINGS The iron and folic acid-containing groups of the study were stopped early in November , 2003 , on the recommendation of the data and safety monitoring board ; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed . We continued to enroll children to the placebo and zinc alone groups . 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up . There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo ( HR 1.03 , 95 % CI 0.78 - 1.37 , and 1.00 , 0.74 - 1.34 , respectively ) . There were no significant differences in the attack rates for diarrhoea , dysentery , or respiratory infections between groups , although all the relative risks except one indicated modest , non-significant protective effects . INTERPRETATION Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death , but might protect against diarrhoea , dysentery , and acute respiratory illness OBJECTIVE . Lead exposure in children has been associated with both global and specific cognitive deficits . Although chelation therapy is advised for children with blood lead concentrations of > 44 μg/dL , treatment options for children with lower blood lead values are limited . Because lead absorption is related to children 's nutritional status , micronutrient supplements may be 1 strategy for combating low-level , chronic lead exposure . This study was design ed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city . METHODS . This r and omized , double-blind , placebo-controlled field trial was conducted in public elementary schools in Torreón , an industrialized city in northern Mexico . A metal foundry , located close to the city center and within 3.5 km of 9 schools , was the main source of lead exposure . A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled . Children were given 30 mg of iron , 30 mg of zinc , both , or a placebo daily for 6 months . A total of 527 completed the treatment , and 515 were available for long-term follow-up , after another 6 months without supplementation . Eleven cognitive tests of memory , attention , visual-spatial abilities , and learning were administered at baseline and each follow-up . RESULTS . There were no consistent or lasting differences in cognitive performance among treatment groups . CONCLUSIONS . Daily supplementation with iron and /or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren . However , these treatments may be effective in setting s with higher prevalence of nutritional deficiencies or in younger children The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture . In a r and omized , double-blind trial in 2296 children in New Delhi , India , we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged ( ≥ 7 d duration ) and acute diarrhea . Children aged 6 - 30 mo received zinc or placebo daily for 4 mo . We measured plasma concentrations of folate , cobalamin , total homocysteine ( tHcy ) , and methylmalonic acid ( MMA ) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables . The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile . The OR ( 95 % CI ) for children below and above the 25th percentile for cobalamin were 0.53 ( 0.35 - 0.78 ) and 0.90 ( 0.73 - 1.11 ) , respectively ( P-interaction = 0.015 ) . There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA ( P-interaction = 0.045 and 0.188 , respectively ) . Baseline folate status did not modify the effect of zinc on prolonged diarrhea . Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea . Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea Physical growth disorders in under 5-year-old children are a common health problem in many countries including Iran . The aim of this study was to determine effects of supplemental zinc on physical growth in preschool children with retarded linear growth . This study was a community-based r and omized controlled trial on 2–5-year-old children with height-for-age below 25th percentile of National Center for Health Statistics growth chart . Ninety children were r and omly assigned in zinc group ( ZG ) or placebo group ( PG ) . After 6 months of zinc or placebo supplementation , we followed up the children for another 6 months . Anthropometric indicators were measured before the intervention and then monthly for 11 months . Forty children in ZG and 45 in PG concluded the study . Zinc supplementation increased weight gain in boys ( P = 0.04 ) and girls ( P = 0.05 ) compared to placebo but had no significant effect on mid-upper arm circumference increment in either sexes . The most significant ( P = 0.001 ) effect of Zinc supplementation was seen in boys ’ height increment at the end of follow-up period . Stunted growth rate in ZG changed significantly ( P = 0.01 ) from 26.7 % to 2.5 % throughout the study . This study showed that daily supplementation of 5 mg elemental zinc for 6 months improves physical growth in terms of height increment and weight gain in children with undesirable linear growth , especially in boys BACKGROUND Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa . However , there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful . METHODS We did a r and omised , placebo-controlled trial , of children aged 1 - 35 months and living in Pemba , Zanzibar . We assigned children to daily oral supplementation with : iron ( 12.5 mg ) and folic acid ( 50 mug ; n=7950 ) , iron , folic acid , and zinc ( n=8120 ) , or placebo ( n=8006 ) ; children aged 1 - 11 months received half the dose . Our primary endpoints were all-cause mortality and admission to hospital . Analyses were by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59549825 . FINDINGS The iron and folic acid-containing groups of the trial were stopped early on Aug 19 , 2003 , on the recommendation of the data and safety monitoring board . To this date , 24 076 children contributed a follow-up of 25,524 child-years . Those who received iron and folic acid with or without zinc were 12 % ( 95 % CI 2 - 23 , p=0.02 ) more likely to die or need treatment in hospital for an adverse event and 11 % ( 1 - 23 % , p=0.03 ) more likely to be admitted to hospital ; there were also 15 % ( -7 to 41 , p=0.19 ) more deaths in these groups . INTERPRETATION Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death . In the presence of an active programme to detect and treat malaria and other infections , iron-deficient and anaemic children can benefit from supplementation . However , supplementation of those who are not iron deficient might be harmful . As such , current guidelines for universal supplementation with iron and folic acid should be revised Nasopharyngeal ( NP ) carriage is necessary for Streptococcus pneumoniae ( Spn ) transmission and invasive infection . This study evaluated the effect of zinc prophylaxis on the association between NP colonization with Spn and acute lower respiratory infection ( ALRI ) in children aged 1 - 35 mo living in a rural district in southern Nepal . We compared carriage prevalence of Spn in 550 ALRI cases with that of healthy age- and season-matched controls . This study , conducted from December 2003 to July 2005 , was nested in a community-r and omized trial design ed to evaluate the effect of zinc on morbidity and mortality in 1- to 36-mo-old children . They were r and omized to receive either 10-mg tablets of zinc or placebo daily until discharge . Approximately 75 % of cases and controls were Spn carriers . There was an interaction between zinc and Spn carriage ( P = 0.091 ) . Spn carriage increased the risk of ALRI in the placebo group [ adjusted matched odds ratio ( AMOR ) = 2.57 ; P = 0.025 ] but not in the zinc group ( AMOR = 0.95 ; P = 0.890 ) . Among the subset of symptomatic cases and their controls , the odds of ALRI for Spn carriers in the placebo group was 30 times greater ( AMOR = 78.09 ; P = 0.006 ) than in the zinc group ( AMOR = 2.77 ; P = 0.288 ) . These findings suggest that zinc prophylaxis may protect children against ALRI associated with carriage of Spn and that the effect may differ by infectious etiology Objective : To describe the distribution of hemoglobin and prevalence of anemia in Nepali children living in the Terai region by potential risk factors for deficiency . Design : This was a cross-sectional , community-based study of baseline characteristics of children enrolled in a r and omized , placebo-controlled clinical trial between January and March 2002 . Participants were weighed and measured and had their blood drawn . Their mothers contributed demographic , morbidity , and feeding data .Subjects : There were 569 4- to 17-month-old children . Statistical models were based on 490 children . Results : Anemia was prevalent : 58 % of the children had a hemoglobin < 105 g/l . Iron-deficiency anemia ( anemia with erythrocyte protoporphyrin ( EP ) ⩾90 μmol/mol heme ) was present in 43 % of the children . Severe anemia was rare : less than 2 % of the children had a hemoglobin < 70 g/l . The mean ( s.d . ) hemoglobin concentration was 101 ( 12.5 ) g/l . Stunting and wasting were prevalent : 30.8 % were stunted ( length-for-age Z-score < −2 ) and 18.1 % were wasted ( weight-for-length Z-score < −2 ) . Bivariate analyses revealed that age , caste , socioeconomic status , dietary diversity , stunting , and underweight were associated with hemoglobin concentration and /or anemia . In multivariate models with and without EP , age and caste were found to be strong predictors of both hemoglobin concentration and anemia . Conclusions : Anemia and iron deficiency increased strongly with age and low-caste status among the study children . The data reveal the importance of targeting interventions to children in the first year of life before they become anemic and iron deficient BACKGROUND Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children . We assessed the effects of provision of two micronutrient powder formulations , with or without zinc , to children in Pakistan . METHODS We did a cluster r and omised trial in urban and rural sites in Sindh , Pakistan . A baseline survey identified 256 clusters , which were r and omly assigned ( within urban and rural strata , by computer-generated r and om numbers ) to one of three groups : non-supplemented control ( group A ) , micronutrient powder without zinc ( group B ) , or micronutrient powder with 10 mg zinc ( group C ) . Children in the clusters aged 6 months were eligible for inclusion in the study . Powders were to be given daily between 6 and 18 months of age ; follow-up was to age 2 years . Micronutrient powder sachets for groups B and C were identical except for colour ; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion . Parents knew whether their child was receiving supplementation , but did not know whether the powder contained zinc . Primary outcomes were growth , episodes of diarrhoea , acute lower respiratory tract infection , fever , and incidence of admission to hospital . This trial is registered with Clinical Trials.gov , number NCT00705445 . RESULTS The trial was done between Nov 1 , 2008 , and Dec 31 , 2011 . 947 children were enrolled in group A clusters , 910 in group B clusters , and 889 in group C clusters . Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group ( odds ratio [ OR ] for micronutrient powder without zinc=0·20 , 95 % CI 0·11 - 0·36 ; OR for micronutrient powder with zinc=0·25 , 95 % CI 0·14 - 0·44 ) . Compared with the control group , children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm ( 95 % CI 0·03 - 0·59 ) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm ( 0·29 - 0·84 ) . We recorded strong evidence of an increased proportion of days with diarrhoea ( p=0·001 ) and increased incidence of bloody diarrhoea ( p=0·003 ) between 6 and 18 months in the two micronutrient powder groups , and reported chest indrawing ( p=0·03 ) . Incidence of febrile episodes or admission to hospital for diarrhoea , respiratory problems , or febrile episodes did not differ between the three groups . INTERPRETATION Use of micronutrient powders reduces iron-deficiency anaemia in young children . However , the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in population s with malnourished children and high diarrhoea burdens . FUNDING Bill & Melinda Gates Foundation We assessed the effect of zinc supplementation on growth velocity in 79 children and adolescents ( 48 males , 38 females ) with idiopathic short stature . Their height‐for‐age was < 5th percentile ( NCHS st and ards ) and their weight‐for‐age was normal . Patients were assigned r and omly to a supplemented group ( S ) to receive Zn 10 mg/day or to a placebo ( P ) group , according to gender and age , and were followed‐up for 12 months using a double‐blind design . Weight , height , armspan , length of lower segment and plasma and hair concentrations of Zn were measured at 0 , 3 , 6 and 12 months . On admission and at 6 months , energy , protein , dietary fiber and zinc intakes were similar for groups S and P ; mean zinc intake was < 6.5mg/day . No differences were found in plasma zinc , hair zinc , weight . armspan or lower segment increments . Pre‐adolescent males in group S had a significantly greater increase in stature compared with group P ( 6.2 ± 2.1 versus 4.5 ± 1.2 cm/year p < 0.025 ) ; z score improved from —2.42 to —2.24 in group S and from — 2.63 to — 2.61 in group P. For adolescent males , the difference was also significant ( 8.3 ± 1.5 versus 6.2 & 2.1 cm/year ; p < 0.025 ) . No differences were noted in females . In Chilean male schoolchildren and adolescents with idiopathic short stature , zinc supplementation increases growth velocity over a 12‐month period OBJECTIVES To determine whether continuing with zinc supplementation after zinc treatment ( ZT ) of an acute diarrhoea episode will result in additional clinical benefits beyond ZT alone . METHODS Children 6 - 23 months of age , living in an urban slum in Dhaka , Bangladesh with acute childhood diarrhoea ( ACD ) , were enrolled in a r and omized , double-blind field trial . All children received 10 days of ZT ( 20 mg/day ) and were then r and omized to zinc ( 10 mg/day ) or placebo supplementation for 3 months . Weekly follow-up of all children occurred over a period of 9 months . RESULTS A total of 353 subjects were enrolled , with 93 % of the zinc supplemented and 96 % of the placebo children followed for 9 months . The incidence density of ACD among those receiving zinc supplementation compared to those receiving placebo was reduced by 28 % ( 2.64 vs.3.66 episodes/p-y follow-up ) over the 3 months while on supplementation and by 21 % ( 2.05 vs.2.59 episodes/p-y follow-up ) over the 9 months of follow-up . There was no observed effect on the incidence of acute respiratory infections ( ARIs ) or on growth . CONCLUSIONS Zinc supplementation after treatment provides additional preventive ACD benefits to children in early childhood . Larger , effectiveness trials of this strategy are warranted OBJECTIVE To determine the efficacy of iron and zinc supplementation on behavior ratings of lead-exposed children . STUDY DESIGN In this double-blind , r and omized trial , 602 first- grade children received 30 mg ferrous fumarate , 30 mg zinc oxide , both , or placebo daily for 6 months . Lead , iron , and zinc status were determined at baseline and follow-up . Parents and teachers provided ratings of child behavior using the Conners Rating Scales . RESULTS The baseline mean ( SD ) blood lead concentration was 11.5 ( 6.1 ) mug/dL , with 51 % of children > or = 10 microg/dL. The prevalence of attention deficit hyperactivity disorder , estimated by combined parent and teacher ratings , was 6 % . At follow-up , parent ratings of oppositional , hyperactive , cognitive problems , and attention deficit hyperactivity disorder decreased by 1.5 , 1.2 , 2.5 , and 3.4 points , respectively ( P < .05 ) . Teacher ratings of hyperactivity increased by 1.1 points ( P = .008 ) , and the mean cognitive problem score declined by 0.7 points ( P = .038 ) . There were no treatment effects on mean change in scores , but children receiving any zinc had a higher likelihood of no longer receiving clinical ly-significant teacher ratings of oppositional behaviors . CONCLUSIONS This regimen of supplementation did not result in consistent improvements in ratings of behavior in lead-exposed children over 6 months Objectives : To study the different responses by sex to zinc supplementation among young children . Study Children and Methods : Double-blind r and omized controlled trial of zinc supplementation in 686 children aged 6–30 months , conducted in Nouna , a rural area of Burkina Faso . Children received either a 12.5-mg zinc sulfate tablet or a placebo every day for about 6 months . Outcomes were morbidity , nutritional status , and mortality . Results : Results revealed significant differences between boys and girls in their responses to zinc supplementation . Boys who received the zinc preparation had fewer days with diarrhea than did control boys ( RR = 0.88 , P = 0.05 ) , especially less nonfebrile diarrhea ( RR = 0.72 , P < 0.001 ) and less dysentery ( RR = 0.65 , P = 0.05 ) , but more ear infections ( RR = 4.00 , P < 0.001 ) . By contrast , girls who received the zinc supplement had the same prevalence of diarrhea as did control girls , but more dysentery ( RR = 3.70 , P < 0.001 ) , fewer ear infections ( RR = 0.39 , P < 0.001 ) , and fewer eye infections ( RR = 0.41 , P < 0.001 ) . The effect of supplementation on nutritional status was not detectable in boys , but girls who received supplementation experienced a faster growth velocity in height than did control girls ( P = 0.004 ) and a faster growth velocity for weight and height if they were wasted and not stunted at baseline ( P = 0.003 ) . Conclusions : Zinc supplementation had positive , nil , or negative effects depending on pathological condition , and the effects were different for boys than for girls Aim : To determine the role of zinc supplementation in reducing diarrhoeal morbidity in children . Methods : A r and omized , double‐blind , community‐based intervention study was conducted in 280 rural children aged between 6 and 41 mo . Children were r and omly allocated into three groups . One group received a daily dose of 10 mg zinc for 5 d wk−1 , another group received 50 mg zinc once weekly and the remaining group received placebo . Zinc was supplemented for 16 wk from November 1999 . Diarrhoeal episodes were detected by weekly surveillance during the supplementation period . Results : Eighty diarrhoeal episodes were detected among 59 children in all 3 groups . The groups were compared with each other at baseline and as regard to the outcome variable ( incidence of diarrhoea ) . The proportion of children suffering from diarrhoea during the period was significantly lower in the zinc‐supplemented groups ( 15.8 % in daily and 16.5 % in weekly group ) than in the placebo group ( 30.8 % ) . The incidence of diarrhoea in the daily and weekly zinc‐supplemented groups was 0.68 and 0.69 episodes child−1 y−1 , and that in the placebo group was 1.67 episodes child−1 y−1 ( relative risk 0.41 , 95 % confidence interval 0.24–0.71 ) . Diarrhoeal incidence of > 4d duration was found to occur significantly less often in the supplemented groups . There was no difference in diarrhoeal incidence between the daily and weekly zinc‐supplemented children . There were no detected adverse reactions in any of the supplemented groups OBJECTIVES To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels . METHODS On 2 consecutive days , we performed 5-hour observations with momentary time sampling ( instant activity every 10 minutes ) in children selected from an ongoing double-blind , r and omized trial of zinc supplementation . The study was conducted in Kalkaji , a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition . A total of 93 children ( 48 zinc and 45 control ) 12 to 23 months of age from an ongoing community-based , r and omized , controlled trial received supplements for at least 1 month before study ; 71 % had received supplementation for more than 120 days . Zinc gluconate ( 10 mg of elemental zinc ) was given daily , with both zinc and control groups receiving vitamins A , B1 , B2 , B6 , D3 , and E and niacinamide in addition . RESULTS Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores . Children in the zinc group spent 72 % more time performing activities in the high-movement group . Among the zinc-supplemented children , the activity rating by the children 's activity rating score was 12 % higher and by the energy expenditure score was 8.3 % higher than in the control group . CONCLUSIONS In conclusion , zinc supplementation , given along with selected vitamins , was associated with significantly greater activity levels in children . The relationship between the activity increase and locomotor development needs to be investigated , as do the long-term implication s of zinc supplementation in terms of developmental status and school performance In rural Mexico and in many developing countries micronutrient deficiencies , growth stunting , and morbidity from infectious diseases are highly prevalent in young children . We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and /or iron supplementation . In a double-blind , r and omized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine , 20 mg Fe as ferrous sulfate , 20 mg Zn + 20 mg Fe , or a placebo . After 12 mo , plasma zinc increased significantly in the two zinc-treated groups , and plasma ferritin was significantly higher in the two iron-treated groups . There was no effect of treatments on growth velocity or body composition . Children in both zinc-supplemented groups had fewer episodes of disease ( zinc alone , 3.9 + /- 0.3 ; zinc+iron , 3.7 + /- 0.4 ; placebo , 4.6 + /- 0.5 ; P < 0.03 ) , including diarrhea ( zinc alone , 0.7 + /- 0.1 ; zinc+iron , 0.8 + /- 0.1 ; placebo , 1.1 + /- 0.2 ; P < 0.01 ) . Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition OBJECTIVE To determine whether supplemental zinc , with or without additional micronutrients , affects the severity and duration of persistent childhood diarrhea and the rate of nutritional recovery . DESIGN The study was a community-based , double-blind , r and omized trial implemented in a shanty town in Lima , Peru . Children aged 6 to 36 months with persistent ( > /=14 days ) diarrhea received daily , for 2 weeks , a placebo ( group P , n = 136 ) or a supplement of 20 mg of zinc , either with ( group Z+VM , n = 137 ) or without ( group Z , n = 139 ) additional vitamins and minerals . Symptoms of illness were recorded daily , and biochemical and anthropometric assessment s were completed at baseline and on day 15 . RESULTS The treatment groups were similar at baseline with regard to the characteristics of the presenting episode , anthropometric data , and plasma zinc concentration . The children consumed , on average , 95 % ( group P ) , 94 % ( group Z ) , or 88 % ( group Z+VM ) of the supplement ( P < .001 ) . The plasma zinc concentration did not change significantly from baseline to day 15 in group P ( 4 microg/dL ) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM . The median duration of diarrhea after starting treatment was 1 day ; among children who continued to have diarrhea , there was a significant effect of treatment on diarrheal duration ( P = .04 , analysis of covariance ) . Specifically , the duration of illness was significantly reduced by 28 % in children in group Z ( P = .01 ) and by 33 % in girls in group Z+VM ( P = .04 ) . There were no differences in the severity of the episode by treatment group . CONCLUSION There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population Background / Objectives : Many children have diets deficient in both iron and zinc , but there has been some evidence of negative interactions when they are supplemented together . The optimal delivery approach would maximize clinical benefits of both nutrients . We studied the effectiveness of different iron and zinc supplement delivery approaches to improve diarrhea and anemia in a rural Bangladesh population . Study Design : R and omized , double blind , placebo-controlled factorial community trial . Results : Iron supplementation alone increased diarrhea , but adding zinc , separately or together , attenuated these harmful effects . Combined zinc and iron was as effective as iron alone for iron outcomes . All supplements were vomited < 1 % of the time , but combined iron and zinc were vomited significantly more than any of the other supplements . Children receiving zinc and iron ( together or separately ) had fewer hospitalizations . Separating delivery of iron and zinc may have some additional benefit in stunted children . Conclusions : Separate and combined administration of iron and zinc are equally effective for reducing diarrhea , hospitalizations and improving iron outcomes . There may be some benefit in separate administration in stunted children Objective : We investigated whether there was a growth or morbidity response to zinc supplementation . Design : The study was r and omized , placebo-controlled , and double-blind . Setting : Children were recruited at clinics in Kingston , Jamaica , and supplemented at home . Subjects : Children selected were singletons aged 6–24 months , and stunted ( < –2.0 s.d . length for age , NCHS references ) . They were stratified by sex and age and r and omly assigned to receive zinc supplement ( n=31 ) or placebo ( n=30 ) . Four children were excluded because of hospitalization ; all others had all measurements . Adequately nourished children ( n=24 ) were recruited from a well-baby clinic . Interventions : The supplement provided 5 mg elemental zinc in a syrup daily for 12 weeks ; the placebo comprised the syrup only . Main outcome measures : Caretakers were interviewed to obtain social background data , number of clinic visits and hospitalizations . Anthropometric measurements were done on enrolment , and after 6 weeks , 12 weeks and 12 months . Children 's health was determined by weekly question naire to caretakers of the undernourished groups during the supplementation period . Results : The supplemented and placebo groups were similar on enrolment . The adequately nourished children were from significantly better socio-economic circumstances . Mean initial hair zinc content was 5.5±4.8μmol/g ( supplemented group ) and 6.7±12.1 μmol/g (placebo)(n.s . ) . Regression analyses showed that there were no significant effects of supplementation on length , height or head circumference , nor on the incidence of any morbidity symptom . Mean duration of the episodes was significantly shorter for skin rashes in the supple-mented group compared with the control group ( ANCOVA , P=0.02 ) , and longer for vomiting ( P=0.02 ) . The incidence of hospitalization was significantly greater in the control group ( Fisher 's exact test , P=0.02 ) . Conclusions : Zinc supplementation reduced the hospitalizations which probably reflect severity of morbidity , but did not improve growth . Sponsorship : The study was funded by the Commonwealth Caribbean Medical Research Council and a Research and Publications Grant , University of the West Indies , Mona . Tropivite Vitamin Drops were donated by Federated Pharmaceutical Co. Ltd , Jamaica ; and zinc sulphate donated by Lascelles Laboratories Ltd. , Jamaica Background . Increased acute lower respiratory infection incidence , severity , and mortality are associated with malnutrition , and reduced immunological competence may be a mechanism for this association . Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status , we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection . Methods . We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind , r and omized , controlled trial in 609 children ( zinc , n = 298 ; control , n = 311 ) 6 to 35 months of age . Supplementation and morbidity surveillance were done for 6 months . Results . After 120 days of supplementation , the percentage of children with plasma zinc concentrations < 60 μg/dL decreased from 35.6 % to 11.6 % in the zinc group , whereas in the control group it increased from 36.8 % to 43.6 % . Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children . After correction for correlation of data using generalized estimating equation regression methods , there was a reduction of 45 % ( 95 % confidence interval , 10 % to 67 % ) in the incidence of acute lower respiratory infections in zinc-supplemented children . Conclusions . A dietary zinc supplement result ed in a significant reduction in respiratory morbidity in preschool children . These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries BACKGROUND & AIM Acute lower respiratory infections are the most frequent illnesses globally in children less than 5 years old . The aim of this r and omized double blind controlled trial is to assess the effectiveness of zinc gluconate supplementation for 2 months period compared to placebo in reducing respiratory morbidity in acute lower respiratory infected children up to 5 years of age living in zinc poor population . METHODS Children were r and omly assigned to receive either 10 mg zinc gluconate or placebo for 60 days . Demographic and clinical data were collected at baseline and every two weeks for 180 days . RESULTS The final analysis included 96 children allocated equally to the two groups . The number of episodes of acute lower respiratory infections and severe acute lower respiratory infections were significantly lower in zinc group compared to placebo group ( 20.8 % vs. 45.8 % ( P = 0.009 ) and 21.7 % vs. 58.3 % ( P < 0.001 ) , respectively ) . The acute lower respiratory infections free days were higher in the zinc supplemented group ( P < 0.001 ) . The median recovery time of morbidity was significantly shorter in zinc group ( P < 0.001 ) . CONCLUSIONS Zinc supplement may result in significant reduction in respiratory morbidity among children with acute lower respiratory infections in zinc poor population . This study was registered under Clinical Trials.gov Identifier no. NCT00536133 OBJECTIVE Zinc is essential for growth and cognition of experimental animals . Past research found zinc repletion improved growth of stunted Chinese children . Therefore we measured effects of zinc repletion on growth and neuropsychological functions of children . DESIGN Double-blind r and omized controlled treatment trial . SETTING Elementary schools in low income districts of Chongqing , Qingdao and Shanghai . SUBJECTS Three hundred-seventy-two 6 to 9 year old first grade rs . INTERVENTIONS Treatments were 20 mg zinc , 20 mg zinc with micronutrients , or micronutrients alone . The micronutrient mixture was based on guidelines of the US NAS/NRC . Treatments were assigned to classrooms of 40 or more children each , and administered by teachers 6 days per week for 10 weeks . MEASURES OF OUTCOME Changes in knee height and neuropsychological functions . RESULTS Zinc alone had the least effect on growth while zinc with micronutrients had the largest effect ; micronutrients alone had an intermediate effect . Zinc-containing treatments improved neuropsychological functions , but micronutrients alone had little effect . CONCLUSIONS The findings confirm the essentiality of zinc for growth of children , and show , for the first time , the essentiality of zinc for neuropsychological functions of children . In addition , the need for repletion of other potentially limiting nutrients in studies examining the effects of specific nutrients on growth and neuropsychological functions was confirmed We evaluated the effect of one year of supplementation with iron plus zinc ( 12 mg/day of Fe+++ and 12.5 mg/day of Zn++ ) , zinc alone ( 12.5 mg/day of Zn++ ) and placebo on growth and on the iron , zinc , copper and selenium tissue contents in 30 well-selected children of short stature ( 16 M and 14 F ; 4 - 11 years old ) . Before and after supplementation , we measured the concentrations of iron , transferrin , ferritin , zinc and copper in serum , of zinc in erythrocytes and leukocytes , and of zinc , copper and selenium in hair , as well as glutathione peroxidase activity in erythrocytes . Before supplementation , ferritin and serum , erythrocyte and hair zinc contents were significantly lower than in age-matched controls , while the other measured indices were in the normal range . Iron plus zinc supplementation caused an improvement in growth rate in all subjects , i.e. , the median Z-score increased from -2.22 + /- 0.45 to -0.64 + /- 0.55 ; ( p < 0.01 ) . In the zinc-supplemented group , only the subjects whose ferritin levels were higher than 20 ng/L before supplementation showed a similar improvement of growth rate . Iron plus zinc supplementation could be a reasonable treatment in short , prepubertal children affected by marginal zinc and iron deficiency Among breastfed infants , growth faltering in comparison with reference growth curves is common in both developing and developed countries . We performed a zinc supplementation trial in Paris , France , to find out whether such growth faltering is due to nutritional zinc deficiency . 57 breastfed infants aged 4 - 9 ( mean 5.7 ) months were r and omly assigned to receive either 5 mg zinc daily or a placebo for 3 months . Most of the infants were from low-income immigrant families and the majority were of African origin . Before supplementation there were no significant differences between the zinc and placebo groups in weight , length , or corresponding Z-scores for age . After 3 months ' supplementation , the length-for-age Z-score had increased in the zinc group and fallen in the placebo group ( + 0.21 vs -0.13 , p = 0.029 ) . This difference was due mainly to greater linear growth of boys in the zinc than in the placebo group ( 6.0 vs 4.6 cm , p = 0.02 ) . Weight gain was also significantly greater with zinc supplementation ( 1.64 vs 1.28 kg , p = 0.047 ) . Among infants breastfed for longer than 4 months , decreases in growth velocity result partly from inadequate zinc intake OBJECTIVE To evaluate the effect of zinc supplementation on mental and psychomotor scores in children aged 12 to 18 months . STUDY DESIGN In this double-blind , r and omized , placebo-controlled trial , children aged 6 to 30 months received daily elemental zinc ( 10 mg for infants and 20 mg for others ) or placebo for 4 months . Bayley Scales of Infant Development II were used for development assessment in the 12- to 18-month subgroup at enrollment and the end of the study . RESULTS At the end of the study , the adjusted mean mental ( P = .36 ) and psychomotor ( P = .28 ) index scores were similar in the intervention and control groups . In a multivariate model , the baseline mental development index score was positively associated with the mother 's schooling , the child 's height for age , packed cell volumes , hospital birth , and attendance at a day care center , and was negatively associated with the child 's age . Breastfeeding , the child 's weight for height , and packed cell volumes were positively associated with the baseline psychomotor index score . CONCLUSION Zinc supplementation did not affect the mental or psychomotor development index scores in a setting in which zinc deficiency is common BACKGROUND Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years . Most deaths occur during infancy and in developing countries . Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea , and to reduce child mortality . We aim ed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years . METHODS 1665 poor , urban children aged 60 days to 12 months were r and omly assigned zinc ( 70 mg ) or placebo orally once weekly for 12 months . Children were assessed every week by field research assistants . Our primary outcomes were the rate of pneumonia and diarrhoea . The rates of other respiratory tract infections were the secondary outcomes . Growth , final serum copper , and final haemoglobin were also measured . Analysis was by intention to treat . FINDINGS 34 children were excluded before r and om assignment to treatment group because they had tuberculosis . 809 children were assigned zinc , and 812 placebo . After treatment assignment , 103 children in the treatment group and 44 in the control group withdrew . There were significantly fewer incidents of pneumonia in the zinc group than the control group ( 199 vs 286 ; relative risk 0.83 , 95 % CI 0.73 - 0.95 ) , and a small but significant effect on incidence of diarrhoea ( 1881 cases vs 2407 ; 0.94 , 0.88 - 0.99 ) . There were two deaths in the zinc group and 14 in the placebo group ( p=0.013 ) . There were no pneumonia-related deaths in the zinc group , but ten in the placebo group ( p=0.013 ) . The zinc group had a small gain in height , but not weight at 10 months compared with the placebo group . Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation . INTERPRETATION 70 mg of zinc weekly reduces pneumonia and mortality in young children . However , compliance with weekly intake might be problematic outside a research programme Abstract The tuberculin test ( PPD ) is used frequently in the diagnosis of tuberculosis . PPD , however , relies on an intact cell-mediated immunity and infected children often have false negative results . This study assessed whether a single oral zinc supplement modifies the PPD in duration size and its association with nutritional status in Brazilian children . Ninety-eight children below 15 years of age who had been exposed to adults with smear-positive pulmonary TB in 1998 were tested by PPD in 1998 and 2000 . Children were r and omised in 2000 to receive a single oral dose of zinc sulphate or a placebo at the time of administering the PPD . Forty-three ( 44 % ) children were PPD-positive in 1998 and 54 ( 55 % ) in 2000 . A higher proportion of children were classified as PPD-positive in 2000 in the zinc-supplemented group ( 57.1 % ) than in the placebo group ( 53.1 % ) . PPD in duration s were larger in children receiving zinc ( mean 18.5 and 15.5 mm in the zinc and placebo groups , respectively ) ( p<0.03 ) . Mean in duration sizes in 2000 were larger in zinc-supplemented children , regardless of their nutritional status . Our study demonstrates that zinc increases the PPD in duration size in children irrespective of nutritional state . Zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a non-specific booster of immunological mechanisms ( whether or not there is a deficiency ) Micronutrient deficiencies are a public health concern among young children in low-income countries , and novel strategies are needed to improve the nutritional status of children at risk . One promising approach is the use of lipid-based nutrient supplements ( LNS ) , which can be added to complementary food at the time of consumption . The optimal amount of zinc to include in LNS is uncertain , and concerns have been expressed about possible adverse effects of zinc on sensory characteristics of LNS . We conducted a series of acceptability studies of LNS containing either 0 or 10 mg of zinc per daily 20 g LNS dose among Burkinabe children 9 - 15 months old and their mothers . These acceptability studies included observations of children 's consumption , maternal and child sensory reaction to the products using a 5-unit hedonic scale , a triangle test for detection of differences and a review of maternal reports of their child-feeding experiences during a 2-week home-feeding trial . The LNS products were well appreciated by the mothers and children during the sensory trials and the 2-week home-feeding trial . The addition of 10 mg zinc to LNS did not affect the consumed proportion of the offered porridge-LNS-mixture ( P = 0.43 ) . Results of the triangle test with mothers confirmed that there was no detectable difference between products containing 0 or 10 mg zinc per 20 g LNS dose . Most importantly , interviews and focus groups following the 2-week home-feeding trial indicated good acceptability of the products by mothers and their children Over a 2-year period , dietary and socioeconomic data were collected from 793 food records of 90 toddlers , aged 1 to 2 years , who were predominantly U.S. Hispanics living in low-income households in Denver , CO . This study was part of a larger investigation design ed to assess the efficacy of vitamin and mineral supplements in young children . The toddlers were r and omly assigned to one of five treatment groups : multivitamin ; multivitamin and iron ; multivitamin , iron , and zinc ; multivitamin and zinc ; or placebo . Three-day food records that were collected from the toddlers at the beginning of the study , at 3 months , and at 6 months were used to assess the dietary and nutrient intakes . Meal patterns were devised on the basis of the frequency of food consumption and common food combinations . Nutrient values were calculated using a diet analyzer program . Nutrient analysis of the toddlers ' diets indicated that iron and magnesium were consumed least frequently , whereas more than adequate amounts of protein ( 193 % of the Recommended Dietary Allowance ) and sodium ( 207 % of minimum requirements for healthy persons ) were consumed . No significant differences in nutrient intakes were observed among the treatment groups , suggesting that the vitamin and mineral supplements had no effect . A difference in energy intake was observed over time with the 6-month and 3-month intakes significantly higher than the initial intakes . There was also a high consumption of carbonated beverages . Despite the low income levels of the families , these toddlers were consuming adequate amounts of food ; however , an educational component aim ed at reducing the toddlers ' high intakes of protein , sodium , and carbonated drinks may help improve the present feeding practice s of the mothers Abstract Objectives : To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia . Design : Double masked , r and omised placebo controlled trial . Setting : A slum community in New Delhi , India . Participants : 2482 children aged 6 to 30 months . Interventions : Daily elemental zinc , 10 mg to infants and 20 mg to older children or placebo for four months . Both groups received single massive dose of vitamin A ( 100 000 IU for infants and 200 000 IU for older children ) at enrolment . Main outcome measures : All households were visited weekly . Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians . Results : At four months the mean plasma zinc concentration was higher in the zinc group ( 19.8 ( SD 10.1 ) v 9.3 ( 2.1 ) μmol/l , P<0.001 ) . The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups ( absolute risk reduction −0.2 % , 95 % confidence interval −3.9 % to 3.6 % ) . Zinc supplementation result ed in a lower incidence of pneumonia than placebo ( absolute risk reduction 2.5 % , 95 % confidence interval 0.4 % to 4.6 % ) . After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74 , 95 % confidence interval 0.56 to 0.99 . Conclusions : Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin BACKGROUND Zinc supplementation can reduce subsequent morbidity in children recovering from diarrhoea and respiratory illness in developing countries . However , whether routine supplementation would decrease morbidity and mortality in population s with zinc deficiency is unclear . We assessed the effect of daily zinc supplementation on children in southern Nepal . METHODS We did a community-based , cluster-r and omised , double-masked , placebo-controlled , 2x2 factorial trial in children aged 1 - 35 months . Treatment groups were placebo , iron and folic acid , zinc , and iron and folic acid with zinc , with daily doses of 12.5 mg iron , 50 microg folic acid , and 10 mg zinc . Study staff gave children tablets on 2 days each week and left tablets with caregivers for other days . All children received vitamin A supplementation twice per year . Results of the iron arm of the trial have been reported previously . Between October , 2001 , and January , 2006 , 41,276 children were enrolled into the placebo ( n=20,308 ) or zinc ( n=20,968 ) groups and were followed-up for 60,636.3 person-years . The primary outcome was child mortality , and analyses were by intention to treat . Daily reports of signs and symptoms of common morbidities in stratified r and om sub sample s of children were assessed every week for 12 months . This study is registered at Clinical Trials.gov , number NCT00109551 . FINDINGS 2505 children refused to continue the trial and 3219 children were lost to follow-up . There was no significant difference in mortality between the zinc and placebo groups ( 316 vs 333 deaths ; hazard ratio 0.92 , 95 % CI 0.75 - 1.12 ) . Zinc had no effect on mortality in children younger than 12 months ( 181 vs 168 deaths ; 1.04 , 0.83 - 1.31 ) ; mortality was lower , but not statistically significantly so , in older children receiving zinc ( 135 vs 165 ; 0.80 , 0.60 - 1.06 ) . The frequency and duration of diarrhoea , persistent diarrhoea , dysentery , and acute lower respiratory infections did not differ between the groups . INTERPRETATION Total mortality of children receiving zinc supplementation was not significantly different from that of children receiving placebo . Further data are needed from other population s with endemic zinc deficiency to confirm the potential age-specific effects reported in this study OBJECTIVE To study the relationship between micronutrient supplementation and children growth . METHODS A double-blind , placebo-controlled trial was conducted in 156 growth retarded preschool children . They were r and omly assigned to five groups : supplemental control ( S-control , n = 28 ) , zinc supplementation ( + Zn , 3.5 mg Zn/day , n = 34 ) , zinc and calcium supplementation ( + ZnCa , 3.5 mg Zn + 250 mg Ca/day , n = 37 ) , zinc and calcium and vitamin A supplementation ( + ZnCaVA , 3.5 mg Zn + 250 mg Ca + 200 g VA/day , n = 28 ) , Calcium , and vitamin A supplementation ( + CaVA , 250 mg Ca + 200 g VA/day , n = 29 ) . Another 34 children with normal height were selected as normal control ( N-control ) . Supplementation continued for twelve months . RESULTS The height gain in + Zn group ( 7.84 cm per year ) and + ZnCa group ( 7.70 cm per year ) was significantly higher than that in S-control group ( 6.74 cm per year , P < 0.05 ) ; The weight gain in + ZnCaVA group ( 2.55 kg per year ) and + CaVA group ( 2.57 kg per year ) was also significantly higher than that in S-control group ( 2.19 kg per year , P < 0.05 ) ; The average days of illness in each supplementation group were lower than that in S-control ( 13 days per year compared with 23 days per year ) . No significant difference was observed on bone age . CONCLUSION Zinc and Zinc + Calcium supplementation can improve the height gain , and vitamin A can improve weight gain in growth retarded preschool children , but do not affect the maturity of bone . Micronutrient supplementation can lower the morbidity of these children There is limited evidence about the effects of systemic zinc supplementation on oral health in healthy children . The aim of this study is to determine the effect of oral zinc supplementation on oral health in low socioeconomic level primary school children . In this double-blind r and omized study , 68 children were r and omly separated into two groups ( study and placebo ) to receive 15 mg/day elemental zinc or placebo syrup five days a week for 10 weeks . Oral examinations were performed before and after supplementation . After supplementation , the Gingival Index improved statistically in both groups ( p < 0.05 ) . However , the Plaque Index improved statistically only in the zinc group ( p = 0.02 ) . After supplementation , the Plaque Index scores increased in 13 cases and decreased in 15 in the placebo group ( p = 0.70 ) and increased in only 6 cases and decreased in 18 in the study group ( p = 0.02 ) . Oral zinc supplementation may contribute to the prevention of dental caries in low socioeconomic level primary school healthy children OBJECTIVE . Gastrointestinal parasites continue to be an important cause of morbidity and stunting among children in developing countries . We evaluated the effect of vitamin A and zinc supplementation on infections by Giardia lamblia , Ascaris lumbricoides , and Entamoeba histolytica . METHODS . A r and omized , double-blind , placebo-controlled trial was conducted among 707 children who were 6 to 15 months of age and from periurban areas of Mexico City , Mexico , between January 2000 and May 2002 . Children , who were assigned to receive either vitamin A every 2 months , a daily zinc supplement , a combined vitamin A and zinc supplement , or a placebo , were followed for 1 year . The primary end points were the 12-month rates and duration s of infection for the 3 parasites and rates of parasite-associated diarrheal disease as determined in stools collected once a month and after diarrheal episodes . RESULTS . G lamblia infections were reduced and A lumbricoides infections increased among children in the combined vitamin A and zinc group or the zinc alone group , respectively . Duration s of Giardia infections were reduced among children in all 3 treatment arms , whereas Ascaris infections were reduced in the vitamin A and zinc group . In contrast , E histolytica infection duration s were longer among zinc-supplemented children . Finally , E histolytica– and A lumbricoides – associated diarrheal episodes were reduced among children who received zinc alone or a combined vitamin A and zinc supplement , respectively . CONCLUSIONS . We found that vitamin A and zinc supplementation was associated with distinct parasite-specific health outcomes . Vitamin A plus zinc reduces G lamblia incidence , whereas zinc supplementation increases A lumbricoides incidence but decreases E histolytica – associated diarrhea Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies . The objective of this r and omized , placebo-controlled clinical trial was to identify the effect of daily supplementation with iron , zinc , and iron plus zinc on the morbidity experience of 855 children 0.5 - 15 years of age in Peru . Single nutrient supplementation with zinc reduced diarrhea morbidity by 23 % in all children . In older children ( more than five years of age ) , iron supplementation increased morbidity due to Plasmodium vivax and diarrhea . In younger children , iron combined with zinc provided protection against P. vivax malaria , but also interfered with some of the diarrhea protection associated with zinc supplementation . No statistically significant effect was observed of either supplement on incidence of respiratory infection or anthropometric indices . Iron and zinc deficiencies should be remedied , and combined supplementation may be a good option , particularly in younger children in P. vivax malaria-endemic areas , although local endemicity and species-specific prevalence should be considered carefully when design ing any supplementation program involving iron in a malaria-endemic area The objective of this study was to determine whether zinc deficiency is one of the factors involved in nutritional failure to thrive in infants and toddlers . Participants were selected on the basis of anthropometric criteria , particularly a decline in weight velocity preceding changes in length gains . The investigation was design ed as a double-blind , r and omized , pair-matched , controlled study of dietary zinc supplementation of 6 months ' duration . Anthropometric data were collected at 0 , 1 , 3 , and 6 months . Twenty-five pairs of infants completed the project . When compared with placebo-treated control children , the zinc-supplemented group ( combined sexes ) and the supplemented boys showed significant improvements in st and ard deviation scores for weight for all three intervals , the largest differences occurring for the 0- to 3-month interval ( P less than or equal to .0001 ) . The zinc-supplemented girls demonstrated a trend toward improvements in changes in st and ard deviation scores for weight ( P = .056 ) . There were no differences in length gains for either boys or girls . This improvement in weight gains after zinc supplementation demonstrates that mild zinc deficiency can be one of the etiologic factors in nutritional failure to thrive during infancy BACKGROUND Iron and zinc are important micronutrients for child growth and development . One would expect that iron and zinc supplementation in infancy would affect long-term cognitive development and school achievement , but this has not been evaluated . OBJECTIVE We investigated the effect of iron or zinc supplementation or both during infancy on cognitive performance 8 y later . DESIGN A follow-up study was performed in 560 children aged 9 y or 92 % of those who had participated in a r and omized controlled trial involving 4 groups who received daily iron , zinc , iron plus zinc , or a placebo at 4 - 6 mo of age for 6 mo . Cognitive performance was assessed by using the Wechsler Intelligence Scale for Children-Third Edition ( Thai version ) , the Raven 's Colored Progressive Matrices ( CPM ) , and school performance tests . General linear mixed models were used to assess long-term effects . RESULTS No significant differences in any of the outcomes at 9 y of age were observed at follow-up between the 4 groups . Mean intelligence quotients ranged across groups from 92.9 to 93.7 for full scale , 93.9 - 95.4 for verbal , and 93.1 - 94.0 for performance . The Raven 's CPM score ranged from 21.4 to 22.4 . CONCLUSION Supplementation with iron or zinc or both during infancy does not lead to long-term cognitive improvement in 9-y-old children . This trial was registered at clinical trials.gov as NCT00824304 Twenty-one prepubertal , short Japanese children ( 11 boys ) without endocrine abnormalities were identified as having mild-to-moderate zinc deficiency by zinc kinetics studies ( zinc body clearance > or = 20 ml/kg per hour ) . Only one child had a serum zinc level < 65 micrograms/dl ( cutoff level ) . A total of 10 children ( 5 boys ) received 5 mg/kg per day of zinc sulfate for 6 months ; 11 untreated children ( 6 boys ) served as control subjects . During treatment , calorie intake ( p < 0.01 ) , growth velocity ( p < 0.01 ) , serum zinc , calcium , and phosphorus concentrations , alkaline phosphatase activity ( p < 0.001 ) , percentage of tubular reabsorption of phosphorus ( p < 0.05 ) , ratio of maximal tubular reabsorption rate for phosphorus to the glomerular filtration rate ( p < 0.05 ) , serum osteocalcin level ( p < 0.01 ) , and plasma insulin-like growth factor 1 ( p < 0.05 ) were significantly increased , but urinary excretion of growth hormone was unchanged in the zinc-supplemented group . All these values were unchanged in the untreated children . We conclude that zinc supplementation is effective for inducing growth in short children with zinc deficiency , and that body zinc clearance tests facilitate detection of marginal zinc deficiency OBJECTIVE To assess the effect of zinc supplementation on respiratory tract disease , immunity and growth in malnourished children . DESIGN A r and omized double-blind placebo-controlled trial . SETTING A day-care center in Quito , Ecuador . SUBJECTS Fifty children ( 12 - 59 months old ) recruited by height-for-age and weight-for-age deficit . INTERVENTIONS Twenty-five children ( supplemented , S group ) received 10 mg/day of zinc as zinc sulfate , and 25 ( nonsupplemented , NS group ) received a placebo during 60 days . All were also observed during a 60-day postsupplementation period . Two children of the S group dropped out . Daily the clinical presence of cough , respiratory tract secretions , and fever , was recorded . On days 0,60 and 120 , the cutaneous delayed-type hypersensitivity ( DTH ) to multiple antigens , and anthropometric parameters were assessed . On days 0 and 60 serum zinc levels were also measured . RESULTS On day 60 , DTH was significantly larger ( 20.8 + /- 7.1 vs 16.1 + /- 9.7 mm ) , and serum zinc levels were significantly higher ( 118.6 + /- 47.1 vs 83.1 + /- 24.5 micrograms/dl ) in the S group than in the NS group ( P < 0.05 for each ) . The incidence of fever [ relative risk ( RR ) : 0.30 , c.i . = 0.08- 0.95 , P = 0.02 ] , cough ( RR ) : 0.52 , c.i . = 0.32 - 0.84 , P = 0.004 ) and upper respiratory tract secretions (RR):0.72 , c.i . = 0.59 - 0.88 , P = 0.001 ) was lower in the S group than in the NS group at day 60 . At the end of the postsupplementation observation period ( day 120 ) , the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups . The incidence of cough was higher at day 120 in the S group than in the NS group ( RR ) : 2.28 , c.i . = 1.37 - 3.83 , P = 0.001 ) . CONCLUSIONS This study supports a role for zinc in immunity , and immunity to respiratory infections , while pointing out the need for larger studies BACKGROUND Zinc deficiency is associated with impaired immune function and an increased risk of infection . Supplementation can decrease the incidence of diarrhoea and pneumonia in children in re source -poor countries . However , in children with HIV-1 infection , the safety of zinc supplementation is uncertain . We aim ed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence . METHODS We did a r and omised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey 's Hospital in Pietermaritzburg , South Africa . 96 children with HIV-1 infection were r and omly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months . Baseline measurements of plasma HIV-1 viral load and the percentage of CD4 + T lymphocytes were established at two study visits before r and omisation , and measurements were repeated 3 , 6 , and 9 months after the start of supplementation . The primary outcome measure was plasma HIV-1 viral load . Analysis was per protocol . FINDINGS The mean log(10 ) HIV-1 viral load was 5.4 ( SD 0.61 ) for the placebo group and 5.4 ( SD 0.66 ) for the zinc-supplemented group 6 months after supplementation began ( difference 0.0002 , 95 % CI -0.27 to 0.27 ) . 3 months after supplementation ended , the corresponding values were 5.5 ( SD 0.77 ) and 5.4 ( SD 0.61 ) , a difference of 0.05 ( -0.24 to 0.35 ) . The mean percentage of CD4 + T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation . Two deaths occurred in the zinc supplementation group and seven in the placebo group ( p=0.1 ) . Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo . Watery diarrhoea was diagnosed at 30 ( 7.4 % ) of 407 clinic visits in the zinc-supplemented group versus 65 ( 14.5 % ) of 447 visits in the placebo group ( p=0.001 ) . INTERPRETATION Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea . RELEVANCE TO PRACTICE Programmes to enhance zinc intake in deficient population s with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication . In view of the reductions in diarrhoea and pneumonia morbidity , zinc supplementation should be used as adjunct therapy for children with HIV-1 infection OBJECTIVE A community-based , r and omized , double-blind intervention trial was conducted to measure the impact of zinc supplementation on young Guatemalan children 's morbidity from diarrhea and respiratory infections . METHODS Children aged 6 to 9 months were r and omly assigned to receive 4 mL of a beverage containing 10 mg of zinc ( as zinc sulfate ) daily ( 7 d/wk ) for 7 months ( n = 45 ) or a placebo ( n = 44 ) . Morbidity data were collected daily . Diagnoses of diarrhea , fever , and anorexia were based on mothers ' definitions . Respiratory infections were defined as the presence of at least two of the following symptoms : runny nose , cough , wheezing , difficulty breathing , or fever . RESULTS High rates of diarrhea and respiratory infections were reported . Children from the placebo group had a 20 % episodic prevalence of diarrhea , with 8 episodes/100 d , and a 7 % episodic prevalence of respiratory infections , with 3 episodes/100 d. The median incidence of diarrhea among children who received zinc supplementation was reduced by 22 % ( Wilcoxon rank test ) , with larger reductions among boys and among children with weight-for-length at baseline lower than the median of the sample ( 39 % reductions in both subgroups ) . Zinc supplementation also produced a 67 % reduction in the percentage of children who had one or more episodes of persistent diarrhea ( chi2 test ) . No significant effects were found on the episodic prevalence of diarrhea , the number of days per episode , or the episodic prevalence or incidence of respiratory infections . CONCLUSIONS The large impact of zinc supplementation on diarrhea incidence suggests that young , rural Guatemalan children may be zinc deficient and that zinc supplementation may be an effective intervention to improve their health and growth The aim of this study was to investigate the effects of supplementation of iron and zinc , alone or combined , on iron , zinc and vitamin A status in primary school children . The study was a r and omized double-blind clinical trial in which 79 primary school children , 11 year of age , were r and omly supplemented for 4 months with iron ( 20 mg day(-1 ) ) , zinc ( 20 mg day(-1 ) ) , or iron+ zinc ( 20 mg of each day(-1 ) ) . Serum zinc significantly increased in all supplemented groups . Compared with iron alone , zinc supplementation and zinc plus iron were associated with higher serum zinc and plasma ferritin levels . Zinc supplementation result ed in a decrease in serum ferritin . Children deficient in zinc at the beginning of the study had a significantly greater increase in serum zinc than did children with adequate serum zinc . Four months after supplementation , hemoglobin remained unchanged in all supplemented group . Plasma retinol levels decreased in all supplemented groups . Supplementation with iron plus zinc improved serum zinc and plasma ferritin . However , since plasma retinol levels decreased as a result of supplementation , more studies are needed on the matter Aim : To determine the efficacy of prophylactic administration of zinc sulphate in reducing the occurrence of the common cold in children , and to evaluate the efficacy of zinc sulphate in reducing the duration and severity of cold symptoms . Methods : A total of 200 healthy children were r and omly assigned to receive oral zinc sulphate ( zinc group , n=100 ) or placebo ( placebo group , n=100 ) . Zinc sulphate ( 15 mg of zinc ) or placebo syrup were administered for prophylaxis once daily during a 7‐mo study period . The dose was increased to two times per day ( 30 mg of zinc ) at the onset of cold , until symptoms resolved . Results : The mean number of colds in the zinc group was significantly less than in the placebo group ( 1.2 vs 1.7 colds per child ; p=0.003 ) . The mean cold‐related school absence was 0.9 d per child in the zinc group versus 1.3 d in the placebo group ( p=0.04 ) . Compared to the placebo group , the zinc group had shorter mean duration of cold symptoms and decreased total severity scores for cold symptoms ( p<0.0001 ) . Adverse effects were mild and similar in both groups A double-blind , pair-matched 12-mo study examined the effects of a zinc supplement ( 10 mg Zn/d as ZnSO4 ) on linear growth , taste acuity , attention span , biochemical indices , and energy intakes of 60 boys ( aged 5 - 7 y ) with height less than or equal to 15th and midparent height greater than 25th percentiles . Boys with initial hair Zn less than 1.68 mumol/g ( n = 16 ) had a lower mean ( + /- SD ) weight-for-age Z score ( -0.44 + /- 0.59 vs -0.08 + /- 0.84 ) , and a higher median recognition threshold for salt ( 15 vs 7.5 mmol ; p = 0.02 ) than those with hair Zn greater than 1.68 mumol/g . Only boys with hair Zn less than 1.68 mumol/g responded to the Zn supplement with a higher mean change in height-for-age Z score ( p less than 0.05 ) ; taste acuity , energy intakes , and attention span were unaffected . A growth-limiting Zn deficiency syndrome exists in boys with low height percentiles , hair Zn levels less than 1.68 mumol/g , and impaired taste acuity Background : There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a r and omized iron supplementation trial . Objective : We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 r and omized , placebo-controlled trials from Pemba Isl and , Zanzibar , and Nepal . Design : In both studies , which had parallel design s and were carried out in years 2002 to 2003 , infants received iron – folic acid with or without zinc daily for 12 months , and assessment s of development were made every 3 months for the duration of the study . Eight hundred seventy-seven Pemban ( 12.5 ± 4.0 months old ) and 567 Nepali ( 10.8 ± 4.0 months ) infants participated . Maternal reports of sleep patterns ( napping frequency and duration , nighttime sleep duration , frequency of night waking ) were collected . Results : Mean Hb concentration was 9.2 ± 1.1 for Pemban and 10.1 ± 1.2 g/dL for Nepali infants . Approximately , one-third of the children were stunted . Supplemental iron was consistently associated with longer night and total sleep duration . The effects of zinc supplementation also included longer sleep duration . Conclusions : Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking We sought to determine the effect of supplementation with zinc , vitamin A , or a combination of the two on proliferation of T lymphocytes to concanavalin A ( ConA ) , tetanus toxoid ( TT ) , or tuberculin ( PPD ) of children living in a region endemic for suboptimal vitamin A and zinc intake . The children ( n = 140 , aged 6 - 13 y ) were r and omly assigned and supplemented with either zinc ( 25 mg/d ) , vitamin A ( 1500 mg RE/d ) , zinc + vitamin A , or placebo for 6 mo . After a baseline blood collection , subjects were boosted with diphtheria-tetanus antigen . Proliferative responsiveness of T lymphocytes to ConA and TT in each treatment group ( n = 35 ) was not different at baseline or postsupplementation . Children supplemented with zinc + vitamin A tended to show higher proliferative responsiveness of T lymphocytes to PPD than did those treated with placebo ( P = 0.08 ) . This tendency was observed in females but not in males . Increased zinc and vitamin A intake could result in health benefits for children living in regions endemic for suboptimal micronutrient nutriture OBJECTIVES The present study was aim ed at assessing the effect of zinc- and micronutrient-rich food supplementation compared with ayurvedic zinc tablets on the blood levels of zinc and vitamin A in adolescent girls . METHODS One hundred eighty apparently healthy schoolgirls ( 12.5 ± 0.85 y old ) were recruited for a 10-wk intervention trial . They were r and omized to three groups : one group received a food supplement that was prepared using zinc- and micronutrient-rich foods and by adopting food-processing methods that increase zinc bioavailability ; the second group received ayurvedic zinc ( Jasad ) tablets as a natural elemental zinc supplement ; and the third group served as the control without any supplementation . Diet was assessed by 24-h recall on 3 non-consecutive days . Fasting blood sample s were analyzed for plasma levels of zinc , β-carotene , retinol , vitamin C , and hemoglobin at baseline and the end of the study period . RESULTS Food supplementation showed a significant increase in plasma levels of zinc ( 9.9 % ) , β-carotene ( 56.2 % ) , and vitamin C ( 28.0 % , P < 0.05 ) and a non-significant increase in hemoglobin ( 1.7 % ) , although small , non-significant changes in blood micronutrient levels were observed in the control group ( P > 0.1 ) . Food supplementation decreased the prevalence of zinc deficiency ( 73 % to 53.1 % ) , β-carotene deficiency ( 31.1 % to 17.4 % ) , and mild anemia ( 32.2 % to 23.7 % ) . Ayurvedic zinc supplementation significantly improved plasma zinc ( 61.3 % ) and plasma retinol ( 38.2 % ) and decreased the prevalence of zinc deficiency ( 73.7 % to 36.2 % ) and vitamin A deficiency ( 65.4 % to 20.4 % , P < 0.05 ) . CONCLUSION Zinc- and micronutrient-rich food supplementation was effective in improving the zinc and vitamin A status of adolescent girls BACKGROUND Simple , low-cost methods are needed to evaluate the effect of zinc-fortification programs . Plasma zinc concentration is a useful biomarker of zinc intake from supplementation , but responses to zinc fortification are inconsistent . OBJECTIVE The objective was to compare the change in plasma zinc concentrations in young children who received zinc from either a liquid supplement or a zinc-fortified complementary food . DESIGN A double-blind intervention trial was conducted in 137 young Senegalese children aged 9 - 17 mo who were r and omly assigned to receive one of the following treatments for 15 d : 1 ) 30 g dry weight of an iron-fortified cereal porridge and a liquid multivitamin supplement without zinc ( control group ) , 2 ) the same porridge and multivitamin supplement with 6 mg Zn added to the supplement dose ( ZnSuppl group ) , or 3 ) the same porridge with added zinc to provide 6 mg Zn per 25 g dry weight of porridge and multivitamin without zinc ( ZnFort group ) . RESULTS Mean ( ±SD ) plasma zinc concentration ( μg/dL ) increased by 4.7 ± 1.6 ( P = 0.004 ) in the ZnSuppl group , which was significantly greater ( P = 0.009 ) than the mean change in the control group ( -1.0 ± 1.6 ; P = 0.51 ) and in the ZnFort group ( -1.8 ± 1.7 ; P = 0.29 ) . The latter 2 groups did not differ from each other ( P = 0.99 ) . CONCLUSIONS Plasma zinc concentration increased in children who received daily zinc supplementation for 15 d but not in those who received a zinc-fortified complementary food containing a similar amount of zinc . Additional longer-term studies are needed to assess the effect of zinc-fortification programs on zinc-related functional outcomes and the usefulness of plasma zinc as a biomarker of program effect . This trial was registered at www . clinical trials.gov as study NCT0094398 |
12,680 | 12,458,993 | Important trends in prostate cancer incidence and mortality also occurred at that time .
Disease-specific mortality rates paralleled trends in prostate cancer incidence ( 15 , 16 ) .
The argument that the decline in mortality can be attributed to PSA screening would be stronger if it could be shown that the decline was largest in areas with more screening .
Currently available prognostic markers can distinguish a small number of men with excellent prognosis for long-term survival and a small number of men with | The American Cancer Society estimates that 189 000 men will receive a diagnosis of prostate cancer in 2002 and that 30 200 men will die of the disease ( 1 ) .
Many more men receive a diagnosis of prostate cancer than die of it ( lifetime risk , about 1 in 6 vs. about 1 in 29 ) .
Among types of cancer , only lung cancer kills more men each year .
The cause of prostate cancer is unknown , and the best-documented risk factors ( age , ethnicity , and family history ) are not modifiable .
The burden of prostate cancer falls disproportionately on men who are older or black .
The median age at diagnosis is approximately 71 years , and the median age at death is 78 years ( 2 ) .
More than 75 % of all cases of prostate cancer are diagnosed in men older than 65 years of age , and 90 % of deaths occur in this age group ( 2 , 3 ) .
Incidence is approximately 60 % higher and mortality rate is twofold higher in black men than in white men ( 2 ) .
Asian-American men and Hispanic men have lower incidence rates than non-Hispanic white persons ( 3 ) .
Although approaches to primary prevention of prostate cancer are being tested , to date none are known to be effective .
The most common strategy for reducing the burden of prostate cancer is screening , but screening remains controversial .
Many studies on this topic have been published since 1996 , when the U.S. Preventive Services Task Force ( USPSTF ) last examined prostate screening ( 4 ) .
Attribution bias suggests that some deaths are mistakenly attributed to prostate cancer .
If the percentage of deaths so attributed is stable , then the prostate cancer mortality rate would be expected to increase and decrease in close approximation with the incidence of prostate cancer in the population ( 16 ) .
Second , the reference st and ard ( prostate biopsy ) for diagnosing prostate cancer after positive results on a screening test is imperfect .
Third , few studies perform biopsy on men with negative results on screening tests .
Prostate cancer is a heterogeneous tumor .
Different cases of prostate cancer have widely varying growth rates and potential for causing death . | BACKGROUND The currently recommended frequency for prostate-specific antigen ( PSA ) screening tests for prostate cancer is 1 year , but the optimal screening interval is not known . Our goal was to determine if a longer interval would compromise the detection of curable prostate cancer . METHODS A cohort of 4491 men aged 55 - 75 years , all participants in the Rotterdam section of the European R and omized Study of ( population -based ) Screening for Prostate Cancer , were invited to participate in an initial PSA screening . Men who received that screening were invited for a second screen 4 years later . Pathology findings from needle biopsy cores were compared for men in both rounds . Statistical tests were two-sided . RESULTS A total of 4133 men were screened in the first round ( the prevalence screen ) , and 2385 were screened in the second round . The median amount of cancer in needle biopsy sets was 7.0 mm ( 95 % confidence interval [ CI ] = 5.4 mm to 8.6 mm ) in the first round and 4.1 mm ( 95 % CI = 2.6 mm to 5.6 mm ) in the second round ( P = .001 ) . Thirty-six percent of the adenocarcinomas detected in the first round but only 16 % of those detected in the second round had a Gleason score of 7 or higher ( mean difference = 20 % [ 95 % CI = 10 % to 30 % ] ; P<.001 ) . Whereas 25 % of the adenocarcinomas detected in the first round had adverse prognostic features , only 6 % of those detected in the second round did ( mean difference = 19 % [ 95 % CI = 11 % to 26 % ] ; P<.001 ) . Baseline PSA values were predictive for the amount of tumor in biopsies in men with cancer in the first round but not for that in the second round . CONCLUSION Most large prostate cancers with high serum PSA levels were effectively detected in a prevalence screen . In this population , a screening interval of 4 years appears to be short enough to constrain the development of large tumors , although it is inconclusive whether this will result in a survival benefit The objective was to investigate how prostate cancer and its treatment affects sexual , urinary and bowel functions and to what extent eventual complications cause distress . A question naire was sent to 431 men aged 50 - 80 years with prostate cancer diagnosed in 1992 in the Stockholm area ( Sweden ) and 435 r and omly selected men with a similar age distribution . Sexual function , as compared with their youth , was diminished in a majority of all men . The prostate cancer patients were , however , more likely to report low frequency and /or intensity in all aspects of sexual function . A majority of the men were distressed by a waning sexual capacity . The proportion of men with prostate cancer who were severely distressed owing to a decline in sexual function was larger than in the reference group . The willingness to trade off an intact sexual function for long-term survival varied considerably among the men in the reference group . Urinary and bowel symptoms were less common than a waning sexual function in both groups , and few appeared to be severely distressed by urinary or bowel symptoms . A decline in sexual functions was the most common cause of disease-specific distress in men with prostate cancer OBJECTIVE To describe the incidence , time to onset and extent of anaemia occurring in patients with prostate cancer receiving combined hormone blockade ( CHB ) and the timing and extent of recovery from anaemia in those patients where CHB was discontinued . PATIENTS AND METHODS Patients with prostate cancer were evaluated prospect ively by physical examination and laboratory tests at baseline and at routine intervals while receiving CHB . Of 142 patients who received CHB , 133 were evaluable for the assessment of anaemia ; CHB was discontinued in 76 patients , of whom 64 were assessable for recovery from their anaemia . RESULTS Haemoglobin levels declined significantly in all patients from a mean baseline of 149 g/L to means of 139 g/L , 132 g/L and 131 g/L at 1 , 2 and 3 months , respectively . Haemoglobin levels continued to decline during CHB to a mean nadir of 123 g/L at a mean of 5.6 months of CHB , representing a mean absolute haemoglobin decline at nadir of 25.4 g/L. In 120 of the 133 ( 90 % ) patients , the relative decline in haemoglobin at nadir was > or = 10 % and was > or = 25 % in 17 ( 13 % ) others , representing a mean absolute haemoglobin decline in this subset of 42.7 g/L. Significant symptoms related to anaemia occurred in 17 patients ( 13 % ) . Anaemia and symptoms in these patients were easily corrected with the subcutaneous administration of recombinant human erythropoietin . CONCLUSIONS The anaemia associated with and rogen deprivation is significant and occurs routinely in men receiving CHB . It is normochromic , normocytic , temporally-related to the initiation of and rogen blockade and usually resolves after CHB is discontinued . We suggest that patients receiving CHB undergo haematological testing at baseline , 1 - 2 months after initiating CHB and periodically thereafter . Patients developing anaemia should be question ed about symptoms reflecting physiological compromise ( e.g. angina , dyspnoea on exertion ) . In the absence of other causes , CHB should be suspected in the development of anaemia in patients receiving this treatment BACKGROUND Most studies that have described the sensitivity and specificity of prostate-specific antigen ( PSA ) as a screening test have been conducted in urology practice setting s or in media-based screening programs . The control patients from these setting s may have a higher prevalence of urologic disorders that increase serum PSA levels than that of the general population in which screening efforts might take place , leading to biased estimates of sensitivity and specificity . OBJECTIVE To determine the sensitivity and specificity of serum PSA levels for the early detection of prostate cancer in a population -based setting . PATIENTS AND METHODS This population -based case-control study was conducted in Olmsted County , Minnesota , where the Rochester Epidemiology Project could identify all incident cases of prostate cancer through passive surveillance of medical care provided to local residents . Case patients were all 177 men ( age range , 50 - 79 years ) who were newly diagnosed as having prostate cancer from 1990 through 1992 and had a prediagnostic serum PSA determination ( 90 % of all incident cases ) . Control patients were r and omly selected from the Olmsted County population and had undergone a clinical examination to exclude prostate cancer . RESULTS The median ( 25th and 75th percentiles ) of serum PSA levels was 9.4 ng/mL ( 5.4 and 18.6 ng/mL , respectively ) for case patients and 1.2 ng/mL ( 0.7 and 2.1 ng/mL , respectively ) for control patients ( P < .001 ) . When sensitivity was plotted against 1-specificity , the area under the receiver operating characteristic curve was 0.94 ( SE , 0.01 ) . The predictive power declined somewhat with age , with areas under the curve of 0.96 , 0.94 , and 0.90 for men in their 50s , 60s , and 70s , respectively . When cases were restricted to the 155 men with clinical ly localized disease , the area under the curve was essentially unchanged ( 0.94 ; SE , 0.01 ) and still much greater than the estimates of 0.75 that were reported from urology practice - and media-based setting s. CONCLUSIONS In a community-based setting , serum PSA levels provide better discrimination between men with and without clinical ly localized prostate cancer than has been observed in studies that were conducted in urologic practice s. These results suggest that previous decision analyses may have underestimated the predictive value of PSA for the detection of prostate cancer in a primary care or community-wide screening program OBJECTIVES To evaluate the effect of immediate and rogen suppression in conjunction with st and ard external beam irradiation ( RT ) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment . METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group [ RTOG ] 85 - 31 ) comparing st and ard external beam RT plus immediate and rogen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate . One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy ( eg , capsular penetration , seminal vesicle involvement ) . Seventy-one of the patients received RT with immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) ; 68 patients received RT alone with hormonal manipulation instituted only at the time of relapse . RESULTS With a median follow-up of 5 years , the estimated progression-free survival rate ( failure defined as prostate-specific antigen [ PSA ] greater than 0.5 ng/mL ) was 65 % for the men who received combination therapy and 42 % for those treated by RT alone with hormones reserved for relapse ( P = 0.002 ) . Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL ( 71 % versus 46 % ; P = 0.008 ) and PSA greater than 4.0 ng/mL ( 76 % versus 55 % ; P = 0.05 ) , respectively . No differences were observed between the groups with respect to the end points of local control , distant failure , and overall survival . The use of immediate and rogen suppression ( ie , LHRH agonists ) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis . CONCLUSIONS Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation . Because statistically significant advantages for this experimental approach could not be defined for all end points studied ( in particular , overall survival ) , efforts should be made to enroll these patients in the recently activated RTOG trial ( 96 - 01 ) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting BACKGROUND The utility of digital rectal examination ( DRE ) as a screening test for early detection of prostate cancer has not been established . Therefore , we evaluated the usefulness of DRE as a st and -alone screening test and in conjunction with measured serum prostate-specific antigen ( PSA ) levels of 0 - 3.9 ng/mL and transrectal ultrasonography ( TRUS ) . METHODS Our study population consisted of 10,523 men aged 54 - 76 years who were r and omly assigned to the screening arm of the Rotterdam , The Netherl and s , section of the European R and omized Study of Screening for Prostate Cancer . The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test . Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed ( and missed ) by DRE . RESULTS The overall detection rate for prostate cancer in this population when serum PSA measurement , DRE , and TRUS were used was 4.5 % , and the detection rate with DRE alone was 2.5 % . The positive predictive value of DRE ranged from 4 % to 11 % in men with PSA levels of 0 - 2.9 ng/mL and from 33 % to 83 % in men with PSA levels of 3.0 - 9.9 ng/mL or more . Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small ( mean volumes = 0.24 - 0.83 mL ) , and most were well differentiated ( Gleason scores of 6 or less ) . Minimal , moderate , and advanced cancers were seen in 42 % , 42 % , and 16 % of men , respectively , with a PSA level of 4.0 ng/mL or less . DRE alone allowed detection of 264 ( 55.8 % ) of 473 cancers ; 82 ( 17.3 % ) of the 473 cancers would have remained undetected by PSA-based screening alone ( i.e. , no follow-up procedures for PSA values of 0 - 3.9 ng/mL ) . CONCLUSIONS For PSA values of 0 - 3.9 ng/mL , the positive predictive value and sensitivity of DRE , tumor volume , and tumor grade were strongly dependent on PSA level . DRE has a poor performance in low PSA ranges It has been noted that the most important evidence for a benefit of early detection of prostate cancer using prostate-specific antigen ( PSA ) testing would be a decline in prostate cancer mortality rates to levels below those existing before diagnostic use of PSA testing . We document a decrease in U.S. prostate cancer mortality rates in white men less than 85 years of age to levels below those existing in 1986 , the year use of PSA testing was approved . In fact , for men 60 - 79 years of age , prostate cancer mortality rates were lower in 1997 than in any year since 1950 . Although it has been argued that the decrease in prostate cancer mortality rates began too soon to be explained by PSA testing , stage-specific survival rates indicate that a rapid decrease in mortality may be explained by the large number of high- grade prostate cancers detected before metastasis . If recent decreases in U.S. prostate cancer mortality rates are due to early detection using PSA testing , r and omized clinical trials investigating PSA testing will show early evidence of a mortality benefit Objectives : Trends in first-time and later PSA procedure rates are ascertained using longitudinal data from a population -based cohort . These trends are compared to trends in prostate cancer incidence to determine the role of PSA in the recent decline in prostate cancer incidence . Methods : Medicare data were linked with tumor registry data from the National Cancer Institute 's Surveillance , Epidemiology , and End Results ( SEER ) Program . A 5 percent r and om sample ( n=39985 ) of Medicare beneficiaries from the SEER areas without a previous diagnosis of prostate cancer as of January 1 , 1988 was followed through 1994 . Trends in first-time PSA use were distinguished from those of second or later for men without diagnosed prostate cancer . Results : Trends in the rate of first-time PSA procedures track closely with trends in prostate cancer incidence rates , increasing until 1992 and decreasing thereafter . Similar patterns were observed by race and age group . Geographic variability in the dissemination of PSA screening was observed , yet the association between testing and incidence remained . Men in the cohort had a 4.7 percent chance of being diagnosed within three months of an initial PSA test , with the percentage falling for subsequent tests . Conclusions : It is informative to distinguish first from later tests when assessing the effect of the diffusion of a test in a population . Taking this approach was useful in illuminating the role of PSA testing in a reversal of a long-term increase in prostate cancer incidence rates PURPOSE Gleason score ( GS ) , T stage , and pathologic lymph node status have been described as major independent predictors of death due to prostate cancer in men treated with external beam radiotherapy ( XRT ) . In this analysis we combine these three factors to define prognostic subgroups that correlate with disease-specific survival ( DSS ) death from prostate cancer . METHODS AND MATERIAL S Men entered on one of four Radiation Therapy Oncology Group ( RTOG ) Phase III r and omized trials between 1975 and 1992 , for clinical ly localized prostate cancer ( CAP ) ( n = 1557 ) , were selected for this analysis . Patients were included if : 1 ) they were evaluable , and eligible for the trial ; 2 ) they received no hormonal therapy with their initial treatment ; and 3 ) follow-up was available . For this study a DSS event was declared if : 1 ) death was certified as due to CAP ; 2 ) death was due to complications of treatment ; or 3 ) death was from unknown causes with active malignancy . The median follow-up for patients treated on early and late RTOG studies exceeded 11 and 6 years respectively . Subgroups were identified based on their pretreatment GS , T-stage , and lymph node such that patients with similar risk of dying from prostate cancer were combined . RESULTS By combining patients with similar DSS , four subgroups were identified . Risk Group 1 patients had a GS = 2 - 6 , and T1 - 2Nx ; Group 2 : GS = 2 - 6 , T3Nx ; or GS = 2 - 6 , N+ , or GS = 7 , T1 - 2Nx ; Group 3 : T3Nx , GS = 7 ; or N+ , GS = 7 , or T1 - 2Nx , GS = 8 - 10 ; and Group 4 patients were T3Nx , GS = 8 - 10 , or N+ , GS = 8 - 10 . The 5- , 10- , and 15-year DSS was 96 % , 86 % , and 72 % ; 94 % , 75 % , and 61 % ; 83 % , 62 % , and 39 % ; and 64 % , 34 % , and 27 % for Groups 1 through 4 , respectively . CONCLUSIONS Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospect i ve r and omized trials Voiding and sexual function after treatment are major determinants of quality of life in prostate carcinoma patients . Erectile dysfunction , incontinence , and urinary symptoms , both obstructive and irritative , have a significant negative impact on patient quality of life . This prospect i ve study was undertaken to evaluate voiding , sexual function , and their impact on patients with localized prostate carcinoma who were treated with radical retropubic prostatectomy ( RP ) and to compare these patients with patients who were undergoing hormonobrachytherapy with external bean radiotherapy ( HBTC ) and patients who were undergoing hormonobrachytherapy without external beam radiotherapy ( HBT ) Between 1984 and 1991 , a total of 177 patients with adenocarcinoma of the prostate were treated with transcutaneous , transperineal radioactive gold seeds . Of these 177 patients , 20 were determined to have pelvic lymph node involvement and were excluded from this review . The remaining 157 patients received a median radioactivity dose of 164 mCi with a median follow-up of 48 months . Cancer-specific survival at 5 years was 100 % for stage A2 and B1 , 90 % for stage B2 , and 76 % for stage C cancer . Covariates of grade , total radioactivity administered , age of the patient , and number of seeds implanted did not influence disease-free survival in a statistically significant manner . Significant complications were observed in two patients . The survival rates of patients treated with 198Au seed implantation for localized cancer are equivalent or better when compared to historical data of patients treated with 125I implantation , external beam radiotherapy , combination radioactive gold seed implantation and external irradiation , and radical prostatectomy . In addition , these comparable survival rates using interstitial 198Au seeds may be achieved with less morbidity OBJECTIVE To evaluate prostate-specific antigen ( PSA ) testing intervals that maintain the detection of curable cancer and reduce unnecessary testing . DESIGN AND PATIENTS Historical prospect i ve study of serial PSA measurements at 2- and 4-year intervals from frozen serum sample s of 40 men who eventually developed prostate cancer and 272 men without prostate cancer who were participants in a prospect i ve aging study ( Gerontology Research Center of the National Institute on Aging , the Baltimore Longitudinal Study of Aging ) and the case series of 389 consecutive men treated surgically for nonpalpable prostate cancer . MAIN OUTCOME MEASURES Probability of a PSA conversion to 4.1 to 5.0 ng/mL and to greater than 5.0 ng/mL at 2 and 4 years and probability of detecting curable prostate cancer by age and PSA level . RESULTS When the pretreatment PSA level was less than or equal to 4.0 ng/mL , nonpalpable prostate cancers were highly likely ( 34/36 , 94 % ) to be curable ( organ-confined or capsular penetration with Gleason score < 7 and negative margins ) , and the majority ( 25/36 , 69 % ) were small cancers ( confined tumor < or = 0.5 cm3 with no Gleason pattern 4 or 5 ) . When the pretreatment PSA level was greater than 4.0 ng/mL and less than or equal to 5.0 ng/mL , cancers were highly likely to be curable ( 32/36 , 89 % ) , and a minority were small cancers ( 12/36 , 33 % ) . When the pretreatment PSA level was greater than 5.0 ng/mL , 96 ( 30 % ) of 317 cancers were noncurable . The PSA conversion ( for cancer cases ) to a level at which cure is less likely ( > 5.0 ng/mL ) is rare ( 0 % ) after 2 or 4 years when the initial PSA is less than 2.0 ng/mL. PSA conversion to a range at which cancers are likely to be curable and less likely to be small ( 4.1 - 5.0 ng/mL ) is rare after 2 years ( 0%-4 % ) when the baseline PSA level is less than 2.0 ng/mL but common when the baseline PSA level is between 2.1 and 3.0 ng/mL ( 27 % ) or 3.1 and 4.0 ng/mL ( 36 % ) . CONCLUSIONS These data suggest that for men with no cancer suspected on digital rectal examination , a PSA level of 4.0 to 5.0 ng/mL is an acceptable range for maintaining the detection of curable prostate cancer and a 2-year PSA testing interval is not likely to miss a curable prostate cancer when the initial PSA level is less than 2.0 ng/mL. Recognizing that 70 % of a screened population between the ages of 50 years and 70 years have PSA levels less than 2.0 ng/mL , elimination of annual PSA testing for these men would result in large health care cost savings Summary Approximately 20 000 men 55–67 years of age from two areas in Finl and were identified from the Population Registry and r and omized either to the screening arm ( 1/3 ) or the control arm ( 2/3 ) of a prostate cancer screening trial . In the first round , the participation rate in the screening arm was 69 % . Of the 5053 screened participants , 428 ( 8.5 % ) had a serum prostate-specific antigen ( PSA ) concentration of 4.0 ng/ml or higher , and diagnostic examinations were performed on 399 of them . A total of 106 cancers were detected among them corresponding to a positive predictive value of 27 % , which is comparable with mammography screening for breast cancer . The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml–1 or higher was 2.1 % . Approximately nine out of ten screen-detected prostate cancers were localized ( 85 % clinical stage T1–T2 ) and well or moderately differentiated ( 42 % World Health Organization ( WHO ) grade I and 50 % grade II ) , which suggests a higher proportion of curable cancers compared with cases detected by other means PURPOSE We defined the yield and nature of prostate cancer in the setting of population based , r and omized prostate specific antigen ( PSA ) guided screening in men with PSA levels between 3 and 4 ng./ml . who were 50 to 65 years old at the time of r and omization . MATERIAL S AND METHODS Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml . Therapy decisions were based on core cancer length , histological grade and life expectancy . RESULTS Of the men 32 ( 13.2 % ) had prostate cancer constituting 23 % of all of the 137 prostate cancers to data detected in the first round of our screening study . Age and PSA were similar in men with and without prostate cancer . Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio , and higher PSA density . Cancer was clinical stage T1c in 27 cases and stage T2 in 5 . Hypoechoic areas were noted at transrectal ultrasound in 10 cases . Digital rectal examination and transrectal ultrasound were normal in 21 cases ( 66 % ) . To date 14 patients have undergone prostatectomy . Surgical specimens showed a mean tumor volume of 1.8 cc ( range 0.6 to 4.4 ) and significant amounts of high grade tumor were present in only 3 cases . Margins were positive in 5 cases , and pathological stage was pT2 in 8 cases and pT3 in 6 . CONCLUSIONS By lowering the PSA cutoff from 4 to 3 ng./ml . an increase in cancer detection by 30 % was achieved . While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15 % with sensitivity maintained at 90 % , systematic sextant biopsies were necessary in most of these mean as 66 % of the tumors were negative on transrectal ultrasound and digital rectal examination . The majority of these cancers were clinical ly significant and suitable for curative treatment . If therapy decisions are based on the pathological findings of the biopsies , the risk of treating insignificant cancers seems low OBJECTIVES Various methods have been proposed to increase the specificity of prostate-specific antigen ( PSA ) , including age-specific PSA reference ranges , PSA density ( PSAD ) , and percent free PSA ( % fPSA ) . In this multicenter study , we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinical ly localized , Stage T1c cancer . METHODS Seven hundred seventy-three men ( 379 with prostate cancer , 394 with benign prostatic disease ) , 50 to 75 years old , from seven medical centers were enrolled in this prospect i ve blinded study . All subjects had a palpably benign prostate , PSA 4.0 to 10.0 ng/mL , and a histologically confirmed diagnosis . Hybritech 's T and em PSA and free PSA assays were used . RESULTS % fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection , but % fPSA maintained significantly higher sensitivities . Age-specific PSA cutoffs missed 20 % to 60 % of cancers in men older than 60 years of age . % fPSA and PSAD performed equally well for detection ( 95 % sensitivity ) if cutoffs of 25 % fPSA or 0.078 PSAD were used . The commonly used PSAD cutoff of 0.15 detected only 59 % of cancers . % fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage . Patients with cancer with higher % fPSA values ( greater than 15 % ) or lower PSAD values ( 0.15 or less ) tended to have less aggressive disease . CONCLUSIONS The results of this study demonstrated that cancer detection ( sensitivity ) is significantly higher with % fPSA than with age-specific PSA reference ranges . % fPSA and PSAD provide comparable results , suggesting that % fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of % fPSA does not require ultrasound OBJECTIVES To perform a prospect i ve study using confidential patient-completed question naires about their urinary habits before and after laparoscopic radical prostatectomy . Published reports on urinary continence after radical prostatectomy vary depending on the definitions of urinary continence and methods of data collection . METHODS From May 1998 to February 2000 , 228 men underwent laparoscopic radical prostatectomy for clinical ly localized prostate cancer . The patients were given question naires before surgery and at 1 , 3 , 6 , and 12 months postoperatively . RESULTS Before surgery , no patient reported incontinence . At 1 , 3 , 6 , and 12 months postoperatively , perfect diurnal urinary control ( no pads , no leakage at all ) was reported in 9.9 % , 28.6 % , 57.4 % , and 56.8 % of patients , respectively . No pads were used in 18.8 % , 58.4 % , 68.9 % , and 78.4 % at 1 , 3 , 6 , and 12 months , respectively . No patient reported use of more than 1 pad daily at 6 months of follow-up . CONCLUSIONS Continence after laparoscopic radical prostatectomy is comparable to the results after traditional radical retropubic prostatectomy . Ongoing use of the laparoscopic route for treating clinical ly localized prostate cancer is warranted PURPOSE We evaluated the effect of three-dimensional conformal radiation therapy ( 3D-CRT ) with or without hormonal therapy ( HT ) on sexual function ( SF ) in prostate cancer patients whose SF was known before all treatment . METHODS AND MATERIAL S Between March 1996 and March 1999 , 144 patients received 3D-CRT ( median dose = 70.2 Gy , range 66.6 - 79.2 Gy ) for prostate cancer and had pre- and post-therapy SF data . All SF data were obtained with the O'Leary Brief SF Inventory , a self-administered , multidimensional , vali date d instrument . We defined total sexual potency as erections firm enough for penetration during intercourse . Mean follow-up time was 21 months ( SD + /- 11 months ) . The Wilcoxon signed-rank test was used to test for significance of the change from baseline . RESULTS Before 3D-CRT , 87 ( 60 % ) of 144 men were totally potent as compared to only 47 ( 47 % ) of 101 at 1-year follow-up . Of the 60 men totally potent at baseline and followed for at least 1 year , 35 ( 58 % ) remained totally potent . These changes corresponded to a significant reduction in SF ( p < 0.05 ) . Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT ( 56 % vs. 31 % , p = 0.012 ) ; however , they were also more likely to be potent at baseline ( 71 % vs. 44 % , p = 0.001 ) . Although these two groups had a significant reduction in SF from baseline , their change was not significantly different from each other . CONCLUSION These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline . The addition of HT does not appear to increase the risk of sexual dysfunction OBJECTIVE To evaluate longitudinal changes in prostate-specific antigen ( PSA ) levels in men with and without prostate disease . DESIGN Case-control study of men with and without prostate disease who were participants in a prospect i ve aging study . SETTING Gerontology Research Center of the National Institute on Aging ; the Baltimore ( Md ) Longitudinal Study of Aging . PATIENTS Sixteen men with no prostate disease ( control group ) , 20 men with a histologic diagnosis of benign prostatic hyperplasia ( BPH ) , and 18 men with a histologic diagnosis of prostate cancer . OUTCOME MEASURES Multiple PSA and and rogen determinations on serum sample s obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease . RESULTS Changes in and rogen levels with age did not differ between groups . Control subjects did not show a significant change in PSA levels with age . There was a significant difference in the age-adjusted rate of change in PSA levels between groups ( prostate cancer greater than BPH greater than control ; P less than .01 ) . At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer , rate of change in PSA levels ( 0.75 micrograms/L per year ) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH . Also , rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90 % and 100 % , respectively . CONCLUSIONS The most significant factor affecting serum PSA levels with age is the development of prostate disease . Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer OBJECTIVE To evaluate measurement of percentage of free prostate-specific antigen ( PSA ) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL. DESIGN Retrospective , nonr and omized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results . SETTING General community outpatient prostate cancer screening program at a university center . PATIENTS One hundred thirteen men aged 50 years or older , 99 % of whom were white , with serum PSA concentrations of 4.1 to 10.0 ng/mL , including 63 men with histologically confirmed benign prostatic hyperplasia , 30 with prostate cancer with an enlarged gl and , and 20 with cancer with a normal-sized gl and . All study volunteers had undergone prostatic ultrasonography and biopsy . MAIN OUTCOME MEASURES Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90 % sensitivity for prostate cancer detection . RESULTS Median percentage of free PSA was 9.2 % in men with cancer and a normal-sized gl and , 15.9 % in men with cancer and an enlarged gl and , and 18.8 % in men with benign prostatic hyperplasia ( P < .001 ) . The percentage of free PSA cutoff was higher in men with an enlarged gl and and in those with a palpably benign gl and . In men with an enlarged , palpably benign gl and , a free PSA cutoff of 23.4 % or lower detected at least 90 % of cancers and would have eliminated 31.3 % of negative biopsies . CONCLUSIONS Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate ; however , further studies are needed to define optimal cutoffs . Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer BACKGROUND Radical prostatectomy is widely used in the treatment of early prostate cancer . The possible survival benefit of this treatment , however , is unclear . We conducted a r and omized trial to address this question . METHODS From October 1989 through February 1999 , 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b , T1c , or T2 were r and omly assigned to watchful waiting or radical prostatectomy . We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death . The primary end point was death due to prostate cancer , and the secondary end points were overall mortality , metastasis-free survival , and local progression . RESULTS During a median of 6.2 years of follow-up , 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died ( P=0.31 ) . Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting ( 8.9 percent ) and in 16 of 347 of those assigned to radical prostatectomy ( 4.6 percent ) ( relative hazard , 0.50 ; 95 percent confidence interval , 0.27 to 0.91 ; P=0.02 ) . Death due to other causes occurred in 31 of 348 men in the watchful-waiting group ( 8.9 percent ) and in 37 of 347 men in the radical-prostatectomy group ( 10.6 percent ) . The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting ( relative hazard , 0.63 ; 95 percent confidence interval , 0.41 to 0.96 ) . CONCLUSIONS In this r and omized trial , radical prostatectomy significantly reduced disease-specific mortality , but there was no significant difference between surgery and watchful waiting in terms of overall survival OBJECTIVE To define the characteristics of serum prostate-specific antigen ( PSA ) in a population of healthy men without clinical ly evident prostate cancer , but who are at risk for developing the malignancy . The influence of patient age and prostatic size on the serum PSA concentration was assessed in order to use PSA more appropriately to detect clinical ly significant prostate cancer at an early , potentially curable stage . DESIGN Prospect i ve , community-based study . PARTICIPANTS Between December 1989 and March 1991 , 2119 healthy men aged 40 to 79 years from Olmsted County , Minnesota , were entered into a prospect i ve study to assess the natural history of benign prostatic hyperplasia . Of these , 537 ( 25 % ) were r and omly chosen to participate in a detailed clinical examination that included a serum PSA determination ( T and em-R PSA assay ) , digital rectal examination , and transrectal ultrasonography . Four hundred seventy-one ( 88 % ) completed the prostatic evaluation and had no evidence of prostate cancer by any of these three diagnostic tests ; these men formed the study population on which all analyses were performed . MAIN OUTCOME MEASURE Serum PSA concentration , prostatic volume , and PSA density ( serum PSA level/prostatic volume ) as a function of patient age . RESULTS The serum PSA concentration is correlated with patient age ( r = .43 ; P < .0001 ) and prostatic volume ( r = .55 ; P < .0001 ) . Prostatic volume , in turn , is directly correlated with patient age ( r = .43 ; P < .0001 ) , whereas the PSA density value is only weakly correlated with patient age ( r = .25 ; P < .001 ) . For a healthy 60-year-old man with no evidence of prostate cancer , the serum PSA concentration increases by approximately 3.2 % per year ( 0.04 ng/mL per year ) . The recommended reference range for serum PSA ( 95th percentile ) for men aged 40 to 49 years is 0.0 to 2.5 ng/mL ; for 50 to 59 years , 0.0 to 3.5 ng/mL ; 60 to 69 years , 0.0 to 4.5 ng/mL ; and 70 to 79 years , 0.0 to 6.5 ng/mL. CONCLUSIONS The serum PSA concentration is directly correlated with patient age and prostatic volume , the latter of which also is directly related to age . Thus , rather than rely on a single reference range for men of all age groups , it is more appropriate to have age-specific reference ranges . These age-specific reference ranges have the potential to make serum PSA a more discriminating tumor marker for detecting clinical ly significant cancers in older men ( increasing specificity ) and to find more potentially curable cancers in younger men ( increasing sensitivity ) OBJECTIVES To determine the true-negative and false-negative rates of sextant prostate biopsies , the most common method of prostate cancer diagnosis . METHODS Forty-three men scheduled for prostatectomy as part of a surgical procedure for bladder pathologic findings agreed to participate in this study . All patients had normal digital rectal examination findings . Immediately before prostatectomy all patients underwent sextant biopsies . The location , amount , and Gleason grade of any cancer identified on the biopsies were recorded . After surgery , the prostate was serially sectioned . The location , grade , and volume of any prostatic adenocarcinoma identified was recorded and compared with the results of the biopsy specimens . RESULTS There were 33 patients without prostate cancer in either the biopsies or the prostatectomy specimen . No patients had cancer on the biopsies and no cancer in the prostatectomy specimen . In 6 patients , cancer was found in both the biopsies and the prostatectomy specimens ; these cancers were 0.9 , 2.1 , 2.8 , 3 . 1 , 4.2 , and 6.5 cc in volume . In the remaining 4 patients , there was no cancer on the biopsies but the prostatectomy specimen revealed cancers of 0.05 , 0.1 , 0.3 , and 2.5 cc . The overall sensitivity for sextant biopsies was 60.0 % , with a specificity of 100 % . When only cancers greater than 2 cc or cancers in the peripheral zone were considered , the sensitivity rose to 83.3 % and 71.4 % , respectively , with a minimal decrease in specificity ( 97.3 % and 97.2 % , respectively ) . In contrast , when transition zone cancers were evaluated , the sensitivity fell to 33.3 % . CONCLUSIONS Sextant biopsies are fairly sensitive for the detection of tumors greater than 2 cc and those in the peripheral zone ; however , repeat biopsies should be strongly considered in patients with a high clinical suspicion for prostate cancer and negative initial sextant biopsies Treatment of localized prostate carcinoma is often accompanied by disturbances in sexual function . The patient 's own opinion and experience with these problems can be of great importance for his quality of life . In men older than 50 years , disturbances in sexual function are common . Treatment such as radiotherapy ( RT ) , which can induce sexual dysfunction , should be evaluated in relation to the problems in an age‐matched population without prostate carcinoma PURPOSE At low prostate specific antigen ( PSA ) the indication for prostate biopsy is usually an abnormal digital rectal examination . We evaluate the diagnostic value of PSA , digital rectal examination , transrectal ultrasonography and tumor characteristics at low PSA ( 0 to 4.0 ng./ml . ) . We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed . MATERIAL S AND METHODS From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were r and omized to screening in the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer . Of the participants 9,211 ( 87.5 % ) had PSA less than 4.0 ng./ml . , and underwent digital rectal examination and transrectal ultrasonography . Expected rates of prostate cancer detection were calculated using logistic regression analysis . Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer . Tumors were characterized by pT category , Gleason score and cancer volume in 166 processed radical prostatectomy specimens . In 50 of these cases PSA was 0 to 4.0 ng./ml . RESULTS The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml . was only 9.7 % . Positive predictive value strongly depended on PSA . Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers . Of 760 detectable cancers 478 ( 67 % ) were diagnosed irrespective of PSA in men screened with digital rectal examination , transrectal ultrasonography and PSA . Only 127 of 348 detectable prostate cancers ( 36.5 % ) were actually diagnosed in men with PSA 2 to 4 mg./ml . The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges . CONCLUSIONS Approximately half of the tumors missed with PSA 0 to 4 ng./ml . had aggressive characteristics ( Gleason score 7 or greater , Gleason 4 - 5 components ) and were organ confined . These tumors should be diagnosed and treated according to the present underst and ing of their natural history . More sensitive and selective screening strategies are needed . Presently a wrong " window of opportunity " is used for early detection of prostate cancer Treatment of localized prostate carcinoma ( LPC ) using radiotherapy ( RT ) can induce disturbances in a patient 's quality of life ( QOL ) and urinary and intestinal function . Late symptoms and QOL were evaluated in a r and omized trial between RT and deferred treatment ( DT ) PURPOSE Erectile dysfunction is a common side effect in men treated for prostate cancer . Previously published studies document the incidence of erectile dysfunction in men treated for prostate cancer to be between 20 % and 88 % . To our knowledge a prospect i ve evaluation focused on the development of erectile dysfunction in men treated for prostate cancer has not eluci date d components of its chronology or risk factors . MATERIAL S AND METHODS A central ized prospect i ve data base of 2,956 patients diagnosed with prostate cancer at a single institution was studied in regard to pretreatment and posttreatment erectile dysfunction . Of these 2,956 patients 802 had sufficient information regarding erectile function and comprise our study population . Factors analyzed in regard to treatment and erectile dysfunction include treatment modality , that is radical prostatectomy , external beam radiation therapy and watchful waiting , and ethnicity , patient age , clinical stage and tumor histological grade . RESULTS No significant difference was noted in the posttreatment erectile function between patients treated with radical prostatectomy or external beam radiation ( 10 % versus 15 % ) . Patients selecting watchful waiting had the lowest risk of erectile dysfunction . Clinical stage and race were significant predictors for the development of erectile dysfunction in the watchful waiting and external beam radiation treatment groups . CONCLUSIONS Erectile dysfunction develops in greater than 80 % of patients treated for prostate cancer . External beam radiation has the same risk for erectile dysfunction as radical prostatectomy To examine prospect ively the usefulness of measurement of rate of change in serum prostate specific antigen levels ( PSA slope ) in detecting prostate cancer in a PSA-based prostate cancer screening study , we evaluated 982 serially screened men whose initial screening was negative for cancer . All men had at least 1 PSA value greater than 4.0 ng./ml . and all ultimately underwent prostatic biopsy . For those who entered the study with normal PSA levels , a PSA slope cutoff point of 0.75 ng./ml . per year or more maximized sensitivity and specificity for predicting cancer ( odds ratio 7.20 , 95 % confidence interval 4.52 to 11.47 ) . This cutoff point was most predictive for men 70 years old or younger . For men who entered the study with elevated PSA levels ( greater than 4.0 ng./ml . ) a lower PSA slope cutoff point ( 0.4 ng./ml . per year or more ) maximized sensitivity and specificity for predicting cancer ( odds ratio 2.73 , 95 % confidence interval 1.82 to 4.07 ) . We conclude that PSA slope is useful for serial prostate cancer screening , although its predictive value varies with patient age and initial PSA level PURPOSE RTOG 83 - 07 is a Phase II r and omized protocol design ed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol ( DES ) used as cytoreductive agents prior to and during radiotherapy . The end points of this study include tumor clearance rate , effect on serum testosterone , loco-regional control , disease-free interval , and survival . METHODS AND MATERIAL S Eligible patients were those with histologically confirmed locally advanced adenocarcinoma , clinical Stage B2 ( T2B ) and C ( T3 ) without regional lymph node involvement , or with lymph node involvement limited to the pelvis . Patients were stratified by clinical stage , histological grade , and nodal status , and were r and omized to receive either Megestrol 40 mg three times per day by mouth , or Diethylstilbestrol 1 mg three times per day by mouth . The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course . Radiotherapy consisted of 44 - 46 Gy , 1.8 - 2 Gy per day to the regional lymphatics , followed by a boost to the prostate consisting of 20 - 25 Gy , 1.8 - 2 Gy per day , to a total of 65 - 70 Gy . Serum testosterone levels were recorded throughout the treatment course . Tumor response was assessed clinical ly and radiographically ( CT scan ) . From March 1983 through June 1986 a total of 203 patients were accessioned to the study ; 198 were analyzable . RESULTS Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol ( DES ) arm . The most prominent were the differences in the incidence of gynecomastia ( 55 % vs. 7 % ) and fluid retention ( 21 % vs. 6 % ) . The incidence of thromboembolic phenomena was comparable ( 8 % vs. 5 % in the Megestrol arm ) . Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level . Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms . At 7 years , 16 % of patients on the Megace arm and 21 % of patients on the DES arm manifested evidence of local failure . CONCLUSIONS The results of the study indicate comparable efficacy ( using tumor clearance as an end point ) of DES and Megestrol . Although DES appears more effective in suppressing testosterone , it is also associated with a higher incidence of drug-related toxicity Background : This article summarizes the experience and results of different prostate carcinoma screening projects using total prostate-specific antigen ( PSA ) and percent free PSA as the initial test . Methods : The twelve projects studied included : ( 1 ) a mass screening study using PSA as the initial test in 21,079 volunteers ; ( 2 ) an investigation of the usefulness of normal and age-referenced PSA cut-offs in 1,618 men ; ( 3 ) a PSA-based screening study of 2,272 asymptomatic blood donors ; ( 4 ) an investigation of the evidence and significance of transition zone carcinoma in 340 men with negative digital rectal examination findings ; ( 5 ) determination of percent free PSA in one retrospective and two prospect i ve studies to determine the appropriate cutpoints for percent free PSA ; ( 6 ) evaluation of the diagnostic benefit of PSA transition zone density in 308 screening volunteers ; ( 7 ) a study of the impact of PSA-based screening on the percentage of incidental prostate carcinoma in 1,543 men undergoing transurethral resection of the prostate ; ( 8) an evaluation of the changes in total PSA and pathologic stages in radical prostatectomy over 5 years in a PSA-based mass screening program ; ( 9 ) a study evaluating the probability of having prostate cancer given the patient ’s age , total PSA and digital rectal examination findings ; ( 10 ) an evaluation of the correlation between preoperative predictors and pathologic features in radical prostatectomy specimens ; ( 11 ) an investigation of the correlation of total PSA with pathologic stage and tumor volume in patients undergoing radical prostatectomy with low PSA cut-off level , and ( 12 ) a study whether age has an impact on the extension of prostate cancer . Results : ( 1 ) of the 21,079 volunteers , 1,618 ( 8 % ) had elevated PSA levels . Of these men , 778 ( 48 % ) underwent biopsies ; 197 biopsies were positive for prostate carcinoma and 135 underwent radical prostatectomy . Ninety-five were found to be organ-confined . ( 2 ) A PSA cut-off of 2.5 ng/ml in men aged 45–49 years and of 3.5 ng/ml in men aged 50–59 years result ed in an 8 % increase in the detection rate of organ-confined disease . ( 3 ) Of the 2,272 men , 284 had elevated PSA levels and prostate carcinoma was detected in 62 men . All patients underwent radical prostatectomy and histologic examination revealed organ-confined tumor in all but 8 men . ( 4 ) Ninety-eight of 340 men had biopsies positive for carcinoma ; 28 of these patients ( 28.5 % ) had carcinoma that originated in the transition zone only . ( 5 ) In the retrospective study , receiver-operating characteristic curve analysis showed that by using a percent free PSA of 18 % as a biopsy criterion , 37 % of the negative biopsies could be eliminated although 94 % of all carcinomas would still be detected . In the first prospect i ve study , 106 of 158 men with elevated PSA levels < 10.0 ng/ml were further evaluated and 37 prostate carcinomas were detected . By using a % free PSA of < 22 % as a biopsy criterion , 30 % of the negative biopsies could be eliminated although 98 % of the carcinomas would still be detected . In the second prospect i ve study , 120 of 465 men with total PSA levels between 1.25 and 6.49 ng/ml and a % free PSA < 18 % were further evaluated and 27 ( 22.5 % ) were found to have prostate carcinomas . ( 6 ) Receiver-operating characteristic curve analysis for PSA transition zone density showed that by using a PSA transition zone density of > 22 ng/ml/cm3 as a biopsy criterion , 24.4 % of negative biopsies could be avoided without missing a single carcinoma . ( 7 ) In the prescreening era the incidence of T1a grade 1 and 2 carcinomas was 3.1 % and the incidence of T1a grade 3 and T1b carcinoma was 2.3 % whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03 % respectively . ( 8) The rate of organ-confined tumors increased from 28.7 % in 1993 to 65.7 % in 1997 . ( 9 ) In this evaluation a new approach to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cutpoint was developed . ( 10 ) High total PSA levels , PSA density and PSA transition zone density correlated significantly with high Gleason scores , capsular penetration , a high percentage of cancer in the prostatectomy specimen and a high cancer volume . ( 11 ) In this evaluation all of the 95 patients with PSA levels < 3.99 ng/ml who underwent radical prostatectomy showed clinical ly significant , organ-confined prostate cancer with negative surgical margins . ( 12 ) The results of this evaluation suggest that older men have larger tumor volumes compared to younger men with the same PSA levels . Conclusions : These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinical ly significant , organ-confined and potentially curable prostate cancer . Percent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA PURPOSE We assess whether the complex between prostate specific antigen ( PSA ) and alpha1-protease inhibitor in serum can be used to reduce further the number of false-positive PSA screen results independent of total and free PSA . MATERIAL S AND METHODS Sera from 304 consecutive screen positive subjects , including 78 with and 226 without prostate cancer , and serum PSA of 4 to 10 microg./l . or higher in the Finnish , r and omized , population based prostate cancer screening trial were analyzed for PSA-alpha-protease inhibitor , and total and free PSA . Main outcome measures were specificity , sensitivity and area under receiver operating characteristics curve for proportions of free PSA and PSA-alpha 1-protease inhibitor , and for a combination of these among screen positive cases . RESULTS The proportion of serum PSA-alpha 1-protease inhibitor of total PSA was lower in cancer cases than in controls ( 0.9 % versus 1.6 % , p < 0.001 ) . Logistic regression analysis of total PSA , free PSA and PSA-alpha 1-protease inhibitor showed that PSA-alpha 1-protease inhibitor in serum was an independent variable for discrimination between subjects with and without prostate cancer ( p = 0.006 ) in the PSA range of 4 to 10 microg./l . The proportion of PSA-alpha 1-protease inhibitor alone improved specificity less than the proportion of free PSA but when these were combined by logistic regression they performed better than the proportion of free PSA alone at sensitivities of 85 % to 95 % ( p < 0.001 ) . CONCLUSIONS Serum PSA-alpha 1-protease inhibitor improves the specificity of total and free PSA in a screening population with total PSA 4 to 10 microg./l PURPOSE We compare the ability of total prostate specific antigen ( PSA ) , percent free PSA , PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml . who were diagnosed with benign prostatic hyperplasia after initial biopsy . MATERIAL S AND METHODS In this prospect i ve study 1,051 men with total PSA 4 to 10 ng./ml . underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies . In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination . All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy . The ability of total PSA , percent free PSA , PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics ( ROC ) curves . RESULTS Initial biopsy was positive ( prostate cancer ) in 231 and negative ( benign prostatic hyperplasia ) in 820 of the 1,051 subjects . Prostate cancer was detected on repeat biopsy in 10 % of subjects ( 83 of 820 ) with negative initial biopsy . Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects . At a cutoff of 30 % percent free PSA would have detected 90 % of cancers ( sensitivity ) and eliminated 50 % of unnecessary repeat biopsies ( specificity ) . Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78 % and 52 % , respectively . ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA , PSA density and transition zone PSA density . The area under the ROC curve was 74.5 % for percent free PSA , 69.1 % for transition zone PSA density , 61.8 % for PSA density and 60.3 % for total PSA . CONCLUSIONS At least 10 % of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy . Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy . Repeat biopsy should be performed in patients with percent free PSA less than 30 % or transition zone PSA density 0.26 ng./ml./cc or greater . In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens OBJECTIVES To evaluate the late effects more than 2 years after radiotherapy using a patient-reported question naire in patients with prostate cancer enrolled in a r and omized dose-response study comparing 70 Gy ( conventional ) and 78 Gy ( conformal ) radiotherapy ( RT ) . METHODS The first 112 patients in the study were sent question naires to evaluate late bladder , rectal , and sexual function . There were 101 evaluable responses , with 50 in the conventional ( Conven-RT ) arm and 51 in the conformal ( 3DCRT ) arm . RESULTS The overall rate of persistent incontinence was 29 % , with 36 % reporting urgency-related and 8 % stress-related incontinence at some time after radiation . Use of a urinary protective device was required in 2 % . The majority noticed leakage less than once per day ( 52 % ) . In comparing the Conven-RT group with the 3DCRT group , similar incontinence rates were seen . However , fewer of those who received 3DCRT reported daily leakage of urine ( 33 % versus 63 % , P = 0.044 ) . The majority ( 78 % ) of patients experienced no or mild change in bowel function after RT . Urgency of bowel movements ( BMs ) was of concern for 27 % of patients ; however , 90 % reported their BMs were controlled without accidents , and 1 % were taking antidiarrheal medications once a week or daily . The Conven-RT group had more moderate or major changes in bowel function than the 3DCRT group ( 34 % versus 10 % ) , more frequent BMs ( 47 % versus 27 % ) , and more urgent BMs ( 37 % versus 18 % ) ( P < or = 0.040 for all three comparisons ) . Hematochezia was uncommon , occurring once a week in 7 % and daily in 4 % of patients . Before RT , 80 % of patients were potent , with erections adequate for intercourse at least a few times over the prior year . After RT , potency was decreased to 51 % , with erections adequate for intercourse at least a few times since the completion of RT . CONCLUSIONS The overall rates of significant complications were extremely low . Although 30 % reported incontinence , relatively few patients ( 2 % ) required pads . This rate compares favorably with the 31 % of patients requiring protection after radical prostatectomy reported previously . Despite the higher treatment doses in the 3DCRT arm , slightly fewer long-term bowel side effects were noted . These data indicate that 78 Gy may safely be delivered using the conformal RT boost treatment technique described PURPOSE To use data from a prospect i ve quality -of-life study to assess differences in disease-specific and general health-related quality -of-life changes after treatment with different external-beam irradiation techniques for prostate cancer . PATIENTS AND METHODS Patients were divided into three groups based on their pretreatment field size and planning technique : whole pelvis , small field , or conformal . Measures of bowel , urinary , and sexual function and of global health-related quality -of-life parameters ( from the Health Survey Short Form [ SF-36 ] and the Profile of Mood States [ POMS ] ) were obtained from self-report question naires completed before initiation of therapy and at 3 and 12 months after therapy . RESULTS Irritative gastrointestinal and genitourinary side effects were frequent 3 months after treatment , but were substantially improved at 12 months . Sexual dysfunction increased steadily over the study period . The POMS and the SF-36 did not demonstrate significant changes over time . Despite small patient numbers , we found trends in favor of conformal therapy across several symptom measures , including sexual function . In the fatigue , energy , and vigor subscales , patients who received whole-pelvis treatment fared significantly worse than those in the other two groups . CONCLUSION Prospect i ve , detailed data from a feasibility study allowed us to assess the effect of technique on quality of life following external-beam irradiation . Although limited by the small planned sample size , these results suggest that smaller radiation fields limit treatment-related complications , including , unexpectedly , sexual dysfunction . However , confirmation in a larger study is necessary PURPOSE To test the hypothesis that and rogen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may , by reducing tumor bulk and enhancing tumor cell kill , improve locoregional control and ultimately survival . METHODS AND MATERIAL S The study was conducted from 1987 to 1991 . Eligible patients were those with bulky tumors ( T2 - -T4 ) with or without pelvic lymph node involvement and without evidence of distant metastases . They were r and omized to receive goserelin , 3.6 mg every 4 weeks ; and flutamide , 250 mg t.i.d . for 2 months before radiation therapy and during radiation therapy ( Arm I ) , or radiation therapy alone ( Arm II ) . Of 471 r and omized patients , 456 were evaluable : 226 on Arm I and 230 on Arm II . RESULTS As of November 1999 , the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients . At 8 years , and rogen ablation has been associated with an improvement in local control ( 42 % vs. 30 % , p = 0.016 ) , reduction in the incidence of distant metastases ( 34 % vs. 45 % , p = 0.04 ) , disease-free survival ( 33 % vs. 21 % , p = 0.004 ) , biochemical disease-free survival = PSA < 1.5 ( 24 % vs. 10 % , p < 0.0001 ) , and cause-specific mortality ( 23 % vs. 31 % , p = 0.05 ) . However , subset analysis indicates that the beneficial effect of short-term and rogen ablation appears preferentially in patients with Gleason score 2 - -6 . In that population , there is a highly significant improvement in all endpoints , including survival ( 70 % vs. 52 % , p = 0.015 ) . In patients with Gleason 7 - -10 tumors , the regimen has not result ed in a significant enhancement in either locoregional control or survival . CONCLUSION In patients with Gleason score 2 - -6 carcinoma of the prostate , a short course of and rogen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control , reduction in disease progression , and overall survival In 1,002 men aged 45 - 80 y , 81 % of the cancers detectable by serum prostate-specific antigen ( PSA ) , digital rectal examination ( DRE ) , and transrectal ultrasonography ( TRUS ) were present in a sub population ( 19 % of total ) identified by serum PSA above the threshold value of 3.0 micrograms/L. This study was extended to 7,350 men using serum PSA and DRE as first approach , followed by TRUS only when 1 of these 2 tests was abnormal . Because the aim of prostate cancer detection is to find cancers at an early , potentially curable stage , it is of major interest that 71.8 % of evaluable cancers were clinical stage B ; 8.4 % and 10.7 % were stages C1 and C2 , respectively ; only 9.2 % were stage D ( metastatic ) at first visit while none was at stage D at follow-up visits . This study , the first performed in an unselected , unscreened population , shows that serum PSA is the most sensitive technique to identify men at high risk of having prostate cancer and that 12 % more cancers can be found at first visit by doing DRE in addition to PSA . Follow-ups can be done every second year using serum PSA alone , as 97 % of the cancers detected at annual follow-up by DRE + PSA were PSA+ . Cancers are discovered by the present approach at an estimated cost of $ 2,665 per cancer . Such cancers are potentially curable in at least 80 % of cases detected at first visit and in 97 % of cases at follow-up . This strategy offers the possibility to improve markedly morbidity and mortality from prostate cancer , presently the second leading cause of cancer death in North American men OBJECTIVE : Calculation of likelihood ratios for serum prostate-specific antigen ( PSA ) levels to discriminate potentially-curable prostate cancer in men selected for having benign prostatic hyperplasia ( BPH ) or in r and omly selected men . DESIGN : Retrospective analysis of prospect ively measured PSA levels . SETTING : A tertiary referral center , a multicenter r and omized controlled trial , and a community-based study , all providing PSA data . PATIENTS : We used PSA measurements from four groups of men aged 50 to 79 years : 276 men with organ-confined prostate cancer treated with radical prostatectomy , 305 r and omly selected men without clinical evidence of prostate cancer or a history of surgery for BPH recruited for a community study , 173 men without cancer but with BPH coming to prostatectomy , and 770 men without cancer and with symptoms of BPH enrolled in the North American finasteride clinical trial . MEASUREMENTS AND MAIN RESULTS : Age-st and ardized , stratum-specific likelihood ratios for organ-confined prostate cancer were calculated separately for unselected men in the community sample and for selected men with BPH ( pooling both BPH population s ) . Likelihood ratios ranged from 0.2 for PSA between 0.0 and 2.0 ng/mL to 54.8 for a PSA level of 10.1 ng/mL or higher in unselected men , but rose to only 2.9 for PSA values of 10.1 ng/mL or higher in men with BPH . Forty percent of the men in the community study had moderate to severe lower urinary tract symptoms . In these men , likelihood ratios ranged from 0.2 for PSA values between 0.0 and 2.0 ng/mL to 17.2 for PSA values of 6.1 ng/mL or higher , while in men with no or mild symptoms , likelihood ratios rose to 26.9 for PSA values of 6.1 ng/mL or higher . CONCLUSIONS : Likelihood ratios for PSA test results allow stratification of men along a continuum of risk for prostate cancer . Likelihood ratios demonstrate that the ability of the PSA test to discriminate potentially curable prostate cancer from BPH is dramatically lower in men selected with lower urinary tract symptoms than in r and omly selected men CONTEXT The percentage of free prostate-specific antigen ( PSA ) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection , but earlier studies provided only preliminary cutoffs for clinical use . OBJECTIVE To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied . DESIGN Prospect i ve blinded study using the T and em PSA and free PSA assays ( Hybritech Inc , San Diego , Calif ) . SETTING Seven nationwide university medical centers . PARTICIPANTS A total of 773 men ( 379 with prostate cancer , 394 with benign prostatic disease ) 50 to 75 years of age with a palpably benign prostate gl and , PSA level of 4.0 to 10.0 ng/mL , and histologically confirmed diagnosis . MAIN OUTCOME MEASURES A percentage of free PSA cutoff that maintained 95 % sensitivity for prostate cancer detection , and probability of cancer for individual patients . RESULTS The percentage of free PSA may be used in 2 ways : as a single cut-off ( ie , perform a biopsy for all patients at or below a cutoff of 25 % free PSA ) or as an individual patient risk assessment ( ie , base biopsy decisions on each patient 's risk of cancer ) . The 25 % free PSA cutoff detected 95 % of cancers while avoiding 20 % of unnecessary biopsies . The cancers associated with greater than 25 % free PSA were more prevalent in older patients , and generally were less threatening in terms of tumor grade and volume . For individual patients , a lower percentage of free PSA was associated with a higher risk of cancer ( range , 8%-56 % ) . In the multivariate model used , the percentage of free PSA was an independent predictor of prostate cancer ( odds ratio [ OR ] , 3.2 ; 95 % confidence interval [ CI ] , 2.5 - 4.1 ; P < .001 ) and contributed significantly more than age ( OR , 1.2 ; 95 % CI , 0.92 - 1.55 ) or total PSA level ( OR , 1.0 ; 95 % CI , 0.92 - 1.11 ) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. CONCLUSIONS Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer , with a minimal loss in sensitivity in detecting cancer . A cutoff of 25 % or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gl and , regardless of patient age or prostate size . To our knowledge , this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice 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 OBJECTIVES To determine the percentage of localized and potentially curable prostate cancers diagnosed at follow-up screening visits compared with the first screening visit . METHODS Within the context of a prospect i ve screening study performed in r and omly chosen men aged between 45 and 80 years , up to 6-year follow-up screening visits have been performed with serum prostate-specific antigen ( PSA ) measurement and digital rectal examination ( DRE ) followed by transrectal ultrasonography of the prostate when PSA or DRE is abnormal . RESULTS Of the 117 prostate cancers diagnosed at 14,554 annual follow-up visits , only 1 cancer ( 0.9 % ) was metastatic compared with 8 % ( 26/322 ) at 8029 first visits . Moreover , 97 % of the cancers detected at follow-up visits could be identified by PSA alone compared with 86 % at first visit . The incidence of 0.8 % per year during 15 years of screening between the ages of 55 and 70 years would diagnose localized prostate cancer in 12 % of the population , a value not too different from the 10 % diagnosed with prostate cancer during life-time in the absence of screening . CONCLUSIONS The present data show that annual screening with PSA diagnoses clinical ly localized prostate cancer in more than 95 % of cases , thus almost completely eliminating the diagnosis of metastatic prostate cancer . Moreover , the number of prostate cancers diagnosed is not significantly increased by screening PURPOSE Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer , the true incidence of false-negative biopsies is not well defined . We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy . MATERIAL S AND METHODS A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospect i ve r and omized trial of radical prostatectomy with or without neoadjuvant hormonal therapy . Clinical parameters were assessed to determine potential sources of bias . Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies . RESULTS Of the 118 patients 27 ( 23 % ) had a negative repeat sextant biopsy . Except for initial clinical stage , no differences were noted in the clinical or pathological parameters , or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies . CONCLUSIONS Our findings suggest that this 23 % incidence of false-negative biopsies represents significant cancer . This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy PURPOSE To assess complications of therapy for early ( nonmetastatic ) prostate cancer . PATIENTS AND METHODS A prospect i ve study of a cohort of 279 men who sought treatment advice and completed required pretreatment forms . The measures were self-reported patient symptoms and other measures of quality of life before therapy and at 3 and 12 months afterward . RESULTS Bowel and bladder symptoms were uncommon pretreatment . Patients frequently reported irritative bowel and bladder symptoms at 3 months after radiotherapy , although these subsided somewhat at 12 months . Substantial ( " a lot " ) urinary incontinence and wearing of absorptive pads were reported by 11 % and 35 % at 12 months after surgery and varied little by age . Incontinence occurred after radiotherapy infrequently , and only in men more than 65 years old . Inadequate erections , present in one third of men pretreatment , were nearly universal at 3 months after surgery , although some improvement , primarily in men under 65 years of age , was evident at 12 months . Sexual dysfunction after radiotherapy increased less but continually through 12 months , suggesting that observed treatment-related differences would decline with further follow-up . CONCLUSION External-beam radiotherapy of early prostate cancer is followed by bowel and bladder irritability , by increasingly severe sexual dysfunction and , in men aged more than 65 years , occasional urinary incontinence . Greater sexual dysfunction and urinary incontinence occur in the year following radical prostatectomy . These postsurgical complication rates from patient question naires are greater than have been reported in other treatment series and confirm the results of two retrospective studies of patient-reported complications OBJECTIVES To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen ( PSA ) and free PSA ( fPSA ) while maintaining a 90 % detection rate . Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL , approximately 13 % of men older than 50 would be added to the patient biopsy pool . METHODS One hundred fifty-one men were enrolled in a prospect i ve , Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme , and all biopsy specimens were examined by one pathologist . All men had a second blood specimen drawn before the biopsy for a determination of serum PSA , creatinine kinase , prostatic acid phosphatase , and fPSA . A new neural network algorithm was developed with PSA , creatinine kinase , prostatic acid phosphatase , fPSA , and age as input variables to produce a single-valued prostate cancer detection index ( PCD-I ) . This new algorithm was then prospect ively tested in the 151 men . Performance parameters ( including sensitivity , specificity , positive and negative predictive values , and biopsies saved ) were calculated , and a comparative analysis was performed to evaluate the differences among the new algorithm , percent fPSA , PSA density , and PSA density-transition zone . RESULTS Cancer was histologically confirmed in 24.5 % ( 37 of 151 ) of the men . The median age of the men was 62 years ( range 43 to 74 ) . At a sensitivity of 92 % , the specificity for percent fPSA was 11 % . The new algorithm ( PCD-I ) demonstrated an additional enhancement of specificity to 62 % at 92 % sensitivity . Clinical ly , the PCD-I would result in a savings of 49 % ( 74 of 151 ) of all biopsies or 63.6 % ( 71 of 114 ) of all unnecessary biopsies . CONCLUSIONS A new generation algorithm , derived from a neural network ( PCD-I ) incorporating the parameters of age , creatinine kinase , PSA , prostatic acid phosphatase , and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92 % sensitivity rate In 1978 the National Prostate Cancer Project launched two protocol s evaluating adjuvant therapy following surgery ( Protocol 900 ) or irradiation ( Protocol 1,000 ) for clinical ly localized prostate cancer . All patients underwent staging pelvic lymphadenectomy . Following definitive treatment , patients were r and omized to either cyclophosphamide 1 gram/m2-IV every 3 weeks for 2 years , estramustine phosphate 600 mg/m2-po daily for up to 2 years , or to observation only . Patient accession closed in 1985 and includes 184 to Protocol 900 ( 170 evaluable ) and 253 to Protocol 1,000 ( 233 evaluable ) . Lymph node involvement was identified in 198 patients ( 49 % of total ) , 29 % in Protocol 900 , 63 % in Protocol 1,000 . Median progression-free survival ( PFS ) for patients with nodal involvement in Protocol 1,000 receiving estramustine phosphate adjuvant was longer ( 37.3 mo ) compared to cyclophosphamide ( 30.9 mo ) and to no treatment ( 20.9 mo ) . Median PFS for patients with limited nodal disease in Protocol 1,000 was longer ( 39.9 mo ) , regardless of adjuvant , compared to extensive nodal disease ( 20.7 mo ) . However for patients with extensive nodal involvement , those receiving adjuvant estramustine phosphate experienced a significantly longer median PFS ( 32.8 mo ) compared to adjuvant cyclophosphamide ( 22.7 mo ) and no adjuvant ( 12.9 mo ) . We conclude that adjuvant estramustine phosphate is of benefit in prostate cancer patients with extensive pelvic node involvement receiving irradiation as definitive treatment PURPOSE We identified factors that affect sexual function in men 50 to 80 years old and , therefore , may confound the comparison among groups of elderly men . In particular , we identified factors that may influence a comparison between prostate cancer patients and the general population , or confound the relationship when comparing subgroups of patients in nonr and omized studies . MATERIAL S AND METHODS A question naire , including the Radiumhemmet Scale of Sexual Function and modules assessing potential risk factors for waning sexual function , was sent to 431 patients 50 to 80 years old with prostate cancer diagnosed 1.5 to 2 years previously in the Stockholm area ( Sweden ) and a reference group of 435 age matched r and omly selected men . RESULTS Factors associated with physiological impotence included prostate cancer ( relative risk 1.9 ) , diabetes mellitus ( relative risk 2.3 ) , myocardial infa rct ion ( relative risk 1.5 ) , medication with diuretics ( relative risk 1.5 ) , hydrogen blockers ( relative risk 2.3 ) and warfarin type anticoagulants ( relative risk 1.7 ) . Patients treated for prostate cancer were more likely to be physiologically impotent compared to those with no initial treatment , and this was true for all treatment protocol s after adjustment for confounding factors . Men treated with radical prostatectomy were more likely to be physiologically impotent than men treated with external beam radiation therapy ( relative risk 1.5 ) . CONCLUSIONS Waning sexual function in the prostate cancer patients was largely due to side effects of the treatment and this could not be explained by confounding factors . In particular , confounding could not explain the greater risk of impotence after radical prostatectomy compared to external beam radiation therapy PURPOSE We investigated the role of performing 2 consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate in a single office visit as the protocol for detecting prostate cancer in men presenting for the first time with an abnormal digital rectal examination and /or elevated serum prostate specific antigen ( PSA ) . MATERIAL S AND METHODS A total of 137 consecutive men presenting for the first time with a clinical ly localized prostate nodule on digital rectal examination and /or elevated serum PSA based upon age specific reference ranges underwent 2 consecutive sets of sextant prostate biopsies under transrectal ultrasound guidance in a single office visit . The 2 sets of biopsies were processed and analyzed separately by pathologists . RESULTS Adenocarcinoma of the prostate was diagnosed in 43 of the patients ( 31 % ) undergoing biopsy . Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies in 13 cases ( 10 % ) . High grade prostatic intraepithelial neoplasia without adenocarcinoma of the prostate was observed in 18 of the first set of biopsies ( 15 % ) . High grade intraepithelial neoplasia without adenocarcinoma of the prostate was the only pathological diagnosis in the second set of biopsies in 3 cases . The second set of biopsies provided important new clinical information related to prostate cancer in 20 cases ( 28 % ) and increased the number of cancers detected by 30 % . In addition , 14 patients with high grade intraepithelial neoplasia who would have required a second set of biopsies were found not to have adenocarcinoma of the prostate . Prostate cancer was detected in 43 , 27 and 24 % of men with prostate volumes less than 30 , 30 to 50 and greater than 50 cc , respectively . The percentage of prostate cancers detected only in the second set of biopsies was not significantly related to prostate size . CONCLUSIONS Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate performed in a single office visit represent a cost-effective biopsy strategy for men presenting with an abnormal digital rectal examination and /or elevated serum PSA . The benefits include increasing the detection of adenocarcinoma of the prostate and providing the recommended second set of biopsies for high grade intraepithelial neoplasia without increased morbidity or cost BACKGROUND Choice of treatment in localised prostate cancer has been hampered by a lack of unbiased , representative data on outcome . Most existing data have come from small cohorts at specialised academic centres ; precise overall and cancer- grade -specific data are not available , and the data are subject to differential staging bias . R and omised clinical trials have been undertaken , but the results will not be available for another decade . We have carried out a large population -based study to ascertain overall and prostate-cancer-specific survival in men treated by prostatectomy , radiotherapy , or conservative management . METHODS Data for 59,876 cancer-registry patients aged 50 - 79 were analysed . We examined the effect of differential staging of prostate cancer by analysing the data both by intention to treat and by treatment received . Estimated survival was calculated by the Kaplan-Meier method . FINDINGS By the intention-to-treat approach , 10-year prostate-cancer-specific survival for grade 1 cancer was 94 % ( 95 % CI 91 - 95 ) after prostatectomy , 90 % ( 87 - 92 ) after radiotherapy , and 93 % ( 91 - 94 ) after conservative management . The corresponding survival figures in grade 2 cancers were 87 % ( 85 - 89 ) , 76 % ( 72 - 79 ) , and 77 % ( 74 - 80 ) ; those in grade 3 cancer were 67 % ( 62 - 71 ) , 53 % ( 47 - 58 ) , and 45 % ( 40 - 51 ) . Although the intention-to-treat and treatment-received analyses yielded similar results for radiotherapy and conservative management , the 10-year disease-specific survival after prostatectomy differed substantially ( 83 % [ 81 - 84 ] by intention to treat vs 89 % [ 87 - 91 ] by treatment received ) . INTERPRETATION The overall and cancer- grade -specific survival found in this study differ substantially from those in previous studies . Previous studies that used a treatment-received approach have generally overestimated the benefits of radical prostatectomy . We found that grade 3 tumours are highly aggressive irrespective of stage To compare the efficacy of digital rectal examination and serum prostate specific antigen ( PSA ) in the early detection of prostate cancer , we conducted a prospect i ve clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination ( Hybritech T and em-E or T and em-R assays ) and digital rectal examination . Quadrant biopsies were performed if the PSA level was greater than 4 micrograms/l or digital rectal examination was suspicious , even if transrectal ultrasonography revealed no areas suspicious for cancer . The results showed that 15 % of the men had a PSA level of greater than 4 micrograms/l , 15 % had a suspicious digital rectal examination and 26 % had suspicious findings on either or both tests . Of 1,167 biopsies performed cancer was detected in 264 . PSA detected significantly more tumors ( 82 % , 216 of 264 cancers ) than digital rectal examination ( 55 % , 146 of 264 , p = 0.001 ) . The cancer detection rate was 3.2 % for digital rectal examination , 4.6 % for PSA and 5.8 % for the 2 methods combined . Positive predictive value was 32 % for PSA and 21 % for digital rectal examination . Of 160 patients who underwent radical prostatectomy and pathological staging 114 ( 71 % ) had organ confined cancer : PSA detected 85 ( 75 % ) and digital rectal examination detected 64 ( 56 % , p = 0.003 ) . Use of the 2 methods in combination increased detection of organ confined disease by 78 % ( 50 of 64 cases ) over digital rectal examination alone . If the performance of a biopsy would have required suspicious transrectal ultrasonography findings , nearly 40 % of the tumors would have been missed . We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection . Prostatic biopsy should be considered if either the PSA level is greater than 4 micrograms/l or digital rectal examination is suspicious for cancer , even in the absence of abnormal transrectal ultrasonography findings Although commonly thought to be an effective method of screening for prostatic cancer , digital rectal examinations have yet to be shown by controlled study to help prevent advanced forms of this disease . 139 men with metastatic ( stage D ) prostatic cancer ( cases ) were compared with an equal number of matched men free of this condition ( controls ) , with respect to rectal examinations recorded in the medical records up to , on average , 23 years before the cases ' initial diagnosis of prostatic cancer . Cases and controls were members of a large health maintenance organisation in northern California . In the 10 years before initial diagnosis ( excluding the last three months ) the average number of examinations for routine screening ( 2.45 vs 2.52 ) or to evaluate intestinal or rectal symptoms ( 0.44 in both ) were similar in cases and controls , respectively . After adjustment for racial differences , the relative risk of metastatic prostatic cancer for men with one or more screening rectal examinations compared with men with none was 0.9 with a 95 % confidence interval of 0.5 - 1.7 . Screening by routine digital rectal examination appears to have little if any effect in preventing metastatic prostatic cancer . If there is a small benefit , it will be difficult to demonstrate by conventional epidemiological study PURPOSE Although and rogen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate , its potential value as an adjuvant has not been substantiated . MATERIAL S AND METHODS In 1987 , the Radiation Therapy Oncology Group ( RTOG ) initiated a r and omized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate . A total of 977 patients had been accessioned to the study . Of these , 945 remained analyzable : 477 on the adjuvant arm and 468 on the observation arm . RESULTS Actuarial projections show that at 5 years , 84 % of patients on the adjuvant goserelin arm and 71 % on the observation arm remain without evidence of local recurrence ( P < .0001 ) . The corresponding figures for freedom from distant metastases and disease-free survival are 83 % versus 70 % ( P < .001 ) and 60 % and 44 % ( P < .0001 ) . If prostate-specific antigen ( PSA ) level greater than 1.5 ng is included as a failure ( after > or = 1 year ) , the 5-year disease-free survival rate on the adjuvant goserelin arm is 53 % versus 20 % on the observation arm ( P < .0001 ) . The 5-year survival rate ( for the entire population ) is 75 % on the adjuvant arm versus 71 % on the observation arm ( P = .52 ) . However , in patients with central ly review ed tumors with a Gleason score of 8 to 10 , the difference in actuarial 5-year survival ( 66 % on the adjuvant goserelin arm v 55 % on the observation arm ) reaches statistical significance ( P = .03 ) . CONCLUSION Application of and rogen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression . At this point , with a median follow-up time of 4.5 years , a significant improvement in survival has been observed only in patients with central ly review ed tumors with a Gleason score of 8 to 10 OBJECTIVE To describe the natural history of initially untreated early-stage prostate cancer . A key secondary objective was to calculate long-term survival rates by stage , grade , and age at diagnosis . DESIGN Prospect i ve cohort study . SETTING Population -based in 1 county of Sweden , without screening for prostate cancer . PATIENTS A group of 642 patients with prostate cancer of any stage , consecutively diagnosed between 1977 and 1984 at a mean age of 72 years with complete follow-up to 1994 . MAIN OUTCOME MEASURES Proportion of patients who died from prostate cancer , and 15-year survival ( with 95 % confidence interval [ CI ] ) , corrected for causes of death other than prostate cancer . RESULTS In the entire cohort , prostate cancer accounted for 201 ( 37 % ) of all 541 deaths . Among 300 patients with a diagnosis of localized disease ( T0-T2 ) , 33 ( 11 % ) died of prostate cancer . In this group , the corrected 15-year survival rate was similar in 223 patients with deferred treatment ( 81 % ; 95 % CI , 72%-89 % ) and in 77 who received initial treatment ( 81 % ; 95 % CI , 67%-95 % ) . The corrected 15-year survival was 57 % ( 95 % CI , 45%-68 % ) in 183 patients with locally advanced cancer ( T3-T4 ) and 6 % ( 95 % CI , 0%-12 % ) in those 159 who had distant metastases at the time of diagnosis . CONCLUSION Patients with localized prostate cancer have a favorable outlook following watchful waiting , and the number of deaths potentially avoidable by radical initial treatment is limited . Without reliable prognostic indicators , an aggressive approach to all patients with early disease would entail substantial overtreatment . In contrast , patients with locally advanced or metastatic disease need trials of aggressive therapy to improve their poor prognosis BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer A prospect i ve clinical trial of prostate cancer screening was conducted at 6 university centers including 6,630 men 50 years old or older who underwent a serum prostate specific antigen ( PSA ) determination and digital rectal examination . Biopsies were performed if the PSA level was greater than 4.0 ng./ml . ( Hybritech T and em assay ) or digital rectal examination was suspicious for cancer . We evaluated the effect on biopsy rate and cancer detection if the cutoff value was shifted from 4.0 to age-specific reference ranges recommended in the literature . In men 50 to 59 years old with normal digital rectal examination findings a decrease from 4.0 to 3.5 ng./ml . would have result ed in a 45 % increase in the number of biopsies ( 39 of 87 ) and a projected 15 % increase in cancer detection . An increase from 4.0 to 4.5 ng./ml . in men 60 to 69 years old would result in 15 % fewer biopsies ( 35 of 238 ) and would miss 8 % of the organ confined tumors ( 2 of 25 ) . Increasing the cutoff to 6.5 ng./ml . in men 70 years old or older would result in 44 % fewer biopsies ( 70 of 159 ) and would miss 47 % of the organ confined cancers ( 7 of 15 ) . The number of biopsies performed for each cancer detected with a PSA level of greater than 4.0 ng./ml . remains constant across age groupings , which suggests that the cutoff of 4.0 ng./ml . does not need to be altered in the older men , since it is apparently unaffected by the simultaneously increasing prevalence of benign prostatic hyperplasia and cancer with age . We conclude that a serum PSA concentration of 4.0 ng./ml . should be used as a general guideline for biopsy in all age groups Prostate cancer has become the most common cancer and the second cause of death due to cancer in men in North America . Since curative therapies are limited to early stages of the disease , the availability of an efficient , easy to perform , widely acceptable and cost-effective method of early detection of prostate cancer is particularly important . Thus , digital rectal examination , transrectal ultrasonography of the prostate as well as measurements of serum prostate specific antigen ( PSA ) were performed independently in a series of 1,002 men between 45 and 80 years old r and omly selected from the electoral rolls of Quebec City and its vicinity as part of a screening program for prostate cancer . Using this population of r and omly chosen men , various cutoff serum PSA values were selected in an attempt to find the optimal decision threshold that would indicate a much greater risk of having prostatic cancer . At a threshold value of 3.0 micrograms./l . the sensitivity and specificity of the test are 80.7 and 89.6 % , respectively , while the area under the receiver operating characteristic curve reflecting the accuracy of the test is 87.8 + /- 3.3 % ( plus or minus st and ard deviation ) . Moreover , the negative predictive value was estimated at 98.6 % , thus leaving only a 1.4 % chance of missing cancer when the serum PSA value was 3.0 micrograms./l . or less . Most importantly , such a threshold level of serum PSA retains only 19 % of the whole cohort as c and i date s for transrectal ultrasonography and expensive diagnostic procedures , thus leading to the finding of 1 prostate cancer of 4 such examinations . The present data indicate that simple measurement of serum PSA can be used efficiently as a pre-screening test for prostate cancer in the general population to identify , at a low cost , the sub population of men at a much greater risk of having prostate cancer , and who should then be su bmi tted to the more elaborate and expensive diagnostic procedures Objectives : To investigate the prevalence of urinary and bowel symptoms in population -based groups of men with and without prostate cancer . Methods : A self-administered question naire , assessing 5 urinary and 3 bowel symptoms , was sent to the 431 men diagnosed as having prostate cancer in the Stockholm area in 1992 who were still alive in October 1993 and to 435 r and omly selected control subjects with an age distribution matching men with newly diagnosed prostate cancer in the same area . The results were evaluated as ratios of proportions . Results : Among the prostate cancer patients , all urinary and bowel symptoms assessed were more common and the risk of having the various symptoms was 1.3–4.5 times that of the controls . The risks of having leakage of urine after radical prostatectomy and bowel urgency after external beam radiation therapy were fourfold when compared with the control group . We noted an increased risk ratio of proportions of leakage of faeces after radical prostatectomy and this risk was significantly increased when men with any of 11 specified diseases were excluded from the analysis to reduce confounding . Conclusions : Prostate cancer and its treatment affects urinary and bowel functions . The increased risk of having leakage of faeces after radical prostatectomy may be a chance phenomenon due to few patients subjected to surgery , but warrants further investigation OBJECTIVE To evaluate the validity of prostate-specific antigen ( PSA ) in identifying men who subsequently were or were not clinical ly diagnosed with prostate cancer , assess optimal test cutoff , measure lead time , and estimate relative risks ( RRs ) associated with discrete PSA levels . DESIGN S Nested case-control study of men providing plasma sample s before a 10-year follow-up . SETTING The Physicians ' Health Study , an ongoing r and omized trial that enrolled 22,071 men aged 40 to 84 years in 1982 . PARTICIPANTS A total of 366 men ( cases ) diagnosed with prostate cancer and 1098 men ( three controls per case ) , matched by age , r and omly selected from all cohort members at risk at the time of case diagnosis . MAIN OUTCOME MEASURES Sensitivity and specificity for each year of follow-up and for aggressive and nonaggressive cancers separately . RESULTS At a cutoff of 4.0 ng/mL , sensitivity for the entire 10-year follow-up was 46 % for total cases . Sensitivities for detection of total , aggressive , and nonaggressive cancers occurring in the first 4 years were 73 % , 87 % , and 53 % . Overall , specificity was 91 % and changed little by year of follow-up . Optimal validity was achieved at a cutoff of 3.3 ng/mL. Estimated mean lead time for all cancers was 5.5 years . Only 40 % of cancers detected more than 5 years from baseline were nonaggressive . Compared with men with PSA levels less than 1.0 ng/mL , those with PSA levels between 2.0 and 3.0 ng/mL had an RR of 5.5 ( 95 % confidence interval , 3.7 to 9.2 ) . CONCLUSIONS A single PSA measurement had a relatively high sensitivity and specificity for detection of prostate cancers that arose within 4 years . Prostate-specific antigen values less than the usual cutoff were associated with substantial increases in risk compared with the lowest levels . Final evaluation of PSA screening must also consider cost and the ability of current treatments to improve the prognosis of screen-detected cases BACKGROUND Many men diagnosed with clinical ly localized prostate cancer are initially treated conservatively , receiving neither surgery nor radiotherapy for the first year . Treatment patterns and quality -of-life outcomes have not been previously reported for a population -based sample of such men . METHODS A population -based r and om sample of men ( n = 661 ) from six geographic regions who had been newly diagnosed with clinical ly localized prostate cancer from 1994 through 1995 were followed for up to 1 year . Eligible subjects received neither surgery nor radiotherapy within 1 year of initial diagnosis . We assessed disease-specific and generic quality -of-life outcomes in men receiving and rogen deprivation therapy ( ADT ) compared with men receiving no therapy . All statistical tests were two-sided . RESULTS Two hundred and forty-five study patients received ADT and the remaining 416 patients received no therapy . Approximately two thirds of the patients ( n = 159 ) receiving ADT had either baseline Gleason scores greater than six or serum prostate-specific antigen values above 20 ng/mL. Among men who were sexually potent before diagnosis ( ADT = 88 patients ; no therapy = 223 patients ) , 80 % of those on ADT reported being impotent after 1 year compared with 30 % of those receiving no treatment ( P < .001 ) . Patients receiving ADT reported more physical discomfort 1 year after diagnosis than did men who had received no therapy . However , patients receiving ADT , compared with those receiving no therapy , were more likely to be satisfied with their treatment decision ( 56 % pleased versus 45.3 % ; P = .001 ) . Patients on ADT also experienced a statistically significant decline in vitality , but not in physical function , after adjustment for the confounding factors ( P = .05 ) . CONCLUSION ADT is a commonly used primary therapy for clinical ly localized prostate cancer . Therefore , men considering ADT as an initial treatment should be aware that sexual function and some aspects of physical well-being are likely to be affected in the first year following this treatment OBJECTIVES Digital rectal examination ( DRE ) is an important method of prostate cancer detection used by primary care physicians and medical specialists to identify patients in whom a prostatic biopsy is warranted . However , there is little empirical evidence assessing the degree of interexaminer variability in the use of DRE for the detection of prostate cancer . We addressed this issue within the framework of a prostate cancer screening study . METHODS We performed DRE examinations in 116 consecutive volunteers twice on the same day , with different urologists performing the examinations . The urologists were blinded to the results of the other examination and to the subject 's serum prostate-specific antigen ( PSA ) level . DRE results were coded as being benign or sufficiently suspicious for cancer to warrant a prostatic biopsy . RESULTS Examiners independently agreed on the DRE findings in 98 of the 116 ( 84 % ) subjects . However , when adjusted for chance agreement , the interexaminer agreement among urologists was only fair ( ie , kappa = 0.22 , P = 0.009 ) . Interexaminer variability was greater between faculty and resident examiners than among faculty examiners . CONCLUSIONS Our results suggest that the reproducibility of DRE for detecting prostate cancer is only fair among urologists . Further studies are indicated to evaluate interexaminer variability between primary care physicians and urologists Objectives : We compared the ability of three prostate – specific antigen ( PSA ) ratios – free – to– total PSA ratio ( fPSA/tPSA ) , free – to – complexed PSA ratio ( fPSA/cPSA ) , and complexed – to – total PSA ratio ( cPSA/tPSA ) – to distinguish prostate cancer from benign prostatic hyperplasia ( BPH ) . Methods : We tested 258 consecutive patients who underwent transrectal ultrasound – guided prostate needle biopsy because of an abnormal digital rectal examination or a T and em – R PSA of > 4.1 ng/ml . Free PSA ( fPSA ) and total PSA ( tPSA ) were measured by T and em – R assay . α1–Antichymotrypsin – complexed PSA ( cPSA ) was measured by Markit – M PSA – ACT assay . Results : Of the 258 patients , 204 had BPH , and 54 had prostate cancer . The specificity at 96 % sensitivity for fPSA/tPSA , fPSA/cPSA , and cPSA/tPSA was 23 , 25 , and 33 % , respectively . Of 162 patients with tPSA between 4.1 and 10.0 ng/ml , 132 had BPH and 30 had prostate cancer . The specificity at 96 % sensitivity for f/tPSA , f/cPSA and c/tPSA was 32 , 44 , and 41 % , respectively . There was no significant difference in the area under the receiver – operating characteristic curves among fPSA/tPSA , fPSA/cPSA , and cPSA/tPSA in the overall PSA range or in tPSA between 4.1 and 10.0 ng/ml . Conclusion : fPSA/tPSA , fPSA/cPSA , and cPSA/tPSA did not differ in their ability to distinguish prostate cancer from BPH BACKGROUND We evaluated symptoms and self- assessment s of quality of life in men with localized prostate cancer who participated in a r and omized comparison between radical prostatectomy and watchful waiting . METHODS Between 1989 and 1999 , a group of Swedish urologists r and omly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting . In this follow-up study , we obtained information from 326 of 376 eligible men ( 87 percent ) concerning certain symptoms , symptom-induced distress , well-being , and the subjective assessment of quality of life by means of a mailed question naire . RESULTS Erectile dysfunction ( 80 percent vs. 45 percent ) and urinary leakage ( 49 percent vs. 21 percent ) were more common after radical prostatectomy , whereas urinary obstruction ( e.g. , 28 percent vs. 44 percent for weak urinary stream ) was less common . Bowel function , the prevalence of anxiety , the prevalence of depression , well-being , and the subjective quality of life were similar in the two groups . CONCLUSIONS The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction , urinary leakage , and urinary obstruction , but on average , the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years |
12,681 | 17,054,164 | Complex approaches show promise , with some persistence of abstinence ( 30 days point prevalence abstinence at six months ) , especially those incorporating elements sensitive to stage of change .
Psycho-social interventions have not so far demonstrated effectiveness , although pooled results for the Not on Tobacco trials suggest that that this approach may yet prove to be effective ; however , their definition of cessation ( one or more smoke-free days ) may not adequately account for the episodic nature of much adolescent smoking . | BACKGROUND Teenage smoking prevalence is around 15 % in developing countries ( with wide variation from country to country ) , and around 26 % in the UK and USA .
Although most tobacco control programmes for adolescents are based around prevention of uptake , there are also a number of initiatives to help those who want to quit .
Since those who do not smoke before the age of 20 are significantly less likely to start as adults , there is a strong case for programmes for young people that address both prevention and treatment .
OBJECTIVES To evaluate the effectiveness of strategies that help young people to stop smoking tobacco . | This study evaluates a youth subject-directed smoking prevention and cessation program titled Breathe Easy ! The program was delivered at two sites and a control group was recruited from two additional sites . Surveys were administered prior to the program and either 1 month or 6 months after completion at the exposure sites . The same survey administration procedure was used as the control . After controlling for invalid responses and including only those that completed both surveys , 251 exposure subjects and 159 control subjects remained for analysis . At sites with 1-month follow-up , no significant difference was noted between intervention and control groups . At the sites with 6-month follow-up , prevalence dropped from 18.7 % to 8.9 % , which is statistically significant , while at the control site prevalence changed from 14.1 % to 9.4 % , which is not significant . Additional outcomes examined in the exposed group showed trends toward smoking cessation and prevention at higher rates than those of the unexposed group This investigation evaluated the efficacy of expressive writing as a treatment adjunct to a brief office smoking cessation intervention plus nicotine patch therapy in young adults . Participants aged 18 - 24 years were r and omized to a brief office intervention ( n=99 ) or to an expressive writing plus brief office intervention ( n=97 ) . Both conditions received four individual visits plus 6 weeks of nicotine patch therapy , which began on the quit date following the week 2 visit . Participants in the expressive writing plus brief intervention condition wrote for 2 consecutive days before and 3 consecutive days after the quit date . The brief office intervention group completed a control writing assignment . At end of treatment ( week 8) , biochemically confirmed 7-day point-prevalence abstinence for the expressive writing plus brief office intervention condition was significantly greater than for the brief office condition ( 33 % vs. 20 % , p=.043 , OR=2.0 , 95 % CI=1.0 - 3.7 , from a logistic regression adjusting for gender ) . At 24 and 52 weeks , abstinence rates were similar for the brief office intervention versus expressive writing plus brief office intervention ( 12 % vs. 11 % at 24 weeks ; 11 % vs. 11 % at 52 weeks ) . The results suggest that expressive writing has promise as a smoking cessation treatment adjunct for young adults . Lengthier interventions or the use of boosters should be tested to extend treatment effects . However , participants reported a low level of enthusiasm for the expressive writing , which may be a barrier to implementing it over a longer time frame . Therefore , other modes of delivering expressive writing to young adult cigarette smokers should be explored BACKGROUND Community dental clinics are good setting s for smoking intervention . The aim here was to put forward a strategy for preventing adolescent smoking by means of a brief intervention . METHODS A total of 2,586 12-year-olds participated in this follow-up study . They were asked upon arrival for their annual routine dental examination to complete a smoking question naire and were r and omly assigned to either the intervention group or the usual care control group according to the last digit of their date of birth ( odd or even ) . The intervention comprised annually inquiring about smoking , showing photographs of the harmful effects of smoking on the teeth , allowing participants to examine their own mouth with a mirror , and finally counselling them in accordance with their answer to the question on smoking habits . The smoking status reported was not verified by other means . RESULTS The prevalence of smoking at the end of the 2-year follow-up was 18.1 % , in the intervention group and 20.8 % among the controls . However , no statistically significant differences between groups were found . CONCLUSIONS These results reflect the difficulties of achieving successful results with long-term smoking cessation programs with adolescents in unstable conditions During June 2000-May 2001 , the American Cancer Society conducted a r and omized trial of telephone counseling among more than 3,500 current smokers who called to seek assistance in quitting . All eligible callers were r and omized to receive either self-help booklets through the mail or booklets and up to 5 sessions of telephone counseling . Approximately 12 % ( 420/3,522 ) of study participants were 18 - 25 years of age . Using intent to treat analyses , 3- and 6-month quit rates among both younger and older smokers were significantly higher among those who received telephone counseling than among those who received self-help booklets only . Three-month rates were 20 % versus 9 % for 18 - 25 year olds and 15 % versus 10 % for older adults . Results indicate that younger smokers can benefit from telephone counseling Smoking cessation interventions are needed for young adults . Innovative approaches to behavior change for this population should be tested . Formative research and process evaluation of those approaches would result in more effective programs . This paper presents the development process and process evaluation of a web-based smoking cessation program . A description of the stages of development is presented with formative research , development of the web-based intervention , formative evaluation , and process evaluation . The smokers reported high usage of the intervention and satisfaction with the intervention in that it helped to raise their consciousness about quitting , encouraged them to set behavioral goals , provided stages of change feedback , and offered interactivity in presenting information and strategies about quitting . The Internet may be a promising tool for patient education according to the process results Background Happy Ending ( HE ) is an intense 1-year smoking cessation program delivered via the Internet and cell phone . HE consists of more than 400 contacts by email , Web pages , interactive voice response , and short message service technology . HE includes a craving helpline and a relapse prevention system , providing just-in-time therapy . All the components of the program are fully automated . Objective The objectives were to describe the rationale for the design of HE , to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy , and to explore the potential effect of HE on coping planning and self-efficacy ( prior to quitting ) and whether coping planning and self-efficacy mediate treatment effect . Methods A two-arm r and omized controlled trial was used . Subjects were recruited via Internet advertisements and r and omly assigned to condition . Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older . The intervention group received HE , and the control group received a 44-page self-help booklet . Abstinence was defined as “ not even a puff of smoke , for the last seven days ” and was assessed by means of Internet surveys or telephone interviews 1 , 3 , 6 , and 12 months postcessation . The main outcome was repeated point abstinence ( ie , abstinence at all four time points ) . Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase ( ie , after 2 weeks of treatment , but prior to cessation day ) . Results A total of 290 participants received either the HE intervention ( n=144 ) or the control booklet ( n=146 ) . Using intent-to-treat analysis , participants in the intervention group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants ( 20 % versus 7 % , odds ratio [ OR ] = 3.43 , 95 % CI = 1.60 - 7.34 , P = .002 ) . Although no differences were observed at baseline , by the end of the preparation phase , significantly higher levels of coping planning ( t 261 = 3.07 , P = .002 ) and precessation self-efficacy ( t 261 = 2.63 , P = .01 ) were observed in the intervention group compared with the control group . However , neither coping planning nor self-efficacy mediated long-term treatment effect . For point abstinence 1 month after quitting , however , coping planning and self-efficacy showed a partial mediation of the treatment effect . Conclusions This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy . The study adds to the promise of using digital media in supporting behavior change Background Epidemiologic data indicate most adolescents and adults experience multiple , simultaneous risk behaviors . Purpose The purpose of this study is to examine the efficacy of a brief image-based multiple-behavior intervention ( MBI ) for college students . Methods A total of 303 college students were r and omly assigned to : ( 1 ) a brief MBI or ( 2 ) a st and ard care control , with a 3-month postintervention follow-up . Results Omnibus treatment by time multivariate analysis of variance interactions were significant for three of six behavior groupings , with improvements for college students receiving the brief MBI on alcohol consumption behaviors , F(6 , 261 ) = 2.73 , p = 0.01 , marijuana-use behaviors , F(4 , 278 ) = 3.18 , p = 0.01 , and health-related quality of life , F(5 , 277 ) = 2.80 , p = 0.02 , but not cigarette use , exercise , and nutrition behaviors . Participants receiving the brief MBI also got more sleep , F(1 , 281 ) = 9.49 , p = 0.00 , than those in the st and ard care control . Conclusions A brief image-based multiple-behavior intervention may be useful in influencing a number of critical health habits and health-related quality -of-life indicators of college students OBJECTIVES . Nicotine nasal spray has been 1 of the most successful forms of nicotine-replacement therapy in adult population s. The nasal sprayer has not been studied in adolescent smokers . The objective of this pilot study was to determine the feasibility and utility of using nicotine nasal spray for adolescent smokers who wanted to quit smoking . METHODS . Forty adolescent smokers who were between 15 and 18 years of age and smoked ≥5 cigarettes daily for at least 6 months were recruited from several San Francisco Bay area schools from 2005 to 2007 . Using a r and omized , open-label , 12-week trial , adolescent smokers were assigned to receive either weekly counseling alone ( control ) for 8 weeks or 8 weeks of counseling along with 6 weeks of nicotine nasal spray . Self-reported smoking abstinence was verified by both expired-air carbon monoxide and salivary cotinine . RESULTS . There was no difference in cessation rates , the numbers of cigarettes smoked per day , or cotinine levels at 12 weeks . Fifty-seven percent of participants stopped using their spray after only 1 week . The most commonly reported adverse effect was nasal irritation and burning ( 34.8 % ) followed by complaints about the taste and smell ( 13 % ) . CONCLUSIONS . The unpleasant adverse effects , poor adherence , and consequent lack of efficacy observed in our pilot study do not support the use of nicotine nasal spray as an adjunct to counseling for adolescent smokers who wish to quit OBJECTIVE The purpose of this study was to develop a smoking cessation program combined with an Internet-assisted instruction ( IAI ) program to help youth smokers quit smoking , and to evaluate the effectiveness of the program in changing youth 's attitudes toward smoking , smoking behavior , and self-efficacy for smoking cessation . METHODS To achieve this goal , a comparative study of 77 senior high students divided into two groups was conducted . One group , design ated as the experimental group , accepted a 6-week smoking cessation program plus an IAI program and the other group did not receive any intervention as the comparison group . All participants completed question naires before and after the program . RESULTS The results showed that the strategy of combining the smoking cessation program and an IAI program was highly effective in terms of effects upon the youth 's attitude towards smoking , smoking behavior , and self-efficacy . There was a highly positive correlation between the participants ' attitude toward smoking and self-efficacy . In contrast , cigarette consumption was in a strongly negative correlation with self-efficacy . CONCLUSION Most of all participants in the experimental group recognized the effectiveness of the program , and thought the smoking cessation program with an IAI program was helpful and welcomed by youth . This study can serve as reference for future design and implementation of IAI programs for youth smoking cessation The majority of regular adult smokers begin smoking in adolescence and there is a clear need for youth-targeted smoking cessation interventions . The present r and omized , controlled trial tested the effectiveness of motivational enhancement therapy ( MET ) to reduce smoking among 81 adjudicated adolescents . Participants received either MET or an education control . Smoking abstinence , quantity , and frequency were assessed at 1 and 6 months post treatment . Results suggest that although between-group differences on outcome measures were not significant at follow-up , smoking behavior decreased in both groups with approximately 10 % achieving 1-month smoking abstinence at 6-month follow-up . Furthermore , participant response to MET varied by level of alcohol use and impulsivity such that participants with lower levels of alcohol use and impulsivity had significantly greater response to MET . In contrast , participants who endorsed higher rates of alcohol use and impulsivity responded better to the control than the MET condition . Results suggest that MET may be an effective intervention for some adolescent smokers but may be contraindicated for adolescents who have concomitant problems with alcohol use or impulsivity The use of alternative medicine for smoking cessation have been increasing steadily in recent years . A series of clinical group studies was performed to clarify the effect , outcome and success rate of an acupuncture treatment for smoking cessation . This study was conducted for four weeks using 238 smoking students at 2 high schools . The subjects were separated into two groups : 159 students were treated with acupuncture on the anti-smoking acupoints of the ear , which is known to be effective for cessation of smoking ( case group ) , and 79 students were treated at other sites of the ear ( control group ) . The acupuncture treatment was alternately administered at each side of the ears on a weekly basis for 4 weeks . The smoking cessation success was only 1 case ( 0.6 % ) in the case group and none in the control group after 4 weeks . The change in the taste of tobacco and the intensity of the desire to smoke were not significantly different between the case and control groups , but the case group showed a tendency of reduction in the taste of tobacco and the intensity of the desire to smoke . In addition , the reduction in cigarette consumption was not significant , but the tendency of reduction in the study group was significant . It is believed that the site of auricular acupuncture for smoking cessation is not important . However , there was a significant tendency in terms of the reduction in cigarette consumption , the taste of tobacco and the intensity of the desire to smoke in the case group , indicating that auricular acupuncture in smoking cessation has some effect Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly OBJECTIVES This study aim ed to develop an Internet-assisted smoking cessation program accompanied with auricular acupressure , and compare the quit rate and self-efficacy of youth smokers receiving auricular acupressure with and without the Internet-assisted smoking cessation program . DESIGN A Website was constructed on IBM Websphere 5.0 and DB2 data base using HTML , Javascript , and JSP . A quasiexperimental research design was adopted . Subjects were assigned nonr and omly to two groups . Group 1 received auricular acupressure plus the Internet-assisted smoking cessation program , whereas group 2 received auricular acupressure only . MEASUREMENTS The data of demographic factors , serum cotinine , quitting rate , nicotine dependence , and self-efficacy of subjects were collected before and after a 4-week intervention . RESULTS After intervention , the quit rate was 15.78 % in group 1 and 2.56 % in group 2 . Nicotine dependence was significantly lowered in group 1 , but remained unchanged in group 2 . The improvement of self-efficacy between groups 1 and 2 was significantly different . CONCLUSIONS The combination of auricular acupressure and Internet-assisted smoking cessation program was more efficacious than auricular acupressure alone in terms of quit rate Introduction Motivational interviewing techniques have been minimally research ed as a function of a teenage smoking intervention . The present study examined the efficacy of a theory-based motivational tobacco intervention ( MTI ) . Methods A r and omized two-group design was used to compare 6-month post-baseline quit and reduction rates among teenagers who received the MTI with those who received brief advice or care as usual . Participants were smokers aged 14 to 19 years ( N = 75 ) who presented for treatment in a university-affiliated hospital emergency department ( ED ) . Motivational interviewing techniques were used by trained providers to facilitate individual change ; stage-based take-home material s also were provided . Results Similar to past clinic-based studies of motivational interviewing with teenage smokers , our study found negative results in terms of intervention efficacy for cessation . Six-month follow-up cessation rates were nonsignificant — two teenagers quit smoking . Among teenagers who were available at follow-up , a medium effect size ( Cohen 's h = .38 ) was found for reduction and a large effect size ( Cohen 's h = .69 ) was found for percentage reduction , although these results also were not statistically significant . Conclusion Although the major findings of this study were not significant , the reductions in tobacco use suggest that motivational interviewing may be a clinical ly relevant counseling model for use in teenage smoking interventions . However , many questions remain , and the current literature lacks studies on trials with significant outcomes using motivational interviewing in smoking cessation . Additionally , more research is needed to examine the suitability of the ED for MTI-type interventions The enrollment process determines the study sample and external validity of clinical trial results ; however , few reports describe the process and outcome of screening efforts for smoking cessation studies among adolescents . We describe and evaluate a screening protocol to enroll adolescent smokers for a r and omized clinical trial of nicotine replacement therapy . Adolescent smokers obtained the recruitment call-in number ( 1 - 800-NO-SMOKE ) via media and other advertisements . Trained recruitment staff collected information using an internally developed , targeted telephone screening interview , which was used to determine pre- eligibility for the clinical trial . Correlates of qualification and of study enrollment were determined . Among 1,347 adolescents screened , 329 ( 24.4 % ) were eligible to participate in the trial . Light smoking ( 39.1 % ) and lack of parental support ( 14.8 % ) were the biggest contributors to in eligibility . Eligible adolescents were more likely to be female ( 66.9 % vs. 58.2 % , p = .0052 ) and more likely to be European American ( 63.5 % vs. 52.2 % , p = .0003 ) . The higher rates of in eligibility for African Americans and boys were partly explained by lower scores on the Fagerström Test for Nicotine Dependence . Of those eligible to participate in the trial , 159 ( 48.3 % ) enrolled . Results underscore the need for screening instruments that are measurement-invariant across ethnicities and gender , and for enrollment strategies that maximize inclusion of eligible participants OBJECTIVE . The purpose of this work was to determine whether a pediatric practice -based smoking prevention and cessation intervention increases abstinence rates among adolescents . METHODS . Eight pediatric primary care clinics were r and omly assigned to either intervention or usual care control condition . The provider- and peer-delivered intervention tested was based on the 5A model recommended by the US Public Health Service clinical practice guidelines and the American Academy of Pediatrics and consisted of brief counseling by the pediatric provider followed by 1 visit and 4 telephone calls by older peer counselors aged 21 to 25 years . A consecutive sample of patients aged 13 to 17 years scheduled for an office visit was eligible regardless of smoking status . Of 2711 patients who agreed to participate , 2709 completed baseline assessment s , and 2700 ( 99.6 % ) and 2690 ( 99.2 % ) completed 6- and 12-month assessment s , respectively . RESULTS . Compared with the usual care condition , nonsmokers who received the provider- and peer-delivered intervention were significantly more likely to self-report having remained abstinent at 6-month and 12-month follow-up ; smokers who received the provider- and peer-delivered intervention were more likely to report having quit at the 6-month but not the 12-month follow-up . A number of adolescent characteristics ( eg , age , peer smoking , tobacco dependence , and susceptibility ) were found to be predictive of abstinence at follow-up . CONCLUSIONS . A pediatric practice -based intervention delivered by pediatric providers and older peer counselors proved feasible and effective in discouraging the initiation of smoking among nonsmoking adolescents for 1 year and in increasing abstinence rates among smokers for 6 months This study was design ed to create , implement , and test a school-based multiple risk factor reduction program for high school students . All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in the study . Within each district , one school was assigned at r and om to receive a special 20-session CVD risk reduction intervention and one school served as a control . The schools were matched for size and distribution of racial groups before r and omization . At a two-month follow-up , knowledge gains were significantly greater for students in the treatment group on each of the risk factor domains tested : nutrition/diet ( p less than 0.0001 ) , physical activity ( p less than 0.0001 ) , and cigarette smoking ( p less than 0.0001 ) . Compared to controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline , reported regular exercise at follow-up ( p less than 0.0003 ) . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared to 10.3 % in the control group ( p = 0.009 ) . Students in the treatment group were more likely to report that they would choose heart healthy snack items ( p less than 0.0001 ) . Beneficial treatment effects were observed for resting heart rate ( p less than 0.0001 ) , BMI ( p = 0.05 ) , triceps skinfold thickness ( p = 0.003 ) , and subscapular skinfold thickness ( p = 0.01 ) . The results suggest that it is feasible to provide CVD risk reduction training to a large segment of the population through school-based primary prevention approaches The goal of this longitudinal study was to test an innovative approach to smoking cessation that might be particularly attractive to adolescent smokers . The study was a participatory research effort between academic and school partners . The intervention used an Internet-based , virtual reality world combined with motivational interviewing conducted in real-time by a smoking cessation counselor . Participants were 136 adolescent smokers recruited from high schools r and omized to the intervention or a measurement-only control condition . Those who participated in the program were significantly more likely than controls to report at the immediate post-intervention assessment that they had abstained from smoking during the past week ( p < or=.01 ) , smoked fewer days in the past week ( p < or=.001 ) , smoked fewer cigarettes in the past week ( p < or=.01 ) , and considered themselves a former smoke ( p < or=.05 ) . Only the number of times quit was statistically significant at a one-year follow-up assessment ( p < or=.05 ) . The lack of longer-term results is discussed , as are method ological challenges in conducting a cluster-r and omized smoking cessation study BACKGROUND This paper presents the student outcomes of a large-scale , social-influences-based , school and media-based tobacco use prevention and cessation project in Southern California . METHODS The study provided an experimental comparison of classroom delivery with television delivery and the combination of the two in a 2 x 2 plus 1 design . Schools were r and omly assigned to conditions . Control groups included " treatment as usual " and an " attention control " with the same outcome expectancies as the treatment conditions . Students were surveyed twice in grade 7 and once in each of grade s 8 and 9 . The interventions occurred during grade 7 . RESULTS We observed significant effects on mediating variables such as knowledge and prevalence estimates , and coping effort . The knowledge and prevalence estimates effects decayed partially but remained significant up to a 2-year follow-up . The coping effort effect did not persist at follow-ups . There were significant main effects of both classroom training and TV programming on knowledge and prevalence estimates and significant interactions of classroom and TV programming on knowledge ( negative ) , disapproval of parental smoking , and coping effort . There were no consistent program effects on refusal/self-efficacy , smoking intentions , or behavior . CONCLUSIONS Previous reports demonstrated successful development and pilot testing of program components and measures and high acceptance of the program by students and parents . The lack of behavioral effects may have been the result of imperfect program implementation or low base rates of intentions and behavior Objectives . To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking . Design . Double-blind , double-dummy , r and omized , 3-arm trial with a nicotine patch ( 21 mg ) , nicotine gum ( 2 and 4 mg ) , or a placebo patch and gum ; all participants received cognitive-behavioral group therapy . Setting . Inner-city , outpatient clinic on the East Coast . Subjects . Thirteen- to 17-year-old adolescents who smoked ≥10 cigarettes per day ( CPD ) , scored ≥5 on the Fagerström Test of Nicotine Dependence , and were motivated to quit smoking . Intervention . Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy , with a follow-up visit at 6 months ( 3 months after the end of treatment ) . Main Outcome Measures . Safety assessed on the basis of adverse event reports for all 3 groups , prolonged abstinence , assessed through self-report and verified with exhaled carbon monoxide ( CO ) levels of ≤6 ppm , in intent-to-treat analyses , and smoking reduction ( CPD and thiocyanate concentrations ) among trial completers . Results . A total of 120 participants were r and omized ( 72 % white , 70 % female ; age : 15.2 ± 1.33 years ; smoking : 18.8 ± 8.56 CPD ; Fagerström Test of Nicotine Dependence score : 7.04 ± 1.29 ) from 1999 to 2003 . Participants started smoking at 11.2 ± 1.98 years of age and had been smoking daily for 2.66 ± 1.56 years ; 75 % had at least 1 current psychiatric diagnosis . Mean compliance across groups was higher for the patch ( mean : 78.4–82.8 % ) than for the gum ( mean : 38.5–50.7 % ) . Both the patch and gum were well tolerated , and adverse events were similar to those reported in adult trials . Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant . Intent-to-treat analyses of all r and omized participants showed CO-confirmed prolonged abstinence rates of 18 % for the active-patch group , 6.5 % for the active-gum group , and 2.5 % for the placebo group ; the difference between the active-patch and placebo arms was statistically significant . There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes . Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group . Mean smoking rates , but not CO or thiocyanate concentrations , decreased significantly in all 3 arms but not as a function of treatment group . Conclusions . Nicotine patch therapy combined with cognitive-behavioral intervention was effective , compared with placebo , for treatment of tobacco dependence among adolescent smokers . Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking . Additional study of nicotine gum , with enhanced instructional support , is needed to assess its efficacy among adolescent smokers Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates Objective : To test the hypothesis that among adolescent smokers hospitalised for psychiatric and substance use disorders , motivational interviewing ( MI ) would lead to more and longer quit attempts , reduced smoking , and more abstinence from smoking over a 12 month follow up . Design : R and omised control trial of MI versus brief advice ( BA ) for smoking cessation , with pre- and post-intervention assessment of self efficacy and intentions to change , and smoking outcome variables assessed at one , three , six , nine , and 12 month follow ups . Setting : A private , university affiliated psychiatric hospital in Providence , Rhode Isl and , USA . Patients or other participants : Consecutive sample ( n = 191 ) of 13–17 year olds , admitted for psychiatric hospitalisation , who smoked at least one cigarette per week for the past four weeks , had access to a telephone , and did not meet DSM-IV criteria for current psychotic disorder . Interventions : MI versus BA . MI consisted of two , 45 minute individual sessions , while BA consisted of 5–10 minutes of advice and information on how to quit smoking . Eligible participants in both conditions were offered an eight week regimen of transdermal nicotine patch upon hospital discharge . Main outcome measures : Point prevalence abstinence , quit attempts , changes in smoking rate and longest quit attempt . Proximal outcomes included intent to change smoking behaviour ( upon hospital discharge ) , and self efficacy for smoking cessation . Results : MI did not lead to better smoking outcomes compared to BA . MI was more effective than BA for increasing self efficacy regarding ability to quit smoking . A significant interaction of treatment with baseline intention to quit smoking was also found . MI was more effective than BA for adolescents with little or no intention to change their smoking , but was actually less effective for adolescents with pre-existing intention to cut down or quit smoking . However , the effects on these variables were relatively modest and only moderately related to outcome . Adolescents with comorbid substance use disorders smoked more during follow up while those with anxiety disorders smoked less and were more likely to be abstinent . Conclusions : The positive effect of MI on self efficacy for quitting and the increase in intention to change in those with initially low levels of intentions suggest the benefits of such an intervention . However , the effects on these variables were relatively modest and only moderately related to outcome . The lack of overall effect of MI on smoking cessation outcomes suggests the need to further enhance and intensify this type of treatment approach for adolescent smokers with psychiatric comorbidity AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking Objective . To evaluate the impact of a school-based smoking cessation program targeting adolescents interested in quitting . Design . R and omized clinical trial over one school year . Setting . Large public high school . Participants . Students interested in quitting smoking . Intervention . Seventy-four students were r and omized to receive either : 1 ) a 6-week , 8-session , classroom-based , smoking cessation curriculum design ed for adolescents ( n = 35 ) or 2 ) an informational pamphlet on how to quit smoking with promise of the classroom curriculum in 3 months ( n = 39 ) . Outcome Measures . Change in smoking behavior measured by : 1 ) self-reported smoking cessation and exhaled carbon monoxide < 6 parts per million ( smoke-free ) ; 2 ) self-reported quit attempts ; and 3 ) change in cigarettes per day ( cpd ) at the end of the 6-week curriculum and then 4 , 10 , and 20 weeks later . Saliva cotinine was also measured at these points to vali date these outcome measures . Analysis . Intention-to-treat . Results . Participants in the classroom group attended an average of 4.4 sessions . At the end of the curriculum , the classroom group was significantly more likely to be smoke-free ( 59 % vs 17 % ) , to have tried to quit smoking ( 82 % vs 54 % ) , and to reduce mean cpd ( 7.0 vs 1.0 ) . Four weeks later , these differences persisted : smoke-free ( 52 % vs 20 % ) , quit attempt ( 85 % vs 60 % ) , and reduction in mean cpd ( 6.6 vs 1.6 ) . Changes in saliva cotinine were consistent with reported outcome measures ; those who were smoke-free had a significant reduction in saliva cotinine at the end of the intervention , and at 4 weeks . At 10 and 20 weeks after the curriculum , 41 % and 31 % , respectively , of the classroom group remained smoke-free . Once participants in the pamphlet group underwent the classroom intervention ( average attendance of 2.2 sessions ) their cessation rates were similar to the initial group : 31 % at the end of the curriculum and 27 % 10 weeks later . Conclusion . A school-based curriculum for adolescent smoking cessation is more effective than an informational pamphlet alone and reduces cigarette use by adolescents . More research is needed to test the reproducibility , sustainability , and generalizability of this curriculum to offer more smoking cessation options to teenagers OBJECTIVE To evaluate the impact of a classroom-based , Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents . DESIGN A two-group r and omized control trial with 1,402 male and female students in grade s 9 through 11 from 14 secondary schools in Toronto , Canada . Participants were r and omly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up . The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine ( http://www.smokingzine.org ) integrated into a program that included a paper-based journal , a small group form of motivational interviewing , and tailored e-mails . MAIN OUTCOME MEASURE Resistance to smoking , behavioral intentions to smoke , and cigarette use were assessed at baseline , postintervention , and three- and six-month follow-up . Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time . RESULTS The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months . The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period . CONCLUSION The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months . By providing an accessible and attractive method of engaging young people in smoking prevention and cessation , this interactive and integrated program provides a novel vehicle for school- and population -level health promotion We conducted a 2-arm r and omized trial to test the efficacy of self-help material s with or without proactive telephone counseling to increase cessation among teen smokers . Teen smokers ( N = 402 ) recruited from 11 shopping malls and 1 amusement park in the southeastern United States were r and omized to 1 of 2 groups : written self-help material plus video ; or written self-help material , video , and telephone counseling . Cessation rates based on 7-day point-prevalent abstinence for the self-help and counseling arms were 11 % and 16 % , respectively ( p = .25 ) , at 4 months postbaseline and 19 % and 21 % , respectively ( p = .80 ) , at 8 months postbaseline . Sustained abstinence , reflecting 7-day abstinence at both time points , in the self-help and counseling arms was 7 % and 9 % ( p = .59 ) . Results suggest that minimal self-help cessation approaches that target youth have comparable success to that shown among adult smokers . However , refinements in telephone-counseling approaches may be needed to achieve the success observed in adult population This experiment tested the transtheoretical model ( J.O. Prochaska & C.C. DiClemente , 1983 ) of smoking cessation by matching or mismatching interventions to smokers in a particular stage . The interventions were tested against a no-intervention condition with 92 college-aged daily smokers in the precontemplation stage of change . The stage-matched intervention asked smokers to think more about quitting smoking ; the stage-mismatched intervention provided action-oriented activities typically used for those ready to quit smoking . The results failed to support the value of matching interventions to a smoker 's stage of change . Instead , more smokers who received the action intervention tried to quit smoking . Matching interventions to an individual 's current stage may be less important than the transtheoretical model suggests Adolescent cigarette smokers from r and omly selected classrooms from 24 California and Illinois high schools were assessed regarding their interest in cessation , reasons for quitting , and smoking temptation circumstances . These data were analyzed by gender . Males and females were not found to differ in quit stage or perceived likelihood of ever quitting smoking , although males reported being somewhat more likely to have ever tried to quit in the past . The associations of reasons for quitting were not found to vary by gender in most comparisons . On the other h and , the associations of smoking temptation circumstances with gender showed that a greater percentage of females than males reported more circumstances that would make them tempted to smoke . Smoking cigarettes to regulate one 's affective states , and to avoid nicotine withdrawal , may be functions of smoking that impede efforts at quitting , particularly among adolescent females Background : Smoking is common in young people , particularly in disadvantaged groups , and continued smoking has a major impact on quality and quantity of life . Although many young smokers want to stop smoking , little is known about the design and effectiveness of cessation services for them . Objective : To determine whether nicotine replacement therapy ( NRT ) when combined with counselling is effective in young smokers in a deprived area of Nottingham , UK Methods and subjects : We surveyed smoking prevalence and attitudes to smoking and quitting in young people accessing an open access youth project in a deprived area of Nottingham , and used the information gained to design a community based smoking cessation service incorporating a r and omised controlled trial of nicotine patches against placebo given in association with individual behavioural support . We resurveyed smoking prevalence among project attendees after completing the pilot study . Results : Of 264 young people surveyed ( median age 14 years , range 11–21 ) , 49 % were regular smokers . A total of 98 young people were recruited and r and omised to receive either active nicotine patches on a six week reducing dose regimen ( 49 participants ) , or placebo ( 49 participants ) . Adherence to therapy was low , the median duration being one week , and 63 participants did not attend any follow up . At four weeks , five subjects receiving active NRT and two receiving placebo were abstinent , and at 13 weeks none were . Adverse effects were more common in the active group but none were serious . Smoking prevalence among 246 youth project attendees surveyed after the trial was 44 % . Conclusions : This study suggests that NRT in this context is unlikely to be effective in young smokers , not least because of low adherence to therapy . It also suggests that young smokers want help with smoking cessation , but that establishing the efficacy of smoking cessation services for young people who need them most will be very difficult OBJECTIVE To assess the safety and efficacy of sustained-release bupropion hydrochloride for adolescent smoking cessation . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled , dose-ranging trial . SETTING Metropolitan areas of Tucson and Phoenix , Arizona . PARTICIPANTS Adolescents ( N = 312 ) recruited through media and various community venues from March 1 , 1999 , through December 31 , 2002 , who were aged 14 to 17 years , smoked 6 or more cigarettes per day , had an exhaled carbon monoxide level of 10 ppm or greater , had at least 2 previous quit attempts , and had no other current major psychiatric diagnosis . INTERVENTION Sustained-release bupropion hydrochloride , 150 mg/d ( n = 105 ) or 300 mg/d ( n = 104 ) , or placebo ( n = 103 ) for 6 weeks , plus weekly brief individual counseling . Subjects were followed up at 12 weeks ( by telephone call ) and 26 weeks . MAIN OUTCOME MEASURE Confirmed 7-day point prevalence abstinence at 6 weeks and 30-day prolonged abstinence ( carbon monoxide level < 10 ppm at each visit ; urinary cotinine level < or = 50 microg/L at weeks 2 and 6 ) . RESULTS Cotinine-confirmed 7-day point prevalence abstinence rates at 6 weeks were as follows : placebo , 5.6 % ; 150 mg , 10.7 % ; and 300 mg , 14.5 % ( P = .03 , 300 mg vs placebo ) . At 26 weeks , confirmed point prevalence abstinence rates were as follows : placebo , 10.3 % ; 150 mg , 3.1 % ; and 300 mg , 13.9 % ( P = .049 ) . During treatment , confirmed point prevalence rates were significantly higher for 300 mg than placebo at every week except week 4 . CONCLUSIONS Sustained-release bupropion hydrochloride , 300 mg/d , plus brief counseling demonstrated short-term efficacy for adolescent smoking cessation . Abstinence rates were lower than those reported for adults , with rapid relapse after medication discontinuation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00344695 PURPOSE This article describes baseline data collection and the intervention design of Partnership for Health , a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study . The purpose of this article is to evaluate demographic , psychosocial , and cancer-related factors that are associated with smoking behavior and mediators of smoking cessation . PATIENTS AND METHODS This study includes 796 smokers from the Childhood Cancer Survivors Study data base who were diagnosed with cancer before the age of 21 , had survived at least 5 years , and were at least 18 years of age at the time of the baseline survey . Correlates of smoking behaviors included smoking rate , number of recent quit attempts , and nicotine dependence ; two key mediators of smoking cessation , readiness to quit smoking and self-efficacy , were also assessed . RESULTS Participants smoked , on average , 14 cigarettes/day ; 53.2 % were nicotine dependent , and 58 % had made at least one quit attempt in the past year . Smoking behaviors were primarily associated with demographic variables ; mediators of cessation were primarily associated with age at cancer diagnosis and perceived vulnerability to smoking-related illnesses . Severity of psychologic symptoms was associated with increased smoking rate , high nicotine dependence , and low self-efficacy . Support for quitting was related to smoking rate , number of quit attempts , readiness to quit smoking , and self-efficacy . CONCLUSION These findings indicate that many cancer survivors who smoke are receptive to smoking cessation interventions . Factors related to mediators of smoking cessation might be particularly good targets for intervention All tenth grade rs in four senior high schools ( N = 1447 ) from two school districts participated in a cardiovascular disease risk-reduction trial . Within each district , one school was assigned at r and om to receive a special 20-session risk-reduction intervention and one school served as a control . At a two-month follow-up , risk factor knowledge scores were significantly greater for students in the treatment group . Compared with controls , a higher proportion of those in the treatment group who were not exercising regularly at baseline reported regular exercise at follow-up . Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up , while only 5.6 % of baseline experimental smokers in the treatment group graduated to regular smoking compared with 10.3 % in the control group . Students in the treatment group were more likely to report that they would choose " heart-healthy " snack items . Beneficial treatment effects were observed for resting heart rate , body mass index , triceps skin fold thickness , and subscapular skin fold thickness . The results suggest that it is feasible to provide cardiovascular disease risk-reduction training to a large segment of the population through school-based primary prevention approaches BACKGROUND The aim of the present study was to evaluate the efficacy of a school nurse-delivered smoking cessation intervention to improve abstinence rates among adolescents interested in quitting . METHODS Seventy-one high schools in Massachusetts were r and omized to either a four-session one-on-one school nurse-delivered smoking cessation intervention ( 37 schools , n = 571 ) or usual smoking cessation care control condition ( 34 schools , n = 577 ) . Adolescents in grade s 9 - 12 who smoked in the past 30 days completed surveys at baseline , 6 weeks and 3 months . The study was conducted during the 2002 - 2003 school year . RESULTS Thirty-day self-reported abstinence rates were significantly greater in students in the intervention compared to control condition at 6 weeks ( 18 % vs. 2 % , respectively ) and 3 months ( 24 % vs. 5 % , respectively ) . After adjusting for school and potential confounders , students in the intervention schools had odds of quitting 8 times greater than students in the control schools at 6 weeks ( OR = 8.4 ; 95 % CI 3.7 , 20.6 ) and 6 times greater at 3 months ( OR = 6.4 ; 95 % CI 3.4 , 11.4 ) . School nurses delivered intervention with a high degree of fidelity . CONCLUSIONS A four-session smoking cessation intervention can feasibly be delivered by school nurses and increase self-reported short-term abstinence rates among students interested in quitting smoking Programs to reduce adolescent cigarette or alcohol use by users in general population s have only recently been evaluated . Moreover , in spite of the substantial influence families have on their children , few family-directed programs design ed to reduce the prevalence of adolescent smoking and drinking have been rigorously evaluated . This paper reports the findings of research design ed to determine whether a family program reduced use of cigarettes or alcohol by users . The program consisted of a series of booklets mailed to families and follow-up telephone calls by health educators . A r and omized experimental design involved families with children ages 12–14 throughout the United States . Data were collected by telephone at baseline and 3 and 12 months after the program was completed . No statistically significant program effects were observed for cessation or decrease in smoking and drinking by users The lack of promising smoking cessation interventions targeting young adults is a recognized public health problem . This study was design ed to determine the feasibility of a young-adult-oriented program , the X-Pack Program , when administered to college student smokers , and to estimate its effect on smoking cessation . Participants ( N = 83 ) were r and omized after enrollment to receive either a moderately intensive , E-mail-based , young-adult intervention ( the X-Pack group ) or a less-intensive program aim ed at a general adult audience ( the Clearing the Air group ) . Participants were assessed at baseline and at 3 and 6 months after enrollment . Participants in the X-Pack group rated their treatment more favorably overall , were more engaged in program activities , and quit for more consecutive days at the 3- and 6-month follow-ups , compared with the Clearing the Air group . Differences in quit rates favored the X-Pack group at the two follow-ups , but the differences were not significant . These findings offer some support for the X-Pack Program when administered to college smokers Summary Background Schools in many countries undertake programmes for smoking prevention , but systematic review s have shown mixed evidence of their effectiveness . Most peer-led approaches have been classroom-based , and rigorous assessment s are scarce . We assessed the effectiveness of a peer-led intervention that aim ed to prevent smoking uptake in secondary schools . Methods We undertook a cluster r and omised controlled trial of 10 730 students aged 12–13 years in 59 schools in Engl and and Wales . 29 schools ( 5372 students ) were r and omly assigned by stratified block r and omisation to the control group to continue their usual smoking education and 30 ( 5358 students ) to the intervention group . The intervention ( ASSIST [ A Stop Smoking In Schools Trial ] programme ) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke . Follow-up was immediately after the intervention and at 1 and 2 years . Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake , which was identified at baseline as occasional , experimental , or ex-smokers . Analysis was by intention to treat . This study is registered , number IS RCT N55572965 . Findings The odds ratio of being a smoker in intervention compared with control schools was 0·75 ( 95 % CI 0·55–1·01 ) immediately after the intervention ( n=9349 students ) , 0·77 ( 0·59–0·99 ) at 1-year follow-up ( n=9147 ) , and 0·85 ( 0·72–1·01 ) at 2-year follow-up ( n=8756 ) . The corresponding odds ratios for the high-risk group were 0·79 ( 0·55–1·13 [ n=3561 ] ) , 0·75 ( 0·56–0·99 [ n=3483 ] ) , and 0·85 ( 0·70–1·02 [ n=3294 ] ) , respectively . In a three-tier multilevel model with data from all three follow-ups , the odds of being a smoker in intervention compared with control schools was 0·78 ( 0·64–0·96 ) . Interpretation The results suggest that , if implemented on a population basis , the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance . Funding MRC ( UK ) Study objective : The aim of this study was to determine the effect of a multilevel school based intervention on adolescents ’ emotional wellbeing and health risk behaviours . Design : School based cluster r and omised controlled trial . Students were surveyed using laptop computers , twice in the first year of intervention and annually thereafter for a further two years . Setting : Secondary schools . Participants : 2678 year 8 students ( 74 % ) participated in the first wave of data collection . Attrition across the waves was less than 3 % , 8 % , and 10 % respectively with no differential response rate between intervention and control groups at the subsequent waves ( 98 % v 96 % ; 92 % v 92 % , and 90 % v 89 % respectively ) . Main results : A comparatively consistent 3 % to 5 % risk difference was found between intervention and control students for any drinking , any and regular smoking , and friends ’ alcohol and tobacco use across the three waves of follow up . The largest effect was a reduction in the reporting of regular smoking by those in the intervention group ( OR 0.57 , 0.62 , and 0.72 at waves 2 , 3 , and 4 respectively ) . There was no significant effect of the intervention on depressive symptoms , and social and school relationships . Conclusions : While further research is required to determine fully the processes of change , this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours In autumn 1995 The Norwegian Cancer Society in cooperation with The Research Center for Health Promotion , University of Bergen started a study of school-based interventions aim ing at preventing smoking among pupils in Norwegian secondary schools . The study comprised a nationwide sample of 4441 students at 99 schools ( 195 classes ) . This panel of students is followed through annual data collection s till they graduate in spring 1997 . Written consensus from students and parents was obtained from 95 % . Schools were systematic ally allocated to one of four groups : Group A , control ; Group B , intervention , containing classroom program , involvement of parents and teacher courses ; Group C , like B , but without teacher courses ; Group D , like B , but without parental involvement . Baseline data were collected by question naires administered in class in November 1994 and the first follow-up survey was carried out in May 1995 . At follow-up the proportion of smokers had increased by 8.3 percentage points in Group A ( control ) and by 1.9 percentage points in Group B ( most extensive intervention ) . As expected , the recruitment of smokers was higher in Groups C and D than in the ideal intervention , but lower than in the control group . Effects of the most extensive program among subgroups of students were examined by comparing Groups A and B. Students are categorized as high risk or low risk based on scores on scales measuring sensation seeking , physical maturity , antisocial behavior and parental smoking . The effect of the program on recruitment of smokers seems to have been at least as strong or even stronger among ' high-risk ' students than among other students This paper provides a review of the last two and a half decades of research in adolescent and young-adult tobacco use cessation . A total of 66 tobacco cessation intervention studies – targeted or population – are review ed . In addition , an exhaustive review is completed of adolescent self-initiated tobacco use cessation , involving 17 prospect i ve survey studies .Average reach and retention across the intervention studies was 61 % and 78 % , respectively , and was higher when whole natural units were treated ( e.g. , classrooms ) , than when units created specifically for the program were treated ( e.g. , school-based clinics ) . The mean quit-rate at a three to 12-month average follow-up among the program conditions was 12 % , compared to approximately 7 % across control groups . A comparison of intervention theories revealed that motivation enhancement ( 19 % ) and contingency-based reinforcement ( 16 % ) programs showed higher quit-rates than the overall intervention cessation mean . Regarding modalities ( channels ) of change , classroom-based programs showed the highest quit rates ( 17 % ) . Computer-based ( expert system ) programs also showed promise ( 13 % quit-rate ) , as did school-based clinics (12%).There was a fair amount of missing data and wide variation on how data points were measured in the programs ' evaluations . Also , there were relatively few direct comparisons of program and control groups . Thus , it would be difficult to conduct a formal meta- analysis on the cessation programs . Still , these data suggest that use of adolescent tobacco use cessation interventions double quit rates on the average . In the 17 self-initiated quitting survey studies , key predictors of quitting were living in a social milieu that is composed of fewer smokers , less pharmacological or psychological dependence on smoking , anti-tobacco beliefs ( e.g. , that society should step in to place controls on smoking ) and feeling relatively hopeful about life . Key variables relevant to the quitting process may include structuring the context of programming for youth , motivating quit attempts and reducing ambivalence about quitting , and making programming enjoyable as possible . There also is a need to help youth to sustain a quit-attempt . In this regard , one could provide ongoing support during the acute withdrawal period and teach youth social/life skills . Since there is little information currently available on use of nicotine replacement in young people , continued research in this arena might also be a useful focus for future work Background To date , no school-based intervention has been proven to be effective in preventing adolescent smoking , despite continuing concern about smoking levels amongst young people in the United Kingdom . Although formal teacher-led smoking prevention interventions are considered unlikely to be effective , peer-led approaches to reducing smoking have been proposed as potentially valuable . Methods / design ASSIST ( A Stop Smoking in Schools Trial ) is a comprehensive , large-scale evaluation to rigorously test whether peer supporters in Year 8 ( age 11–12 ) can be recruited and trained to effect a reduction in smoking uptake among their fellow students . The evaluation is employing a cluster r and omised controlled trial ( RCT ) design with secondary school as the unit of r and omisation , and is being undertaken in 59 schools in South East Wales and the West of Engl and . Embedded within the trial are an economic evaluation of the intervention costs , a process evaluation to provide detailed information on how the intervention was delivered and received , and an analysis of social networks to consider whether such a peer group intervention could work amongst schoolchildren in this age group . Schools were r and omised to either continue with normal smoking education ( n = 29 schools , 5562 students ) , or to do so and additionally receive the ASSIST intervention ( n = 30 schools , 5481 students ) . No schools withdrew once the trial had started , and the intervention was successfully implemented in all 30 schools , with excellent participation rates from the peer supporters . The primary outcome is regular ( weekly ) smoking , vali date d by salivary cotinine , and this outcome has been obtained for 94.4 % , 91.0 % and 95.6 % of eligible students at baseline , immediate post-intervention , and one-year follow-up respectively . Discussion Comprehensive evaluations of complex public health interventions of this scale and nature are rare in the United Kingdom . This paper demonstrates the feasibility of conducting cluster RCTs of complex public health interventions in schools , and how the rigour of such design s can be maximised both by thorough implementation of the protocol and by broadening the scope of questions addressed in the trial by including additional evaluative components To assess whether Health Risk Appraisal ( HRA ) , a computer-scored lifestyle analysis question naire , can result in significant changes in health behavior , a controlled clinical trial with one-year follow-up was conducted among entering freshmen at an urban state university . Three hundred fifty entering freshmen were each assigned to one of four groups : HRA with feedback , HRA without feedback , initial control , and final control . Twenty-two per cent of the nonsmokers in the no-feedback group , as compared with 5 % in the feedback group , acquired the habit of cigarette smoking ( p<0.001 ) . Furthermore , 26 % of the smokers in the feedback group , as compared with 6 % in the no-feedback group , were able to quit smoking ( p<0.05 ) . Among those unable to quit smoking , 59 % in the feedback group , as compared with 19 % in the no-feedback group , were able to reduce their cigarette consumption by more than six cigarettes per day ( p<0.01 ) . Health Risk Appraisal , when accompanied by feedback counseling , was an effective health promotion tool to help prevent nonsmokers from acquiring the habit and to modify cigarette smoking behavior among college freshmen Objective : The SMART Teens Against the Risks of Tobacco Study was design ed to test the feasibility and efficacy of tobacco control intervention methods for employed teens . Methods : A r and omized controlled pilot study tested the efficacy of a behavioral intervention delivered between September , 1999 , and August , 2000 . Baseline and final survey data were collected on 560 teens in four intervention and five control stores . Results : Although smoking prevalence decreased and intention to quit increased more among teens in the intervention stores compared to those in the control stores , the differences were not statistically significant . Conclusions : The worksite holds promise as a possible venue for tobacco prevention and cessation interventions for youth although further research is needed to increase the efficacy of interventions for this setting This study evaluated the efficacy of using a brief motivational intervention to reduce smoking among adolescent patients treated in a hospital outpatient clinic or Emergency Department . Patients aged 14 - 19 years ( N=85 ) were r and omly assigned to receive either one session of motivational interviewing ( MI ) or st and ardized brief advice ( BA ) to quit smoking . The assessment and intervention were conducted in the medical setting proximal to the patient 's medical treatment . Patients were proactively screened and recruited , and were not seeking treatment for smoking . Follow-up assessment s were conducted at 1 , 3 , and 6 months post-intervention . Self-report data indicated that 7-day abstinence rates at 6-month follow-up were significantly higher in the MI group than in the BA group , but this difference was not confirmed biochemically . Self-reported smoking rate ( average cigarettes per day ) was significantly lower at 1 , 3 , and 6 months follow-up than it was at baseline . Cotinine levels indicated reduced smoking for both groups at 6 months , but not at 1 month . At 3-month follow-up , only those in MI showed cotinine levels that were significantly reduced compared to baseline . Findings offer some support for MI for smoking reduction among non-treatment-seeking adolescents , but overall changes in smoking were small A multilevel logistic regression model is presented for the analysis of clustered and repeated binary response data . At the subject level , serial dependence is expected between repeated measures recorded on the same individual . At the cluster level , correlations of observations within the same subgroup are present due to the inherent hierarchical setting . Two r and om components are therefore incorporated explicitly within the linear predictor to account for the simultaneous heterogeneity and autoregressive structure . Application to analyse a set of longitudinal data from an adolescent smoking cessation intervention that motivated this study is illustrated PURPOSE The purpose of this study was to test the effectiveness of a comprehensive smoking cessation program for Korean adolescents . METHOD The study design was quasi-experimental with one pre and three post-tests . The three posttests were done immediately after , three months later , and six months after the completion of the program . A total of 43 high school students who smoked participated in the study with 22 in the experimental group and 21 in the control group . The smoking cessation program consisted of 9 sessions with content on enhancement of self-efficacy , stress management , correction of distorted thoughts , consciousness raising , and assertiveness training . The study variables were urine cotinine levels , self-efficacy , stress , and stages of changed behavior . RESULTS Urine cotinine levels significantly decreased in the experimental group after the program ( F=3.02 , p=.06 ) but significantly increased in the control group ( F=6.32 , p=.004 ) . Self-efficacy and the degree of stress did not change in either group . The stages of smoking cessation behavior tended to change when compared with raw data for the experimental group . For most participants , the stages of change had been precontemplation and contemplation , but changed to action and maintenance stage among the experimental group . CONCLUSION The program was effective in smoking cessation and influencing stages of change but did not change psychosocial factors such as self-efficacy and stress . It is suggested a program should be developed to change psychosocial variables on a long-term basis . It is also desirable to involve peers and families of adolescents who smoke when planning programs to enhance social support This study examined the association between mental health and smoking cessation among rural youth . Participants were 113 male and 145 female adolescents ages 14–19 from rural West Virginia and North Carolina . Participants were enrolled in the American Lung Association 's 10-week Not On Tobacco ( N-O-T ) program or a 15-min single-dose brief intervention . Baseline and postprogram measures were completed on smoking status ( i.e. , quit , reduction ) , nicotine dependence , smoking history , and depression and anxiety . Results showed that more N-O-T participants quit and reduced smoking than did brief intervention participants . Intervention group , baseline smoking rate , and the Group × Gender , Group × Anxiety , and Group × Depression interactions were significant predictors of change in smoking behavior from baseline to postprogram . In conclusion , more N-O-T participants demonstrated favorable changes in smoking than did brief intervention participants . Approximately 1/3 of youth exhibited mental health pathology ; more females than males . Levels of depression and anxiety improved from baseline to postprogram , overall . Although the extent of the impact of mental health on cessation outcomes was inconclusive , findings suggest that rural youth who smoke may be at risk for pathological depression and anxiety . Future cessation programming with rural youth should consider the inclusion of coping and stress management skills and mental health referral protocol s as significant program components Tobacco use is prevalent among youth with alcohol and other drug problems , yet this issue has received limited research and clinical attention . This study reports on a controlled evaluation of a cigarette smoking intervention with 54 adolescents in treatment for substance abuse , ages 13 - 18 ( 22 % female ) . Participants were assessed at 4 time points . A greater proportion of participants in the treatment condition ( n = 26 ) reported cessation attempts and point abstinence than did control participants ( n = 28 ) at all time points . However , significant differences were found only for point abstinence at a 3-month follow-up . These findings provide initial support for the efficacy of a smoking cessation intervention delivered in the context of adolescent substance abuse treatment An examination of the applicability of the theory of planned behavior ( TPB ) to the intention to quit smoking across workplaces was conducted . Subjects were r and omly selected from three workplaces in southern Taiwan . Those from a large public steel-manufacturing company were used for model building , and those from two private auto-parts-manufacturing companies served to cross-vali date the model . Eligible subjects were divided into three study sample s : a learning sample and two test sample s. Three predictors -- priority of quitting , past behavior ( measured as previous quit attempt ) , and habit ( measured as nicotine dependence)--were added to the TPB model . The results of this study show that TPB based on the learning sample fit well in another sample from the same workplace but poorly in other workplaces . When priority of quitting and past behavior were added to the TPB model , prediction to other workplaces significantly improved . Habit had no significant contribution to the intention to quit in the TPB model . Detailed discussion s of the results are provided AIM To test whether a single session of motivational interviewing ( discussing alcohol , tobacco and illicit drug use ) would lead successfully to reduction in use of these drugs or in perceptions of drug-related risk and harm among young people . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either motivational interviewing ( n=105 ) or non-intervention education-as-usual control condition ( n=95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people ( age range 16 - 20 years ) currently using illegal drugs , with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from the literature on motivational interviewing in the form of a 1-hour single-session face-to-face interview structured by a series of topics . MEASUREMENTS Changes in self-reported cigarette , alcohol , cannabis and other drug use and in a range of drug-specific perceptions and other indicators of risk and harm . Measurement at recruitment and follow-up interview 3 months later . FINDINGS A good follow-up rate ( 89.5 % ; 179 of 200 ) was achieved . In comparison to the control group , those r and omized to motivational interviewing reduced their of use of cigarettes , alcohol and cannabis , mainly through moderation of ongoing drug use rather than cessation . Effect sizes were 0.37 ( 0.15 - 0.6 ) , 0.34 ( 0.09 - 0.59 ) and 0.75 ( 0.45 - 1.0 ) for reductions in the use of cigarettes , alcohol and cannabis , respectively . For both alcohol and cannabis , the effect was greater among heavier users of these drugs and among heavier cigarette smokers . The reduced cannabis use effect was also greater among youth usually considered vulnerable or high-risk according to other criteria . Change was also evident in various indicators of risk and harm , but not as widely as the changes in drug consumption . CONCLUSIONS This study provides the first substantial evidence of non-treatment benefit to be derived among young people involved in illegal drug use in receipt of motivational interviewing . The targeting of multiple drug use in a generic fashion among young people has also been supported This study examined the effects of the nicotine patch on craving and withdrawal symptoms , safety , and compliance among adolescents . The secondary goal was to conduct a preliminary investigation of the effectiveness of the nicotine patch in helping adolescents quit smoking . The study design was a double-blind , placebo-controlled , r and omized trial of the nicotine patch . The intervention also provided intensive cognitive-behavioral therapy and a contingency-management procedure . Participants ( n=100 ) attended 10 treatment visits over 13 weeks . Compared with the placebo patch group , the active nicotine patch group experienced a significantly lower craving score and overall withdrawal symptom score ( p=.011 and p=.025 , respectively ) , as well as a time trend toward lower scores ( p<.001 ) in craving only . Moreover , the nicotine patch appeared safe for adolescents to use . No differences by treatment group were found in experiencing adverse events , except that the participants in the placebo patch group reported more headaches than those in the active nicotine patch group . As another measure of safety , the overall mean salivary cotinine levels were significantly lower at 1 , 6 , 8 , and 10 weeks postquit ( all p<.05 ) compared with baseline levels , although these results were confounded by dropouts . Additionally , a significant number of participants were compliant with using the nicotine patch daily . Finally , point prevalence ( 7-day and 30-day abstinence rates ) and survival analysis of participant abstinence indicated no significant differences between treatment groups . The results of this study suggest that the nicotine patch is a promising medication and a larger clinical trial of the nicotine patch among adolescents is warranted AIMS To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori . METHODS A single-blind r and omised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori . The intervention included regular , personalised text messages providing smoking cessation advice , support , and distraction . Maori text messages related to Maori language , support messages ( in Maori and English ) and information on Maori traditions . Text messaging was free for 1 month . After 6 weeks , the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up . RESULTS Participants included 355 Maori and 1350 non-Maori . Maori in the intervention group were more likely to report quitting ( no smoking in the past week ) at 6 weeks ( 26.1 % ) than those in the control group ( 11.2 % ) RR 2.34 , 95 % CI : 1.44 - 3.79 . There was no significant difference between the RR for Maori and that for non-Maori ( RR : 2.16 , 95%CI : 1.72 - 2.71 ) . CONCLUSIONS A mobile phone-based cessation programme was successful in recruiting young Maori , and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates . This shows clear potential as a new public health initiative BACKGROUND Although many sociodemographic and psychosocial factors have been identified as related to adolescent smoking , few studies have examined the role of nicotine-dependence ( ND ) symptoms . The objective was to study the association between ND symptoms and smoking status among adolescents in the early stages of the smoking onset process . METHODS The McGill University Study on the Natural History of Nicotine Dependence is an ongoing 6-year prospect i ve investigation of the natural history of ND among 1267 grade 7 students in ten Montreal high schools . The baseline response was 55.4 % . Subjects for this cross-sectional analysis of baseline data , collected in 1999 , included 241 past 3-month smokers ( mean age [SD]=13.0+/-0.7 years at baseline ) . ND symptoms were measured in five indicators , including a measure based on the criteria for tobacco dependence in the International Classification of Diseases-10th Revision ( ICD-10 ) , the Hooked on Nicotine Checklist , and three symptom clusters ( withdrawal , self-medication , and ND/cravings symptoms ) . The association between ND symptom indicators and each of sporadic , monthly , weekly , and daily smoking relative to less frequent smoking was investigated in multiple logistic regression analysis . RESULTS Despite low cigarette exposure , 16.6 % ( 95 % confidence interval [ CI ] , 11.9%-21.3 % ) of past 3-month smokers were tobacco dependent . The proportion increased from 0 % , 3.1 % ( 95 % CI , 0.0%-9.2 % ) , and 4.6 % ( 95 % CI , 0.2%-9.0 % ) among triers , sporadic smokers , and monthly smokers , respectively , to 19.4 % ( 95 % CI , 5.5%-33.3 % ) and 65.9 % ( 95 % CI , 51.9%-79.9 % ) among weekly and daily smokers , respectively . ND/cravings consistently distinguished each smoking category from less frequent smokers ; the odds ratios ( 95 % CI ) for ND/cravings symptoms were 1.16 ( 0.99 - 1.35 ) in sporadic smokers ; 1.17 ( 1.06 - 1.29 ) in monthly smokers ; 1.34 ( 1.19 - 1.50 ) in weekly smokers ; and 1.39 ( 1.22 - 1.59 ) in daily smokers . CONCLUSIONS These data challenge current smoking onset models , which suggest that ND develops only after several years of heavy or daily smoking . ND symptoms are associated , at least cross-sectionally , with increased smoking in adolescents . To increase the likelihood of being effective , tobacco-control programs for children and adolescents will need to take early ND symptoms into account Objectives : To describe the feasibility of implementing evaluation methods for a worksite tobacco control intervention for teens . Indicators of feasibility included employment stability , response rates to multiple surveys , and self reported 30 day smoking . Design : Grocery stores that were part of a single chain were r and omised to four intervention stores and five control stores as part of the SMART project , a phase II methods development study design ed to reduce smoking among working adolescents . Subjects : Data on smoking in the last 30 days and employment patterns were collected from working teens aged 15–18 years at seven data points over the 12 month intervention period using cross sectional surveys . Results : Data on employment stability indicate that employee turnover rates averaged 21 % over the seven administrations . Response rates for the seven surveys ranged from 43–77 % and were slightly greater in the control stores than the interventions stores ( 71 % v 59 % , p = 0.06 ) . Mean current smoking at the individual store level ranged from 9–32 % and there was a negative correlation between smoking prevalence and response rate by survey and by store ( –0.029 , p = 0.03 ) . Among smokers who completed at least two surveys , there were no significant differences between intervention and control store on changes in the frequency of smoking . Conclusions : Evaluating a tobacco control intervention in the grocery store setting requires multiple survey assessment s to monitor changes in smoking among adolescents . Strategies are needed to maintain high response rates and increase the number of multiple responses from eligible teens To investigate the effectiveness and tolerability of a transdermal nicotine system ( TNS ) as an aid towards easing smoking cessation , two double-blind placebo-controlled r and omized field studies were performed . The TNS was available in sizes of 10 , 20 and 30 cm2 , delivering 7 , 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors ( Practitioner Study ) . This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group . The second trial was performed in 112 young people , 56 in each treatment group , at the Universities of Basle and Zurich ( University Study ) . The placebo and the nicotine groups were comparable in both studies . Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system . When abstinence , as verified by CO measurements , was achieved , the next smaller system was applied . In the Practitioner Study , the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks ' treatment period took place every 3 weeks . Abstainers in both studies will be followed up until 12 months after treatment was begun . After 1 , 2 and 3 months of treatment 41 % , 36 % and 36 % of the participants in the nicotine group of the Practitioner Study were abstinent . The corresponding figures in the placebo group were 19.4 % , 20.4 % and 22.5 % . The differences were statistically significant for all three months ( p = 0.001 ; p = 0.018 and p = 0.043 ) . Body weight did not increase in the TNS group , but did in the placebo group ( + 4.4 kg ) . The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution . Abstinence rates in the University Study were initially higher with 51.8 % in the nicotine group and 28.6 % in the placebo group after 3 weeks of treatment , but then declined to 42.9 % after 6 weeks and 39.3 % after 9 weeks in the nicotine group and to 25 % and 19.6 % , respectively , in the placebo group . The differences between the groups were statistically significant on all 3 occasions , with p = 0.012 , p = 0.046 and p = 0.023 . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Well-documented challenges have hampered both intervention development and research in teen smoking cessation . Addressing these challenges , the Hutchinson Study of High School Smoking ( HS Study ) , the largest group-r and omized trial in adolescent smoking cessation to date , incorporates several design innovations to investigate the effect of a counselor-initiated , individually tailored telephone counseling smoking cessation intervention for older adolescents . This paper presents and discusses these innovative design features , and baseline findings on the result ing study population . METHOD The trial used a population -based survey to proactively identify and recruit all high school juniors who had smoked in the past month - potentially exp and ing intervention reach to all smokers , even those who smoked less than daily and those not motivated to quit . For ethical and intervention reasons , some nonsmokers were enrolled in the intervention , also . Other important design features included the r and om allocation of schools into experimental conditions ( intervention vs. no-intervention control ) and a multi-wave design . RESULTS AND CONCLUSION The design innovations address problems and challenges identified in adolescent smoking cessation literature . The heterogeneous baseline characteristics of the study population , well-balanced between the two arms , have three significant implication s : They ( 1 ) demonstrate the effectiveness of the trial 's design features , ( 2 ) highlight several intervention-related issues , and ( 3 ) provide assurance that the trial 's evaluation of intervention effectiveness will be unbiased Adolescent smokers ( N = 211 ) were r and omized to 1 of 2 groups : ( a ) nicotine patch plus bupropion SR ( sustained release ; 150 mg per day ) or ( b ) nicotine patch plus placebo . Group skills training sessions were conducted each week by research staff . Abstinence rates at Weeks 10 and 26 were as follows : ( a ) patch plus bupropion , 23 % and 8 % , ( b ) patch plus placebo , 28 % and 7 % . Despite the lack of a treatment effect , a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time . Similarly , an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking . These findings are encouraging and suggest new avenues for research . For example , treatments of the kind examined in this report , augmented by extended maintenance therapies , may yield higher long-term success rates OBJECTIVE To evaluate the efficacy of a short-term tobacco-focused intervention for high school students referred by school administrators because of tobacco use . METHOD A sample of 56 adolescents ( 66 % male , mean age 15 years ) was recruited through referrals from three state high schools . Participants were r and omly assigned to a one-hour motivational interview ( MI ) session or to st and ard care ( advice/education ) . The two groups were followed up at one , three , and six-month intervals . RESULTS The MI intervention result ed in significant short-term reductions in quantity and frequency of smoking relative to st and ard care , however , effects were not maintained at 3- and 6-month follow-up . Improvements in refusal self-efficacy were significant relative to st and ard care . CONCLUSION For adolescents who are established smokers and at high risk of other problems , motivational interviewing was associated with modest short-term gains relative to st and ard care This investigation examined the feasibility and magnitude of the effect of a stress management intervention involving expressive writing as an adjunct to brief office smoking cessation intervention for young adults . Participants aged 18 - 21 years were r and omized to brief office intervention ( N=30 ) or expressive writing plus brief office intervention ( N=30 ) . Biochemically confirmed 30-day point-prevalence tobacco abstinence , smoking reduction , perceived stress , negative affect , and treatment compliance were assessed at 4 , 12 , and 24 weeks post r and omization . The expressive writing adjunct was not found to be effective . The 30-day smoking abstinence rates were 0 % versus 0 % ( p=1.000 ) at week 4 , 20 % versus 3 % ( p=0.103 ) at week 12 , and 20 % versus 10 % ( p=0.472 ) at week 24 for the brief office intervention only versus expressive writing plus brief office intervention groups , respectively . Participants stated they benefited most from the support and structure associated with the brief office intervention . Enthusiasm was lacking for the expressive writing treatment adjunct BACKGROUND The transtheoretical model ( TTM ) and computer technology are promising technologies for changing health behavior , but there is little evidence of their effectiveness among adolescents . METHOD Four thous and two hundred twenty-seven Year 9 ( ages 13 - 14 ) pupils in 26 schools were r and omly allocated to control and 4,125 in 26 schools were allocated to TTM intervention . TTM pupils received three whole class lessons and three sessions with an interactive computer program . Control pupils received no special intervention . Positive change in stage and smoking status was assessed from a question naire completed at baseline , 1 year , and 2 years . R and om effects logistic regression was used to compare the change in stage and smoking status between the arms . RESULTS Eighty-nine percent of the TTM group and 89.3 % of the control group were present at 1-year and 86.0 and 83.1 % , respectively , were present at 2-year follow-up . The adjusted odds ratio ( 95 % confidence interval ) for positive stage movement in the TTM relative to control was 1.13 ( 0.91 - 1.41 ) at 1 year and 1.25 ( 0.95 - 1.64 ) at 2 years and for regular smoking was 1.14 ( 0.93 - 1.39 ) at 1 year and 1.06 ( 0.86 - 1.31 ) at 2 years . Subgroup analysis by initial smoking status revealed no benefit for prevention or cessation . CONCLUSIONS The intervention was ineffective A double blind , r and omized , placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers . Three hundred and thirty adolescent smokers at the Smoking Cessation Clinic of Child Guidance Clinic , Institute of Health , Singapore , were r and omly assigned in equal numbers to laser acupuncture treatment and sham acupuncture ( control ) groups . The proportions of patients with complete smoking cessation after completing treatment for four weeks were 21.9 % in the treatment group and 21.4 % in the control group . At three months post-treatment , the rates for complete cessation were 24.8 % and 26.2 % , respectively . Thus , there was no significant difference in the rates of smoking cessation in the treatment and control groups This article reports on the feasibility of using a contingency management intervention with adolescent smokers that has proven efficacious in adult substance abuse treatment . The study used 8 adolescent participants in an A ( 1 week)-B ( 1 week)-A ( 1 week ) reversal design . During the 2 baseline phases , no contingencies were placed on cigarette smoking , and adolescents received money noncontingently . During the experimental intervention week , adolescents received payment contingent on not smoking . The magnitude of reimbursement available during the baseline and intervention phases was equated . Results indicated that the contingency management intervention was effective in reducing smoking , both in terms of increasing the total number of abstinences and consecutive abstinences . In addition , changes in adolescents ' affective states during smoking cessation were found . Anxiety , depression , anger , and fatigue were reported , and these negative states ceased once smoking resumed Objective . To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care . Methods . Both smoking and nonsmoking teens , 14 to 17 years of age , who were being seen for routine visits were eligible for this 2-arm controlled trial . Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group- practice health maintenance organization . Of 3747 teens invited at ≥1 visits , 2526 ( 67 % ) consented and were r and omized to tobacco intervention or brief dietary advice . The tobacco intervention was individually tailored on the basis of smoking status and stage of change . It included a 30-second clinician advice message , a 10-minute interactive computer program , a 5-minute motivational interview , and up to two 10-minute telephone or in-person booster sessions . The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables . Follow-up smoking status was assessed after 1 and 2 years . Results . Abstinence rates after 2 years were significantly higher for the tobacco intervention arm , relative to the control group , in the combined sample of baseline smokers and nonsmokers ( odds ratio [ OR ] : 1.23 ; 95 % confidence interval [ CI ] : 1.03–1.47 ) . Treatment effects were particularly strong among baseline self-described smokers ( OR : 2.42 ; 95 % CI : 1.40–4.16 ) but were not significant for baseline nonsmokers ( OR : 1.25 ; 95 % CI : 0.97–1.61 ) or for those who had “ experimented ” in the past month at baseline ( OR : 0.95 ; 95 % CI : 0.45–1.98 ) . Conclusions . Brief , computer-assisted , tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset OBJECTIVES To test whether high school students ' participation in advocacy activities related to the advertising , availability , and use of tobacco in their communities would prevent or reduce their own tobacco use . DESIGN Ten continuation high schools in northern California , r and omly assigned to a semester-long program in which students either carried out advocacy activities to counter environmental-level smoking influences in their communities ( treatment ) or learned about drug and alcohol abuse prevention ( control ) . PARTICIPANTS Eleventh and 12th grade high school students ; 5 ( advocacy ) treatment and 5 control schools over 4 semesters from 2000 through 2002 . MAIN OUTCOME MEASURES Self-reported smoking defined as nonsmokers ( those who had never smoked tobacco or those who were former smokers ) , light smokers ( those who smoked < 1 pack per week ) , or regular smokers ( those who smoked > or=1 pack per week ) , and confirmed by carbon monoxide level readings . The following 3 constructs related to social cognitive theory- perceived incentive value , perceived self-efficacy , and outcome expectancies-were assessed . RESULTS There was a significant net change from baseline to the end of the semester ( after the intervention ) between treatment and control schools for students who were regular smokers , but not for students who were nonsmokers or light smokers . Regular smoking decreased 3.8 % in treatment schools and increased 1.5 % in control schools ( P<.001 ) . Regular smoking continued to decrease at 6 months after the intervention in treatment schools , with a total change in prevalence from 25.1 % to 20.3 % . Involvement in community-advocacy activities and the 3 social constructs-perceived incentive value , perceived self-efficacy , and outcome expectancies-also showed significant net changes between treatment and control schools ( all P values < .01 ) . CONCLUSION Student engagement in community-advocacy activities that addressed environmental influences of cigarette smoking result ed in significant decreases in regular smoking The purpose of this study is twofold : 1 ) to evaluate the effects of a smoking cessation clinic ( Project EX ) on changing motivation to quit smoking , and 2 ) to assess differences in quit rates based on these changes in motivation . Student smokers in 18 continuation high schools in the Los Angeles county area were invited to participate in a tobacco cessation clinic design ed to enhance motivation to quit tobacco use . The 18 schools were r and omly assigned to one of three conditions . Compared to students in the control group , students who participated in the program conditions were more likely to express higher motivation to quit tobacco use . Higher motivation was also significantly related to higher quit rates . Motivation to quit as defined by constituents of the energy/direction model of motivation appears to be a plausible mediator of cessation program effects Abstract Objectives : To examine whether a year long programme based on the transtheoretical model of behaviour change , incorporating three sessions using an expert system computer program and three class lessons , could reduce the prevalence of teenage smoking . Design : Cluster r and omised trial comparing the intervention to a control group exposed only to health education as part of the English national curriculum . Setting : 52 schools in the West Midl and s region . Participants : 8352 students in year 9 ( age 13 - 14 years ) at those schools . Main outcome measures : Prevalence of teenage smoking 12 months after the start of the intervention . Results : Of the 8352 students recruited , 7444 ( 89.1 % ) were followed up at 12 months . The intention to treat odds ratio for smoking in the intervention group relative to control was 1.08 ( 95 % confidence interval 0.89 to 1.33 ) . Sensitivity analysis for loss to follow up and adjustment for potential confounders did not alter these findings . Conclusions : The smoking prevention and cessation intervention based on the transtheoretical model , as delivered in this trial , is ineffective in schoolchildren aged 13 - 14 . Key messages The transtheoretical model proposes that individuals move through a series of stages in behaviour change A computer programme gave 13 and 14 year old school students tailored information about what stage they were in and what to do to move to the next stage Students given this information were no more likely to move stage , refrain from smoking , or stop smoking than those exposed to ordinary classroom health education There is no evidence that the computerised expert system based on the transtheoretical model is effective in smoking prevention and STUDY OBJECTIVE To assess the efficacy and safety of long-term bupropion therapy for nicotine dependence in adolescents . DESIGN Prospect i ve , double-blind , placebo-controlled trial . SETTING Outpatient clinic in Innsbruck , Austria . SUBJECTS Twenty-two adolescents , aged 16 - 19 years , with nicotine dependence . INTERVENTION Participants were r and omly assigned to receive bupropion 150 mg/day or placebo for 90 days . MEASUREMENTS AND MAIN RESULTS Patients were classified as abstinent or relapsed on day 0 ( when study drug was started ) and again on days 30 and 90 , according to their self-reports . Treatment failure was defined as relapse or nonattendance . Time to first treatment failure was the primary outcome measure . Mean cumulative abstinence duration was significantly greater in the bupropion group than in the placebo group ( 78.4 + /- 39.6 vs 30.2 + /- 19.2 days . p=0.0042 ) . CONCLUSION Bupropion seems to be an effective and well-tolerated pharmacologic adjunct to psychosocial and behavioral treatment programs for some adolescent nicotine-dependent patients . However , experienced clinicians should continuously monitor patients for adverse effects To assess efficacy and tolerance of a transdermal nicotine system ( TNS ) as adjuvant to tobacco withdrawal , 112 young , nicotine-dependent cigarette smokers were treated for nine weeks with TNS ( n = 56 ) or placebo ( n = 56 ) . Initial doses of nicotine ( 21 or 14 mg/24 h ) were based on previous smoking habits and stepwise reduced to 7 mg/24 h if abstinence was achieved during medication . After treatment , 39.3 % of the TNS users were abstinent versus 19.6 % on placebo ( p less than 0.05 ) . The craving for cigarettes diminished steadily , but not more significantly on TNS medication . Tenseness , difficulty in concentration and feelings of hunger were consistently and in part significantly lessened in the TNS group . The other withdrawal symptoms were not influenced by TNS treatment . Nine-month follow-up cotinine-verified abstinence rates were 12.5 % in the TNS and 3.6 % in the placebo group ( n. s. ) . Transient mild or moderate erythema at the application site appeared in 20 % of the TNS and 6.3 % of the placebo group , and 7.1 % of the TNS users dropped out because of severe localized erythema . Other mild , transient , systemic side effects reported by 33.9 % of the TNS and 26.8 % of the placebo users ( n. s. ) did not lead to drop-outs Objective : To examine the feasibility , acceptability , and effectiveness of a school based smoking cessation programme among students caught smoking at school . Design : A r and omised controlled trial comparing cessation rates among students in a behavioural cessation programme and those receiving self help material s only . Setting : Eighteen schools in the Memphis , Tennessee area . Subjects : Two hundred and sixty one adolescent cigarette smokers ( 166 male , 95 female ) averaging 15.8 years of age . Intervention : Students assigned to the intervention received a four session behavioural treatment programme administered individually by a health educator . In addition , these students received stage matched intervention in brief phone calls monthly until the one year follow up . Main outcome measure : Self reported and biochemically verified smoking cessation at post-test and 12 month follow up . Results : Recruiting students who were caught smoking at school proved to be highly successful . Participants rated the programme favourably , and retention rates were high . Although treated participants improved more in tobacco related knowledge relative to controls ( p = 0.002 ) , there were no group differences in changes in attitudes toward smoking . In addition , treated and control participants demonstrated no significant differences in cessation rates both at post-test and follow up . Comparisons between self reported cessation rates and those obtained under bogus pipeline conditions or with biochemical verification suggested significant falsification of cessation among participants . Conclusions : Our results failed to demonstrate any significant effect of the cessation programme on smoking rates for treated adolescents compared with controls . Our findings also highlight the importance of utilising strong methodology in research on adolescent smoking cessation , including control groups and biochemical verification of smoking status Although group-based programs remain the most common treatment approach for adolescent smoking cessation , success rates for these programs have been relatively modest , and their reach may be limited . Web-based adjuncts may be one way to boost the efficacy and reach of group-based approaches . The purpose of this study was to evaluate the effectiveness of enhancing the American Lung Association 's Not on Tobacco program ( NOT ) with a Web-based adjunct ( NOT Plus ) . Twenty-nine high schools were r and omly assigned to either the NOT program alone or to the NOT Plus condition , which included access to a specially design ed Web site for teens , along with proactive phone calls from the group facilitator to the participant . Self-reported smoking behavior was obtained at end-of-program and at a 3-month follow-up . Using hierarchical linear modeling , accounting for the clustering of students in schools , and controlling for student gender , grade , race , and baseline smoking rate , there was a marginally significant ( p=.06 ) condition effect at end-of-treatment and a significant effect at 3-month follow-up ( p<.05 ) favoring the NOT Plus condition . Approximately 57 % of adolescents reported visiting the Web site , and among the NOT Plus condition , use of the Web site was associated with cessation significantly at end-of-program ( p<.05 ) , but not at 3 months . Adolescents in urban schools were more likely to access the Web site than those in rural schools . Participants who visited the Web site rated it positively on several dimensions . Reasons for not using the Web site will be discussed , as well as its value as an adjunct This study tested the feasibility and efficacy of a brief smoking intervention for adolescents in a hospital setting . Forty adolescent patients were r and omized to receive either brief advice or a motivational interview , a nonconfrontational therapeutic intervention . Feasibility of brief smoking interventions with teen patients was supported by high rates of recruitment , retention , and quit attempts , and long periods of continuous abstinence . Although between-groups differences on smoking measures were not significant at 3-month follow-up , an effect size of h = .28 was noted . The sample showed significant decreases in smoking dependence and number of days smoked . Baseline stage of change , smoking rate , and depression were significant prospect i ve predictors of smoking outcome . Implication s for smoking intervention research with adolescents are discussed BACKGROUND This paper describes one outcome of a r and omized controlled trial of community action for cancer prevention , Cancer Action in Rural Towns . The aims are to [ 1 ] explore the effectiveness of community action in decreasing adolescent smoking in rural Australian towns ; and [ 2 ] describe the relationship between adolescent smoking rates and demographic variables . METHODS In 1992 , 20 rural Australian towns were selected . Community action involved formation of community committees and utilization of access-point networks to initiate and maintain intervention strategies . Cross-sectional surveys of smoking behaviors for all Year 9 and Year 10 students ( 13 - 16 years ) in each town were conducted pre- and posttest . The main outcome measure was self-reported smoking in the past 4 weeks . SUDAAN software was used to look at differences between treatment . RESULTS The results showed strong secular trends toward increased adolescent smoking , regardless of treatment group , particularly for females . There was no significant intervention effect . CONCLUSIONS Increasing adolescent smoking rates found in this and other studies highlight that the definitive strategy to stem the adolescent smoking epidemic has not been found . Hope may remain for recent legislative strategies , but rigorous evaluation is essential , and compliance with legislation should be carefully monitored OBJECTIVE Research ers continue to try to develop effective teen tobacco use prevention and cessation programs . Three previous school clinic-based studies established the efficacy of Project EX for teen smoking cessation . This fourth study adapts Project EX to the classroom context . This paper reports the findings based on pretest and posttest surveys conducted immediately prior and post-intervention . METHODS An eight-session classroom-based curriculum was developed and tested with a r and omized controlled trial that involved a total of 1097 students in six program and six control continuation high schools . Program-specific knowledge and smoking measures were assessed at both the pretest and posttest surveys , and were used to evaluate the program 's effect on the immediate outcomes . The immediate outcomes effects were analyzed with multi-level r and om coefficients models . RESULTS Program students provided favorable process ratings of the overall program and each session . Compared with the students in the control condition , students in the program condition showed a greater change in correct knowledge responses from pretest to posttest ( beta=+5.5 % , p=0.0003 ) . Students in the program condition also experienced a greater reduction in weekly smoking ( beta=-6.9 % , p=0.038 ) , and intention for smoking in the next 12 months ( beta=-0.21 in 5-level scale , p=0.023 ) . CONCLUSIONS EX-4 immediate outcome results revealed favorable student responses to the program , increases in knowledge , and decreases in smoking relative to a st and ard care control condition OBJECTIVE This study evaluated the efficacy of a version of Project EX that was adapted for implementation in the classroom context ( Project EX-4 ) . This paper reports the program outcomes based on pretest , six-month , and one-year follow-up surveys . METHODS An 8 session classroom-based curriculum was tested with a clustered r and omized controlled trial that involved a total of 1097 students in 6 program and 6 control alternative high schools . Weekly and monthly smoking was assessed at the three time points . Outcome effects were analyzed with multi-level r and om coefficients models . RESULTS Students in the program condition experienced a greater reduction in weekly smoking and monthly smoking , at 6- and -12-month follow-ups . The net change varied between -5.1 % and -7.6 % , comparing the program condition to the control condition . CONCLUSIONS The implementation of Project EX in a classroom setting produced decreases in smoking among students in the program , relative to those in the st and ard care control condition . It is likely that a classroom-based smoking prevention/cessation program can lead to lower overall smoking prevalence than a cessation program that is implemented in a school-based smoking cessation clinic format OBJECTIVE Evaluation of novel treatment delivery methods , such as the Internet are notably absent from the adolescent smoking treatment literature . METHODS Adolescent smokers ages 11 - 18 years were r and omized to a clinic-based , brief office intervention ( BOI ; N=69 ) consisting of four individual counseling sessions ; or to Stomp Out Smokes ( SOS ) , an Internet , home-based intervention ( N=70 ) . Adolescents in SOS had access to the SOS site for 24 weeks . RESULTS The 30-day , point-prevalence smoking abstinence rates for BOI and SOS were 12 % versus 6 % at week 24 and 13 % versus 6 % at week 36 , with no significant treatment differences . Among participants who continued to smoke , SOS was associated with a significantly greater reduction in average number of days smoked than BOI ( P=0.006 ) . The BOI was found to be feasible with high session attendance rates . SOS participants accessed the site a mean+/-S.D. of 6.8+/-7.1 days . SOS use dropped to less than one-third of participants by week 3 . CONCLUSION Additional research is needed to tap the potential capabilities of the Internet for adolescent smoking cessation using proactive , personalized , patient-education components . PRACTICE IMPLICATION S Augmenting the SOS type of intervention with more structured , personal and proactive patient-education components delivered in-person or by telephone or electronic mail is recommended Sixty-five college-student smokers were r and omly assigned to a four-week computer-administered , stage-based smoking control program or a four-week computer-administered general health education control condition . At post-test , the percentage of students advancing to a higher stage of readiness to change was slightly higher among those in the stage-based program compared to the control condition . At seven month follow-up , both groups reported abstinence rates of approximately 30 % . Continuous abstinence for 6 months was 19 % for the stage-based group and 14 % for the control group at the final follow-up Project EX is an eight-session teen school-based clinic tobacco use cessation program that involves the inclusion of enjoyable , motivating activities ( " games , " " talk show , " and alternative medicine-type ) to try to enhance quit rates among youth . This clinic program was tested in a three-group experimental design : clinic-only , clinic plus a school-as-community ( SAC ) component , and st and ard care control . Eighteen schools were assigned to the three conditions using a r and omized block design . A total of 335 smokers participated in the study , making this the largest controlled teen smoking cessation field trial conducted to date . Seventeen percent of the smokers enrolled in the clinics had reports of having quit smoking for at least the last 30 days at 3-month follow-up ( 5 months after the program quit day ) , compared to only 8 % of the control condition smokers over than same time period . The Project EX clinic component appears to be an effective means of tobacco use cessation among teens This observational study examined whether adolescents who were not interested in quitting could reduce cigarette smoking and if cigarette reduction led to a corresponding and significant reduction in biomarkers of exposure . The study design was a r and omized , open-label trial of nicotine patch and nicotine gum with an added placebo control . Participants ( n=103 ) attended 4 treatment visits over 4 weeks and follow-up visits at 3- and 6-months . Participants were told to reduce their smoking by 25 % of baseline smoking during the 1st week and by 50 % of baseline smoking during the subsequent 3 weeks . Of consented participants , 91.3 % ( n=94/103 ) completed the study until the end-of-treatment , 85.1 % ( n=80/94 ) completed the 3-month follow-up visit and 71.3 % ( n=67/94 ) completed the 6-month follow-up visit . Participants had a very high prevalence of co-morbidity . With regard to the percentage of participants who achieved a 50 % reduction of baseline smoking , there were no significant differences among treatment groups ( p=.89 ) . At the end-of-treatment , 49.4 % of participants ( n=41 ) had reduced smoking by at least 50 % . Additionally , there was no significant group , visit or interaction effect of a biomarker measure for carcinogen exposure ( p>.05 ) . The results suggest that reduction may be a potential aid to engage adolescents who are unable or unwilling to quit , but should not be an end goal . The effect of treatment methods on outcome measures did not differ significantly |
12,682 | 30,370,232 | MP techniques which have per se the potential to alleviate ischaemia-reperfusion injury : Such as hypothermic MP and NRP , have also reported lower rates of ITBL .
Other biliary complications , such as biliary leak and anastomotic biliary strictures , are reported with similar incidences with all MP techniques .
There is currently less clinical evidence available to support normothermic MP as a mitigator of biliary complications following liver transplantation .
On the other h and , restoration of organ to full metabolism during normothermic MP allows assessment of hepatobiliary function before transplantation , although universally accepted criteria have yet to be vali date d. CONCLUSION MP of the liver has the potential to have a positive impact on post-transplant biliary complications , specifically ITBL , and exp and extended criteria donor livers utilisation | AIM To review the clinical impact of machine perfusion ( MP ) of the liver on biliary complications post-transplantation , particularly ischaemic-type biliary lesions ( ITBL ) . | The European trial investigating normothermic ex vivo liver perfusion ( NEVLP ) as a preservation technique for liver transplantation ( LT ) uses gelofusine , a non-US Food and Drug Administration-approved , bovine-derived , gelatin-based perfusion solution . We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution . Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 ° C with Steen solution , plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage ( CS ) as the preservation technique . Ten liver grafts were perfused for 480 minutes ( 340 - 580 minutes ) . All livers cleared lactate ( final lactate 1.46 mmol/L ; 0.56 - 1.74 mmol/L ) and produced bile ( 61 mL ; 14 - 146 mL ) during perfusion . No technical problems occurred during perfusion , and all NEVLP-preserved grafts functioned well after LT . NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1 - 3 without reaching significance . No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio ( 1.1 [ 1 - 1.56 ] versus 1.1 [ 1 - 1.3 ] ; P = 0.5 ) and bilirubin ( 1.5 ; 1 - 7.7 mg/dL versus 2.78 ; 0.4 - 15 mg/dL ; P = 0.5 ) . No difference was found in the duration of intensive care unit stay ( median , 1 versus 2 days ; range , 0 - 8 versus 0 - 23 days ; P = 0.5 ) and posttransplant hospital stay ( median , 11 versus 13 days ; range , 8 - 17 versus 7 - 89 days ; P = 0.23 ) . Major complications ( Dindo-Clavien ≥ 3b ) occurred in 1 patient in the NEVLP group ( 10 % ) compared with 7 ( 23 % ) patients in the CS group ( P = 0.5 ) . No graft loss or patient death was observed in either group . Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT . Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America . Liver Transplantation 22 1501 - 1508 2016 AASLD Experimental studies have suggested that end‐ischaemic dual hypothermic oxygenated machine perfusion ( DHOPE ) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death ( DCD ) liver grafts . The aim of this prospect i ve case – control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation Dual hypothermic oxygenated machine perfusion ( DHOPE ) of the liver has been advocated as a method to reduce ischemia/reperfusion injury ( IRI ) . This study aim ed to determine whether DHOPE reduces IRI of the bile ducts in donation after circulatory death ( DCD ) liver transplantation . In a recently performed phase 1 trial , 10 DCD livers were preserved with DHOPE after static cold storage ( SCS ; http://www.trialregister.nl NTR4493 ) . Bile duct biopsies were obtained at the end of SCS ( before DHOPE ; baseline ) and after graft reperfusion in the recipient . Histological severity of biliary injury was grade d according to an established semiquantitative grading system . Twenty liver transplantations using DCD livers not preserved with DHOPE served as controls . Baseline characteristics and the degree of bile duct injury at baseline ( end of SCS ) were similar between both groups . In controls , the degree of stroma necrosis ( P = 0.002 ) and injury of the deep peribiliary gl and s ( PBG ; P = 0.02 ) increased after reperfusion compared with baseline . In contrast , in DHOPE‐preserved livers , the degree of bile duct injury did not increase after reperfusion . Moreover , there was less injury of deep PBG ( P = 0.04 ) after reperfusion in the DHOPE group compared with controls . In conclusion , this study suggests that DHOPE reduces IRI of bile ducts after DCD liver transplantation . Liver Transplantation 24 655–664 2018 AASLD Liver transplantation is a highly successful treatment , but is severely limited by the shortage in donor organs . However , many potential donor organs can not be used ; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively . Normothermic machine perfusion maintains the liver in a physiological state , avoids cooling and allows recovery and functional testing . Here we show that , in a r and omized trial with 220 liver transplantations , compared to conventional static cold storage , normothermic preservation is associated with a 50 % lower level of graft injury , measured by hepatocellular enzyme release , despite a 50 % lower rate of organ discard and a 54 % longer mean preservation time . There was no significant difference in bile duct complications , graft survival or survival of the patient . If translated to clinical practice , these results would have a major impact on liver transplant outcomes and waiting list mortality . Normothermic machine perfusion of the liver improved early graft function , demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates , and improved organ utilization and preservation times , although no differences were seen in graft or patient survival Non‐anastomotic biliary stricture ( NAS ) formation is a major complication of liver transplantation . We prospect ively determined the time to development of responsiveness to treatment , and clinical outcomes following NAS formation . In addition , an extensive analysis of the association of recipient , donor , and clinical variables with NAS formation was performed . A total of 749 consecutive patients was studied in a prospect i ve , protocol ‐based fashion . Seventy‐two patients ( 9.6 % ) developed NAS at a mean of 23.6 ± 34.2 weeks post‐transplantation . Non‐anastomotic biliary stricture formation resolved in only 6 % of affected patients . Although patient survival was not affected , retransplantation and graft loss rates were significantly greater in recipients who developed NAS . In contrast to previous reports , a pretransplant diagnosis of HCV was associated with a low frequency of NAS formation . The incidence of NAS was independently associated with pretransplant diagnoses of PSC and autoimmune hepatitis . Hepatic artery thrombosis , and prolonged warm and cold ischemia times were also independent risk factors for NAS formation . We conclude that NAS developed in ∼10 % of primary liver transplant recipients . A pretransplant diagnosis of autoimmune hepatitis has been identified as a novel independent risk factor for NAS formation . Development of NAS significantly attenuates graft but not patient survival The use of livers from donation after circulatory death ( DCD ) is increasing , but concerns exist regarding outcomes following use of grafts from “ marginal ” donors . To compare outcomes in transplants using DCD and donation after brain death ( DBD ) , propensity score matching was performed for 973 patients with chronic liver disease and /or malignancy who underwent primary whole‐liver transplant between 2004 and 2014 at University Hospitals Birmingham NHS Foundation Trust . Primary end points were overall graft and patient survival . Secondary end points included postoperative , biliary and vascular complications . Over 10 years , 234 transplants were carried out using DCD grafts . Of the 187 matched DCDs , 82.9 % were classified as marginal per British Transplantation Society guidelines . Kaplan – Meier analysis of graft and patient survival found no significant differences for either outcome between the paired DCD and DBD patients ( p = 0.162 and p = 0.519 , respectively ) . Aspartate aminotransferase was significantly higher in DCD recipients until 48 h after transplant ( p < 0.001 ) . The incidences of acute kidney injury and ischemic cholangiopathy were greater in DCD recipients ( 32.6 % vs. 15 % [ p < 0.001 ] and 9.1 % vs. 1.1 % [ p < 0.001 ] , respectively ) . With appropriate recipient selection , the use of DCDs , including those deemed marginal , can be safe and can produce outcomes comparable to those seen using DBD grafts in similar recipients Objective : To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death ( DCD ) at one single large institution . Background : Shortage of available cadaveric organs is a significant limiting factor in liver transplantation ( LT ) . The use of DCD offers the potential to increase the organ pool . However , early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy ( IC ) , leading to several programs to ab and oning this source of organs . Methods : A retrospective analysis of a prospect i ve data base from April 2001 to 2010 focused on 167 consecutive DCD-LT . Each DCD transplant was matched with 2 brain death donors ( DBD ) grafts ( n = 333 ) according to the period of transplantation . Primary outcome measures were biliary complications including the severity of complications , graft survival and patient survival . Minimum follow-up was 3 months . Results : Anastomotic stricture was the most common biliary complication ( DCD = 30 , 19 % vs. DBD = 41 , 13 % ) . Most were treated endocoscopically ( grade IIIa = 72 % ) , whereas hepatico-jejunostomy ( grade IIIb ) was performed in 22 % . Primary IC occurred in 4 ( 2.5 % ) recipients from the DCD group and was absent in the DBD group ( P = 0.005 ) . However , none of these patients required retransplantation . Patient and graft survival at 1 , 3 , and 5 years were similar between DCD and DBD groups ( P = 0.106 , P = 0.138 , P = 0.113 , respectively ) . Conclusions : The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia – reperfusion injury . We present the first patients transplanted using a normothermic machine perfusion ( NMP ) device that transports and stores an organ in a fully functioning state at 37 ° C . In this Phase 1 trial , organs were retrieved using st and ard techniques , attached to the perfusion device at the donor hospital , and transported to the implanting center in a functioning state . NMP livers were matched 1:2 to cold‐stored livers . Twenty patients underwent liver transplantation after NMP . Median NMP time was 9.3 ( 3.5–18.5 ) h versus median cold ischaemia time of 8.9 ( 4.2–11.4 ) h. Thirty‐day graft survival was similar ( 100 % NMP vs. 97.5 % control , p = 1.00 ) . Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ( 417 IU [ 84–4681 ] ) versus ( 902 IU [ 218–8786 ] , p = 0.03 ) . This first report of liver transplantation using NMP‐preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation , including transportation . NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs Hypothermic machine perfusion ( HMP ) is widely used to preserve kidneys for transplantation with improved results over cold storage ( CS ) . To date , successful transplantation of livers preserved with HMP has been reported only in animal models . In this , the first prospect i ve liver HMP study , 20 adults received HMP‐preserved livers and were compared to a matched group transplanted with CS livers . HMP was performed for 3–7 h using centrifugal perfusion with Vasosol ® solution at 4–6 ° C . There were no cases of primary nonfunction in either group . Early allograft dysfunction rates were 5 % in the HMP group versus 25 % in controls ( p = 0.08 ) . At 12 months , there were two deaths in each group , all unrelated to preservation or graft function . There were no vascular complications in HMP livers . Two biliary complications were observed in HMP livers compared with four in the CS group . Serum injury markers were significantly lower in the HMP group . Mean hospital stay was shorter in the HMP group ( 10.9 ± 4.7 days vs. 15.3 ± 4.9 days in the CS group , p = 0.006 ) . HMP of donor livers provided safe and reliable preservation in this pilot case‐controlled series . Further multicenter HMP trials are now warranted Introduction The use of marginal or extended criteria donor livers is increasing . These organs carry a greater risk of initial dysfunction and early failure , as well as inferior long-term outcomes . As such , many are rejected due to a perceived risk of use and use varies widely between centres . Ex situ normothermic machine perfusion of the liver ( NMP-L ) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres . Methods and analysis Viability testing and transplantation of marginal livers is an open-label , non-r and omised , prospect i ve , single-arm trial design ed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival . The procured rejected livers must meet predefined criteria that objective ly denote their marginal condition . The liver is subjected to NMP-L following a period of static cold storage . Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters — bile production , metabolism of glucose , a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min , a pH ≥7.30 and /or maintain a homogeneous perfusion — will be considered viable and transplanted into a suitable consented recipient . The co primary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival . Ethics and dissemination The protocol was approved by the National Research Ethics Service ( London — Dulwich Research Ethics Committee , 16/LO/1056 ) , the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research , Innovation and Novel Technologies Advisory Group . The findings of this trial will be disseminated through national and international presentations and peer- review ed publications . Trial registration number NCT02740608 ; Pre- results After extensive experimentation , outcomes of a first clinical normothermic machine perfusion ( NMP ) liver trial in the United Kingdom demonstrated feasibility and clear safety , with improved liver function compared with st and ard static cold storage ( SCS ) . We present a preliminary single‐center North American experience using identical NMP technology . Ten donor liver grafts were procured , four ( 40 % ) from donation after circulatory death ( DCD ) , of which nine were transplanted . One liver did not proceed because of a technical failure with portal cannulation and was discarded . Transplanted NMP grafts were matched 1:3 with transplanted SCS livers . Median NMP was 11.5 h ( range 3.3–22.5 h ) with one DCD liver perfused for 22.5 h. All transplanted livers functioned , and serum transaminases , bilirubin , international normalized ratio , and lactate levels corrected in NMP recipients similarly to controls . Graft survival at 30 days ( primary outcome ) was not statistically different between groups on an intent‐to‐treat basis ( p = 0.25 ) . Intensive care and hospital stays were significantly more prolonged in the NMP group . This preliminary experience demonstrates feasibility as well as potential technical risks of NMP in a North American setting and highlights a need for larger , r and omized studies |
12,683 | 26,490,760 | An analysis of multiple time points suggested that effects decrease over time , and our analysis provided no evidence that an effect remains six months after a corticosteroid injection | BACKGROUND Knee osteoarthritis is a leading cause of chronic pain , disability , and decreased quality of life .
Despite the long-st and ing use of intra-articular corticosteroids , there is an ongoing debate about their benefits and safety .
This is an up date of a Cochrane review first published in 2005 .
OBJECTIVES To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain , physical function , quality of life , and safety . | OBJECTIVE --To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide ( THA ) in knee osteoarthritis ( OA ) and examine factors which may relate to treatment efficacy . METHODS --Eighty four patients with clinical and radiographic evidence of knee OA were recruited and r and omly allocated to receive either THA ( 20 mg in 1 ml ) or placebo ( 0.9 % normal saline , 1 ml ) . Follow up assessment s evaluated the following outcome variables : patient opinion of overall change in the treated knee , visual analogue pain score ( VAS ) , distance walked in one minute ( WD ) , and Health Assessment Question naire modified for lower limb function ( HAQ ) . RESULTS --Seventy eight percent of THA and 49 % of placebo treated patients reported overall improvement at week 1 ( p < 0.05 ) . At week 6 , improvement was reported in 57 % and 55 % of patient groups , respectively . VAS improved in both groups at week 1 ( THA , p < 0.001 ; placebo , p < 0.05 ) and week 6 ( both p < 0.01 ) . Improvement in VAS was significantly greater among THA treated patients at week 1 only ( p < 0.01 ) . Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion ( p < 0.05 ) , and those who had synovial fluid successfully aspirated at the time of injection ( p < 0.01 ) . WD improved in THA treated patients at week 1 ( p < 0.001 ) , and in both groups at week 6 ( THA , p < 0.001 ; placebo , p < 0.01 ) . Improvements in HAQ were seen in THA patients only at weeks 1 and 6 ( p < 0.05 ) . Regression analysis did not identify any additional clinical , radiographic , or synovial fluid characteristics which influenced the response . CONCLUSIONS --THA provided short term pain relief in knee OA . Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection We report the results of a double-blind three-centre study , employing a cross-over design , set up to compare the efficacy of intra-articular injections of Myc 2095 ( 20 mg ) , triamcinolone hexacetonide ( Lederspan ) ( 20 mg ) and placebo in 40 patients with synovitis of the knee joint . Each patient included in the study contributed data on 2 of the 3 treatment variables being compared . Seven clinical parameters were assessed every 6 weeks , while the doctor 's and the patient 's assessment s were scored . Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective . Placebo response was also very high . After the first Myc 2095 injection , improvement in " tenderness " , " pain under load " and " swelling and hydrops " was significantly superior to that following placebo treatment . The evaluation of the second injections indicated a marked carry-over effect from the first course . This was also evident from the doctor 's and patient 's assessment s. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials , emerged from this study BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) IMPORTANCE Osteoarthritis ( OA ) of the knee is the most frequent form of arthritis and a cause of pain and disability . Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach , but no evidence supports the recommendation . OBJECTIVE To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee . DESIGN , SETTING , AND PARTICIPANTS We performed a r and omized , blinded , placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1 , 2012 , through April 2 , 2014 . The participants had radiographic confirmation of clinical OA of the knee , clinical signs of localized inflammation in the knee , and knee pain during walking ( score > 4 on a scale of 0 to 10 ) . INTERVENTIONS Participants were r and omly allocated ( 1:1 ) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate ( Depo-Medrol ) , 40 mg/mL , dissolved in 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( corticosteroid group ) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( placebo group ) . Two weeks after the injections , all participants started a 12-week supervised exercise program . MAIN OUTCOMES AND MEASURES The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) question naire ( range , 0 - 100 ; higher scores indicate greater improvement ) at week 14 . Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation . Outcomes were measured at baseline , week 2 ( exercise start ) , week 14 ( exercise stop ) , and week 26 ( follow-up ) . RESULTS One hundred patients were r and omized to the corticosteroid group ( n = 50 ) or the placebo group ( n = 50 ) ; 45 and 44 patients , respectively , completed the trial . The mean ( SE ) changes in the KOOS Pain subscale score at week 14 were 13.6 ( 1.8 ) and 14.8 ( 1.8 ) points in the corticosteroid and placebo groups , respectively , corresponding to a statistically insignificant mean difference of 1.2 points ( 95 % CI , -3.8 to 6.2 ; P = .64 ) . We found no statistically significant group differences in any of the secondary outcomes at any time point . CONCLUSIONS AND RELEVANCE No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee . Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2012 - 002607 - 18 ; clinical trials.gov Identifier : NCT01945749 Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVES : To show whether intra-articular steroid injections are effective in osteoarthritis ; to determine factors that predict response ; and to determine whether injection has a beneficial effect on muscle strength . METHODS : Double blind , placebo controlled , crossover study in 59 patients with symptomatic osteoarthritis of the knee . Outcome measure- Primary outcome measure : change in visual analogue score for pain at three weeks . Predictors of response analysed using logistic regression with a 15 % decrease in pain score at three weeks defining response . RESULTS : Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline ( median change -2.0 mm , interquartile range -16.25 to 4.0 ) and placebo ( median 0.0 mm , interquartile range -9.0 to 6.25 ) . No clinical predictors of response could be identified . Muscle strength was not significantly improved in the short term by intra-articular injection . CONCLUSIONS : Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible . There may be a place for their more widespread use Background Studies have evaluated the concomitant use of hyaluronan ( HA ) with steroids , anti-inflammatory drugs and analgesic agents in an attempt to magnify the extent and duration of pain relief due to knee osteoarthritis . To date there has not been an intra-articular combination therapy available for relief of knee osteoarthritis symptoms – one that combines the fast acting onset of symptom relief provided by a corticosteroid with the long-lasting symptom relief provided by HA in a single injection . The objective of this study was to evaluate the safety and preliminary performance of two new HA formulations , Hydros ( hyaluronan-based hydrogel suspended in hyaluronan solution ) and Hydros-TA ( HA plus 10 mg of triamcinolone acetonide [ TA ] ) in subjects with knee osteoarthritis . Methods We conducted a Phase 2 prospect i ve , multicenter , r and omized , double-blind feasibility trial . Participants ( n = 98 ; mean age 60 years ) with knee osteoarthritis ( Kellgren-Lawrence grade 2 or 3 ) were r and omized to three treatment groups : Hydros , Hydros-TA , and Synvisc-One ® ( hylan G-F 20 ) . Participants received one 6 ml intra-articular injection in the treatment knee and were evaluated at 2 , 6 , 13 , and 26 weeks post-treatment . Safety was assessed from adverse events at all study visits . The primary efficacy outcome was the change from baseline on the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) A ( Pain ) score for the treatment knee . Results Adverse events were similar across treatment groups with the most common being arthralgia , joint swelling , back pain , and joint stiffness . Arthralgia was reported 5 times with Synvisc-One , 4 with Hydros , and 1 with Hydros-TA . Each group demonstrated a reduction in the WOMAC A ( Pain ) score over 26 weeks : [ least-square mean ( st and ard error ) ] 30.5 ( 5.1 ) mm for Hydros ; 34.4 ( 4.7 ) mm for Hydros-TA ; 28.0 ( 5.4 ) mm for Synvisc-One and an observed improvement of 2.5 mm ( p = 0.64 ) and 6.4 mm ( p = 0.24 ) over Synvisc-One for Hydros and Hydros-TA , respectively . Conclusions A single injection of Hydros or Hydros-TA was well-tolerated and relieved pain associated with knee osteoarthritis over 26 weeks . Data indicate that Hydros-TA had a more rapid pain relief compared to Hydros alone . A Phase 3 trial is underway to confirm these preliminary results .Trial registration numberNCT01134406 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 R and omized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic review s of effectiveness . Search ing for reports of r and omized trials in data bases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter . Objectives The objectives of this study are to devise a search strategy for identifying reports of r and omized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library , with the permission of Elsevier , the publishers of EMBASE . Methods A highly sensitive search strategy was design ed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles , abstract s , EMTREE terms ( or some combination of these ) of reports of trials indexed in EMBASE . This search strategy was run against EMBASE from 1980 to 2005 ( 1974 to 2005 for four of the terms ) and records retrieved by the search , which were not already indexed as r and omized trials in MEDLINE , were downloaded from EMBASE , printed and read . An analysis of the language of publication was conducted for the reports of trials published in 2005 ( the most recent year completed at the time of this study ) . Results Twenty-two search terms were used ( including nine which were later rejected due to poor cumulative precision ) . More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as r and omized trials in MEDLINE . These are now easily identifiable in CENTRAL , in The Cochrane Library . Cumulative sensitivity ranged from 0.1 % to 60 % and cumulative precision ranged from 8 % to 61 % . The truncated term ' r and om$ ' identified 60 % of the total number of reports of trials but only 35 % of the more than 130,000 records retrieved by this term were reports of trials . The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as r and omized trials in MEDLINE , 959 ( 5 % ) were in language s other than English . The EMBASE search identified an additional 658 reports in language s other than English , of which the highest number were in Chinese ( 320 ) . Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE , especially in some language s other than English . The search strategy used was subjectively derived from a small ' gold st and ard ' set of test records and was not vali date d in an independent test set . We intend to design an objective ly-derived vali date d search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of r and omized trials identified compared with the frequency of these terms across the entire EMBASE data base Background Patients with osteoarthritis of the knee are at risk for poorer outcomes after arthroscopic meniscectomy . Intra-articular corticosteroid injections have been shown to be efficacious both in patients with osteoarthritis and postarthroscopy patients . Hypothesis A postoperative , intra-articular methylprednisolone and lidocaine injection in patients with chondromalacia undergoing meniscectomy will improve patient-rated pain and function compared with control patients . Study Design R and omized , controlled trial ; Level of evidence , 1 . Methods A total of 58 patients ( 59 knees ) were r and omized in a double-blinded fashion to receive either saline plus lidocaine ( saline ) or methylprednisolone plus lidocaine ( steroid ) after arthroscopic meniscectomy in which chondromalacia ( modified Outerbridge grade 2 or higher ) was confirmed . Preoperatively and at follow-up—6 weeks and 6 , 9 , and 12 months— patients underwent an examination and completed a subjective functioning survey . Scores were calculated using several vali date d scoring systems including the Lysholm , International Knee Documentation Committee ( IKDC ) , and Short Form–12 ( SF-12 ) . Results No statistically significant differences were observed between the saline ( n = 30 ) and steroid ( n = 29 ) groups in their demographics and preoperative scores . At 6 weeks , the steroid group had higher scores than the saline group on multiple scales , including the IKDC . No differences in outcome scores existed at later time points . At 12 months , 86 % of the steroid and 69 % of the saline group were completely or mostly satisfied with the procedure ( P = .01 ) . In the saline group , 4 patients required reinjection and 2 underwent joint replacements within 12 months , while the steroid group had 3 reinjections and 2 meniscus transplants . Conclusion The addition of a postoperative corticosteroid injection result ed in improved pain and function at an early time point ; however , it provided no lasting difference compared with only local anesthetic injection Background The 20-meter walk test is a physical function measure commonly used in clinical research studies and rehabilitation clinics to measure gait speed and monitor changes in patients ’ physical function over time . Unfortunately , the reliability and sensitivity of this walk test are not well defined and , therefore , limit our ability to evaluate real changes in gait speed not attributable to normal variability . The aim of this study was to assess the test-restest reliability and sensitivity of the 20-meter walk test , at a self-selected pace , among patients with mild to moderate knee osteoarthritis ( OA ) and to suggest a st and ardized protocol for future test administration . Methods This was a measurement reliability study . Fifteen consecutive people enrolled in a r and omized-controlled trial of intra-articular corticosteroid injections for knee OA participated in this study . All participants completed 4 trials on 2 separate days , 7 to 21 days apart ( 8 trials total ) . Each day was divided into 2 sessions , which each involved 2 walking trials . We compared walk times between trials with Wilcoxon signed-rank tests . Similar analyses compared average walk times between sessions . To confirm these analyses , we also calculated Spearman correlation coefficients to assess the relationship between sessions . Finally , smallest detectable differences ( SDD ) were calculated to estimate the sensitivity of the 20-meter walk test . Results Wilcoxon signed-rank tests between trials within the same session demonstrated that trials in session 1 were significantly different and in the subsequent 3 sessions , the median differences between trials were not significantly different . Therefore , the first session of each day was considered a practice session , and the SDD between the second session of each day were calculated . SDD was −1.59 seconds ( walking slower ) and 0.15 seconds ( walking faster ) . Conclusions Practice trials and a st and ardized protocol should be used in administration of the 20-meter walk test . Changes in walk time between −1.59 seconds ( walking slower ) and 0.15 seconds ( walking faster ) should be considered within the range of normal variability of 20-meter walking speed . The primary limitation of our study was a small sample size , which may influence the generalizability of our findings Objective To determine the effectiveness of intensive structured care to optimise blood pressure control based on individual absolute risk targets in primary care . Design Pragmatic multicentre r and omised controlled trial . Setting General practice s throughout Australia , except Northern Territory , 2009 - 11 . Participants Of 2185 patients from 119 general practice s who were eligible for drug treatment for hypertension according to national guidelines 416 ( 19.0 % ) achieved their individual blood pressure target during a 28 day run-in period of monotherapy . After exclusions , 1562 participants not at target blood pressure ( systolic 150 ( SD 17 ) mm Hg , diastolic 88 ( SD 11 ) mm Hg ) were r and omised ( 1:2 ratio ) to usual care ( n=524 ) or the intervention ( n=1038 ) . Intervention Computer assisted clinical profiling and risk target setting ( all participants ) with intensified follow-up and stepwise drug titration ( initial angiotensin receptor blocker monotherapy or two forms of combination therapy using angiotensin receptor blockers ) for those r and omised to the intervention . The control group received usual care . Main outcome measures The primary outcome was individual blood pressure target achieved at 26 weeks . Secondary outcomes were change in mean sitting systolic and diastolic blood pressure , absolute risk for cardiovascular disease within five years based on the Framingham risk score , and proportion and rate of adverse events . Results On an intention to treat basis , there was an 8.8 % absolute difference in individual blood pressure target achieved at 26 weeks in favour of the intervention group compared with usual care group ( 358/988 ( 36.2 % ) v 138/504 ( 27.4 % ) ) : adjusted relative risk 1.28 ( 95 % confidence interval 1.10 to 1.49 , P=0.0013 ) . There was also a 9.5 % absolute difference in favour of the intervention group for achieving the classic blood pressure target of ≤140/90 mm Hg ( 627/988 ( 63.5 % ) v 272/504 ( 54.0 % ) ) : adjusted relative risk 1.18 ( 1.07 to 1.29 , P<0.001 ) . The intervention group achieved a mean adjusted reduction in systolic blood pressure of 13.2 mm Hg ( 95 % confidence interval −12.3 to −14.2 mm Hg ) and diastolic blood pressure of 7.7 mm Hg ( −7.1 to −8.3 mm Hg ) v 10.1 mm Hg ( −8.8 to 11.3 mm Hg ) and 5.5 mm Hg ( −4.7 to −6.2 mm Hg ) in the usual care group ( P<0.001 ) . Among 1141 participants in whom five year absolute cardiovascular risk scores were calculated from baseline to the 26 week follow-up , the reduction in risk scores was greater in the intervention group than usual care group ( 14.7 % ( SD 9.3 % ) to 10.9 % ( SD 8.0 % ) ; difference −3.7 % ( SD 4.5 % ) and 15.0 % ( SD 10.1 % ) to 12.4 % ( SD 9.4 % ) ; −2.6 % ( SD 4.5 % ) : adjusted mean difference −1.13 % ( 95 % confidence interval −0.69 % to −1.63 % ; P<0.001 ) . Owing to adverse events 82 ( 7.9 % ) participants in the intervention group and 10 ( 1.9 % ) in the usual care group had their drug treatment modified . Conclusions In a primary care setting intensive structured care result ed in higher levels of blood pressure control , with clinical ly lower blood pressure and absolute risk of future cardiovascular events overall and with more people achieving their target blood pressure . An important gap in treatment remains though and applying intensive management and achieving currently advocated risk based blood pressure targets is challenging OBJECTIVE The study was part of a r and omized open-label clinical trial design ed to evaluate the effects of intra-articular injections of hyaluronan ( Hyalgan ) ( HY ) in osteoarthritis ( OA ) of the human knee . Data were compared with those obtained after treatment with methylprednisolone acetate ( Depomedrol ) ( MP ) . METHODS Synovial membranes from patients with OA of the knee , primary or secondary to a traumatic event and classified according to the American College of Rheumatology criteria , were examined by arthroscopy and by light and electron microscopy before and 6 months after local injection of HY ( 2 ml of 500 - 730 000 MW hyaluronan , 10 mg/ml in saline , one injection per week for 5 weeks ) or MP ( 1 ml of methylprednisolone acetate , 40 mg/ml , one injection per week for 3 weeks ) . RESULTS Arthroscopy revealed a significant decrease in inflammatory score after both treatments . Histology showed that HY treatment was effective ( P < or = 0.05 ) in reducing the number and aggregation of lining synoviocytes , as well as the number and calibre of the vessels . MP treatment significantly reduced the number of mast cells in primary OA . Both treatments tended to decrease the number of hypertrophic and to increase the number of fibroblast-like lining cells , to decrease the numbers of macrophages , lymphocytes , mast cells and adipocytes , and to decrease oedema , especially in primary OA , and to increase the number of fibroblasts and the amount of collagen . These phenomena were evident throughout the thickness of the synovial tissue . CONCLUSION At least in the medium term , both HY and MP modified a number of structural variables of the synovial membrane of the osteoarthritic human knee towards the appearance of that of normal synovium . The effect was more evident in primary OA than in OA secondary to a traumatic event . This is the first evidence that local hyaluronan injections modify the structural organization of the human knee synovium in OA Objective . To assess whether inflammation on ultrasound is predictive of clinical response to intraarticular ( IA ) corticosteroid injections in patients with knee osteoarthritis ( OA ) . Methods . Patients with symptomatic knee OA were r and omized to receive either an IA injection of 40 mg triamcinolone acetonide in the treatment group or 1 cc 0.9 % saline in the placebo group . Clinical response was assessed by changes in baseline Western Ontario and McMaster Universities ( WOMAC ) index scores and physician global assessment at 4 and 12 weeks . Ultrasounds were performed at each visit . Patients and assessors were blinded to treatment status . Results . Seventy-nine patients were enrolled into the study . Four-week data were available for 67 patients in the primary analysis comparing change in WOMAC pain score from baseline to 4 weeks . There was almost no change in the WOMAC pain subscale score from baseline to 4 weeks in the control group , but there was a significant improvement in WOMAC pain subscale score from 10.8 ( SD ± 3.2 ) at baseline to 8.75 ( SD ± 4.0 ) at 4 weeks in the treatment group ( adjusted p = 0.001 ) . Of the 34 patients in the treatment group ; 16 ( 47 % ) had inflammatory disease and 18 ( 53 % ) had noninflammatory disease as determined by ultrasound . There was no difference in the change in WOMAC pain score between the inflammatory and noninflammatory patients in the treatment group at 4 weeks . There was a statistically significant greater improvement in pain subscale scores among noninflammatory patients than among inflammatory patients at 12 weeks . Conclusion . Intraarticular corticosteroid injections are an effective short-term treatment for symptomatic knee OA compared to placebo . Patients with noninflammatory characteristics on ultrasound had a more prolonged benefit from IA corticosteroids compared to inflammatory patients The goal of this study was to assess the safety and efficacy of hyaluronan ( HA ) with/without corticosteroid in patients with knee osteoarthritis ( OA ) . In a 1-year , r and omized , single-blind trial , 24 patients were treated with HA weekly for 3 weeks , then three injections on the 6th month for a total of six injections . Sixteen patients were treated the same but with the addition of 1 ml triamcinolone acetonide prior to the first and fourth HA injection . The treatment was repeated at the sixth month . The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and the visual analog pain scale ( VAS ) . After 1 year , progression of OA was evaluated with magnetic resonance imaging ( MRI ) . During the study , pain relief was marked in patients who received combined treatment with respect to WOMAC pain and VAS ( p<0.05 ) . At the first year , no progression was observed in either treatment group . Although all patients had improvement for both pain and function , HA together with corticosteroid was superior to HA alone for early pain relief . The MRI findings showed that neither treatment showed a progression on the damage of the cartilage OBJECTIVE To assess the efficacy of intra-articular steroid injections following arthroscopy and joint lavage in symptomatic OA of the knee . METHODS Seventy-seven patients with OA of the knee were r and omized to receive either 120 mg methylprednisolone acetate ( MPA ) or placebo following arthroscopy . Clinical assessment s included severity of pain on movement and at rest , stiffness , the presence of joint effusions , range of movement , WOMAC ( Western Ontario and McMaster Universities Osteoarthritis Index ) score and Lequesne functional assessment . The outcome measures were evaluated at baseline and 2 , 4 , 8 , 12 and 24 weeks . Further arthroscopies and synovial biopsies were performed at the time of clinical response and at relapse . RESULTS An intention-to-treat analysis was performed on 71 patients ( 38 MPA , 33 placebo ) . Using the OARSI ( Osteoarthritis Research Society International ) response criteria , 58 % of the steroid group vs 33 % of the placebo group ( adjusted relative risk = 2.38 ) ( P = 0.004 ) responded at 4 weeks . At other time points , there were no significant differences between the treatment groups . There were no significant differences between the two treatment groups for pain , stiffness or WOMAC or Lequesne assessment s at any time point . CONCLUSIONS The response to intra-articular corticosteroids following joint lavage is short-lived ( 2 - 4 weeks ) , achievement of an OARSI response criterion being the only difference between the two groups Compare the medium-term effectiveness and tolerance between joint lavage ( JL ) in combination with triamcinolone hexacetonide ( TH ) intra-articular injection ( IAI ) and IAI with TH alone for treatment of primary osteoarthritis ( OA ) of the knee . A r and omized , double-blind , controlled study was carried out on 60 patients with primary OA of the knee , r and omized into two intervention groups : JL/TH group , joint lavage in combination with TH intra-articular injection and TH group , TH intra-articular injection . Patients were followed for 12 weeks by a blind observer using the following outcome measurements : visual analogue scale for pain at rest and in movement , goniometry , WOMAC , Lequesne ’s index , timed 50-ft walk , perception of improvement , Likert scale for improvement assessment , use of nonsteroidal anti-inflammatory drugs and analgesics , and local side effects . There were no statistical differences in the inter-group analysis for any of the variables studied over the 12-week period . Although both groups demonstrated statistical improvement in the intra-group evaluation ( except for Likert scale according to patient and the use of anti-inflammatory drugs ) . In the Kellgren – Lawrence scale ( KL ) 2 and 3 sub- analysis , there was a statistical difference regarding joint flexion among patients classified as KL 2 , favoring the TH group ( p = 0.03 ) . For the KL 3 patients , there were statistical differences favoring the JL/TH group regarding Lequesne ( p = 0.021 ) , WOMAC pain score ( p = 0.01 ) , and Likert scale according to the patient ( p = 0.028 ) and the physician ( p = 0.034 ) . The combination of joint lavage and IAI with TH was not more effective than IAI with TH alone in the treatment of primary OA of the knee . However , KL 3 patients may receive a major benefit from this combination OBJECTIVE To evaluate the efficacy of joint lavage and intraarticular steroid injection , alone and in combination , in the treatment of patients with symptomatic knee osteoarthritis ( OA ) . METHODS Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospect i ve , r and omized , controlled , 2 x 2 factorial- design trial of 6 months ' duration . The 4 treatment groups consisted of 1 ) intraarticular placebo ( 1.5 ml of 0.9 % normal saline ) , 2 ) intraarticular corticosteroids ( 3.75 mg of cortivazol in 1.5 ml ) , 3 ) joint lavage and intraarticular placebo , and 4 ) joint lavage and intraarticular corticosteroid . Outcome measures evaluated at baseline , week 1 , week 4 , week 12 , and week 24 included severity of pain ( 100-mm visual analog scale [ VAS ] ) , global status ( 100-mm VAS ) , and Lequesne 's functional index . RESULTS No interaction between steroid injection and joint lavage was demonstrated . Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 ( P = 0.020 ) . In contrast , corticosteroid injection had no long-term effect ( P = 0.313 ) ; corticosteroid injection was associated with a decrease in pain only at week 1 ( P = 0.003 ) and week 4 ( P = 0.020 ) . After week 4 , Lequesne 's functional index was not significantly improved regardless of the assigned treatment . CONCLUSION Compared with placebo , both treatments significantly relieved pain but did not improve functional impairment . The effects of the 2 treatments were additive . Cortivazol provided short-term relief of pain ( up to week 4 ) . The effects of joint lavage persisted up to week 24 OBJECTIVE To evaluate the safety and efficacy of long-term intraarticular ( IA ) steroid injections for knee pain related to osteoarthritis ( OA ) . METHODS In a r and omized , double-blind trial , 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg ( 34 patients ) or saline ( 34 patients ) into the study knee every 3 months for up to 2 years . The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years . Measurements of minimum joint space width were performed by an automated computerized method on st and ardized fluoroscopically guided radiographs taken with the patient st and ing and with the knee in a semiflexed position . The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index ( WOMAC ) . Efficacy measures of secondary interest were the total score on the WOMAC , physician 's global assessment , patient 's global assessment , patient 's assessment of pain , range of motion ( ROM ) of the affected knee , and 50-foot walking time . Clinical symptoms were assessed just before each injection . RESULTS At the 1-year and 2-year followup evaluations , no difference was noted between the two treatment groups with respect to loss of joint space over time . The steroid-injected knees showed a trend toward greater symptom improvement , especially at 1 year , for the WOMAC pain subscale , night pain , and ROM values ( P = 0.05 ) compared with the saline-injected knees . Using area under the curve analyses , knee pain and stiffness were significantly improved throughout the 2-year study by repeated injections of triamcinolone acetonide , but not saline ( P < 0.05 ) . CONCLUSION Our findings support the long-term safety of IA steroid injections for patients with symptomatic knee OA . No deleterious effects of the long-term administration of IA steroids on the anatomical structure of the knee were noted . Moreover , long-term treatment of knee OA with repeated steroid injections appears to be clinical ly effective for the relief of symptoms of the disease BACKGROUND The OARSI St and ing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains ( pain , function , and patient 's global assessment ) as a single variable for clinical trials ( 1 ) . For each domain , a response was defined by both a relative and an absolute change , with different cut-offs with regard to the drug , the route of administration and the OA localization . OBJECTIVE To propose a simplified set of responder criteria with a similar cut-off , whatever the drug , the route or the OA localization . METHODS Data driven approach : ( 1 ) Two data bases were considered : the " elaboration " data base with which the formal OARSI sets of responder criteria were elaborated , and the " revisit " data base . ( 2 ) Six different scenarios were evaluated : The two formal OARSI sets of criteria ; Four proposed scenarios of simplified sets of criteria . Data from clinical r and omized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different data bases ( " elaboration " versus " revisit " ) and those of the four proposed simplified scenarios within the " revisit " data base . The placebo effect , active effect , treatment effect , and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios . Experts ' opinion approach : Results were discussed among the participants of the OMERACT VI meeting , who voted to select the definite OMERACT-OARSI set of criteria ( one of the six evaluated scenarios ) . RESULTS Data driven approach : Fourteen trials totaling 1886 OA patients and fifteen studies involving 8164 OA patients were evaluated in the " elaboration " and the " revisit " data bases respectively . The variability of the performances observed in the " revisit " data base when using the different simplified scenarios was similar to that observed between the two data bases ( " elaboration " versus " revisit " ) when using the formal scenarios . The treatment effect and the required sample arm size were similar for each set of criteria . Experts ' opinion approach : According to the experts , these two previous performances were the most important of an optimal set of responder criteria . They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response , with similar cut-offs whatever the drug , the route of administration or the OA localization . CONCLUSION This data driven and experts ' opinion approach is the basis for proposing an optimal simplified set of responder criteria for OA clinical trials . Other studies , using other sets of OA patients , are required in order to further vali date this proposed OMERACT-OARSI set of criteria Osteoarthritis is a chronic disease that causes serious pain and limitations in activities . Intraarticular corticosteroid injections combined with pharmacological treatment and physiotherapy have been used for years to control the local inflammation and relieve pain in the patients with osteoarthritis . There are several animal experiments which suggested that the intraarticular corticosteroid injections impair cartilage protein synthesis . However , there are no serious evidence s suggesting the increase of cartilage impairment . The aim of our study was to compare the efficacy of placebo and intraarticular corticosteroid agents in the patients with symptomatic knee osteoarthritis . One hundred and twenty patients with painful knee osteoarthritis were included in the prospect i ve , r and omized , controlled study . The patients were r and omized into four groups . Each group consisted of thirty patients . Intraarticular single dose of methylprednisolone acetate ( 40 mg , 1 ml ) , Betametazone disodium phosphate ( 3 mg , 1 ml ) , Triamsinolon acetonate ( 40 mg , 1 ml ) , and serum physiological ( 0.09 % NaCl , 1 ml ) were administrated to the groups , respectively . The patients were evaluated by Visual Analog Scale ( 0–10 cm [ VAS ] ) for the pain severity , and by Lequesne Functional Index for functional state before treatment , and at the 1st , 3rd , 6th , and 12th weeks . Our results showed that single doses of three agents provided symptomatic and functional relief and their effects reduced at the 12th week . However , methylprednisolone acetate was a statistically more effective analgesic as compared to the other agents until the sixth week SUMMARY Purpose : Joint lavage ( JL ) , involves the passage of cold sterile 0.9 % saline through the knee joint in order to have the fluid reach the inside of the joint capsule . This technique was evaluated as a local treatment for osteoarthritis ( OA ) of the knee alone ( JL ) and in combination with intra-articular infiltration with glucocorticoids ( JLC ) . Patients and methods : An overall 299 knees belonging to 205 patients ( 22 % males , 78 % females ) with a mean age of 67 ± 8 years and osteoarthritis of the knee of radiological grade II or III on the Kellgren scale were r and omised in the ratio of 1:4 into two therapeutic groups , namely : JL ( n = 62 ) and JLC ( n = 237 ) . All patients received joint lavage on day 0 ; in those of the JLC group , joint lavage was followed by infiltration of 40 mg of triamcinolone acetonide . The efficacy of both treatments was assessed by recording the corresponding values for the following variables : pain strength as measured by a visual analogy scale ( VAS ) , effusion , crepitation , restricted motion , spontaneous pain , pain on pressure , pain on passive motion and pain on active motion ; all of these were recorded at the onset of the study , and after 1 and 3 months . Results : There were no significant differences in the values of the variables at the different follow-up times . Also , pain severity was similar in both treatment groups . Thus , VAS for pain was 7.3 ± 0.3 for the JL group and 7.1 ± 0.2 for the JLC group at the onset , and decreased to 3.0 ± 0.3 in the former and 2.8 ± 0.2 in the latter after 1 month ; the decrease was statistically significant in both cases . After 3 months , the JL and JLC groups had a VAS of 3.5 ± 0.3 and 3.8 ± 0.2 , respectively . Conclusions : The results of this work suggest the absence of significant differences between the two treatments , such that both joint lavage alone and with infiltration with corticoids can be concluded as similarly effective for the symptomatic management of osteoarthritis of the knee We studied the effect of intraarticular saline , sufentanil , or sufentanil plus methylprednisolone after knee arthroscopic meniscectomy . In a double-blind r and omized study , 60 patients undergoing knee arthroscopic meniscectomy were allocated to groups receiving intraarticular saline , intraarticular sufentanil 10 & mgr;g , or sufentanil 10 & mgr;g plus methylprednisolone 40 mg at the end of arthroscopy during general anesthesia . Postoperatively , pain levels at rest and during movement ( i.e. , active flexion of the knee ) were measured by a visual analog scale and were significantly decreased in the sufentanil and sufentanil plus methylprednisolone groups compared with the control group . Moreover , we found that there was a significant reduction in intraarticular sufentanil and sufentanil plus methylprednisolone in the postoperative consumption of analgesics . We also found that the use of intraarticular sufentanil or sufentanil plus methylprednisolone after knee arthroscopic meniscectomy decreases the amount of supplementary analgesic needed for pain relief during the early postoperative period . In addition , we detected that sufentanil provided prolonged pain relief up to 24 h when compared with control , whereas when we combined sufentanil plus methylprednisolone , we found that it further reduced pain and use of analgesics when compared with sufentanil Abstract Convalescence after arthroscopic meniscectomy is dependent on pain and the inflammatory response . The aim of the study was therefore to investigate the effect of intra‐articular bupivacaine+morphine+methylprednisolone versus bupivacaine+morphine or saline on post‐meniscectomy pain , mobilisation and convalescence . In a double‐blind r and omized study 60 patients undergoing arthroscopic meniscectomy were allocated to intra‐articular saline , intra‐articular bupivacaine 150 mg+morphine 4 mg or the same dose of bupivacaine+morphine+intra‐articular methylprednisolone 40 mg . All patients were instructed to resume normal activities immediately after operation . Pain during movement and walking , leg muscle force and joint effusion , use of crutches and duration of sick leave were assessed . Combined bupivacaine and morphine significantly reduced pain , time of immobilisation and duration of convalescence . Addition of methylprednisolone further reduced pain , use of additional analgesics , joint swelling and convalescence , improved muscle function and prevented the inflammatory response ( acute phase protein ) ( P<0.05 ) . A multimodal analgesic and anti‐inflammatory treatment may enhance post‐arthroscopic convalescence , which depends on the trauma induced inflammatory response and pain Intra-articular steroid therapy for osteoarthritis of the knee has been reassessed by two placebo-controlled trials of 20 mg of triamcinalone hexacetonide in 48 joints . Steroid injections caused a significantly greater reduction in pain and tenderness than placebo , and were preferred by patients . However , the benefits were small and transient . Maximum pain reduction occurred one week after injection , and was accompanied by a fall in the thermographic index suggesting an anti-inflammatory mode of action . Synovial fluid was unafffected by injections , and there was no correlation between synovial fluid cell counts or the radiological grading , and the degree of pain reduction In vitro studies on the effects of dexamethasone on human synovial cells have shown that with high concentrations of the steroid in the culture medium cellular activity was completely blocked whereas with low concentrations ( 10(-6)M ) , cellular density decreased but there was an increase in the synthesis of RNA , DNA , protein and hyaluronic acid . These data , coupled with clinical experience of using intra-articular hyaluronic acid to treat patients with osteoarthritis of the knee , prompted the investigators to carry out an open , r and omized study of the use of very small doses of dexamethasone in association with hyaluronic acid in 40 osteoarthritic patients . Twenty patients received a weekly intra-articular injection of 20 mg sodium hyaluronate in 2 ml phosphate buffer for 5 weeks ; the other 20 patients followed a similar treatment regimen , the only difference being the addition of 0.4 mg dexamethasone phosphate to the first injection . Clinical examination of the knee was made before each injection , 7 days after the fifth injection and 60 days after the start of the trial . Rating scale assessment s were made at each visit of spontaneous pain , pain during the day , at night , weight bearing and whilst walking . The results showed that whilst a progressive decrease in all pain parameters was evident and persisted after the end of treatment in both patient groups , pain intensity decreased more rapidly and to lower levels in all but weight-bearing pain , as did improvement in joint mobility , in the combined treatment group . Local tolerance was good with both treatment regimens , with no untoward signs or symptoms at any time . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Combining different therapies , physical therapy agents , pharmacological and physical therapies , generally produces better outcomes for symptoms of knee osteoarthritis ( OA ) than do isolated therapies . AIM To demonstrate if horizontal therapy ( HT ) and aspiration alone and corticosteroid injection alone or in combination determine pain relief and functional improvement in a group of patients with knee OA complicated with Baker 's cyst ( BC ) . DESIGN We design ed a r and omized controlled trial ( RCT ) . SETTING Out patients . POPULATION Sixty patients with a knee OA and diagnosis of BC confirmed by means of st and ard ultrasound ( US ) evaluation . METHODS The trial was conducted as a r and omized , controlled trial . Patients who satisfied the inclusion criteria were r and omized to either the US-guided ( Ultrasound Guided BC aspiration and corticosteroid injection group ( Group A ) , the Horizontal Therapy group ( Group B ) or the US-guided BC aspiration and corticosteroid injection plus Horizontal therapy group ( Group C ) . Outcome measures included : 1 ) pain reduction as measured by visual analogue scale ( VAS ) ; 2 ) functional improvement , as measured by WOMAC ; and 3 ) US evaluation at baseline ( T0 ) , at one ( T1 ) and four ( T2 ) weeks follow-up . RESULTS A total of 60 patients were r and omized into group A ( N.=20 ) , group B ( N.=20 ) or Group C ( N.=20 ) . Patients in group A and in group C , but not those in group B maintained lower pain level at T2 than at baseline , with significant lower VAS values in Group C. As regards US measurements , the maximum axial area did not change as a consequence of the treatment in any of the three groups ( P=0.259 ) . Contrarily , sagittal area measurements were influenced by time ( P<0.01 ) . CONCLUSION Our results show that the group with the best performance for pain , functionality and dimension of BC was that in which combined use was made of horizontal and corticosteroid injection therapies . CLINICAL REHABILITATION IMPACT In this study we want to demonstrate the effectiveness of Horizontal Therapy in the treatment of knee OA complicated by BC OBJECTIVE To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration , the expression of the chemokines monocyte chemoattractant protein 1 ( MCP-1 ) and macrophage inflammatory protein 1alpha ( MIP-1alpha ) , and the expression of matrix metalloproteinases 1 and 3 ( MMPs 1 and 3 ) and their inhibitors , the tissue inhibitors of metalloproteinases 1 and 2 ( TIMPs 1 and 2 ) , in osteoarthritis ( OA ) synovial membranes . METHODS Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids . Twenty-one patients received 120 mg of methylprednisolone acetate ( Depo-Medrol ; Upjohn , Kalamazoo , MI ) , and 20 patients received placebo ( 1 patient received placebo in 1 knee and methylprednisolone acetate in the other ) . Immunoperoxidase staining for the expression of CD68 , MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 was performed , and the immunostaining was quantified by color video image analysis . RESULTS CD68 , MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 immunostaining was observed in all synovial membranes . Intraarticular glucocorticoid treatment was associated with a small ( 30 % ) but statistically significant ( P = 0.048 ) reduction in CD68 + macrophage staining in the synovial lining layer , but there was no change in the CD68 expression in the synovial sublining layer . No significant differences were observed for MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 immunostaining in the synovial lining or sublining layers . CONCLUSION Intraarticular glucocorticoids may reduce CD68 + macrophage infiltration into the synovial lining layer , but not the expression of MCP-1 , MIP-1alpha , MMP-1 , MMP-3 , TIMP-1 , and TIMP-2 in the synovial membrane , in patients with OA Background Intraarticular injections , mainly using long-lasting corticosteroid suspensions , have long been used to treat knee osteoarthritis . Viscosupplementation is a relatively new approach with injection of a variety of agents . When comparing viscosupplementation with intraarticular injections of corticosteroids from baseline to the fourth week , steroids have been more effective for pain relief . By the fourth week they provide similar relief , but beyond that viscosupplementation appears to provide greater pain reduction . The delayed onset of symptomatic improvement combined with reports of reactive synovitis may discourage physicians and patients . Questions / Purpose sWe therefore addressed three questions : Does the addition of triamcinolone to viscosupplementation ( 1 ) improve first-week pain and function compared with viscosupplementation alone , ( 2 ) diminish adverse effects of viscosupplementation alone , and ( 3 ) alter 6-month pain and function of viscosupplementation alone ? Methods We prospect ively enrolled 104 patients with knee osteoarthritis and r and omized them to receive either a single intraarticular injection ( 6 mL ) of hylan GF-20 ( Group viscosupplementation [ Group VS ] ) , or a single intraarticular injection of hylan GF-20 ( 6 mL ) and 1 mL ( 20 mg ) of triamcinolone hexacetonide ( Group VS + T ) . VAS , WOMAC ™ , and Lequesne question naires were completed at baseline and at Weeks 1 , 4 , 12 , and 24 . Results At Week 1 the WOMAC and VAS scores were lower in Group VS + T , compared with Group VS . There was no difference regarding the adverse effects . At Weeks 4 , 12 , and 24 there were no differences in the groups . Conclusions The addition of triamcinolone hexacetonide improves first-week symptom and functional scores of viscosupplementation , but not beyond . It does not seem to increase the likelihood of adverse effects . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Introduction : Primary therapeutic aim in treatment of osteoarthritis of the knee is to relieve the pain of osteoarthritis . The aim of this study was to compare the efficacy of intra-articular triamcinolone with intra-articular morphine in pain relief due to osteoarthritis of the knee in the elderly population . Material s and Methods : Patients between 50 and 80 years of age were r and omized into three groups . Group M received morphine plus bupivacaine intra-articularly , Group T received triamcinolone plus bupivacaine intra-articularly , and Group C received saline plus bupivacaine intra-articularly . Patients were evaluated before injection and in 2nd , 4th , 6th , and 12th weeks after injection . First-line supplementary analgesic was oral paracetamol 1500 mg/day . If analgesia was insufficient with paracetamol , oral dexketoprofen trometamol 50 mg/day was recommended to patients . Results : After the intra-articular injection , there was statistically significant decrease in visual analog scale ( VAS ) scores in Groups M and T , when compared to Group C. The decrease of VAS scores seen at the first 2 weeks continued steadily up to the end of 12th week . There was a significant decrease in Groups M and T in the WOMAC scores , when compared to Group C. There was no significant difference in the WOMAC scores between morphine and steroid groups . Significantly less supplementary analgesics was used in the morphine and steroid groups . Conclusion : Intra-articular morphine was as effective as intra-articular triamcinolone for analgesia in patients with osteoarthritis knee . Intra-articular morphine is possibly a better option than intra-articular steroid as it has lesser side effects |
12,684 | 28,762,235 | Beyond eight hours postintervention , serum bilirubin was similar between the two groups .
AUTHORS ' CONCLUSIONS There is no evidence that IV fluid supplementation affects important clinical outcomes such as bilirubin encephalopathy , kernicterus , or cerebral palsy in healthy , term newborn infants with unconjugated hyperbilirubinaemia requiring phototherapy .
In this review , no infant developed these bilirubin-associated clinical complications .
Low- to moderate- quality evidence shows that there are differences in total serum bilirubin levels between fluid-supplemented and control groups at some time points but not at others , the clinical significance of which is uncertain .
There is no evidence of a difference between the effectiveness of IV and oral fluid supplementations in reducing serum bilirubin .
Similarly , no infant developed adverse events or complications from fluid supplementation such as vomiting or abdominal distension . | BACKGROUND Neonatal hyperbilirubinaemia is a common problem which carries a risk of neurotoxicity .
Certain infants who have hyperbilirubinaemia develop bilirubin encephalopathy and kernicterus which may lead to long-term disability .
Phototherapy is currently the mainstay of treatment for neonatal hyperbilirubinaemia .
Among the adjunctive measures to compliment the effects of phototherapy , fluid supplementation has been proposed to reduce serum bilirubin levels .
The mechanism of action proposed includes direct dilutional effects of intravenous ( IV ) fluids , or enhancement of peristalsis to reduce enterohepatic circulation by oral fluid supplementation .
OBJECTIVES To assess the risks and benefits of fluid supplementation compared to st and ard fluid management in term and preterm newborn infants with unconjugated hyperbilirubinaemia who require phototherapy . | OBJECTIVE : Bronchopulmonary dysplasia ( BPD ) is the focus of many intervention trials , yet the outcome measure when based solely on oxygen administration may be confounded by differing criteria for oxygen administration between physicians . Thus , we wished to define BPD by a st and ardized oxygen saturation monitoring at 36 weeks corrected age , and compare this physiologic definition with the st and ard clinical definition of BPD based solely on oxygen administration . METHODOLOGY : A total of 199 consecutive very low birthweight infants ( VLBW , 501 to 1500 g birthweight ) were assessed prospect ively at 36±1 weeks corrected age . Neonates on positive pressure support or receiving > 30 % supplemental oxygen were assigned the outcome BPD . Those receiving ≤30 % oxygen underwent a stepwise 2 % reduction in supplemental oxygen to room air while under continuous observation and oxygen saturation monitoring . Outcomes of the test were “ no BPD ” ( saturations ≥88 % for 60 minutes ) or “ BPD ” ( saturation < 88 % ) . At the conclusion of the test , all infants were returned to their baseline oxygen . Safety ( apnea , bradycardia , increased oxygen use ) , inter-rater reliability , test – retest reliability , and validity of the physiologic definition vs the clinical definition were assessed . RESULTS : A total of 199 VLBW were assessed , of whom 45 ( 36 % ) were diagnosed with BPD by the clinical definition of oxygen use at 36 weeks corrected age . The physiologic definition identified 15 infants treated with oxygen who successfully passed the saturation monitoring test in room air . The physiologic definition diagnosed BPD in 30 ( 24 % ) of the cohort . All infants were safely studied . The test was highly reliable ( inter-rater reliability , κ=1.0 ; test – retest reliability , κ=0.83 ) and highly correlated with discharge home in oxygen , length of hospital stay , and hospital readmissions in the first year of life . CONCLUSIONS : The physiologic definition of BPD is safe , feasible , reliable , and valid and improves the precision of the diagnosis of BPD . This may be of benefit in future multicenter clinical trials OBJECTIVE To determine whether an earlier observation , that infants fed a casein-hydrolysate formula ( Nutramigen ) have lower neonatal jaundice levels than those fed st and ard formulas , would be repeated in a larger independent group of infants with more frequent measurements and more rigorous statistical analysis . DESIGN Newborn infants were fed human milk , a st and ard whey-predominant formula ( Enfamil ) , or Nutramigen ( n = 20 for each group ) during the first 3 weeks of life . Transcutaneous jaundice index was measured daily for the first week of life and every 2 to 3 days thereafter , using a noninvasive jaundice meter . Linear regression models of the data were constructed , vali date d , and compared statistically . SETTING General community hospital with subsequent home visitation . PARTICIPANTS Healthy , term newborn infants selected by convenience , based on time of birth . INTERVENTION Infants were exclusively fed human milk , Enfamil , or Nutramigen . Formulas were r and omly assigned . MAIN OUTCOME MEASURE Jaundice index , a transcutaneous measurement of jaundice . RESULTS The jaundice index differed significantly among the 3 groups . Paired comparisons showed that the jaundice index of the Nutramigen group was significantly lower than that of the Enfamil group ( on days 6 - 16 ) and the human milk group ( on days 3 - 20 ) . The jaundice index of the Enfamil-fed group was significantly lower than that of the human milk group on days 13 to 19 . CONCLUSIONS Jaundice levels are lower in neonates fed Nutramigen rather than Enfamil and both these groups have lower jaundice levels than breast-fed infants OBJECTIVE To evaluate the effectiveness of fluid supplementation in decreasing the rate of exchange transfusion and the duration of phototherapy in term neonates with severe nonhemolytic hyperbilirubinemia . STUDY DESIGN This was a r and omized controlled trial conducted in a tertiary care referral unit in northern India . Seventy-four term neonates with severe nonhemolytic hyperbilirubinemia ( total serum bilirubin > 18 mg/dL [ 308 micromol/L ] to < 25 mg/dL [ 427 micromol/L ] ) . The subjects were r and omized to an " extra fluids " group ( intravenous fluid supplementation for 8 hours and oral supplementation for the duration of phototherapy ; n = 37 ) or a control group ( n = 37 ) . RESULTS At inclusion , 54 infants ( 73 % ) had high serum osmolality , including 28 ( 75 % ) in the extra fluids group and 26 ( 70 % ) in the control group . The proportion of infants who underwent exchange transfusion was lower in the extra fluids group than in the control group : 6 ( 16 % ) versus 20 (54%)(P = .001 ; relative risk = 0.30 ; 95 % confidence interval = 0.14 to 0.66 ) . The duration of phototherapy was also shorter in the extra fluids group : 52 + /- 18 hours versus 73 + /- 31 hours ( P = .004 ) . CONCLUSION Fluid supplementation in term neonates presenting with severe hyperbilirubinemia decreased the rate of exchange transfusion and duration of phototherapy OBJECTIVE To compare the effectiveness of two methods of vascular access in newborns . DESIGN R and omized controlled trial . SETTING Neonatal intensive care unit in Regional Hospital of Valdivia , Chile . PARTICIPANTS Seventy-four high-risk newborns . INTERVENTIONS Peripherally inserted central catheter and peripheral intravenous catheter . MAIN OUTCOME MEASURES Length of neonatal intensive care unit stay and incidence of sepsis and phlebitis . RESULTS / DATA ANALYSIS : There were no statistically significant differences in the length of the neonatal intensive care unit stay and in the incidence of sepsis between groups . There was a significant higher incidence of phlebitis in the peripheral intravenous catheter group . CONCLUSIONS Although there was not a significant effect of the kind of catheter on length of neonatal intensive care unit stay , the peripherally inserted central catheter is recommended because of the decreased risk of phlebitis and the decreased number of venipuncture attempts and catheters needed to complete intravenous therapy Abstract Background : This study compared the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy . Methods : A r and omized controlled study was carried out in the neonatal intensive care unit of Zeynep Kamil Maternity and Children Hospital ( Istanbul , Turkey ) over a 4-month period . Two hundred fifty healthy term infants with hyperbilirubinemia were r and omized to receive either solely breastmilk ( n=125 ) or both breastmilk and intravenous fluid ( n=125 ) during phototherapy . Results : There were no significant differences ( p>0.05 ) in the mean birth weight , mean gestastional age , modes of delivery , mean time of admission age , mean serum osmolality , and hematocrit and reticulocyte count between the two groups . Similarly , there was no significant difference ( p>0.05 ) in the mean indirect serum bilirubin level at the time of admission to the neonatal intensive care unit and at 4 , 8 , 12 , 24 , and 48 hours after commencement of phototherapy between the two groups . There was no significant difference ( p>0.05 ) in the mean duration of phototherapy or in the median duration of hospitalization between the two groups . Conclusions : Based on our results , intravenous fluid support has no effect on the rate of decrease in serum bilirubin and decrease in duration of phototherapy in healthy term newborns with no dehydratation . However , using the oral route avoided the need for intravenous cannulae and their attendant complications . Insensible fluid loss is increased during phototherapy , so protection of hydration status with oral feeding is important for newborns OBJECTIVE Our purpose was to evaluate the effect of breast-feeding frequency on serum bilirubin levels in the first 3 days after birth . STUDY DESIGN Two hundred seventy-five infants were r and omly assigned to a frequent or dem and breast-feeding schedule . RESULTS Infants in the frequent group ( n = 131 ) nursed nine ( 7.5 to 10.5 ) times per day ( median and inner 80 % ) , and the dem and group ( n = 143 ) fed 6.5 ( 5.5 to 8.0 ) times per day . The serum bilirubin level was measured in all infants between 48 and 80 hours ( median 53 hours , inner 80 % 48 to 68 hours ) and was 7.4 ( 1.8 to 10.7 ) mg/dl in the frequent group and 8.0 ( 2.9 to 11.2 ) mg/dl in the dem and group ( p = 0.103 ) . There was no correlation between the frequency of breast-feeding and the serum bilirubin level . CONCLUSION Within the range of the frequency of nursing observed in this study , we could not demonstrate a significant effect on serum bilirubin levels in the first 3 days after birth We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well-baby nursery . The maximum serum bilirubin concentration exceeded 12.9 mg/dL ( 221 mumol/L ) in 147 infants ( 6.1 % ) , and these infants were compared with 147 r and omly selected control infants with maximum serum bilirubin levels less than or equal to 12.9 mg/dL. In 66 infants ( 44.9 % ) , we identified an apparent cause for the jaundice , but in 81 ( 55 % ) , no cause was found . Of infants for whom no cause for hyperbilirubinemia was found , 82.7 % were breast-fed v 46.9 % in the control group ( P less than .0001 ) . Breast-feeding was significantly associated with hyperbilirubinemia , even in the first three days of life . The 95th percentile for bottle-fed infants is a serum bilirubin level of 11.4 mg/dL v 14.5 mg/dL for the breast-fed population , and the 97th percentiles are 12.4 and 14.8 mg/dL , respectively . Of the formula-fed infants , 2.24 % had serum bilirubin levels greater than 12.9 mg/dL v 8.97 % of breast-fed infants ( P less than .000001 ) . When compared with previous large studies , the incidence of " readily visible " jaundice ( serum bilirubin level greater than 8 mg/dL ) appears to be increasing . The dramatic increase in breast-feeding in the United States in the last 25 years may explain this observation . There is a strong association between breast-feeding and jaundice in the healthy newborn infant . Investigations for the cause of hyperbilirubinemia in healthy breast-fed infants may not be indicated unless the serum bilirubin level exceeds approximately 15 mg/dL , whereas in the bottle-fed infant , such investigations may be indicated if the serum bilirubin exceeds approximately 12 mg/dL. ( ABSTRACT TRUNCATED AT 250 WORDS Objectives : To determine the incidence of severe hyperbilirubinaemia in the newborn , and to identify associated clinical and demographic variables , and short-term outcomes . Design : Prospect i ve , population -based study . Setting : UK and Republic of Irel and , between 1 May 2003 and 31 May 2005 . Participants : Infants in the first month of life with severe hyperbilirubinaemia ( maximum unconjugated serum bilirubin ⩾510 & mgr;mol/l ) . Results : 108 infants met the case definition , 106 from the UK and 2 from the Republic of Irel and . The UK incidence of severe hyperbilirubinaemia was 7.1/100 000 live births ( 95 % CI 5.8 to 8.6 ) . Only 20 cases presented in hospital ; 88 were admitted with severe jaundice . 64 ( 60.4 % ) cases were male , and 56 ( 51.8 % ) were of ethnic minority origin . 87 ( 80.5 % ) cases were exclusively breast fed . Co-morbidity included haemolysis , dehydration , infection and bruising . 14 infants showed evidence of bilirubin encephalopathy , of whom 3 died . The UK incidence of bilirubin encephalopathy was 0.9/100 000 live births ( 95 % CI 0.46 to 1.5 ) . Conclusions : This is the first large , prospect i ve , population -based study of the incidence of severe hyperbilirubinaemia in the newborn . The clinical and demographic associations , and short-term outcomes identified , are the same as those reported recently in North America and Europe Thirty to 50 % of very low-birth-weight infants have parenteral nutrition-associated cholestasis . To test the hypothesis that the incidence of cholestasis would be decreased if parenteral amino acids were avoided and protein given enterally , infants with a gestational age of less than 30 weeks were r and omized to two groups . One group received amino acid-free parenteral nutrition and whey protein enterally with added premature infant formula . The control group received st and ard parenteral nutrition with amino acids and enteral premature formula . At the end of 3 weeks of parenteral nutrition , infants who had a direct serum bilirubin level of greater than 3 mg/dl were considered to have significant cholestasis . Twenty-nine infants required parenteral nutrition for 3 weeks , 17 in the whey group and 12 in the control group . No instances of significant cholestasis were observed in the whey group ( 0/17 ) , whereas seven of 12 infants ( 58 % ) in the amino acid control group had cholestasis ( p less than 0.001 ) OBJECTIVE To evaluate the role of intravenous extra fluid therapy in accelerating the reduction of jaundice in newborns who received phototherapy . METHODS This study was performed on 100 terms , jaundiced neonates who had a total bilirubin of 18 mg/dl or more in the Pediatrics Ward of Ghaem Hospital , Mashhad , Iran from October 2007 to April 2008 . The patients were r and omly divided into 2 equal groups ; group I ( case group ) were given extra parenteral fluid besides breast feeding , and group II ( control group ) received only breast milk . The rate of bilirubin decrement , length of hospital stay , and rate of blood exchange were compared . RESULTS The rate of serum bilirubin decrease per hour in the first 12 hours after admission in group I ( 0.41 mg/dl [ 95%CI 0.1 ] versus 0.38 mg/dl in group II [ 95 % CI 0.3 ] , [ p=0.22 ] ) . It was 0.41 mg/dl for group I ( 95 % CI 0.0001 ) , and 0.21 mg/dl ( 95%CI 0.06 ) for group II in the second 12 hours ( p=0.02 ) . After 24 hours , it was 0.38 mg/dl in group I ( 95 % CI 0.0001 ) , and 0.29 mg/dl in group II ( 95 % CI=0.09 ) ( p=0.037 ) . The mean hospital stay was 68.5 hours in group I , and 67.4 hours in group II ( p=0.95 ) . CONCLUSION Additional parenteral fluid therapy in icteric newborns can accelerate reduction in serum bilirubin levels in the first 24 hours Thirty nine very low birthweight neonates ( with a birth weight of 820 to 1500 g and gestation of 27 to 34 weeks ) who required total parenteral nutrition were r and omly assigned to one of three regimens of administration of fat emulsion for a period of eight days . Groups 1 and 2 received the emulsion at a constant rate over 24 and 16 hours , respectively , beginning with a daily dosage of 1 g/kg and increasing daily by 1 g/kg to a maximum of 4 g/kg . Group 3 received the emulsion at a constant rate of 4 g/kg a day over 24 hours . Plasma concentrations of free fatty acids and serum concentrations of total bilirubin , apparent unbound bilirubin , and albumin were measured at regular intervals . Effects of the three regimens on serum bilirubin measurements were determined . The regimen of fat infusion and rate of infusion seemed to have no effect on serum concentrations of total and apparent unbound bilirubin , although there was a trend towards greater variability in apparent unbound concentrations with the intermittent regimen INTRODUCTION Neonatal hypernatermic dehydration ( NHD ) is a potentially very serious condition , which has been reported to occur in infants who have breast feeding problems in the first week of the life . This study looked at the incidence , risk factors , clinical symptoms and complications of NHD in healthy breastfed term neonates . METHODS A prospect i ve case-control study was conducted on 53 neonates with serum sodium concentrations of > or=150 mmol/L ( as the case group ) who were recruited between June 2006 and June 2007 from the Ghaem hospital ( Mashhad , Iran ) to investigate the relationship between NHD and breastfeeding . Fifty-three healthy breastfed full-term neonates ( serum sodium<150 mmol/L ) from the same hospital were also recruited as the control group . RESULT The results showed an average weight loss of 1.6 % in the healthy neonates vs. 16.2 % in infants with NHD ( p<0.001 ) . The frequency of feeds received per day was 10.2 for the healthy neonates vs. 7.6 in the NHD group ( p<0.001 ) . The NHD group had mothers who had a higher frequency of breast problems ( 23 vs. 7 , p<0.001 ) . Mean serum sodium concentration was significantly lower in the control group compared with the cases ( 137.80 vs.160.06 mmol/L , p<0.001 ) . The main presenting features of the infants with NHD were fever , lethargy and jaundice . CONCLUSION Breastfeeding problems are associated with the presence of NHD . Therefore , more breast examination during prenatal and postnatal periods and careful neonatal weight watch during the first week of life could decrease the incidence of NHD Background : This study was undertaken to investigate the effects of early parenteral nutrition on prevention of neonatal jaundice in term and near-term neonates who could not be enterally fed . Patients and Methods : Seventy-two infants were r and omized into 2 groups : the early parenteral nutrition group ( group 1 ) received 1.0 g/kg/d amino acids beginning within the first day and 1.0 g/kg/d lipid added the next day . The conventional nutrition group ( group 2 ) started on a solution containing 10 % glucose and electrolytes in the first 72 hours of life , followed by 0.5 g/kg/d amino acids and lipid . Amino acids and lipid were each increased by 0.5 g/kg/d to a maximum of 3.0 g/kg/d in both groups . Main outcome measures were energy intake ; serum bilirubin levels at 24 , 48 , and 72 hours ; need for phototherapy ; and duration of phototherapy . Results : Higher energy intake was achieved after the first day in group 1 . Daily serum bilirubin levels did not significantly differ between groups . Nine patients in each group required phototherapy . The initiation times of phototherapy were 92.9 hours ± 25.5 in group 1 and 83.1 hours ± 28.5 in group 2 . Duration s of phototherapy were 37.3 hours ± 11.1 in group 1 and 52.0 hours ± 20.7 in group 2 . There were no significant differences in the requirement , initiation time , and duration of phototherapy . Conclusions : Early parenteral nutrition has no proven benefit in terms of therapy requirement or severity and duration of neonatal jaundice compared with conventional parenteral nutrition in term and near-term infants who could not be enterally fed Serum bilirubin was higher in low birth weight neonates who were starved for the first 48 hours of life than in groups of those who , beginning at 4 hours of age , were fed water , glucose solution , or hypotonic sodium chloride solution with glucose . No difference in average bilirubin values was demonstrable between the groups of infants fed early . Therefore , neither the intake of salt nor of glucose is essential for the effect . The study suggests that lower serum bilirubin levels result from as little as 23 ml . per kilogram of water daily or from a physiologic process stimulated by feeding regardless of the material ingested . No relationship between blood glucose and bilirubin concentrations was apparent TEWL and skin hydration was measured in 7 body areas before and during phototherapy in 31 preterm infants ( gestational age 25 to 36 weeks ) . Each patient served as his/her own control . There was a mean increase of 26.4 % in TEWL during phototherapy . Most prominent increases were recorded in the cubital fossa ( 45.9 % ) , groin ( 36.4 % ) , and back ( 29 % ) . There were no significant differences in stratum corneum moisture in six of the seven body areas before and during phototherapy . This study provides a better underst and ing of skin physiology during phototherapy in preterm infants and has important implication s for the estimation of fluid replacement The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes This case-control study sought to determine whether rehospitalisation for jaundice in newborns is associated with the length of hospital stay after birth and to identify risk factors for and outcomes of rehospitalisation for jaundice . It was carried out among women who delivered a normal , term infant vaginally at any of 10 medical centres from 1992 to 1994 . Cases were infants rehospitalised with jaundice within 14 days of birth . Controls were r and omly selected from normal , term infants delivered vaginally but not rehospitalised within 90 days of birth . Maternal medical records for pregnancy , labour and delivery care , records for all the birth hospitalisations , and rehospitalisations for the cases were abstract ed . The length of birth hospitalisation did not differ between case and control infants , whether length was measured as a categorical variable or as a continuous measure ( median = 22.8 h for cases and 23.3 h for controls , P = 0.931 ) . Rehospitalisation for jaundice was associated with race/ethnicity , primiparity , preterm birth , breast feeding and suspicion of jaundice during the birth hospitalisation . None of the rehospitalised infants died , were diagnosed with kernicterus or required resuscitation . Attention to risks associated with jaundice rehospitalisation might reduce this undesirable , but not commonly severe , outcome In a prospect i ve r and omized trial , we studied the effects of early hypocaloric enteral feedings ( PO ) begun at 48 hours of age in 19 infants compared with 20 infants who received no enteral feedings ( NPO ) for at least the first 9 days of life . Both groups initially received the majority of their calories by parenteral alimentation . The groups were similar with respect to birth weight , gestational age , sex , Apgar score , and major neonatal diagnoses . The early enteral feeds proved to be significantly beneficial without an increased incidence of complications . The PO group reached full enteral feedings faster than the NPO group ( 31.2 vs 47.3 days ) . The PO group had a greater decline in serum bilirubin concentration over the first 2 weeks of life and spent less time under phototherapy ( 6.8 vs 9.5 days ) . Less cholestasis was observed among the PO infants ( 6.7 % vs 33 % ) , and peak direct bilirubin levels were also lower ( 0.7 vs 2.5 mg/dL ) . Osteopenia of prematurity , manifested by significantly lower alkaline phosphatase activity , was also decreased in the PO group , perhaps because of greater calcium intake during the first month among PO infants ( 1.3 vs 0.8 g ) . Compared with complete bowel rest , early onset of hypocaloric enteral feedings has beneficial effects on indirect hyperbilirubinemia , cholestatic jaundice , and metabolic bone disease of very low birth weight infants 200 mature healthy newborn infants ( birthweight 3382 + /- 377 g ) were r and omly divided into 2 groups of 100 each : all were breast fed according to the guidelines recommended by ' La Leche League ' . If possible breast feeding was commenced in the delivery room . When breast feeds did not suffice infants of group A were supplemented ad libitum with a fully adapted formula ( 67 kcal/dl ) , those of group B with a 13 % maltodextrine solution ( 52 kcal , 160 mOsm/l ) . Total fluid intake was similar in both groups . Group A took less supplementary feeds on day 2 , the caloric uptake , however , was not different from that of group B. On day 4 group A had a somewhat higher caloric uptake due to supplementation , whereas group B needed less supplementation but had a higher intake of breast milk . On day 5 all babies were entirely breast fed . No supplementation was h and ed over to the mothers for at home use . The frequency of breast meals and supplementary meals was almost equal for both groups , as were sucking activity , appetite and degree of saturation . 18.6 % of the infants in both groups had no need for any supplementary feeding at all . Temperature , stools , weight loss , blood glucose and bilirubin ( taken on day 4 simultaneously with the Guthrie test ) were almost identical . The red blood cell count showed slightly higher values in group A. Supplementation with fully adapted formula was not advantageous over supplementation with 13 % maltodextrine solution . The latter was , indeed , tolerated well in all cases and satisfied all infants who remained hungry after being breast fed ; additional early exposure to cow-milk protein was , thus , avoided in all these cases |
12,685 | 24,092,529 | contract referral , 4 .
Where measured , there was no statistical evidence of differences in the incidence of adverse effects between PN strategies .
The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI .
When combining trials of STI causing urethritis or cervicitis , expedited partner therapy was more successful than simple patient referral for preventing re-infection of the index patient but was not superior to enhanced patient referral .
Expedited partner therapy interventions should include all components that were part of the trial intervention package .
There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy . | BACKGROUND Partner notification ( PN ) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection ( STI ) and the need to obtain treatment .
For the person ( index patient ) with a curable STI , PN aims to eradicate infection and prevent re-infection .
For sexual partners , PN aims to identify and treat undiagnosed STIs .
At the level of sexual networks and population s , the aim of PN is to interrupt chains of STI transmission .
For people with viral STI , PN aims to identify undiagnosed infections , which can facilitate access for their sexual partners to treatment and help prevent transmission .
OBJECTIVES To assess the effects of different PN strategies in people with STI , including human immunodeficiency virus ( HIV ) infection . | Background : Sexually transmitted disease ( STD ) , including AIDS , disproportionately affects African-American and Hispanic women . Goal : To evaluate efficacy of st and ard and enhanced ( addition of optional support groups ) gender- and culture-specific , small-group behavioral interventions , compared to interactive STD counseling , in high risk minority women for two years . Methods : Women with a non-viral STD were treated and enrolled in a r and omized trial . Follow-up screens and interviews occurred at 6 months , 1 year , 18 months ( short interview , optional exam ) and 2 years . The primary outcome was subsequent infection with chlamydia and /or gonorrhea . Secondary outcomes included risky sexual behaviors . We employed logistic regression based on intention-to-treat . Results : Data from 775 women were included ; the retention rate was 91 % . Adjusted infection rates were higher in the controls in Year 1 ( 26.8 % ) , Year 2 ( 23.1 % ) , and cumulatively ( 39.8 % ) than in the enhanced ( 15.4 % , P = 0.004 ; 14.8 % , P < 0.03 ; 23.7 % , P < 0.001 , respectively ) and st and ard ( 15.7 % , P = 0.006 ; 14.7 % , P = 0.03 ; 26.2 % , P < 0.008 , respectively ) intervention arms at these time points . Enhanced-intervention women who opted to attend support groups ( attendees ) had the lowest adjusted infection rates in Year 1 ( 12.0 % ) and cumulatively ( 21.8 % ) . Intervention women in general , but particularly attendees , were significantly less likely than controls to have repeat infections . Multiple partners and unprotected sex with an untreated or incompletely treated partner helped explain group differences in infection . Conclusions : Risk-reduction interventions significantly decreased both single and multiple infective episodes with chlamydia and /or gonorrhea and risky sexual behaviors in the two-year study period . Support-group attendance appeared to contribute additional risk reduction in Year 1 OBJECTIVES We sought to assess the effectiveness of approaches targeting improved sexually transmitted infection ( STI ) sexual partner notification through patient referral . METHODS From January 2002 through December 2004 , 600 patients with Neisseria gonorrhoeae or Chlamydia trachomatis were recruited from STI clinics and r and omly assigned to either a st and ard-of-care group or a group that was counseled at the time of diagnosis and given additional follow-up contact . Participants completed an interview at baseline , 1 month , and 6 months and were checked at 6 months for gonorrhea or chlamydial infection via nucleic acid amplification testing of urine . RESULTS Program participants were more likely to report sexual partner notification at 1 month ( 86 % control , 92 % intervention ; adjusted odds ratio [ AOR ] = 1.8 ; 95 % confidence interval [ CI ] = 1.02 , 3.0 ) and were more likely to report no unprotected sexual intercourse at 6 months ( 38 % control , 48 % intervention ; AOR = 1.5 ; 95 % CI = 1.1 , 2.1 ) . Gonorrhea or chlamydial infection was detected in 6 % of intervention and 11 % of control participants at follow-up ( AOR = 2.2 ; 95 % CI = 1.1 , 4.1 ) , with greatest benefits seen among men ( for gender interaction , P = .03 ) . CONCLUSIONS This patient-based sexual partner notification program can help reduce risks for subsequent STIs among urban , minority patients presenting for care at STI clinics The objective of this study was to determine acceptability and feasibility of patient-based partner referral ( PBPR ) and patient-delivered partner medication ( PDPM ) among female sexually transmitted infection ( STI ) patients in a community-based STI screening study . Women were r and omized to STI screening at home or at a clinic . STI patients could choose between PBPR and PDPM . Six-week follow-up interviews , and in-depth interviews , were conducted . STI prevalence was high . Most of the 106 women with an STI chose PDPM , mainly because partners would not have time or would not want to attend a clinic , and to ensure that partners received treatment . Nearly all partners reportedly took medication ( 94 ; 89 % took it in front of the woman ) or went to a clinic for treatment ( 92 % ) . No adverse events were reported . Good communication emerged as the key to successful partner notification . In conclusion , PDPM could be used as a strategy to improve STI treatment coverage Background : Expedited partner therapy ( EPT ) has been shown to reduce the risk of persistent or recurrent gonorrhea and chlamydial infection in heterosexuals , and to increase the proportion of sex partners receiving treatment . The objective of this analysis was to evaluate the consistency of EPT 's effect across sociodemographic and behavioral subgroups . Methods : Subset analyses from a r and omized controlled trial compared EPT to st and ard partner referral ( SPR ) in sociodemographic and behaviorally defined subgroups . Outcomes included persistent or recurrent infection in study participants and participants ' report that their partners received treatment . Results : Reinfection risk was lower among EPT recipients than nonrecipients in 21 of 22 subgroups , with relative risks ( RRs ) varying from 0.4 to 0.94 . Compared to persons receiving SPR , persons receiving EPT were more likely to report that their partners were very likely to have been treated in 33 of 34 subgroups ( RRs range , 1.03 - 1.36 ) . Although EPT reduced the risk of persistent or recurrent infection somewhat more in men ( RR , 0.56 ; 95 % CI , 0.3 - 1.08 ) than in women ( RR , 0.81 ; 95 % CI , 0.61 - 1.07 ) and more in persons with gonorrhea ( RR , 0.32 ; 95 % CI , 0.13 - 0.78 ) than those with chlamydial infection ( RR , 0.82 ; 95 % CI , 0.63 - 1.07 ) , the RR of partners being treated associated with EPT was similar in men ( RR , 1.21 ; 95 % CI , 1.05 - 1.39 ) and women ( RR , 1.18 ; 95 % CI , 1.10 - 1.27 ) , and also in persons with gonorrhea ( RR , 1.33 ; 95 % CI , 0.80 - 2.23 ) and chlamydial infection ( RR , 1.33 ; 95 % CI , 1.07 - 1.66 ) . Conclusions : In this study , EPT is shown to be superior to SPR across a wide spectrum of sociodemographic and behaviorally defined subgroups Background Repeated infection with Chlamydia trachomatis increases the risk for serious sequelae : pelvic inflammatory disease , ectopic pregnancy , infertility , and chronic pelvic pain . A substantial proportion of women treated for C trachomatis infection are reinfected by an untreated male sex partner in the first several months after treatment . Effective strategies to ensure partner treatment are needed . Goal The goal of the study was to determine whether repeated infections with C trachomatis can be reduced by giving women doses of azithromycin to deliver to male sex partners . Study Design A multicenter r and omized controlled trial was conducted among 1787 women aged 14 to 34 years with uncomplicated C trachomatis genital infection diagnosed at family planning , adolescent , sexually transmitted disease , and primary care clinics or emergency or other hospital departments in five US cities . Women treated for infection were r and omized to one of two groups : patient-delivered partner treatment ( in which they were given a dose of azithromycin to deliver to each sex partner ) or self-referral ( in which they were asked to refer their sex partners for treatment ) . The main outcome measure was C trachomatis DNA detected by urine ligase chain reaction ( LCR ) or polymerase chain reaction ( PCR ) by 4 months after treatment . Results The characteristics of study participants enrolled in each arm were similar except for a small difference in the age distribution . Risk of reinfection was 20 % lower among women in the patient-delivered partner treatment arm ( 87/728 ; 12 % ) than among those in the self-referral arm ( 106/726 ; 15 % ) ; however , this difference was not statistically significant ( odds ratio , 0.80 ; 95 % confidence interval , 0.62–1.05;P = 0.102 ) . Women in the patient-delivered partner treatment arm reported high compliance with the intervention ( 82 % ) . Conclusion Patient-delivered partner treatment for prevention of repeated C trachomatis infection among women is comparable to self-referral and may be an appropriate option for some patients OBJECTIVES To determine the effectiveness of an intervention for pharmacy workers in improving their recognition and management of sexually transmitted disease ( STD ) syndromes . METHODS We r and omly selected 14 districts ( total population nearly 4 million ) from the 24 districts of low socioeconomic status in Lima , Peru . We r and omly assigned paired districts to receive training and support for management and prevention of STDs or a control intervention about management of diarrhoea . The STD intervention included interactive luncheon seminars on recognition and management of four STD syndromes ( urethral discharge , vaginal discharge , genital ulcers , and pelvic inflammatory disease ) and STD/HIV prevention counselling ; monthly pharmacy visits by " prevention salespersons " who distributed material s that included " STD/HIV prevention packets " containing information , condoms , and cards given to patients for referral of their sex partners ; and workshops for physicians on managing patients with STD syndromes referred from pharmacies . St and ardized simulated patients visited pharmacies in intervention and control districts at one , three , and six months after training to assess outcomes . FINDINGS St and ardized simulated patients reported significantly better recognition and management ( appropriate antimicrobial regimens provided for discharge syndromes and referral to specially trained physicians for genital ulcers or pelvic inflammatory disease ) by pharmacy workers of all four STD syndromes . They also reported significantly more frequent recommendations for use of condoms and treatment of partners at pharmacies in intervention districts than in control districts ( by " intention-to-train " analyses , P<0.05 for 47/48 primary outcome comparisons ) . CONCLUSION Training was feasible and effectively improved pharmacy workers ' practice BACKGROUND We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus ( HIV ) or persons who had shared needles with them ( needle-sharing partners ) : " patient referral , " in which the responsibility for notifying partners was left to the patient , and " provider referral , " in which providers attempted to notify partners . METHODS Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina . The subjects were r and omly assigned to a patient-referral group ( in which patients had the initial responsibility for notifying their partners ) or a provider-referral group ( in which the study counselor notified the partners ) . The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department . RESULTS Of 534 HIV-positive persons identified at the health departments , 247 ( 46 percent ) did not return for counseling after the test , 8 were counseled outside the study , and 117 ( 22 percent ) were ineligible . Of the 162 invited to participate , 88 ( 54 percent ) declined and 74 ( 46 percent ) agreed . The subjects were mostly male ( 69 percent ) , black ( 87 percent ) , homosexual or bisexual ( 76 percent of the men ) , and had a median age of 30 years . Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group . In the provider-referral group 78 of 157 partners ( 50 percent ) were successfully notified , whereas in the patient-referral group only 10 of 153 ( 7 percent ) were notified . Of the partners notified by the counselors , 94 percent were not aware that they had been exposed to HIV . Overall , 23 percent of the partners notified and tested were HIV-positive . CONCLUSIONS In this trial , leaving the notification of partners up to the subjects ( patient referral ) was quite ineffective , despite the North Carolina law requiring that partners be notified . Partner notification by public health counselors ( provider referral ) was significantly more effective . Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients , counselors who notify the partners of an infected patient can refer them to educational , medical , and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior Background : Screening has been recommended to reduce the prevalence and morbidity associated with genital chlamydia infection in the United Kingdom . Methods : We describe the rationale and study design of the Chlamydia Screening Studies ( ClaSS ) , a collaborative project design ed to evaluate screening outside genitourinary medicine clinics . A non-selective , active screening approach in 16–39 year olds r and omly sample d from 27 general practice lists in the Bristol and Birmingham areas formed the basis of interlinked studies : a case-control study was used to investigate factors to improve the targeting of screening ; participants with chlamydia were invited to enrol in a r and omised controlled trial to evaluate partner notification conducted in primary care ; and laboratory based studies were used to assess the best specimens and tests . We also explored psychosocial effects of screening and partner notification and modelled the cost effectiveness of the programme . Conclusion : Results from four pilot practice s show that mailing of specimens for chlamydia testing is feasible but that it is difficult to achieve high response rates with postal screening . The high prevalence of asymptomatic infection in men suggests that efforts to screen men for chlamydia should be strengthened Objectives To assess the impact of computer-assisted interview compared with pen and paper on disclosure of sexual behaviour , diagnostic testing by clinicians , infections diagnosed and referral for counselling . Methods Two-centre parallel three-arm r and omised controlled open trial . Computer-generated r and omisation with allocation concealment using sealed envelopes . Setting Two London teaching hospital sexual health clinics . Participants 2351 clinic attenders over the age of 16 years . Interventions Computer-assisted self-interview ( CASI ) . Computer-assisted personal interview ( CAPI ) . Pen and paper interview ( PAPI ) . Main Outcome Measures Diagnostic tests ordered , sexually transmitted infections ( STI ) . Secondary Outcomes Disclosure of sexual risk , referral for counselling . Results 801 , 763 and 787 patients r and omly allocated to receive CASI , CAPI and PAPI . 795 , 744 and 779 were available for intention-to-treat analysis . Significantly more diagnostic testing for hepatitis B and C and rectal sample s in the CAPI arm ( odds for more testing relative to PAPI 1.32 ; 95 % CI 1.09 to 1.59 ) . This pattern was not seen among CASI patients . HIV testing was significantly lower among CASI patients ( odds for less testing relative to PAPI 0.73 ; 95 % CI 0.59 to 0.90 ) . STI diagnoses were not significantly different by trial arm . A summary measure of seven prespecified sensitive behaviours found greater reporting with CASI ( OR 1.4 ; 95 % CI 1.2 to 1.6 ) and CAPI ( OR 1.4 ; 95 % CI 1.2 to 1.7 ) compared with PAPI . Conclusion CASI and CAPI can generate greater recording of risky behaviour than traditional PAPI . Increased disclosure did not increase STI diagnoses . Safeguards may be needed to ensure that clinicians are prompted to act upon disclosures made during self-interview . Trial registration IS RCT N : 97674664 BACKGROUND The aim of this study was to determine whether postal testing kits ( PTKs ) or patient-delivered partner therapy ( PDPT ) for partners of women with Chlamydia trachomatis reduce re-infection rates in women , compared with partner notification by patient referral . METHODS Three hundred and thirty women testing positive for chlamydia , at clinics for genitourinary medicine , family planning and termination of pregnancy in Edinburgh , were r and omized to one of three partner interventions : patient referral , PTK ( partners post urine for testing ) or PDPT ( 1 g azithromycin for partners ) . Women su bmi tted urine for chlamydia testing every 3 months . The primary outcome was re-infection assessed as time to first positive result by the Cox proportional hazard regression . The proportion of partners tested or treated with each intervention was determined . RESULTS Out of 330 women , 215 ( 65 % ) were retested over 12 months . There were 32 of 215 women ( 15 % ) who retested positive ( 7 , 15 and 10 women from the patient referral , PTK and PDPT groups , respectively ) . There was no significant difference in re-infection between PDPT versus patient referral ( HR 1.32 , 95 % CI 0.50 - 3.56 ) , PTK versus patient referral ( HR 2.35 , 95 % CI 0.94 - 5.88 ) or PDPT versus PTK ( HR 0.55 , 95 % CI 0.24 - 1.24 ) . There was no significant difference in the proportion of partners confirmed tested/treated between the patient referral ( 34 % ) and PTK ( 41 % , P = 0.32 ) or PDPT ( 42 % , P = 0.28 ) groups . CONCLUSIONS PTK and PDPT do not reduce re-infection rates in women with chlamydia compared with patient referral . However , PDPT may offer other advantages such as simplicity and cost compared with patient referral Background : The efficacy of patient-delivered partner therapy ( PDPT ) and inSPOT , a web-based partner notification service , in increasing partner treatment and /or notification among men who have sex with men ( MSM ) has not been evaluated . Methods : We enrolled MSM with chlamydia and /or gonorrhea in a r and omized , controlled trial with the following 4 arms : inSPOT , PDPT , combined inSPOT and PDPT ( inSPOT/PDPT ) , and st and ard partner management . Men were offered enrollment when contacted for partner services . Participants completed baseline and follow-up interviews approximately 2 weeks apart . Results : We offered enrollment to 393 eligible MSM , of whom 75 ( 19 % ) enrolled and 318 ( 81 % ) declined enrollment . The study was halted early due to low enrollment . Among the 75 enrollees , 53 ( 71 % ) completed baseline and follow-up interviews . Of these 53 men , 13 , 10 , 17 , and 13 were assigned to the PDPT , inSPOT , inSPOT/PDPT , and st and ard arms , respectively ; participants provided information about 186 partners . The number of partners treated per original patient was 2.33 in the PDPT arm and 1.52 in the non-PDPT arms . PDPT assignment increased the mean number of partners treated per original patient by 54 % ( ratio of means = 1.54 , 95 % confidence interval : 1.01–2.34 ) , after adjustment for inSPOT assignment . Among 27 men assigned to inSPOT or inSPOT/PDPT , 1 ( 4 % ) used inSPOT to notify ≥1 partner . inSPOT did not affect partner notification , but decreased partner human immunodeficiency virus testing ( ratio of means : 0.42 , 95 % confidence interval : 0.18–0.99 ) . Conclusions : PDPT may increase partner treatment among MSM . Few MSM appear to be willing to use inSPOT to notify their sex partners . Traditional r and omized trials of partner notification strategies may not be feasible among MSM Objectives : To evaluate the effectiveness and cost effectiveness of syndromic sexually transmitted infection ( STI ) packages on appropriate treatment and preventive management during primary care consultations . Methods : Cluster r and omised trial of 37 Durban primary care clinics r and omised to use syndromic packages ( containing antibiotics , condoms , partner notification cards , and written information ) or not . We assessed outcomes using simulated patients who reported STI symptoms and recorded how they were managed , before and after implementation ( 269 and 256 simulated patient consultations ) . We adjusted for baseline values and intra-clinic correlation of outcomes statistically . We used health department information to estimate the extra re sources needed to provide the packages to 20 clinics for 1 year and their costs . Results : Simulated patients in intervention clinics were more likely to receive appropriate syndromic STI management ( correct treatment plus condoms offered plus partner notification cards offered ; prevalence rate ratio 2.3 ; 95 % confidence intervals ( CI ) 1.6 to 3.0 ) and to receive more STI advice and information ( odds ratio 1.5 ; 95 % CI 1.01 to 2.1 ) . Women were less likely to receive appropriate syndromic STI management . The intervention increased STI information provision in women more than in men . The extra cost per extra patient appropriately managed was $ 1.51 . Conclusions : Syndromic packages improved syndromic STI management at a reasonable cost and should be used more widely OBJECTIVE This analysis describes the Outreach-Assisted Model of Partner Notification , an innovative strategy for encouraging seropositive injecting drug users ( IDUs ) to inform their partners of shared human immunodeficiency virus ( HIV ) exposure . The analysis focuses on two core components of the notification process : the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus . METHODS Using community outreach techniques , 386 IDUs were recruited for HIV pretest counseling , testing , and partner notification over a 12-month period . Of these , 63 tested HIV seropositive , and all but three returned for their test results . The 60 who were informed of their serostatus were r and omly assigned to either a minimal or an enhanced intervention condition . Participants assigned to the minimal ( self-tell ) group were strongly encouraged to inform their partners of possible exposure . Those assigned to the enhanced ( outreach-assisted ) group had the option of either informing one or more of their partner(s ) themselves or choosing to have the project 's outreach team do so . RESULTS Together , the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years . By itself , drug use accounted for half of all partners named . Sexual behavior alone accounted for 25 % of named partners . Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner ; the team was requested to notify 71 % of the total number of partners whom this group named . CONCLUSIONS Findings suggest that IDUs want to notify their partners of shared HIV exposure . Outreach assistance was the preferred mode in the majority of cases . Exp and ing traditional community-based HIV outreach activities to include delivering street-based counseling , test , a partner notification appears to be a positive and workable prevention strategy BACKGROUND Interventions to treat STDs have been reported to reduce HIV incidence . Interventions to improve treatment-seeking for STDs may impact on the duration and prevalence of STDs . Nigeria has high rates of STDs and an increasing incidence of HIV . OBJECTIVE To evaluate the impact of an intervention on STD treatment-seeking behavior and STD prevalence among Nigerian youth . METHODS A r and omized controlled trial in 12 schools in Edo State was conducted to evaluate an intervention to improve STD treatment-seeking and STD treatment provision . The intervention , based on formative research , consisted of community participation , peer education , public lectures , health clubs in the schools , and training of STD treatment providers , including those with no formal training . A question naire measured outcomes before and 10 months into the intervention . The effect of the intervention among four r and omly selected intervention schools compared to eight r and omly selected control schools was assessed using logistic regression with Huber 's formula to account for school clusters . RESULTS One thous and eight hundred and ninety-six and 1858 youths 14 - 20 years of age were enrolled in the pre- and post-intervention surveys . Youths in the intervention schools , compared to control schools , reported statistically significant improvements in knowledge of STDs , condom use , partner awareness that the youth had an STD , and STD treatment-seeking behavior . Treatment by private physicians increased ( OR=2.1 , 95 % CI=1.1 - 4.0 ) , and treatment by patent medicine dealers or pharmacists decreased ( OR=0.44 , 95 % CI=0.22 - 0.88 ) . The reported prevalence of STD symptoms in the past 6 months was significantly reduced in the intervention compared to control schools ( OR=0.68 , 95 % CI=0.48 - 0.95 ) . CONCLUSION Significant improvements in treatment-seeking for STD symptoms can be effected among Nigerian youths . The prevalence of reported STD symptoms can be decreased by improving treatment-seeking for and awareness of STDs Unlike contact-tracing procedures for syphilis and gonorrhea , field follow-up to locate and treat patients with Chlamydia trachomatis infections has not been extensively applied in the United States . We implemented two studies to assess the efficiency and cost-effectiveness of using field follow-up for contact of two groups : patients with chlamydial infection detected as part of a screening program and women who were sexual partners of men with nongonococcal urethritis ( NGU ) . Of the 142 patients with chlamydial infection who had not been treated empirically , 112 ( 79 % ) returned for treatment when a reminder system was used , as compared with a return rate of 97 % ( 259/266 ) achieved by field follow-up ( P less than 0.0001 ) . Among the 678 men with NGU enrolled in a r and omized trial of field follow-up vs. two self-referral methods , field follow-up yielded over three times as many partners returning to the clinic for treatment as did either of the other two methods ( P less than 0.001 ) . Analyses using the estimated costs of the intervention strategies and the medical costs associated with an untreated chlamydial infection showed that field follow-up by trained investigators proved to be not only the most efficient method for locating patients with chlamydial infection and /or patients who were at risk for it , but also the most cost-effective in terms of total health-care dollars spent BACKGROUND Traditional partner referral for sexually transmitted diseases ( STDs ) is ineffective at assuring that partners are treated . Alternative methods are needed . We sought to determine whether patient-delivered partner treatment ( PDPT ) is better than 2 different methods of partner referral in providing antibiotic treatment to sex partners of men with urethritis and in reducing recurrence of Chlamydia trachomatis and Neisseria gonorrhoeae . METHODS Men who received a diagnosis of urethritis at a public STD clinic in New Orleans , Louisiana , during the period of December 2001 through March 2004 were r and omly assigned according to the month of treatment for either st and ard partner referral ( PR ) , booklet-enhanced partner referral ( BEPR ) , or PDPT . At baseline and after 1 month , men were asked to provide information about each partner and were tested for C. trachomatis and N. gonorrhoeae . RESULTS Most enrolled index men ( n = 977 ) were > 24 years of age ( 51.6 % ) and African American ( 95 % ) and had > or = 2 partners ( 68.3 % ) . They reported information on 1991 partners , and 78.8 % were reinterviewed 4 - 8 weeks later . Men in the PDPT arm were more likely than men in the BEPR and PR arms to report having seen their partners , having talked to their partners about the infection , having given the intervention to their partners , and having been told by their partners that the antibiotic treatment had been taken ( 55.8 % , 45.6 % , and 35.0 % , respectively ; P < .001 ) . Of men who were reinterviewed , 37.5 % agreed to follow-up testing for N. gonorrhoeae and C. trachomatis infection . Those tested were similar to those not tested with regard to the study variables measured . Among those tested , men in the PDPT and BEPR arms were less likely than those in the PR arm to test positive for C. trachomatis and /or N. gonorrhoeae ( 23.0 % , 14.3 % , and 42.7 % , respectively ; P < .001 ) . CONCLUSION Among heterosexual men with urethritis , PDPT was better than st and ard partner referral for treatment of partners and prevention of recurrence of C. trachomatis or N. gonorrhoeae infection Background : Sexual partners of persons with newly diagnosed HIV infection require HIV counseling , testing and , if necessary , evaluation for therapy . However , many African countries do not have a st and ardized protocol for partner notification , and the effectiveness of partner notification has not been evaluated in developing countries . Methods : Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe , Malawi , were r and omized to 1 of 3 methods of partner notification : passive referral , contract referral , or provider referral . The passive referral group was responsible for notifying their partners themselves . The contract referral group was given seven days to notify their partners , after which a health care provider contacted partners who had not reported for counseling and testing . In the provider referral group , a health care provider notified partners directly . Results : Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252 . Among locatable partners , 107 returned for HIV counseling and testing ; 20 of 82 [ 24 % ; 95 % confidence interval ( CI ) : 15 % to 34 % ] partners returned in the passive referral arm , 45 of 88 ( 51 % ; 95 % CI : 41 % to 62 % ) in the contract referral arm , and 42 of 82 ( 51 % ; 95 % CI : 40 % to 62 % ) in the provider referral arm ( P < 0.001 ) . Among returning partners ( n = 107 ) , 67 ( 64 % ) of were HIV infected with 54 ( 81 % ) newly diagnosed . Discussion : This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa . Active partner notification was feasible , acceptable , and effective among sexually transmitted infections clinic patients . Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners Background Public health partner notification ( PN ) services currently affect only a small minority of patients with gonorrhea or chlamydial infection and new approaches to PN are needed . Objectives To exp and PN for gonorrhea and chlamydial infection to private sector patients and to assess the feasibility of treating sex partners through commercial pharmacies . Methods Selected patients were offered PN assistance and were r and omly offered medication to deliver to their partners . Results Providers permitted the health department to contact 3613 ( 91 % ) of 3972 potentially eligible patients , and 1693 ( 67 % ) of 2531 successfully contacted patients consented to interview . Of these , 1095 ( 65 % ) reported at least one untreated partner . Most patients ( 90 % ) wished to notify partners themselves . Patients were more likely to have partners who had not yet been treated and to request PN assistance if they had more than one sex partner in the preceding 60 days or a partner they did not anticipate having sex with in the future . These two factors characterized 49 % of all patients interviewed , 70 % of those with a partner that was untreated 7 or more days after index patient treatment , and 83 % of those accepting PN assistance . Among 458 r and omly selected patients with untreated partners at time of study interview , 346 ( 76 % ) agreed to deliver treatment to a partner . Of these , most ( 266 ) chose to obtain medication for a partner at a pharmacy , of whom 223 ( 84 % ) successfully did so . Conclusion A substantial minority of private sector patients have untreated partners more than 7 days after their own treatment ; some need help with PN , but most will agree to deliver medication to partners themselves Urogenital infections with Chlamydia trachomatis are widespread and usually asymptomatic . Major complications from infection include ectopic pregnancies and female infertility.1 Although contact tracing reduces the prevalence of chlamydia infection,2 the test rate among partners is often low , partly because male contacts have to have a urethral swab taken by a doctor . As the polymerase chain reaction can successfully detect infection in urine sample s,3 we investigated whether the test rate could be increased by asking the male contacts of infected women to send a urine sample directly from home to a laboratory instead of having a doctor take a urethral swab . Ninety six women with C trachomati s infection seen in general practice s in Aarhus County , Denmark , were r and omly divided according to their date of birth into an intervention group ( 45 patients ) and a Objective : To determine the cost and effectiveness of three approaches to partner notification for infectious syphilis . Study Design : People with syphilis were r and omly assigned to : ( 1 ) notification of partners by patients themselves within 2 days or disease intervention specialists would notify them ; ( 2 ) immediate notification by intervention specialist ; or ( 3 ) immediate notification by intervention specialists , who had the option of drawing blood in the field . Costs of intervention specialists ' time , travel , and overhead were measured . Intention‐to‐treat analysis measured outcomes per r and omized index patient . Results : From December , 1990 through March , 1993 , 1,966 index patients with syphilis ( primary 9 % ; secondary 18 % ; and early latent 73 % ) were r and omized in Broward County ( Ft . Lauderdale ) , Florida ( 1,191 ) ; Tampa , Florida ( 569 ) ; and Paterson , New Jersey ( 206 ) . Index patients reported 11,272 potentially exposed partners and sufficient information to initiate investigations for 2,761 . Of these , 2,236 were located , 367 had newly identified infections , and 870 others received preventive treatment . The three partner notification approaches had similar success locating partners ( 1.1–1.2 per index patient ) and treating partners ( 0.61–0.67 per index ) . The cost was $ 317 to $ 362 per partner treated ; the optimal strategy differed by study site . Conclusions : Partner notification identified many infected and potentially infected people . The cost and effectiveness of the three types of provider notification were similar . Alternative approaches are needed to reach infected partners who could not be notified Abstract Objective To evaluate the effectiveness of a practice nurse led strategy to improve the notification and treatment of partners of people with chlamydia infection . Design R and omised controlled trial . Setting 27 general practice s in the Bristol and Birmingham areas . Participants 140 men and women with chlamydia ( index cases ) diagnosed by screening of a home collected urine sample or vulval swab specimen . Interventions Partner notification at the general practice immediately after diagnosis by trained practice nurses , with telephone follow up by a health adviser ; or referral to a specialist health adviser at a genitourinary medicine clinic . Main outcome measures Primary outcome was the proportion of index cases with at least one treated sexual partner . Specified secondary outcomes included the number of sexual contacts elicited during a sexual history , positive test result for chlamydia six weeks after treatment , and the cost of each strategy in 2003 sterling prices . Results 65.3 % ( 47/72 ) of participants receiving practice nurse led partner notification had at least one partner treated compared with 52.9 % ( 39/68 ) of those referred to a genitourinary medicine clinic ( risk difference 12.4 % , 95 % confidence interval −1.8 % to 26.5 % ) . Of 68 participants referred to the clinic , 21 ( 31 % ) did not attend . The costs per index case were £ 32.55 for the practice nurse led strategy and £ 32.62 for the specialist referral strategy . Conclusion Practice based partner notification by trained nurses with telephone follow up by health advisers is at least as effective as referral to a specialist health adviser at a genitourinary medicine clinic , and costs the same . Trial registration Clinical trials : NCT00112255 The objective of this research was to determine the factors associated with disclosure of three treatable sexually transmitted diseases ( STDs ) . Data were obtained from two intervention trials to determine the ideal means of partner referral . Men diagnosed with urethritis and women diagnosed with trichomoniasis at public clinics in New Orleans , Louisiana were r and omly assigned to partner referral ( PR ) , booklet-enhanced partner referral ( BEPR ) , or patient-delivered partner treatment ( PDPT ) . Participants were asked about sex partners at baseline , then whether they disclosed to them at follow-up . The male trial was conducted from December 2001 to March 2004 and the female trial from December 2001 to August 2004 . Data on men and women were analyzed separately . Nine hundred seventy-seven men and 463 women-reporting information on 1991 and 521 sex partners-were respectively enrolled in each trial . Disclosure occurred to 57.8 % and 87.3 % of their partners , respectively . Most men ( 68.3 % ) reported having two or more partners and disclosure was more likely to occur in : those who reported only one sex partner ( adjusted odds ratio [ aOR ] 95 % confidence interval [ CI ] : 1.54 [ 1.10 , 2.16 ] ) ; those in steady relationships ( OR [ 95 % CI ] : 1.37 [ 1.08,1.74 ] ) ; and those assigned PDPT [ OR [ 95 % CI ] : 2.71 [ 1.93,3.82 ] ) . Most women reported having only one partner ( 86.8 % ) and disclosure was more likely to occur in steady relationships ( OR [ 95 % CI ] : 2.65 [ 1.24,5.66 ] ) , and when sex was reinitiated with partners during the follow-up period ( OR [ 95 % CI ] : 3.30 [ 1.54,7.09 ] ) . The provision of PDPT was associated with increased STD disclosure among men but not among women . Both men and women were less likely to disclose to casual partners . Women had high rates of disclosure irrespective of intervention arm Objectives : Infections with Trichomonas vaginalis ( TV ) are common and recurrence rates are high . Better methods of treating partners of women with trichomoniasis are needed . Goal : To determine if patient-delivered partner treatment ( PDPT ) is better and more cost-effective than partner referral . Study Design : Women attending a family planning clinic who were culture-positive and treated for TV ( N = 463 ) were r and omized to either st and ard partner referral ( PR ) , booklet-enhanced partner referral ( BEPR ) , or PDPT . At baseline and 1 month , women were interviewed and cultured for TV . Detailed cost information was also collected . Results : Most women had 1 partner , were less than 24 years old , and were black . The percentage of women reporting that their partners were treated was similar for PDPT but significantly lower for BEPR compared to PR . TV follow-up rates were similar . PDPT cost less and was cost saving compared to PR and BEPR . Conclusion : Among women with TV , PDPT did not result in more partners taking the medicine or lower follow-up rates than PR but was less costly BACKGROUND Many sex partners of persons with gonorrhea or chlamydial infections are not treated , which leads to frequent reinfections and further transmission . METHODS We r and omly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or st and ard referral . Patients in the expedited-treatment group were offered medication to give to their sex partners , or if they preferred , study staff members contacted partners and provided them with medication without a clinical examination . Patients assigned to st and ard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners . The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment . RESULTS Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients ( 13 percent ) assigned to st and ard partner referral and 92 of 929 ( 10 percent ) assigned to expedited treatment of sexual partners ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ) . Expedited treatment was more effective than st and ard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea ( 3 percent vs. 11 percent , P=0.01 ) than in those with chlamydial infection ( 11 percent vs. 13 percent , P=0.17 ) ( P=0.05 for the comparison of treatment effects ) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up ( relative risk , 0.75 ; 95 percent confidence interval , 0.57 to 0.97 ) . Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to st and ard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner . CONCLUSIONS Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection This study was design ed to determine whether a better partner notification outcome could be achieved by giving female index patients with genital chlamydial infection a home sampling kit instead of contact slips only . Two hundred female patients attending a sexually transmitted infection clinic with a diagnosis of genital chlamydial infection were r and omized to either the conventional partner notification arm using contact slips ( swab testing arm ) or the urine sampling kit for partner notification arm ( urine testing arm ) . There were no differences in the number of partners treated per index case ( 0.67 in the swab testing group versus 0.62 in the urine testing group , P = 0.46 ) , the median number of traceable partners and the number of index patients with at least one partner treated within 28 days . The addition of a urine testing kit to contact slips for male partners of women with genital chlamydial infection did not increase the partner notification rates for genital chlamydial infection In this sexually transmitted infection ( STI ) prevention study , we compared the efficacy of the Well Woman Program ( WWP ) , a nurse practitioner-directed , culturally specific , intensive intervention , to minimal intervention ( MI ) , brief lecture , and referral to usual care , in a community-based r and omized controlled trial . African American women having past STIs and residing in high-risk communities were r and omly assigned to the two groups . STI outcome was measured at baseline and three later points . A r and om effects logistic longitudinal regression model showed that , at baseline , approximately 75 % of participants tested positive for an STI , predominantly trichomoniasis . At month 15 , the estimated probability of a WWP participant having an STI was 20 % less than an MI participant . Better STI outcomes were due to the intensive individualized intervention The primary outcome was to determine the acceptability of the Internet , specifically a website for use in st and ard partner notification . A secondary objective was to determine if a website would enhance the outcomes of currently used partner notification methods . In a r and omized control trial , 105 participants diagnosed with chlamydia and non-gonoccocal urethritis ( NGU ) were r and omized and 97 completed the study . About 30 % of participants were provided a st and ard partner letter and 70 % were provided the st and ard partner letter and website . All participants reported that their partners had no objections to the website ( 0 % , 95 % confidence interval [ CI ] 0–5 % ) . There were no complaints received from any partner . The odds ratio for contacting partners was not significantly different between the two groups of participants . The results of this study indicate that providing a website with specific information about the infection to which a partner has been exposed is not harmful The object of this study was to determine the factors associated with partner notification ( PN ) of sexually transmitted infection ( STI ) exposure among pregnant , low income , Mexican-American ( MA ) and African-American ( AA ) women and their male sexual partners . We used a cross-sectional analysis of 166 pregnant women with an STI , enrolled in a r and omized controlled trial of behavioural intervention to prevent recurrent STIs . The primary outcome , PN , is notification of , or intent to notify male sexual partner(s ) of STI exposure . Pregnant women with one ( n = 136 ) versus multiple ( n = 30 ) partners reported PN for 88.2 % and 54.5 % of male partners , respectively ( P < 0.001 ) . Multivariate logistic regression demonstrated three variables that independently predicted PN : a steady relationship , with one male sexual partner and recent ( < 30 days ) intercourse with the partner . Among the low income , pregnant MA and AA women , the three relationship variables predicted 81.6 % of PN and correctly classified 78.5 % of males notified and 65.7 % of males not notified Background Patient-based partner referral ( PBPR ) , which is the main method for treating sexual partners of patients with sexually transmitted diseases ( STDs ) , has limited effectiveness . Goal The authors compared the efficacy of PBPR with patient-delivered partner medication ( PDPM ) among patients attending the Mulago STD clinic in Kampala , Ug and a. Study Design A total of 383 patients ( 187 women , 196 men ) with STDs were r and omized to the PBPR or PDPM group . The proportion of sexual partners treated in either group was compared using the chi-square statistic by intention to treat for partners whose follow-up status was unknown . Results The two groups had similar background characteristics . Of the 237 partners elicited , 176 ( 74 % ) were reported treated in the PDPM group . In the PBPR group , in which 234 partners were elicited , 79 ( 34 % ) were referred to the treatment clinic . This difference was statistically significant ( risk ratio [ RR ] , 2.44 ; 95 % CI , 1.95–3.07;P < 0.001 ) . Furthermore , PDPM was more effective than PBPR for women and for casual partners for whom PBPR is considered difficult . For women , 86 of 103 partners in the PDPM group were reported treated , compared with 23 of 104 partners in the PBPR group ( RR , 4.55 ; 95 % CI , 2.92–7.08;P < 0.001 ) . For casual partners , 18 of 51 ( 34 % ) were reported treated in the PDPM group , compared with only three of 45 partners ( 7 % ) who were referred in the PBPR group ( RR , 1.43 ; 95 % CI , 1.40–2.65;P < 0.01 ) . Conclusion Patient-delivered partner medication is more effective than patient-based partner referral in the treatment of sexual partners Background : Sexually transmitted diseases ( STD ) are a major health problem in Zambia . Partner notification , which is a recommended strategy to decrease STD , must be improved . Goal : To assess whether individual counseling of patients with STD , combined with contact slip(s ) , had any impact on the proportion of sex partners traced in an urban setting in Zambia . Study Design : A r and omized trial comprised of 94 women and 302 men with STD . Results : Women and men in the intervention group informed more partners than did those in the control group . In the intervention group , 1.8 partners per man was treated compared to 1.2 in the control group ( P < 0.001 ) . There was no difference between the two groups of women . There was a gradual decline from numbers of partners informed to numbers of partners treated according to the patient to number of contact slips filed . Conclusions : Individual counseling of men with STD improved partner notification OBJECTIVE The objective of this research was to examine the effectiveness of a brief behavioral intervention , provided at the time of diagnosis of pelvic inflammatory disease , on subsequent behaviors by patients who were urban adolescents in a community in which sexually transmitted infection was prevalent . METHODS 121 adolescents aged 15 to 21 years with mild to moderate pelvic inflammatory disease were enrolled in a r and omized trial . All participants received st and ardized care , completed baseline audio computerized self-interviews , received full courses of medication at discharge , and were interviewed after the 2-week treatment course . The intervention group also watched a 6-minute intervention video . MAIN OUTCOME MEASURES Medication completion , temporary sexual abstinence during the 14-day treatment period , partner notification , partner treatment , and return for 72-hour follow-up were studied . Data were evaluated using multivariate regression analysis . RESULTS Of the participants , 61 % were located and could participate in the 2-week interview by the disease intervention specialist . The intervention participants had higher rates of 72-hour follow-up ( 32 % vs. 16 % ) and partner treatment ( 71 % vs. 53 % ) in bivariate analyses at a P = 0.1 level . There were no differences in medication completion ( 66 % vs. 66 % ) , sexual abstinence ( 78 % vs. 89 % ) , or partner notification ( 88 % vs. 92 % ) . Only the partner-treatment finding persisted in multivariate models ( AOR = 3.10 ; 95 % CI , 1.03 - 9.39 , P = .045 ) . CONCLUSIONS Adolescent girls r and omized to a community-specific video intervention at diagnosis of pelvic inflammatory disease were three times more likely to have their partners treated than those in the control group . Given the value of partner treatment in secondary prevention of sexually transmitted diseases , this video may be an essential component of discharge programming in urgent care setting s. Additional structural supports may be necessary to facilitate improved adherence to other key adherence behaviors Background : Trichomoniasis is associated with adverse pregnancy outcomes and increased risk for human immunodeficiency virus . Males are usually asymptomatic , and thus there is heavy reliance on partner notification for identifying infected male partners . The usual approach is partner referral but it is estimated that only a minority of men seek care . We conducted a r and omized trial to compare the effectiveness of 3 methods of partner notification . Methods : Women were r and omized to self-referral of partners ( PR ) , partner-delivered therapy ( PDPT ) , or public health disease intervention ( DIS ) locating partners and delivering medication in the field , if needed . Test-of-cure visits were conducted at 5 to 9 days after enrollment . Repeat infections at 1 and 3 months of follow-up were the measure of effectiveness . Results : A total of 484 women were r and omized . Initial cure rates were 95.3 % . At the 1- and 3-month follow-up visits , there was no significant difference in repeat infection rates when PDPT or DIS were compared to the reference of PR . However , when PDPT was compared to DIS or PR/DIS combined , at 1 month the PDPT group had a lower repeat infection rate ( 5.8 vs. 15 % and 5.8 vs. 12.5 % , respectively ) . Of these , 80 % of women r and omized to PDPT reported delivering medication and 89 % thought it likely that partners took the medication . No serious adverse events were reported . Conclusions : PDPT for trichomoniasis was well accepted and safe in this study . Rates of repeat infection in women in this intervention were lower than those in the DIS arm and DIS/PR arm combined although when compared directly to PR there was no significant difference PURPOSE Among adolescent women , having older sexual partners has been associated with initial Chlamydia trachomatis ( Ct ) infection and high-risk behaviors . This study evaluates the role of older partners in the risk of three outcomes : recurrent Ct , lack of condom use , and nonadherence with partner management ( PM ) strategies . METHODS Female participants aged 14 to 18 years enrolled in a r and omized clinical trial of patient-delivered partner treatment ( PDPT ) with at least one follow-up visit were included in this secondary analysis . Patient- and partner-level data were collected at baseline , one , and four months follow-up . Generalized estimating equations ( GEE ) and logistic regression were used to examine unadjusted and adjusted associations . RESULTS The majority of the 496 women were African-American ( 63.3 % ) , aged 16 to 18 years ( 62.3 % ) , and asymptomatic for Ct ( 66.7 % ) . At baseline , all of the women had laboratory-demonstrated Ct and were treated ; they had 622 partners during the last 60 days , 21.4 % reported having more than one partner with a mean ( SD ) of 1.5 ( .78 ) partners per woman , and 46.3 % of the partners were at least three years older than the woman . Over follow-up , 16.1 % of the women experienced Ct recurrence , in 41.9 % of the partnerships a condom was not used at last sex , and 80.6 % of women reported giving PM . After adjusting for confounders , having a partner at least three years older was not associated with increased risk of Ct recurrence , lack of condom use , or nonadherence to PM strategies . CONCLUSIONS Risk of Ct recurrence , lack of condom use , and nonadherence to PM strategies was not higher among adolescent women with older partners CONTEXT Sexual communication and appropriate treatment of sexual partners is critical to the success of STD and HIV/AIDS prevention and control . AIMS To underst and factors influencing intention of STD patients to inform their regular sexual partners and identify predictors influencing actual return of the partners . SETTING S AND DESIGN A non-r and omised survey of patients attending STD clinic in a district hospital between May and November 2000 . METHODS AND MATERIAL 182 patients were administered structured question naires to underst and their intention to notify their regular sexual partners and encouraged to refer their regular sexual partners to the clinic for management . Factors related to intent to notify partners and actual partner referral were analysed . STATISTICAL ANALYSIS USED Chi square test and forward stepwise logistic regression . RESULTS Of the 182 STD patients 77.47 % expressed their positive intention to notify their regular sexual partners . However , overall partner return rate was 40.65 % . Patients from a better economic class ( p=0.014 ) , those who had sex since having the disease ( p=0.001 ) , those who felt it was easy to tell their partners ( p=0.047 ) and perceived the necessity of investigating their partners ( p<0.001 ) were more likely to have an intention to notify their partners . Independent predictors of actual return of sexual partners were patients ' perception of partners ' susceptibility ( p=0.044 ) , positive intention to notify partners ( p=0.001 ) , partners already informed before clinic visit ( p=0.030 ) and presence of genital ulcerative diseases ( p=0.033 ) . CONCLUSIONS STD clinic counselling and education should focus on risk reduction , partner susceptibility , role of STDs in HIV transmission and improving spousal communication BACKGROUND Few data are available on the risk of unintended pregnancy in women with STD or how contraceptive services can be integrated into STD control activities . OBJECTIVE To define the risk for unintended pregnancy and assess the effectiveness of family-planning ( FP ) referral and interest in advanced provision emergency contraception ( APEC ) among women with gonorrhea or chlamydial infection . METHODS Female participants in a r and omized trial of different approaches to partner notification were interviewed , offered referral for FP services and asked if they would want APEC . RESULTS Among participants ages 14 - 24 , the observed past pregnancy rate and age-adjusted anticipated past pregnancy rate were , respectively , 196 and 72 per 1000 women-years . Of 474 nonpregnant participants who did not desire pregnancy , 127 ( 34 % ) were using no contraception or condoms alone , of whom 8 ( 6 % ) requested a FP appointment and 81 % wanted APEC . CONCLUSIONS Women treated for STD are at high-risk for unintended pregnancy . Although referral for FP was ineffective , interest in APEC was very high Introduction Gonorrhea has emerged recently as an epidemic disease of major proportions in the United States , with more than one million cases reported to state and local health departments in 1975.1 True incidence is unknown , but significant under-reporting is likely . A control program facing over a million cases per year must choose the general focus and specific techniques that best utilize its limited re sources . Except in some special geographic areas , interviewing and contact investigation of a significant proportion of the infected population appears to be an insurmountable task . Our purpose was to examine the efficacy of an alternative to the st and ard case interview and investigation . Although we recognized from the outset that a short-term evaluation could not provide data on disease control , we were able to evaluate the ability of the alternative to detect new cases , and on that basis we developed a sense of its comparative effectiveness and cost The impact of a ten-minute , soap opera-style videotape on knowledge and treatment behavior of black men with gonorrhea was tested in r and omized clinical trials . The videotape , shown to individual patients after diagnosis , produced a sizeable increase in the percentage of patients who returned for their test-of-cure examination : while only 43.3 % of control group patients returned , 53.5 % of those in the videotape group did so ; chi 2(1 ) = 9.0 ; P less than 0.003 . In a follow-up study , similar results were found : videotape group ( 59.0 % ) , control group ( 39.1 % ) ; chi 2(1 ) = 6.2 ; P less than 0.015 . The videotape also produced large , significant increases in patient knowledge , as measured by a test administered during patients ' clinic visit ( P less than 0.0001 ) . No measureable effect of the videotape was detected on patients ' willingness to refer sexual contacts for treatment . The findings suggest that clinic-based educational material s , particularly soap opera-style videotapes that engender audience identification , create emotional significance for the viewer , and model requisite communication skills , may have a significant role to play in control of sexually transmitted diseases |
12,686 | 26,614,425 | Magnetic field strength had no significant effect on accuracy . | Abstract Purpose To determine the diagnostic accuracy of magnetic resonance imaging ( MRI ) and ultrasound ( US ) in the diagnosis of anterior cruciate ligament ( ACL ) , medial meniscus and lateral meniscus tears in people with suspected ACL and /or meniscal tears . | Objective To evaluate the clinical efficacy of magnetic resonance imaging ( MRI ) of the knee in acute injuries with indeterminate clinical findings , using arthroscopy as a gold st and ard . Design A prospect i ve double-blind study was performed . All patients underwent MRI on a 1.5 T magnet using dual spin echo pulse sequences . This was followed by arthroscopy . Setting Tertiary care referral center . Patients Twenty-three patients with an average age of 26 years satisfied the study criteria . Patients had to have been seen by one of two orthopaedic surgeons within 6 weeks of sudden trauma to the knee complicated by a hemarthrosis , clinical assessment of which was equivocal . Results The respective sensitivity and specificity for MRI of the knee were 90 % ( 18/20 ) and 67 % ( 2/3 ) for detecting any anterior cruciate ligament injury , 50 % ( 1/2 ) and 86 % ( 18/21 ) for detecting medial meniscal tears , and 88 % ( 7/8 ) and 73 % ( 11/15 ) for detecting lateral meniscal tears . MRI also identified injuries that could not be assessed on arthroscopy , including 14 bone bruises , five posterior cruciate ligament tears , nine medial collateral ligament tears , and one lateral collateral ligament tear . The detection of composite injury requiring surgical intervention yielded a sensitivity of 100 % ( 16/16 ) and a specificity of 71 % ( 5/7 ) . Prospect i ve use of MRI evaluation of the knee could have prevented 22 % ( 5/23 ) of diagnostic arthroscopic procedures . Conclusion Equivocal clinical findings in patients with acute knee injury should lead to use of MRI in an appropriate clinical setting . To our knowledge a prospect i ve study of the efficacy of MRI of the knee in this patient population has not been reported . In the presence of such inclusion criteria , the results of our study support the use of early MRI to guide further surgical management Abstract The results of magnetic resonance imaging ( MRI ) were compared with those of arthroscopy in a prospect i ve series of 244 patients . A dedicated system for MRI of limbs and peripheral joints – the 0,2-T Artoscan ( Esaote , Italy ) – was used for imaging knee joint lesions . T1-weighted spin-echo sagittal images , T2-weighted gradient-echo coronal images , and axial views for lesions of the femoropatellar joint were acquired . Paraxial sagittal and oblique coronal views were obtained for imaging of the cruciate ligaments . This protocol allowed excellent visualization of the cruciate ligaments and medial and lateral meniscus in almost all patients . Compared with arthroscopy performed within 48 h after imaging , the sensitivity , specificity , and accuracy were respectively 93 % , 97 % , and 95 % for tears of the medial meniscus ; 82 % , 96 % , and 93 % for tears of the lateral meniscus ; 100 % , 100 % , and 100 % for tears of the posterior cruciate ligament ; 98 % , 98 % , and 97 % for tears of the anterior cruciate ligament ; and 72 % , 100 % , and 92 % for full-thickness articular cartilage lesions . The examination can be performed within 30–45 min at lower cost than diagnostic arthroscopy . MRI with a 0.2-T magnet is a safe and valuable adjunct to the clinical examination of the knee and an aid to efficient preoperative planning A prospect i ve double-blind study was undertaken to evaluate the usefulness of magnetic resonance imaging in the accurate interpretation of pathological intra-articular changes in the knee . Forty-seven patients who were scheduled to have arthroscopy and three patients who wer to have arthrotomy volunteered for magnetic resonance imaging preoperatively . The radiologists had no clinical or roentgenographic information about the patients before the evaluation of the magnetic resonance images , and the radiologists ' interpretations were unknown to the surgeon before the arthroscopy or arthrotomy was done . Our important observations were limited to the findings in the menisci and in the anterior cruciate ligament . Magnetic resonance imaging had a positive predictive value of 75 per cent , a negative predictive value of 90 per cent , a sensitivity of 83 per cent , and a specificity of 84 per cent for pathological findings in the menisci . For complete tears of the anterior cruciate ligament , the positive predictive value was 74 per cent ; the negative predictive value , 70 per cent ; the sensitivity , 61 per cent ; and the specificity , 82 per cent . We believe that magnetic resonance imaging , when combined with clinical and roentgenographic examination , provides the most accurate non-invasive source of information that is currently available for pathological findings in the menisci and in the anterior cruciate ligament The aim of this study was to detect the accuracy of routine magnetic resonance imaging ( MRI ) done in different centres and its agreement with arthroscopy in meniscal and ligamentous injuries of the knee . We prospect ively examined 70 patients ranging in age between 22 and 59 years . History taking , plain X-ray , clinical examination , routine MRI and arthroscopy were done for all patients . Sensitivity , specificity , accuracy , positive and negative predictive values , P value and kappa agreement measures were calculated . We found a sensitivity of 47 and 100 % , specificity of 95 and 75 % and accuracy of 73 and 78.5 % , respectively , for the medial and lateral meniscus . A sensitivity of 77.8 % , specificity of 100 % and accuracy of 94 % was noted for the anterior cruciate ligament ( ACL ) . We found good kappa agreements ( 0.43 and 0.45 ) for both menisci and excellent agreement ( 0.84 ) for the ACL . MRI shows high accuracy and should be used as the primary diagnostic tool for selection of c and i date s for arthroscopy . Level of evidence : 4.RésuméLe but de cette étude est de détecter un examen de routine l’IRM et la bonne correspondance entre ces constatations et les constatations arthroscopiques des lésions méniscales ou des lésions ligamentaires du genou . Nous avons réalisé une étude prospect i ve de 70 patients âgés de 22 à 59 ans avec analyse de l’histoire clinique , des radiographies , de l’examen clinique , de l’examen IRM et des constatations arthroscopiques . La sensitivité , la spécificité et l’exactitude des constatations ont été évaluées de manière statistique . Nous avons trouvé respectivement une sensitivité de 47 % et 100 % , une spécificité de 95 % et 75 % et une exactitude des constatations de 73 % et 78,5 % , pour les lésions du ménisque interne ou du ménisque latéral . En ce qui concerne les ligaments croisés , la sensitivité est de 77,8 % , la spécificité de 100 % et l’exactitude des constatations de 94 % avec une bonne correspondance Kappa ( 0,43 et 0,45 ) pour les ménisques et 0,84 pour le ligament croisé antérieur . L’IRM peut donc être utilisée comme un élément tout à fait sûr et routinier concernant le diagnostic primaire des lésions miniscales ou des lésions ligamentaires chez les patients devant bénéficier d’une arthroscopie . Niveau d’évidence : 4 Rapidly progressing medical technology sometimes obscures the importance of history and physical examination . This study was design ed to assess the value of MRI and clinical examination in the diagnosis of ligamentous and meniscal knee injuries in comparison with arthroscopic findings . In the year 2003 - 2004 , we conducted a prospect i ve , single blind study to assess ligamentous and meniscal injuries of the knee in patients with acute knee trauma . The mean age was 27.9 years . The sex distribution was 81.4 % male and 18.6 % female ; 42.9 % of injuries affected the right knee and 57.1 % the left knee . All the included patients were ordered a MRI , executed in five separate centres . All patients underwent arthroscopy by the author . Arthroscopic findings were the diagnostic reference . Clinical examination was accurate in 91.4 % , and MRI in 88.5 % of anterior cruciate ligament injuries . For posterior cruciate ligament injuries , clinical accuracy was 100 % and MRI 94.6 % . Clinical examination was accurate in 96.9 % and MRI in 85.9 % of medial meniscal injuries . For lateral meniscus injuries , clinical accuracy was 85.4 % and MRI 73.8 % . MRI findings showed the lowest correlation with arthroscopic findings in lateral meniscus injuries ( r = 0/47 ) . Clinical diagnostic performance was poorest in case of combined cruciate ligament and meniscal injuries . We found an excellent correlation between MRI and clinical findings . However , when MRI is normal , high clinical suspicion and a skilled clinical examination are more reliable This prospect i ve double-blind study was design ed to evaluate the capability of magnetic resonance imaging to serve as a diagnostic tool in patients who have a clinical ly suspected disorder of the meniscus . The imaging studies provided a diagnostic accuracy of 72 per cent , a sensitivity of 88 per cent , and a specificity of 57 per cent . The positive and negative predictive values were 66 and 83 per cent . The diagnostic sensitivity was 94 per cent for lesions of the medial meniscus ; this value differed significantly from that of 78 per cent for lesions of the lateral meniscus ( p less than 0.05 ) . The 37 per cent specificity for lesions of the medial meniscus was extremely low compared with the rate of 69 per cent for lesions of the lateral meniscus ( p less than 0.01 ) . In the intermediate part of the meniscus , the diagnostic sensitivity was 37 per cent on the medial side and 23 per cent on the lateral side ; these values were significantly less than the average of 74 per cent for the other meniscal segments ( p less than 0.001 ) . The imaging studies provided an over-all accuracy of 67 per cent in the detection of degeneration of the meniscus , 78 per cent in the identification of meniscal tears , and 82 per cent in the delineation of postoperative lesions Abstract Purpose Rupture of the anterior cruciate ligament ( ACL ) is a common injury , often presenting with a typical injury pattern . Historically , the literature indicates that the accuracy of diagnosis of ACL ruptures is poor at the initial medical consultation . The aims of this study were to determine : the mechanism of injury ; changes in accuracy of diagnosis of ACL ruptures at initial presentation over the last decade ; and the effect of subsequent delay in diagnosis and definitive treatment . Methods A prospect i ve cohort of one hundred and thirty-two consecutive patients who underwent ACL reconstruction between 2005 and 2009 were analysed . The median age of the patients was 18 years ( 12–57 ) . Sixteen patients were excluded due to chronic ACL injury . Results One hundred and sixteen patients ( 117 ACL ruptures ) were included in the analysis . A typical injury pattern was documented in 87 ( 74.4 % ) of cases . The most common sporting activities associated with an ACL injury were football ( 35.3 % ) , skiing ( 21.6 % ) and rugby ( 10.3 % ) . The majority of patients ( 67.5 % ) sought medical attention within 1 week from time of injury . The correct diagnosis of an ACL rupture was made in 33 cases ( 28.2 % ) at the initial medical consultation . The diagnosis was made following medical consultation in 13 ( 11.1 % ) of cases with the use of magnetic resonance imaging and 6 ( 5.1 % ) cases at arthroscopy . The median time to diagnosis was 6 weeks ( 0–192 ) , and the median time to ACL reconstruction was 24 weeks ( 1–240 ) . A delay in diagnosis of > 6 months was associated with a medial meniscal tear rate of 72.2 % compared to 23.1 % if the diagnosis was made within 4 months of the injury ( p < 0.05 ) . Conclusions Despite a ‘ typical ’ mechanism of injury leading to ACL rupture , the rate of initial diagnosis in the UK still remains poor . This often leads to an unnecessary delay in the diagnosis and subsequent treatment and increases the risk of secondary injury to the knee . A delay in diagnosis of > 6 months was associated with an increased medial meniscal tear rate . Patients who present with a ‘ typical ’ injury pattern should therefore be referred for further assessment by a knee specialist within 6 weeks . Level of evidence IV The results of selective magnetic resonance imaging of the knee were compared with those of arthroscopy in a prospect i ve series of fifty patients . A specifically design ed protocol for imaging , producing T1 sagittal images interleaved at four millimeters while the patient 's foot was in 20 degrees of external rotation , was utilized . This technique , called selective magnetic resonance imaging , yielded excellent visualization of the posterior cruciate ligament , medial meniscus , and lateral meniscus in all patients . However , in only 76 per cent of the patients was the anterior cruciate ligament well visualized . Compared with arthroscopy , the sensitivity , specificity , and accuracy of selective magnetic resonance imaging were , respectively , 95.8 , 100 , and 98 per cent for tears of the medial meniscus ; 66.7 , 95.1 , and 90 per cent for tears of the lateral meniscus ; undefined , 100 , and 100 per cent for tears of the posterior cruciate ligament ; and 100 , 96.9 , and 97.3 per cent for tears of the anterior cruciate ligament , when that ligament was well visualized . Our selective sequence can be performed in fifteen minutes at a cost that is comparable with that of arthrography . It is totally non-invasive and requires no exposure to ionizing radiation . Selective magnetic resonance imaging can be a safe and valuable adjunct to the clinical evaluation of the knee and an aid to efficient preoperative planning We compared the diagnostic and predictive value of magnetic resonance imaging ( MRI ) and clinical findings with arthroscopy in 61 knees in a prospect i ve study . In meniscal tears , the accuracy and positive predictive value of MRI was found to be nearly twice that of clinical examination . The sensitivity , specificity , and negative predictive value of MRI were comparable to the figures found in other studies . We recommend MRI as a clarifying diagnostic tool when a clinical examination indicates a lesion of the meniscus . In our study , the clinical relevance of MRI in anterior cruciate ligament lesions and especially in cartilage lesions was more doubtful . The combination of clinical and MRI findings would reduce the number of blank arthroscopies to 5 % . MRI is a valuable diagnostic tool in planning the type of anesthesia and treatment , and could significantly reduce the need for a second arthroscopy Purpose To prospect ively evaluate whether age of patient affects diagnostic accuracy of sonography and magnetic resonance imaging ( MRI ) in the diagnosis of medial meniscal tears . Methods We prospect ively evaluated 74 consecutive patients ( 54 males and 20 females ) , in two different groups [ group A ( 37 patients ≤ 30 years ; mean age : 23.5 ± 5 years ) and group B ( 37 patients > 30 years ; mean age : 43.5 ± 9.35 years ) ] with clinical suspicion of medial meniscal tear . After inclusion , patients underwent ultrasonography and then MRI for signs of tearing . The ultrasonographic and MRI findings were compared with arthroscopic findings , which served as a gold st and ard for accurate detection of meniscal tearing . Results The sensitivity , specificity , positive and negative predictive values and accuracy of ultrasonography in detecting medial meniscal tears in group A were 100 , 88.9 , 96.5 , 100 , 97.3 % and in group B were 83.3 , 71.4 , 92.6 , 50 , 81.1 % , respectively . The sensitivity , specificity , positive and negative predictive values and accuracy of MRI in group A were 100 , 88.9 , 96.5 , 100 , 97.3 % and in group B were 96.7 , 85.7 , 96.7 , 85.7 , 94.6 % , respectively . Conclusions Given the fact that the sensitivity and specificity of the results of knee sonography matched that of MRI in patients who were 30 years old or less , we suggest ultrasonography as an effective initial investigation for tears of medial meniscus in this group of patients . Patients with negative ultrasonographic findings will need no further investigation . Level of evidence Diagnostic studies —investigating a diagnostic test , Level II In a prospect i ve double-blind study we investigated internal knee disorders with ultrasound and compared the results with Magnetic Resonance Imaging ( MRI ) and arthroscopy . The aim was to determine the effectiveness of ultrasound in diagnosing Internal Derangement of the Knee ( IDK ) and to compare the results with MRI . Over an 18-months period , 81 patients were examined . All were male ; they had a mean age of 35 years . For various technical reasons 21 patients were subsequently excluded from the study . After initial clinical examinations , patients had an ultrasound and MRI scan at the same visit . Arthroscopy was performed within a month of this . Different radiologists who were unaware of the clinical findings independently reported on the ultrasound and MRI . The surgeon performing the arthroscopy was made aware only of the MRI findings . Structures accessed were the lateral and medial menisci and the anterior ( ACL ) and posterior ( PCL ) cruciate ligaments . Arthroscopy was taken as the gold st and ard . Ultrasound showed good sensitivity , ranging from 76 % for the ACL to 90 % for the medial meniscus , and excellent specificity , ranging from 92 % for the medial meniscus to 100 % for the ACL . Accuracy ranged from 86 % for the ACL to 98 % for the lateral meniscus . These figures were comparable to the MRI findings . We concluded that ultrasound is a simple , accurate , inexpensive and non-invasive way of assessing internal knee disorders . There is a learning curve , but results are similar to MRI The diagnostic performance of low field ( 0.1 T ) magnetic resonance imaging ( MRI ) was studied prospect ively and double-blindly among 33 patients with acute knee injuries . The subsequent arthroscopy was the golden st and ard . For lesions of the medial meniscus low field MR had a sensitivity of 88 % and a specificity of 80 % ; for lesions of the lateral meniscus the sensitivity was 25 % and the specificity 97 % . For anterior cruciate ligament tears , low field MRI had a sensitivity of 83 % and a specificity of 85 % . The specificity for posterior cruciate ligament tears was 97 % . The performance of low field MRI equalled that reported earlier for high field MRI , the only exception being the sensitivity for lateral meniscus lesions OBJECTIVE We attempted to determine the potential cost savings of prearthroscopic knee MR imaging examinations . SUBJECTS AND METHODS This prospect i ve study involved 50 consecutive patients . The patients met the surgical-indications-for-monitoring-appropriateness criteria for knee arthroscopy and underwent MR imaging of the knee before arthroscopy . For all patients , we compared MR imaging and arthroscopic findings . On the basis of a cost of $ 1000 for each MR imaging examination and $ 4000 for each diagnostic arthroscopy , we decided that cost-effective MR imaging would require 25 % true negativity . RESULTS The respective sensitivities and specificities of MR imaging of the knee were 100 % and 90 % for revealing anterior cruciate ligament interruption , 100 % and 84 % for revealing posterior cruciate ligament tears , 90 % and 97 % for revealing medial meniscal tears , 60 % and 100 % for revealing lateral meniscal tears , and 94 % and 93 % for revealing composite injury ( one or more of these abnormalities ) . With MR imaging examinations obtained before surgery , we found 21 ( 42 % ) of 50 arthroscopies to be unnecessary . CONCLUSION Despite stringent clinical criteria used in selecting patients for arthroscopy , 42 % of our patients could have been spared surgery on the basis of the anatomy revealed by MR imaging . Our study indicates that MR imaging obtained before arthroscopy of the knee can produce a savings of as much as $ 680 per MR imaging examination performed on the knee We present the results of a prospect i ve study comparing the accuracy of magnetic resonance imaging with arthroscopy in the assessment of knee complaints . Using a low field strength magnet , MRI was able to achieve a high diagnostic accuracy within the setting of a district general hospital We compared the findings of low-field MRI of the knee with those of subsequent arthroscopy . In a double-blind set-up , 47 patients with knee joint injuries were enrolled . Two radiologists independently interpreted the MRI examinations and consensus was obtained in case of discrepancy . Arthroscopy was performed without knowledge of the MRI findings . The accuracy rates of MRI for evaluating the medial meniscus , lateral meniscus and anterior cruciate ligament were 77 % , 91 % and 96 % , respectively , when arthroscopy was considered the " golden st and ard " . When MRI was considered the st and ard , the figures for arthroscopy were 74 % , 91 % and 96 % . MRI found the indication for treatment in 18 of 21 patients who were treated at the arthroscopy . In 17 patients , neither MRI nor arthroscopy detected any lesion . In the remaining 9 patients , MRI demonstrated a lesion , but no lesion was found at the subsequent arthroscopy . Our conclusion is that low-field MRI can be used as a first-line diagnostic examination in patients with suspected meniscus or cruciate ligament injuries and thus a substantial number of negative diagnostic arthroscopies can be avoided BACKGROUND MRI ( magnetic resonance imaging ) is widely used to diagnose meniscal pathology and ACL ( anterior cruciate ligament ) tears . Because of the enhanced signal-to-noise ratio and improved image quality at higher field strength , knee MRI equipment is shifting from 1.5 to 3.0 T. To date , objective evidence of improved diagnostic ability at 3.0 T is lacking . The purpose of this prospect i ve study was to assess the accuracy of 1.5 and 3.0-T MRI of the knee , in the same individuals , for diagnosing meniscal pathology and ACL tears , utilizing arthroscopy as the reference st and ard . METHODS Two hundred patients underwent MRI of the knee at 1.5 and 3.0 T. All MRI examinations consisted of multiplanar turbo spin-echo sequences . One hundred patients underwent subsequent knee arthroscopy . Two blinded independent radiologists assessed all MRI studies to identify meniscal pathology and ACL tears . In patients with MRI results indicating the need for surgical treatment , the sensitivity and specificity of the 1.5 and 3.0-T protocol s for detecting these lesions were determined , utilizing arthroscopy as the reference st and ard , and compared with use of the McNemar test . The kappa statistic for inter-reader agreement in the 200 patients was calculated . RESULTS For medial meniscal tears , the mean sensitivity and specificity for the two readers were 93 % and 90 % , respectively , at 1.5 T and 96 % and 88 % , respectively , at 3.0 T. For lateral meniscal tears , the mean sensitivity and specificity were 77 % and 99 % , respectively , at 1.5 T and 82 % and 98 % , respectively , at 3.0 T. For ACL tears , the mean sensitivity and specificity were 78 % and 100 % , respectively , at 1.5 T and 80 % and 100 % , respectively , at 3.0 T. None of the values for either reader differed significantly between the 1.5 and 3.0-T MRI protocol s. Inter-reader agreement was almost perfect to perfect ( kappa = 0.82 to 1.00 ) . CONCLUSIONS Routine use of a 3.0-T MRI protocol did not significantly improve accuracy for evaluating the knee menisci and ACL compared with a similar 1.5-T protocol We made a prospect i ve study of 58 patients with suspected internal derangement of the knee . They were examined by magnetic resonance imaging using 3-D gradient echo intermediate-weighted studies before having an arthroscopy . The preoperative clinical assessment was found to have a diagnostic sensitivity of 77 % and a specificity of 43 % , compared with 100 % and 63 % respectively for magnetic resonance imaging . Comparison of magnetic resonance imaging and arthroscopy confirmed the accuracy of magnetic resonance imaging in the diagnosis of internal derangement but the results for articular cartilage lesions were much less good , with a sensitivity of only 18 % but a specificity of 100 % . Acceptance of the magnetic resonance imaging findings could have result ed in a 29 % reduction in the number of arthroscopies without missing any significant meniscal lesion |
12,687 | 27,875,340 | A recent review has , however , identified a number of clinical /imaging features that may be associated with higher rates of stroke on medical therapy .
Summary The majority of surgeons/interventionists are unlikely to accept radical changes in practice until new r and omized trials confirm that the risk of stroke on modern medical therapy is significantly lower than that previously accepted . | Purpose of review To summarize why there are polarized opinions regarding the management of patients with asymptomatic carotid disease and whether it is possible to identify patients who might benefit from carotid interventions . | OBJECTIVE To assess the effect of more intensive medical therapy on the rate of transcranial Doppler ( TCD ) microemboli and cardiovascular events in patients with asymptomatic carotid stenosis ( ACS ) . DESIGN A prospect i ve study . SETTING A teaching hospital . PATIENTS Four hundred sixty-eight patients with ACS greater than 60 % by Doppler peak velocity . MAIN OUTCOME MEASURES We compared ( 1 ) the proportion of ACS patients who had microemboli on TCD , ( 2 ) cardiovascular events , ( 3 ) rate of carotid plaque progression , and ( 4 ) baseline medical therapy , before and since 2003 . RESULTS Among 468 ACS patients , 199 were enrolled between January 1 , 2000 , and December 31 , 2002 ; and 269 were enrolled between January 1 , 2003 , and July 30 , 2007 . Microemboli were present in 12.6 % before 2003 and 3.7 % since 2003 ( P < .001 ) . The decline in microemboli coincided with better control of plasma lipids and slower progression of carotid total plaque area . Since 2003 , there have been significantly fewer cardiovascular events among patients with ACS : 17.6 % had stroke , death , myocardial infa rct ion , or carotid endarterectomy for symptoms before 2003 , vs 5.6 % since 2003 ( P < .001 ) . The rate of carotid plaque progression in the first year of follow-up has declined from 69 mm(2 ) ( SD , 96 mm(2 ) ) to 23 mm(2 ) ( SD , 86 mm(2 ) ) ( P < .001 ) . CONCLUSIONS Cardiovascular events and microemboli on TCD have markedly declined with more intensive medical therapy . Less than 5 % of patients with ACS now st and to benefit from revascularization ; patients with ACS should receive intensive medical therapy and should only be considered for revascularization if they have microemboli on TCD Background and Purpose — This study aim ed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction . Methods — One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospect ively evaluated for a 3-year period . At entry , demographics , vascular risk profile , and pharmacological treatments were defined . Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up . Cerebral hemodynamics was assessed by transcranial Doppler – based breath-holding index test . As a measure of the extent of systemic atherosclerotic disease , common carotid artery intima-media thickness was measured . A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness . Results — The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index , reaching the highest probability in patients with bilaterally abnormal breath-holding index ( P<0.0001 ) . Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change . Conclusions — Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment . The evaluation of the hemodynamic status , besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease , may be of help for the individuation of subjects deserving earlier and more aggressive treatments Background and Purpose — Progression of asymptomatic carotid stenoses with > 50 % luminal narrowing is associated with an increased risk of stroke . The significance of the progression rate in these patients is unknown . The main aim of this study was to evaluate the rate of change of carotid luminal narrowing over 1 year , as a risk factor for ipsilateral ischemic events , in patients with a > 50 % asymptomatic carotid stenosis . Secondary aims were to establish the incidence of changes in carotid luminal narrowing and establish additional risk factors for ipsilateral neurological events . Methods — A retrospective analysis was conducted of data derived from the deferred endarterectomy arm of the Asymptomatic Carotid Surgery Trial . Patients were followed up for ≥5 years with serial carotid duplex examinations . Data were derived from information obtained at r and omization and annual follow-up visits with carotid duplex examination . Potential risk factors for ipsilateral neurological events were analyzed in Poisson regression models . Results — Data from 1469 patients were included . Two hundred forty-four had ipsilateral events ; 240 had ipsilateral carotid surgery ; 370 died from nonstroke causes ; and 82 had an asymptomatic carotid occlusion . The annual incidence of progression in the cohort as a whole was 5.2 % . Ipsilateral events occurred in 17 % of patients . Diabetes and previous contralateral symptoms showed a significant independent association with ipsilateral neurological events . Ipsilateral events were associated with high rates of progression over 1 year but not with low progression rates or regression . Conclusions — Fast rates of progression of carotid luminal narrowing should be interpreted as a sign of significantly increased risk of future ipsilateral neurological events BACKGROUND Previous clinical trials have suggested that carotid-artery stenting with a device to capture and remove emboli ( " embolic protection " ) is an effective alternative to carotid endarterectomy in patients at average or high risk for surgical complications . METHODS In this trial , we compared carotid-artery stenting with embolic protection and carotid endarterectomy in patients 79 years of age or younger who had severe carotid stenosis and were asymptomatic ( i.e. , had not had a stroke , transient ischemic attack , or amaurosis fugax in the 180 days before enrollment ) and were not considered to be at high risk for surgical complications . The trial was design ed to enroll 1658 patients but was halted early , after 1453 patients underwent r and omization , because of slow enrollment . Patients were followed for up to 5 years . The primary composite end point of death , stroke , or myocardial infa rct ion within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points . RESULTS Stenting was noninferior to endarterectomy with regard to the primary composite end point ( event rate , 3.8 % and 3.4 % , respectively ; P=0.01 for noninferiority ) . The rate of stroke or death within 30 days was 2.9 % in the stenting group and 1.7 % in the endarterectomy group ( P=0.33 ) . From 30 days to 5 years after the procedure , the rate of freedom from ipsilateral stroke was 97.8 % in the stenting group and 97.3 % in the endarterectomy group ( P=0.51 ) , and the overall survival rates were 87.1 % and 89.4 % , respectively ( P=0.21 ) . The cumulative 5-year rate of stroke-free survival was 93.1 % in the stenting group and 94.7 % in the endarterectomy group ( P=0.44 ) . CONCLUSIONS In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications , stenting was noninferior to endarterectomy with regard to the rate of the primary composite end point at 1 year . In analyses that included up to 5 years of follow-up , there were no significant differences between the study groups in the rates of non-procedure-related stroke , all stroke , and survival . ( Funded by Abbott Vascular ; ACT I Clinical Trials.gov number , NCT00106938 . ) BACKGROUND For an asymptomatic patient with severe carotid stenosis the most important question is how to prevent an ischemic stroke . Carotid artery stenosis is the estimated cause of stroke in 8 - 20 % of the cases . Today more than 50 % of procedures for carotid stenosis are done on asymptomatic patients , but few of the r and omized controlled trials comparing carotid endarterectomy and stenting examined specifically these patients . METHODS All patients with severe ( > 70 % ) asymptomatic carotid artery stenosis seen in the Carmel medical center vascular clinic were prospect ively screened and r and omized 1:1 for carotid endarterectomy ( CEA ) or carotid stenting ( CAS ) . Patients eligible for both procedures were enrolled . The primary objectives of the study were : 1 ) periprocedural complications - stroke ( CVA ) , transient ischemic attack ( TIA ) , myocardial infa rct ion ( MI ) , and death ; 2 ) long-term results : mortality , prevention of ipsilateral stroke or TIA , and freedom from restenosis . RESULTS One-hundred and thirty-six patients were treated with mean follow-up of 26 months . There was no difference in short and long term results between the two groups . Thirty day morbidity included : 1 CVA in each group with no MI . Long-term results included 4 deaths in each group ; none from CVA . One TIA was noted after CAS , and 3 cases of restenosis were found in CEA and one in CAS . CONCLUSIONS CAS is a maturing procedure and has improved significantly over the past several years . Future developments of stents and protection devices will achieve better perioperative results . This along with our excellent long term results will promote the use of stenting for suitable patients OBJECTIVES This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors . METHODS Patients ( n=1115 ) with asymptomatic internal carotid artery ( ICA ) stenosis greater than 50 % in relation to the bulb diameter were followed up for a period of 6 - 84 ( mean 37.1 ) months . Stenosis was grade d using duplex , and clinical and biochemical risk factors were recorded . RESULTS The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method , but S-shaped if expressed by the NASCET method . In addition to the ECST grade of stenosis ( RR 1.6 ; 95 % CI 1.21 - 2.15 ) , history of contralateral TIAs ( RR 3.0 ; 95 % CI 1.90 - 4.73 ) and creatinine in excess of 85 micromol/L ( RR 2.1 ; 95 % CI 1.23 - 3.65 ) were independent risk predictors . The combination of these three risk factors can identify a high-risk group ( 7.3 % annual event rate and 4.3 % annual stroke rate ) and a low risk group ( 2.3 % annual event rate and 0.7 % annual stroke rate ) . CONCLUSIONS Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used . Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy BACKGROUND Because of recent advances in best medical treatment ( BMT ) , it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit , in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses . The aim was to compare the stroke-preventive effects of BMT alone , with that of BMT in combination with carotid endarterectomy ( CEA ) or carotid artery stenting ( CAS ) in patients with high grade asymptomatic extracranial carotid artery stenosis . METHODS SPACE-2 was planned as a three-armed , r and omized controlled trial ( BMT alone vs. CEA plus BMT vs. CAS plus BMT , IS RCT N 78592017 ) . However , because of slow patient recruitment , the three-arm study design was amended ( July 2013 ) to become two parallel r and omized studies ( BMT alone vs. CEA plus BMT , and BMT alone vs. CAS plus BMT ) . RESULTS The change in study design did not lead to any significant increase in patient recruitment , and trial recruitment ceased after recruiting 513 patients over a 5 year period ( CEA vs. BMT ( n = 203 ) ; CAS vs. BMT ( n = 197 ) , and BMT alone ( n = 113 ) ) . The 30 day rate of death/stroke was 1.97 % for patients undergoing CEA , and 2.54 % for patients undergoing CAS . No strokes or deaths occurred in the first 30 days after r and omization in patients r and omized to BMT . There were several potential reasons for the low recruitment rates into SPACE-2 , including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial , an inability to convince patients ( who had come " mentally prepared " that an intervention was necessary ) to accept BMT , and other economic constraints . CONCLUSIONS Because of slow recruitment rates , SPACE-2 had to be stopped after r and omizing only 513 patients . The German Research Foundation will provide continued funding to enable follow up of all recruited patients , and it is also planned to include these data in any future meta- analysis prepared by the Carotid Stenosis Trialists Collaboration Carotid artery stenting ( CAS ) is now a wellestablished technique for the treatment of both symptomatic and asymptomatic cervical bifurcation disease . CAS procedures are typically performed from a femoral access , but there are limitations to this route ( Table 1 ) . Multiple singlecenter studies and r and omized trials have proven the safety , efficacy , and reduced vascular complication rates of transradial ( TR ) catheterization and percutaneous coronary intervention ( PCI ) . These same techniques have been adapted for the performance of CAS . Transradial CAS has several potential advantages compared with transfemoral ( TF ) access ( Table 2 ) . Limitations of TRA-CAS will also be review ed ( Table 3 ) . Herein , we present a case report of TRA-CAS , review the data , and offer a suggested CAS access algorithm ( Figure 1 ) Effective prevention is inarguably the best option for reducing the individual and societal burden of stroke . For each patient , clinicians balance the benefits of a given preventive therapy against its associated risks and costs . Where possible , these assessment s should be based on the results of r and omized clinical trials . Carotid endarterectomy ( CEA ) , the most-commonly used surgical procedure to prevent stroke , has been subjected to several r and omized trials . These underlie evidence -based guideline and consensus statements providing recommendations for its use.1–7 The evidence base for endarterectomy for symptomatic stenosis is considerable,8,9 but guidelines on surgery for asymptomatic stenosis have been largely based on the results of the Asymptomatic Carotid Atherosclerosis Study (ACAS)10 in conjunction with other smaller trials.11,12 Guidance differs from endorsement of the operation for selected patients ( eg , based on patient age , life expectancy , concomitant illnesses , etc . ) with varying degrees of asymptomatic stenosis ( generally either 60 % to 99 % or 80 % to 99 % ) in whom the procedure can be performed with low ( ie , < 3 % ) complication rates to advising that endarterectomy not be performed in patients without referable symptoms . ACAS reported a 47 % relative reduction in the risk of ipsilateral stroke and perioperative death in patients r and omized to surgery despite a 5-year risk of ipsilateral stroke without the operation of only 11%.10 The results led to major increases in rates of endarterectomy for asymptomatic stenosis in some countries , most notably the United States . Of the approximate 150 000 endarterectomies performed in the United States each year , at least half are done for stenoses that have never been symptomatic.13 In contrast , the ACAS results had little effect on endarterectomy rates in other countries such as the United Kingdom , where it was felt that the benefit ( it was estimated that 40 operations were needed to prevent 1 disabling or fatal BACKGROUND The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis , clinical features , and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery ( ICA ) stenosis . METHODS This was a prospect i ve , multicenter , cohort study of patients undergoing medical intervention for vascular disease . Hazard ratios for ICA stenosis , clinical features , and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic ( CORI ) events were calculated using proportional hazards models . RESULTS A total of 1121 patients with 50 % to 99 % asymptomatic ICA stenosis in relation to the bulb ( European Carotid Surgery Trial [ ECST ] method ) were followed-up for 6 to 96 months ( mean , 48 ) . A total of 130 ipsilateral CORI events occurred . Severity of stenosis , age , systolic blood pressure , increased serum creatinine , smoking history of more than 10 pack-years , history of contralateral transient ischemic attacks ( TIAs ) or stroke , low grayscale median ( GSM ) , increased plaque area , plaque types 1 , 2 , and 3 , and the presence of discrete white areas ( DWAs ) without acoustic shadowing were associated with increased risk . Receiver operating characteristic ( ROC ) curves were constructed for predicted risk versus observed CORI events as a measure of model validity . The areas under the ROC curves for a model of stenosis alone , a model of stenosis combined with clinical features and a model of stenosis combined with clinical , and plaque features were 0.59 ( 95 % confidence interval [ CI ] 0.54 - 0.64 ) , 0.66 ( 0.62 - 0.72 ) , and 0.82 ( 0.78 - 0.86 ) , respectively . In the last model , stenosis , history of contralateral TIAs or stroke , GSM , plaque area , and DWAs were independent predictors of ipsilateral CORI events . Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke , with predicted risk close to observed risk . Of the 923 patients with ≥ 70 % stenosis , the predicted cumulative 5-year stroke rate was < 5 % in 495 , 5 % to 9.9 % in 202 , 10 % to 19.9 % in 142 , and ≥ 20 % in 84 patients . CONCLUSION Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features . These findings need to be vali date d in additional prospect i ve studies of patients receiving optimal medical intervention alone Objective : We compared microemboli on transcranial Doppler ( TCD ) with carotid ulcerations on 3D ultrasound ( US ) as an additional method for identifying the small proportion of patients with asymptomatic carotid stenosis ( ACS ) who can benefit from revascularization such as endarterectomy or stenting . Methods : Patients with ACS ( n = 253 ) with carotid stenosis > 60 % by Doppler ultrasound were studied prospect ively with TCD embolus detection and 3D US to detect ulcers ( the total number of ulcers in both internal carotids ) and followed for 3 years . Results : Mean age was 69.66 ( SD 8.51 ) years ; 11 ( 4 % ) had ≥3 ulcers ( Ulcer 3 ) , 11 ( 6 % ) had microemboli , and 25 ( 10 % ) had microemboli or ≥3 ulcers . Ulcer 3 patients were more likely to have a stroke or death in 3 years ( 18 % vs 2 % ; p = 0.03 ) , regardless of the side on which the ulcers were found . The 3-year risk of stroke or death was 20 % with microemboli vs 2 % without ( p = 0.003 ) . The annual rate of ipsilateral stroke was 0.8 % . Conclusion : Adding 3D US detection of ulcers doubles ( to 10 % ) the proportion of patients with ACS who may benefit from endarterectomy or stenting . However , until 3-year event rates of stroke or death with endarterectomy or stenting reach < 2 % , 90 % of patients with ACS would be better treated medically until they develop symptoms , ulcers , or emboli . Neurology ® |
12,688 | 23,177,797 | The most solid data in this area indicate that CML patients receiving TKIs have a worse HRQOL profile when compared to their peers , without cancer , in the general population and interventions to improve HRQOL outcomes are thus needed .
However , HRQOL assessment in these studies emphasize the unique information provided by the patient 's perspective . | null | null |
12,689 | 21,039,773 | In a small cohort of women , distress levels are heightened to worrying levels that may have long-term implication s. There was strong evidence for relationships among medical history , education and trait anxiety with distress .
There was no substantiation of the association between younger age and increased psychological distress that has been consistently reported with other cancers . | AIM This paper is a report of a review conducted to define the manifestations that characterize psychological distress during the diagnostic phase for suspected breast cancer , define the extent of psychological distress associated with the threat of potential cancer , and identify factors influencing psychological distress levels .
BACKGROUND Raising the possibility that a malignancy might be present is threatening .
The result ing distress is believed to influence treatment outcomes in those diagnosed with cancer and result in behavioural changes in those with benign disease .
RESULTS It is well-documented that distress , manifested as anxiety , exists . | Delay in follow-up after an abnormal mammogram is associated with advanced disease stage , poorer survival , and increased anxiety . Despite the implementation of many patient navigator programs across the country , there are few published , peer- review ed studies documenting its effectiveness . We tested the effectiveness of a patient navigator in improving timeliness to diagnosis , decreasing anxiety , and increasing satisfaction in urban minority women after an abnormal mammogram . Women with suspicious mammograms were r and omly assigned to usual care ( N = 50 ) or usual care plus intervention with a patient navigator ( N = 55 ) . There were no demographic differences between the two groups . Women in the intervention group had shorter times to diagnostic resolution ( mean 25.0 vs. 42.7 days ; p = .001 ) , with 22 % of women in the control group without a final diagnosis at 60 days vs. 6 % in the intervention group . The intervention group also had lower mean anxiety scores ( decrease of 8.0 in intervention vs. increase of 5.8 in control ; p < .001 ) , and higher mean satisfaction scores ( 4.3 vs. 2.9 ; p < .001 ) . Patient navigation is an effective strategy to improve timely diagnostic resolution , significantly decrease anxiety , and increase patient satisfaction among urban minority women with abnormal mammograms The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Objectives To assess the long term psychological impact on women who were recalled for further investigation after mammography screening and to find any factors that might predict coping ability in order to identify those subjects who require additional support at an earlier stage . Setting Counties of Västerbotten and Västernorrl and , Sweden . Methods A prospect i ve design was used in which 252 recalled women completed question naires twice — once within a week of having received the all-clear and again at follow up six months later . A group of 1104 r and omly selected , screen negative women were followed up in the same way for comparison . The question naire included the Psychological Consequences Question naire ( PCQ ) and basic sociodemographic data . The main outcome measure was the total score on the PCQ at six months . Results Of the 252 women , 235 ( 93 % ) completed both question naires . In the control group , 987 ( 89.4 % ) women responded . Six months after the all-clear , recalled women were still significantly more anxious ( p<0.001 ) than those who had been screened but not recalled . The strongest predictor of psychological distress at six months was the PCQ score at the first measurement . Other predictors were a low level of education , living in high density urban areas , and having only one child or no children at all . Widows appeared to cope better than other women . Conclusions It is possible to define a group of women with false positive results who are already at risk of coping less effectively at the time of recall . Offering these women counselling or other types of support should be considered The aim was to investigate the psychological consequences of further investigation after breast cancer screening . Study participants include 509 women ( 61 % ) recalled due to suspicious findings on screening mammograms , and a matched control group of 285 women ( 68 % ) with normal mammograms . Psychological distress was prospect ively assessed with the Hospital Anxiety and Depression Scale ( HADS ) . 46 % of the women reported borderline or clinical ly significant anxiety prior to the recall visit . A few days after the visit , anxiety and depression had decreased significantly ( P<0.01 ) in women informed about normal or benign results at the recall clinic , while reported distress remained at relatively high levels in women referred to surgical biopsy . The results demonstrate the adverse short-term effect of a delay in receiving false-positive results , but do not indicate that the recall experience results in long-term anxiety or depression for a majority of women The purpose of this study was to evaluate a woman 's psychological and immunological response to breast biopsy before and after the procedure . Women were enrolled into the study when notified of the need for breast biopsy . Psychological and immunological assessment s were made at enrollment , on the day of breast biopsy , as well as 1 month and 4 months after notification of biopsy results . Psychological assessment s demonstrated that perceived stress , anxiety , and mood disturbance were heightened before biopsy and remained elevated after biopsy regardless of the diagnosis . Immunologically , the women exhibited reduced natural killer cell activity and INF gamma production before biopsy with reductions significant 1 month after the procedure . In contrast , IL-4 , IL-6 , and IL-10 production were increased before and after the procedure with most significant increases prior to the procedure and continuing 1 month after the procedure . These results demonstrate that undergoing biopsy of the breast for cancer diagnosis is an emotional experience , characterized by increased perceived stress , anxiety , and mood disturbance . This emotional distress is accompanied by reduced NK cell activity and cytokine dysregulation . The psychological and immunological impact of breast biopsy is not transient , but persists well beyond the actual experience of the biopsy procedure . Noteworthy is the observation that women with benign or malignant biopsy results experienced similar psycho-immune consequences . Hence , these observations are of relevance not only to women diagnosed with malignancy , who face the challenges of cancer treatment and adaptation to illness , but also to women with benign biopsy findings PURPOSE / OBJECTIVES To investigate distress and its association with immune function among women with suspected breast cancer . DESIGN Prospect i ve , descriptive , correlational study . SETTING An outpatient breast clinic at a tertiary urban hospital . SAMPLE A convenience sample of women who had either a fine needle aspiration or open breast biopsy for a suspicion of breast cancer . Thirty-five women comprised the study sample , 6 with malignant and 29 with benign tumors . METHODS Data were collected at three points in time . The first time ( T1 ) was after the physician visit when the need for breast biopsy was ascertained . The second time ( T2 ) was 7 - 10 days postbiopsy , and the third time ( T3 ) was 7 - 10 days after T2 . At T1 , T2 , and T3 , participants filled out the Brief Symptom Inventory ( a measure of psychological distress ) and the Adapted Symptom Distress Scale ( a measure of symptom distress ) and provided a blood sample . Demographic data also were collected at T1 . Immune function was measured by serum cytokine levels of transforming growth factor beta ( TGF beta ) and tumor necrosis factor alpha ( TNF alpha ) . MAIN RESEARCH VARIABLES Psychological distress , symptom distress , and immune function . FINDINGS Psychological distress scores were moderate to high . Symptom distress was either nonexistent or slight . Significant correlations between psychological distress and symptom distress were found at T2 and T3 . At T2 , significant relationships between psychological distress and TNF alpha and between symptom occurrence and TNF alpha were found . Psychological and symptom distress scores were significantly different between women with malignant versus benign tumors at all three times . No differences in cytokine levels were found between the groups . CONCLUSIONS These results suggest the strong effect that the diagnostic process has on psychological distress and its potential effects on immune functioning . Distress was significantly greater for women with malignant disease ; however , women with benign disease continued to have elevated levels of distress . IMPLICATION S FOR NURSING PRACTICE Nurses should be aware of the extremely stressful nature of the diagnostic phase and should continue to provide support , knowing that this distress continues throughout this phase , particularly for women diagnosed with malignancy The objective of this study was to evaluate and document pain and psychological distress related to imaging-guided core needle biopsy ( CNB ) of the breast . This prospect i ve study of 52 consecutive patients undergoing CNB of the breast assessed anxiety , pain , acute stress disorder , and activities of daily living both preprocedure and at 24 hours , 5 days , and 30 days postprocedure . Survey instruments included the State-Trait Anxiety Inventory ( STAI ) , a visual analog pain scale , the SF-36 Physical Functioning Scale , and DSM IV criteria for acute stress disorder . Preprocedure the mean scores for self-reported levels of state and trait anxiety were 47.11 ( SD = 13.53 ) and 37.71 ( SD = 11.24 ) , respectively . At 24 hours postprocedure , the mean score for self-reported state anxiety was 38.74 ( SD = 17.77 ) , a significant reduction from the preprocedure level reported by patients ( p < 0.005 ) . Further reductions in state anxiety levels were reported at 5 and 30 days postprocedure . The mean scores for state anxiety fell within the normal range at 30 days postprocedure ( mean 32.75 , SD = 10.97 ) . However , at 5 days post-CNB , patients with confirmed malignancies reported significantly more anxiety than patients without malignancies ( p = 0.002 ) . This difference was not present at 30 days post-CNB ( p = 0.17 ) . Patients reported average pain scores of 2.0 ( on a scale of 0 - 10 ) during the biopsy . This decreased to 1.3 at 24 hours , 0.3 at 5 days , and 0.2 at 30 days . Reported symptoms of acute stress related to the procedure significantly increased over the period between the 5-day interview and the 30-day interview . One ( 2 % ) patient reported avoidance of thoughts about CNB 5 days postprocedure and 5 ( 12 % ) patients reported this at 30 days postprocedure ( p < 0.05 ) . Patients undergoing CNB reported significant levels of state anxiety which were greatest at the time of biopsy . A significant decrease was observed at 24 hours postprocedure , despite the fact that biopsy results were not available to the patients . Self-reported levels of anxiety for the group , regardless of biopsy results , fell within the normal range by 30 days . Further research and interventions are recommended to address the management of anxiety for patients undergoing CNB Five community- design ed pilot projects were undertaken to reduce the time to diagnosis following an abnormal mammogram . One thous and five hundred and seventy-eight women with abnormal mammograms completed a self-administered question naire ( 71 % response ) which inquired about experiences and satisfaction with time delay from screening to diagnosis , the information received and support given by health professionals , and measures of anxiety and stress during this time interval . Four of the five pilot project initiatives shortened the time interval from screening to diagnosis , the greatest improvement occurring with facilitated referral from screening to diagnostic breast imaging . There was little difference among the pilot projects and control for most measures of client satisfaction and anxiety . Differences were found between biopsied and nonbiopsied women for several of these measures . Shortening the time to diagnosis positively influenced the client 's perception of unnecessary delay |
12,690 | 20,689,584 | Findings , based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women .
Some clinical ly important exceptions , however , were apparent : women experienced substantially lower response rates with newer antiemetics than men ( 45 % vs. 58 % ; relative risk 1.49 , 95 % confidence interval 1.35 - 1.64 ) ; men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder ; women discontinued lovastatin more frequently than men because of adverse events .
Overall , for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment . | Being male or female is an important determinant of risks for certain diseases , patterns of illness and life expectancy .
Although differences in risks for and prognoses of several diseases have been well documented , sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear .
The objective of this umbrella review was to determine whether clinical ly relevant differences in efficacy and safety of commonly prescribed medications exist between men and women . | OBJECTIVE This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania . METHOD Patients with DSM-IV bipolar I disorder experiencing an acute manic episode ( baseline Young Mania Rating Scale score > /== " BORDER="0">20 ) were r and omly assigned to 3 weeks of treatment with risperidone ( flexible dose : 1 - 6 mg/day ) or placebo . The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale . Secondary efficacy measures included the Clinical Global Impression ( CGI ) severity rating and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and Global Assessment Scale ( GAS ) . Safety assessment s consisted of monitoring adverse events , vital signs , electrocardiogram and laboratory results , and scores on the Extrapyramidal Symptom Rating Scale . RESULTS Subjects ( N=259 ) received treatment with either risperidone ( N=134 ) or placebo ( N=125 ) . The mean modal dose of risperidone was 4.1 mg/day . Improvement in mean Young Mania Rating Scale total score ( adjusted for covariates ) was significantly greater in the risperidone than in the placebo group at endpoint ( mean change=-10.6 [ SD=9.5 ] versus -4.8 [ SD=9.5 ] , respectively ) , with significant between-group differences seen as early as 3 days after start of treatment ( change with risperidone : mean=-6.8 [ SD=5.8 ] ; change with placebo : mean=-4.0 [ SD=5.8 ] ) and continuing throughout all time points . Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and GAS were also significantly greater among patients receiving risperidone than those given placebo . The most common adverse event reported among risperidone patients was somnolence . While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone , mean total and subscale scores were low . CONCLUSIONS Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action . Risperidone was well tolerated by patients in this study The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid‐related disease Background — Clinical trials have demonstrated that , compared with placebo , intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease . However , no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes . Methods and Results — A total of 893 ambulatory coronary artery disease patients ( 30 % women ) 65 to 85 years of age with ≥1 episode of myocardial ischemia that lasted ≥3 minutes during 48-hour ambulatory ECG at screening were r and omized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months . The primary efficacy parameter ( absolute change from baseline in total duration of ischemia at month 12 ) was significantly reduced in both groups at month 3 and month 12 ( both P<0.001 for each treatment group ) with no significant difference between the treatment groups . Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients , a trend toward fewer major acute cardiovascular events ( hazard ratio , 0.71 ; 95 % confidence interval , 0.46 , 1.09 ; P=0.114 ) , and a significantly greater reduction in all-cause death ( hazard ratio , 0.33 ; 95 % confidence interval , 0.13 , 0.83 ; P=0.014 ) . Conclusions — Compared with moderate pravastatin therapy , intensive atorvastatin therapy was associated with reductions in cholesterol , major acute cardiovascular events , and death in addition to the reductions in ischemia observed with both therapies . The contrast between the therapies ’ differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol – lowering thresholds for ischemia and major acute cardiovascular events may differ . The Study Assessing Goals in the Elderly ( SAGE ) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy BACKGROUND Despite the use of aspirin , there is still a risk of ischaemic events after percutaneous coronary intervention ( PCI ) . We aim ed to find out whether , in addition to aspirin , pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI . METHODS 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been r and omly assigned double-blind treatment with clopidogrel ( n=1313 ) or placebo ( n=1345 ) . Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission , and for a median of 10 days overall . After PCI , most patients ( > 80 % ) in both groups received open-label thienopyridine for about 4 weeks , after which study drug was restarted for a mean of 8 months . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , or urgent target-vessel revascularisation within 30 days of PCI . The main analysis was by intention to treat . FINDINGS There were no drop-outs . 59 ( 4.5 % ) patients in the clopidogrel group had the primary endpoint , compared with 86 ( 6.4 % ) in the placebo group ( relative risk 0.70 [ 95 % CI 0.50 - 0.97 ] , p=0.03 ) . Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death , myocardial infa rct ion , or any revascularisation ( p=0.03 ) , and of cardiovascular death or myocardial infa rct ion ( p=0.047 ) . Overall ( including events before and after PCI ) there was a 31 % reduction cardiovascular death or myocardial infa rct ion ( p=0.002 ) . There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group ( p=0.001 ) . At follow-up , there was no significant difference in major bleeding between the groups ( p=0.64 ) . INTERPRETATION In patients with acute coronary syndrome receiving aspirin , a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events , compared with placebo BACKGROUND The objective of the current study was to examine possible clinical predictors of positive response to lamotrigine or gabapentin monotherapy in treatment-refractory affectively ill patients . METHODS Forty-five patients with treatment refractory bipolar ( n = 35 ) or unipolar ( n = 10 ) affective disorder participated in a clinical study evaluating six weeks of treatment with lamotrigine , gabapentin , or placebo monotherapy given in a double-blind , r and omized fashion with two subsequent cross-overs to the other agents . Patients received daily mood ratings and weekly cross-sectional scales . Much or very much improved on the Clinical Global Impression scale modified for bipolar illness was considered a positive response . Degree of response was correlated with a number of baseline demographic and course of illness variables in a univariate analysis and then by linear regression . RESULTS Response rates to lamotrigine ( 51 % ) exceeded those to gabapentin ( 28 % ) and placebo ( 21 % ) . A positive response to lamotrigine monotherapy was associated with a bipolar diagnosis ; fewer hospitalizations ; fewer prior medication trials ; and male gender ( of which the latter two variables survived logistic regression ) . For gabapentin , degree of response correlated with shorter duration of illness ; younger age ; and lower baseline weight ( with the latter two surviving linear regression ) . CONCLUSIONS In this highly treatment-refractory population , lamotrigine appeared most effective for male patients with fewer prior medication trials . Gabapentin monotherapy , although not better than placebo , appeared most effective in those with younger age and lower baseline weight . These preliminary data in a treatment refractory subgroup may help in the further definition of the range of clinical utility of these widely used anticonvulsants OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features AIM To compare the efficacy , safety and tolerability of a fixed combination glyburide/metformin preparation with those of glyburide or metformin alone in patients with type 2 diabetes inadequately controlled by sulphonylurea , diet and exercise . METHODS In this 16-week , r and omized , double-blind , parallel group study , 639 patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea were r and omly assigned to : glyburide 10 mg b.i.d . ( n = 164 ) ; metformin 500 mg ( n = 153 ) ; glyburide/metformin 2.5 mg/500 mg ( n = 160 ) ; or glyburide/metformin 5 mg/500 mg ( n = 162 ) . Titration was allowed to maximum doses of 2000 mg for metformin or 10 mg/2000 mg and 20 mg/2000 mg for glyburide/metformin 2.5 mg/500 mg and 5 mg/500 mg respectively . The primary outcome measure was HbA1c level after 16 weeks ; secondary end-points included fasting and 2-h post-pr and ial plasma glucose . Adverse events ( AEs ) were recorded and summarized by treatment group . RESULTS Both strengths of glyburide/metformin equally reduced mean HbA1c by 1.7 % more than did glyburide alone ( p < 0.001 ) , and by 1.9 % more than did metformin alone ( p < 0.001 ) . Final mean fasting plasma glucose concentrations were also lower in both glyburide/metformin groups than in the glyburide ( -2.8 mmol/l , -51.3 mg/dl ; p < 0.001 ) and metformin groups ( -3.6 mmol/l , -64.2 mg/dl ; p < 0.001 ) . Safety and tolerability were similar across all treatment groups , except for a higher incidence of gastrointestinal AEs in the metformin monotherapy group , and more patients reporting mild or moderate symptoms of hypoglycaemia while taking glyburide/metformin . CONCLUSIONS Both glyburide/metformin tablet strengths produced , with equal efficacy , significantly better glycaemic control than monotherapy with either agent . These data also confirm that glycaemic efficacy does not require maximal sulphonylurea doses in combination with metformin AIMS In observational studies , prolonged lower blood total cholesterol levels - down at least to 3 mmol . l-1 - are associated with lower risks of coronary heart disease . Cholesterol-lowering therapy may , therefore , be worthwhile for individuals at high risk of coronary heart disease events irrespective of their presenting cholesterol levels . Observational studies also suggest that increased dietary intake of antioxidant vitamins may be associated with lower risks of coronary heart disease . The present r and omized trial aims to assess reliably the effects on mortality and major morbidity of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of different categories of high-risk patients . METHODS AND RESULTS Men and women aged 40 to 80 years were eligible provided they were considered to be at elevated risk of coronary heart disease death because of past history of myocardial infa rct ion or other coronary heart disease , occlusive disease of non-coronary arteries , diabetes mellitus or treated hypertension ; had baseline blood total cholesterol of 3.5 mmol . l-1 or greater ; and no clear indications for , or contraindications to , either of the study treatments . Eligible patients who completed a pre-r and omization run-in phase on active treatment were r and omly allocated to receive simvastatin ( 40 mg daily ) or matching placebo tablets and , in a ' 2x2 factorial ' design , antioxidant vitamins ( 600 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene daily ) or matching placebo capsules . Follow-up visits after r and omization are scheduled at 4 , 8 and 12 months , and then 6-monthly , for at least 5 years . Between July 1994 and May 1997 , 15 454 men and 5082 women were r and omized , with 9515 aged over 65 years at entry . Diagnostic criteria overlapped , with 8510 ( 41 % ) having had myocardial infa rct ion ( most of whom were either female , or elderly or with low blood cholesterol ) , 4869 ( 24 % ) some other history of coronary heart disease , 3288 ( 16 % ) cerebrovascular disease , 6748 ( 33 % ) peripheral vascular disease , 5963 ( 29 % ) diabetes mellitus ( of whom 3985 had no history of coronary heart disease ) and 8455 ( 41 % ) treated hypertension . Baseline non-fasting total cholesterol levels were less than 5.5 mmol . l-1 in 7882 ( 38 % ) participants , and LDL ( low density lipoprotein ) cholesterol less than 3.0 mmol . l-1 in 6888 ( 34 % ) . During a mean follow-up of 25 months ( range : 13 to 47 months ) , no significant differences had been observed between the treatment groups in the numbers of patients with muscle symptoms , other possible side-effects leading to termination of study treatment , or elevated liver and muscle enzymes . After 30 months of follow-up , 81 % of r and omized patients remained compliant with taking their study simvastatin or placebo tablets , and allocation to simvastatin produced average reductions in non-fasting blood total and LDL cholesterol of about 1.5 - 1.6 mmol . l-1 and 1.1 - 1.2 mmol . l-1 respectively . Eighty-seven per cent of patients remained compliant with taking their vitamin or placebo capsules , and allocation to the vitamin supplement produced an average increase in plasma vitamin E levels of about 24 micromol . l-1 . Based on this initial follow-up period , the estimated annual rate of non-fatal myocardial infa rct ion or fatal coronary heart disease is 2.4 % , annual stroke rate is 1.3 % , and annual all-cause mortality rate is 2 . 2 % . CONCLUSION The Heart Protection Study is large , it has included a wide range of patients at high risk of vascular events , and the treatment regimens being studied are well-tolerated and produce substantial effects on blood lipid and vitamin levels . The study should , therefore , provide reliable evidence about the effects of cholesterol-lowering therapy and of antioxidant vitamin supplements on all-cause or cause-specific mortality and major morbidity in a range of different categories of individuals for whom uncertainty remains about the balance of benefits and risks of these treatments . CONTEXT Following percutaneous coronary intervention ( PCI ) , short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone . However , the optimal duration of combination oral antiplatelet therapy is unknown . Also , although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI , the practical application of this therapy has not been prospect ively studied . OBJECTIVES To evaluate the benefit of long-term ( 12-month ) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose , both in addition to aspirin therapy . DESIGN , SETTING , AND PARTICIPANTS The Clopidogrel for the Reduction of Events During Observation ( CREDO ) trial , a r and omized , double-blind , placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI , enrolled at 99 centers in North America from June 1999 through April 2001 . INTERVENTIONS Patients were r and omly assigned to receive a 300-mg clopidogrel loading dose ( n = 1053 ) or placebo ( n = 1063 ) 3 to 24 hours before PCI . Thereafter , all patients received clopidogrel , 75 mg/d , through day 28 . From day 29 through 12 months , patients in the loading-dose group received clopidogrel , 75 mg/d , and those in the control group received placebo . Both groups received aspirin throughout the study . MAIN OUTCOME MEASURES One-year incidence of the composite of death , myocardial infa rct ion ( MI ) , or stroke in the intent-to-treat population ; 28-day incidence of the composite of death , MI , or urgent target vessel revascularization in the per- protocol population . RESULTS At 1 year , long-term clopidogrel therapy was associated with a 26.9 % relative reduction in the combined risk of death , MI , or stroke ( 95 % confidence interval [ CI ] , 3.9%-44.4 % ; P = .02 ; absolute reduction , 3 % ) . Clopidogrel pretreatment did not significantly reduce the combined risk of death , MI , or urgent target vessel revascularization at 28 days ( reduction , 18.5 % ; 95 % CI , -14.2 % to 41.8 % ; P = .23 ) . However , in a prespecified subgroup analysis , patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6 % ( 95 % CI , -1.6 % to 62.9 % ; P = .051 ) for this end point compared with no reduction with treatment less than 6 hours before PCI . Risk of major bleeding at 1 year increased , but not significantly ( 8.8 % with clopidogrel vs 6.7 % with placebo ; P = .07 ) . CONCLUSIONS Following PCI , long-term ( 1-year ) clopidogrel therapy significantly reduced the risk of adverse ischemic events . A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days , but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events BACKGROUND Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder . Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse , compared with lithium or valproate alone . METHOD Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium ( 0.6 - 1.2 mmol/l ) or valproate ( 50 - 125 microg/ml ) received lithium or valproate plus either olanzapine 5 - 20 mg/day ( combination therapy ) or placebo ( monotherapy ) , and were followed in a double-masked trial for 18 months . RESULTS The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse ( median time to relapse : combination therapy 94 days , monotherapy 40.5 days ; P=0.742 ) , but was significant for symptomatic relapse ( combination therapy 163 days , monotherapy 42 days ; P=0.023 ) . CONCLUSIONS Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission , but not syndromic remission , for longer than those receiving lithium or valproate monotherapy AIMS Large r and omized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure . The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain . The SENIORS study was performed to assess effects of the beta-blocker , nebivolol , in patients > /=70 years , regardless of ejection fraction . METHODS AND RESULTS We r and omly assigned 2128 patients aged > /=70 years with a history of heart failure ( hospital admission for heart failure within the previous year or known ejection fraction < /=35 % ) , 1067 to nebivolol ( titrated from 1.25 mg once daily to 10 mg once daily ) , and 1061 to placebo . The primary outcome was a composite of all cause mortality or cardiovascular hospital admission ( time to first event ) . Analysis was by intention to treat . Mean duration of follow-up was 21 months . Mean age was 76 years ( SD 4.7 ) , 37 % were female , mean ejection fraction was 36 % ( with 35 % having ejection fraction > 35 % ) , and 68 % had a prior history of coronary heart disease . The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg . The primary outcome occurred in 332 patients ( 31.1 % ) on nebivolol compared with 375 ( 35.3 % ) on placebo [ hazard ratio ( HR ) 0.86 , 95 % CI 0.74 - 0.99 ; P=0.039 ] . There was no significant influence of age , gender , or ejection fraction on the effect of nebivolol on the primary outcome . Death ( all causes ) occurred in 169 ( 15.8 % ) on nebivolol and 192 ( 18.1 % ) on placebo ( HR 0.88 , 95 % CI 0.71 - 1.08 ; P=0.21 ) . CONCLUSION Nebivolol , a beta-blocker with vasodilating properties , is an effective and well-tolerated treatment for heart failure in the elderly Objectives : A large-scale postmarketing surveillance ( PMS ) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis ( RA ) . Methods : The PMS study was performed for all patients with RA who were treated with infliximab . They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospect ively monitored with all adverse events noted for a period of 6 months . All case reports , which include safety-related events , were collected monthly . Results : Adverse drug reactions ( ADRs ) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study . The incidence rates of total and serious ADRs were 28.0 % and 6.2 % , respectively . “ Infections ” or “ respiratory disorders ” were most commonly observed among serious ADRs . Bacterial pneumonia developed in 2.2 % , tuberculosis in 0.3 % , suspected Pneumocystis jiroveci pneumonia ( PCP ) in 0.4 % and interstitial pneumonitis in 0.5 % . Bacterial pneumonia ( for which individuals of male gender , of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk ) began to develop immediately after the start of treatment , while tuberculosis , PCP and interstitial pneumonitis developed about 1 month later . Serious infusion reactions were observed in 0.5 % and were more likely to occur in patients who had participated in previous clinical trials of infliximab . Conclusion : This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA PURPOSE : To compare the efficacy and safety of oral ondansetron with i.v . granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy . PATIENTS AND METHODS : Chemotherapy-naive patients with histologically confirmed malignancies were r and omized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v . infusion of normal saline , or a single 10 µg/kg ( 50 ml ) i.v . infusion of granisetron plus a placebo tablet in this multicenter , double-blind , parallel-group trial . Study drug was administered 30 min prior to a single i.v . infusion of cisplatin ( 50 - 75 mg/m² ) , given over a period of < /= 3 h. Concurrent administration of corticosteroids was not allowed . Efficacy measurements included the number of emetic episodes , need for rescue medication , and patient assessment s of nausea and appetite . Complete response ( CR ) was defined as no emetic episodes , rescue , or withdrawal ; major response was defined as one or two episodes . Safety was evaluated by monitoring adverse events and changes in laboratory parameters . RESULTS : A total of 371 patients entered the study and received study drug , of whom 184 received ondansetron and 187 received granisetron . For all parameters tested , a single 24 mg oral ondansetron tablet was at least as effective as i.v . granisetron . CR was achieved in 58 % of ondansetron-treated patients and 51 % of granisetron-treated patients ( 95 % confidence interval on the difference : -4 % to 17 % ) . Subjective assessment s revealed no difference with regard to complete control of nausea , appetite , or satisfaction with antiemetic therapy . Both drugs were well tolerated ; the most common adverse event was headache . CONCLUSION : A single 24 mg oral dose of ondansetron is at least as safe and effective as a single i.v . infusion of 10 µg/kg of granisetron in preventing nausea and vomiting induced by highly emetogenic cisplatin chemotherapy Aims /hypothesisThe aim of this study was to assess the efficacy and safety of sitagliptin ( MK-0431 ) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control ( HbA1c ≥7 % and ≤10 % ) on exercise and diet . Methods A total of 521 patients aged 27–76 years with a mean baseline HbA1c of 8.1 % were r and omised in a 1:2:2 ratio to treatment with placebo , sitagliptin 100 mg once daily , or sitagliptin 200 mg once daily , for 18 weeks . The efficacy analysis was based on an all- patients -treated population using an analysis of covariance , excluding data obtained after glycaemic rescue . Results After 18 weeks , HbA1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo ( placebo-subtracted HbA1c reduction : −0.60 % and −0.48 % , respectively ) . Sitagliptin also significantly decreased fasting plasma glucose relative to placebo . Patients with higher baseline HbA1c ( ≥9 % ) experienced greater placebo-subtracted HbA1c reductions with sitagliptin ( −1.20 % for 100 mg and −1.04 % for 200 mg ) than those with HbA1c < 8 % ( −0.44 % and −0.33 % , respectively ) or ≥8 % to 8.9 % ( −0.61 % and −0.39 % , respectively ) . Homeostasis model assessment beta cell function index and fasting proinsulin : insulin ratio , markers of insulin secretion and beta cell function , were significantly improved with sitagliptin . The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo . Sitagliptin had a neutral effect on body weight . Conclusions /interpretationSitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet OBJECTIVE To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender . METHODS A pooled data set from eight r and omized , controlled trials of patients with major depressive disorder ( MDD ) was reanalyzed to compare remission rates following therapy with venlafaxine ( n = 851 ) , one of several selective serotonin reuptake inhibitors ( SSRIs ) ( n = 748 ) , or placebo ( n = 446 ) . Remission was defined as a final Hamilton Rating Scale for Depression ( HAM-D ) score < or = 7 . Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment , sex , and age ( younger : < 50 ; older : > or = 50 ) . Among older women , the impact of hormone replacement therapy ( HRT ) on remission rates also was examined . RESULTS Remission rates on venlafaxine therapy were not affected by age , sex , or HRT use . Among women , but not men , there was a significant interaction reflecting poorer SSRI response in the older age group ( Wald chi-square = 4.21 , df = 1 , p = 0.04 ) ; HRT appeared to eliminate this difference . Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women ( 6%-9 % ) , the difference among older women not taking HRT was 23 % . CONCLUSIONS These findings provide further evidence that age , gender , and HRT moderate response to antidepressant medications BACKGROUND Differences in pharmacodynamic and pharmacokinetic characteristics among serotonin-receptor antagonists have been reported in pre clinical studies . This prompted us to carry out a study to determine whether such differences are important in terms of clinical efficacy or tolerability . PATIENTS AND METHODS 973 consecutive cancer patients scheduled to receive cisplatin for the first time ( at doses > or = 50 mg2 ) , entered a double-blind multicenter r and omized study comparing intravenous ondansetron 8 mg versus granisetron 3 mg . Dexamethasone 20 mg was added to both serotonin antagonists . On days 2 to 4 after chemotherapy all patients received oral metoclopramide plus intramuscular dexamethasone as antiemetic prophylaxis for delayed emesis . Nausea and vomiting were assessed daily until day 6 after chemotherapy . RESULTS We evaluated 966 patients ( 483 receiving ondansetron and 483 granisetron ) . Complete protection from acute vomiting/nausea was obtained in 79.3%/72.0 % of patients receiving ondansetron and in 79.9%/71.8 % of those receiving granisetron . Complete protection from delayed vomiting/nausea as obtained in 69.7%/52.9 % and 70.0%/49.6 % of patients receiving the ondansetron or granisetron regimens , respectively . Adverse effects were mild and not significantly different between the two antiemetic regimens . CONCLUSIONS Ondansetron 8 mg and granisetron 3 mg , both combined with dexamethasone , showed similar efficacy and tolerability in the prevention of cisplatin-induced emesis . The choice between the two regimens can be dictated by their respective purchase prices Efficacy and tolerability of sitagliptin , a dipeptidyl peptidase-4 inhibitor , were assessed in Japanese patients with type 2 diabetes . In a multicenter , double-blind , r and omized , placebo-controlled trial in Japan , 151 patients with inadequate glycemic control [ HbA(1c ) > or = 6.5 % to < 10 % , fasting plasma glucose ( FPG ) > or = 126 to < or = 240 mg/dL ] were r and omized to once-daily sitagliptin 100 mg or placebo for 12 weeks . After 12 weeks , the least squares ( LS ) mean change from baseline HbA(1c ) was -0.65 % ( 95 % CI : -0.80 , -0.50 ) with sitagliptin versus 0.41 % ( 0.26 , 0.56 ) with placebo [ between-group difference=-1.05 % ( -1.27 , -0.84 ) ; p<0.001 ] . LS mean change from baseline FPG was -22.5mg/dL ( 95 % CI : -28.0 , -17.0 ) with sitagliptin versus 9.4 mg/dL ( 3.9 , 14.9 ) with placebo [ between-group difference=-31.9 mg/dL ( 95 % CI : -39.7,-24.1 ) ; p<0.001 ] . More patients achieved HbA(1c ) < 7 % or < 6.5 % with sitagliptin than with placebo ( p<0.001 ) . Following a meal tolerance test , 2-h postpr and ial glucose was significantly reduced with sitagliptin relative to placebo . Clinical and laboratory adverse experiences were similar between treatments , with no reported hypoglycemia adverse events with sitagliptin . Body weight was unchanged relative to baseline in the sitagliptin group ( -0.1 kg ) , but significantly ( p<0.01 ) different relative to the placebo group ( -0.7 kg ) . In this study , once-daily sitagliptin 100 mg for 12 weeks improved fasting and postpr and ial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes This multicentre , double-blind , double-dummy , r and omised trial was design ed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose ( > or = 80 mg/m2 ) cisplatin . Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period , beginning 30 min prior to cisplatin ( > or = 80 mg/m2 ) administration . The number and timing of emetic episodes , time to administration of escape anti-emetic medication , severity of nausea by visual analogue scale ( VAS ) , and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy . Investigators ' evaluations of overall efficacy and patients ' satisfaction with therapy were recorded at the end of the 24-h study period . Of the 474 patients evaluable for efficacy , complete responses were achieved by 54 , 47 and 48 % of patients given dolasetron mesilate 1.8 mg/kg , dolasetron mesilate 2.4 mg/kg and granisetron , respectively . Statistically , treatment groups had comparable complete and complete plus major responses , times to first emesis , and use of escape medication ; patient maximum nausea severity and treatment satisfaction ratings ; and physician nausea severity and overall efficacy assessment s. For the majority of efficacy endpoints , 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose . Gender and prior chemotherapy were significant predictors of complete response ; males and chemotherapy-naive patients had higher responses . The overall incidences of adverse events were comparable among the treatment groups ; headache and diarrhoea were most common . In conclusion , 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron ( 3 mg ) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy . In addition , because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose , the lower dose of 1.8 mg/kg is optimal for further clinical development Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors . Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer Background : Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders , especially those at high risk Irritable bowel syndrome is a common gastrointestinal disorder characterized by abdominal pain and discomfort and altered bowel habit . Antagonism at the 5‐HT3 receptor may be of benefit in the treatment of irritable bowel syndrome PURPOSE To assess the comparative antiemetic efficacy of single-dose intravenous ( IV ) dolasetron mesylate and ondansetron in preventing cisplatin-induced nausea and vomiting . PATIENTS AND METHODS Cancer patients ( n = 609 ) receiving first-course cisplatin chemotherapy were r and omized to one of three treatments : 1.8 or 2.4 mg/kg dolasetron mesylate salt ( equivalent to 1.3 and 1.8 mg/kg dolasetron base , respectively ) or 32 mg ondansetron . Each treatment was infused over 15 minutes , 30 minutes before cisplatin administration . Patients were stratified to cisplatin doses of > or = 70 and less than 91 mg/m2 ( n = 368 ) or > or = 91 mg/m2 ( n = 241 ) , administered over < or = 3 hours . Protocol -defined efficacy criteria included complete response ( zero emetic episodes and no rescue medication ) , major response ( 1 to 2 emetic episodes and no rescue medication ) , and patients ' report of nausea severity and satisfaction recorded on a 100-mm visual analog scale ( VAS ) . RESULTS The three treatments met protocol -specified criteria for equivalence . Complete response rates for dolasetron mesylate 1.8 mg/kg , 2.4 mg/kg , and ondansetron , respectively , were 49.2 % , 45.6 % , and 50.4 % for patients in the lower cisplatin stratum ( mean , 74.7 mg/m2 ) and 36.8 % , 31.3 % , and 31.8 % in the higher cisplatin stratum ( mean , 100.6 mg/m2 ) . No significant differences were observed in the extent of nausea with either dolasetron dose compared with ondansetron . Less nausea was noted with 1.8 mg/kg dolasetron compared with the 2.4 mg/kg dose ( P = .044 ) All three antiemetic treatments were well tolerated . Asymptomatic electrocardiogram changes were recorded with both dolasetron and ondansetron . CONCLUSION A single IV dose of dolasetron mesylate ( 1.8 or 2.4 mg/kg ) has comparable safety and efficacy to a single 32-mg IV dose of ondansetron in patients receiving cisplatin chemotherapy Abstract Background : Unstable bladder symptoms are a common problem in general practice . Drug therapy with anticholinergic drugs is frequently used in the management of this condition . However such drugs are associated with a high incidence of anticholinergic adverse effects . Tolterodine is a competitive anticholinergic agent , selective for the bladder as opposed to the salivary gl and s. Objective : To monitor the safety of tolterodine as used in general practice patients in Engl and for the treatment of urinary frequency , urgency and incontinence . Design : Prospect i ve observational cohort study . Patients and participants : 14 526 patients [ mean age 62.7 ( SD 16.4 ) years ; 68.6 % female ] . Methods : Patients prescribed tolterodine in general practice , soon after the release of the drug in the UK , were followed up for a minimum of 6 months using the technique of prescription-event monitoring ( PEM ) . Results : The most common adverse events reported were dry mouth , headache , malaise , constipation , dyspepsia , nausea and vomiting and pain in abdomen . We identified some uncommon events as possible adverse drug reactions — notably hallucinations , tachycardia and palpitations . The prevalence of these events was compared with that in patient cohorts for other drugs on the PEM data base . The age- and sex-adjusted relative risk of hallucinations on tolterodine compared with 10 drugs of other therapeutic classes , and with terodiline , another drug indicated for bladder instability , was 4.85 [ 95 % confidence interval ( CI ) 2.72 to 8.66 ] and 1.25 ( 95 % CI 0.62 to 2.53 ) , respectively . There was no significant difference for tachycardia/palpitation in this comparison . Conclusions : Tolterodine is well tolerated in general practice at the recommended daily dose . Hallucinations , tachycardia and palpitations are infrequently associated with the drug The risk for coronary heart disease death for younger adults is 3 to 10 times greater in men than in women , but this differential diminishes with advancing age [ 1 ] . Among women older than 50 years , 53 % of deaths are due to heart disease and stroke [ 2 ] . Annually , more women than men die of either coronary heart disease or stroke [ 2 ] . Once diagnosed with coronary heart disease , women often have a worse prognosis than men . Women have a higher mortality rate after symptomatic myocardial infa rct ion [ 3 ] . Women undergoing coronary bypass grafting have less complete revascularization , reduced patency rate , less relief of symptoms , and a higher mortality rate than do men [ 4 , 5 ] . Percutaneous transluminal angioplasty also appears to have a lower initial success rate and higher procedure-associated mortality rate among women [ 6 ] . The prevention of coronary heart disease in women , as well as in men , is increasingly recognized as being of great public health importance . In this report , we evaluated the efficacy and tolerability of lovastatin in women who participated in the Exp and ed Clinical Evaluation of Lovastatin ( EXCEL ) study [ 7 ] . Patients in the EXCEL study had moderately elevated baseline levels of plasma total and low-density lipoprotein ( LDL ) cholesterol , typical of those seen in the usual clinical practice . The study design provided for large treatment groups so that the incidence of abnormal laboratory safety tests and clinical adverse events ( particularly involving liver and muscle ) could be reliably determined among treatment groups even at low frequency . Although an analysis based on gender was not an a priori objective of the EXCEL study design , the large sample size provided an opportunity to investigate the effect of lovastatin in women , to assess the effect of concomitant administration of estrogen-replacement therapy on the efficacy of lovastatin , and to detect any clinical ly important gender differences in efficacy and tolerability . Methods The design of this study and the methods used have been described previously [ 7 ] . In summary , the EXCEL study evaluated the efficacy and tolerability of lovastatin using a diet- and placebo-controlled , r and omized , double-blind design . The protocol excluded premenopausal women unless surgically sterilized ; however , data classifying women as surgically sterilized or postmenopausal were not collected . After a minimum of 4 weeks on an American Heart Association Step I diet , 8245 patients ( 3390 women ) with moderate primary hypercholesterolemia ( total cholesterol , 6.21 to 7.76 mmol/L [ 240 to 300 mg/dL ] ; LDL cholesterol 4.14 mmol/L ( 160 mg/dL ) ; and triglycerides < 3.95 mmol/L [ 350 mg/dL ] ) from 362 clinical centers were instructed to continue diet and were r and omly assigned to 48 weeks of treatment with one of the following five regimens : placebo , or 20 or 40 mg lovastatin once daily , or 20 or 40 mg twice daily . The study was approved by institutional review boards and participants gave written informed consent . Laboratory tests were performed by SmithKline Beecham Laboratories ( Clinical Trials Division , Van Nuys , California ) . Efficacy Analyses Total cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglycerides were measured using st and ard enzymatic techniques [ 7 ] . The LDL cholesterol was calculated using the Friedewald approximation [ 8 ] . Response to treatment was calculated by the formula percent change equals ( [ baseline level minus treatment level ] divided by baseline level ) 100 . A patient 's baseline level was the mean of two measurements in 91 % to 92 % of patients in each treatment group . The treatment values represented the mean of up to four measurements taken every 12 weeks during treatment . In calculations of LDL cholesterol response , data from 606 to 650 ( 92.5 % [ lovastatin , 20 mg once daily ] to 93.5 % [ lovastatin , 20 mg twice daily ] ) women and 897 to 941 ( 94.3 % [ lovastatin , 20 mg twice daily ] to 95.3 % [ lovastatin , 20 mg once daily ] ) men in each treatment group were available for both baseline and treatment period measurements . For total LDL and HDL cholesterol , two-sided t-tests were used to assess differences in mean percentage change between placebo and each lovastatin treatment group . The Wilcoxon rank sum test was used for testing differences in triglyceride levels . A less extensive approach , using linear statistical models , was used to assess the effects of concomitant use of estrogen . The covariates included in this modeling were baseline effects of age and lipid/lipoprotein levels . Safety Analyses Elevations in serum alanine aminotransferase and aspartate aminotransferase and muscle symptoms ( complaints of pain , tenderness , or weakness ) with increased levels of serum creatine kinase represent clinical and laboratory abnormalities associated with lovastatin therapy . Analyses presented here examine gender differences in both the incidence of elevations greater than the upper limit of normal and the mean levels of change from baseline to the end of treatment . Survival analysis methods specific for analyzing incidence have been described previously [ 9 ] . For serum transaminases , 95 % confidence intervals for mean differences between women and men that did not overlap zero were considered statistically significant . The Cochran-Mantel-Haenszel test [ 10 ] , after stratification by treatment group , was used to assess gender differences in muscle symptoms and in the incidence of elevated serum transaminases and creatine kinase . The Fisher exact test was used to evaluate treatment differences between placebo and lovastatin groups ; this test was done separately for women and men . The proportion of patients having a clinical adverse experience ( any change in health status ) that investigators rated blindly ( without knowledge of treatment group assignment ) as being possibly , probably , or definitely drug related was examined by gender and by estrogen use with lovastatin . These were categorized into serious drug-related adverse experiences ( result ed in death ; required or prolonged hospitalization ; were cancers ; or caused permanent disability ) , nonserious adverse experiences , and adverse experiences requiring discontinuation of therapy . The Cochran-Mantel-Haenszel test [ 10 ] was used to test for gender differences after stratification by treatment group . Results Characteristics of Women at Baseline Of the total 8245 patients , 3390 ( 41 % ) were women ( Table 1 ) . The number of women r and omized to each treatment group ranged from 655 to 695 . The average age was 58.4 years , 89.8 % were white , 18.3 % reported that they currently smoked cigarettes , and 42.1 % were hypertensive . The mean baseline total cholesterol level was 6.74 mmol/L ( 261 mg/dL ) , and the mean LDL cholesterol level was 4.60 mmol/L ( 178 mg/dL ) . Although gender differences were not evident in most baseline characteristics , the mean age of women was 4.5 years older . They were less likely to have a history of coronary heart disease ( 16.3 % versus 37.3 % ) , less likely to consume alcohol ( 43 % versus 65 % ) and particularly seven or more drinks per week ( 5 % versus 19 % ) , had higher mean HDL cholesterol levels ( 1.32 mmol/L [ 51 mg/dL ] versus 1.05 mmol/L [ 41 mg/dL ] ) , and lower median triglyceride levels ( 1.65 mmol/L [ 147 mg/dL ] versus 1.94 mmol/L [ 173 mg/dL ] ) . Table 1 . Baseline Characteristics of R and omized Women * Lipid and Lipoprotein Response Lovastatin produced dose-dependent ( 20 to 80 mg/d ) reductions of 24.4 % to 40.4 % in LDL cholesterol and 9.4 % to 17.9 % in triglycerides , and increases of 6.7 % to 8.6 % in HDL cholesterol ( Table 2 ) . Lovastatin treatment groups differed ( P < 0.001 ) from placebo in the mean percentage changes from baseline for all lipid and lipoprotein parameters . Overall , these results were similar to those found in men . Table 2 . Change from Baseline in Plasma Lipid/Lipoprotein Levels of Women * To assess the achievement of National Cholesterol Education Program ( NCEP ) [ 11 ] LDL cholesterol goals after 48 weeks of lovastatin treatment , patients were categorized into two groups : a lower-risk group without coronary heart disease and with fewer than two coronary heart disease risk factors , and a high-risk group with coronary heart disease or at least two coronary heart disease risk factors , or both . In the lower-risk women , the NCEP LDL cholesterol goal of less than 4.14 mmol/L ( 160 mg/dL ) was reached by 26 % given placebo and from 82 % to 95 % treated with lovastatin ( 20 to 80 mg/d ) ( Figure 1 ) . In high-risk women , the NCEP LDL cholesterol goal of less than 3.36 mmol/L ( 130 mg/dL ) was reached by 4 % given placebo and from 40 % to 87 % treated with lovastatin ( 20 to 80 mg/d ) . Similar results were observed in men . Figure 1 . Percentage of women achieving National Cholesterol Education Program target levels for low-density cholesterol at week 48 . In both women and men , lovastatin-associated elevations in HDL cholesterol were dose dependent , and the percentage increases were larger when baseline levels of HDL cholesterol were low . When baseline HDL cholesterol levels were less than 0.91 mmol/L ( 35 mg/dL ) , lovastatin ( 20 to 80 mg/d ) increased the placebo-corrected mean HDL cholesterol level in women by 1.6 % to 11.5 % . When baseline HDL cholesterol levels were 0.91 mmol/L or higher , the corresponding placebo-corrected increases were 4.7 % to 5.9 % . Fewer women than men ( 5 % to 8 % , versus 25 % to 30 % ) had HDL cholesterol levels less than 0.91 mmol/L. Safety Analyses Successive elevations in alanine aminotransferase or aspartate aminotransferase greater than three times the upper limit of normal were found in one woman ( 0.2 % ) given placebo ; two ( 0.4 % ) given 20 mg/d ; three ( 0.5 % ) given 40 mg every evening ; five ( 1.0 % ) given 20 mg twice daily , and eight ( 1.6 % ) given 80 mg/d . No statistically significant gender differences in incidence were observed . Mean alanine aminotransferase levels , however , showed less increase with lovastatin treatment in women ( up to 0.05 kat/L [ 26.3 % ] at 80 mg/d ) than in men ( 0.06 to 0.11 kat/L [ 19.6 % to 30.1 % ] Breakthrough depression is a common problem in the treatment of bipolar disorder . Only one , recently published , double-blind , placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients . This report describes , in further detail , the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder . A r and omized , double-blind , parallel-group , multicenter study was conducted over a 52-week maintenance period . Bipolar I patients , who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode , were r and omized to maintenance treatment with divalproex , lithium , or placebo in a 2 : 1 : 1 ratio . Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase . Outcome measures were the rate of early discontinuation for depression , time to depressive relapse , proportion of patients with depressive relapse , mean change in Depressive Syndrome Scale score , proportion of patients receiving antidepressants , and time in the study . Among patients taking an antidepressant , a higher percentage of patients on placebo than divalproex discontinued early for depression . Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period . Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance . Indices of severity of pre study illness course predicted worse outcome in all treatment groups . Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder , particularly in patients who had responded to divalproex when manic , and among patients with a more severe course of illness BACKGROUND Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality , although typically their plasma concentrations of LDL cholesterol are similar to those in the general population . Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited , and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk . METHODS 5963 UK adults ( aged 40 - 80 years ) known to have diabetes , and an additional 14573 with occlusive arterial disease ( but no diagnosed diabetes ) , were r and omly allocated to receive 40 mg simvastatin daily or matching placebo . Prespecified analyses in these prior disease subcategories , and other relevant subcategories , were of first major coronary event ( ie , non-fatal myocardial infa rct ion or coronary death ) and of first major vascular event ( ie , major coronary event , stroke or revascularisation ) . Analyses were also conducted of subsequent vascular events during the scheduled treatment period . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , intention to treat ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Both among the participants who presented with diabetes and among those who did not , there were highly significant reductions of about a quarter in the first event rate for major coronary events , for strokes , and for revascularisations . For the first occurrence of any of these major vascular events among participants with diabetes , there was a definite 22 % ( 95 % CI 13 - 30 ) reduction in the event rate ( 601 [ 20.2 % ] simvastatin-allocated vs 748 [ 25.1 % ] placebo-allocated , p<0.0001 ) , which was similar to that among the other high-risk individuals studied . There were also highly significant reductions of 33 % ( 95 % CI 17 - 46 , p=0.0003 ) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry , and of 27 % ( 95 % CI 13 - 40 , p=0.0007 ) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L ( 116 mg/dL ) . The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied , including : those with different duration , type , or control of diabetes ; those aged over 65 years at entry or with hypertension ; and those with total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . In addition , among participants who had a first major vascular event following r and omisation , allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period . INTERPRETATION The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied . After making allowance for non-compliance , actual use of this statin regimen would probably reduce these rates by about a third . For example , among the type of diabetic patient studied without occlusive arterial disease , 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event ( and , among these 45 people , to prevent about 70 first or subsequent events during this treatment period ) . Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events , irrespective of their initial cholesterol concentrations Objective : The primary objective was to evaluate sexual function ( SF ) separately in men and women with major depressive disorder ( MDD ) before and during treatment with bupropion sustained release ( SR ) or paroxetine . The secondary objectives involved a comparative evaluation of the Sex Effects Scale ( Sex FX ) and the Investigator-Rated Sexual Desire and Functioning Scale ( IRSD-F ) , as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time . Method : There were 141 patients ( 68 women and 73 men ) who met DSM-IV criteria for a current major depressive episode . They were r and omly assigned to receive bupropion SR ( 150 to 300 mg daily ) or paroxetine ( 20 to 40 mg daily ) under double-blind trial conditions . Patients were assessed at baseline and at 2 , 4 , 6 , and 8 weeks with the 17-item Hamilton Depression Rating Scale ( HDRS17 ) , Sex FX , and IRSD-F. Results : Prior to treatment , women reported significantly lower SF on both the Sex FX and IRSD-F scales , compared with men . During treatment , there were no significant drug differences on measures of SF over time for women ; however , men who were treated with paroxetine reported a worsening of SF , whereas bupropion SR did not significantly alter SF . Both bupropion SR and paroxetine produced clinical ly and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission . There was a statistically significant correlation between the 2 measures of SF at all visits . There was also a significant inverse relation between depression and SF in women , but not in men , irrespective of drug . Conclusion : According to the Sex FX scale , a significant difference in antidepressant-related sexual dysfunction was detected in men , but not women , during treatment with bupropion SR or paroxetine BACKGROUND Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder with symptoms of abdominal pain , discomfort , and altered bowel function . Antagonists of the type 3 serotonin receptor ( 5-HT3 ) have shown promising results in the relief of IBS-associated symptoms . We aim ed to confirm these findings by doing a r and omised , placebo-controlled trial . METHODS We studied 647 female IBS patients with diarrhoea-predominant or alternating bowel patterns ( diarrhoea and constipation ) . 324 patients were assigned 1 mg alosetron and 323 placebo orally twice daily for 12 weeks , followed by a 4-week post-treatment period . Adequate relief of abdominal pain and discomfort was the primary endpoint ; secondary endpoints included improvements in urgency , stool frequency , and stool consistency . Analysis was by intention to treat . FINDINGS 79 ( 24 % ) of patients in the alosetron group and 53 ( 16 % ) in the placebo group dropped out . The difference in the drop-out rate between groups was mainly due to a greater occurrence of constipation in the alosetron group . A greater proportion of alosetron-treated patients than placebo-treated patients ( 133 [ 41 % ] vs 94 [ 29 % ] , respectively ) reported adequate relief for all 3 months of treatment ( difference 12 % [ 4.7 - 19.2 ] ) . Alosetron also significantly decreased urgency and stool frequency , and increased stool firmness . Constipation occurred in 30 % and 3 % of patients in the alosetron and placebo groups , respectively . INTERPRETATION Alosetron was well tolerated and clinical ly effective in alleviating pain and bowel-related symptoms in this population of women with IBS AIM To assess the addition of sitagliptin to ongoing metformin therapy in patients with type 2 diabetes who were inadequately controlled [ haemoglobin A(1c ) ( HbA(1c ) ) 7 - 11 % ] on metformin monotherapy . METHODS Patients ( n = 273 ) on metformin ( > /=1500 mg/day ) were r and omized to receive the addition of once-daily placebo , sitagliptin 100 mg or rosiglitazone 8 mg in a 1 : 1 : 1 ratio for 18 weeks . The efficacy analysis was based on the all- patients -treated population using an analysis of co-variance with change in HbA(1c ) from baseline as the primary endpoint . RESULTS The mean baseline HbA(1c ) was 7.7 % for the entire cohort . After 18 weeks , both active add-on therapies led to greater improvements in HbA(1c ) from baseline : -0.73 % for sitagliptin ( p < 0.001 vs. placebo ) and -0.79 % for rosiglitazone compared with -0.22 % for placebo . No difference was observed between the sitagliptin and rosiglitazone treatments ( 0.06 % [ 95 % confidence interval ( CI ) : -0.14 to 0.25 ] ) . The proportion of patients achieving an HbA(1c ) < 7 % was greater with sitagliptin ( 55 % ) and rosiglitazone ( 63 % ) compared with placebo ( 38 % ) . Body weight increased from baseline with rosiglitazone ( 1.5 kg ) compared with body weight reduction with sitagliptin ( -0.4 kg ) and placebo ( -0.8 kg ) . The difference in body weight between the sitagliptin and rosiglitazone groups was 1.9 kg ( 95 % CI : 1.3 - 2.5 ) . In a prespecified analysis , the proportion of patients experiencing a greater than 3-kg increase in body weight was 21 % in the rosiglitazone group compared with 2 % in both the sitagliptin and placebo groups . Both active treatments were generally well tolerated , with no increased risk of hypoglycaemia or gastrointestinal adverse events compared with placebo . CONCLUSIONS In this 18-week study , the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy . Treatment with sitagliptin produced similar reductions in HbA(1c ) compared with the addition of rosiglitazone We report the results of the Ticlopidine Aspirin Stroke Study , a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride ( 500 mg daily ) with those of aspirin ( 1300 mg daily ) on the risk of stroke or death . The medications were r and omly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia . Follow-up lasted for two to six years . The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin -- a 12 percent risk reduction ( 95 percent confidence interval , -2 to 26 percent ) with ticlopidine ( P = 0.048 for cumulative Kaplan-Meier estimates ) . The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin -- a 21 percent risk reduction ( 95 percent confidence interval , 4 to 38 percent ) with ticlopidine ( P = 0.024 for cumulative Kaplan-Meier estimates ) . Ticlopidine was more effective than aspirin in both sexes . The adverse effects of aspirin included diarrhea ( 10 percent ) , rash ( 5.5 percent ) , peptic ulceration ( 3 percent ) , gastritis ( 2 percent ) , and gastrointestinal bleeding ( 1 percent ) . With ticlopidine , diarrhea ( 20 percent ) , skin rash ( 14 percent ) , and severe but reversible neutropenia ( less than 1 percent ) were noted . The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin ( P less than 0.01 ) . The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups . We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population , although the risks of side effects were greater Gender differences in the incidence of many cardiovascular diseases may be due to the effects of sex hormones . Both alpha(1)- and alpha(2)-adrenergic receptors produce vasoconstriction in peripheral blood vessels and have demonstrated gender effects in previous studies . In addition , race has been shown to influence the effects of some alpha-adrenergic stimuli . We therefore sought to determine the effects of the menstrual cycle and race on peripheral blood flow responses to the intra-arterial infusion of phenylephrine ( alpha(1)-agonist ) and clonidine ( alpha(2)-agonist ) . Ten white and 8 black women were studied during the early luteal phase and the follicular phase ; these phases were verified in each woman through measurements of plasma estradiol and progesterone . Plasma norepinephrine was measured with HPLC . During phenylephrine infusion , there was significantly greater vasoconstriction in the luteal phase versus the follicular phase ( P<0.05 ) . There were no differences ( P>0.8 ) between white and black women . During clonidine infusion , white women showed significantly more vasoconstriction in the follicular phase than during the luteal phase ( P<0.006 ) . For black women , the responses for both phases did not differ ( P>0.9 ) . Blood pressures were significantly higher in the black women ( diastolic P<0.005 , systolic P<0.05 ) . The luteal-phase elevation of alpha(1)-adrenergic responses may be due to elevated levels of estradiol , progesterone , or both . The lack of luteal-phase reduction in alpha(2)-adrenergic vasoconstriction in black women may contribute to their increased pressor responses to adrenergic stimuli OBJECTIVE The investigation of attention-deficit/hyperactivity disorder ( ADHD ) in girls raises complex questions of referral bias and selection criteria . The authors sought to determine whether they could recruit a research sample of comparably affected girls using a combination of sex-independent diagnostic criteria and sex-normed cutoffs on teacher ratings . They also report on the largest placebo-controlled crossover comparison of methylpheni date and dextroamphetamine in girls with ADHD . METHOD Subjects were 42 girls with DSM-III-R/DSM-IV ADHD ( combined type ) contrasted to 56 previously studied boys with ADHD on comorbid diagnoses , behavioral ratings , psychological measures , psychiatric family history , and stimulant drug response . RESULTS Girls with ADHD were statistically indistinguishable from comparison boys on nearly all measures . Girls exhibited robust beneficial effects on both stimulants , with nearly all ( 95 % ) responding favorably to one or both drugs in this short-term trial . Dextroamphetamine produced significantly greater weight loss than methylpheni date . CONCLUSIONS This highly selected group of ADHD girls was strikingly comparable with comparison boys on a wide range of measures . The results confirm that girls with ADHD do not differ from boys in response to methylpheni date and dextroamphetamine and that both stimulants should be tried when response to the first is not optimal The Study on COgnition and Prognosis in the Elderly ( SCOPE ) assessed the effect of c and esartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension . Patients were r and omized to c and esartan 8–16 mg daily ( n = 2477 ) or placebo ( n = 2460 ) . Due to extensive add‐on therapy , blood pressure reduction was only about 3/2 mmHg greater in the c and esartan group than in the control group . Nevertheless , non‐fatal stroke was reduced by 28 % ( p = 0.04 ) in the c and esartan group compared to the control group , and there was a non‐significant 11 % reduction in major cardiovascular events ( p = 0.19 ) . This report provides results in pre‐specified subgroups of patients ( age , gender , diabetes , history of stroke , smoking and cardiovascular risk at r and omization ) . Reductions in major cardiovascular events and stroke with c and esartan‐based therapy were indicated in all subgroups . A significant interaction between treatment and subgroups was found for one pair of subgroups only ; the reduction in major cardiovascular events with c and esartan was greater in patients with a previous stroke ( 64 % reduction , p = 0.004 ) than in those without ( 5 % reduction , p>0.20 ) . In conclusion , this analysis indicates consistent favourable effects of c and esartan‐based therapy on major cardiovascular events and stroke across the different subgroups of patients . However , the benefit was particularly pronounced in patients who entered the study with a previous stroke The effects of 0.3 mg/kg methylpheni date were compared for 12 ADD boys and 12 ADD girls participating in a summer treatment program for children with behavior and /or learning problems . Previous investigations have suggested that ADD girls may differ from ADD boys in some important respects . No information exists regarding whether the effects of the most common treatment for these children , methylpheni date , has comparable effects on boys and girls . The boys and girls were matched for age and IQ . The results revealed equivalent and beneficial effects of methylpheni date for both boys and girls . Methylpheni date therefore would appear to be as useful a treatment for ADD girls as for ADD boys This multicentre , r and omised , double-blind study was design ed to compare the anti-emetic efficacy and safety of single oral doses of dolasetron mesilate with that of the approved oral , multiple-dose regimen of ondansetron in 399 cancer patients receiving moderately emetogenic chemotherapy . Single oral doses of 25 , 50 , 100 or 200 mg of dolasetron mesilate were administered 1 h prior to the initiation of moderately emetogenic chemotherapy . Multiple doses of ondansetron ( 8 mg x 3 or 8 mg x 4 ) capsules , or matching placebo for patients r and omised to dolasetron , were given 1.5 h before and 6.5 , 14.5 and 22.5 h after the start of chemotherapy ( total dose = 32 mg ) . Efficacy was evaluated for 24 h after the initiation of chemotherapy . The most frequently used moderately emetogenic chemotherapeutic agents included cyclophosphamide , doxorubicin and carboplatin ( 28.4 , 23.1 and 20.6 % of patients , respectively ) . A statistically significant ( P < 0.001 ) linear dose-response relationship was observed over the entire dolasetron dosage range for all efficacy parameters . Complete response rates were 45.0 , 49.4 , 60.5 and 76.3 % for 25 , 50 , 100 and 200 mg dolasetron mesilate , respectively , and 72.3 % of ondansetron patients . A single oral 200 mg dolasetron mesilate dose was therapeutically equivalent to ondansetron for all efficacy parameters and patient satisfaction was high . Overall , there were no significant differences in the incidence of adverse events between any of the dolasetron mesilate doses , or between dolasetron and ondansetron . Headache was most frequently reported ( approximately 15 % for each drug ) . No clinical ly important changes in vital signs or clinical laboratory parameters were observed with either drug . In conclusion , a single oral 200 mg dolasetron mesilate dose was therapeutically equivalent to multiple-dose ondansetron in the prevention of emesis and nausea following moderately emetogenic chemotherapy BACKGROUND The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients , compared with captopril , an angiotensin-converting-enzyme ( ACE ) inhibitor . We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated . METHODS We undertook a double-blind , r and omised , controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40 % or less . Patients , stratified for beta-blocker use , were r and omly assigned losartan ( n=1,578 ) titrated to 50 mg once daily or captopril ( n=1,574 ) titrated to 50 mg three times daily . The primary and secondary endpoints were all-cause mortality , and sudden death or resuscitated arrest . We assessed safety and tolerability . Analysis was by intention to treat . FINDINGS Median follow-up was 555 days . There were no significant differences in all-cause mortality ( 11.7 vs 10.4 % average annual mortality rate ) or sudden death or resuscitated arrests ( 9.0 vs 7.3 % ) between the two treatment groups ( hazard ratios 1.13 [ 95.7 % CI 0.95 - 1.35 ] , p=0.16 and 1.25 [ 95 % CI 0.98 - 1.60 ] , p=0.08 ) . Significantly fewer patients in the losartan group ( excluding those who died ) discontinued study treatment because of adverse effects ( 9.7 vs 14.7 % , p<0.001 ) , including cough ( 0.3 vs 2.7 % ) PURPOSE To compare the efficacy and safety of granisetron and ondansetron , serotonin ( 5-HT3 ) receptor antagonists shown to be effective in the prevention of chemotherapy-induced emesis . PATIENTS AND METHODS In a double-blind , r and omized , stratified , parallel-group study , the efficacy and safety of granisetron and ondansetron were compared in 987 chemotherapy-naive patients who received cisplatin in doses > or = 60 mg/m2 . Granisetron was administered as a single dose of 10 or 40 micrograms/kg before the start of chemotherapy . Ondansetron was administered in doses of 0.15 mg/kg before and 4 and 8 hours after the start of chemotherapy . The three treatment groups were well-matched with respect to demographic characteristics and the dose of cisplatin administered . RESULTS For all evaluations , single doses of granisetron 10 or 40 micrograms/kg were as effective as three 0.15-mg/kg doses of ondansetron . Total control ( no vomiting , no retching , no nausea , and no use of rescue ) was attained by 38 % , 41 % , and 39 % of all patients who received granisetron 10 microgram/kg , granisetron 40 micrograms/kg , and ondansetron , respectively . No vomiting or retching and no use of rescue antiemetics were reported in 47 % , 48 % , and 51 % of patients who received granisetron 10 micrograms/kg , granisetron 40 micrograms/kg , and ondansetron , respectively ; no nausea and no use of rescue antiemetics were reported in 39 % , 42 % , and 40 % of patients , respectively . CONCLUSION All three treatment regimens were well-tolerated . The results of this study indicate that a single dose of granisetron 10 or 40 micrograms/kg is as effective as three doses of ondansetron 0.15 mg/kg in the prevention of nausea and vomiting induced by cisplatin chemotherapy Two doses of Ritalin ( 0.15 mg/kg and 0.35 mg/kg BID ) were evaluated for their differential effects on the mother-child interactions of hyperactive girls and boys . The effects of Ritalin on these interactions were similar for both sexes . During task performance , the children increased their duration of compliance to the tasks . Mothers responded with decreased comm and s and control over compliance , while increasing their level of more general , non-directive interactions and passive observation of their children . The findings are consistent with previous studies of stimulant drug effects on the social interactions of hyperactive children |
12,691 | 24,220,691 | Simulation-based airway management curriculum is superior to no intervention and nonsimulation intervention for important education outcomes . | OBJECTIVE To perform a systematic review and meta- analysis of the literature on teaching airway management using technology-enhanced simulation . | An interactive , self- study learning system for airway management instruction that utilizes a “ sensorized ” manikin head ( Actronics Inc. , Pittsburgh , PA ) was compared to didactic instruction from anesthesiologists during third-year medical student anesthesia rotations . Before students were allowed to participate in airway management on anesthetized patients , they were r and omly separated into two groups . One group received instruction from the learning system , and the other group was given a lecture with guided practice on a st and ard tracheal intubating manikin . Differences between groups were then assessed using 22 separate variables as all students performed actual airway management on patients undergoing general anesthesia . Anesthesia faculty , residents , and nurse anesthetists , blinded to group , served as assessors . There were 48 and 49 students in the didactic instruction and learning system groups , respectively . Beginning experience level of students with respect to airway management was similar between groups before the anesthesia rotations . There were 185 and 188 evaluation forms completed to assess the didactic instruction and learning system groups , respectively . Demographic data regarding patients were recorded . Patients in the learning system group on whom students performed airway management were older , had a larger average body mass index , and their airways more frequently received higher Mallampati classifications ( glottic structures more difficult to visualize ) . No difference in the quality of airway management efforts or in students ' appraisal of their own performances was seen between groups . Neither group demonstrated more rapid development of psychomotor skills . Students were equally satisfied with both methods of instruction . We conclude that the airway management self- study learning system is as efficacious as didactic instruction for pre clinical airway management instruction during third-year medical student anesthesia rotations Objective : To compare the usefulness for training of a porcine model ( larynx , trachea , and pig skin ) and a manikin model using a Portex cricothyrotomy kit ( PCK ) . Methods : In a prospect i ve r and omised crossover trial , participants in the airway workshop performed crico-thyrotomy using a PCK on the porcine and manikin models ( Tracheostomy Trainer and Case ) . The porcine model was made with larynxes and trachea from freshly slaughtered pigs and covered with a piece of thinned pigskin stapled to a wooden board . Participants were asked to assess the following : reality of skin turgor ; difficulty with skin penetration , l and mark recognition and procedure ; reality of the model ; and preference for each model using a visual analogue scale ( VAS ) of 0–10 cm . The VAS scores for each model were compared . Results : 49 participants were included in the study . Mean ( SD ) VAS scores for the reality of skin turgor , degree of difficulty with skin penetration and l and mark recognition were higher with the porcine model than with the manikin model ( 7.0 ( 2.1 ) vs 4.7 ( 2.0 ) , 6.4 ( 2.4 ) vs 3.6 ( 2.2 ) , 5.1 ( 2.2 ) vs 4.2 ( 2.5 ) , respectively ) . There was no difference between the models in the difficulty of the procedure ( 5.0 ( 2.4 ) vs 4.7 ( 3.2 ) ) . The porcine model had a higher VAS score for overall reality and preference of the model ( 7.1 ( 2.0 ) vs 4.8 ( 2.3 ) and 7.1 ( 2.0 ) vs 4.8 ( 2.2 ) , respectively ) . Conclusion : The porcine model is a more useful training tool than the manikin model for cricothyrotomy with PCK because of its reality and similarity to human anatomy INTRODUCTION The human patient simulator has proved to be an effective educational device for teaching physicians and paramedical personnel . METHODOLOGY To determine whether veterinary medicine students would benefit from similar educational sessions , 90 students each took a turn being the patient 's clinician as real-life scenarios were played out on the simulator . The students induced and maintained anesthesia on their patient and monitored vital signs . Several critical events were presented for the students to diagnose and treat as they occurred . All students su bmi tted a written evaluation of the course upon completion . The last 40 students were r and omly divided into two groups of 20 students each . The students in Group I experienced the simulator before their clerkship examination , and those in Group II took the examination before their simulator experience . RESULTS The students rapidly gained confidence in treating their simulated patient . This carried over to the clinical setting , where they appeared to be more confident when anesthetizing live patients . The simulator experience brought together much of the previous didactic material that they had been exposed to so they could appreciate its clinical relevance . The overwhelming response to the simulator experience was positive . The students in Group I had a significantly higher score on the clerkship examination dealing with concepts review ed by simulation than those in Group II , who engaged in self- study instead of the simulation exercise ( p < 0.001 ) . CONCLUSION We conclude that the human patient simulator was a valuable learning tool for students of veterinary medicine . It was exciting for the students to work with , made them deal with " real-life " scenarios , permitted them to learn without subjecting live patients to complications , enabled them to retrace their steps when their therapy did not correct the simulated patient 's problems , and facilitated correlation of their basic science knowledge with clinical data , thus accelerating their ability to h and le complex clinical problems in healthy and diseased patients Background With increasing pressure to use operating room time efficiently , opportunities for residents to learn fiberoptic orotracheal intubation in the operating room have declined . The purpose of this study was to determine whether fiberoptic orotracheal intubation skills learned outside the operating room on a simple model could be transferred into the clinical setting . Methods First-year anesthesiology residents and first- and second-year internal medicine residents were recruited . Subjects were r and omized to a didactic-teaching-only group ( n = 12 ) or a model-training group ( n = 12 ) . The didactic-teaching group received a detailed lecture from an expert bronchoscopist . The model-training group was guided , by experts , through tasks performed on a simple model design ed to refine fiberoptic manipulation skills . After the training session , subjects performed a fiberoptic orotracheal intubation on healthy , consenting , anesthetized , paralyzed female patients undergoing elective surgery with predicted “ easy ” laryngoscopic intubations . Two blinded anesthesiologists evaluated each subject . Results After the training session , the model group significantly outperformed the didactic group in the operating room when evaluated with a global rating scale ( P < 0.01 ) and checklist ( P < 0.05 ) . Model-trained subjects completed the fiberoptic orotracheal intubation significantly faster than didactic-trained subjects ( P < 0.01 ) . Model-trained subjects were also more successful at achieving tracheal intubation than the didactic group ( P < 0.005 ) . Conclusion Fiberoptic orotracheal intubation skills training on a simple model is more effective than conventional didactic instruction for transfer to the clinical setting . Incorporating an extraoperative model into the training of fiberoptic orotracheal intubation may greatly reduce the time and pressures that accompany teaching this skill in the operating room GOAL Isolate and evaluate the impact of mental imagery on the acquisition of an emergency surgical technique . METHOD We studied 44 first-year medical students performing a cricothyrotomy on a mannequin to determine the impact of teaching using mental imagery ( MI ) and /or kinesiology ( KG ) compared to the st and ard Adv and ec Trauma Life Support ( ATLS ) approach . Students were r and omly assigned to one of three groups : MI and KG , KG alone or control ( ATLS ) . Two weeks after the one-hour teaching session , they were evaluated with an OSCE testing the performance of the different steps of the technique , the time required and its fluidity . RESULTS Total results ( maximum : 25 marks ) are as follows : KG + MI = 20.3 + /- 1.5 ; KG = 19.3 + /- 2.9 ; ATLS = 18.2 + /- 2.5 . The only statistically significant difference for total results was in the use of MI and KG compared to the control group . Kinesiology alone or with mental imagery improved the fluidity of the performance . CONCLUSION Many factors influence the acquisition of a surgical technique . This study showed that acquisition and performance of an emergency procedure ( cricothyrotomy ) was improved when mental imagery and kinesiology were combined to teach it Abstract Simulation-based teaching ( SBT ) is increasingly used in medical education . As an alternative to other teaching methods there is a lack of evidence concerning its efficacy . The aim of this study was to evaluate the potency of SBT in anesthesia in comparison to problem-based discussion ( PBD ) with students in a r and omized controlled setting . Thirty-three fourth-year medical students attending a curricular anesthesiology course were r and omly allocated to either a session of SBT or a session of PBD on an emergency induction method . Ten days later all students underwent examination in a simulator . The performance of each student was evaluated by weighted tasks , established according to a modified Delphi process . Confidence and a multiple-choice question naire were additionally performed pre- and post-intervention . A total of 32 students completed the study . Participants in the SBT group presented with significantly higher self- assessment scores after the intervention than students in the PBD group . However , students in the SBT group achieved only slightly and statistically insignificantly higher scores in the theoretical and simulator examination ( p > 0.05 ) with only a moderate effect size of d = 0.52 . The current study demonstrates that both PBD and SBT lead to comparable short-term outcomes in theoretical knowledge and clinical skills . However , undesirably , SBT students overrated their anticipated clinical abilities and knowledge improvement OBJECTIVE To compare the ' 4-stage ' teaching technique ( demonstration , deconstruction , formulation , performance ) with the traditional ' 2-stage ' teaching technique ( deconstruction , performance ) in laryngeal mask airway ( LMA ) insertion . METHODS Using a prospect i ve r and omised study design , participants were taught LMA insertion on a manikin by either the ' 2-stage ' or ' 4-stage ' teaching method . Subjects were eligible if they had never inserted a LMA . Skill acquisition was assessed immediately following training , and skill retention assessed a number of weeks later . The primary outcome was LMA insertion on a manikin , with successful ventilation within 30 s. Other outcomes included overall time to LMA insertion , and number of errors . Assessors were blinded to the teaching method used for each subject . RESULTS A total of 120 participants were r and omised between the two teaching groups ( 60 subjects in each group ) . Mean time to LMA insertion at acquisition was 39.7 s for 2-stage and 34.7 s for 4-stage ( p>0.05 ) , and proportion completing within 30 s was 41.67 % for 2-stage and 48.33 % for the 4-stage teaching group ( p>0.05 ) . With skill retention assessment , mean time to LMA insertion was 44.3 s for 2-stage and 42.5 s for the 4-stage teaching group ( p>0.05 ) . Proportion completing task within 30 s was 34.0 % for 2-stage and 41.67 % for 4-stage group ( p>0.05 ) . Overall , there was no significant difference found in skill acquisition or in skill retention between the 2 or 4-stage teaching method . CONCLUSION The 2-stage teaching technique is not statistically different to the 4-stage teaching method in efficacy of LMA insertion skill acquisition or retention OBJECTIVES The primary purpose of this study was to determine whether the endotracheal intubation ( ETI ) success rate is different among paramedic students trained on a human patient simulator versus on human subjects in the operating room ( OR ) . METHODS Paramedic students ( n = 36 ) with no prior ETI training received identical didactic and mannequin teaching . After r and omization , students were trained for ten hours on a patient simulator ( SIM ) or with 15 intubations on human subjects in the OR . All students then underwent a formalized test of 15 intubations in the OR . The primary outcome was the rate of successful intubation . Secondary outcomes were the success rate at first attempt and the complication rate . The study was powered to detect a 10 % difference for the overall success rate ( alpha = 0.05 , beta = 0.20 ) . RESULTS The overall intubation success rate was 87.8 % in the SIM group and 84.8 % in the OR group ( difference of 3.0 % [ 95 % confidence interval { CI } = -4.2 % to 10.1 % ; p = 0.42 ] ) . The success rate on the first attempt was 84.4 % in the SIM group and 80.0 % in the OR group ( difference of 4.4 % [ 95 % CI = -3.4 % to 12.3 % ; p = 0.27 ] ) . The complication rate was 6.3 % in the SIM group and 4.4 % in the OR group ( difference of 1.9 % [ 95 % CI = -2.9 % to 6.6 % ; p = 0.44 ] ) . CONCLUSIONS When tested in the OR , paramedic students who were trained in ETI on a simulator are as effective as students who trained on human subjects . The results support using simulators to teach ETI Introduction : Major resuscitation councils endorse the use of the laryngeal mask airway ( LMA ) by paramedics for lifesaving airway interventions . Learning and maintaining adequate skill level is important for patient safety . The aim of this project was to develop a training program that provides student paramedics with initial knowledge and experience in LMA insertion skills but equally important to provide ongoing skill retention . Methods : After ethics approval and informed consent , 55 first year Paramedic degree students watched a manufacturer 's LMA instruction video and practice d insertion in three different part task trainers . Six months later , subjects were r and omized to an intervention ( review ing the video and 10 minutes unsupervised practice ) or control group before participating in a high-fidelity simulated clinical scenario . For equity of training , the control group received the intervention after the scenario . Main outcomes measured were time to insertion ; success rate ; and LMA skill retention ( sum of LMA orientation ; cuff inflation ; bite block ; securing ; patient positioning ; and overall subject performance ) . Results : Fifty subjects completed the study . Those in the intervention group displayed significantly shorter insertion times ( P = 0.029 ) , fewer attempts to achieve success ( P = 0.033 ) , and had significantly higher LMA skill performance levels ( P = 0.019 ) at 6 months . Conclusions : We devised a short intervention based on our training program using a video and practice in part task trainers . In an assessment using high-fidelity simulation , we demonstrated significant improvements in maintenance of LMA insertion skills in student paramedics at 6 months . Our model of just-in-time assessment and reinforcement of training prevents skill decay and has implication s for healthcare skills training in general Background and objective The aim of the study was to compare the effectiveness of teaching of general anaesthesia induction to medical students using either full-scale simulation or traditional supervised teaching with patients in the operating theatre . Methods Forty-six fourth year students attending their course in anaesthesiology were enrolled . The students were r and omly assigned to two groups . The simulation group received training in the simulator . The traditional training group was supervised by a senior consultant anaesthetist . After the training sessions all students were tested in the simulator setting . The test was assessed using a 40-item evaluation list . Results Thirty-three per cent of students in the traditional group and 87 % of the students in the simulation group passed the test . Statistically significant differences were : request of glycopyrrolate ( P < 0.001 ) , SpO2 monitoring ( P < 0.001 ) , used gloves when placing an intravenous cannula ( P = 0.012 ) , intubation attempt within 30 s ( P < 0.04 ) , anaesthesia gas set at MAC at least 1 ( P < 0.04 ) , instructed anaesthetic nurse to keep SpO2 at least 95 % ( P < 0.05 ) , keep MAP at least 60 mmHg ( P < 0.05 ) , keep heart rate more than 50 beats per minute ( P < 0.002 ) , keep end-tidal pCO2 4–5.5 kPa ( P < 0.002 ) . Conclusion The simulation group performed better in 25 % of the tasks and similarly in the others compared with the traditional teaching group . With the same time and amount of teaching personnel we trained five or six students in the simulator compared with one student in the operating theatre . Further research will reveal whether these promising results with simulation may be applied more generally in anaesthesiology teaching to medical students We have compared the progress of anaesthetists taught fibreoptic nasotracheal intubation with the aid of a closed circuit television ( CCTV ) system with that of anaesthetists taught by traditional methods . Twenty anaesthetists were allocated r and omly to either the video or traditional training group . A graduated training programme was used in which the first stage was an introduction to techniques and apparatus and the second stage was practice on an airway model . During the third stage , rhinoscopy , pharyngoscopy and laryngoscopy were performed on anaesthetized patients whose lungs were ventilated via an orotracheal tube . A maximum time of 6 min was allowed for completion of laryngoscopy . Trainees aim ed to perform five endoscopies in less than 60 s before moving on to the next stage . During the fourth stage , they carried out five traditional nasotracheal intubations ( plus two video-controlled intubations for the video group ) on apnoeic , anaesthetized patients . The mean number of endoscopies required ( 11.7 vs 21.8 ) , mean total endoscopy time ( 21.5 vs 63.1 min ) and mean number of failed endoscopies ( 0.8 vs 3.9 ) were significantly less in the video group . All the video-controlled intubations were successful . There was no significant difference between the number of successful traditional intubations in the two groups ( 90 % video , 92 % traditional ) . CCTV appears to enhance substantially the rate of acquisition of fibreoptic nasotracheal intubation skills STUDY OBJECTIVES To determine the effect of manikin-only training on field success of endotracheal intubation by paramedics . DESIGN Prospect i ve evaluation of individual field endotracheal intubation success rates for paramedics after they participated in a manikin-only or a manikin-plus-cadaver training program . TYPES OF PARTICIPANTS Paramedics responding to emergency calls involving adult medical or trauma victims . INTERVENTIONS All participants were trained using a controlled manikin training program ; then , half were r and omly selected for additional instruction using fresh human cadavers . MEASUREMENTS AND MAIN RESULTS Individuals trained using only the manikin program had mean + /- SD individual success rates of 82 + /- 32 % , and individuals who received additional cadaver training had mean individual success rates of 83 + /- 31 % . Overall success rates for the two groups were 86 % for the manikin-only group and 85 % for the manikin-plus-cadaver-trained group . The sample size was not adequate to allow rejection of the null hypothesis . CONCLUSION Paramedics trained in endotracheal intubation using a systematic manikin-only teaching program can attain acceptable individual success rates in the actual field setting Nurses without prior experience in the use of the laryngeal mask airway ( LMA ) were r and omly allocated to one of two groups to be trained in the emergency technique of insertion of an LMA . Group A ( 32 nurses ) were trained only on a manikin and group B ( 20 nurses ) were trained on a manikin and with live anaesthetised patient practice in theatre ( five successful insertions ) . Without further practice , both groups were asked to insert an LMA in a live patient in theatre 3 months after initial training . Three attempts per nurse were allowed . In group A , 75 % passed the LMA successfully at the first attempt , 22 % at the second attempt and 3 % ( one nurse ) at the third attempt . In group B , 80 % were successful at first attempt and 20 % at the second attempt . Skill performance and retention were shown to be high following either training method , with no significant difference between the performance of either group ( chi 2 ) . We have shown that manikin-only training in the emergency technique for LMA insertion is as effective as live patient training . It is proposed that manikin training alone may be adopted as a future training modality if , as is expected , the use of the LMA in resuscitation becomes more commonplace PRIMARY OBJECTIVE To determine whether using live actors to increase the reality of the scenario improves knowledge retention in Advanced Cardiac Life Support ( ACLS ) Courses . MAIN SECONDARY OBJECTIVES : To determine the effects of age , time since graduation from nursing or medicine , sex , medical specialty , and workplace in knowledge retention . METHODS From December 2004 to October 2005 , 19 selected ACLS courses were divided at r and om in two groups : group A ( ACLS courses with conventional manikins plus live actors ) and group B ( ACLS courses with conventional manikins ) . The live actors vocalized appropriately to create more realistic scenarios . The participants ' relevant theoretical knowledge was assessed before the course ( pre-test ) , immediately after the course ( post-test ) , and 6 months after the course ( final-test ) . RESULTS Four hundred and thirty-five participants were recruited and allocated at r and om allocated to either group A or B. Overall , the data of 225 participants ( 51.7 % ; 111 in group A and 114 in group B ) who completed the entire sequence of pre- , post- , and final-tests were analysed . On univariate analysis , the use of live actors , workplace , gender , and healthcare provider profession did not affect pre- , post- , and final-test results ( p>0.1 ) . The results in all three tests correlated negatively with time since medical or nursing graduation ( 95 % C.I. -0.53 to -0.17 , -0.43 to -0.2 , and -0.42 to -0.11 , respectively , p<0.05 ) and age ( and 95 % C.I. -0.56 to -0.21 , -0.42 to -0.2 , and -0.38 to -0.07 , respectively , p<0.05 ) . CONCLUSION The use of live actors did not affect knowledge retention in this group . Older age and a longer period since graduation were associated with the worst scores and the lowest levels of knowledge retention CONTEXT Simulators provide an effective platform for the learning of clinical motor skills such as endotracheal intubation , although the optimal learning technique remains unidentified . We hypothesised that , for novices , experiential learning would improve the learning and retention of endotracheal intubation compared with guided learning . METHODS Year 4 medical students were r and omised to either guided or experiential learning . Students in the guided group were taught using the conventional step-by-step technique . Students in the experiential group had to work out the correct technique for intubation on their own . Both groups had further opportunities to intubate manikins and patients during their postings . The students were recalled 3 , 6 , 9 and 12 months later , and their intubation skills assessed in four major categories : equipment preparation ; intubation technique ; successful intubation , and placement confirmation . RESULTS A total of 210 students ( 107 guided , 103 experiential ) participated in the study . At 3 months , 64.5 % of the students in the experiential group successfully intubated the manikin , compared with 36.9 % in the guided group ( P < 0.001 ) . The experiential group also had higher overall scores , signifying quality of intubation attempts , at 3 months ( 79 % versus 70 % ; P < 0.001 ) . Success rates and overall scores for both groups were comparable at 6 and 9 months , but were better in the experiential group at 12 months . Success rates improved with time , reaching 86 % at 12 months . CONCLUSIONS Novices learned and retained the skill of endotracheal intubation better with experiential learning . This study suggests that experiential learning should be adopted for the teaching of endotracheal intubation and that refresher tuition at 3-monthly intervals will prevent the decay of this skill in infrequent users This study compared a graduated training programme with that of a traditional teaching method to facilitate the learning of the technique of fibreoptic nasotracheal intubation . Thirty-two anaesthesia trainees were r and omly assigned to two groups . The graduated programme involved : practice on a bronchoscopy teaching model ; exposure of the epiglottis and vocal cords in patients recovering from general anaesthesia ; performance of fibreoptic nasotracheal intubation in awake se date d patients . The traditional programme involved : demonstration ( on a patient ) of one fibreoptic nasotracheal intubation by the instructor ; performance of fibreoptic nasotracheal intubation ( by the trainee ) in awake se date d patients . Nasotracheal intubation was accomplished significantly more often by the trainees in the graduated programme ( 86 out of 96 ( 89.6 % ) v. 64 out of 96 ( 66.5 % ) ( P less than 0.01 ) . The results demonstrate that trainees who undergo a graduated training programme using simulators are initially more successful at awake fibreoptic nasotracheal intubation than those who have learned in the traditional manner , and that the conditions of the investigation were acceptable to the trainees and patients Objective : To compare the acceptability and preference between manikin models and fresh frozen cadaver ( FFC ) for direct laryngoscopic orotracheal intubation training . Methods : In this prospect i ve crossover trial , participants in the airway workshop performed direct laryngoscopic orotracheal intubation on four airway training manikins : Airway Management Trainer ( Ambu , St Ives , UK ) , Airway Trainer ( Laerdal , Medical , Stavanger , Norway ) , Airsim ( Trucorp , Belfast , Northern Irel and ) and “ Bill 1 ” ( VBM , Sulz , Germany ) , and FFC . Participants were asked to access the following : reality of jaw mobility , difficulty with mouth opening , reality of neck flexibility , difficulty with intubation , overall model reality and model preference for each model using a visual analogue scale ( VAS ) of 0–10 cm . The VAS scores for each model were compared . Results : Fifty-six participants were included in the study . The FFC had a highest VAS score for reality of jaw mobility , overall reality and preference of model . Trucorp manikin and Laerdal manikin followed cadaver . There were no significant statistical differences between Trucorp manikin and Laerdal manikin . In difficulty with mouth opening and difficulty with intubation , Trucorp manikin had the lowest VAS score . Conclusion : The FFC is a more realistic and preferred model for direct laryngoscopic orotracheal intubation training . Trucorp and Laerdal manikin can be used as alternative models STUDY OBJECTIVE This study was conducted to determine the natural history of airway management skill decay and examine the effect of independent practice and periodic feedback on airway management skill maintenance . METHODS This prospect i ve , r and omized controlled study conducted at Dalhousie University in Halifax , Nova Scotia , Canada , between November 1997 and September 1998 . A convenience sample of 84 health sciences students with no prior airway management experience was used . Participants were trained using an advanced airway manikin and then were r and omly assigned to control ( n=24 ) , periodic feedback only ( n=30 ) , and independent practice plus periodic feedback ( n=30 ) groups . Performance was measured by a 52-point weighted checklist at 0 , 16 , 25 , and 40 weeks after the initial program . RESULTS Group scores were analyzed using a mixed-model repeated- measures analysis of variance and Bonferroni-adjusted P values . Overall group ( P = .0002 ) and time ( P = .0001 ) effects were significant . At time 0 , there was no statistical difference in mean scores between groups ( range 45.0 to 45.2 ) . Control group performance fell over the first time interval ( 0 to 16 weeks ) ( mean score=34.0 , P = .002 ) and remained lower at all intervals without further significant change . Scores in the independent practice plus feedback group revealed no significant changes over time and were significantly higher than the control group throughout . Performance in the periodic feedback only group showed a nonsignificant trend to improved performance over the control group . CONCLUSION Airway management skill performance declines early after initial training . Independent practice combined with periodic feedback was effective in maintaining performance scores in an advanced airway management simulation . Periodic evaluation with feedback alone showed a nonsignificant trend toward improvement over control Background : Previous studies have indicated that fiberoptic orotracheal intubation ( FOI ) skills can be learned outside the operating room . The purpose of this study was to determine which of two educational interventions allows learners to gain greater capacity for performing the procedure . Methods : Respiratory therapists were r and omly assigned to a low-fidelity or high-fidelity training model group . The low-fidelity group was guided by experts , on a nonanatomic model design ed to refine fiberoptic manipulation skills . The high-fidelity group practice d their skills on a computerized virtual reality bronchoscopy simulator . After training , subjects performed two consecutive FOIs on healthy , anesthetized patients with predicted “ easy ” intubations . Each subject 's FOI was evaluated by blinded examiners , using a vali date d global rating scale and checklist . Success and time were also measured . Results : Data were analyzed using a two-way mixed design analysis of variance . There was no significant difference between the low-fidelity ( n = 14 ) and high-fidelity ( n = 14 ) model groups when compared with the global rating scale , checklist , time , and success at achieving tracheal intubation ( all P = not significant ) . Second attempts in both groups were significantly better than first attempts ( P < 0.001 ) , and there was no interaction between “ fidelity of training model ” and “ first versus second attempt ” scores . Conclusions : There was no added benefit from training on a costly virtual reality model with respect to transfer of FOI skills to intraoperative patient care . Second attempts in both groups were significantly better than first attempts . Low-fidelity models for FOI training outside the operating room are an alternative for programs with budgetary constraints Background The availability of simulator technology at the University of Toronto ( Toronto , Ontario , Canada ) provided the opportunity to compare the efficacy of video-assisted and simulator-assisted learning . Methods After ethics approval from the University of Toronto , all final-year medical students were invited to participate in the current r and omized trial comparing video-based to simulator-based education using three scenarios . After an introduction to the simulator environment , a 5-min performance-based pretest was administered in the simulator operating room requiring management of a critical event . A posttest was administered after students had participated in either a faculty-facilitated video or simulator teaching session . St and ardized 12-point checklist performance protocol s were used for assessment purpose s. As well , students answered focused questions related to the educational sessions on a final examination . Student opinions regarding the value of the teaching sessions were obtained . Results One hundred forty-four medical students participated in the study ( scenario 1 , n = 43 ; scenario 2 , n = 48 ; scenario 3 , n = 53 ) . There was a significant improvement in posttest scores over pretest scores in all scenarios . There was no statistically significant difference in scores between simulator or video teaching methods . There were no differences in final examination marks when the two educational methods were compared . Student opinions indicated that the experiential simulator sessions were more enjoyable and valuable than the video teaching sessions . Conclusions Both simulator and video types of faculty-facilitated education offer a valuable learning experience . Future work is needed that addresses the long-term effects of experiential learning in the retention of knowledge and acquired skills Objectives To compare the effectiveness of training with an airway model simulator versus digital video disc (DVD)-based instruction in placement of double-lumen endotracheal ( DLT ) tubes by anaesthesiologists with limited thoracic experience . Design Single academic centre parallel r and omised controlled trial with computer-generated r and om allocation . Participants Sixty patients undergoing elective thoracic or oesophageal surgeries requiring one-lung ventilation . Twenty-seven non-thoracic anaesthesiologists were r and omised to place a DLT . Intervention DLT placement instruction by an interactive airway simulator or computer-based DVD training . The main outcome measure was successful DLT placement . Results Twenty-seven anaesthesiologists were r and omised to one of the two intervention groups . Sixty consecutive patients were assigned to a r and omised anaesthesiologist ( n = 30 in each group ) . Participants failed to correctly place or position the DLT tubes in 14 of 60 patients ( failure rate of 23 % ) . There was no difference in the probability of satisfactory placement or time for positioning of the DLT between the training groups ; 80.5 % ( 95 % confidence interval 58.2–96.2 % ) of tubes were successfully placed following intubation model simulator training versus 73.6 % ( 95 % confidence interval 49.8–88.5 % ) in the DVD group ( P = 0.378 ) . Conclusion Both teaching methods had similar outcomes for placement of DLTs by anaesthesiologists with limited thoracic anaesthesia experience . Both groups performed better than individuals in our prior study . Therefore , these methods should be considered when training anaesthesiologists to successfully place DLTs |
12,692 | 28,544,551 | The meta-analyses demonstrated a significant result for limiting gestational weight gain , losing postnatal weight in 1 - 2 months , increasing self-reported moderate and vigorous physical activity and reducing caloric intake using diet-related software .
Our review shows that an e-based lifestyle intervention is an acceptable approach . | Electronic-based ( e-based ) lifestyle interventions provide potential and cost-effective delivery of remote interventions for overweight and obese perinatal women .
To date , no meta- analysis has reported the efficacy of maternal and neonatal outcomes . | Background Postnatal women ( < 12 months postpartum ) are at increased risk of physical inactivity . Purpose To evaluate the efficacy and feasibility of a theory-based physical activity ( PA ) intervention delivered to postnatal women primarily via mobile telephone short message service ( SMS ) . Methods Eighty-eight women were r and omized to the intervention ( n = 45 ) or minimal contact control ( n = 43 ) condition . The 12-week intervention consisted of a face-to-face PA goal - setting consultation , a goal - setting magnet , three to five personally tailored SMS/week and a nominated support person who received two SMS per week . SMS content targeted constructs of social cognitive theory . Frequency ( days/week ) and duration ( min/week ) of PA participation and walking for exercise were assessed via self-report at baseline , 6 and 13 weeks . Results Intervention participants increased PA frequency by 1.82 days/week ( SE ± 0.18 ) by 13 weeks ( F(2,85 ) = 4.46 , p = 0.038 ) and walking for exercise frequency by 1.08 days/week ( SE ± 0.24 ) by 13 weeks ( F(2,85 ) = 5.38 , p = 0.02 ) . Positive trends were observed for duration ( min/week ) of PA and walking for exercise . Conclusions Intervention exposure result ed in increased frequency of PA and walking for exercise in postnatal women Background Recent studies have shown the potential of Web-based interventions for changing dietary and physical activity ( PA ) behavior . However , the pathways of these changes are not clear . In addition , nonusage poses a threat to these interventions . Little is known of characteristics of participants that predict usage . Objective In this study we investigated the users and effect of the Healthy Weight Assistant ( HWA ) , a Web-based intervention aim ed at healthy dietary and PA behavior . We investigated the value of a proposed framework ( including social and economic factors , condition-related factors , patient-related factors , reasons for use , and satisfaction ) to predict which participants are users and which participants are nonusers . Additionally , we investigated the effectiveness of the HWA on the primary outcomes , self-reported dietary and physical activity behavior . Methods Our design was a two-armed r and omized controlled trial that compared the HWA with a waiting list control condition . A total of 150 participants were allocated to the waiting list group , and 147 participants were allocated to the intervention group . Online question naires were filled out before the intervention period started and after the intervention period of 12 weeks . After the intervention period , respondents in the waiting list group could use the intervention . Objective usage data was obtained from the application itself . Results In the intervention group , 64 % ( 81/147 ) of respondents used the HWA at least once and were categorized as “ users . ” Of these , 49 % ( 40/81 ) used the application only once . Increased age and not having a chronic condition increased the odds of having used the HWA ( age : beta = 0.04 , P = .02 ; chronic condition : beta = 2.24 , P = .003 ) . Within the intervention group , users scored better on dietary behavior and on knowledge about healthy behavior than nonusers ( self-reported diet : χ2 2 = 8.4 , P = .02 ; knowledge : F1,125 = 4.194 , P = .04 ) . Furthermore , users underestimated their behavior more often than nonusers , and nonusers overestimated their behavior more often than users ( insight into dietary behavior : χ2 2 = 8.2 , P = .02 ) . Intention-to-treat analyses showed no meaningful significant effects of the intervention . Exploratory analyses of differences between pretest and posttest scores of users , nonusers , and the control group showed that on dietary behavior only the nonusers significantly improved ( effect size r = −.23 , P = .03 ) , while on physical activity behavior only the users significantly improved ( effect size r = −.17 , P = .03 ) . Conclusions Respondents did not use the application as intended . From the proposed framework , a social and economic factor ( age ) and a condition-related factor ( chronic condition ) predicted usage . Moreover , users were healthier and more knowledgeable about healthy behavior than nonusers . We found no apparent effects of the intervention , although exploratory analyses showed that choosing to use or not to use the intervention led to different outcomes . Combined with the differences between groups at baseline , this seems to imply that these groups are truly different and should be treated as separate entities . Trial registration Trial ID number : IS RCT N42687923 ; http://www.controlled-trials.com/IS RCT N42687923/ ( Archived by WebCite at http://www.webcitation.org/5xnGmvQ9Y The aim of this study was to evaluate dietary changes during and after a dietary treatment shown to result in significant and sustained weight loss among lactating overweight and obese women . This is crucial before clinical implementation . Data were collected from the LEVA ( in Swedish : Livsstil för Effektiv Viktminskning under Amning [ Lifestyle for Effective Weight Loss During Lactation ] ) r and omized controlled factorial trial with a 12-week intervention and a 1-year follow up . At 10 to 14 weeks postpartum , 68 lactating Swedish women with a prepregnancy body mass index ( calculated as kg/m(2 ) ) of 25 to 35 were r and omized to structured dietary treatment , physical exercise treatment , combined treatment , or usual care ( controls ) for a 12-week intervention , with a 1-year follow-up . Dietary intake was assessed with 4-day weighed dietary records . Recruitment took place between 2007 and 2010 . The main outcome measures were changes in macro- and micronutrient intake from baseline to 12 weeks and 1 year . Main and interaction effects of the treatments were analyzed by a 2 × 2 factorial approach using a General Linear Model adjusted for relevant covariates ( baseline intake and estimated underreporting ) . It was found that at baseline , the women had an intake of fat and sucrose above , and an intake of total carbohydrates and fiber below , recommended levels . At 12 weeks and 1 year , the dietary treatment led to reduced intake of energy ( P<0.001 and P=0.005 , respectively ) , fat ( both P values < 0.001 ) , and sucrose ( P<0.001 and P=0.050 ) . At 12 weeks , total carbohydrates were reduced ( P<0.001 ) . A majority of women in all groups reported low intakes of vitamin D , folate , and /or iron . In conclusion , a novel dietary treatment led to reduced intake of fat and carbohydrates . Diet composition changed to decreased proportions of fat and sucrose , and increased proportions of complex carbohydrates , protein and fiber . Weight loss through dietary treatment was achieved with a diet in line with macronutrient recommendations Background Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas . Methods Madres para la Salud [ Mothers for Health ] was a 12-month , r and omized controlled trial exploring a social support intervention with moderate-intensity physical activity ( PA ) seeking to effect changes in body fat , fat tissue inflammation , and depression symptoms in sedentary postpartum Latinas . This report describes the efficacy of the Madres intervention . Results The results show that while social support increased during the active intervention delivery , it declined to pre-intervention levels by the end of the intervention . There were significant achievements in aerobic and total steps across the 12 months of the intervention , and declines in body adiposity assessed with bioelectric impedance . Conclusions Social support from family and friends mediated increases in aerobic PA result ing in decrease in percent body fat . Trial registration Clinical Trials.gov Identifier : NCT01908959 OBJECTIVE To examine the feasibility , acceptability , and initial efficacy of a technology-based weight loss intervention for urban , low-income mothers . METHODS Eighteen obese , ethnic minority , socioeconomically disadvantaged mothers in the first year after childbirth were r and omly assigned to either : 1 ) technology-based intervention , which included empirically supported behavior-change strategies , daily skills , and self-monitoring text messages with personalized feedback , biweekly counseling calls from a health coach , and access to a Facebook support group , or 2 ) usual-care control . RESULTS After 14 weeks of treatment , the technology-based intervention participants had significantly greater weight loss ( -2.9 ± 3.6 kg ) than usual care ( 0.5 ± 2.3 kg ; adjusted mean difference : -3.2 kg , 95 % confidence interval -6.2 to -0.1 kg , P = .04 ) . One-third of intervention participants ( 3 of 9 ) and no control participants lost > 5 % of their initial body weight at follow up . CONCLUSIONS AND IMPLICATION S Results suggest the potential for using technology to deliver a postpartum weight loss intervention among low-income racial/ethnic minorities OBJECTIVE Optimizing gestational weight gain ( GWG ) in early pregnancy is of clinical and public health importance , especially in higher risk pregnancies . DESIGN AND METHODS In a robustly design ed , r and omized controlled trial , 228 pregnant women at risk of developing gestational diabetes mellitus ( GDM ) were allocated to either control ( written health information only ) or intervention ( four-session lifestyle program ) . All women received st and ard maternal care . Measures were completed at 12 - 15 and 26 - 28 weeks gestation . Measures included anthropometrics ( weight and height ) , physical activity ( pedometer and International Physical Activity Question naire ) , question naires ( risk perception ) , and GDM screening . RESULTS The mean ( SD ) age [ 31.7 ( 4.5 ) and 32.4 ( 4.7 ) years ] and body mass index [ BMI ; 30.3 ( 5.9 ) and 30.4 ( 5.6 ) kg/m(2 ) ] were similar between control and intervention groups , respectively . By 28 weeks , GWG was significantly different between control and intervention groups [ 6.9 ( 3.3 ) vs. 6.0 ( 2.8 ) kg , P < 0.05 ] . When stratified according to baseline BMI , overweight women in the control group gained significantly more weight compared to overweight women in the intervention group [ 7.8 ( 3.4 ) vs. 6.0 ( 2.2 ) kg , P < 0.05 ] , yet in obese women , GWG was similar in both groups . Physical activity levels declined by 28 weeks gestation overall ( P < 0.01 ) ; however , the intervention group retained a 20 % higher step count compared to controls [ 5,203 ( 3,368 ) vs. 4,140 ( 2,420 ) steps/day , P < 0.05 ] . Overall , GDM prevalence was 22.8 % [ Corrected ] , with a trend toward less cases in the intervention group ( P = 0.1 ) . CONCLUSIONS Results indicate that a low-intensity lifestyle intervention , integrated with antenatal care , optimizes healthy GWG and attenuates physical activity decline in early pregnancy . Efficacy in limiting weight gain was greatest in overweight women and in high-risk ethnically diverse women OBJECTIVE To determine if an interactive , computerized Video Doctor counseling tool improves self-reported diet and exercise in pregnant women . METHODS A r and omized trial comparing a Video Doctor intervention to usual care in ethnically diverse , low-income , English-speaking pregnant women was conducted . Brief messages about diet , exercise , and weight gain were delivered by an actor-portrayed Video Doctor twice during pregnancy . RESULTS In the Video Doctor group ( n=158 ) , there were statistically significant increases from baseline in exercise ( + 28 min ) , intake of fruits and vegetables , whole grains , fish , avocado and nuts , and significant decreases in intake of sugary foods , refined grains , high fat meats , fried foods , solid fats , and fast food . In contrast , there were no changes from baseline for any of these outcomes in the usual care group ( n=163 ) . Nutrition knowledge improved significantly over time in both groups but more so in the Video Doctor group . Clinician-patient discussion s about these topics occurred significantly more frequently in the Video Doctor group . There was no difference in weight gain between groups . CONCLUSION A brief Video Doctor intervention can improve exercise and dietary behaviors in pregnant women . PRACTICE IMPLICATION S The Video Doctor can be integrated into prenatal care to assist clinicians with effective diet and exercise counseling BACKGROUND Behavioural interventions might improve clinical outcomes in pregnant women who are obese . We aim ed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants . METHODS The UK Pregnancies Better Eating and Activity Trial ( UPBEAT ) is a r and omised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic , inner-city locations in the UK . We recruited pregnant women ( 15 - 18 weeks plus 6 days of gestation ) older than 16 years who were obese ( BMI ≥30 kg/m(2 ) ) . We r and omly assigned participants to either a behavioural intervention or st and ard antenatal care with an internet-based , computer-generated , r and omisation procedure , minimising by age , ethnic origin , centre , BMI , and parity . The intervention was delivered once a week through eight health trainer-led sessions . Primary outcomes were gestational diabetes ( diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups ) and large-for-gestational-age infants ( ≥90th customised birthweight centile ) . Analysis was by intention to treat . This trial is registered with Current Controlled Trials , ISCRTN89971375 . Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing . FINDINGS Between March 31 , 2009 , and June 2 , 2014 , we assessed 8820 women for eligibility and recruited 1555 , with a mean BMI of 36·3 kg/m(2 ) ( SD 4·8 ) . 772 were r and omly assigned to st and ard antenatal care and 783 were allocated the behavioural intervention , of which 651 and 629 women , respectively , completed an oral glucose tolerance test . Gestational diabetes was reported in 172 ( 26 % ) women in the st and ard care group compared with 160 ( 25 % ) in the intervention group ( risk ratio 0·96 , 95 % CI 0·79 - 1·16 ; p=0·68 ) . 61 ( 8 % ) of 751 babies in the st and ard care group were large for gestational age compared with 71 ( 9 % ) of 761 in the intervention group ( 1·15 , 0·83 - 1·59 ; p=0·40 ) . Thus , the primary outcomes did not differ between groups , despite improvements in some maternal secondary outcomes in the intervention group , including reduced dietary glycaemic load , gestational weight gain , and maternal sum-of-skinfold thicknesses , and increased physical activity . Adverse events included neonatal death ( two in the st and ard care group and three in the intervention group ) and fetal death in utero ( ten in the st and ard care group and six in the intervention group ) . No maternal deaths were reported . Incidence of miscarriage ( 2 % in the st and ard care group vs 2 % in the intervention group ) , major obstetric haemorrhage ( 1 % vs 3 % ) , and small-for-gestational-age infants ( ≤5th customised birthweight centile ; 6 % vs 5 % ) did not differ between groups . INTERPRETATION A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes , or to reduce the incidence of large-for-gestational-age infants . FUNDING National Institute for Health Research , Guys and St Thomas ' Charity , Chief Scientist Office Scotl and , Tommy 's Charity R and omized controlled trials often suffer from two major complications , i.e. , noncompliance and missing outcomes . One potential solution to this problem is a statistical concept called intention-to-treat ( ITT ) analysis . ITT analysis includes every subject who is r and omized according to r and omized treatment assignment . It ignores noncompliance , protocol deviations , withdrawal , and anything that happens after r and omization . ITT analysis maintains prognostic balance generated from the original r and om treatment allocation . In ITT analysis , estimate of treatment effect is generally conservative . A better application of the ITT approach is possible if complete outcome data are available for all r and omized subjects . Per- protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations Background Pregnancy is a recognised high risk period for excessive weight gain , contributing to postpartum weight retention and obesity development long-term . We aim ed to reduce postpartum weight retention following a low-intensity , self-management intervention integrated with routine antenatal care during pregnancy . Methods 228 women at increased risk of gestational diabetes , < 15 weeks gestation were r and omised to intervention ( 4 self-management sessions ) or control ( generic health information ) . Outcomes , collected at baseline and 6 weeks postpartum , included anthropometrics ( weight and height ) , physical activity ( pedometer ) and question naires ( health behaviours ) . Results Mean age ( 32.3 ± 4.7 and 31.7 ± 4.4 years ) and body mass index ( 30.4 ± 5.6 and 30.3 ± 5.9 kg/m2 ) were similar between intervention and control groups , respectively at baseline . By 6 weeks postpartum , weight change in the control group was significantly higher than the intervention group with a between group difference of 1.45 ± 5.1 kg ( 95 % CI : -2.86,-0.02 ; p < h0.05 ) overall , with a greater difference in weight found in overweight , but not obese women . Intervention group allocation , higher baseline BMI , GDM diagnosis , country of birth and higher age were all independent predictors of lower weight retention at 6 weeks postpartum on multivariable linear regression . Other factors related to weight including physical activity , did not differ between groups . Conclusions A low intensity intervention , integrated with st and ard antenatal care is effective in limiting postpartum weight retention . Implementation research is now required for scale-up to optimise antenatal health care . Trial registration Australian New Zeal and Clinical Trial Registry Number : ACTRN12608000233325 . Registered 7/5/2008 Objective Evidence is lacking regarding effective weight control treatments in pregnancy for ethnic minority women with obesity . This study evaluated whether a technology-based , behavioral intervention could decrease the proportion of overweight or obese African American women who exceeded Institute of Medicine ( IOM ) guidelines for gestational weight gain . Methods We conducted a 2-arm pilot r and omized clinical trial . Participants were 66 socioeconomically disadvantaged African American pregnant women ( 12.5 ± 3.7 weeks ’ gestation ; 36 % overweight , 64 % obese ) recruited from 2 outpatient obstetric practice s at Temple University between 2013 and 2014 . We r and omized participants to usual care ( n = 33 ) or a behavioral intervention ( n = 33 ) that promoted weight control in pregnancy . The intervention included : 1 ) empirically-supported behavior change goals ; 2 ) interactive self-monitoring text messages ; 3 ) biweekly health coach calls ; and 4 ) skills training and support through Facebook . Results The intervention reduced the proportion of women who exceeded IOM guidelines compared to usual care ( 37 % vs. 66 % , p = 0.033 ) . Intervention participants gained less weight during pregnancy ( 8.7 vs. 12.3 kg , adjusted mean difference −3.1 kg , 95 % CI −6.2 , −0.1 ) . No group differences in neonatal or obstetric outcomes were found . Conclusions The intervention result ed in lower prevalence of excessive gestational weight gain In this study , we sought to investigate the effects of a continuous glucose monitoring system ( CGMS ) on maternal and neonatal outcomes . A total of 106 women with gestational diabetes mellitus ( GDM ) in gestational weeks 24–28 were r and omly allocated to the antenatal care plus CGMS group or the self-monitoring blood glucose ( SMBG ) group . The CGMS group was subdivided into early and late subgroups . There were no significant differences in prenatal or obstetric outcomes , e.g. , caesarean delivery rate , Apgar score at 5 min , macrosomia or neonatal hypoglycaemia , between the CGMS and SMBG groups . The CGMS group had lower glycated haemoglobin ( HbA1C ) levels than the SMBG group ; however , the difference was not statistically significant . The proportion of GDM women with excessive gestational weight gain was lower in the CGMS group than in the SMBG group ( 33.3 % vs. 56.4 % , P = 0.039 ) , and women who initiated CGMS earlier gained less weight ( P = 0.017 ) . The mode of blood glucose monitoring ( adjusted OR 2.40 ; 95 % CI 1.030–5.588 ; P = 0.042 ) and pre-pregnancy BMI ( adjusted OR 0.578 ; 95 % CI 0.419–0.798 ; P = 0.001 ) were independent factors for weight gain . In conclusion , early CGMS for GDM mothers reduces gestational weight gain . A follow-up study with a large cohort is needed OBJECTIVE This study sought to evaluate the feasibility of a pilot , dyad-based lifestyle intervention , the Unidas por la Vida program , for improving weight loss and dietary intake among high-risk Mexican American mothers who have Type 2 diabetes and their overweight/obese adult daughters . METHOD Mother-daughter dyads ( N = 89 ) were recruited from two federally qualified health centers and r and omly assigned to either the Unidas intervention or to the control condition . The 16-week Unidas intervention consisted of the following : ( a ) four group meetings , ( b ) eight home visits , and ( c ) booster telephone calls by a lifestyle community coach . The control condition consisted of educational material s mailed to participants ' homes . Participants completed surveys at T1 ( baseline ) and T2 ( 16 weeks ) that assessed various demographic , social network involvement , and dietary variables . RESULTS Unidas participants lost significantly more weight at T2 ( p < .003 ) compared with the control participants . Furthermore , intervention participants also were more likely to be eating foods with lower glycemic load ( p < .001 ) and less saturated fat ( p = .004 ) at T2 . Unidas participants also reported a significant increase in health-related social support and social control ( persuasion control only ) and a decrease in undermining . CONCLUSIONS The Unidas program promoted weight loss and improved dietary intake , as well as changes in diet-related involvement of participants ' social networks . The results from this study demonstrate that interventions that draw upon multiple people who share a health-risk have the potential to foster significant changes in lifestyle behaviors and in social network members ' health-related involvement . Future research that builds on these findings is needed to eluci date the specific dyadic and social network processes that may drive health behavior change OBJECTIVE Few postpartum ethnic minority women perform leisure-time moderate-to-vigorous physical activity ( MVPA ) . The study tested the effectiveness of a 12-month tailored intervention to increase MVPA in women with infants 2 - 12months old . METHODS From 2008 to 2011 , women ( n=311 ) with infants ( average age=5.7months ) from Honolulu , Hawaii were r and omly assigned to receive tailored telephone calls and access to a mom-centric website ( n=154 ) or access to a st and ard PA website ( n=157 ) . MVPA was measured at baseline , 6 , and 12months using self-report and acclerometers . RESULTS Controlling for covariates , the tailored condition significantly increased self-reported MVPA from an average of 44 to 246min/week compared with 46 to 156min/week for the st and ard condition ( p=0.027 ) . Mothers with≥2 children had significantly greater increases in MVPA in response to the tailored intervention than those with one child ( p=0.016 ) . Accelerometer-measured MVPA significantly increased over time ( p=0.0001 ) , with no condition differences . There was evidence of reactivity to initially wearing accelerometers ; the tailored intervention significantly increased MVPA among women with low baseline accelerometer MVPA minutes , but not among those with high minutes ( pinteraction=0.053 ) . CONCLUSION A tailored intervention effectively increased MVPA over 12months in multiethnic women with infants , particularly those with more than one child BACKGROUND Excessive weight gain during pregnancy is a risk factor for postpartum weight retention and future weight gain and obesity . Whether a behavioral intervention in pregnancy can reduce long-term weight retention is unknown . OBJECTIVE This r and omized trial tested whether a low-intensity behavioral intervention to prevent excessive gestational weight gain could increase the proportion of women who returned to prepregnancy weight by 12 mo postpartum . DESIGN Women ( n = 401 , 13.5 wk of gestation , 50 % normal weight , 50 % overweight/obese ) were r and omly assigned into an intervention or control group ; 79 % completed the 12-mo assessment . The telephone-based intervention targeted gestational weight gain , healthy eating , and exercise and was discontinued at delivery . RESULTS In modified intent-to-treat analyses that excluded women with miscarriages ( n = 6 ) , gestational diabetes ( n = 32 ) , or subsequent pregnancies ( n = 32 ) , the intervention had no significant effect on the odds of achieving prepregnancy weight at 12 mo postpartum ( n = 331 ; 35.4 % compared with 28.1 % ; P = 0.18 ) . Completer analyses suggested that the intervention tended to increase the percentages of women who reached prepregnancy weight ( n = 261 ; 45.3 % compared with 35.3 % ; P = 0.09 ) and significantly reduced the magnitude of mean ± SD postpartum weight retained ( 1.4 ± 6.3 compared with 3.0 ± 5.7 kg ; P = 0.046 ) at 12 mo . Women in the intervention group reported higher dietary restraint through 6 mo postpartum ( P = 0.023 ) and more frequent self-monitoring of body weight ( P < 0.02 for all ) throughout the study . CONCLUSIONS A low-intensity behavioral intervention in pregnancy can reduce 12-mo postpartum weight retention and improve dietary restraint and self-weighing in study completers . Future research is needed to test the long-term effects of more intensive behavioral interventions in pregnancy . This trial was registered at clinical trials.gov as NCT01117961 Introduction Physical inactivity is prevalent in pregnant women , and innovative strategies to promote physical activity are strongly needed . The purpose of the study was to test a 12-week mobile health ( mHealth ) physical activity intervention for feasibility and potential efficacy . Methods Participants were recruited between December 2012 and February 2014 using diverse recruitment methods . Thirty pregnant women between 10 and 20 weeks of gestation were r and omized to an intervention ( mobile phone app plus Fitbit ) or a control ( Fitbit ) group . Both conditions targeted gradual increases in physical activity . The mHealth intervention included daily messages and a mobile phone activity diary with automated feedback and self-monitoring systems . Results On monthly average , 4 women were screened for initial eligibility by telephone and 2.5 were r and omized . Intervention participants had a 1096 ± 1898 step increase in daily steps compared to an increase of 259 ± 1604 steps in control participants at 12 weeks . The change between groups in weekly mean steps per day during the 12-week study period was not statistically significant ( p = 0.38 ) . The intervention group reported lower perceived barrier to being active , lack of energy , than the control group at 12-week visit ( p = 0.02 ) . The rates of responding to daily messages and using the daily diary through the mobile app declined during the 12 week study period . Discussion It was difficult to recruit and r and omize inactive women who wanted to increase physical activity during pregnancy . Pregnant women who were motivated to increase physical activity might find using mobile technologies in assessing and promoting PA acceptable . Possible reasons for the non-significant treatment effect of the mHealth intervention on physical activity are discussed . Public awareness of safety and benefits of physical activity during pregnancy should be promoted . Clinical trials . Gov Identifier NCT01461707 BACKGROUND Current evidence suggests a combined treatment of postpartum weight loss of diet and exercise . However , to our knowledge , neither their separate and interactive effects nor long-term outcomes have been evaluated . OBJECTIVE We evaluated whether a 12-wk dietary behavior modification ( D ) treatment to decrease energy intake , physical exercise behavior modification ( E ) treatment to implement moderate aerobic exercise , or combined dietary and physical exercise behavior modification ( DE ) treatment compared with control ( usual care ) ( C ) reduces body weight in lactating women measured at the end of treatment and at a 1-y follow-up 9 mo after treatment termination . DESIGN At 10 - 14 wk postpartum , 68 lactating Swedish women with a prepregnancy BMI ( in kg/m² ) of 25 - 35 were r and omly assigned to D , E , DE , or C groups . Measurements were made at baseline , after the intervention , and again at a 1-y follow-up 9 mo later . A 2 × 2 factorial approach was used to analyze main and interaction effects of treatments . RESULTS Weight changes after the intervention and 1-y follow-up were -8.3 ± 4.2 and -10.2 ± 5.7 kg , respectively , in the D group ; -2.4 ± 3.2 and -2.7 ± 5.9 kg , respectively , in the E group ; -6.9 ± 3.0 and -7.3 ± 6.3 kg , respectively , in the DE group ; and -0.8 ± 3.0 and -0.9 ± 6.6 kg , respectively , in the C group . The main effects of D treatment , but not of E treatment , on weight were significant at both times ( P < 0.001 ) . CONCLUSIONS Dietary treatment provided clinical ly relevant weight loss in lactating postpartum women , which was sustained at 9 mo after treatment . The combined treatment did not yield significant weight or body-composition changes beyond those of dietary treatment alone BACKGROUND Failure to return to pregnancy weight by 6 months postpartum is associated with long-term obesity , as well as adverse health outcomes . This research evaluated a postpartum weight management programme for women with a body mass index ( BMI ) > 25 kg m(-2 ) that combined behaviour change principles and a low-intensity delivery format with postpartum nutrition information . METHODS Women were r and omised at 24 - 28 weeks to control ( supported care ; SC ) or intervention ( enhanced care ; EC ) groups , stratified by BMI cohort . At 36 weeks of gestation , SC women received a ' nutrition for breastfeeding ' re source and EC women received a nutrition assessment and goal - setting session about post-natal nutrition , plus a 6-month correspondence intervention requiring return of self-monitoring sheets . Weight change , anthropometry , diet , physical activity , breastfeeding , fasting glucose and insulin measures were assessed at 6 weeks and 6 months postpartum . RESULTS Seventy-seven percent ( 40 EC and 41 SC ) of the 105 women approached were recruited ; 36 EC and 35 SC women received a programme and 66.7 % and 48.6 % completed the study , respectively . No significant differences were observed between any outcomes . Median [ interquartile range ( IQR ) ] weight change was EC : -1.1 ( 9.5 ) kg versus SC : -1.1 ( 7.5 ) kg ( 6 weeks to 6 months ) and EC : + 1.0 ( 8.7 ) kg versus SC : + 2.3 ( 9 ) kg ( prepregnancy to 6 months ) . Intervention women breastfed for half a month longer than control women ( 180 versus 164 days ; P = 0.10 ) . An average of 2.3 out of six activity sheets per participant was returned . CONCLUSIONS Despite low intervention engagement , the high retention rate suggests this remains an area of interest to women . Future strategies must facilitate women 's engagement , be individually tailored , and include features that support behaviour change to decrease women 's risk of chronic health issues The Internet offers a valuable re source for promotion of healthy eating and Web-based communication between the dietetics practitioner and client . In a 16-week intervention examining the effects of energy restriction ( 500 kcal/day ) and exercise on body composition in overweight/obese lactating women , MyPyramid Menu Planner for Moms was used to support dietary counseling . R and om assignment occurred at 4 weeks postpartum to either an Intervention group ( n=14 ) or Minimal Care group ( n=13 ) from 2008 through 2010 . Three 24-hour dietary recalls were obtained using the Nutrition Data System at 4 and 20 weeks postpartum . Individual MyPyramid Menu Planner accounts were created for the Intervention group and used in face-to-face dietary counseling . Repeated measures analysis of variance was used to test for differences between groups for change in dietary intake and weight . Changes in energy , saturated fat , and percent of energy from added sugars were significantly different between Intervention group and Minimal Care group ( -613 [ 521 ] kcal vs -171 [ 435 ] kcal ; P=0.03 ; -14.9 [ 14.0 ] g vs + 0.9 [ 13.4 ] g ; P<0.01 ; and -3.5 % [ 5.3 % ] vs + 2.2 % [ 4.8 % ] ; P<0.01 , respectively ) . The Intervention group significantly increased their whole fruit servings and decreased their total grain and milk servings compared with the Minimal Care group ( P<0.05 ) . The Intervention group lost significantly more weight ( -5.8 [ 3.5 ] kg ) than the Minimal Care group ( -1.6 [ 5.4 ] kg ) ( P=0.03 ) . Although participants must have access to an Internet-based computer and possess basic food knowledge , these results suggest MyPyramid Menu Planner might prove to be an effective dietary counseling support tool for improving dietary intake and promoting weight loss during lactation OBJECTIVES Excessive gestational weight gain ( GWG ) puts women and children at risk of obesity . We piloted an SMS-texting intervention to promote healthy GWG among overweight and obese women . METHODS We recruited 35 women and r and omized them in a 2:1 fashion to : a tailored SMS-texting intervention ( Preg CHAT ) vs. a generic texting intervention ( Txt4baby ) . Preg CHAT texts provided personalized feedback based on women 's intake of sweetened beverages , fruits and vegetables , fast food , daily steps taken , and weight . We abstract ed women 's weights from charts and surveyed women at baseline and 32 weeks gestation . RESULTS Few women refused the study ; many ( 30 % ) did not complete the study , however . Of those in the Preg CHAT arm , 86 % responded to texts , and 80 % said they would recommend this program to a friend . For women who completed the surveys ( n=23 ) , those in the Preg CHAT arm had a mean gain of 6 less pounds than women in the Txt4Baby arm ( 95 % CI -15.9 , 4.0 ; p=0.24 ) . CONCLUSIONS This pilot study shows feasibility , acceptability , and potential efficacy of a low-intensity and disseminable intervention to help overweight and obese women reduce GWG . PRACTICE IMPLICATION S An SMS texting program might help overweight women reduce excessive GWG BACKGROUND Excessive weight gain during pregnancy is a major risk factor for postpartum weight retention and future weight gain and obesity in women , but few adequately powered r and omized controlled trials have examined the efficacy of a behavioral weight-control intervention during pregnancy . OBJECTIVE This study examined whether a behavioral intervention during pregnancy could decrease the proportion of women who exceeded the 1990 Institute of Medicine ( IOM ) recommendations for gestational weight gains and increase the proportion of women who returned to pregravid weights by 6 mo postpartum . DESIGN This study was a r and omized , assessor-blind , controlled trial . Participants were pregnant ( 13.5 wk gestation ) , normal-weight ( NW ; n = 201 ) and overweight or obese ( OW/OB ; n = 200 ) women whose average age was 28.8 y. Participants were r and omly assigned within the 1990 IOM weight category ( NW compared with OW/OB ) to st and ard care ( n = 200 ) or to a behavioral intervention to prevent excessive gestational weight gain ( n = 201 ) . The intervention included one face-to-face visit ; weekly mailed material s that promoted an appropriate weight gain , healthy eating , and exercise ; individual graphs of weight gain ; and telephone-based feedback . The retention at the 6-mo postpartum assessment was 82 % . RESULTS Intent-to-treat analyses showed that the intervention , compared with st and ard care , decreased the percentage of NW women who exceeded IOM recommendations ( 40.2 % compared with 52.1 % ; P = 0.003 ) and increased the percentages of NW and OW/OB women who returned to their pregravid weights or below by 6 mo postpartum ( 30.7 % compared with 18.7 % ; P = 0.005 ) . CONCLUSION A low-intensity behavioral intervention during pregnancy reduced excessive gestational weight gains in NW women and prevented postpartum weight retention in NW and OW/OB women . This trial was registered at clinical trials.gov as NCT01117961 |
12,693 | 23,010,368 | Before surgery , the lowest detectable threshold corresponded to a mean of 0.07 to 0.16 g. At 1 month after surgery , the lowest detectable threshold averaged 6 g , and at 1 year after surgery , the mean value was 0.16 to 0.4 g. CONCLUSIONS After bilateral sagittal split osteotomy , at 1 month after surgery , the sensory threshold increases approximately 35- to 85-fold compared with the presurgery threshold .
Within 1 year , the threshold normally decreases almost to presurgery levels , representing 96 % to 98 % sensory recovery . | PURPOSE To evaluate neurosensory disturbance of the inferior alveolar nerve , after bilateral sagittal split osteotomy , from before surgery to 1 year postoperatively , by quantitatively evaluating published data using Semmes-Weinstein monofilaments . | PURPOSE This prospect i ve study evaluated the neurosensory recovery pattern of the inferior alveolar nerve following the bilateral sagittal split osteotomy ( BSSO ) . PATIENTS AND METHODS Forty-two consecutive patients undergoing BSSO were studied using five neurosensory tests : 1 ) static light touch , 2 ) moving touch discrimination , 3 ) two-point discrimination , 4 ) nociception , and 5 ) thermoreception . Intraoperative assessment of inferior alveolar nerve damage was made ; other variables recorded included type of fixation , age , concomitant procedures , advancement vs setback , and magnitude of the movement . A subjective question naire was completed by the patient . RESULTS The variables that affected neurosensory function following BSSO were degree of nerve damage and the amount of time elapsed following surgery . Larger myelinated fibers ( A-alpha ) recovered slower and to a lesser degree at all time intervals up to 2 years when compared with small myelinated and unmyelinated nerve fibers . The magnitude of nerve damage directly correlated with early neurosensory deficit , but equalized over time . CONCLUSION The long term ( 6 months and greater ) chance for neurosensory recovery is good despite intraoperative nerve manipulation . Patients seem to adapt and report normal neurosensory function even though objective testing indicates continued neurosensory deficit Three hundred seventeen normal fingers and 612 fingers in 153 h and s with carpal tunnel syndrome were tested for sensibility using the Weinstein Enhanced Sensory Test ( WEST ) with calibrated monofilaments , by static two-point discrimination ( s2PD ) and moving two-point discrimination ( m2PD ) , using the Disk-Criminator , and by Strauch 's ten test . Equivalent Semmes-Weinstein monofilament ( SWM ) test values were also determined as a gold st and ard for comparison . With both the WEST and SWM test values , the norms for interpretation have an unacceptably wide latitude because of the use of an ordinal scale of increasingly unequal intervals . With the WEST and Disk-Criminator tests , some cases of early sensory loss were missed . The SWM test apparatus , although producing relatively reliable values , is not easily portable , and its use is time-consuming in a busy office ; the WEST device is prohibitively expensive . The ten test is rapid , simple , and sensitive in evaluation . It measures sensibility on a continuous analog scale , and allows for multiple points of testing in the h and , with good inter- and intra-examiner reliability . It is accurate in detecting very early loss of sensibility . In addition , the ten test requires no instrumentation Objectives Semmes-Weinstein monofilaments are too long for use in parts of the oral cavity . The present study used shortened Semmes-Weinstein monofilaments to evaluate reliability and spatial differences in the intraoral tactile detection threshold ( TDT ) and the filament-prick pain detection threshold ( FPT ) in healthy volunteers . Methods For practical purpose s , classic Semmes-Weinstein monofilaments with 20 different diameters were cut to half their length ( ie , 19 mm ) and the bending forces were measured . Eighteen men and 18 women ( age range , 20 to 33 y ) were recruited to evaluate the reliability and reproducibility of measurements using half-cut monofilaments . The TDT and the FPT were measured on the labial maxillary gingiva , on the palatal maxillary gingiva , and at the anterior tip of the tongue , using a double r and om staircase method . Results According to the forces needed to bend the half-cut filaments , they were renumbered from 2.55 to 6.86 . There were significant differences of bending force between the half-cut and original monofilaments ( P<0.001 ) , Using half-cut filaments , the following differences could be detected ; the labial maxillary gingiva had a significantly higher TDT threshold compared with the other test sites ( P<0.001 ) . By contrast , the palatal posterior maxillary gingiva had a significantly higher FPT threshold compared with the other test sites ( P<0.001 ) . Discussion s The present study illustrated that in healthy participants , half-cut Semmes-Weinstein monofilaments reliably and easily assess TDT and FPT intraorally . A combined examination of sensory and pain thresholds using these filaments contributes to the clinical examination for orofacial pain The aim of this study was to conduct a prospect i ve clinical trial comparing the neurosensory function of the inferior alveolar nerve ( IAN ) after m and ibular advancement surgery with either bilateral sagittal split osteotomies ( BSSO ) or m and ibular distraction ostoegenesis ( MDO ) . 23 Class II m and ibular hypoplasia patients requiring m and ibular advancement were r and omized into two groups for either BSSO or MDO . Subjective and objective neurosensory evaluations were performed preoperatively and at the following postoperative times : 2 weeks ( TBD1 ) , 6 weeks ( TBD2 ) , 12 weeks ( TBD3 ) , 6 months ( TBD4 ) and 12 months ( TBD5 ) . Subjective evaluation included the use of a visual analogue scale ( VAS ) . Objective evaluation included the use of light touch ( LT ) , two-point discrimination ( 2PD ) and pain detection threshold ( PD ) tests . Intra-operative or postoperative complications were recorded . Using a mixed model , no significant differences were reported in subjective VAS scores and objective LT , 2PD and PD scores between the BSSO and MDO groups over 12 months ( p>0.05 ) . Common postoperative complications included localized wound infection ( BSSO=2 , MDO=6 ) and condylar resorption ( BSSO=1 , MDO=1 ) PURPOSE The purpose of this analysis was to compare the frequency and severity of nerve damage with rigid and wire fixation in patients participating in a prospect i ve , r and omized clinical trial . PATIENTS AND METHODS One hundred twenty-six patients who required a bilateral sagittal split osteotomy and m and ibular advancement were r and omly assigned to receive either rigid or wire fixation . Tactile sensation in the mental nerve region bilaterally was determined presurgically and throughout the subsequent 2 years by using monofilament detection and brush stroke direction . Neurosensory levels were compared between the types of fixation over time . RESULTS Evaluation with monofilament detection showed no significant difference between types of fixation throughout the 2-year follow-up . However , brush stroke determination showed significantly greater hypesthesia with rigid compared with wire fixation from 8 weeks through 2 years postoperatively . CONCLUSION Rigid fixation result ed in more anesthesia in the mental nerve distribution than wire fixation when tested with brush stroke direction . However , increased anesthesia was not present when measured with monofilament determination PURPOSE This study investigated neurosensory disturbances in patients after orthognathic surgery in relation to differences in m and ibular splitting methods and degree of surgical skill . PATIENTS AND METHODS Forty-five patients who had undergone bilateral sagittal split ramus osteotomies ( SSRO ) , and 21 ( group L ) who had undergone intraoral inverted L ramus osteotomies ( ILRO ) , were examined for postsurgical neurosensory disturbances . Twenty-two ( group S1 ) of the SSRO patients were treated by 11 surgeons who had little experience , and the others ( 23 patients ; group S2 ) were treated by 2 skilled surgeons who had considerable experience . One of the 2 skilled surgeons was the only surgeon carrying out the ILRO procedure . The neurosensory tests employed included light touching using a Semmes-Weinstein monofilament tester ( SW tester ) , electrical stimulation , and a question naire to determine changes in subjective sensations , at the time of each sensory evaluation . Neurosensory examinations were carried out bilaterally ( 132 sides ) at 1 , 3 , 6 , and 12 months after surgery . RESULTS More patients showed abnormal thresholds for the 2 measurement techniques in the SSRO group than in the ILRO group , and furthermore there were more such patients in group S1 than in group S2 , at each measurement point . At 6 months after surgery , the number of patients with reduced sensitivity was significantly higher in group S1 than in group L ( P < .05 ) . In the SSRO group at each measurement point , the thresholds for the lower lip and chin were unrelated to the set-back ( or advance ) distance . By contrast , in group L only at the 1-month evaluation point , the thresholds for the lower lip and chin were significantly raised in patients whose setback distances were larger than average ( P < .05 ) . CONCLUSIONS Postsurgical neurosensory disturbances of the lower lip and chin occur more frequently in SSRO patients treated by surgeons having little experience than in those treated by skilled surgeons , although the difference is not significant . Long-term prognosis for resolution of postsurgical neurosensory disturbances is better in ILRO patients than in SSRO patients . Although the width of movement of the split bone fragments has an influence on postsurgical neurosensory disturbances immediately after ILRO , the relationship becomes less obvious with time The criteria and scoring method for a system to evaluate the quality of r and omized control trials ( RCTs ) in dental research based on published reports is presented . This sytem is based on one devised for evaluation of RCTs in medicine . Items assessed in this system include r and omization and blinding procedures , subject selection criteria , treatment protocol s , and statistical analyses . Assessing the quality of RCTs can contribute to improved study design , implementation and reporting by investigators , and evaluation of reports by referees and editors of scientific journals Deficits in the neurosensory function ( NF ) of the inferior alveolar nerve ( IAN ) are often encountered after bilateral sagittal split osteotomy of the m and ible . A prospect i ve follow-up study was performed to examine the long-term effect of especially gentle h and ling of the soft tissues on the medial side of the ascending ramus . After the initial incision , the soft tissues of the ramus were either retracted extremely gently and minimally ( test side ) or , as was the earlier routine , more widely ( contralateral control side ) . NF was tested with 2-point discrimination ( 2-PD ) and vitality scanner tests ( VST ) preoperatively and four times postoperatively up to 1 year . Patients ' subjective sensations were also assessed . The results showed a difference between the sides , which was most distinct at the 6-month follow-up ( P=0.028 ) measured with VST , while 2-PD did not show any statistical differences . Our findings support the earlier intraoperative neurophysiologic reports that dissection trauma to the IAN around the m and ibular foramen may cause NF deficits in the IAN even before the actual splitting of the m and ible . Therefore , minimal distraction of the soft tissues in the ramus is indicated . Higher age is an evident risk factor , and subjective sensation correlates with 2-PD in the lower lip Sensory impairment after bilateral sagittal split osteotomy ( BSSO ) due to inferior alveolar nerve ( IAN ) lesions may be either temporary or permanent and either complete or partial . The aim of this prospect i ve study is to evaluate , by means of objective sensory testing , IAN sensory disturbances development in patients who underwent BSSO.IAN sensory disturbances development at the first week , fourth week , sixth month , and twelfth month of follow-up review in a group of 60 patients who underwent BSSO from January 1 , 1998 , to July 31 , 1999 , at the Maxillofacial Surgery Department of the “ La Sapienza ” University of Rome . The 60 patients were examined in the presurgical period ; the IAN functionality regarding thermal sensibility , nociception , and two-point discrimination , was assessed at follow-up in 120 sides . In our study the highest rate of spontaneous recovery of the entire IAN functionality was observed at the sixth month . This finding witnesses how neuropraxia and axonotmesis give a spontaneous recovery that most frequently occurs within 6 months from surgery , independently from age and sex of the patient . The persistence of anesthesia over 12 months could be a sign of neurotmesis PURPOSE The aim of this prospect i ve study was to objective ly evaluate the inferior alveolar nerve ( IAN ) sensory disturbances in patients who underwent sagittal split ramus osteotomy ( SSRO ) and its spontaneous recovery and to define the incidence of sensibility loss , time , and area at which the recovery occurs . PATIENTS AND METHODS Clinical evaluation of the IAN sensory disturbance was undertaken preoperatively and at the first week , fourth week , 2 months , and 6 months postoperatively in 30 patients who underwent SSRO at the Oral and Maxillofacial Surgery Division of the Araraquara Dental School -- Unesp and at the Plastic Surgery Division of the Medical Sciences School -- Unicamp . The 30 patients were examined at all periods regarding the IAN functionality by Semmes-Weinstein testing . RESULTS The mean age of the patients included in this study was 29.36 years old . All patients showed sensibility loss at the 7-day evaluation time . The comparison between sides , gender , and age did not show any significant difference . In most of the examined zone , the data collected at 6 months were statistically similar to the data collected at the preoperative period . All zones presented significant recovery , starting from 30 days after surgery . Twenty patients had total spontaneous recovery at the final period , in all examined zones . CONCLUSIONS The SSRO presents the disadvantage of temporary paresthesia ; however , spontaneous nerve function recovery does occur . The Semmes-Weinstein test is a reliable , inexpensive , and easy-to-apply tool , which can be used for clinical evaluation on a daily basis at offices and hospitals |
12,694 | 23,216,066 | Patients who were treated with long-acting injectable risperidone showed high maintenance of remission status .
Studies comparing second-generation antipsychotics versus haloperidol showed higher remission rates for the former .
The variables most frequently associated with remission were better premorbid function , milder symptoms at baseline ( especially negative symptoms ) , early response to treatment , and shorter duration of untreated psychosis .
Variability in the length and frequency of follow-ups , as well as differences in dropout rates , could partially explain the differences in reported rates .
Rates of symptomatic remission exceeded reported rates for functional recovery . | In 2005 , the Remission in Schizophrenia Working Group published consensus criteria to define remission .
These criteria have been widely accepted and utilized and have provided further insights about schizophrenia management and prognosis . | To evaluate the maintenance of efficacy of risperidone long‐acting injectable ( RLAI ) in stable patients with schizophrenia or schizoaffective disorders . The prevalence of patients who met st and ardized remission criteria will be also evaluated as well as the predictors factors of remission according to psychopathological , psychosocial and subjective correlates Background A number of recently published r and omized controlled trials conducted in developed countries have reported no advantage for assertive interventions over st and ard care models . One possible explanation could be that so-called " st and ard care " has become more comprehensive in recent years , incorporating some of the salient aspects of assertive models in its modus oper and i. Our study represents the first r and omised controlled trial assessing the effect of a modified assertive treatment service on readmission rates and other measures of outcome in a developing country . Methods High frequency service users were r and omized into an intervention ( n = 34 ) and a control ( n = 26 ) group . The control group received st and ard community care and the active group an assertive intervention based on a modified version of the international model of assertive community treatment . Study visits were conducted at baseline and 12 months with demographic and illness information collected at visit 1 and readmission rates documented at study end . Symptomatology and functioning were measured at both visits using the PANSS , CDSS , ESRS , WHO-QOL and SOFAS . Results At 12 month follow-up subjects receiving the assertive intervention had significantly lower total PANSS ( p = 0.02 ) as well as positive ( p < 0.01 ) and general psychopathology ( p = 0.01 ) subscales ' scores . The mean SOFAS score was also significantly higher ( p = 0.02 ) and the mean number of psychiatric admissions significantly lower ( p < 0.01 ) in the intervention group . Conclusions Our results indicate that assertive interventions in a developing setting where st and ard community mental services are often under re source d can produce significant outcomes . Furthermore , these interventions need not be as expensive and comprehensive as international , first-world models in order to reduce inpatient days , improve psychopathology and overall levels of functioning in patients with severe mental illness BACKGROUND Recently , remission criteria for schizophrenia have been proposed , based on low symptom severity of core symptoms ( severity criterion ) , sustained over minimally 6 months ( time criterion ) . Little is known , however , about the added value of the time criterion in addition to the cross-sectional severity criterion . METHODS In order to evaluate whether remission is a valid concept for daily clinical practice , the cumulative incidence of patients meeting remission criteria was evaluated in a large naturalistic prospect i ve study of patients with schizophrenia or schizoaffective disorder in different treatment setting s in Belgium . The impact of being in remission on global and daily functioning was evaluated . RESULTS Over time , nearly 1 out of 3 patients with a diagnosis of schizophrenia or schizoaffective disorder ( 29 % ) met criteria for remission at study endpoint . Patients in remission had better insight in their disorder , a higher level of global functioning and functioned better with respect to daily living tasks , both compared to patients never meeting remission criteria and to patients only meeting the severity criterion but not the time criterion . Of the patients not meeting remission criteria at baseline , 21 % attained remission at study endpoint . CONCLUSION The remission severity and time criteria appear to combine into a valid concept for daily clinical practice and should be a target for treatment BACKGROUND Recently , the " Remission in Schizophrenia Working Group " proposed remission criteria consisting of a reduction to mild levels on key symptoms for at least 6 months . AIMS This study applied these remission criteria to a large first-episode psychosis sample in order to ( 1 ) determine the rates of remission ; ( 2 ) explore predictors of remission ; and ( 3 ) test the external validity of these criteria . METHODS We analyzed data from 462 subjects with a first-episode of psychosis who participated in a long-term , multinational , r and omized , double-blinded trial of risperidone and haloperidol over 2 to 4 years . RESULTS At some time point in the study 323 ( 70 % ) of the 462 subjects had a reduction to mild levels on the key symptoms as measured by the PANSS although only 109 ( 23.6 % ) maintained this level for at least 6 months thereby meeting remission criteria . The two strongest predictors of remission were shorter duration of untreated psychosis ( p=0.01 ) and treatment response at 6 weeks ( p=0.001 ) . Compared to non-remitted patients , those in remission experienced greater improvement on all PANSS subscales ( p<.0001 ) , CGI-S ( p<.0001 ) , better quality of life ( p=0.006 ) , fewer relapses ( p<.0001 ) , displayed a more favorable attitude towards their medication ( p=.002 ) , had lower EPS levels according to the ESRS ( p=<.0001 ) and received lower doses of antipsychotic medication ( p=0.003 ) . The remission and non-remission groups did not differ significantly regarding composite cognitive scores , suicidality and body mass index . CONCLUSIONS The results suggest that the remission criteria , although based solely on core symptom improvement , can effectively identify patients who have a more favorable overall outcome OBJECTIVE This study examined the treatment response of patients with first-episode schizophrenia and schizoaffective disorder and potential predictors of response . METHOD First-episode patients were assessed on measures of psychopathology , cognition , social functioning , and biological parameters and treated according to a st and ardized algorithm . RESULTS One hundred eighteen patients ( 52 % male , mean age 25.2 years ) entered the study . The cumulative percentage of patients responding by 1 year was 87 % ; the median time to response was 9 weeks . The following variables were significantly associated with less likelihood of response to treatment : male sex , obstetric complications , more severe hallucinations and delusions , poorer attention at baseline , and the development of parkinsonism during antipsychotic treatment . Variables not significantly related to treatment response were diagnosis ( schizophrenia versus schizoaffective disorder ) , premorbid functioning , duration of psychotic symptoms prior to study entry , baseline disorganization , negative and depressive symptoms , baseline motor function , akathisia and dystonia during treatment , growth hormone and homovanillic acid measures , psychotic symptom activation to methylpheni date , and magnetic resonance measures . CONCLUSIONS Patients with first-episode schizophrenia and schizoaffective disorder have high rates of response to antipsychotic treatment ; there are specific clinical and pathobiologic predictors of response OBJECTIVE Switching medications is common in the treatment of schizophrenia . This study examines the effectiveness of olanzapine therapy following a clinical ly warranted switch from risperidone during treatment of patients with schizophrenia . RESEARCH DESIGN AND METHODS This post-hoc analysis used data from the risperidone arm of a r and omized , open-label , 1-year study of patients with schizophrenia . Study protocol permitted antipsychotic switching when clinical ly warranted , and outcomes were assessed with st and ard psychiatric measures . Statistical analyses assessed changes from pre- to post-medication switch and endpoint comparisons between patients switched from risperidone to olanzapine and patients continued on risperidone . RESULTS Most patients who switched from risperidone switched to olanzapine ( 43/60 ; 71.7 % ) . Average duration of risperidone treatment prior to switching was 86 days ( mean modal dose 4.0 mg/day ) . Most switchers ( 86 % ) completed the 1-year study on olanzapine ( average duration 241 days ; mean modal dose 12.0 mg/day ) . Following switch to olanzapine , patients experienced significant improvements on clinical ( Brief Psychiatric Rating Scale ) and social ( Quality of Life Inventory ) parameters , with similar proportions of patients achieving remission status at endpoint compared with risperidone patients not requiring medication switch ( 41.9 vs. 35.5 % ) . Mean weight gain for switchers was approximately 0.4 kg while on risperidone ( average treatment duration < 3 months ) and 2.4 kg on olanzapine ( average treatment duration approximately 8 months ) . CONCLUSIONS This study suggests that olanzapine is an effective treatment option for schizophrenia patients requiring a switch from risperidone . Given the small sample size and lack of a comparative group , one can not determine if other medication options would have been as effective as the switch to olanzapine . Thus , further research is warranted Although the concept of remission has been widely accepted and utilized in depression and anxiety disorders , there has been much less emphasis on defining remission in schizophrenia . Recently , an expert consensus definition of remission in schizophrenia was proposed along specific operational criteria for the attainment of remission focusing on the three core dimensions of psychopathology identified within schizophrenia : psychoticism , disorganization and negative symptoms . To date , the criteria have been applied retrospectively to several clinical studies , and these have demonstrated that the proposed definition of remission correlates significantly with established measures of symptom severity , functioning and quality of life , and appears achievable for a significant proportion of patients receiving at least 3 months of pharmacotherapy . In this article we extend the notion of remission to include an examination of the possible association of several modifiable and unmodifiable factors and co-morbidities on remission status . We also propose an investigation into the likelihood of different patient population s in achieving remission as well as assessing the impact of remission on health care costs and family burden . Since cognitive dysfunction and negative symptoms may be strongly correlated with a lower likelihood of achieving remission , we recommend retrospective and /or prospect i ve studies to determine the relationship between neurocognitive status and the predominance of negative symptoms at treatment start and the probability of achieving remission . Taken together , these studies should help identify key predictors of remission , further define the remitted state , reduce therapeutic pessimism , raise treatment expectations and chart a strategy for further research in this important area PURPOSE Although treatment advances have improved outcomes in schizophrenia , definitions of remission and recovery are still evolving . Recently proposed criteria for remission ( mild or less on multiple core-symptom ratings for at least 6 months ) have been applied to a 1-year study of long-acting risperidone injection . METHODS In a 50-week , open-label trial , stable patients with schizophrenia or schizoaffective disorder who received long-acting risperidone injection every 2 weeks were assessed using the Positive and Negative Syndrome Scale ( PANSS ) . Remission criteria for the PANSS were applied ; global illness severity ( Clinical Global Impressions ) and patient-rated health status ( 36-Item Short-form Health Survey ) were measured . RESULTS Groups were identified by initial remission status ( excluding the time component ) . Although considered clinical ly " stable , " 68.2 % ( 394/578 ) did not meet the symptom-severity component of remission criteria at baseline . Following long-acting , injectable risperidone treatment , 20.8 % ( 82 ) of nonremitted patients achieved symptom remission for at least 6 months , with significant decreases in mean PANSS total and cluster scores ( P < 0.0001 ) and significantly improved patient-rated health status ( P < 0.0001 ) . Percentages rated as not ill , very mild , or mild increased from 39 % to 88 % . Among 31.8 % ( 184/578 ) of patients meeting the symptom-severity component of remission criteria at baseline , 84.8 % ( 156 ) maintained these criteria at endpoint . CONCLUSIONS Among previously " stable , " nonremitted patients , many achieved symptom remission after long-acting , injectable risperidone treatment , with significant improvements in multiple symptom domains and patient-rated health status . These results warrant further study as these remission criteria may represent a meaningful clinical endpoint and an important step towards functional recovery BACKGROUND The goal of these secondary analyses of clinical trial data was to characterize clinical outcomes in patients with schizophrenia who met symptom severity or duration thresholds for two alternative definitions of remission , and to explore their relationships to improvement duration and quality of life outcomes . METHODS Definition 1 used threshold criteria for selected PANSS items sustained over at least 6-months Definition 2 used Brief Psychiatric Rating Scale ( BPRS ) % change , a threshold score for the Clinical Global Improvement-Severity ( CGI-S ) maintained for at least 8 weeks , and threshold scores for selected BPRS items . Positive and Negative Symptom Scale ( PANSS ) and Quality of Life scale ( QLS ) total scores were pooled from 6 clinical trials . The extent to which the alternative severity thresholds from these two definitions and duration of clinical improvement were associated with different clinical and QLS outcomes was explored . Regression analysis also assessed the relative contribution of each of the components of the two definition severity thresholds to improvements in QLS Total score . RESULTS Increases in QLS scores were greater for those patients who met either threshold criteria relative to those who met neither ( p<.0001 ) . Significantly greater improvements in QLS scores were observed for patients who met either threshold criteria at the 8- , 16- and 24-week visits relative to those who met criteria at weeks 16 and 24 , or at week 24 only ( p<0.001 ) , as well as for the subset of patients who met threshold criteria at both 24 and 52 weeks relative to those who met criteria at only one of these 2 time points . Only 31 % to 47 % of patients meeting threshold criteria for either definition at the 8- , 16- or 24-week visits remained in remission at the 52-week visit . Among the severity threshold components analyzed , BPRS total % change from baseline was the strongest predictor of improvement in QLS scores . CONCLUSIONS Quality of life improved most for patients who achieved severity thresholds associated with either remission criteria and who stayed improved for longer periods . Total BPRS change scores accounted for the greatest percentage of the QLS scores variance . Only a fraction of patients who meet severity criteria for either remission definition early in treatment will remain at that level of improvement within the subsequent 9 - 12 months INTRODUCTION The aim of this prospect i ve study was to compare the predictive validity of early improvement of subjective experience and early improvement of rater assessed symptoms on enduring symptomatic remission ( ESR ) status during 5 years follow . METHODS 110 consecutively admitted patients suffering from a first episode of schizophrenia or related disorders were investigated . We defined early improvement of subjective well-being as a delta-score of the total Subjective Well-being under Neuroleptics scale-20 item version ( SWN-K ) at admission and after 6 weeks treatment . The severity of psychopathology was assessed with the Positive and Negative Syndrome Scale ( PANSS ) at admission , 6 weeks , 6 months , 3 and 5 years after admission . Enduring symptomatic remission ( ESR ) was defined as complying to the symptomatic remission criteria at PANSS assessment at 6 months and 5 years and continuing this state between 6 months and 5 years follow-up . Paired- sample s and independent t-test were used to compare means . RESULTS Patients with ESR ( n=30 ) had a higher mean improvement of subjective well-being during early treatment as assessed with the SWN-K than those without ESR ( n=74 ) ( p=0.004 ) . Early symptomatic improvement as assessed with the PANSS was not related to ESR ( p=0.95 ) . DISCUSSION Early improvement of subjective well-being is related to ESR in first episode schizophrenia or related disorders This analysis characterizes patients with schizophrenia or schizoaffective disorder treated with risperidone who met remission criteria . In a 50-week , open-label trial , stable patients received long-acting injectable risperidone every 2 weeks . Remission criteria included severity ( absent – mild ratings on core symptoms of the Positive and Negative Syndrome Scale ) and duration ( ≥6 months ) components . The patients not remitted ( severity component only ) at baseline ( n=394 ) are the subjects of this report . Measures applied included the PANSS , Clinical Global Impressions – Severity , patient-rated mental health status ( Short Form-36 ) , and Drug Attitude Inventory . Among patients who met remission criteria during the study ( n=82 ) , mean scores for all 30 PANSS items reflected absent – mild ratings at endpoint . The highest items represented an ‘ interpersonal ’ cluster , although mean ratings were still minimal to mild . Remitted patients experienced substantial improvements in Short Form-36 and Drug Attitude Inventory scores at endpoint . Although improvement occurred , it was less robust in patients who remained nonremitted ( n=312 ) . Logistic regression analysis found that remission ( severity component only ) was associated with a 97.1 % probability of a ‘ not ill ’ rating on the Clinical Global Impressions – Severity . These remission criteria identified patients who differed from the nonremitted population on symptoms of psychopathology , medication attitude , health status , and overall clinical status , supporting the clinical validity of the remission criteria Recently proposed criteria for remission by a ‘ Remission in Schizophrenia Working Group ’ have generated considerable interest . We assessed rates , predictors , and correlates of remission in a sample of patients with first-episode schizophrenia treated with injectable , long-acting risperidone . This allowed us to examine remission among patients known to be receiving medication . This was a single-site open-label study in which 50 newly diagnosed cases of schizophreniform disorder or schizophrenia aged 16 to 43 years were treated with injectable , long-acting risperidone 25–50 mg every 2 weeks for 2 years . Remission , according to Remission in Schizophrenia Working Group criteria , was achieved in 64 % of the patients . Of those achieving remission , 97 % maintained this status until study completion . Remission was associated with greater improvements in other symptom domains , insight , and social and occupational functioning . Patients in remission received lower doses of antipsychotic medication , had fewer extrapyramidal symptoms , and a more favorable attitude toward medication . The results of this open-label study suggest that a majority of first-episode patients who receive long-acting injectable antipsychotic medication may achieve sustained remission . Double-blind-controlled studies using long-acting injectable antipsychotics in early psychosis are warranted to further test this BACKGROUND Previous attempts to identify clinical ly useful predictors of treatment outcome in schizophrenia have been hampered by method ological inconsistencies , including a lack of st and ardized outcome measures . Recently proposed operationally defined criteria for remission provide an opportunity to readdress this topic . METHOD We applied the remission criteria to a sample of 57 subjects with first-episode psychosis ( DSM-IV schizophrenia , schizoaffective disorder , or schizophreniform disorder ) , treated according to a fixed protocol in a prospect i ve study . Subjects were recruited between April 1999 and January 2000 and were followed for 2 years . Various demographic , baseline clinical , and early-response variables were subjected to discriminant analysis for their ability to predict remission or nonremission . We also assessed the symptom improvement patterns over time and compared endpoint psychopathology in the remitters and nonremitters . RESULTS A model incorporating neurologic soft signs , 6-week treatment response , duration of untreated psychosis , marital status , and Positive and Negative Syndrome Scale excited factor baseline score was able to correctly predict 89 % of the remitters and 86 % of the nonremitters . Symptom reduction at 6 weeks , including core psychotic symptoms , was significant in both groups ( remitters , p < .0001 ; nonremitters , p < .0001 ) , although reduction was substantially greater in the remission group ( p = .004 ) . Thereafter , the remission group continued to improve ( p < .01 ) , while the nonremitting group failed to do so ( p = .55 ) . Considerable overlap of endpoint symptoms was observed , and depressive symptom scores were similar in remitters and nonremitters . CONCLUSION A combination of demographic , baseline clinical , and acute treatment response variables may accurately predict treatment outcome . Persistent noncore psychotic symptoms in subjects meeting proposed remission criteria require further investigation A significant proportion of subjects drop out of medium to long-term clinical studies prior to trial completion . This may bias reported study outcomes and reduce the statistical power of analyses . There is therefore a need for research ers to better underst and the characteristics of dropout population s to increase completion rates . Data from a set of participants recruited as part of a 24-week placebo-controlled trial were used to determine the relationship between the five Lindenmayer factors of positive , negative , cognitive , anxiety/depression and excitement symptoms and dropout at trial completion . Results indicated that the rate of trial dropout was significantly predicted by scores on the negative Lindenmayer factor ( X² ( 6 , N = 126 ) = 15.60 , p < .05 ) . By trial completion , participants with ' high ' negative Lindenmayer scores dropped out at a rate of 64 % , whereas ' medium ' and ' low ' groups dropped out at 43 % and 30 % , respectively . No other relationship between symptom severity scores and dropout across the remaining Lindenmayer factors was found . These findings reflect important considerations for the future design of clinical trials involving people with schizophrenia and may also provide clues into treatment compliance issues more generally OBJECTIVE To measure symptomatic and functional remission in patients treated with risperidone long-acting injectable ( RLAI ) . METHODS Stable patients with psychotic disorders requiring medication change were switched to open-label RLAI in the switch to risperidone microspheres ( StoRMi ) trial . In this post-hoc analysis of the trial extension , follow-up was < or=18 months . Symptomatic remission was based on improvement in positive and negative syndrome scale ( PANSS ) scores and global remission ( best outcome ) was based on symptomatic remission , functional level , and mental-health quality of life . Predictive factors were evaluated . RESULTS Among 529 patients from seven European countries , mean participation duration was 358.7+/-232.4 days , with 18 months completed by 39.9 % of patients . Symptomatic remission lasting > or=6 months occurred at some point during treatment in 33 % of patients ; predictors included comorbid disease , country , baseline symptom severity , baseline functioning , type of antipsychotic before switching , and duration of untreated psychosis . Best outcome occurred in 21 % of patients ; predictors included baseline symptom severity , baseline functioning , country , schizophrenia type , and early positive treatment course . CONCLUSIONS One in three patients with stable schizophrenia switching to RLAI experienced symptomatic remission , with combined symptomatic , functional , and quality -of-life remission in one in five patients . Symptomatic remission was predicted by better baseline symptom severity and country of origin , with a significantly greater likelihood of remission occurring among patients in Estonia/Slovenia compared with Portugal . Relapse was predicted by higher mode doses of RLAI , additional use of psychoactive medications , male gender , and country of origin , with relapse occurring most frequently in France and least frequently in Portugal . RLAI dose , additional use of psychoactive medications , and country of origin predicted best outcome , with best outcome occurring most frequently in Estonia/Slovenia and least frequently in Portugal BACKGROUND Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales . We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics ( SGAs ) on > or=50 % response and remission . METHODS In an open r and omized clinical trial in 14 countries , 498 unselected first-episode patients with schizophrenia were assigned to haloperidol ( 1 - 4 mg/d ; n=103 ) , amisulpride ( 200 - 800 mg/d ; n=104 ) , olanzapine ( 5 - 20mg/d ; n=105 ) , quetiapine ( 200 - 750 mg/d ; n=104 ) , or ziprasidone ( 40 - 160 mg/d ; n=82 ) . Primary outcomes were > or=50 % response and remission within 12 months , as measured with the Positive and Negative Syndrome Scale . Analysis was by intention-to-treat . RESULTS Within 12 months , the proportions of patients with > or=50 % response were 37 % for haloperidol , 67 % for amisulpride , 67 % for olanzapine , 46 % for quetiapine , and 56 % for ziprasidone . Comparisons with haloperidol showed a higher likelihood for > or=50 % response with amisulpride ( hazard ratio [ HR ] 2.27 , [ 95 % CI 1.51 - 3.42 ] ) , olanzapine ( HR 2.07 [ 1.38 - 3.10 ] ) , and ziprasidone ( HR 1.62 [ 1.02 - 2.56 ] ) . Within 12 months , the proportions of patients in remission were 17 % for haloperidol , 40 % for amisulpride , 41 % for olanzapine , 24 % for quetiapine , and 28 % for ziprasidone . Comparisons with haloperidol showed a better chance for remission on amisulpride ( HR 2.49 , [ 95 % CI 1.43 - 4.35 ] ) , olanzapine ( HR 2.58 [ 1.48 - 4.48 ] ) , quetiapine ( HR 1.96 [ 1.06 - 3.64 ] ) , and ziprasidone ( HR 2.03 [ 1.07 - 3.87 ] ) . CONCLUSIONS Substantial proportions of first-episode patients with schizophrenia showed clinical ly meaningful response and remission rates within 12 months . The proportions of response and remission were higher for most SGAs as compared to haloperidol Although pharmacologic treatment remains a critical element in the short- and long-term management of schizophrenia , the past decade has been a challenging time in terms of real progress . Despite the introduction of several new medications as well as the conduct of larger and more diverse clinical trials , there remains considerable debate as to how far we have progressed in addressing some of the fundamental unmet needs in treating this disorder . A theme in this issue of Schizophrenia Bulletin addresses a number of topics in this context . Although the notion of careful , systematic , and critical summaries of all relevant r and omized controlled trials is not a new one , the Cochrane Schizophrenia Group is relatively young . Clive Adams , one of its founders , and colleagues provide the rationale and history of the group as well as review ing its methods and contributions . The Bulletin also carries a “ Cochrane Corner ” in each issue to alert the field to schizophrenia-related review s. Systematic meta-analyses are playing an increasingly important role in informing both the research agenda and clinical practice . The work of the Cochrane collaboration has been enormously valuable in this process . In recent years , the field of schizophrenia research has benefited from the application of various clinical trial method ologies to enhance the study of treatment outcomes and determine generalizability . Large effectiveness trials have provided data to exp and our knowledge base beyond that which is provided by traditional efficacy trials . Stroup and Geddes provide examples of each type of trial to illustrate their relative advantages and disadvantages . Within the context of different trial design s , Leucht et al provide an overview addressing critical aspects of trial design , potential population sampling bias , endpoint choices and definitions , quality of assessment s , data analysis and reporting , as well as , other potential sources of bias or confounds relevant to the interpretation of clinical trials data in schizophrenia . One of the most difficult challenges in the design , conduct , analysis , and interpretation of clinical trials is the problem of dropouts — those individuals who do not complete the trial , often for unknown reasons . A variety of statistical techniques have been developed and applied in order to address this issue ; however , none is entirely satisfactory . Rabinowitz and Davidov discuss the association of dropout and outcome in trials of antipsychotic medication and its implication s for strategies to address missing data . Another strategy to minimize dropouts in acute treatment trials would be to shorten the length of the trial , particularly when placebo control groups are included . Addressing this issue and drawing on recent meta- analysis suggesting that a substantial proportion of antipsychotic drug response occurs within the first 2 weeks , McMahon and colleagues present an exploratory analysis from short-term placebo controlled clinical trial data suggesting the potential feasibility of reducing the duration of such trials . Much more work needs to be done to determine the benefits and risks of such an approach , but this is a very valuable first step . In the final article , we provide a review of unanswered questions in the pharmacologic treatment of schizophrenia . Despite numerous trials being conducted with antipsychotic medication , there are many clinical decisions that must be made on a day-to-day basis for which sufficient data are not available to provide an adequate evidence base . We hope that these articles will provide a snapshot of current challenges and opportunities for further progress in the design , conduct , and interpretation of psychopharmacologic trials in schizophrenia Early response to antipsychotic medication has been shown to accurately predict later response to continued use of the same treatment in patients with chronic schizophrenia . This study examines whether this predictive pattern exists for patients with first-episode psychosis . We used a data -driven threshold for early response of ≥ 26.2 % improvement from baseline on the Positive and Negative Syndrome Scale ( PANSS(0 - 6 ) ) Total score to determine whether response at Week 2 of treatment may predict response at Week 12 in a r and omized , double-blind trial of olanzapine versus haloperidol for treatment of patients with first-episode psychosis ( N=225 ) . Later response was defined as a ≥ 40 % and ≥ 50 % improvement in PANSS Total(0 - 6 ) score and as remission . At Week 2 , 43 % ( 97/225 ) of patients were identified as early responders . At a threshold for later response of ≥ 50 % improvement in PANSS(0 - 6 ) Total score , early non-response most strongly predicted later non-response , demonstrating high specificity ( 74 % ) and high negative predictive value ( 80 % ) . As had been seen in the treatment of patients with chronic schizophrenia , early non-response was a robust predictor of subsequent non-response in the treatment of patients with first-episode psychosis OBJECTIVE To examine the course and potential predictors of treatment response in the early phase of schizophrenia . DESIGN Prospect i ve study of an inception cohort . SETTING Psychiatric division of an academic medical center with a suburban metropolitan catchment area . PATIENTS AND INTERVENTION Seventy first-episode patients who had undergone four biologic assessment procedures ( brain magnetic resonance imaging , behavioral response to methylpheni date hydrochloride , growth hormone levels , eye tracking ) were treated with a st and ardized antipsychotic drug protocol until recovery . Response was measured in terms of psychopathology and degree of remission . RESULTS Using survival analysis , the proportion of patients remitting by 1 year was estimated at 83 % . Mean and median times to remission were 35.7 weeks and 11 weeks , respectively . No baseline demographic or psychopathologic measure significantly predicted time to or level of remission . However , males tended to be nonresponders to treatment and have diagnoses of schizophrenia rather than schizoaffective disorder . Brain pathomorphology and abnormal basal growth hormone significantly predicted time to remission . CONCLUSIONS These results indicate that the antipsychotic treatment response of first-episode schizophrenics is better than chronic multiepisode patients and suggest that specific pathobiologic markers reflect pathophysiologic processes that mediate antipsychotic treatment response |
12,695 | 24,302,546 | No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment .
Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity .
Morbidity was lower than with laser conisation , although the trials did not provide data for every outcome measure .
There were not enough data to assess the effect on morbidity when compared with laser ablation .
AUTHORS ' CONCLUSIONS The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity | BACKGROUND Cervical intraepithelial neoplasia ( CIN ) is the most common pre-malignant lesion .
Atypical squamous changes occur in the transformation zone of the cervix with mild , moderate or severe changes described by their depth ( CIN 1 , 2 or 3 ) .
Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques .
Choice of treatment depends on the grade and extent of the disease .
OBJECTIVES To assess the effectiveness and safety of alternative surgical treatments for CIN . | A r and omized study was performed to compare efficacy and side effects of laser and cryotherapy : 51 patients were treated with laser vaporization and 50 patients with cryotherapy . Success rates for laser and cryotherapy were not significantly different . Success rates were significantly related to lesion size . Grade of CIN , positive endocervical curettage , parity , and age at treatment were not found to be related . Vaginal discharge , both in duration and amount , was significantly less in patients treated with laser vaporization , compared with cryotherapy , but pain and bleeding occurred more often in patients treated with laser vaporization . A brief review of possible sources of bias in comparative studies on laser and cryotherapy is given , indicating the preference for a r and omized study . It is concluded that widespread introduction of laser facilities in smaller centers is not justified , because the success rates are not better than those of cryotherapy , and because the advantages of less discharge are outweighed by the high cost OBJECTIVE To evaluate the usefulness of bipolar electrocautery scissors for cervical conization . METHODS AND MATERIAL S Forty patients with severe dysplasia/in situ carcinoma of the uterine cervix underwent cervical conization : 20 r and omly selected patients were operated on with the unipolar energy scalpel and the other 20 were operated on with bipolar electrocautery scissors . In both groups operating time , number of ligations , blood loss , duration of recovery , perioperative complications and adequacy of the margins of the lesion were assessed . Data were compared by analysis of variance . RESULTS In the bipolar group the average operating time and duration of recovery were significantly reduced ( halved ) , no ligations were needed and the amount of blood loss was significantly reduced . Regarding perioperative complications , in the bipolar group there were no hemorrhages nor need of a second operation or transfusion . Infections did not occur in either group . We found no difference between the two groups regarding adequacy of the margins of the lesion for a good pathologic examination . CONCLUSION Bipolar electrocautery scissors were safe and useful in cervical conization by reducing the operating time and blood loss without increasing postoperative morbidity Fifty‐five patients were r and omized in a double‐blinded manner to large loop excision of the transformation zone ( LLETZ ) ( 29 patients ) or radical cervical diathermy with fulgaration ( RCDF ) ( 26 patients ) for treatment of cervical intraepithelial neoplasia ( CIN ) . Patients completed a 2‐month diary of symptoms and completed a 10‐week postoperative question naire . White vaginal discharge lasted 7.3 ( 4.6 ) days ( SD ) for RCDF compared to 3.4 ( 1.6 ) days ( SD ) for LLETZ . There was no significant difference in any other symptoms on analysis This appears to be the first report clearly assessing the length and severity of postoperative symptoms following LLETZ or RCDF . There is no reason on length and severity of postoperative symptoms to choose 1 of these 2 treatment methods over the other Objective To determine whether loop diathermy excision of the transformation zone and laser vaporisation are equally effective in the treatment of cervical intraepithelial neoplasia The results of laser and cryosurgical treatment in 106 patients with histologically proven carcinoma in situ of the uterine cervix ( CIN III ) are presented . Seventy-one patients were treated with the laser and in 63 of these further follow-up with colposcopy and cytology failed to show any abnormality . This represents an initial success rate of 89 % . In 8 patients ( 11 % ) initial treatment was considered to have failed because of persistent dyskaryotic smears and histological evidence of cervical intraepithelial neoplasia ( CIN II-III ) . Six of these patients were treated successfully with a further laser application and two patients had conization . The overall success rate for the laser was 97 % . Thirty-five patients were treated with cryosurgery and subsequent follow-up was negative in 29 of these patients ( 83 % ) . The 6 treatment failures ( 17 % ) were subsequently successfully treated with local destructive therapy ( 4 with cryosurgery , 1 with laser , and 1 with needle diathermy ) . The overall success rate for cryofreezing was 94.2 % . In cases of CIN III the laser is more likely to achieve eradication of the lesion with a single application than cryofreezing In a r and omized trial concerning 123 women with CIN , 59 were treated with laser conization under colposcope without further hemostatic remedy and 64 with cold knife conization guided by Schiller 's iodine dyeing supported by side sutures , vaginal packing and postoperative oral administration of tranexam acid . Follow‐up with colposcopy and cytology was done 3 and 12 weeks post‐conization and then every 6 months . The average follow‐up period was 36 months ( 28–48 ) . Peroperative bleeding was rather less pronounced in the laser group . Postoperatively , however , bleeding requiring treatment was significantly less common in the laser group ( 5 % ) than in the cold knife group ( 17 % ) BACKGROUND Cervical intraepithelial neoplasia ( CIN ) can be managed by ablative or excisional procedures . We have compared the excision time , effectiveness , and safety of loop diathermy ( loop ) against laser conization . METHODS In a prospect i ve study in two hospital departments 222 women were r and omized to loop or laser conization . Data were collected by question naires after operation and at two follow-up examinations . RESULTS At department A ( 122 women ) , two physicians performed 27 % of the loop and 35 % of the laser excisions ; at department B ( 100 women ) , the corresponding figures were 69 % and 59 % . Loop was quicker than laser conization in both departments ( median 3 - 4 min versus 10 - 20 min ) , while laser conization was more time consuming in department A ( median A/B = 20/10 min ) . Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups ( 41.8 % , 52.7 % , 59.2 % , 64.7 % ) . At both departments , bleeding for more than two weeks was reported twice as often after laser conization ( A:13.8 % , B:24.2 % ) , when compared to loop excision ( A:7.1 % , B:13.7 % ) . Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens . CONCLUSIONS Loop was quicker than laser excision , per- and postoperative bleeding diminished , and the success rates were comparable . Physicians mastered Loop excision after a few attempts . However , the results improved , when performed by a restricted number of physicians . Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN OBJECTIVES Loop electrosurgical excision of the transformation zone ( LEETZ ) was recently associated with relatively high failure rates . We evaluated whether the combination of LEETZ with laser vaporization is superior to LEETZ alone in reducing the rates of recurrent abnormal cytology and residual disease . METHODS The study population included 426 women with histologic diagnosis of cervical intraepithelial neoplasia ( CIN ) 2 - 3 , of whom 289 ( study group ) were treated by LEETZ followed by laser vaporization of the crater base and walls and 137 ( control group ) were treated by LEETZ alone . All women were followed scrupulously at regular intervals for recurrent abnormal cytology and residual disease . The mean follow-up periods were 43 and 59 months for the study and control groups , respectively . RESULTS Both groups were derived from the same community and were similar in epidemiologic characteristics and disease severity . Although the incidence of positive surgical margins was similar in both groups ( 10.4 and 9.5 % for the study and control groups , respectively ) , recurrent abnormal cytology ( 10.2 % vs 5.5 % , P = 0.07 ) and histologic residual disease ( 21.4 % vs 0 % , P = 0.05 ) were more frequent among women in the control group . This applied to women with both negative and positive surgical margins . Both study and control women with positive surgical margins , especially at the endocervix , were at higher risk for recurrence . CONCLUSION The addition of laser vaporization to LEETZ may improve outcome of both women with positive margins and women with negative margins . Our results support conservative management for all treated women , regardless of cone margin status We compared the pain of excisional cervical surgery by the laser or loop diathermy ( LLETZ ) in a r and omised controlled clinical trial . Eighty women with CIN III were recruited from a laser colposcopy clinic specifically adapted to run r and omized trials . They were scheduled for excision of their cervical transformation zone and both groups were matched for age , parity , and size of lesion . We measured linear analogue pain scores , subjective pain scores , and operative time . The laser and loop diathermy inflicts similar discomfort and there is no detectable difference between the median pain scores of women in either group ( P = 0.99 ) . However , in the h and s of an experienced surgeon it takes 4 min extra to excise the cervical transformation zone with a laser compared to loop diathermy . The average time from sitting in the chair to the end of the procedure was 13.02 min ( SD 3.65 ) for the group allocated diathermy surgery compared to 17.30 min ( SD 5.33 ) for a laser excision log transformed t(log transformed data ) = 3.7 ( P < 0.001 ) The objective of this r and omized controlled trial was to determine whether the pure cut setting results in less thermal artefact than the traditional blend setting when performing a large loop excision of the transformation zone ( LLETZ ) . Forty-nine consenting women were r and omized to undergo an LLETZ procedure using either the pure cut or the blend setting . Two histopathologists , who were blind to the r and omization , examined the specimens and then grade d and measured the degree of thermal artefact . No significant difference was noted at the epithelial margin . At the deep stromal margins , in the blend group , the mean thickness of thermal artefact was 0.382 mm ( 95 % CI , 0.350–0.414 ) and in the cut group 0.325 mm ( 95 % CI , 0.297–0.353 ) . This was statistically significant . No significant difference was detected in terms of grading of thermal artefact , the presence of dysplasia at the specimen margins , or in positive follow-up smears . Although there was less thermal artefact at the deep stromal margin , cautery at this margin does not generally interfere with pathological assessment of the specimen and the pure cut setting does not produce a clinical ly significant decrease in the degree of thermal artefact Ninety patients with cervical intraepithelial neoplasia ( CIN ) were r and omly assigned to loop excision ( n = 38 ) or cold-knife conization ( n = 52 ) . All specimens were well evaluable at histology . The average width of the lesions at histology was 10.2 and 9.7 mm , respectively ( ns ) . The average weight of the specimens was 2.6 and 5.6 g ( P < 0.01 ) and the average depth was 9.2 and 15.8 mm ( P < 0.01 ) , respectively . The distance between the cervical resection margin and CIN was 14 mm after loop excision and 24 mm after cold-knife conization ( P < 0.06 ) . The margins of the specimen were not clear of disease in 8 patients after loop excision and in 12 patients after conization ( ns ) . Two patients after loop excision and in three patients after cold-knife conization had postoperative bleeding . The results suggest that , compared with cold-knife conization , loop excision removes less healthy tissue without reducing the chances for cure In a r and omized study , 204 patients with exocervical intra‐epithelial neoplasia were allocated to either laser evaporation ( 103 ) or cryocoagulation ( 101 ) . The patients were treated on an outpatient basis without anesthesia . In the case of initial treatment failure the same method was to be used for retreatment . One hundred and eighty‐seven patients were followed‐up for an average of 50 months ( 12‐80 ) . Eighty‐six of 94 laser‐evaporated patients ( 91 % ) and 89 of 93 cryocoagulated patients ( 96 % ) were cured after one treatment . Five of 8 laser failures and 3 of 4 cry0 failures were cured by retreatment . The cure rate after one or two laser evaporations was 97 % ( 91 of 94 patients ) , and after one or two cryo coagulations , 99 % ( 92 of 93 patients ) . Eighty per cent of residual or recurrent neoplasia occurred within 15 months and 96 % within 2 years of treatment . No invasive neoplasia occurred during the follow‐up period and no tendency was seen towards higher grade s of intra‐epithelial neoplasia in the failures compared with the initial diagnoses . It is concluded that laser evaporation and cryocoagulation are equally effective for the treatment of exocervical intra‐epithelial neoplasia The objective of the treatment of cervical intraepithelial neoplasia ( CIN ) is the prevention of invasive carcinoma of the cervix , which still remains the most common cancer in Zimbabwean women , as in most other low-re source countries where screening facilities are grossly inadequate . We conducted a r and omised prospect i ve study to compare CIN treatment outcome after cryotherapy and loop electrosurgical excision procedure ( LEEP ) in 400 women with histologically confirmed high grade squamous intra-epithelial lesions ( HGSIL ) . Treatment outcome measures were immediate complications , persistent disease and recurrent disease evaluated at follow-up visits . Eighty-two per cent of the women ( 159 cryotherapy , 168 LEEP ) completed their 6-month and 12-month follow-up visits . LEEP had a significantly higher overall cure rate of 96.4 % ( absence of persistent or recurrent disease ) compared to 88.3 % cryotherapy ( P=0.026 ) . Although cryotherapy was not superior to LEEP , its cure rate ( 88.3 % ) is acceptable and therefore provides a viable treatment option for low re source countries such as Zimbabwe where the majority of women at risk for cervical cancer reside in rural areas OBJECTIVE To compare the histomorphologic and colposcopic results of cold knife conization and loop excision . METHODS Sixty-six women were r and omly allocated to have the cone specimen removed by cold knife excision ( n = 38 ) or loop excision ( n = 28 ) . Subjects eligible for inclusion were those who presented histologically verified grade 3 cervical intraepithelial neoplasia ( CIN ) or grade 2 CIN with squamocolumnar junction not seen . RESULTS The mean height of the cone specimens was greater in the cold knife group [ 18.9 mm ( SD = 5 . 5 ) and 12.8 mm ( SD = 4.3 ) , respectively ; P = 0.0001 ] , as was the frequency of clear margins ( 100 and 80 % , respectively ; P = 0.001 ) . In the loop excision group , thermal injuries were present in half of the cone sections . The median ( range ) thickness of thermal injury was 0.98 mm ( 0 - 1.5 mm ) in the ectocervix and 0.95 mm ( 0 - 1.75 mm ) in the endocervix . Histologic evaluation of the endocervical margins was not possible in 2 cases ( 7 % ) . At follow-up colposcopy , evaluation of the entire squamocolumnar junction was possible in 15 ( 39 % ) and 20 ( 71 % ) women , respectively ( P < 0.01 ) . Four patients in the cold knife group and 6 in the loop group had histologically confirmed persistent dysplasia ( P > 0.05 ) , yielding success rates of 90 and 79 % , respectively ( P > 0.05 ) . CONCLUSIONS Loop excision provides a sample that is adequate for histologic evaluation in most cases , results in the same success rate as cold knife conization , and allows optimal colposcopic surveillance in significantly more cases than cold knife excision Abstract . This prospect i ve , r and omized study of 142 women with mild or moderate dysplasia of the uterine ectocervix shows that the double‐freeze technique is significantly more effective than the single‐freeze technique , the recurrence rates being , respectively , 6.2 % and 16.3 % . The highest recurrence rate was found in the group treated with a single freeze and having the most extensive portio involvement . All patients were examined colposcopically before cryosur‐gery in order to exclude patients with lesions extending into the cervical canal and in order to evaluate the size of the lesion . Recurrent lesions were usually diagnosed within the first year ( 75 % ) and in only one patient more than 2 years after treatment . None of the patients developed invasive cancer . The mean follow‐up period was 27 months ( 24‐42 months ) . We consider cryosurgery to be an acceptable treatment for selected patients . Our criteria for entry were 1 ) mild or moderate dysplasia of the uterine ectocervix , and 2 ) colposcopic visualization of the entire transformation zone to ensure that the lesion does not extend into the cervical canal . Our experience from the present study is that the following criteria should be added : 3 ) the portio involvement must not be too extensive , and 4 ) the patient must agree to follow‐up examination . When these conditions are fulfilled , future treatment in our department will consist of a double freeze extending 3 mm beyond the lesion , with a thaw interval of 4 min Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not . One hundred ninety-two patients ( 30 % ) were considered negative . Follow-up evidence d later appearance of CIN in five of them . One hundred fifty-three ( 24 % ) were c and i date s for delayed treatment due to conditions contraindicating same-day treatment . Two hundred ninety-four patients ( 46 % ) were r and omly allocated in LEEP ( 149 ) or excisional laser ( 145 ) arms , and treated the same day under local anesthesia . Both arms were comparable . There were three microinvasive carcinomas diagnosed in the surgical specimen . LEEP was faster and produced less bleeding than laser , although required a mean of four slices to remove the lesion . Arterial hypertension after anesthetic infiltration was detected in 26 % of cases . Two intraoperative and two delayed bleeders required surgery . The size of lesion and surgical defect were larger than those reported in the literature . Margins were involved in 8 patients ( 2.7 % ) . Only 4.7 % ( 7/149 ) of patients r and omized to LEEP and 3.4 % ( 5/145 ) with excisional laser had persistent or recurrent CIN on follow-up . Factors predisposing to failure included depth of surgical defect , grade of lesion , and operator 's expertise . With this approach , 69 % of patients referred for cytology of CIN were adequately managed in the first visit , which contrasts to classical management that reaches the state of treatment in 30 % of patients . LEEP appears to be faster , less costly , and requires less expertise . Its use in conjunction with adequate screening is recommended for developing countries Objective To compare cryotherapy , laser vaporization , and loop electrical excision for treatment of squamous intraepithelial lesions ( SILs ) . Methods Women at least 18 years old with biopsy-proven SIL , negative pregnancy tests , negative findings on endocervical curettage , satisfactory colposcopy examinations , and congruent Papanicolaou smear and biopsy results were assigned r and omly to treatment after stratification by SIL grade , endocervical gl and involvement , and lesion size ; they were evaluated 1 , 4 , 8 , 12 , 16 , 20 , and 24 months after treatment . Data were analyzed using χ2 statistics , logistic regression analysis , and the Cox proportional hazards model . Results Of 498 patients assigned , 108 were excluded ( most because of inadequate follow-up ) , leaving 390 ( 139 cryotherapy , 121 laser vaporization , 130 loop excision ) for analysis . All were followed 6–37 months ( mean 16 ) . There were no statistically significant differences in complications , persistence ( disease present less than 6 months after treatment ) , or recurrence ( disease present more than 6 months after treatment ) . Risk of persistent disease was higher among women with large lesions ( risk ratio [ RR ] , 18.9 ; 95 % confidence interval [ CI ] , 3.2 , 110.6 ) . Recurrence risk was higher among women aged 30 years and older ( RR , 2.1 ; 95 % CI , 1.2 , 4.3 ) , those with human papillomavirus type 16 or 18 ( RR , 2.1 ; 95 % CI , 1.1 , 4.0 ) , and those who had had prior treatment ( RR , 2.1 ; 95 % CI , 1.1 , 3.9 ) . Conclusion The data support a high success rate with all three modalities . No significant difference in success rates was observed between the three treatments in our population . Additional attention and research should be directed toward the higher risk patients identified above In a r and omized study , 204 patients were allocated to either laser or cryo treatment for cervical intra‐epithelial neoplasia ( CIN ) . The patients were treated on an outpatient basis without anesthesia unless other conditions requiring anesthesia had to be dealt with at the same time . Both the laser and the cryo method were highly acceptable to the patients . Slightly more patients experienced moderate or severe pain during laser treatment , compared with cryo treatment ( P=0.05 ) . Peroperative hemorrhage did not exceed 25 cc except for one laser‐treated patient . Postoperative vaginal discharge was more often seen after cryo coagulation , the discharge being malodorous in 36 % of cryo‐treated patients and in 17 % of laser‐treated patients . Pelvic inflammatory disease was found in one patient in each treatment group . Postoperative spotting occurred more often in laser‐treated patients ( 49 % ) than in cryo‐treated patients ( 22 % ) . At follow‐up colposcopy 3 months after treatment , the squamocolum‐nar junction was fully visible significantly more often in laser‐treated patients ( P < 0.001 ) . The cure rates after one laser or cryo treatment were 90 % and 91 % , respectively . Subsequent to 19 initial treatment failures , 8 patients have at present been retreated with the same method as initially used , and all 8 are cured . The cure rates after one or two treatments are 96 % in the laser group and 93 % in the cryo group . The rates are preliminary , due to the short observation time . Publications will appear when all patients have been followed for 2 and 5 years Summary . A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia ( CIN ) grade II or III were allocated by hospital number to receive out‐patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone ( LLETZ ) . All patients received local anaesthesia . The women in the LLETZ group experienced less post operative haemorrhage , less discomfort , operative time was greatly reduced , and histological material was available for confirmation of the diagnosis . There was no significant difference in recurrence of CIN after treatment between the two groups . At 6 month follow‐up , recurrence rates of 8.2 % ( CIN II ) and 7.5 % ( CIN III ) were observed in the laser‐group and 5 % ( CIN II ) and 5.3 % ( CIN III ) in the LLETZ group . Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon , but laser treatment is preferable in patients with widespread vaginal involvement Two methods of obtaining hemostasis after cold knife cone biopsy were compared in a prospect i ve r and omized trial involving 200 patients . One method relied primarily on hemostatic sutures , and the other involved the use of a styptic solution ( Monsel 's solution ) and vaginal pack , thus avoiding the use of sutures altogether . The short- and long-term morbidity in these two groups were compared and 12-month follow-up was completed . The use of sutures did not reduce the incidence of primary hemorrhage . Secondary hemorrhage was twice as frequent in the suture group , although this trend did not quite reach statistical significance . During long-term follow-up , significantly more patients in the suture group developed menstrual symptoms , cervical stenosis , and unsatisfactory colposcopy , requiring further operative intervention as a result OBJECTIVE --To determine the efficacy and morbidity of fine loop diathermy excision of the cervical transformation zone as applied to the management of out patients with abnormal cervical smears . DESIGN -- Prospect i ve programme trial with six month follow up . SETTING --Two hospital based colposcopy clinics . PATIENTS --616 Patients aged 16 - 60 with abnormal cervical smears . INTERVENTIONS --After colposcopic and cytological assessment excision of the cervical transformation zone by fine loop diathermy under local anaesthesia in the outpatient department . MAIN OUTCOME MEASURES --Time to complete the treatment , immediate morbidity in terms of discomfort and bleeding , and cytological and colposcopic findings at six months . RESULTS --Treatment was completed in a mean of 3.47 minutes ( SD 1.99 ) . Immediate morbidity was minimal , and histological specimens were adequate in over 90 % of cases . Almost two thirds of patients were treated at their first visit to the clinic . 58 Patients ( 9.4 % ) failed to attend for follow up at six months and one had had a hysterectomy . Of the 557 patients who attended for colposcopic and cytological follow up at six months , 506 ( 91 % ) were normal cytologically and 19 ( 3.4 % ) had histologically confirmed persistence of cervical intraepithelial neoplasia . The overall confirmed failure rate of the technique was 4.4 % . CONCLUSION --Loop diathermy excision is an effective treatment with low morbidity and is an appropriate modality for patients with abnormal cervical smears OBJECTIVE : To compare specimens obtained with the Fischer cone biopsy excisor or loop electrosurgical excision procedure ( LEEP ) with respect to number of specimens obtained , margin interpretability , adequacy of excision , and ease of use . METHODS : One hundred eligible patients aged 13 years and older were r and omly assigned to treatment with the Fischer cone biopsy excisor or LEEP . Eligibility criteria included : ( 1 ) cervical intraepithelial neoplasia ( CIN ) 2 or 3 , ( 2 ) persistent CIN 1 , or ( 3 ) cytologic/histologic discrepancy . Following excision , providers ranked ease of use on a scale of 1 to 10 . A pathologist blinded to procedure type analyzed specimens for margin interpretability and adequacy of excision . Before study initiation we calculated that a total of 100 patients would be required to demonstrate a significant difference in the interpretable margin rate of 80 % for LEEP and 99 % for cone biopsy excisor ( power 80 % , α = .05 ) . RESULTS : After adjustment for ease of use , lesion size , and degree of neoplasia , the cone biopsy excisor was no more likely to result in a single specimen than LEEP ( 74 % versus 63 % , relative risk [ RR ] 0.93 , 95 % confidence interval [ CI ] 0.79 −1.11 ) , to result in a specimen with interpretable margins ( 65 % versus 73 % , RR 0.97 , 95 % CI 0.78–1.22 ) , or to result in a fully excised cervical lesion ( 72 % versus 62 % for LEEPs , RR 1.08 , 95 % CI 0.77–1.52 ) . Providers found their experiences with both Fischer cone biopsy excisor and LEEP cone biopsies to be similar , even after adjustment for year of training and previous experience ( RR 0.95 , 95 % CI 0.72–1.24 ) . CONCLUSION : The Fischer cone biopsy excisor and LEEP performed similarly with respect to the number of final specimens , margin interpretability , and ease of use . LEVEL OF EVIDENCE : Three different techniques of cervical excision , cold knife conization , laser conization , and loop electrosurgical excisional procedure ( LEEP ) were prospect ively compared with respect to treatment reliability , effectiveness , and safety . One hundred ten women with CIN1 - 2 and the squamnocolumnar junction not seen or CIN3 at the original diagnosis were r and omized to treatment with cold knife conization ( n = 37 ) , laser conization ( n = 37 ) , or LEEP ( n = 36 ) . All three treatments were performed with local anesthesia on an outpatient basis . The mean age , histologic features ( original and histology of the conization ) , endocervical involvement , and ectocervical extension were similar in the three groups . Blood loss and operating time were less ( P < 0.01 ) in the LEEP group ( 5.4 cc of mean blood loss and 5.4 min mean duration time ) than in the two other groups ( 16.2 cc and 14.0 min for cold knife conization , 21.5 cc and 15.6 min for laser conization ) . Volumes of the cones were evaluated : LEEP cones and laser cones were smaller than the cold knife cones ( P < 0.001 ) . During the pathological review of the conization , the major problem was difficulty in evaluating the lesion and its margins due to the coagulation induced by the laser or the LEEP . This alteration was present in 53 % of the LEEP conization specimens and in 51 % of the laser conization specimens . In the majority of the cases the coagulation was mild , but in one case ( LEEP group ) and in two cases ( laser group ) the conization was totally altered by the coagulation , and in 31 % of all the LEEP conizations and 38 % of all the laser conizations , evaluation of the entire margin was not possible due to coagulation of the tissue . During postoperative follow-up , the number of complications was the same in the three groups ( two episodes of post-operative bleeding in each of the three groups ) . Two months after the treatment the cervix was evaluated : the os was diminished in the cold knife group compared to the two other groups and as a result , the squamnocolumnar junction was not seen in entirety in 50 % of cold knife cases , in 19 % of LEEP cases , and in 20 % of laser cases . These results suggest that in our h and s : ( 1 ) laser conization is relatively costly and time consuming and alters the tissues significantly , and ( 2 ) the choice between cold knife and LEEP is more difficult -- cold knife gives a sample adequate for histological evaluation ( including evaluation of the margins ) , while the LEEP procedure is technically easier and less time consuming but sometimes induces electrocautery artifact so that evaluation of the margins is not possible Aims and Background Our aim was to investigate whether loop excision is an acceptable alternative to traditional cold knife conization of the cervix . Patients and Methods 240 with cervical intraepithelial neoplasia ( CIN ) were r and omly assigned to loop excision ( n = 120 ) or cold knife conization ( n = 120 ) . Success and complication rates of both methods were analysed . Results 100 % of cold knife conization and 98 % of loop excision surgical specimens were positive for dysplasia . The rate of complete resection was 91 % in the cold knife and 82 % in the loop excision group , but histologic confirmation of residual CIN was obtained in only 2 ( 1.7 % ) women after cold knife conization and in 5 ( 4.2 % ) after loop excision . Loop excision cones were significantly shallower than those obtained by a cold knife . Secondary surgical procedures due to early hemorrhage were performed in 9 ( 7.5 % ) patients treated with cold knife conization and in 8 ( 6.7 % ) treated with loop excision . Elevated temperature postoperatively was observed in 16.4 % of patients after cold knife conization and in 13.9 % after loop excision . There were no other postoperative complications . Conclusions The results suggest that cold knife conization and loop excision are comparable and equally effective diagnostic and therapeutic procedures for CIN This prospect i ve , r and omized study compares , for the first time , measured blood loss at conization and within 24 hours after using either the cold knife technique or the carbon dioxide laser scalpel . One hundred and ten consecutive patients were evaluated . The median blood loss in the laser group of 55 patients was 4.6 milliliters at , and within , 24 hours after operation compared with 30.1 milliliters in the cold knife group of 55 patients . More important , however , is that the corresponding figures for the range of bleeding were 0.4 to 155.4 milliliters and 5.6 to 1,570.9 milliliters , respectively . The incidence rate for bleeding complications requiring surgical intervention was 1.8 per cet for the laser group and 14.6 per cent for the cold knife group . This difference was statistically significant , p less than 0.015 - -Fischer 's exact test . Conization for treatment of premalignant changes of the cervix uteri will probably remain the treatment of choice for some time to come . It is our opinion that , in the future , laser conization will replace cold knife conization OBJECTIVE The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time , reliability , effectiveness , and safety . STUDY DESIGN Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were r and omized to treatment with either loop diathermy excision ( group 1 , n = 150 ) or carbon dioxide laser excisional conization ( group 2 , n = 150 ) , both performed with local anesthesia on an outpatient basis . Student 's t or Mann-Whitney test were used to compare continuous data ; the chi 2 test was used for categoric data . RESULTS The mean age , parity , histologic features , depth of excision , and occurrence of residual or recurrent disease were similar ; however , the mean time required to complete treatment and hemostasis ( 2.5 + /- 3.6 vs 24.2 + /- 11.8 min ) , patient discomfort , blood loss ( 2.77 + /- 3.76 vs 27.15 + /- 17.51 ml ; p < 0.001 ) , and considerable thermal artifact affecting histologic interpretation of excision margins ( 5 cases vs 25 cases ; p < 0.01 ) were significantly less in group 1 than in group 2 . CONCLUSION In our experience outpatient loop diathermy excision is an equally effective , quicker , safer , and more reliable excisional technique than laser excisional conization Development made on the carcinogenesis process of the cervical lesions and increased detection of the early precancerous lesions enable discontinuance of radical treatments for non-radical techniques which it is of vital importance to young women of the child-bearing capacity . The aim of this study was to determine the efficacy of the non-radical treatment of the cervical lesions using LLETZ procedure ( Large Loop Excision of Transition Zone ) and laser CO2 vaporisation . 2046 women aged 18 - 46 who were diagnosed for cervical lesions were treated in the Institute of Obstetrics and Gynaecology Medical School of Bialystok in the years 1994 - 97 . 216 of which were histologically confirmed for CIN I-III diagnosis . The choice between LLETZ or laser CO2 was made based on a pre-treatment examination ( cytology , colposcopy , microbiology test and punch biopsy ) . The final results were evaluated from 6 months to 4 years after the treatment . The effectiveness of CO2 laser was 94.6 % and was similar to LLETZ--96.4 % . In spite of almost complete agreement in both procedures , the LLETZ seems to be more preferred because of the possibility of histological post-treatment verification OBJECTIVE To evaluate the long-term recurrence rates and complication of different techniques of cervical ablation . METHODS A r and omized trial of three techniques of conization ( cold knife , laser , and loop electrosurgical excisional procedure ( LEEP ) ) for cervical intraepithelial neoplasia ( CIN ) in which 110 patients had been recruited . RESULTS Eighty-six patients were followed-up for more than 3 years . Of these 28 had been treated with the cold knife , 29 with LEEP and 29 by laser . Five recurrences were observed , one in the cold knife group , two in the LEEP group and two in the laser group ( P = NS ) . The only observed complication was cervical stenosis : zero cases in the laser group , one case in the LEEP group and four cases in the cold knife group ( laser versus cold knife : P=0.03 ; LEEP versus cold knife : P=0.06 ) . Fifty pregnancies were observed in 39 patients . First and second trimester outcomes of pregnancy were without complications . One patient treated with the LEEP presented with a premature rupture of membranes and premature labor at 36 weeks . A total of nine cesarean sections were performed with two cases for cervical dystocia . CONCLUSION There is no major difference in obstetrical outcome between the three techniques One hundred patients with histologically confirmed cervical intraepithelial neoplasia suitable for ablative therapy were r and omly allocated to treatment by either laser vaporization or laser excision conization under local anesthesia in the outpatient colposcopy clinic . The two methods were compared with respect to the immediate surgical complications , ease of performance , and long-term complications . They were comparable in most respects , and both were well accepted by the patients . Laser excision had the added advantage of providing further material for histologic examination to confirm the absence of invasion and the completeness of excision of the lesion |
12,696 | 28,158,308 | The clinical utility of sorafenib was established early in development , with low burden on patients and re sources .
However , these early successes were followed by rapid and exhaustive testing against various malignancies and combination regimens , leading to excess patient burden .
Our evaluation of sorafenib development suggests many opportunities for reducing costs and unnecessary patient burden in cancer drug development | Failure in cancer drug development exacts heavy burdens on patients and research systems . | Summary Background Cisplatin and fluoropyrimidine ( CF ) are st and ard first- line treatment in advanced gastric cancer , but no second-line treatment has yet been established . We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib ( S ) , and Oxaliplatin as second-line therapy . Methods Patients with progressive gastric adenocarcinoma after CF- first-line , ECOG 0–2 , and measurable disease were included . The primary objective was PFS . Treatment doses were Oxaliplatin 130 mg/m2/3 weeks and Sorafenib 800 mg/bid/d . Results We included 40 patients . CR was 2.5 % and SD was 47.2 % . Grade 3–4 toxic effects were neutropenia ( 9.8 % ) , thrombocytopenia ( 7.3 % ) , neurotoxicity ( 4.9 % ) and diarrhea ( 4.9 % ) . Median PFS was 3 months ( 95 % CI : 2.3–4.1 ) and median OS was 6.5 months ( 95 % CI : 5.2–9.6 ) . Time to progression ( TTP ) to first line therapy was a prognosis factor . Median OS was 9.7 months when time-to-progression during first-line chemotherapy was > 6 months and 5.6 m when it was < 6 months ( p = 0.04 ) . Conclusions Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis . The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe , but our results do not support the implementation of a phase III trial PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Summary Background Sorafenib is the sole molecular-targeted agent showing a survival benefit in patients with advanced hepatocellular carcinoma ( HCC ) . We evaluated the tolerability and effectiveness of a combination of S-1 with sorafenib in patients with advanced HCC . Methods S-1 was administered during days 1–14 and sorafenib was administered every day . This treatment was repeated every 21 days . In phase I , we determined the maximum tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) . The dose of each drug was planned as follows : cohort 1 : S-1 48 mg/m2/day and sorafenib 400 mg/day , cohort 2a : S-1 48 mg/m2/day and sorafenib 800 mg/day , cohort 2b : S-1 64 mg/m2/day and sorafenib 400 mg/day , cohort 3 : S-1 64 mg/m2/day and sorafenib 800 mg/day , and cohort 4 : S-1 80 mg/m2/day and sorafenib 800 mg/day . In phase II , the patients were treated at the MTD to evaluate safety and efficacy . Results Nineteen patients were enrolled in phase I. One of the six patients in cohort 1 and one of the six patients in cohort 3 experienced DLT . None of the three patients in cohort 2a experienced DLT and three of the four patients in cohort 4 experienced DLT . Therefore , cohort 3 was considered the MTD . Subsequently , 26 patients were enrolled in phase II . The most common grade 3/4 toxicities were an increase of aspartate aminotransferase ( 38.5 % ) , thrombocytopenia ( 23.1 % ) , neutropenia ( 19.2 % ) , hyperbilirubinemia ( 15.4 % ) , an increase of alanine aminotransferase ( 15.4 % ) , hyponatremia ( 11.5 % ) , rash ( 11.5 % ) , and hypophosphatemia ( 11.5 % ) . Sudden death occurred in one patient ( 3.8 % ) . A patient ( 3.8 % ) had a partial response , 15 ( 57.7 % ) had stable disease , and 10 ( 38.5 % ) had progressive disease . The median times to progression and overall survival were 2.4 and 10.5 months , respectively . Conclusion The MTD of S-1 and sorafenib in patients with advanced HCC was 64 mg/m2/day and 800 mg/day , respectively . This dose/regimen demonstrated substantial clinical activity among patients with advanced HCC Background : Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages . On the basis of evidence of dysregulation of the epidermal growth factor receptor , vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers , we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers . Methods : Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function . Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily , respectively . Results : Thirty-four eligible patients were recruited . The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months . There were two unconfirmed partial responses ( 6 % , 95 % CI : 1–20 % ) , with a median progression-free survival of 2 months ( 95 % CI : 2–3 ) , and median overall survival of 6 months ( 95 % CI : 3–8 months ) . Grade 3 and 4 adverse events included hypertension , AST/ALT increase , bilirubin increase , diarrhoea , hypokalaemia , hypophosphatemia and rash . Conclusions : Despite compelling pre clinical rationale , the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers . Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease Purpose : This multicenter , phase II study evaluates the efficacy and safety of erlotinib , an epidermal growth factor receptor ( EGFR ) inhibitor , plus sorafenib , a multityrosine kinase inhibitor against vascular endothelial growth factor receptors , in patients with previously untreated advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Chemotherapy-naïve patients with stage IIIB/IV NSCLC received erlotinib ( 150 mg once a day ) and sorafenib ( 400 mg twice a day ) until disease progression or unacceptable toxicity . The primary end point was the rate of nonprogression at 6 weeks . Secondary end points included objective response rate ( ORR ) , time to progression , overall survival , and adverse events . Exploratory end points included pretreatment EGFR and KRAS mutation status , pharmacokinetics , and cytochrome P450 polymorphisms . Results : Fifty patients initiated therapy . The nonprogression rate at 6 weeks was 74 % : 12 ( 24 % ) partial response and 25 ( 50 % ) stable disease . Ultimately , the ORR was 28 % . Median time to progression was 5.0 months [ 95 % confidence interval ( 95 % CI ) , 3.2 - 6.8 months ] . Median overall survival was 10.9 months ( 95 % CI , 3.8 - 18.1 months ) . Grade 3/4 adverse events included fatigue ( 16 % ) , h and -foot skin reaction ( 16 % ) , rash ( 16 % ) , diarrhea ( 14 % ) , and hypophosphatemia ( 42 % ) . There was one treatment-related fatal pulmonary hemorrhage . Patients with wild-type EGFR had a higher ORR ( 19 % ) than previously reported for single-agent erlotinib/sorafenib . Erlotinib levels were lowered . This was associated with CYP3A4 polymorphism and was possibly due to sorafenib . Conclusion : Despite a possible drug interaction , sorafenib plus erlotinib has promising clinical activity in patients with stage IIIB/IV NSCLC and has an acceptable safety profile . Further evaluation of this combination as potential salvage therapy in EGFR mutation – negative patients and the possible drug interaction is warranted . Clin Cancer Res ; 16(11 ) ; 3078–87 . © 2010 AACR PURPOSE To define the safety , efficacy , and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy ( CRT ) in locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients received gemcitabine 1000 mg/m(2 ) intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT . Weekly gemcitabine 600 mg/m(2 ) intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions . Sorafenib was dosed orally 400 mg twice daily until progression , except during CRT when it was escalated from 200 mg to 400 mg daily , and 400 mg twice daily . The maximum tolerated dose cohort was exp and ed to 15 patients . Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms ( VEGF-A and VEGF-R2 single nucleotide polymorphisms ) . RESULTS Twenty-seven patients were enrolled . No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT . The most common grade 3/4 toxicities were fatigue , hematologic , and gastrointestinal . The maximum tolerated dose was sorafenib 400 mg twice daily . The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months , respectively . The median overall survival for patients with VEGF-A -2578 AA , -1498 CC , and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months . Dynamic contrast-enhanced MRI demonstrated higher baseline K(trans ) in responding patients . CONCLUSIONS Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer . Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival PURPOSE Despite recent advances in the management of high- grade and recurrent gliomas , survival remains poor . Antiangiogenic therapy has been shown to be efficacious in the treatment of high- grade gliomas both in pre clinical models and in clinical trials . We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting . METHODS AND MATERIAL S This was a pre clinical study and an open-label phase I dose escalation trial . Multiple glioma cell lines were analyzed for viability after treatment with radiation , temozolomide , or sorafenib or combinations of them . For patients with primary disease , sorafenib was given concurrently with temozolomide ( 75 mg/m(2 ) ) and 60 Gy radiation , for 30 days after completion of radiation . For patients with recurrent disease , sorafenib was combined with a hypofractionated course of radiation ( 35 Gy in 10 fractions ) . RESULTS Cell viability was significantly reduced with the combination of radiation , temozolomide , and sorafenib or radiation and sorafenib . Eighteen patients ( 11 in the primary cohort , 7 in the recurrent cohort ) were enrolled onto this trial approved by the institutional review board . All patients completed the planned course of radiation therapy . The most common toxicities were hematologic , fatigue , and rash . There were 18 grade 3 or higher toxicities . The median overall survival was 18 months for the entire population . CONCLUSIONS Sorafenib can be safely combined with radiation and temozolomide in patients with high- grade glioma and with radiation alone in patients with recurrent glioma . The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone . To our knowledge , this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide PURPOSE This phase 2 study evaluated the efficacy of radiation therapy ( RT ) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma ( HCC ) . METHODS AND MATERIAL S Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib . Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression , unacceptable adverse events , or death . All patients had underlying Child-Pugh A cirrhosis . The maximal tumor diameter ranged from 3.0 cm to 15.5 cm . Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously . The cumulative RT dose ranged from 40 Gy to 60 Gy ( median , 50 Gy ) . Image studies were done 1 month after RT and then every 3 months thereafter . RESULTS Thirty-three ( 83 % ) completed the allocated RT . During RT , the incidence of h and -foot skin reactions ≥ grade 2 and diarrhea were 37.5 % and 25 % , respectively , and 35 % of patients had hepatic toxicities grade ≥2 . Twenty-two ( 55.0 % ) patients achieved complete or partial remission at the initial assessment , and 18 ( 45 % ) had stable or progressive disease . The 2-year overall survival and infield progression-free survival ( IFPS ) were 32 % and 39 % , respectively . A Cancer of the Liver Italian Program ( CLIP ) score ≥2 was associated with an inferior outcome in overall survival . Six patients ( 15 % ) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase , and 3 of them were fatal . CONCLUSIONS When RT and sorafenib therapy were combined in patients with unresectable HCC , the initial complete or partial response rate was 55 % with a 2-year IFPS of 39 % . A CLIP score ≥2 was associated with an inferior outcome in overall survival . Hepatic toxicities are a major determinant of the safety ; the combination should be used with caution and needs further investigation Summary Background To define maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) , and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer ( AGC ) patients . Methods Four dose-level combinations were tested in a st and ard 3 + 3 dose escalation design . Level 1 : sorafenib 400 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 2 : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 3 : sorafenib 800 mg/d , capecitabine 2,000 mg/m2/d , cisplatin 80 mg/m2 . Level 1A : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 60 mg/m2 . Results There were 1 DLT at Level 2 , and 2 DLTs at Level 3 ( Level 3 was MTD ) . Since the relative dose intensity ( RDI ) of sorafenib and capecitabine could not be maintained at Level 2 , Level 1A was newly investigated . As no DLT was observed and RDI remained above 80 % , Level 1A is the recommended dose for the next clinical trial . Objective response rate was 62.5 % ( 10 of 16 patients , 95 % CI ; 38.8–86.2 % ) . Median progression-free survival and overall survival were 10.0 months ( 95 % CI ; 7.4–13.8 ) and 14.7 months ( 95 % CI ; 12.0–20.0 ) , respectively . Conclusions Sorafenib 400 mg bid daily , capecitabine 800 mg/m2 bid ( days 1–14 ) , and cisplatin 60 mg/m2 ( day 1 ) is recommended for further development in AGC Purpose Sorafenib , an oral inhibitor of B-raf , VEGFR2 , and PDGFR2-beta , acts against pancreatic cancer in pre clinical models . Due to the radio-sensitization activity of both sorafenib and gemcitabine , we design ed a multicenter , phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy . Methods Patients with biopsy-proven , unresectable pancreatic adenocarcinoma ( based on vascular invasion detected by computed tomography ) were treated with gemcitabine ( 300 mg/m2 i.v . weekly ×5 weeks ) concurrently with radiation therapy ( 45 Gy in 25 fractions ) and sorafenib ( escalated doses in a 3 + 3 design , from 200 to 800 mg/day ) . Radiation portals included the primary tumor but not the regional lymph nodes . Patients with planning target volumes ( PTV ) over 500 cc were excluded . Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression . Results Twelve patients were included . Three patients received 200 mg/day , 6 received 400 mg/day , and 3 received 800 mg/day ; PTVs ranged from 105 to 500 cc . No dose-limiting toxicities occurred . The most common grade 2 toxicities were fatigue , neutropenia , nausea , and raised serum transaminases . Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy . There were no treatment-related deaths . Conclusion The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma . A dose of 800 mg/day is recommended for phase II evaluation . Trial Registration EudraCT 2007 - 003211 - 31 Clinical Trials.gov BACKGROUND Based upon pre clinical evidence for improved antitumor activity in combination , this phase I study investigated the maximum-tolerated dose ( MTD ) , safety , activity , pharmacokinetics ( PK ) , and biomarkers of the mammalian target of rapamycin inhibitor , temsirolimus , combined with sorafenib in hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS Patients with incurable HCC and Child Pugh score ≤B7 were treated with sorafenib plus temsirolimus by 3 + 3 design . The dose-limiting toxicity ( DLT ) interval was 28 days . The response was assessed every two cycles . PK of temsirolimus was measured in a cohort at MTD . RESULTS Twenty-five patients were enrolled . The MTD was temsirolimus 10 mg weekly plus sorafenib 200 mg twice daily . Among 18 patients at MTD , DLT included grade 3 h and -foot skin reaction ( HFSR ) and grade 3 thrombocytopenia . Grade 3 or 4 related adverse events at MTD included hypophosphatemia ( 33 % ) , infection ( 22 % ) , thrombocytopenia ( 17 % ) , HFSR ( 11 % ) , and fatigue ( 11 % ) . With sorafenib , temsirolimus clearance was more rapid ( P < 0.05 ) . Two patients ( 8 % ) had a confirmed partial response ( PR ) ; 15 ( 60 % ) had stable disease ( SD ) . Alpha-fetoprotein ( AFP ) declined ≥50 % in 60 % assessable patients . CONCLUSION The MTD of sorafenib plus temsirolimus in HCC was lower than in other tumor types . HCC-specific phase I studies are necessary . The observed efficacy warrants further study BACKGROUND The signal transduction pathways of epidermal growth factor receptor and Ras are both important in the growth of glioblastoma multiforme ( GBM ) . We hypothesized that inhibition of both pathways would improve the survival time of patients with recurrent GBM . METHODS Patients with recurrent/progressive GBM with 0 - 2 prior chemotherapy regimens received erlotinib 150 mg once daily and sorafenib 400 mg twice daily until progression . The primary endpoint was overall survival . Pharmacokinetic sampling was performed during cycle 1 . RESULTS The median overall survival was 5.7 months . Progression-free survival at 6 months was 14 % . Toxicity was manageable . Clearance of erlotinib was markedly enhanced by sorafenib . CONCLUSION The study did not meet its objective of a 30 % increase in overall survival time compared with historical controls . Erlotinib and sorafenib have significant pharmacokinetic interactions that may negatively impact the efficacy of the combination regimen Purpose : We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk ( intermediate/high grade , > 5 cm ) extremity soft tissue sarcoma undergoing limb salvage surgery . We conducted a correlative study of quantitative dynamic contrast-enhanced MRI ( DCE-MRI ) to assess response to treatment . Experimental Design : Patients were treated at increasing dose levels of sorafenib ( 200 mg daily , 400 mg daily , 400 mg twice daily ) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide . Radiation ( 28 Gy ) was administered during cycle 2 with epirubicin omitted . The primary objective was to determine the maximum tolerated dose ( MTD ) of sorafenib . DCE-MRI was conducted at baseline , after 2 weeks of sorafenib , and before surgery . The imaging data were subjected to quantitative pharmacokinetic analyses . Results : Eighteen subjects were enrolled , of which 16 were evaluable . The MTD of sorafenib was 400 mg daily . Common grade 3–4 adverse events included neutropenia ( 94 % ) , hypophosphatemia ( 75 % ) , anemia ( 69 % ) , thrombocytopenia ( 50 % ) , and neutropenic fever/infection ( 50 % ) . Of note , 38 % developed wound complications requiring surgical intervention . The rate of ≥95 % histopathologic tumor necrosis was 44 % . Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response ( R2 = 0.67 , P = 0.012 ) at surgery . Conclusion : The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial . DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma . Clin Cancer Res ; 19(24 ) ; 6902–11 . © 2013 AACR Summary Background This phase I trial assessed safety , pharmacokinetics ( PK ) , dose limiting toxicity ( DLT ) , maximum tolerated dose and recommended dose ( RD ) of the combination of sorafenib plus ifosfamide in patients with advanced sarcoma . Methods Twelve sarcoma patients ( 9 soft-tissue , 3 bone sarcoma ) were treated with sorafenib plus ifosfamide ( starting doses 200 mg bid and 6 g/m2 respectively ) . A 3 + 3 dose escalation design with cohorts of 3–6 patients was used . A study to assess the in vitro efficacy of the combination was also conducted . Results Three DLTs were observed : fatigue grade 4 with sorafenib 400 mg bid plus ifosfamide 6 g/m2 and encephalopathy and emesis grade 3 with sorafenib 400 mg bid plus ifosfamide 7.5 g/m2 . Other toxicities included diarrhea , h and -foot syndrome , mucositis , neutropenia , skin rash and thrombocytopenia . There were no relevant effects on PK of sorafenib but an increase in ifosfamide active metabolite 4-hydroxy-ifosfamide was observed . Eight patients achieved stable disease lasting more than 12 weeks . An additive effect was observed in vitro . Conclusions RD was sorafenib 400 mg bid plus ifosfamide 6 g/m2 , allowing administration of active doses of both agents . Limited preliminary antitumor activity was also observed . A phase II study is currently ongoing Summary Background Sorafenib , an inhibitor of B-raf , VEGFR2 , and PDGFR-β , has activity against pancreatic cancer in pre clinical models . In a phase I trial of gemcitabine plus sorafenib , 57 % of pancreatic cancer patients achieved stable disease . Patients and methods We conducted a multi-center phase II trial of sorafenib plus gemcitabine in chemo-naïve patients with histologically-confirmed , advanced pancreatic cancer . Patients received sorafenib 400 mg twice daily and gemcitabine 1,000 mg/m2 on days 1 , 8 and 15 of a 28 day cycle . Results Seventeen patients enrolled at 4 centers ; 13 were evaluable for response . There were no objective responses ; 18 % had stable disease . Median overall survival was 4.0 months ( 95 % CI : 3.4 , 5.9 ) ; median progression-free survival was 3.2 months ( 95 % CI : 1.6 , 3.6 ) . Grade 3/4 toxicities included thrombosis in 18 % of patients , dehydration or h and -foot syndrome in 12 % , and hypertension or gastrointestinal bleeding in 6 % . Conclusion Gemcitabine plus sorafenib is inactive in advanced pancreatic cancer Summary Purpose Sorafenib is a multi-kinase inhibitor , which was approved as first-line treatment for patients with advanced hepatocellular carcinoma ( HCC ) . We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC . Experimental design We design ed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib . Four dose levels were as follows : level 1 , D1 - 14 S-1 50 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 2 , D1 - 14 S-1 60 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 3 , , D1 - 14 S-1 70 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 4 , D1 - 14 S-1 80 mg/m2/day + D1 - 21 sorafenib 400 mg bid . The treatment was repeated every 3 weeks . Results From August 2009 to July 2010 , 20 patients with advanced HCC were enrolled . The median age was 48 years ( range , 29–74 ) . Eighteen ( 90 % ) patients had hepatitis B viral infection and 19 ( 95 % ) patients were rated as Child-Pugh class A. The dose-limiting toxicities were grade 4 infection and thrombocytopenia . After a median follow-up duration of 8.6 months ( range , 3.7–14.2 months ) , median PFS was 3.9 months ( 95 % CI , 0.8–7.0 months ) and median OS was 10.4 months ( 95 % CI , 0–22.4 months ) . In pharmacokinetic analysis , there was no statistically significant drug interaction between sorafenib and S-1 . Conclusions The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC . The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m2 twice daily , respectively Purpose PR-104 is activated by reductases under hypoxia or by aldo – keto reductase 1C3 ( AKR1C3 ) to form cytotoxic nitrogen mustards . Hepatocellular carcinoma ( HCC ) displays extensive hypoxia and expresses AKR1C3 . This study evaluated the safety and efficacy of PR-104 plus sorafenib in HCC . Methods Patients with advanced-stage HCC , Child-Pugh A cirrhosis , and adequate organ function , were assigned to dose escalating cohorts of monthly PR-104 in combination with twice daily sorafenib . The plasma pharmacokinetics ( PK ) of PR-104 and its metabolites were evaluated . Results Fourteen ( 11 men , 3 women ) HCC patients : median age 60 years , ECOG 0 - 1 , received PR-104 at two dose levels plus sorafenib . Six patients were treated at starting cohort of 770 mg/m2 . In view of one DLT of febrile neutropenia and prolonged thrombocytopenia , a lower PR-104 dose cohort ( 550 mg/m2 ) was added and accrued 8 patients . One patient had a partial response and three had stable disease of ≥8 weeks in the 770 mg/m2 cohort . Three patients at the 550 mg/m2 had stable disease . There were no differences in PK of PR-104 or its metabolites with or without sorafenib , but the PR-104A AUC was twofold higher ( P < 0.003 ) than in previous phase I studies at equivalent dose . Conclusions PR-104 plus sorafenib was poorly tolerated in patients with advanced HCC , possibly because of compromised clearance of PR-104A in this patient population . Thrombocytopenia mainly and neutropenia were the most clinical ly significant toxicities and led to discontinuation of the study . PR-104 plus sorafenib is unlikely to be suitable for development in this setting Sorafenib , an oral VEGFR-2 , Raf , PDGFR , c-KIT and Flt-3 inhibitor , is active against renal cell and hepatocellular carcinomas , and has recently demonstrated promising activity for lung and breast cancers . In addition , various protracted temozolomide dosing schedules have been evaluated as a strategy to further enhance its anti-tumor activity . We reasoned that sorafenib and protracted , daily temozolomide may provide complementary therapeutic benefit , and therefore performed a phase 2 trial among recurrent glioblastoma patients . Adult glioblastoma patients at any recurrence after st and ard temozolomide chemoradiotherapy received sorafenib ( 400 mg twice daily ) and continuous daily temozolomide ( 50 mg/m2/day ) . Assessment s were performed every eight weeks . The primary endpoint was progression-free survival at 6 months ( PFS-6 ) and secondary end points were radiographic response , overall survival ( OS ) , safety and sorafenib pharmacokinetics . Of 32 enrolled patients , 12 ( 38 % ) were on CYP3-A inducing anti-epileptics ( EIAEDs ) , 17 ( 53 % ) had 2 or more prior progressions , 15 had progressed while receiving 5-day temozolomide , and 12 ( 38 % ) had failed either prior bevacizumab or VEGFR inhibitor therapy . The most common grade ≥ 3 toxicities were palmer-planter erythrodysesthesia ( 19 % ) and elevated amylase/lipase ( 13 % ) . Sorafenib pharmacokinetic exposures were comparable on day 1 regardless of EIAED status , but significantly lower on day 28 for patients on EIAEDs ( P = 0.0431 ) . With a median follow-up of 93 weeks , PFS-6 was 9.4 % . Only one patient ( 3 % ) achieved a partial response . In conclusion , sorafenib can be safely administered with daily temozolomide , but this regimen has limited activity for recurrent GBM . Co-administration of EIAEDs can lower sorafenib exposures in this population This trial was design ed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma . An exploratory correlative study analyzing pretreatment serum sample s using a multivariate protein mass spectrometry‐based test ( VeriStrat ® ) , previously shown to correlate with outcomes in lung cancer patients treated with erlotinib , was performed . Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8‐week progression free survival ( PFS ) rate . Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data ; the endpoints were PFS and overall survival ( OS ) . Difference between groups ( by VeriStrat classification ) was assessed using log‐rank P values ; hazard ratios ( HR ) were obtained from Cox proportional hazards model . Thirty‐six patients received study drug and were included in the survival analysis . Eight‐week PFS rate of 46 % ( 95 % confidence interval ( CI ) : 0.32–0.67 ) did not meet the primary endpoint of a rate ≥70 % . Thirty‐two patients were included in the correlative analysis , and VeriStrat “ Good ” patients had superior PFS ( HR = 0.18 , 95 % CI : 0.06–0.57 ; P = 0.001 ) and OS ( HR = 0.31 95 % CI : 0.13–0.77 , P = 0.008 ) compared to VeriStrat “ Poor ” patients . Grade 3 toxicities of this regimen included fever , anemia , diarrhea , dehydration , rash , and altered liver function . This study did not meet the primary endpoint , and this combination will not be further pursued . In this small retrospective analysis , the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies Summary Objectives Unsatisfactory efficacy of current treatments for advanced lung cancer has prompted the search for new therapies , with sorafenib , a multikinase inhibitor , being one c and i date drug . This phase I trial was conducted to evaluate drug safety and pharmacokinetics as well as tumor response of sorafenib in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer ( NSCLC ) . Methods Eligible patients received paclitaxel ( 200 mg/m2 ) and carboplatin ( area under the curve [AUC]of 6 mg min mL−1 ) on day 1 and sorafenib ( 400 mg , twice daily ) on days 2 through 19 of a 21-day cycle . Results Four of the initial six patients ( cohort 1 ) experienced dose-limiting toxicities ( DLTs ) , result ing in amendment of the treatment protocol . An additional seven patients ( cohort 2 ) were enrolled , two of whom developed DLTs . DLTs included erythema multiforme , h and -foot skin reaction , and elevated plasma alanine aminotransferase in cohort 1 as well as gastrointestinal perforation at a site of metastasis and pneumonia in cohort 2 . Most adverse events were manageable . One complete and six partial responses were observed among the 12 evaluable patients . Coadministration of the three drugs had no impact on their respective pharmacokinetics . Conclusion The present study confirmed that sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL−1 and paclitaxel 200 mg/m2 is feasible in Japanese patients with advanced NSCLC . The results of this study also showed that this combination therapy had encouraging antitumor activity and was not associated with relevant pharmacokinetic interaction in Japanese NSCLC patients Background : This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy . Methods : Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m−2 and cisplatin 25 mg m−2 on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily . After the initial 16 patients were enrolled , the chemotherapy doses were amended in view of grade 3 and 4 h and –foot skin reaction and haematologic toxicity . Subsequently , 21 patients received gemcitabine 800 mg m−2 , cisplatin 20 mg m−2 and sorafenib 400 mg . The primary end point was an improvement in 6-month progression-free survival ( PFS6 ) from historical 57–77 % ( 90 % power , type I error of 10 % ) . Pretreatment pERK , evaluated by immunostaining , was correlated with clinical outcome . Results : A total of 39 patients were accrued . The most common grade 3–4 toxicities noted in > 10 % of patients were fatigue , elevated liver function tests and haematologic toxicities including thromboemboli , hyponatraemia and hypophosphataemia . Six-month progression-free survival was 51 % ( 95 % confidence interval ( CI ) 34–66 % ) . Median PFS and overall survival were 6.5 ( 95 % CI : 3.5–8.3 ) and 14.4 months ( 95 % CI : 11.6–19.2 months ) , respectively . No correlation was observed between pERK and outcomes . Conclusion : The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data , and toxicity was increased Purpose : To evaluate the combination of sorafenib and gefitinib in patients with advanced non – small cell lung cancer . Experimental Design : In this dose-escalation trial , patients received oral sorafenib ( 200 - 400 mg ) twice daily with gefitinib ( 250 mg orally ) once daily to identify the recommended dose for phase II trials ( RDP ; part A ) . The pharmacokinetics of the RDP were characterized further in additional patients ( part B ) receiving single-agent gefitinib or sorafenib for 21 days followed by a 7-day washout with crossover to the other agent for an additional 21 days . Patients then received the combination of sorafenib plus gefitinib in 28-day cycles . Safety , pharmacokinetics , and antitumor efficacy were evaluated . Potential drug-drug interactions and the relationship between pharmacokinetics and toxicity were also assessed . Results : Thirty-one patients were treated ( n = 12 , part A ; n = 19 , part B ) . Most adverse events were grade 1/2 . The most frequent grade 3/4 events included diarrhea and elevated alanine aminotransferase ( both 9.7 % ) . One dose-limiting toxicity occurred ( part A : elevated alanine aminotransferase at 400 mg twice daily ) . Gefitinib had no effect on sorafenib pharmacokinetics . However , gefitinib Cmax ( 26 % ) and area under the curve ( 38 % ) were reduced by concomitant sorafenib . One patient had a partial response ; 20 ( 65 % ; n = 8 , part A ; n = 12 , part B ) had stable disease ≥4 months . The RDP was sorafenib 400 mg twice daily with gefitinib 250 mg once daily . Conclusions : Sorafenib combined with gefitinib is well tolerated , with promising efficacy in patients with advanced non – small cell lung cancer . Studies to further investigate the significance of the reduction in gefitinib exposure by sorafenib are warranted Purpose Sorafenib and everolimus are both active against neuroendocrine tumors ( NET ) . Because of potential synergy between VEGF pathway and mTOR inhibitors , we performed a phase I study to evaluate the safety and feasibility of combining sorafenib and everolimus in patients with advanced NET . Methods Patients were treated with everolimus 10 mg daily in combination with sorafenib ( dose level 1 : 200 mg twice daily ; dose level 2 : 200 mg per morning , 400 mg per evening ) using st and ard phase I dose escalation design . Dose-limiting toxicity ( DLT ) was defined within the first cycle ( 28 days ) of therapy . Treatment was continued until tumor progression , unacceptable toxicity , or withdrawal of consent . Twelve additional patients were treated at the maximum tolerated dose ( MTD ) level to further characterize safety and a preliminary assessment of activity . Results One patient in Cohort 1 experienced DLT ( grade 3 skin rash ) ; the cohort was exp and ed to 6 patients with no further DLTs . All 3 patients in Cohort 2 experienced DLT , consisting of thrombocytopenia , h and –foot skin reaction , and rash/allergic reaction . Sorafenib 200 mg twice daily in combination with everolimus 10 mg daily was established as the MTD . Independently review ed best objective responses revealed that 62 % of patients had some degree of tumor shrinkage . By RECIST , we observed partial response in 1 patient , stable disease in 13 patients , and progressive disease in 3 patients . ConclusionS orafenib 200 mg twice daily with everolimus 10 mg daily represents the MTD of this combination in patients with advanced NET . While the combination is active , toxicity concerns may preclude more widespread use BACKGROUND Bevacizumab has provided encouraging results in relapsed glioblastoma multiforme ( GBM ) . Pre- clinical and clinical investigations also showed that continuous low-dose temozolomide has some antiangiogenic activity . Based on this evidence , a phase II trial was design ed to investigate an oral regimen of sorafenib , an oral multikinase inhibitor , and metronomic temozolomide for relapsed GBM . PATIENTS AND METHODS Forty-three patients ( median age=60.0 years ) naive for antiangiogenic agents received 400 mg sorafenib twice daily plus TMZ 40 mg/m(2)/day until disease progression . RESULTS Toxicity , mostly grade 1 - 2 , was manageable . Grade 3 - 4 toxicities were h and -foot syndrome ( n=4 ) , hypertension ( n=2 ) , and fatigue ( n=3 ) . Five patients ( 12 % ) achieved partial response , 18 ( 43 % ) stable disease , 20 ( 48 % ) showed progression . The median time-to-progression was 3.2 months , 6-month progression-free survival was 26 % , and median overall survival was 7.4 months . CONCLUSION This combination of sorafenib and temozolomide was feasible and safe , showing some activity in patients with relapsed GBM Abstract Background Despite effective local therapy with surgery and radiotherapy ( RT ) , ~50 % of patients with high- grade soft tissue sarcoma ( STS ) will relapse and die of disease . Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT , we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent . Methods For the phase I trial , eight patients with intermediate- or high- grade STS > 5 cm in maximal dimension or low- grade STS > 8 cm in maximal dimension received concomitant sorafenib ( dose escalation cohort 1:200 twice daily , cohort 2:200/400 daily ) and preoperative RT ( 50 Gy in 25 fractions ) . Sorafenib was continued during the entire period of RT as tolerated . Surgical resection was completed 4–6 weeks following completion of neoadjuvant sorafenib/RT . Three sorafenib dose levels were planned . Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity ( DLT ) . Results Eight patients were enrolled in the phase I ( five females , median age 44 years , two high- grade pleomorphic , two myxoid/round cell liposarcoma , four other ) . Median tumor size was 16 cm ( range 8–29 ) , and all tumors were located in the lower extremity . Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug re introduction . Other grade 3 side effects included anemia , perirectal abscess , and supraventricular tachycardia . Radiation toxicity ( grade 1 or 2 dermatitis ; N = 8) and post-surgical complications ( three grade 3 wound complications ) were comparable to historical controls and other series of preoperative RT monotherapy . Complete pathologic reponse ( ≥95 % tumor necrosis ) was observed in three patients ( 38 % ) . Conclusion Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS . Further study to determine efficacy at dose level 1 is warranted . ( Clinical Trials.gov identifier NCT00805727 ) BACKGROUND & AIMS Transarterial chemoembolization ( TACE ) is an important palliative treatment for unresectable hepatocellular carcinoma ( HCC ) , but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis . The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC . METHODS The primary objectives of this prospect i ve , single-arm , phase II study were to evaluate safety and time to progression ( TTP ) . Sorafenib was given 3 days after TACE and was administered for up to 24 weeks . Repeated TACE was performed on dem and . Tumor response was assessed every 8 weeks . RESULTS Fifty patients were treated and followed from July 2009 to May 2011 . All patients were in Barcelona Clinic Liver Cancer ( BCLC ) stage B ( 82 % ) or C ( 18 % ) . The median time of follow-up was 14.9 months and a median of 1 TACE session was given ( range , 1 - 4 ) . The median dose intensity of sorafenib was 68.7 % ( range , 37.3 - 100 ) of 800 mg daily . The most common reasons for dose reduction were h and -foot syndrome and thrombocytopenia . Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression . The overall median TTP was 7.1 months ( 95 % confidence interval ( CI ) , 4.8 - 7.5 months ) : 7.3 months in BCLC stage B ; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52 % ( 95 % CI , 37.3 - 66.1 ) . CONCLUSIONS Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy BACKGROUND The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations . A phase II r and omized trial was design ed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer . METHODS Locally advanced or metastatic pancreatic adenocarcinoma patients were r and omized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400 mg bid ( arm A ) or without sorafenib ( arm B ) . RESULTS One hundred and fourteen patients were enrolled ; of these , 43 ( 74.6 % ) patients progressed in arm A and 44 ( 82.4 % ) in arm B. Median progression-free survival was 4.3 months ( 95 % CI : 2.7 - 6.5 ) and 4.5 months ( 95 % CI : 2.5 - 5.2 ) , respectively ( HR=0.92 ; 95 % CI : 0.62 - 1.35 ) . Median overall survival was 7.5 ( 95 % CI : 5.6 - 9.7 ) and 8.3 months ( 95 % CI : 6.2 - 8.7 ) , respectively ( HR=0.95 ; 95 % CI : 0.62 - 1.48 ) . Response rates were 3.4 % in arm A and 3.6 % in arm B. CONCLUSIONS Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients , and therefore should not be assessed in phase III trials Background Sorafenib inhibits several receptor tyrosine kinases involved in tumor progression and angiogenesis . S-1 , an oral fluorouracil antitumor drug , plus cisplatin ( CDDP ) is the st and ard regimen for advanced gastric adenocarcinoma ( AGC ) in Japan . The purpose of this phase I study was to evaluate the safety , pharmacokinetics , and preliminary efficacy of sorafenib in combination with S-1 plus CDDP . Methods Patients with histologically confirmed previously untreated AGC were evaluated for eligibility and treated with sorafenib ( 400 mg bid , days 1–35 ) , S-1 ( 40 mg/m2 bid , days 1–21 ) , and CDDP ( 60 mg/m2 , day 8) . Treatment was continued until disease progression or unacceptable toxicity . Pharmacokinetics for sorafenib , 5-FU , and CDDP were investigated in cycle 1 . Results Thirteen patients were enrolled and received at least one dose of the study treatment . No specific or serious adverse event was newly reported in this study . Five patients had partial response and 8 had stable disease as the best response . Pharmacokinetic analysis showed no significant differences in the exposures of sorafenib when administered alone or in combination with S-1 and CDDP . Conclusions The present phase I study demonstrates the acceptable toxicity and preliminary efficacy of combined treatment with S-1 , CDDP , and sorafenib BACKGROUND Sorafenib is a small-molecule multitargeted kinase inhibitor that blocks the activation of C-RAF , B-RAF , c-KIT , FLT-3 , RET , vascular endothelial growth factor receptor 2 ( VEGFR-2 ) , VEGFR-3 and platelet-derived growth factor receptor β . The aim of this multicenter , r and omized phase II study was to evaluate clinical activity and safety of sorafenib in combination with erlotinib or gemcitabine in unselected untreated elderly patients with non-small-cell lung cancer ( NSCLC ) . METHODS The trial was design ed to select the most promising sorafenib-containing combination in previously untreated elderly ( ≥70 years ) stage IIIB or IV NSCLC patients , with performance status of zero to two . Patients were r and omly assigned to one of the following combinations : gemcitabine , 1200 mg/m(2 ) days 1 and 8 , every 21 days , for a maximum of six cycles , plus sorafenib , 800 mg/day , until disease progression or unacceptable toxicity ( arm 1 ) ; or erlotinib , 150 mg/day , plus sorafenib , 800 mg/day , until disease progression or unacceptable toxicity ( arm 2 ) . A selection design was applied with 1-year survival rate as the primary end point of the study , requiring 58 patients . RESULTS Sixty patients were r and omly allocated to the study ( 31 patients in arm 1 and 29 patients in arm 2 ) . After a median follow-up of 15 months , 10 patients [ 32 % , 95 % confidence interval ( CI ) 16 % to 49 % ] in arm 1 and 13 patients ( 45 % , 95 % CI 27 % to 63 % ) in arm 2 were alive at 1 year . Median overall survival was 6.6 and 12.6 months in arm 1 and arm 2 , respectively . Observed toxic effects were consistent with the expected drug profiles . CONCLUSIONS The combination of erlotinib and sorafenib was feasible in elderly patients with advanced NSCLC and was associated with a higher 1-year survival rate than the other arm . According to the selection design , this combination warrants further investigation in phase III trials Summary Objectives Sorafenib is a multi-tyrosine kinase inhibitor of Raf kinase , VEGFR , and PDGFR . Angiogenesis is important for growth and progression of SCLC . This trial was conducted to evaluate whether the combination of cisplatin and etoposide plus concurrent and sequential sorafenib could prolong survival in patients with previously untreated SCLC . Methods Previously untreated patients with extensive stage SCLC were treated with cisplatin and etoposide days 1 , 2 , 3 for four cycles , concurrent with sorafenib 200 mg orally bid starting day 1 cycle 1 . Patients with no disease progression after four cycles continued sorafenib 400 mg orally bid as maintenance for maximum of 12 months . The primary endpoint was 1 year survival with response rate and safety as secondary endpoints . Results A total of 18 patients were enrolled with 17 evaluable patients . One patient had a complete response , seven patients had a partial response ( overall response rate of 47 % ) and one patient had stable disease . Overall median survival was 7.4 months and 1 year survival was 25 % . The most common treatment-related adverse events included fatigue , anorexia , rash , diarrhea , neutropenia and weight loss . Grade 5 GI bleeding , pulmonary hemorrhage and neutropenia occurred in one pt ( 6 % ) each . Accrual was halted on the basis of safety profile as well as preliminary efficacy data . Conclusions The combination of platinum based chemotherapy and sorafenib has significant toxicity at current dose levels and is associated with disappointing efficacy data PURPOSE This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib , a Raf and multiple receptor tyrosine kinase inhibitor , in patients with advanced renal carcinoma . PATIENTS AND METHODS Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component , no prior systemic therapy , performance status 0 to 1 , and measurable disease . Treatment consisted of interferon alfa-2b 10 x 10(6 ) U subcutaneously three times weekly and sorafenib 400 mg orally bid . The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate . RESULTS Twelve ( 19 % ) of 62 assessable patients achieved an objective confirmed response . An additional 31 ( 50 % ) had an unconfirmed partial response or stable disease as best response . The median progression-free survival was 7 months ( 95 % CI , 4 to 11 months ) . The most common adverse events were fatigue , anorexia , anemia , diarrhea , nausea , rigors/chills , leukopenia , fever , and transaminase elevation . Von Hippel-Lindau gene mutations were detected in four ( 22 % ) of 18 archival tumor specimens . CONCLUSION The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone . The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen Summary Background This phase Ib study was design ed to determine the maximum tolerated doses ( MTD ) and dose limiting toxicities ( DLTs ) of irinotecan and cetuximab with sorafenib . Secondary objectives included characterizing the pharmacokinetics and pharmacodynamics and evaluating preliminary antitumor activity in patients with advanced colorectal cancer ( CRC ) . Methods Patients with metastatic , pretreated CRC were treated at five dose levels . Results Eighteen patients were recruited with median age 56.5 years . In the first five patients treated , 2 irinotecan related DLTs were observed . With reduced dose intensity irinotecan , there were no further DLTs . The most common toxicities were diarrhea , nausea/vomiting , fatigue , anorexia and rash . DLTs included neutropenia and thrombocytopenia . Two patients had partial responses ( one with a KRAS mutation ) and 8 had stable disease ( 8–36 weeks ) . The median progression free survival ( PFS ) and overall survival ( OS ) were 2.5 and 4.7 months respectively . Pharmacokinetic analyses suggest sorafenib and metabolite exposure correlate with OS and DLTs . Conclusions The recommended phase II dose ( RP2D ) is irinotecan 100 mg/m2 i.v . days 1 , 8 ; cetuximab 400 mg/m2 i.v . days 1 and 250 mg/m2 i.v . weekly ; and sorafenib 400 mg orally twice daily in advanced , pretreated CRC . The combination result ed in a modest response rate BACKGROUND Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways . A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer ( APC ) patients . The BAYPAN study was a multicentric , placebo-controlled , double-blind , r and omized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC . PATIENTS AND METHODS The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma , no prior therapy for advanced disease and a performance status of zero to two . The primary end point was progression-free survival ( PFS ) . The patients received gemcitabine 1000 mg/m(2 ) i.v . , weekly seven times followed by 1 rest week , then weekly three times every 4 weeks plus sorafenib 200 mg or placebo , two tablets p.o . , twice daily continuously . RESULTS Between December 2006 and September 2009 , 104 patients were enrolled on the study ( 52 pts in each arm ) and 102 patients were treated . The median and the 6-month PFS were 5.7 months and 48 % for gemcitabine/placebo and 3.8 months and 33 % for gemcitabine/sorafenib ( P = 0.902 , stratified log-rank test ) , respectively . The median overall survivals were 9.2 and 8 months , respectively ( P = 0.231 , log-rank test ) . The overall response rates were similar ( 19 and 23 % , respectively ) . CONCLUSION The addition of sorafenib to gemcitabine does not improve PFS in APC patients BACKGROUND Sorafenib and bevacizumab as single agents have shown efficacy and acceptable toxicity in NETs phase II trials . Sorafenib and bevacizumab combination has shown manageable toxicity in phase I trials in solid tumours . The purpose of this study was to evaluate the safety and efficacy of the combination of sorafenib and bevacizumab in patients with advanced neuroendocrine tumours . METHODS Open-label , uncontrolled , multicenter , phase II clinical trial . ELIGIBILITY CRITERIA age ≥18 years , histologically confirmed measurable advanced NETs ; 1 prior chemotherapy allowed ; ECOG-PS 0 - 2 . Patients were treated during 6 months and followed up for an additional 6 months . TREATMENT sorafenib 200 mg bid ( days 1 - 5 of each week ) and bevacizumab 5mg/kg once every 2 weeks ( day 1 , week 1 ) . Tumour response was performed according to RECIST ( v1.0 ) every 2 months during the treatment period . Adverse events were grade d according to CTCAE ( v3.0 ) . FINDINGS 44 Patients enrolled , 59.1 % men , median age 60 years ( range 32 - 76 ) . 70.5 % carcinoid tumours , 29.5 % pancreatic tumour . Baseline target lesions mainly in the liver ( 86.4 % ) . Global PFSR was 90.9 % ( 91.7 % carcinoid tumours and 88.9 % pancreatic tumours ) . Median PFS was 12.4 months , median TTP was 14.5 months , ORR was 9.4 % and DCR was 95.1 % . Most common grade 3 - 4 toxicities : asthenia ( 11.4 % ) and h and -foot skin reaction ( 15.9 % ) . INTERPRETATION Sorafenib and bevacizumab combination showed clinical benefit but unfavourable safety results compared with drugs in monotherapy . Further development of this combination is not warranted and a sequential approach is recommended instead The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date . The North American Brain Tumor Consortium examined the safety , pharmacokinetics , and efficacy of combination therapy with sorafenib , a small molecule inhibitor of Raf , vascular endothelial growth factor receptor 2 , and platelet-derived growth factor receptor-β , and temsirolimus ( CCI-779 ) , an inhibitor of mammalian target of rapamycin . This was a phase I/II study . The phase I component used a st and ard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy . The phase II component used a 2-stage design ; the primary endpoint was 6-month progression-free survival ( PFS6 ) rate . Thirteen patients enrolled in the phase I component . The maximum tolerated dosage ( MTD ) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly . At the MTD , grade 3 thrombocytopenia was the dose-limiting toxicity . Eighteen patients were treated in the phase II component . At interim analysis , the study was terminated and did not proceed to the second stage . No patients remained progression free at 6 months . Median PFS was 8 weeks . The toxicity of this combination therapy result ed in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose . Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents BACKGROUND There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma ( ACC ) . Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells . OBJECTIVE We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients . We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro . DESIGN Multicenter , prospect i ve phase II trial . Setting Referral centers for ACC . METHODS Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled . The patients received a combination of i.v . paclitaxel ( 60 mg/m(2 ) every week ) and oral sorafenib ( 400 mg twice a day ) till progression . The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity . RESULTS Tumor progression was observed in nine evaluable patients at the first assessment . These results led to the premature interruption of the trial . The treatment was well tolerated . The most relevant toxicities were fatigue , being grade 2 or 3 in four patients , and hypophosphatemia , being grade 3 in three patients . In the in vitro study , sorafenib impaired the viability of H295R cells with dose-response and time-response relationships . The in vitro sorafenib activity was not increased in combination with paclitaxel . CONCLUSIONS Despite the in vitro activity , sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended Purpose : We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab . Experimental Design : This double-blind , r and omized , placebo-controlled phase IIb study ( Clinical Trials.gov NCT00493636 ) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)–negative breast cancer and prior bevacizumab treatment . Patients were r and omized to chemotherapy with sorafenib ( 400 mg , twice daily ) or matching placebo . Initially , chemotherapy was gemcitabine ( 1,000 mg/m2 i.v . , days 1 , 8/21 ) , but later , capecitabine ( 1,000 mg/m2 orally twice daily , days 1–14/21 ) was allowed as an alternative . The primary endpoint was progression-free survival ( PFS ) . Results : One hundred and sixty patients were r and omized . More patients received gemcitabine ( 82.5 % ) than capecitabine ( 17.5 % ) . Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [ 3.4 vs. 2.7 months ; HR = 0.65 ; 95 % confidence interval ( CI ) : 0.45–0.95 ; P = 0.02 ] , time to progression was increased ( median , 3.6 vs. 2.7 months ; HR = 0.64 ; 95 % CI : 0.44–0.93 ; P = 0.02 ) , and overall response rate was 19.8 % versus 12.7 % ( P = 0.23 ) . Median survival was 13.4 versus 11.4 months for sorafenib versus placebo ( HR = 1.01 ; 95 % CI : 0.71−1.44 ; P = 0.95 ) . Addition of sorafenib versus placebo increased grade 3/4 h and –foot skin reaction ( 39 % vs. 5 % ) , stomatitis ( 10 % vs. 0 % ) , fatigue ( 18 % vs. 9 % ) , and dose reductions that were more frequent ( 51.9 % vs. 7.8 % ) . Conclusion : The addition of sorafenib to gemcitabine/capecitabine provided a clinical ly small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab . Combination treatment was associated with manageable toxicities but frequently required dose reductions . Clin Cancer Res ; 19(10 ) ; 2745–54 . © 2013 AACR PURPOSE To provide recommendations to trialists and sponsors that guide the design and implementation of prospect i ve postapproval clinical trials for oncology drugs used outside US Food and Drug Administration-labeled indications for treatment of late-stage cancers . METHODS A meeting was hosted by the Center for Medical Technology Policy in Baltimore , MD , on November 12 , 2009 . Discussion s during the meeting and key informant interviews were conducted before and after this stakeholder meeting . Peer review by multidisciplinary stakeholders was followed by a public comment period . Input was received from patient advocacy groups , medical oncologists , pharmaceutical companies , the US Food and Drug Administration , Centers for Medicare and Medicaid Services , the National Cancer Institute , foreign government agencies involved in health technology assessment , public and private payers , drug compendia , clinical research entities , statisticians , academics , and the American Society of Clinical Oncology . RESULTS To address the needs of patients and their clinical providers , compendia , payers , and policy makers , recommendations are proposed to guide the design of future prospect i ve trials for off-label use of oncology drugs across four areas : trial design and data analysis , patient and site recruitment , comparators , and outcomes . CONCLUSION The US Food and Drug Administration provides guidance to the pharmaceutical industry and others design ing r and omized clinical trials for regulatory approval . However , a gap exists for postregulatory decision makers , including patients , prescribers , and payers , because regulatory trials do not answer the questions most relevant to them . Therefore , guidance is needed for trials performed in the postapproval environment for these postapproval decision makers PURPOSE This phase III , multicenter , r and omized , placebo-controlled trial assessed the efficacy and safety of sorafenib , an oral multikinase inhibitor , in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Nine hundred twenty-six patients were r and omly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2 ) ( CP ) on day 1 , followed by either sorafenib 400 mg twice a day ( n = 464 , arm A ) or placebo ( n = 462 , arm B ) on days 2 to 19 . The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day . The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival and tumor response . RESULTS Overall demographics were balanced between arms ; 223 patients ( 24 % ) had squamous cell histology . On the basis of a planned interim analysis , median OS was 10.7 months in arm A and 10.6 months in arm B ( hazard ratio [ HR ] = 1.15 ; 95 % CI , 0.94 to 1.41 ; P = .915 ) . The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point . A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B ( HR = 1.85 ; 95 % CI , 1.22 to 2.81 ) . Main grade 3 or 4 sorafenib-related toxicities included rash ( 8.4 % ) , h and -foot skin reaction ( 7.8 % ) , and diarrhea ( 3.5 % ) . CONCLUSION No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC Objective To define the safety [ dose limiting toxicity ( DLT ) ] and recommended phase II dose of the combination of sorafenib plus gemcitabine and capecitabine for advanced renal cell carcinoma ( RCC ) . Methods In this phase I dose-escalation study , cohorts of 3 to 6 patients with metastatic RCC received sorafenib ( 200 or 400 mg po BID ) , gemcitabine ( 750 or 1000 mg/m2 intravenous on days 1 and 8) , and capecitabine ( 415 or 622 mg/m2 po BID days 1–14 ) every 21 days using a st and ard 3 + 3 design . Results Fifteen patients with advanced RCC ( 93 % with clear cell histology and 87 % treatment naive ) received treatment . The recommended phase II doses for the combination were sorafenib 200 mg/m2 BID continuously plus gemcitabine 750 mg/m2 intravenous days 1 and 8 and capecitabine 415 mg/m2 BID days 1 to 14 , every 21 days . Of the 15 patients , 3 developed dose-limiting h and -foot syndrome during the first 2 cycles ; 2 additional DLT 's were grade 3 mucositis and transaminase elevation . Four of 14 evaluable patients had a partial response by response evaluation criteria in solid tumors ( 29 % ; 95 % confidence interval ( CI ) : 8 , 58 % ) . Median progression-free survival was 7.5 months ( 95 % CI–0 , 18.7 ) , and median overall survival has not been reached at a median follow-up of 28.8 months . The median number of treatment cycles given was 7 ( range , 2–38 + ) . Conclusions The combination of sorafenib plus gemcitabine and capecitabine is tolerable , but requires attenuation of sorafenib and capecitabine dosing because of the overlapping toxicity of h and -foot syndrome . Antitumor activity was observed leading to an ongoing phase II trial PURPOSE Sorafenib , an oral multikinase inhibitor , has shown preliminary activity in non-small-cell lung cancer ( NSCLC ) . Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial . PATIENTS AND METHODS Key eligibility criteria included the following : stage IIIB or IV NSCLC ; one to two prior regimens ; Eastern Cooperative Oncology Group performance status of 0 to 2 ; and measurable disease . Patients were r and omly assigned 2:1 to sorafenib ( 400 mg orally twice a day ) plus erlotinib ( 150 mg orally daily ) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab . Treatment efficacy , measured by progression-free survival ( PFS ) and overall response rate ( ORR ) , was compared . Treatment of 168 patients allowed detection of 40 % improvement in the historical PFS of 2.2 months with single-agent erlotinib . RESULTS One hundred sixty-eight patients enrolled from February 2008 to February 2009 . Clinical characteristics of the two groups were similar . ORRs for sorafenib/erlotinib and placebo/erlotinib were 8 % and 11 % , respectively ( P = .56 ) ; disease control rates were 54 % and 38 % , respectively ( P = .056 ) . Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib ( hazard ratio , 0.86 ; 95 % CI , 0.60 to 1.22 ; P = .196 ) . Seventy-two patients consented to analyses of tumor epidermal growth factor receptor ( EGFR ) . In 67 patients with EGFR wild-type ( WT ) tumors , median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib ( P = .018 ) ; median overall survival ( OS ) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib ( P = .019 ) . An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization ( FISH ) EGFR-negative tumors ( P = .064 ) . Both regimens were tolerable , with modest toxicity increase with sorafenib . CONCLUSION Although there was little difference in ORR or PFS , subset analyses in EGFR WT and EGFR FISH-negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS |
12,697 | 29,507,593 | Conclusion The Qigong training can improve the blood glucose status of the type 2 DM patients and has positive effects on the management of type 2 DM . | Objective The purpose of this study was to investigate the effects of Qigong on type 2 diabetes mellitus ( DM ) using the systematic review and meta- analysis . | OBJECTIVE To investigate and compare the effects of Buddhist walking meditation and traditional walking on glycemic control and vascular function in patients with type 2 diabetes mellitus . METHODS Twenty three patients with type 2 diabetes ( 50 - 75 years ) were r and omly allocated into traditional walking exercise ( WE ; n=11 ) or Buddhism-based walking meditation exercise ( WM ; n=12 ) . Both groups performed a 12-week exercise program that consisted of walking on the treadmill at exercise intensity of 50 - 70 % maximum heart rate for 30min/session , 3 times/week . In the WM training program , the participants performed walking on the treadmill while concentrated on foot stepping by voiced " Budd " and " Dha " with each foot step that contacted the floor to practice mindfulness while walking . RESULTS After 12 weeks , maximal oxygen consumption increased and fasting blood glucose level decreased significantly in both groups ( p<0.05 ) . Significant decrease in HbA1c and both systolic and diastolic blood pressure were observed only in the WM group . Flow-mediated dilatation increased significantly ( p<0.05 ) in both exercise groups but arterial stiffness was improved only in the WM group . Blood cortisol level was reduced ( p<0.05 ) only in the WM group . CONCLUSION Buddhist walking meditation exercise produced a multitude of favorable effects , often superior to traditional walking program , in patients with type 2 diabetes Diabetes is the leading cause of major complications , such as end-stage renal disease and lower extremity amputations , and is a significant contributor to ischemic heart disease , stroke , peripheral vascular disease , and vision loss ( 1 ) . There has been increasing acceptance of the importance of individualizing glycemic management and assessment of risk for adverse events , especially hypoglycemia ( 26 ) . This is of great importance for all patients , especially older adults ( aged 65 years ) with comorbid conditions . In 2013 , 12.0 million older adults in the United States had diabetes , comprising 40 % of the 30.2 million persons with the disease ( 7 ) . Older adults account for an estimated 60 % to 70 % of the U.S. Department of Veterans Affairs ( VA ) and U.S. Department of Defense ( DoD ) diabetic population ( largely retirees ) ( VA/DoD. Unpublished data ) . These considerations make safe and effective diabetes management a policy priority for health care providers ( physicians , nurses , dietitians , and pharmacists ) and policymakers in both the VA and the DoD. The 2017 VA/DoD Clinical Practice Guideline ( CPG ) for the Management of Type 2 Diabetes Mellitus in Primary Care offers health care providers an evidence -based framework to evaluate , treat , and manage persons with type 2 diabetes mellitus in the context of their individual needs and preferences ( 8) . The current article is a summary of key CPG recommendations , which was developed with multiple stakeholders to ensure representation by a broad spectrum of clinicians . It provides practice recommendations for the care of patients with diabetes , with an emphasis on shared decision making . Guideline Development and Review Process These recommendations were developed using methods established by the VA/DoD Evidence -Based Practice Work Group ( EBPWG ) ( 9 ) , which are aligned with st and ards for trustworthy guidelines ( 10 ) . The EBPWG and the U.S. Army Medical Comm and selected guideline panel cochairs ( 1 each from the VA and the DoD ) . The cochairs then selected a multidisciplinary panel of practicing clinician stakeholders , including primary care physicians ( family and internal medicine ) , endocrinologists , medical nutritionists , pharmacists , diabetes educators , and nurse practitioners . At the start of the CPG development process and at other key points throughout , all members were required to su bmi t disclosure statements for potential conflicts of interest in the previous 24 months . Verbal affirmations of no conflicts were used during meetings throughout the development process . The project team was also subject to r and om Web-based surveillance ( for example , ProPublica ) . The VA/DoD contracted with The Lewin Group , a third party with expertise in clinical practice guideline development , to facilitate meetings . The guideline panel , in collaboration with the ECRI Institute , developed 9 key questions using the PICOTS ( population , intervention , comparator , outcomes , timing of outcomes measurement , and setting ) format . A systematic search of the peer- review ed literature from January 2009 through March 2016 was conducted to find evidence relevant to the key questions that focused on r and omized trials , systematic review s , and meta-analyses of fair or better quality . One key question was up date d through 14 June 2016 . The search methods and results are detailed in the full guideline ( 8) . The guideline panel rated recommendations by using the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) method ( 11 ) . The guideline panel focused on developing new and up date d recommendations using the evidence review for the key questions . The panel also considered , without a complete review of the relevant evidence , the current applicability of recommendations that were included in the 2010 CPG . As part of the development process , a patient focus group was also convened to better underst and the perspectives of patients receiving diabetes treatment in the VA and the DoD. Five patients were included , consistent with the requirements of the federal Paperwork Reduction Act . All patients had type 2 diabetes and were veterans receiving care in the VA . The focus group explored knowledge of treatment options , views on the delivery of care , patients ' needs and preferences , and the effect of diabetes on their lives . Important concepts that emerged from the focus group were shared with the panel and informed guideline development . It was acknowledged that this convenience sample may not be representative of all VA and DoD patients receiving treatment for type 2 diabetes . The draft guideline was sent to more than 15 expert review ers inside and outside the federal sector . Comments were review ed and , where appropriate , were incorporated into the final guideline based on panel consensus . The VA/DoD EBPWG approved the final document on 3 April 2017 and released it on 17 April 2017 . Recommendations are presented in the Table , and an algorithm for establishing a personalized glycemic goal and treatment plan is presented in the Figure . Key recommendations are review ed in this article . Table . Summary of Recommendations From the 2017 VA/DoD CPG on the Management of Type 2 Diabetes Mellitus Figure . Algorithmic approach to evaluating glycemic control risk factors , setting a personalized glycemic control target range , providing self-management ( including lifestyle and nutrition ) education , and initiating or reevaluating medication therapy . Recommendations Provide Patient-Centered Care and Incorporate Shared Decision Making The CPG strongly encourages clinicians to incorporate shared decision making and partner with their patients . Shared decision making is the process by which the patient and family , in conjunction with the care provider , reach an agreement about a plan of care and treatment . Key principles include readiness of the patient and family , tools with underst and able information about the benefits and harms of all options , and strategies to identify and incorporate patient preferences . Patients can not effectively participate in care and shared decision making unless they underst and diabetes and how they can be involved in planning and carrying out the jointly developed care plan . Shared decision making reinforces a trusted therapeutic relationship and increases patient satisfaction and treatment buy-in with regard to the methods used to reach a particular goal or treatment plan ( 1214 ) . It should be used not only for patients with stable glycemic control but also to assist those who are not able or willing to make lifestyle changes and decisions that affect their diabetes at any time during the course of treatment . At a minimum , shared decision making should be included at the time of diagnosis , during difficulties with management , and at times of transition or development of complications ( 14 ) . Benefits include greater knowledge of medications ( 13 ) and underst and ing of risks ( 14 ) . In addition , patient-centered care and shared decision making together may decrease patient anxiety , increase trust in clinicians ( 15 ) , and improve treatment adherence ( 16 ) . Family involvement should be considered if appropriate , especially in older adults ( 17 ) . Patient information should be culturally appropriate ; underst and able and actionable by people with limited literacy skills ; and accessible to those with physical , sensory , or learning needs ( 18 ) . As part of the patient-centered care approach to diabetes management , clinicians should explore with the patient the outcomes of previous opportunities for shared decision making , their ability to self-manage , prior efforts to change health behaviors , past treatment experiences ( including reasons for discontinuing treatment ) , and relevant clinical outcomes . In actively sharing decisions , they should involve the patient in prioritizing problems to be addressed and setting specific goals regardless of the setting or level of care . Assess Patient Characteristics and Nonglycemic Factors When Interpreting Results of Hemoglobin A1c , Fructosamine , and Other Glycemic Biomarker Testing Many factors affect measurement of hemoglobin A1c ( HbA1c ) besides the level of glycemia ( 19 ) . Because HbA1c level depends on the duration of erythrocyte exposure to glucose , conditions that alter erythrocyte life span affect the measured level of HbA1c ( 20 , 21 ) . Iron deficiency anemia , which prolongs erythrocyte life span and exposes the cell to glucose for a longer period , is associated with falsely elevated HbA1c levels ( 22 ) . In contrast , conditions that shorten erythrocyte life span ( such as hemolytic anemia ) may result in falsely low HbA1c levels . Various other conditions , such as chronic kidney disease , may alter HbA1c measurement . Hemoglobin variants can result in falsely elevated or falsely lowered HbA1c levels , depending on the assay used ( 2325 ) . In addition , oral hypoglycemic agents ( metformin or sulfonylureas ) may alter the relationship between blood glucose and HbA1c levels , although the clinical significance is unclear ( 26 ) . There are also racial/ethnic differences in HbA1c levels for a given level of glycemia . A previous study found that African Americans with prediabetes ( 27 ) had HbA1c values that were 0.4 % higher than among white persons ; those who were within 3 years of diagnosis ( 28 ) also had higher HbA1c values than white persons for any measure of glycemia . This difference can not be explained by measured differences in glycemia , clinical factors known to affect HbA1c measurement , or sociodemographic factors ( 27 , 28 ) . Therefore , it is recommended that a new diagnosis of diabetes be based on a confirmatory fasting blood glucose level of at least 7.0 mmol/L ( 126 mg/dL ) if the initial HbA1c value is 6.5 % to 6.9 % . How and where the HbA1c level is measured can also affect results because of intralaboratory variation ( variation in test accuracy and precision ) and interlaboratory variation ( variation related to use of different test methods ) . A single HbA1c measurement , even from a |
12,698 | 21,402,620 | Addition of cytotoxic chemotherapy to cetuximab significantly increases the risk of high- grade acneiform rash compared with cetuximab monotherapy . | BACKGROUND The effect of chemotherapy on the risk of cetuximab-induced acneiform rash is unknown .
We carried out a systematic review and meta- analysis of published studies to quantify the incidence and risk of high- grade acneiform rash with combination therapy . | This trial assessed pharmacokinetic interactions between cetuximab and irinotecan . Patients were placed in either in group A ( irinotecan 350 mg/m2/3 weeks and 400 mg/m2 cetuximab at week 2 then 250 mg/m2/week ) or group B ( cetuximab weekly starting week 1 then irinotecan starting week 4 ) . Patient plasma or serum sample s from each treatment arm were analysed using HPLC and ELISA . Among 14 patients , compartmental model showed no significant differences in mean plasma AUC at week 1 versus week 4 for irinotecan ( 44,388 versus 39,800 microg/ml/h ) and cetuximab ( 20,441 versus 23,363 microg/ml/h ) , respectively . Half-lifes ( st and ard deviations ) for irinotecan were 16.02 ( + /-8.41 ) h at week 1 and 13.99 ( + /-2.14 ) h at week 4 , and for cetuximab 106 ( + /-32 ) at week 3 and 111 ( + /-30 ) h at week 4 . Mean concentration-versus-time profiles either alone or in combination were superimposable for cetuximab and irinotecan . From this study , we conclude that there is no evidence of pharmacokinetic interaction between irinotecan and cetuximab BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin ( TC ) as first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This multicenter , open-label , phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB ( pleural effusion ) or IV NSCLC , without restrictions by histology or epidermal growth factor receptor expression . Patients were r and omly assigned to cetuximab/TC or TC . TC consisted of paclitaxel ( 225 mg/m(2 ) ) or docetaxel ( 75 mg/m(2 ) ) , at the investigator 's discretion , and carboplatin ( area under the curve = 6 ) on day 1 every 3 weeks for < or = six cycles ; cetuximab ( 400 mg/m(2 ) on day 1 , 250 mg/m(2 ) weekly ) was administered until progression or unacceptable toxicity . The primary end point was progression-free survival assessed by independent radiologic review committee ( PFS-IRRC ) ; overall response rate ( ORR ) , overall survival ( OS ) , quality of life ( QoL ) , and safety were key secondary end points . PFS and ORR assessed by investigators were also evaluated . Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC ( hazard ratio [ HR ] = 0.902 ; 95 % CI , 0.761 to 1.069 ; P = .236 ) . Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC ( HR = 0.890 ; 95 % CI , 0.754 to 1.051 ; P = .169 ) . ORR-IRRC was 25.7 % with cetuximab/TC versus 17.2 % with TC ( P = .007 ) . The safety profile of this combination was manageable and consistent with its individual components . CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point , PFS-IRRC . There was significant improvement in ORR by IRRC . The difference in OS favored cetuximab but did not reach statistical significance BACKGROUND The Lung Cancer Cetuximab Study is an open-label , r and omized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone , in patients with advanced EGFR-expressing , non-small-cell lung cancer ( NSCLC ) . End points of the study are activity , safety and pharmacokinetics . PATIENTS AND METHODS Following r and omization , for a maximum of eight cycles , patients received three-weekly cycles of cisplatin ( 80 mg/m(2 ) , day 1 ) and vinorelbine ( 25 mg/m(2 ) on days 1 and 8) alone or following cetuximab treatment ( initial dose 400 mg/m(2 ) , followed by 250 mg/m(2 ) weekly thereafter ) . RESULTS Eighty-six patients were r and omly allocated to the study ( 43 per arm ) . Confirmed response rates were 28 % in the cisplatin/vinorelbine arm ( A ) and 35 % in the cetuximab plus cisplatin/vinorelbine arm ( B ) . Median progression-free survival ( PFS ) was 4.6 months in arm A and 5.0 months in arm B , with PFS rates at 12 months of 0 % and 15 % , respectively . Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0 % and 16 % , respectively . The cetuximab combination was well tolerated . CONCLUSION In the first-line treatment of advanced NSCLC , the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone 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 ] . ) BACKGROUND This two-part phase Ib/II study investigated the feasibility of administering cetuximab in combination with oxaliplatin and infusional 5-fluorouracil (5-FU)/folinic acid ( FA ) in a weekly schedule ( AIO FUFOX protocol ) as first-line treatment in patients with epidermal growth factor receptor-detectable advanced colorectal cancer . PATIENTS AND METHODS Cetuximab was administered weekly : 400 mg/m(2 ) initial dose , then 250 mg/m(2 ) and FUFOX : oxaliplatin 50 mg/m(2 ) , FA 500 mg/m(2 ) and 5-FU as a 24-h infusion at either 1500 or 2000 mg/m(2 ) administered for 4 weeks followed by a 1-week rest ( one cycle ) . RESULTS Dose-limiting toxicity ( grade 3 diarrhea ) occurred in 3 of 14 assessable patients receiving 5-FU at st and ard 2000 mg/m(2 ) . This dose was administered to a further 25 patients . Cetuximab combined with FUFOX was generally well tolerated with the most common grade 3/4 adverse events being diarrhea ( 27 % ) and paresthesia ( 16 % ) . The confirmed response rate for patients receiving 5-FU at st and ard 2000 mg/m(2 ) ( N = 41 ) was 56 % , with a median duration of 9.3 months . Median progression-free and overall survival times including all 49 patients were 8.1 ( 95 % confidence interval 6.0 - 9.7 ) and 28.2 months , respectively . Cetuximab pharmacokinetics seemed not to be different for combination with FUFOX compared with cetuximab/irinotecan combinations . CONCLUSION This protocol is well tolerated and shows promising efficacy supporting further investigation PURPOSE To determine the efficacy of cetuximab in patients with recurrent or progressive non-small-cell lung cancer ( NSCLC ) after receiving at least one prior chemotherapy regimen . PATIENTS AND METHODS This was an open-label , phase II study of patients with epidermal growth factor receptor ( EGFR ) -positive and EGFR-negative advanced NSCLC with Eastern Cooperative Oncology Group performance status 0 to 1 . Patients received cetuximab 400 mg/m2 intravenously ( IV ) during 120 minutes on week 1 followed by weekly doses of cetuximab 250 mg/m2 IV during 60 minutes . A cycle was considered as 4 weeks of treatment and therapy was continued until disease progression or intolerable toxicities . The primary end point was to assess response rate . Secondary end points included an estimation of time to progression and survival . RESULTS Patient and disease characteristics ( n = 66 ) included EGFR-positive status ( n = 60 ) ; EGFR-negative status ( n = 6 ) ; number of prior regimens ( one , n = 28 ; two , n = 27 ; > or = three , n = 11 ) ; male ( n = 41 ) ; female ( n = 25 ) ; adenocarcinoma ( n = 36 ) ; and smoking status ( never , n = 13 ; former , n = 45 ; current , n = 8) . Grade 3/4 toxicities included acne-like rash ( 6.1 % ) , anaphylactic reactions ( 1.5 % ) , and diarrhea ( 1.5 % ) . The response rate for all patients ( n = 66 ) was 4.5 % ( 95 % CI , 0.9 % to 12.7 % ) and the stable disease rate was 30.3 % ( 95 % CI , 19.6 % to 42.9 % ) . The response rate for patients with EGFR-positive tumors ( n = 60 ) was 5 % ( 95 % CI , 1.0 % to 13.9 % ) . The median time to progression for all patients was 2.3 months ( 95 % CI , 2.1 to 2.6 months ) and median survival time was 8.9 months ( 95 % CI , 6.2 to 12.6 months ) . CONCLUSION Although the response rate with single-agent cetuximab in this heavily pretreated patient population with advanced NSCLC was only 4.5 % , the disease control rates and overall survival seem comparable to that of pemetrexed , docetaxel , and erlotinib in similar groups of patients BACKGROUND Use of cetuximab , a monoclonal antibody targeting the epidermal growth factor receptor ( EGFR ) , has the potential to increase survival in patients with advanced non-small-cell lung cancer . We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer . METHODS In a multinational , multicentre , open-label , phase III trial , chemotherapy-naive patients ( > or=18 years ) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy . Chemotherapy was cisplatin 80 mg/m(2 ) intravenous infusion on day 1 , and vinorelbine 25 mg/m(2 ) intravenous infusion on days 1 and 8 of every 3-week cycle ) for up to six cycles . Cetuximab-at a starting dose of 400 mg/m(2 ) intravenous infusion over 2 h on day 1 , and from day 8 onwards at 250 mg/m(2 ) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred . The primary endpoint was overall survival . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS Between October , 2004 , and January , 2006 , 1125 patients were r and omly assigned to chemotherapy plus cetuximab ( n=557 ) or chemotherapy alone ( n=568 ) . Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group ( median 11.3 months vs 10.1 months ; hazard ratio for death 0.871 [ 95 % CI 0.762 - 0.996 ] ; p=0.044 ) . The main cetuximab-related adverse event was acne-like rash ( 57 [ 10 % ] of 548 , grade 3 ) . INTERPRETATION Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer . FUNDING Merck BACKGROUND Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck . We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . METHODS We r and omly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin ( at a dose of 100 mg per square meter of body-surface area on day 1 ) or carboplatin ( at an area under the curve of 5 mg per milliliter per minute , as a 1-hour intravenous infusion on day 1 ) plus fluorouracil ( at a dose of 1000 mg per square meter per day for 4 days ) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab ( at a dose of 400 mg per square meter initially , as a 2-hour intravenous infusion , then 250 mg per square meter , as a 1-hour intravenous infusion per week ) for a maximum of 6 cycles . Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects , whichever occurred first . RESULTS Adding cetuximab to platinum-based chemotherapy with fluorouracil ( platinum-fluorouracil ) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab ( hazard ratio for death , 0.80 ; 95 % confidence interval , 0.64 to 0.99 ; P=0.04 ) . The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months ( hazard ratio for progression , 0.54 ; P<0.001 ) and increased the response rate from 20 % to 36 % ( P<0.001 ) . The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia ( 19 % and 13 % , respectively ) , neutropenia ( 23 % and 22 % ) , and thrombocytopenia ( 11 % in both groups ) . Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group ( P=0.02 ) . Of 219 patients receiving cetuximab , 9 % had grade 3 skin reactions and 3 % had grade 3 or 4 infusion-related reactions . There were no cetuximab-related deaths . CONCLUSIONS As compared with platinum-based chemotherapy plus fluorouracil alone , cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00122460 . PURPOSE To evaluate the ability of either oral minocycline , topical tazarotene or both , to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy . PATIENTS AND METHODS Metastatic colorectal cancer patients preparing to initiate cetuximab were r and omly assigned to receive daily oral minocycline or placebo , and to receive topical tazarotene application to either left or right side of the face . Both therapies were administered for 8 weeks . RESULTS Forty-eight eligible patients were r and omly assigned to minocycline ( n = 24 ) or placebo ( n = 24 ) . Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4 . At week 4 , a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm ( 20 % v 50 % , P = .05 ) . Facial photographs , obtained at week 4 , were review ed for rash global severity . Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo ( 20 % v 42 % , P = .13 ) . The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8 . Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm , and none in the minocycline arm . There was no observed clinical benefit to tazarotene application . Tazarotene treatment was associated with significant irritation , causing its discontinuation in one third of patients . CONCLUSION Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment . Topical tazarotene is not recommended for management of cetuximab-related rash Objective : Epidermal growth factor receptor inhibitors can result in a severe rash in 5–10 % of patients and can detract from quality of life . The objective of this study was to identify clinical predictors of severe rash in the hope of utilizing such factors in the design of future rash palliative and prevention trials . Methods : 933 cetuximab-treated patients enrolled on N0147 , an adjuvant chemotherapy trial for colon cancer , were evaluated for clinical risk factors of severe rash . Results : Within this cohort , 50 patients ( 5 % ) developed a severe rash ( grade 3 ) . More men compared to women developed such a rash : 34 ( 7 % ) versus 16 ( 3 % ) ( multivariate odds ratio = 2.12 ; 95 % confidence interval : 1.14–3.88 ; p = 0.017 ) . A greater number of younger patients ( < 70 years of age ) also developed a rash : 48 ( 6 % ) versus 2 ( 1 % ) ( multivariate odds ratio = 0.21 ; 95 % confidence interval : 0.05–0.88 ; p = 0.032 ) . Race and performance score were not predictive . Conclusion : Men and younger patients are at greater risk for a severe cetuximab-induced rash although overall the risk is low . These observations are particularly important in design ing future rash prevention and palliation trials OBJECTIVES Determine if cetuximab dose escalation to induce grade 2 rash correlates with anti-tumor activity and if sera-based markers could predict likelihood of response . METHODS Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m(2 ) , then 250 mg/m(2 ) weekly for two 3-week cycles . Patients who had stable disease ( SD ) and < grade 2 rash were dose escalated in 75 mg/m(2 ) increments every 3 weeks until grade 2 rash or to a maximum weekly dose of 400 mg/m(2 ) . Pre- and post-treatment serum sample s were evaluated for potential predictive markers of response . RESULTS One of 25 patients achieved partial remission ( PR ) and 9 patients had SD . The median progression free survival was 2.1 months ; the 1-year survival rate was 54.8 % . Rash ( 96 % ) was the most common drug-related adverse event . At first response assessment , 4 patients remained at 250 mg/m(2 ) ; 8 patients were dose-escalated to 325 mg/m(2 ) ; of these , 4 ultimately were increased to 400 mg/m(2 ) . Patients with progressive disease ( PD ) were removed from the study . Ninety-two serologic markers were analyzed from 20 patients to identify markers associated with clinical activity and /or predictive of outcome . Pretreatment levels of twelve markers were significantly elevated in patients exhibiting PD versus SD or PR ; however , changes in marker levels during the course of treatment were not significant indicators of response . CONCLUSIONS Single-agent cetuximab showed minimal activity in patients with recurrent ovarian cancer . Patients with elevated levels of 12 serologic markers at baseline were more likely to have earlier disease progression PURPOSE To determine the response rate , time to disease progression , survival duration and rate , and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer . PATIENTS AND METHODS Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial . Patients were treated with cetuximab at an initial dose of 400 mg/m(2 ) , followed by 250 mg/m(2 ) weekly for 7 weeks . Gemcitabine was administered at 1,000 mg/m(2 ) for 7 weeks , followed by 1 week of rest . In subsequent cycles , cetuximab was administered weekly , and gemcitabine was administered weekly for 3 weeks every 4 weeks . RESULTS Sixty-one patients were screened for EGFR expression , 58 patients ( 95 % ) had at least 1 + staining , and 41 were enrolled onto the trial . Five patients ( 12.2 % ) achieved a partial response , and 26 ( 63.4 % ) had stable disease . The median time to disease progression was 3.8 months , and the median overall survival duration was 7.1 months . One-year progression-free survival and overall survival rates were 12 % and 31.7 % , respectively . The most frequently reported grade 3 or 4 adverse events were neutropenia ( 39.0 % ) , asthenia ( 22.0 % ) , abdominal pain ( 22.0 % ) , and thrombocytopenia ( 17.1 % ) . CONCLUSION Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer . Further clinical investigation is warranted PURPOSE This multicenter , open-label , phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-naïve , epidermal growth factor receptor-positive , stage IV non-small-cell lung cancer . Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate , time to progression , and overall survival . PATIENTS AND METHODS Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab , carboplatin , and gemcitabine . An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week , followed by weekly doses of 250 mg/m2 . Carboplatin ( area under the curve = 5 , day 1 ) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks . Patients were evaluated for tumor response after every two cycles of therapy . RESULTS The most frequently reported adverse events related to cetuximab included an acne-like rash ( 88.6 % ) , dry skin ( 34.3 % ) , asthenia and skin disorders ( 31.4 % ) , mucositis/stomatitis ( 25.7 % ) , fever/chills ( 20 % ) , and nausea/vomiting ( 17.1 % ) . The majority of these toxicities were mild to moderate . One patient withdrew from the study because of a grade 3 allergic reaction . Myelosuppression was the most frequently observed toxicity related to chemotherapy . Responses among 35 assessable patients included 10 partial responses ( 28.6 % ) . Twenty-one patients had stable disease . The median time to progression was 165 days , and the median overall survival was 310 days . CONCLUSION The combination of cetuximab , carboplatin , and gemcitabine was well tolerated with an acceptable toxicity profile . Most grade 3 adverse events were attributable to chemotherapy . The response rate and median survival are encouraging and warrant additional investigation PURPOSE To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor . PATIENTS AND METHODS Phase II , open-label clinical trial . Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation . Patients were required to have received irinotecan , either alone or in a combination regimen , and to have demonstrated clinical failure on this regimen before study entry . Cetuximab was administered weekly by intravenous infusion . The first dose of 400 mg/m(2 ) was given during the course of 2 hours . Subsequent weekly treatments were given at a dose of 250 mg/m(2 ) during the course of 1 hour . RESULTS Fifty-seven eligible patients were treated . All were assessable for toxicity and response . The most commonly encountered grade 3 to 4 adverse events , regardless of relationship to study drug , were an acne-like skin rash , predominantly on the face and upper torso ( 86 % with any grade ; 18 % with grade 3 ) , and a composite of asthenia , fatigue , malaise , or lethargy ( 56 % with any grade , 9 % with grade 3 ) . Two patients ( 3.5 % ) experienced grade 3 allergic reactions requiring discontinuation of study treatment . A third patient experienced a grade 3 allergic reaction that resolved , and the patient continued on the study . Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated . Five patients ( 9 % ; 95 % CI , 3 % to 19 % ) achieved a partial response . Twenty-one additional patients had stable disease or minor responses . The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months . CONCLUSION Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor . Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease |
12,699 | 22,299,707 | There was a statistically significant advantage to the use of and rogen suppression , in terms of both overall survival and disease free survival , when compared to radiotherapy alone .
The use of long-term goserelin ( up to three years ) was the strategy providing the higher magnitude of clinical benefit .
Complete hormonal blockade was not shown to be superior to goserelin monotherapy .
Conclusions Based on the findings of this systematic review , the evidence supports the use of and rogen suppression with goserelin monotherapy as the st and ard treatment for patients with prostate cancer treated with radiotherapy , which are at high risk of recurrence or metastases | Background Locally advanced prostate cancer is often associated with elevated recurrence rates .
Despite the modest response observed , external-beam radiotherapy has been the preferred treatment for this condition .
More recent evidence from r and omised trials has demonstrated clinical benefit with the combined use of and rogen suppression in such cases .
The aim of this meta- analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival , disease-free survival and toxicity . | BACKGROUND It is not known whether short-term and rogen-deprivation therapy ( ADT ) before and during radiotherapy improves cancer control and overall survival among patients with early , localized prostate adenocarcinoma . METHODS From 1994 through 2001 , we r and omly assigned 1979 eligible patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a prostate-specific antigen ( PSA ) level of 20 ng per milliliter or less to radiotherapy alone ( 992 patients ) or radiotherapy with 4 months of total and rogen suppression starting 2 months before radiotherapy ( radiotherapy plus short-term ADT , 987 patients ) . The primary end point was overall survival . Secondary end points included disease-specific mortality , distant metastases , biochemical failure ( an increasing level of PSA ) , and the rate of positive findings on repeat prostate biopsy at 2 years . RESULTS The median follow-up period was 9.1 years . The 10-year rate of overall survival was 62 % among patients receiving radiotherapy plus short-term ADT ( the combined-therapy group ) , as compared with 57 % among patients receiving radiotherapy alone ( hazard ratio for death with radiotherapy alone , 1.17 ; P=0.03 ) . The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8 % to 4 % ( hazard ratio for radiotherapy alone , 1.87 ; P=0.001 ) . Biochemical failure , distant metastases , and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT . Acute and late radiation-induced toxic effects were similar in the two groups . The incidence of grade 3 or higher hormone-related toxic effects was less than 5 % . Re analysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients , with no significant reductions among low-risk patients . CONCLUSIONS Among patients with stage T1b , T1c , T2a , or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less , the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival . According to post hoc risk analysis , the benefit was mainly seen in intermediate-risk , but not low-risk , men . ( Funded by the National Cancer Institute ; RTOG 94 - 08 Clinical Trials.gov number , NCT00002597 . ) Purpose : Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer . Although many of the adverse effects of castration therapy are manageable , they can have a detrimental effect on quality of life . Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ( ‘ Casodex ’ ) 150 mg adjuvant to radiotherapy in patients with T1 - 4 , M0 , any n prostate cancer . Methods : The subset of patients within the early prostate cancer ( EPC ) program who received radiotherapy with curative intent ( n = 1,370 ) were included in the analysis . These patients were r and omized to receive oral bicalutamide 150 mg once daily ( n = 699 ) or placebo ( n = 671 ) . Results : The median follow-up for patients included in this analysis was 7.2 years . In patients with locally advanced disease ( n = 305 ) , bicalutamide adjuvant to radiotherapy significantly improved : progression-free survival ( PFS ) , reducing the risk of objective progression by 44 % compared with radiotherapy alone [ hazard ratio ( HR ) 0.56 ; 95 % confidence interval ( CI ) 0.40 , 0.78 ; P < 0.001 ) . Prostate-specific antigen (PSA)–PFS , reducing the risk of PSA progression by 59 % compared with radiotherapy alone ( HR 0.41 ; 95 % CI 0.30 , 0.55 ; P < 0.001 ) . Overall survival , reducing the risk of death by 35 % compared with radiotherapy alone ( HR 0.65 ; 95 % CI 0.44 , 0.95 ; P = 0.03 ) . This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths ( 16.1 vs 24.3 % , respectively ) . There was no significant difference in PFS or overall survival in patients with localized disease ( n = 1,065 ) . Conclusions : In patients with locally advanced disease , bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival , PFS and PSA – PFS compared with radiotherapy alone . The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy ( Bolla et al. in Lancet 360:103–108 , 2002 ; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285–1290 , 2005 ) . In addition , the clinical benefit of bicalutamide 150 mg in locally advanced patients , but not in those with localized disease , is consistent with the overall results from the EPC program ( McLeod et al. BJU Int 97:247–254 , 2006 ) . Given the quality -of-life advantages of bicalutamide relative to castration , bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer PURPOSE We evaluated the benefits and sequencing of and rogen suppression ( AS ) administered with external beam radiation therapy ( EBRT ) in T2-T3 prostate cancers . MATERIAL S AND METHODS Between 1990 and 1999 , 481 patients were entered in 2 successive , prospect i ve , r and omized studies , including 161 in the study 1 and 325 in study 2 . Eligible patients had clinical stages T2-T3 prostate cancer . In the first study ( L-101 ) subjects were r and omly allocated among EBRT alone ( group 1 ) , EBRT preceded by 3 months of AS ( group 2 ) , and neoadjuvant , concomitant and adjuvant AS for a total of 10 months ( group 3 ) . In the second study ( L-200 ) we analyzed neoadjuvant and concomitant AS ( total 5 months ) vs neoadjuvant , concomitant and short course adjuvant ( total 10 months ) AS with EBRT . In each study we used a total AS ( a luteinizing hormone-releasing hormone agonist plus an anti and rogen ) and a st and ard dose of radiation therapy at that time . Patient characteristics were well balanced in regard to age , stage , prostate specific antigen and Gleason score . No biochemical evidence of disease ( BNED ) was defined as an end point according to the Vancouver rule . RESULTS In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42 % , 66 % and 69 % in groups 1 to 3 , respectively . BNED was significantly different between groups 1 and 2 ( p = 0.009 ) and between groups 1 and 3 ( p = 0.003 ) but not between groups 2 and 3 ( p = 0.6 ) . Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score ( p = 0.001 ) , 1.4 for PSA ( p = 0.002 ) , 0.5 for group 1 vs group 2 ( p = 0.01 ) and 0.35 for group 1 vs group 3 ( p = 0.008 ) . In study 2 BNED at 4 years was 65 % . There was no significant difference between arms 1 and 2 ( p = 0.55 ) . CONCLUSIONS The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers . Moreover , in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients BACKGROUND We conducted a r and omized , prospect i ve trial comparing external irradiation with external irradiation plus goserelin ( an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion ) in patients with locally advanced prostate cancer . METHODS From 1987 to 1995 , 415 patients with locally advanced prostate cancer were r and omly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin . The patients had a median age of 71 years ( range , 51 to 80 ) . Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost . Patients in the combined-treatment group received 3.6 mg of goserelin ( Zoladex ) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years ; those patients also received cyproterone acetate ( 150 mg orally per day ) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin . RESULTS Data were available for analysis on 401 patients . The median follow-up was 45 months . Kaplan-Meier estimates of overall survival at five years were 79 percent ( 95 percent confidence interval , 72 to 86 percent ) in the combined-treatment group and 62 percent ( 95 percent confidence interval , 52 to 72 percent ) in the radiotherapy group ( P=0.001 ) . The proportion of surviving patients who were free of disease at five years was 85 percent ( 95 percent confidence interval , 78 to 92 percent ) in the combined-treatment group and 48 percent ( 95 percent confidence interval , 38 to 58 percent ) in the radiotherapy group ( P<0.001 ) . CONCLUSIONS Adjuvant treatment with goserelin , when started simultaneously with external irradiation , improves local control and survival in patients with locally advanced prostate cancer PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes . PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen < /= 15 ng/mL were r and omly assigned to a total dose of either 70.2 Gray equivalents ( GyE ; conventional ) or 79.2 GyE ( high ) . No patient received and rogen suppression therapy with radiation . Local failure ( LF ) , biochemical failure ( BF ) , and overall survival ( OS ) were outcomes . Results A total of 393 men were r and omly assigned , and median follow-up was 8.9 years . Men receiving high-dose radiation therapy were significantly less likely to have LF , with a hazard ratio of 0.57 . The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4 % for conventional-dose and 16.7 % for high-dose radiation therapy ( P < .0001 ) . This difference held when only those with low-risk disease ( n = 227 ; 58 % of total ) were examined : 28.2 % for conventional and 7.1 % for high dose ( P < .0001 ) . There was a strong trend in the same direction for the intermediate-risk patients ( n = 144 ; 37 % of total ; 42.1 % v 30.4 % , P = .06 ) . Eleven percent of patients subsequently required and rogen deprivation for recurrence after conventional dose compared with 6 % after high dose ( P = .047 ) . There remains no difference in OS rates between the treatment arms ( 78.4 % v 83.4 % ; P = .41 ) . Two percent of patients in both arms experienced late grade > /= 3 genitourinary toxicity , and 1 % of patients in the high-dose arm experienced late grade > /= 3 GI toxicity . CONCLUSION This r and omized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation . This was achieved without an increase in grade > /= 3 late urinary or rectal morbidity PURPOSE In a r and omized study we compared the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for locally advanced prostate cancer . Patients who were treated only with radiotherapy initially underwent castration therapy at clinical progression , providing the opportunity to compare immediate vs deferred endocrine intervention . MATERIAL S AND METHODS In this prospect i ve study 91 patients with locally advanced prostate cancer were r and omized to receive external beam radiotherapy ( 46 ) or combined orchiectomy and radiotherapy ( 45 ) after surgical lymph node staging . Survival rates were calculated . RESULTS During 14 to 19 years of followup 87 % of the patients in the radiotherapy group and 76 % in the combined orchiectomy and radiotherapy group died ( log rank p = 0.03 ) . Prostate cancer mortality was 57 % and 36 % , respectively ( log rank p = 0.02 ) . The difference in favor of combined treatment was mainly caused by lymph node positive tumors . For node negative tumors there was no significant difference in the survival rates . CONCLUSIONS Immediate and rogen deprivation should be considered instead of deferred endocrine treatment started at clinical progression for prostate cancer with spread to regional lymph nodes . While awaiting evidence from r and omized trials , one should consider full dose radiotherapy for local control of locally advanced prostate cancer even when it is lymph node positive PURPOSE Radiation Therapy Oncology Group ( RTOG ) 8610 was the first phase III r and omized trial to evaluate neoadjuvant and rogen deprivation therapy ( ADT ) in combination with external-beam radiotherapy ( EBRT ) in men with locally advanced prostate cancer . This report summarizes long-term follow-up results . MATERIAL S AND METHODS Between 1987 and 1991 , 456 assessable patients ( median age , 70 years ) were enrolled . Eligible patients had bulky ( 5 x 5 cm ) tumors ( T2 - 4 ) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system . Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT , or they received EBRT alone . Study end points included overall survival ( OS ) , disease-specific mortality ( DSM ) , distant metastasis ( DM ) , disease-free survival ( DFS ) , and biochemical failure ( BF ) . RESULTS Ten-year OS estimates ( 43 % v 34 % ) and median survival times ( 8.7 v 7.3 years ) favored ADT and EBRT , respectively ; however , these differences did not reach statistical significance ( P = .12 ) . There was a statistically significant improvement in 10-year DSM ( 23 % v 36 % ; P = .01 ) , DM ( 35 % v 47 % ; P = .006 ) , DFS ( 11 % v 3 % ; P < .0001 ) , and BF ( 65 % v 80 % ; P < .0001 ) with the addition of ADT , but no differences were observed in the risk of fatal cardiac events . CONCLUSION The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinical ly meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events BACKGROUND The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant and rogen deprivation therapy ( NADT ) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer . Here we report the 10-year results . METHODS Between June , 1996 , and February , 2000 , 818 men with T2b , T2c , T3 , and T4 N0 M0 prostate cancers were r and omly assigned to receive radiotherapy alone , 3 months of NADT plus radiotherapy , or 6 months of NADT plus radiotherapy . The radiotherapy dose for all groups was 66 Gy , delivered to the prostate and seminal vesicles ( excluding pelvic nodes ) in 33 fractions of 2 Gy per day ( excluding weekends ) over 6·5 - 7·0 weeks . NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day . NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group . Primary endpoints were prostate-cancer-specific mortality and all-cause mortality . Treatment allocation was open label and r and omisation was done with a minimisation technique according to age , clinical stage , tumour grade , and initial prostate-specific antigen concentration ( PSA ) . Analysis was by intention-to-treat . The trial has been closed to follow-up and all main endpoint analyses are completed . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000237482 . FINDINGS 802 men were eligible for analysis ( 270 in the radiotherapy alone group , 265 in the 3-month NADT group , and 267 in the 6-month NADT group ) after a median follow-up of 10·6 years ( IQR 6·9 - 11·6 ) . Compared with radiotherapy alone , 3 months of NADT decreased the cumulative incidence of PSA progression ( adjusted hazard ratio 0·72 , 95 % CI 0·57 - 0·90 ; p=0·003 ) and local progression ( 0·49 , 0·33 - 0·73 ; p=0·0005 ) , and improved event-free survival ( 0·63 , 0·52 - 0·77 ; p<0·0001 ) . 6 months of NADT further reduced PSA progression ( 0·57 , 0·46 - 0·72 ; p<0·0001 ) and local progression ( 0·45 , 0·30 - 0·66 ; p=0·0001 ) , and led to a greater improvement in event-free survival ( 0·51 , 0·42 - 0·61 , p<0·0001 ) , compared with radiotherapy alone . 3-month NADT had no effect on distant progression ( 0·89 , 0·60 - 1·31 ; p=0·550 ) , prostate cancer-specific mortality ( 0·86 , 0·60 - 1·23 ; p=0·398 ) , or all-cause mortality ( 0·84 , 0·65 - 1·08 ; p=0·180 ) , compared with radiotherapy alone . By contrast , 6-month NADT decreased distant progression ( 0·49 , 0·31 - 0·76 ; p=0·001 ) , prostate cancer-specific mortality ( 0·49 , 0·32 - 0·74 ; p=0·0008 ) , and all-cause mortality ( 0·63 , 0·48 - 0·83 ; p=0·0008 ) , compared with radiotherapy alone . Treatment-related morbidity was not increased with NADT within the first 5 years after r and omisation . INTERPRETATION 6 months of neoadjuvant and rogen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer , particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged and rogen deprivation . FUNDING Australian Government National Health and Medical Research Council , Hunter Medical Research Institute , AstraZeneca , and Schering-Plough Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospect ively r and omized to receive either radiation alone or radiation and adjuvant estrogen ( diethylstilbestrol ) . No patient had received any prior definitive treatment for cancer . Forty patients were r and omized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen . The median follow-up for all surviving patients was 14.5 years . Whether analyzed according to the original r and omization or according to the treatment actually received , disease-free survival in the adjuvant estrogen group was strikingly and significantly higher than in the radiation-only group . At 5 , 10 , and 15 years patients receiving adjuvant estrogen had respective disease-free survival rates of 71 % , 63 % , and 63 % compared with 49 % , 43 % , and 35 % in patients having radiation only ( p = 0.008 ) . However , because of greater intercurrent disease-related mortality in patients receiving estrogen , there was no improvement in survival . This study suggests that a prospect i ve r and omized evaluation of early and rogen deprivation with orchiectomy or with one of the nonestrogenic agents should be undertaken and that patients receiving early and rogen deprivation should not be included in series reporting on the curative potential of radiation as a single modality PURPOSE To up date the effect of immediate and rogen suppression in conjunction with st and ard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate . MATERIAL S AND METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group 85 - 31 ) of st and ard external-beam irradiation plus immediate and rogen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three patients in this trial had histologically involved lymph nodes . Ninety-eight patients received radiation plus immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) , whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median follow-up of 6.5 years for all patients and 9.5 years for living patients , estimated progression-free survival with prostate-specific antigen ( PSA ) level less than 1.5 ng/mL at 5 and 9 years was 54 % and 33 % , respectively , for patients who received immediate LHRH agonist versus 10 % [ corrected ] and 4 % for patients who received radiation alone with hormonal manipulation instituted at time of relapse ( P < .0001 ) . Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed : absolute survival , disease-specific failure , metastatic failure , and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. CONCLUSION Pending the results of r and omized trials , patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes ( pathologic node-positive or clinical stage D1 ) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse PURPOSE We determined the risk of recurrence in men enrolled on a r and omized trial for prostate cancer who were treated with radiation therapy ( RT ) alone or in conjunction with combined or less than combined and rogen suppression therapy ( AST ) . PATIENTS AND METHODS Between 1995 and 2001 , 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were r and omly assigned to receive RT or RT and AST , which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an anti and rogen . A post-r and om assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen ( PSA ) recurrence was significantly associated with months of anti and rogen use ; regression analysis adjusted for known prognostic factors , comorbidity score , and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the anti and rogen . RESULTS After a median follow-up of 8.2 years ( interquartile range,7.0 to 9.5 years ) , 81 men sustained PSA recurrence . An increasing PSA level ( P < .001 ) ; Gleason score of 8 , 9 , or 10 ( P < .001 ) ; and clinical category T2 disease ( P = .005 ) were significantly associated with an increased risk of recurrence . However , recurrence risk was significantly decreased ( adjusted hazard ratio , 0.81 ; 95 % CI , 0.72 to 0.92 ; P = .001 ) with each additional month of anti and rogen use after analysis was adjusted for these known prognostic factors . CONCLUSION Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the anti and rogen |
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