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12,500 | 27,329,288 | Our finding demonstrated that lenalidomide plus anti-CD20 mAbs could be an efficient therapy regimen for relapsed/refractory CLL patients , especially for those with high-risk cytogenetic factor | Therapeutic results of relapsed/refractory chronic lymphocytic leukemia ( CLL ) are very disappointing at present .
Lenalidomide has been proved to be effective for relapsed/refractory CLL as a single agent or in combination with various chemo-immunotherapeutic regimens .
However , current clinical experience in its usage is still limited .
Because of existing considerable variability in different studies , a systematic review and meta- analysis was conducted to describe overall response rate ( ORR ) of lenalidomide in patients with relapsed/refractory CLL . | PURPOSE A phase I/II trial to assess safety and efficacy of the combination bendamustine , rituximab , and lenalidomide ( BRL ) in patients with chronic lymphocytic leukemia ( CLL ) . PATIENTS AND METHODS Seventeen relapsed or refractory ( R/R ) and five previously untreated ( FL ) CLL patients were enrolled in the trial . In the R/R cohort , four different dose levels of lenalidomide ( maximum 15 mg/d ) were used . In the FL cohort , lenalidomide was dose escalated from 5 mg/d to 15 mg/d . Bendamustine was used at doses of 50 or 90 mg/m(2 ) for R/R or FL treatment , respectively . 375 mg/m(2 ) Rituximab were used for the first and 500 mg/m(2 ) for subsequent treatment courses . Treatment consisted of up to six courses of 28 d. RESULTS The maximal tolerable dose of lenalidomide was 5 mg/d . The response rate was 47.1 % in R/R and 60 % in FL patients . Median progression-free survival was 8.0 months . Median overall survival was 22.9 and 12.3 months , respectively , in R/R and FL patients . Grade 3/4 hematological toxicity was observed in 71.4 % , and severe infections in 47.6 % of patients . Due to high toxicity and low response rate of BRL , the trial was closed prematurely . CONCLUSION BRL was associated with a high toxicity rate , a high number of treatment interruptions , and a low remission rate . Therefore , BRL can not be considered an appropriate treatment option for patients with CLL N 1988 , THE National Cancer Institute-sponsored Working Group ( NCI-WC ) on chronic lymphocytic leukemia ( CLL ) published guidelines for the design and conduct of clinical trials in CLL with two major objectives : first , to facilitate comparisons of results of clinical trials in CLL by providing st and ardized eligibility , response , and toxicity criteria ; and , second , to encourage a framework on which to evaluate new scientific studies related to our increasing underst and ing of the biology and immunology of this disease . ' These guidelines were rapidly adopted by the majority of the clinical trials community , and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine . The differences between these guidelines and those subsequently published by the International Working Group on CLL ( IWCLL ) , which were general- practice recommendations ' are listed in Table 1 . For diagnosis , the NCI-WC requires a lymphocyte count of 5 X loy & which is lower than the 10 X 109/L required by the IWCLL , unless the lymphocytes are B cells and the bone marrow is involved . To be considered a complete remission ( CR ) , the NCI-WC criteria specify that less than 30 % lymphocytes must be present in the bone marrow , with a recommendation that the clinical significance of lymphoid nodules be assessed prospect ively ( Table 1 ) ; the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR . The IWCLL uses a shift in clinical stage as the sole index of partial remission ( PR ) , whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift . The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy , hematologic toxicity , and other important components for clinical trials design . The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years . Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and , also , with the experience following the use of newer , more effective agents , such as fludarabine . " ' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group , it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version PURPOSE Patients with relapsed or refractory chronic lymphocytic leukemia ( CLL ) have profound immune defects and limited treatment options . Given the dramatic activity of lenalidomide in other B-cell malignancies and its pleotropic immunomodulatory effects , we conducted a phase II trial of this agent in CLL . PATIENTS AND METHODS Patients with relapsed or refractory B-cell CLL ( B-CLL ) were eligible if they required treatment as per the National Cancer Institute Working Group 1996 guidelines . Lenalidomide was administered orally at 25 mg on days 1 through 21 of a 28-day cycle . Response was assessed after each cycle . Patients were to continue treatment until disease progression , unacceptable toxicity , or complete remission . Rituximab was added to lenalidomide on disease progression . RESULTS Forty-five patients were enrolled , with a median age of 64 years . Sixty-four percent of the patients had Rai stage III or IV disease , and 51 % were refractory to fludarabine . The overall response rate was 47 % , with 9 % of the patients attaining a complete remission . Fatigue , thrombocytopenia , and neutropenia were the most common adverse effects noted in 83 % , 78 % , and 78 % of the patients , respectively . CONCLUSION Lenalidomide is clinical ly active in patients with relapsed or refractory B-CLL . These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder Patients with chronic lymphocytic lymphoma ( CLL ) with high-risk cytogenetics [ del(11q)(q22.3 ) or del(17p)(p13.1 ) ] have limited therapeutic options and their prognosis remains poor . This analysis was conducted to determine the clinical activity of lenalidomide in patients with high-risk disease . Relapsed/refractory patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3 ) or del(17p)(p13.1 ) were included in this analysis . Patients received single agent lenalidomide for 21 days of the 4 week treatment cycle . The overall response rate among patients with high-risk cytogenetics was 38 % , with 19 % of patients achieving a complete response . Median progression-free survival was 12.1 months , which is higher than demonstrated with other agents in comparable patient population s. In addition , the estimated 2-year survival probability was 58 % , demonstrating that the responses achieved with lenalidomide are durable , even in patients with CLL with high-risk disease with poor risk cytogenetics Adequate dosing of lenalidomide in Chronic Lymphocytic Leukemia ( CLL ) remains unclear . This study determined maximum tolerated dose ( MTD ) in relapsed CLL patients ( Cohort A ) and patients achieving a partial response ( PR ) or better to recent therapy ( Cohort B ) . Thirty-seven patients were enrolled . MTD was 2.5 mg followed by 5.0 mg continuous . In Cohort A , tumor flare grade 1 - 2 occurred in 15 patients ( 50 % ) and grade 3 in 1 patient ( 3 % ) . Cohort A had 19 of 23 evaluable ( 83 % ) patients , 4 PR ( 17 % ) and 15 ( 65 % ) stable disease ( SD ) , Cohort B had 6 of 7 patients ( 86 % ) with SD . Despite overall response rate not being high , many patients remained on therapy several months with SD 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 BACKGROUND Ibrutinib , an orally administered covalent inhibitor of Bruton 's tyrosine kinase ( BTK ) , is an effective treatment for relapsed chronic lymphocytic leukaemia ( CLL ) . We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL . METHODS In this single-arm phase 2 study , we enrolled adult patients with high-risk CLL at the MD And erson Cancer Center ( Houston , TX , USA ) . All enrolled participants had high-risk cytogenetic abnormalities ( deletion 17p , TP53 mutation , or deletion 11q ) or a short progression-free survival ( PFS < 36 months ) after previous first-line chemoimmunotherapy . Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab ( 375 mg/m(2 ) , intravenously , every week during cycle 1 , then once per cycle until cycle 6 ) , followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment . The primary endpoint was progression-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov number NCT01520519 , and is no longer accruing patients . FINDINGS Between Feb 28 , 2012 , and Sept 11 , 2012 , we enrolled 40 patients with CLL with high-risk disease features , 20 of whom had deletion 17p ( del[17p ] ) or TP53 mutations ( 16 previously treated , four untreated ) , 13 had relapsed CLL with deletion 11q ( del[11q ] ) , and seven a PFS less than 36 months after first-line chemoimmunotherapy . 18-month PFS in all patients was 78·0 % ( 95 % CI 60·6 - 88·5 ) , whereas in those with a del(17p ) or TP53 mutation it was 72·4 % ( 45·6 - 87·6 ) Toxicity was mainly mild to moderate in severity ( grade 1 - 2 ) . Diarrhoea occurred in ten ( 25 % ) patients ( grade 1 in nine patients and grade 2 in one ) , bleeding events in 14 ( 33 % ) patients ( eight grade 1 and five grade 2 ) , nausea or vomiting in 15 patients ( 38 % ) ( ten grade 1 and five grade 2 ) , and fatigue in seven ( 18 % ) patients ( four grade 1 and three grade 2 ) . Five patients ( 13 % ) had grade 3 infections ( two lung infections , one upper respiratory tract infection , one sepsis , and one mucositis ) , and no grade 4 or 5 infections occurred . One patient had grade 4 neutropenia . INTERPRETATION The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination . FUNDING Pharmacyclics Inc , Cancer Prevention and Research Institute of Texas , Leukemia and Lymphoma Society , National Cancer Institute , MD And erson Cancer Center Abstract Ofatumumab is a fully human anti-CD20 monoclonal antibody with enhanced antibody dependent and complement dependent cytotoxicity . Lenalidomide induces T cell and natural killer ( NK ) cell activation and in vitro enhances clearance of chronic lymphocytic leukemia ( CLL ) cells by monoclonal antibodies . We performed a multi-center , phase 2 trial of sequential treatment with ofatumumab and lenalidomide in patients with advanced , relapsed and refractory ( R/R ) CLL , consisting of ofatumumab 2000 mg intravenously on day 1 and lenalidomide 10 mg on days 8–28 , for up to six cycles . Twenty-one subjects were included with median age of 63 years and two prior lines of therapy . The overall response rate was 47.6 % and 23.8 % had stable disease . Median overall survival was 21.5 months . Neutropenia and thrombocytopenia were the most frequent adverse events . Tumor flare reaction occurred in 43 % of subjects . Intracycle sequential ofatumumab plus lenalidomide is active in high-risk R/R CLL and well tolerated except for frequent cytopenias Abstract Based on clinical activity in phase 2 studies , lenalidomide was evaluated in a phase 2/3 study in patients with relapsed/refractory chronic lymphocytic leukemia ( CLL ) . Following tumor lysis syndrome ( TLS ) complications , the protocol was amended to a phase 1 study to identify the maximum tolerated dose-escalation level ( MTDEL ) . Fifty-two heavily pretreated patients , 69 % with bulky disease and 48 % with high-risk genomic abnormalities , initiated lenalidomide at 2.5 mg/day , with dose escalation until the MTDEL or the maximum assigned dose was attained . Lenalidomide was safely titrated to 20 mg/day ; the MTDEL was not reached . Most common grade 3–4 adverse events were neutropenia and thrombocytopenia ; TLS was mild and rare . The low starting dose and conservative dose escalation strategy result ed in six partial responders and 30 patients obtaining stable disease . In summary , lenalidomide 2.5 mg/day is a safe starting dose that can be titrated up to 20 mg/day in patients with CLL BACKGROUND Patients with relapsed chronic lymphocytic leukemia ( CLL ) who have clinical ly significant coexisting medical conditions are less able to undergo st and ard chemotherapy . Effective therapies with acceptable side-effect profiles are needed for this patient population . METHODS In this multicenter , r and omized , double-blind , placebo-controlled , phase 3 study , we assessed the efficacy and safety of idelalisib , an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase , in combination with rituximab versus rituximab plus placebo . We r and omly assigned 220 patients with decreased renal function , previous therapy-induced myelosuppression , or major coexisting illnesses to receive rituximab and either idelalisib ( at a dose of 150 mg ) or placebo twice daily . The primary end point was progression-free survival . At the first prespecified interim analysis , the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy . RESULTS The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group ( hazard ratio for progression or death in the idelalisib group , 0.15 ; P<0.001 ) . Patients receiving idelalisib versus those receiving placebo had improved rates of overall response ( 81 % vs. 13 % ; odds ratio , 29.92 ; P<0.001 ) and overall survival at 12 months ( 92 % vs. 80 % ; hazard ratio for death , 0.28 ; P=0.02 ) . Serious adverse events occurred in 40 % of the patients receiving idelalisib and rituximab and in 35 % of those receiving placebo and rituximab . CONCLUSIONS The combination of idelalisib and rituximab , as compared with placebo and rituximab , significantly improved progression-free survival , response rate , and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy . ( Funded by Gilead ; Clinical Trials.gov number , NCT01539512 . ) BACKGROUND New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia ( CLL ) , but complete remissions remain uncommon . Venetoclax has a distinct mechanism of action ; it targets BCL2 , a protein central to the survival of CLL cells . METHODS We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma ( SLL ) to assess safety , pharmacokinetic profile , and efficacy . In the dose-escalation phase , 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day . In an expansion cohort , 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day . RESULTS The majority of the study patients had received multiple previous treatments , and 89 % had poor prognostic clinical or genetic features . Venetoclax was active at all dose levels . Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort , with one death . After adjustments to the dose-escalation schedule , clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort . Other toxic effects included mild diarrhea ( in 52 % of the patients ) , upper respiratory tract infection ( in 48 % ) , nausea ( in 47 % ) , and grade 3 or 4 neutropenia ( in 41 % ) . A maximum tolerated dose was not identified . Among the 116 patients who received venetoclax , 92 ( 79 % ) had a response . Response rates ranged from 71 to 79 % among patients in subgroups with an adverse prognosis , including those with resistance to fludarabine , those with chromosome 17p deletions ( deletion 17p CLL ) , and those with unmutated IGHV . Complete remissions occurred in 20 % of the patients , including 5 % who had no minimal residual disease on flow cytometry . The 15-month progression-free survival estimate for the 400-mg dose groups was 69 % . CONCLUSIONS Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL , including those with poor prognostic features . ( Funded by AbbVie and Genentech ; Clinical Trials.gov number , NCT01328626 . ) This study investigated the activity of lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia ( CLL ) . Lenalidomide was given at 10 mg daily with dose escalation up to 25 mg daily . Three patients ( 7 % ) achieved a complete response ( CR ) , one a nodular partial remission , and 10 patients a partial remission ( PR ) , for an overall response ( OR ) rate of 32 % . Treatment with lenalidomide was associated with an OR rate of 31 % in patients with 11q or 17p deletion , of 24 % in patients with unmutated V(H ) , and of 25 % in patients with fludarabine-refractory disease . The most common toxicity was myelosuppression , and the median daily dose of lenalidomide tolerated was 10 mg . Plasma levels of angiogenic factors , inflammatory cytokines , and cytokine receptors were measured at baseline , day 7 , and day 28 . There was a dramatic increase in median interleukin (IL)-6 , IL-10 , IL-2 , and tumor necrosis factor receptor-1 levels on day 7 , whereas no changes were observed in median vascular endothelial growth factor levels ( 20 patients studied ) . According to our experience , lenalidomide given as a continuous treatment has antitumor activity in heavily pretreated patients with CLL PURPOSE Lenalidomide is a novel immunomodulatory agent with antiproliferative activities . Given its efficacy in a wide range of hematologic malignancies , we conducted a phase II trial ( NHL-001 ) of single-agent lenalidomide in indolent non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Patients with relapsed/refractory indolent NHL were eligible , with no limit on the number of previous therapies . Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated , or until disease progression . The primary end point was objective response rate ( ORR ) , with secondary end points of duration of response ( DR ) , progression-free survival ( PFS ) , and safety . RESULTS Forty-three enrolled patients were assessable for response and safety . Patients received a median of three prior systemic therapies ( range , 1 to 17 ) and half were refractory to last therapy . ORR was 23 % ( 10 of 43 ) , including a 7 % complete response ( CR ) or unconfirmed CR rate . Twenty-seven percent ( six of 22 ) of patients with follicular lymphoma grade 1 or 2 , and 22 % ( four of 18 ) with small lymphocytic lymphoma responded to therapy . Median DR was not reached , but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months . Median PFS for the whole group was 4.4 months ( 95 % CI , 2.5 to 10.4 months ) . Adverse events were predictable and manageable ; the most common grade 3 or 4 adverse events were neutropenia ( 30 % and 16 % , respectively ) and thrombocytopenia ( 14 % and 5 % , respectively ) . CONCLUSION Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL , warranting further investigation of treatment for indolent NHL PURPOSE Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia ( CLL ) . We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL . PATIENTS AND METHODS Fifty-nine adult patients ( age 42 to 82 years ) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab . Patients had received prior fludarabine-based therapy or chemoimmunotherapy . Rituximab ( 375 mg/m(2 ) intravenously ) was administered weekly during cycle one and on day 1 of cycles three to 12 . Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously . Each cycle was 28 days . Rituximab was administered for 12 cycles ; lenalidomide could continue indefinitely if patients benefitted clinical ly . RESULTS The overall response rate was 66 % , including 12 % complete responses and 12 % nodular partial remissions . Time to treatment failure was 17.4 months . Median overall survival has not been reached ; estimated survival at 36 months is 71 % . The most common grade 3 or 4 toxicity was neutropenia ( 73 % of patients ) . Fourteen patients ( 24 % ) experienced a grade 3 to 4 infection or febrile episode . There was one episode of grade 3 tumor lysis ; one patient experienced renal failure during the first cycle of therapy , and one venous thromboembolic event occurred during the study . CONCLUSION The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation Lenalidomide is an IMID immunomodulatory agent clinical ly active in patients with chronic lymphocytic leukemia ( CLL ) . We evaluated the activity of lenalidomide inside an in vitro coculture system of endothelial and CLL cells . Lenalidomide was able to inhibit CLL survival advantage mediated by endothelial contact . Moreover , the marked increase of in vitro angiogenesis determined by CLL-derived conditioned media was reduced by lenalidomide . We also analyzed peripheral blood collected from 27 patients with relapsed or refractory CLL being treated with lenalidomide within a phase II trial . Plasma levels of VEGF and THBS-1 decreased , whereas Ang2 and Ang increased during treatment . Patients who respond to lenalidomide showed a more pronounced decrease of VEGF and bFGF than did patients with stable or progressive disease ( p = 0.007 and p = 0.005 ) . Furthermore , lenalidomide reduced circulating endothelial cells and endothelial progenitors by increasing the percentage of apoptotic cells . Conversely , for six matched bone marrow biopsies available before and after treatment , we did not detect any modification in vessel density , suggesting a possible mechanism of vessel normalization rather than regression . In conclusion , our study provides further evidence that the anti-CLL effect of lenalidomide is mediated through the alteration of microenvironmental elements , implying the modulation of several angiogenesis-related factors and disruption of CLL crosstalk with endothelial cells |
12,501 | 24,756,728 | The meta- analysis suggests that there is no enough evidence for associations of A2 M gene polymorphisms ( 5 bp I/D , Ile1000Val ) with AD risk at present , even after stratification by ethnicity and APOE ε4 with genotypes of polymorphism sites . | Abstract Accumulating studies have evaluated the association of Alpha-2-Macroglobulin gene ( A2 M ) 5 bp insertion/deletion ( 5 bp I/D , rs3832852 ) and Ile1000Val ( rs669 ) polymorphisms with Alzheimer ’s disease ( AD ) risk , but the results remain inconclusive . | Alzheimer 's disease ( AD ) is a complex genetic disorder . Linkage analysis has helped unravel a portion of the genetic component of AD by identifying four loci that play a role in the genetics of AD ( amyloid precursor protein , presenilin 1 , presenilin 2 , and apolipoprotein E ) . These loci account for approximately 50 % of the genetic etiology of AD . A total genomic screen is an efficient way to identify additional genetic effects in AD . A series of multiplex late-onset ( > 60 years ) AD families were ascertained ( NINDS-ADRDA diagnostic criteria ) and sample d. A subset ( n = 16 ) of the largest families ( 52 affecteds with DNA , 83 unaffecteds with DNA ) were used to rapidly screen the genome ( n = 280 markers ) for additional major genetic effects . Critical values for regional follow-up were p < or = 0.05 for SimIBD or sibpair analysis and /or a LOD score > or = 1.00 . Fifteen regions warranted initial follow-up based on these criteria . An additional screening set was used ( n = 38 families , 89 affecteds with DNA , 216 unaffecteds with DNA ) for the follow-up analysis . These analyses revealed four regions of continued interest on chromosomes 4 , 6 , 12 , and 20 . Chromosome 12 presented the strongest results . Peak two point " affecteds only " LOD scores were 1.3 , 1.6 , 2.7 , and 2.2 and ( affected relative pair SimIBD ) p values were 0.04 , 0.03 , 0.14 , and 0.04 for D12S373 , D12S1057 , D12S1042 , and D12S390 , respectively . These markers span approximately 30 cm near the centromeric region of chromosome 12 . Sibpair analysis result ed in two point Maximum Lod Score ( MLS ) results of 0.4 , 1.2 , 3.2 , and 1.0 for the above markers . Multipoint MLS analysis supported these findings . Saturation mapping of all available markers in the chromosome 12 region as well as further investigation of the regions on 4 , 6 , and 20 is ongoing with c and i date gene analysis to follow Alpha2-macroglobulin ( alpha2 M ) as well as its receptor , the low-density lipoprotein receptor-related ( LRP ) and the receptor-associated protein ( RAP ) are involved in the clearance of cerebral A beta . Current evidence suggests that polymorphisms in the genes of alpha2 M , LRP and RAP may have functional effects on the proteins . Two independent association sample s of 271 AD patients and 280 representative controls were investigated whether the risk for developing AD is altered in carriers of polymorphisms in the alpha2M-gene ( Va1000Ile ) , in the LRP-gene ( Ala216Val ) and in the RAP-gene ( Val311Met ) . Genotypes were determined by st and ard PCR and restriction fragment length polymorphism . The results were adjusted for age , gender and apolipoprotein E-epsilon4 ( APOE ) polymorphism . Inheritance of alpha2 M conferred a small increased risk for sporadic AD with an estimated Mantel-Haenszel odds ratio of 1.47 . There was no age- or gender-dependent increase in alpha2 M Val1000Ile allele frequencies in AD patients compared to controls . There was no significant difference in the allele frequencies among control and AD subjects for the LRP and RAP polymorphisms . We found no evidence of an interaction between the alpha2 M and RAP or LRP with regard to conferred risk . Our data suggest that the alpha2 M Val1000Ile polymorphism is weakly associated with AD . Although LRP as well as RAP seem to play an essential role in the metabolism of alpha2 M and APOE , there is no increase in the genetic risk for AD in patients carrying the investigated polymorphisms Recent advances in clinical , pathological and neuroscience studies have identified disease-modifying therapeutic approaches for Alzheimer 's disease that are now in clinical trials . This has highlighted the need for reliable and convenient biomarkers for both early disease diagnosis and a rapid signal of drug efficacy . We describe the identification and assessment of a number of c and i date biomarkers in patients with Alzheimer 's disease and the correlation of those biomarkers with rosiglitazone therapeutic efficacy , as represented by a change in the Alzheimer 's Disease Assessment Scale-Cognitive ( ADAS-Cog ) . Plasma from 41 patients with Alzheimer 's disease were analysed by open platform proteomics at baseline and after receiving 8 mg rosiglitazone for 24 weeks . From a comparison of protein expression following treatment with rosiglitazone , 97 proteins were observed to be differentially expressed with a p-value<0.01 . From this analysis and comparison to recently published data from our laboratory , a prioritized list of 10 proteins were analysed by immunoassay and /or functional assay in a wider set of sample s from the same clinical study , representing a rosiglitazone dose response , in order to verify the changes observed . A number of these proteins appeared to show a correlation with change in ADAS-Cog at the higher treatment doses compared with the placebo . Alpha-2-macroglobulin , complement C1 inhibitor , complement factor H and apolipoprotein E expression showed a correlation with ADAS-Cog score at the higher doses ( 4 mg and 8 mg ) . These results are discussed in light of the pathology and other recently published data Recent reports have suggested that genetic polymorphisms in the alpha-2 macroglobulin ( A2 M ) gene are associated with an increased risk for Alzheimer 's disease . In the present study we tested two polymorphisms in the alpha-2 macroglobulin gene , a 5 bp deletion at the 5 ' splice site of exon 18 and a G/A point mutation ( V1000I ) in exon 24 , in a sample of 118 healthy , non demented controls and 238 consecutively recruited gerontopsychiatric patients , diagnosed as : Alzheimer 's disease ( N=88 ) , mild cognitive impairment ( N=32 ) , subjective cognitive complaints ( N=54 ) and depression/other psychiatric disorders ( N=64 ) . The aim of this study was to test whether the investigated polymorphisms has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia , respectively . Also a possible relation to the APOE varepsilon4 polymorphism was examined . Our study failed to show an association between the two investigated polymorphisms in the alpha-2 macroglobulin gene and any of the four different psychogeriatric patient subgroups , either alone or in combination with the APOE varepsilon4 genotype Recently , two studies have reported an association between the α2‐macroglobulin gene on chromosome 12 and late‐onset Alzheimer 's disease , whereas others have not been able to replicate these findings . By using a prospect i ve population ‐based study , we have investigated the relation between two polymorphisms in this gene with the presence of the disease and also with the extent of pathological changes in the cerebral cortex . The Vantaa 85 + Study includes all 601 persons , at least 85 years of age , who were living in Vantaa , Finl and , on April 1 , 1991 . The neocortical β‐amyloid protein load and the number of neurofibrillary tangles were determined on tissue sections by using methenamine silver staining and a modified Bielschowsky staining , respectively . The A/A genotype in exon 24 of the α2‐macroglobulin gene was associated with neuropathologically defined diagnosis of Alzheimer 's disease according to the CERAD ( Consortium to Establish a Registry for Alzheimer 's Disease ) criteria and with an increase in the neocortical β‐amyloid protein load . The effect of this association was stronger in the apolipoprotein E ε4–negative group . Therefore , genetic variability in the α2‐macroglobulin gene is a risk factor associated with neuropathologically defined Alzheimer 's disease in our population , as well as with the extent of neocortical β‐amyloid protein deposition Two genetic markers of the plasma protein alpha2-macroglobulin , a 5 bp deletion/insertion at the 5 ' splice site of exon 18 ( A2MI ) and the GTC/ATC ( VaIIO00IIe ) in exon 24 ( A2M2 ) , may have roles in the development of Alzheimer 's disease ( AD ) . Genotyping and linkage analysis of these markers in 426 Japanese sporadic AD patients , 85 autopsy-confirmed Caucasian AD cases , and , as controls , 382 Japanese and 65 Caucasians who were cognitively normal and 140 Japanese Parkinson 's disease patients showed racial diversity in the frequencies and relationship of the two markers . Comparison of genotype and allele frequencies , stratification of the sample s by the presence of the apolipoprotein E epsilon4 allele , and logistic regression analysis revealed no association of these markers with AD in either racial group |
12,502 | 21,074,116 | However , this advantage does not appear to be maintained in the long term . | BACKGROUND Abdominal aortic aneurysms ( AAAs ) represent a significant health problem in the United States as more than 1 million people are afflicted and the prevalence is only expected to increase .
Given that AAA rupture carries a high mortality rate , there is interest in repairing the aneurysm electively before aneurysm rupture .
Two approaches to aneurysm repair are open repair and endovascular repair .
However , limited data comparing the outcomes of these different methods exist . | OBJECTIVE Compare long-term results of endovascular treatment and st and ard open repair of abdominal aortic aneurysms in a multicenter , concurrent-controlled trial . METHODS 334 subjects were treated with st and ard open repair ( control , n = 99 ) or the original EXCLUDER Bifurcated Endoprosthesis ( test , n = 235 ) . Five-year clinical evaluations and corelab radiographic results are analyzed . RESULTS Overall and aneurysm-related survival are similar . There have been ten open conversions , most frequently for enlarging sacs without endoleak . Two patients died after conversion . Including re interventions and complications of re interventions as adverse events , there is significant , persistent long-term reduction in major adverse events . At 5 years , corelab reported 0 % limb narrowing , 0 % trunk migration , 0 % component ( contralateral leg , aortic extender , and iliac extender ) migration , 0 % fracture , endoleak in 3 % ( 2 type II/68 ) , and aneurysm growth ( > 5 mm compared to baseline ) in 38 % ( 30/78 ) of the test group . There are no aneurysm ruptures in either test or control group . CONCLUSIONS After 5 years follow-up , endovascular repair is a safer and effective treatment compared with open surgical repair for abdominal aortic aneurysms . Major adverse events are less frequent with the endograft despite the need for late re interventions . Aneurysm expansion is observed in nearly two-fifths of patients but is not associated with endoleak or aneurysm rupture . Multicenter clinical trials are evaluating a newer version of this device design ed to avoid this high rate of sac expansion After the introduction of endovascular repair of abdominal aortic aneurysms ( AAA ) , both benefits and drawbacks of this new technique have been reported . To assess whether the new technique is an adequate substitute of conventional AAA repair , a r and omised study is due . The Dutch R and omised Endovascular Aneurysm Management ( DREAM ) trial is a r and omised multicenter trial enrolling patients eligible for elective treatment of infrarenal AAAs . In this study , the cost-effectiveness of endovascular aneurysm repair ( EAR ) is compared with that of conventional transabdominal surgery , in patients that are considered suitable for both types of treatment . The primary endpoint is combined operative mortality and morbidity . Secondary endpoints and additional assessment s include event free survival , quality of life , length of hospital stay and costs . It is expected that the DREAM-trial will lead to a safe and controlled introduction of a new technology . Also , the medical community will obtain valid scientific evidence of the merits of endovascular AAA repair . Finally , policy makers will be provided with accurate cost-effectiveness data for the Dutch healthcare system . The aim of the present paper is to describe the background , methods and design of the DREAM-trial OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of a novel endovascular graft for elective treatment of infrarenal abdominal aortic aneurysm . The device is a modular bifurcated system with nitinol/exp and ed polytetrafluoroethylene components and a smaller profile than currently approved devices . METHODS In a multicenter , concurrent controlled phase II trial , 334 patients underwent treatment with the Excluder bifurcated endoprosthesis ( test , n = 235 ; W. L. Gore & Associates , Inc , Sunnyvale , Calif ) or with st and ard open repair ( control , n = 99 ) . Preoperative characteristics , perioperative variables , follow-up clinical evaluations , and radiographic examination results through the first 2 years were analyzed with univariable and multivariable statistics . RESULTS Patients in the test group had less blood loss ( 310 + /- 19 mL versus 1590 + /- 124 mL ; P < .0001 ) , fewer homologous transfusions ( 6 % versus 32 % ; P < .0001 ) , and shorter lengths of stay ( 2.0 + /- 0.1 days versus 9.8 + /- 1.4 days ; P < .0001 ) . Early major adverse events were markedly reduced in the test group ( 14 % versus 57 % ; P < .0001 ) , and this difference persisted at 2 years . No difference was seen in survival rate ( P = .13 ) . In the first 2 years , no deployment failure , early conversion , or aneurysm rupture occurred . At the 2-year timepoint , core laboratory read trunk migration in 1 % , limb migration in 1 % , limb narrowing in 1 % , endoleak in 20 % , and aneurysm growth in 14 % . One wire discontinuity ( 0.6 % ) was identified in a discharge film . A 7 % annual reintervention rate was seen in the test group in the first 2 years . SUMMARY The test device is a safe and effective treatment compared with open surgical repair for infrarenal abdominal aortic aneurysm . The most striking benefits are reduced blood loss , fewer complications , and faster recovery . Two-year survival rate was similar BACKGROUND Although the initial results of endovascular repair of abdominal aortic aneurysms were promising , current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair . METHODS We conducted a multicenter , r and omized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable c and i date s for both techniques . The outcome events analyzed were operative ( 30-day ) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications . RESULTS The operative mortality rate was 4.6 percent in the open-repair group ( 8 of 174 patients ; 95 percent confidence interval , 2.0 to 8.9 percent ) and 1.2 percent in the endovascular-repair group ( 2 of 171 patients ; 95 percent confidence interval , 0.1 to 4.2 percent ) , result ing in a risk ratio of 3.9 ( 95 percent confidence interval , 0.9 to 32.9 ) . The combined rate of operative mortality and severe complications was 9.8 percent in the open-repair group ( 17 of 174 patients ; 95 percent confidence interval , 5.8 to 15.2 percent ) and 4.7 percent in the endovascular-repair group ( 8 of 171 patients ; 95 percent confidence interval , 2.0 to 9.0 percent ) , result ing in a risk ratio of 2.1 ( 95 percent confidence interval , 0.9 to 5.4 ) . CONCLUSIONS On the basis of the overall results of this trial , endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter . Long-term follow-up is needed to determine whether this advantage is sustained CONTEXT Limited data are available to assess whether endovascular repair of abdominal aortic aneurysm ( AAA ) improves short-term outcomes compared with traditional open repair . OBJECTIVE To compare postoperative outcomes up to 2 years after endovascular or open repair of AAA in a planned interim report of a 9-year trial . DESIGN , SETTING , AND PATIENTS A r and omized , multicenter clinical trial of 881 veterans ( aged > or = 49 years ) from 42 Veterans Affairs Medical Centers with eligible AAA who were c and i date s for both elective endovascular repair and open repair of AAA . The trial is ongoing and this report describes the period between October 15 , 2002 , and October 15 , 2008 . INTERVENTION Elective endovascular ( n = 444 ) or open ( n = 437 ) repair of AAA . MAIN OUTCOME MEASURES Procedure failure , secondary therapeutic procedures , length of stay , quality of life , erectile dysfunction , major morbidity , and mortality . RESULTS Mean follow-up was 1.8 years . Perioperative mortality ( 30 days or inpatient ) was lower for endovascular repair ( 0.5 % vs 3.0 % ; P = .004 ) , but there was no significant difference in mortality at 2 years ( 7.0 % vs 9.8 % , P = .13 ) . Patients in the endovascular repair group had reduced median procedure time ( 2.9 vs 3.7 hours ) , blood loss ( 200 vs 1000 mL ) , transfusion requirement ( 0 vs 1.0 units ) , duration of mechanical ventilation ( 3.6 vs 5.0 hours ) , hospital stay ( 3 vs 7 days ) , and intensive care unit stay ( 1 vs 4 days ) , but required substantial exposure to fluoroscopy and contrast . There were no differences between the 2 groups in major morbidity , procedure failure , secondary therapeutic procedures , aneurysm-related hospitalizations , health-related quality of life , or erectile function . CONCLUSIONS In this report of short-term outcomes after elective AAA repair , perioperative mortality was low for both procedures and lower for endovascular than open repair . The early advantage of endovascular repair was not offset by increased morbidity or mortality in the first 2 years after repair . Longer-term outcome data are needed to fully assess the relative merits of the 2 procedures . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00094575 The prevalence of abdominal aortic aneurysm ( AAA ) in a community‐based sample of men and women aged 65–79 years was correlated with known risk factors . In addition , the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied OBJECTIVES The endovascular aneurysm repair ( EVAR ) trials aim to assess the efficacy of EVAR in the treatment of AAA in terms of mortality , quality of life , durability and cost-effectiveness . DESIGN Male and female patients aged at least 60 years with an AAA diameter measuring at least 5.5 cm on a computed tomography ( CT ) scan are assessed for anatomical suitability for EVAR . Suitable patients are offered entry either into EVAR Trial 1 if they are considered fit for conventional open repair or EVAR Trial 2 if they are considered unfit . EVAR 1 r and omly allocates patients to EVAR or open repair and EVAR 2 r and omly allocates patients to EVAR with best medical treatment or best medical treatment alone . Target recruitment for EVAR Trials 1 and 2 is 900 and 280 patients , respectively . PROGRESS Recruitment began in September 1999 and there are currently 40 UK centres participating in the trials . Monthly targets are being exceeded in EVAR Trial 1 with 1037 patients r and omised by October 2003 . EVAR Trial 2 is also meeting monthly targets with a total of 319 patients r and omised . When recruitment closes in December 2003 patients will need to be followed for at least 1 year from their operation . Publication of full results for both trials is expected in mid 2005 |
12,503 | 10,796,355 | REVIEW ER 'S CONCLUSIONS Evidence that massage for preterm infants is of benefit for developmental outcomes is weak and does not warrant wider use of preterm infant massage . | BACKGROUND It has been argued that infants in Neonatal Intensive Care Units are subject both to a highly stressful environment - continuous , high-intensity noise and bright light - and to a lack of the tactile stimulation that they would otherwise experience in the womb or in general mothering care .
As massage seems to both decrease stress and provide tactile stimulation , it has been recommended as an intervention to promote growth and development of preterm and low-birth weight infants .
OBJECTIVES To determine whether preterm and / or low birth-weight infants exposed to massage experience improved weight gain and earlier discharge compared to infants receiving st and ard care ; to determine whether massage has any other beneficial or harmful effects on this population . | Inactive awake behavioral states have been associated with reduced heart rates and more successful feeding in preterm infants . The purpose of this study was to test the efficacy of three different interventions to facilitate these optimal feeding states . Twenty preterm infants ( gestational ages 27–33 weeks , M = 31.6 , SD = 1.7 ; birth weights 931–2,140 grams , M = 34 , SD = 373 ) serving as their own controls were r and omly administered nonnutritive sucking , nonnutritive sucking plus rocking , and stroking interventions ; and a control condition . There were significantly more inactive awake states with the nonnutritive sucking and nonnutritive sucking plus rocking interventions than with the stroking intervention and the control conditions . The results suggest that there are interventions that can help preterm infants in the transition from gavage to oral feeding and potentially shorten their hospital stays Assigned r and omly 28 neonates born to HIV-positive mothers to a massage therapy or control group . The treatment infants were given three 15-minute massages daily for 10 days . The massaged group showed superior performance on almost every Brazelton newborn cluster score and had a greater daily weight gain at the end of the treatment period unlike the control group who showed declining performance A study was design ed to explore further the hypothesis that a period of close contact between mother and infant immediately after birth facilitates the establishment of a close bond . The study investigated whether the effects of extra contact interact with other variables present in the labor and delivery situation and with the extent of social support available to the mother . Two sets of procedures for the immediate postpartum period were established and mothers were r and omly assigned to one of these conditions . Twenty-nine mothers experienced extracontact procedures in which the baby was placed on the mother 's abdomen for 1 hour . Thirty mothers received routine care procedures in which the baby was shown to the mother and then taken to the nursery . Observations of maternal behavior during a feeding were made two days after birth by an observer blind to the r and omization status of the mother . The mothers who received extra contact exhibited significantly more affectionate behavior toward their infants than did the mothers who received routine care . The extracontact treatment produced more affectionate behaviors in the mothers who had less social support than in those who had more social support . The extra contact was equally effective for multiparous and primiparous mothers . Mothers of female infants exhibited more affectionate behavior to their infants regardless of which postpartum procedures the mothers had experienced BACKGROUND The method of " massage therapy " has consistently shown increased weight gain in preterm infants . The weight gain was apparent during massages administered by professionals . AIMS To replicate the results of increased weight gain in the course of " massage therapy " in preterm infants , and utilize a new , cost-effective application of this method by comparing maternal to nonmaternal administration of the therapy . STUDY DESIGN R and om cluster design . SUBJECTS The study comprised 57 healthy , preterm infants assigned to three groups : two treatment groups -- one in which the mothers performed the massage , and the other in which a professional female figure unrelated to the infant administered the treatment . Both these groups were compared to a control group . RESULTS Over the 10-day study period , the two treatment groups gained significantly more weight compared to the control group ( 291.3 and 311.3 vs. 225.5 g , respectively ) . Calorie intake/kg did not differ between groups . CONCLUSIONS Mothers are able to achieve the same effect size as that of trained professionals , allowing cost-effective application of the treatment within the neonatal intensive care unit Preterm neonates ( mean 32 weeks ' gestation , 1,300 gm birth weight ) were provided a pacifier for nonnutritive sucking during tube feedings in the intensive care nursery . Their clinical course , subsequent bottle feeding behavior , and performance on the Brazelton Neonatal Behavior Assessment scale were compared with those of control group infants . The infants provided with pacifiers averaged 27 fewer tube feedings , started bottle feeding three days earlier , averaged a greater weight gain per day , and were discharged eight days earlier for an average hospital cost savings of approximately $ 3,500 . Formula intake was similar for the two groups , although nurses appeared to provide more feeding stimulation for the control infants . On the Brazelton scale , the infants provided with pacifiers showed weak reflexes more frequently . Increased restfulness and diminished activity level in these infants may have contributed to the appearance of weak reflexes . The consistency between these findings and those of previous investigators suggests that the provision of a pacifier for nonnutritive sucking during tube feedings may be a cost-effective form of intervention The effects of unimodal and multimodal stimulation on mental , psychomotor , and behavioral development of healthy full-term infants were examined longitudinally . Subjects were r and omly assigned to a control group or one of three experimental conditions : daily administration of a stroking procedure , placement on a multisensory hammock during sleep periods , or a combination of the two treatments . Interventions were conducted during the first 3 months of life . Data are presented on 49 infants who were available for 24-month follow up . The experimental conditions did not significantly affect scores on the Bayley Scales of Infant Development . Eyberg 's Child Behavior Inventory , the Nursing Child Assessment Teaching Scales , or the HOME . These findings suggest that supplementary stimulation provided no benefits beyond those associated with natural caregiving and raise questions about the value of the interventions with nonrisk infants in middle-class families . Additional studies need to be conducted with larger sample s of healthy infants to test sensory stimulation protocol s before they are advocated for widespread consumer use We compared the maternal behaviors of women who had extended and early contact ( rooming-in ) with their infants with those who had contact only during feedings . Thirty-one young , unmarried , predominantly black , lower-socioeconomic mothers and their infants were observed in the mother 's hospital room for 15 minutes after a morning feeding approximately 18 hours after delivery . A time sample unit checklist was used to record each mother 's behavior , looking , talking , and touching directed toward their infants and others , as well as watching television and talking on the telephone . Analyses of variance revealed that the rooming-in mothers looked at , talked to , and touched their infants more , watched less television , and talked less on the telephone than mothers with minimal contact with their infants . These findings suggest that increased postpartum contact with infants leads not only to more interaction , but also to more touching as well as touching in more intimate places ( face and head ) , thus highlighting the value of rooming-in arrangements for mothers and infants Thirty preterm cocaine-exposed preterm neonates ( mean gestational age 30 wks , mean birth weight = 1212 g , mean intensive care unit duration = 18 days ) were r and omly assigned to a massage therapy or a control group as soon as they were considered medically stable . Group assignment was based on a r and om stratification of gestational age , birth weight , intensive care unit duration , and entry weight into the study . The treatment group ( N = 15 ) received massages for three 15-minute periods 3 consecutive hours for a 10-day period . Findings suggested that the massaged infants ( 1 ) averaged 28 % greater weight gain per day ( 33 vs 26 g ) although the groups did not differ in intake ( calories or volume ) , ( 2 ) showed significantly fewer postnatal complications and stress behaviors than did control infants , and ( 3 ) demonstrated more mature motor behaviors on the Brazelton examination at the end of the 10-day study period . J Dev Behav Pediatr 14:318–322 , 1993 . Index terms : massage , cocaine , preterm , intervention Abstract The relationship of multimodal stimulation to length of hospitalization and weight gain was studied in 33 premature infants . Subjects were r and omly assigned to treatment ( N = 17 ) and control groups ( N = 16 ) . Subjects in the treatment group received 5 to 10 days of tactile stimulation . Weight gain and length of hospitalization were measured from the onset of entry into the study until discharge from the hospital . The results indicated no significant differences between groups , although trends for greater weight gain and shorter duration of hospitalization were noted . The results suggest that infants may experience some improvement in weight gain and a shorter hospitalization after receiving stimulation Eighty-one healthy , full-term infants were r and omly assigned to a control group or one of three experimental conditions : daily administration of a cephalocaudal stroking procedure ; placement on a multisensory hammock that provided auditory , vestibular , and tactile stimulation during expected sleep cycles ; and a combination of the prior two treatments . All interventions were given during the first 3 months of life . Infants in the control group received the natural stimulation provided in their home environments without additional supplementation . Four- and 8-month assessment s were done using the Bayley Scales of Infant Development and the Revised Infant Temperament Question naire . There were no significant treatment effects on weight or psychomotor development . Although infants receiving unimodal stimulation obtained lower 8-month cognitive development scores than infants in other experimental and control groups , their scores were within normal range . Control group infants achieved the most optimum mood and distractibility scores at both 4 and 8 months 34 very low birthweight babies ( mean 1143 g ) in incubators were r and omly assigned to be continuously nursed on lambswool ( n = 17 ) or ordinary cotton sheets ( n = 17 ) . The weight gain for the periods when babies were well was significantly larger for the wool group , 22.7 g/day vs 18.6 g/day for cotton control ( p less than 0.02 ) . The overall weight gain ( which included weight change during periods of illness ) revealed a similar picture in favour of the wool group , 21.5 g/day vs 18.2 g/day ( p less than 0.05 ) . Movement patterns for the two groups showed no differences , but for all babies a strong correlation was noted between moving and lying suspine ( p less than 0.001 ) , having eyes open ( p less than 0.001 ) , a cooler incubator ( p less than 0.01 ) , and faster weight gain ( p less than 0.01 ) . Lambswool seems to have advantages over cotton sheets as a bedding material for very low birth weight babies The purpose of this study was to evaluate the effects of a gentle human touch ( GHT ) intervention provided to 42 preterm infants ( 27 - 33 weeks gestational age ) , for 10 min , three times daily for 10 days . There was no significant difference in mean HR levels or in percent of abnormal heart rate ( HR ) or O2 saturation comparing 10-min baseline ( B ) , GHT , and 10-min post-touch ( PT ) phases . There were significantly lower levels of active sleep , motor activity , and behavioral distress during GHT compared to B and P phases . There were no differences among the 42 infants in the GHT group and 42 infants in a r and omly assigned control group on any outcome variable including weight gain , morbidity status , or behavioral organization . The findings suggest that GHT generally is a safe and soothing type of touch to provide to young preterm infants , but that individual infant responses to touch need to be continuously monitored by NICU staff and parents To investigate cl aims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development , we performed a r and omized clinical trial using a predetermined sample size . Preterm infants weighing from 750 to 1750 gm at birth were r and omly assigned , by 250 gm strata , to either a conventional mattress ( n = 63 ) or to an air mattress ( n = 59 ) oscillating at 14 to 16 regular pulses per minute . Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age . Apneic episodes occurred and required treatment equally in the two groups ; this lack of an effect was seen for both sexes and all weight groups . Both weight and energy intake were similar . Neurobehavioral development as shown by sleep state , habituation testing , and behavioral assessment at term , 3 , 6 , and 12 months was similar in the two groups . There was no difference in the incidence of neurologic abnormalities . We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development Tactile/kinesthetic stimulation was given to 20 preterm neonates ( mean gestational age , 31 weeks ; mean birth weight , 1,280 g ; mean time in neonatal intensive care unit , 20 days ) during transitional ( " grower " ) nursery care , and their growth , sleep-wake behavior , and Brazelton scale performance was compared with a group of 20 control neonates . The tactile/kinesthetic stimulation consisted of body stroking and passive movements of the limbs for three , 15-minute periods per day for a 10 days . The stimulated neonates averaged a 47 % greater weight gain per day ( mean 25 g v 17 g ) , were more active and alert during sleep/wake behavior observations , and showed more mature habituation , orientation , motor , and range of state behavior on the Brazelton scale than control infants . Finally , their hospital stay was 6 days shorter , yielding a cost savings of approximately $ 3,000 per infant . These data suggest that tactile/kinesthetic stimulation may be a cost effective way of facilitating growth and behavioral organization even in very small preterm neonates BACKGROUND To determine the effects of tactile-kinesthetic stimulation to preterms on physiologic parameters , physical growth and behavioral development . DESIGN Controlled trial . SETTING The premature unit ( growing nursery ) of a large , teaching hospital . SUBJECTS 48 well preterms with birth weights between 1000 - 2000 grams . INTERVENTION The neonates were systematic ally allocated into test and control groups . Test babies received tactile-kinesthetic stimulation in the form of a structured baby massage from day 3 to term corrected age . They were observed for changes in vital parameters ( heart rate , respiration , temperature and oxygen saturation ) during the first few days of stimulation in hospital . Thereafter , massage was continued at home . Changes in weight , length and head circumference and neuro-behavior ( Brazelton Neuro-Behavioral Assessment Scale ) were assessed in both groups before , during and after the study period . RESULTS An increase in heart rate ( within physiologic range ) was seen in the test group during stimulation . This group also showed a weight gain of 4.24 g/day more than controls , which was statistically significant . On the Brazelton Scale the test group showed statistically significant improved scores on the " orientation " , " range of state " , " regulation of state " and " autonomic stability " clusters at follow-up . No significant complications were noted . A positive correlation was found between the duration of stimulation in days and the weight gain in grams but this did not reach statistical significance . CONCLUSIONS Tactile-kinesthetic stimulation when administered to well , preterm infants has a beneficial effect on growth and behavioral development with no adverse effects on physiologic parameters The effects of nursery-based intervention with healthy , prematurely born babies and their socially disadvantaged mothers were evaluated . Mother-infant dyads were r and omly assigned to one of three intervention groups : In group one , the babies received special stimulation design ed to make them more active contributors to the interactions with their mothers ; in group two , mothers received special training to help them become more responsive to cues from their babies ; in group three , infants received stimulation and mothers received training . In addition , a fourth group of preterm babies who received regular hospital care served as a comparison group to assess the short-term effects of the stimulation program . Outcome measures design ed to evaluate various aspects of mother-infant interaction and infant development failed to reflect any effects of the interventions , either at the time the babies were discharged from the hospital or one year later . We attribute the lack of positive findings to the fact that the mothers faced numerous crises in their social environments . We conclude , therefore , that nothing short of massive social change is likely to result in measurable effects ABSTRACT . Ninety-three preterm infants ( M gestational age = 30 wks ; M birth weight = 1204 g ; M ICU duration = 15 days ) were r and omly assigned to a massage therapy group or a control group once they were considered medically stable . The treatment group ( N = 50 ) received three daily 15-minute massages for 10 days . The massage therapy infants gained significantly more weight per day ( 32 vs 29 g ) than did the control infants . Treatment and control groups were divided into high and low weight gainers based on the average weight gain for the control group . Seventy percent of the massage therapy infants were classified as high weight gainers whereas only 40 % of the control infants were classified as high weight gainers . Discriminant function analyses determining the characteristics that distinguished the high from the low weight gainers suggested that the control infants who , before the study , consumed more calories and spent less time in Intermediate care gained more weight . In contrast , for the massage therapy group , the pattern of greater caloric intake and more days in Intermediate care before the study period along with more obstetric complications differentiated the high from the low weight gainers , suggesting that the infants who had experienced more complications before the study benefitted more from the massage therapy . These variables accurately predicted 78 % of the infants who benefited significantly from the massage therapy . Thus , these variables can be used to suggest infants who would benefit most from future massage therapy programs . J Dev Behav Pediatr 14:176–180 , 1993 . Index terms : massage , preterm Preterm infants with periventricular leukomalacia ( PVL ) were evaluated to determine whether multi-sensory stimulation is safe and to assess whether it improved neurobehavior and neurodevelopment . Thirty preterm infants with documented PVL were r and omly assigned to control ( n= 15 ) or experimental ( Group E ) ( n= 15 ) groups at 33 weeks post-conceptional age . Group E infants received 15 minutes of auditory , tactile , visual , and vestibular ( ATVV ) intervention twice a day , five days a week , for four weeks during hospitalization . Repeated measures ANOVA demonstrated that Group E infants experienced significant increases in heart and respiratory rate and a 0.72 % drop in hemoglobin saturation , coinciding with a significant behavioral state shift from sleep to alertness during intervention . No differences were identified in neurobehavioral function and neurodevelopment , indicating that Group E suffered no injury . Group E had an average hospital stay nine days shorter than that of controls , with the associated cost savings of $ 213,840 . The earlier hospital discharge indicates that ATVV intervention promotes alertness without compromising physiologic status in vulnerable infants Behavioral state , heart rate , and respiration were monitored during heelstick procedures in sample s of healthy , term neonates ( N = 48 ) and preterm neonates treated in minimal care ( N = 48 ) and intensive care ( N = 48 ) nurseries . The treated infants who were given pacifiers spent significantly less time fussing and crying during and following the heelstick procedures . Physiologic arousal was monitored in both preterm groups but was attenuated only in the preterm infants who received pacifiers ( minimal care group ) . As similar amounts of sucking were observed in both preterm groups , the inconsistency in treatment effects on behavioral and physiologic arousal was interpreted as a lack of cardiac-somatic coupling in the neonate in intensive care . Results suggest that nonnutritive sucking during heelstick procedures may attenuate behavioral distress in all neonates and physiologic arousal in neonates with less severe postnatal complications Thirty-three mother-infant pairs were r and omly assigned to one of three groups : control , talking , or interactive ( RISS ) . The later treatment included massage , talking , eye contact and rocking . The intervention ( RISS ) was administered to determine whether mothers and their preterm infants who actively interacted with each other would differ on later maternal and infant behaviors . The talking and RISS treatments were administered at specified time intervals 24 hours after delivery . Prior to hospital discharge , mother-infant interaction was assessed during a feeding . Significant differences were identified among the three groups for maternal ( p less than .03 ) and infant ( p less than .05 ) behaviors . These results suggest that active maternal interaction with the premature infant may enhance specific components of mother-infant interaction Attempts to correlate developmental outcome with medical complications affecting the fetus and infant have focused on the prenatal , intrapartum , and postnatal periods . The time beyond the newborn stage has not been explored in detail . The aim of this study was to relate events occurring during the gestational and neonatal periods as well as the infancy periods to later performance by the use of four medical scales . A total of 126 preterm infants were followed up prospect ively from birth to 2 years of age . Medical complications occurring during the prenatal , intrapartum , and postnatal periods as well as the first nine months of life were recovered . No relationship was found between obstetric and neonatal events and developmental outcome . Significant correlations were seen between medical events of later infancy and development at 2 years of age Thirty-seven married first-time fathers attending uncomplicated deliveries of normal infants were r and omly assigned to two groups , holding or not holding at delivery . At 12 to 36 hours postpartum , bonding behavior frequencies were recorded during ten minutes of father-infant interaction . Two observers measured the behaviors ; verbal interaction , smiling , eye contact , fingertip and whole-h and touching . Analysis of the data by multivariate analysis of variance ( MANOVA ) and univariate analysis of variance ( ANOVA ) revealed no difference between the groups ( p greater than .05 ) . More bonding behaviors were noted with increased levels of education , male infants , breastfed infants , and outlet-forcep or cesarean-section deliveries . Early contact did not appear to enhance bonding , although several other factors seemed to be related , indicating a need for further study on paternal bonding OBJECTIVE : Compare responses of nonexposed and drug-exposed newborns to auditory , tactile , visual , and vestibular ( ATVV ) intervention . STUDY DESIGN : Prospect i ve design with r and om assignment of drug-exposed ( N=45 ) and nonexposed ( N=72 ) newborns to control and experimental groups . METHODS : Experimentals received 15 minutes of ATVV twice after birth . Infant behavioral state ( IBS ) and pulse rate ( PR ) were measured . RESULTS : The nonexposed and drug-exposed control groups ( p=0.021 ) differed on the distribution of IBS yet no differences were noted between the two experimental groups . Nonexposed and drug-exposed experimentals experienced more alertness and less quiet sleep than controls ( p<0.05 ) . PR and IBS were significantly correlated for all but the drug-exposed control group ( nonexposed control , r=0.938 , p=0.006 ; nonexposed experimental , r=0.979 , p=0.001 ; drug-exposed experimental , r=0.955 , p=0.003 ) . Within the combined ( control+experimental ) drug-specific groups , only polydrug-exposed infants demonstrated such a correlation ( r=0.584 , p=0.046 ) . A significant correlation was also identified within the cocaine-exposed group for the experimentals only ( r=0.992 , p<0.001 ) . CONCLUSION : The ATVV promoted normal physiologic and behavioral function A prospect i ve observational study of post‐delivery care and neonatal body temperature , carried out at Kathm and u Maternity Hospital , was followed by a r and omized controlled intervention study using three simple methods for maintaining body temperature . There were 500 infants in the initial observation study and 300 in the intervention study . In the observation study , 85 % ( 420/495 ) of infants had temperatures < 36 ° C at 2 h and nearly 50 % ( 198/405 ) had temperatures < 36 ° C at 24 h ( 14 % were < 35 ° C ) . Most of the infants who were cold at 24 h had initially become cold at the time of delivery ( only seven infants had been both well dried and wrapped ) . In the intervention study , all infants were dried and wrapped before r and om assignment to one of the three methods : the “ kangaroo ” method , the traditional “ oil massage ” or a “ plastic swaddler ” . All three were found to be equally effective . Overall , 38 % ( 114/298 ) of the infants had temperatures < 36 ° C at 2 h and 18 % ( 41/231 ) at 24 h ( when none was < 35 ° C ) Thirty-seven infants with severe central nervous system injury or extreme prematurity were r and omly assigned to a multisensory ( auditory-tactile-visual-vestibular ) intervention or control group . Intervention began in the hospital at 33 weeks ' postconceptional age and continued twice daily in the home until 2 months ' corrected age . Mother-infant interactions during feedings were videotaped , and the Bayley Scales of Infant Development were administered . Control mothers stimulated their infants more during feeding , but these significant differences dissipated by 4 months . The presence of periventricular leukomalacia was associated with significantly poorer mental development , regardless of group assignment . Experimental infants tended to exhibit better motor and mental performance and had 23 % fewer cerebral palsy diagnoses at 1 year , but these trends were not statistically significant . The type of brain injury was more important in determining 1-year developmental outcome than type of postnatal experience , suggesting that periventricular leukomalacia presents a major challenge for infant development . ( J Child Neurol 2001;16:493 - 498 ) A nonprobability sample of 14 nonventilated preterm infants , with a mean postconceptional age of 33.9 weeks , was examined to determine their responses to two interventions during apnea . The interventions included a traditional tactile stimulation of moderate shaking applied to the infant 's leg and an experimental oral intervention consisting of taste , smell , and oral tactile stimulation . Infants served as their own control . Each infant received four r and omly assigned trials ( two of each intervention ) when they experienced an apneic episode . The time interval for reinitiation of respiratory effort was significantly shorter after infants received the experimental stimulation ( p = 0.0101 ) . Behavioral state changed to alertness when the infants received the traditional tactile intervention yet remained unchanged when the experimental stimulation was administered during apnea ( p = 0.0202 ) It has been suggested that idiopathic apnea of prematurity is related to hypoxia from pulmonary instability or an immaturity of central respiratory control mechanisms . To explore these hypotheses , 18 preterm infants were studied to examine the therapeutic effects of prophylactic cutaneous stimulation ( 6 ) and continuous positive airway pressure(12 ) . The frequency of apnea using each procedure was reduced by 35 and 69 percent , respectively . These findings constitute the basis for new therapeutic measures for treatment of idiopathic neonatal apnea OBJECTIVE This study examined the effects of stroking and a perioral and intraoral prefeeding stimulation program on healthy , growing , preterm infants in a Level II special care nursery . Only infants without cardiac , gastrointestinal , or central nervous system problems were included in the study . METHOD Two groups of nine r and omly assigned , medically stable preterm infants , born between 30 weeks and 34 weeks gestation , were selected for the study . All infants were introduced to nipple feeding at approximately 34 weeks postconceptual age . The infants in the control group received a 5-min stroking protocol before feeding ; the infants in the experimental group received a 5-min stroking protocol in addition to a perioral and intraoral stimulation program . RESULTS Compared with the control group , the experimental group had a decreased number of gavage feedings , greater weight gain , and fewer days of hospitalization . The experimental group also had higher scores on the Revised-Neonatal Oral Motor Assessment nutritive suck scale than the control group . CONCLUSION On a preliminary basis , the findings from this study establish the efficacy of occupational therapy in a Level II special care nursery for healthy , growing , preterm infants . Further , the specific treatment strategies conducted with the infants receiving the experimental procedures have also been preliminary established as effective in enhancing the infants ' feeding skills , result ing in weight gain and decreased hospital stays as compared with their counterparts in the control group . However , our findings can not be generalized to preterm infant population s who are at greater medical risk than the infants in our study because of the potentially hazardous effects that could result . Implication s of the results for intervention programs and future research are discussed PURPOSE To examine the immediate responses of preterm infants to two forms of unimodal [ auditory only ( A ) and tactile only ( T ) ] and two forms of multimodal sensory stimulation [ auditory , tactile and visual ( ATV ) ; auditory , tactile , visual and vestibular ( ATVV ) ] . METHOD A convenience sample of 54 clinical ly stable preterm infants ( 33 - 34 postconceptional weeks ) was r and omly assigned to 1 of 5 experimental groups [ Control ( C ) ; ( A ) ; ( T ) ; ( ATV ) ; and ( ATVV ) ] . Stimulation was applied for 15 minutes once daily for 4 consecutive days . RESULTS Outcome measures included pulse ( PR ) and respiratory rate ( RR ) , oxygen saturation , behavioral state ( BS ) , and body temperature . Repeated measures ANOVA identified significant differences among the groups during intervention for PR ( p < .001 ) , RR ( p = .01 ) , and BS ( p < .02 ) . Infants receiving any intervention with a tactile component showed increasing arousal ( change in BS ) , and increased PR and RR during stimulation . Group T infants had higher proportions of PR > 180 while Group ATVV had higher proportions of PR < 140 ( p = .0001 ) . Group ATVV showed increased alertness following stimulation ( 24 % ) in contrast to having the least alertness during stimulation ( 11 % ) . CONCLUSIONS Tactile stimulation alone may be too arousing for these infants while the addition of vestibular stimulation may modulate arousal and facilitate optimal arousal prior to feeding |
12,504 | 23,074,403 | SUMMARY OF FINDINGS OF SYSTEMATIC REVIEW : CETUXIMAB OR PANITUMUMAB MONOTHERAPY : Based on moderate GRADE observational evidence , there is improvement in PFS and OS favouring patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation .
CETUXIMAB-IRINOTECAN COMBINATION THERAPY : There is low GRADE evidence that testing for KRAS may optimize survival benefits in patients without the KRAS mutation ( KRAS wildtype , or KRAS WT ) compared to those with the mutation .
However , cetuximab-irinotecan combination treatments based on KRAS status discount any effect of cetuximab in possibly reversing resistance to irinotecan in patients with the mutation , as observed effects were lower than for patients without the mutation .
KRAS status is predictive of outcomes in cetuximab and panitumumab monotherapy , and in cetuximab-irinotecan combination therapy .
While KRAS testing is cost-effective for all strategies considered , it is not equally cost-effective for all treatment options | UNLABELLED In February 2010 , the Medical Advisory Secretariat ( MAS ) began work on evidence -based review s of the literature surrounding three pharmacogenomic tests .
This project came about when Cancer Care Ontario ( CCO ) asked MAS to provide evidence -based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario .
THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER : An Evidence -Based and Economic Analysis Epidermal Growth Factor Receptor Mutation ( EGFR ) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor ( TKI ) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer : an Evidence -Based and Economic Analysis K-RAS testing in Treatment Decisions for Advanced Colorectal Cancer : an Evidence -Based and Economic Analysis .
OBJECTIVE The objective of this systematic review is to determine the predictive value of KRAS testing in the treatment of metastatic colorectal cancer ( mCRC ) with two anti-EGFR agents , cetuximab and panitumumab .
CLINICAL NEED CONDITION AND TARGET POPULATION Metastatic colorectal cancer ( mCRC ) is usually defined as stage IV disease according to the American Joint Committee on Cancer tumour node metastasis ( TNM ) system or stage D in the Duke 's classification system .
Patients with advanced colorectal cancer ( mCRC ) either present with metastatic disease or develop it through disease progression .
KRAS ( Kristen-RAS , a member of the rat sarcoma virus ( ras ) gene family of oncogenes ) is frequently mutated in epithelial cancers such as colorectal cancer , with mutations occurring in mutational hotspots ( codons 12 and 13 ) of the KRAS protein .
Involved in EGFR-mediated signalling of cellular processes such as cell proliferation , resistance to apoptosis , enhanced cell motility and neoangiogenesis , a mutation in the KRAS gene is believed to be involved in cancer pathogenesis .
Such a mutation is also hypothesized to be involved in resistance to targeted anti-EGFR ( epidermal growth factor receptor with tyrosine kinase activity ) treatments such as cetuximab and panitumumab , hence , the important in evaluating the evidence on the predictive value of KRAS testing in this context .
For patients that have not undergone surgery or for whom surgical tissue is not available , a biopsy of either the primary or metastatic site is required to determine their KRAS status .
This is possible as status at the metastatic and primary tumour sites is considered to be similar .
RESEARCH QUESTION To determine if there is predictive value of KRAS testing in guiding treatment decisions with anti-EGFR targeted therapies in advanced colorectal cancer patients refractory to chemotherapy .
Clinical experts have raised concerns about the biological plausibility of this observation and this conclusion would , therefore , be regarded as hypothesis generating . | In a r and omised phase 3 trial , panitumumab significantly improved progression-free survival ( PFS ) in patients with refractory metastatic colorectal cancer ( mCRC ) . This analysis characterises the association of PFS with CRC symptoms , health-related quality of life ( HRQoL ) , and overall survival ( OS ) . CRC symptoms ( NCCN/FACT CRC symptom index , FCSI ) and HRQoL ( EQ-5D ) were assessed for 207 panitumumab patients and 184 best supportive care ( BSC ) patients who had at least one post-baseline patient-reported outcome ( PRO ) assessment . Patients alive at week 8 were included in the PRO and OS analyses and categorised by their week 8 progression status as follows : no progressive disease ( no PD ; best response of at least stable disease ) vs progressive disease ( PD ) . St and ard imputation methods were used to assign missing values . Significantly more patients were progression free at weeks 8–24 with panitumumab vs BSC . After excluding responders , a significant difference in PFS remained favouring panitumumab ( HR=0.63 , 95 % CI=0.52–0.77 ; P<0.0001 ) . At week 8 , lack of disease progression was associated with significantly and clinical ly meaningful lower CRC symptomatology for both treatment groups and higher HRQoL for panitumumab patients only . Overall survival favoured no PD patients vs PD patients alive at week 8 . Lack of disease progression was associated with better symptom control , HRQoL , and OS BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . BACKGROUND 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 ] . ) |
12,505 | 24,353,107 | There is limited quality evidence that water-based exercise training is safe and improves exercise capacity and quality of life in people with COPD immediately after training .
There is limited quality evidence that water-based exercise training offers advantages over l and -based exercise training in improving endurance exercise capacity , but we remain uncertain as to whether it leads to better quality of life .
Little evidence exists examining the long-term effect of water-based exercise training | BACKGROUND L and -based exercise training improves exercise capacity and quality of life in people with chronic obstructive pulmonary disease ( COPD ) .
Water-based exercise training is an alternative mode of physical exercise training that may appeal to the older population attending pulmonary rehabilitation programmes , those who are unable to complete l and -based exercise programmes and people with COPD with comorbid physical and medical conditions .
OBJECTIVES To assess the effects of water-based exercise training in people with COPD . | The aim of this study was to examine the effect of high intensity physical group training in water and on l and for patients with COPD with regard to physical capacity and health related quality of life ( HRQoL ) . A controlled , semi-r and omised study was conducted where 30 patients were r and omised to training either in water or on l and . Thirteen patients constituted a control group . Forty-three out patients , with moderate to severe COPD ( 27w/16 m ) , from two local hospitals in northern Sweden , were included in the study . High intensity physical group training in water ( water group ) or on l and ( l and group ) was performed for 12weeks , three times per week , 45min per session . The control group received no intervention . Pre- and post-intervention , all patients performed incremental and endurance shuttle walking tests ( ISWT and ESWT ) , cycle ergometer tests and responded question naires about HRQoL ( St. Georges Respiratory Question naire -- SGRQ and SF-36 ) . The patients trained with a mean heart rate of 80 - 90 % of peak heart rate . Both training groups increased the distance walked , i.e. l and group in ISWT ( 25 m ) and water group in ESWT ( 179 m ) . The water group increased the distance in ESWT significantly more that both the l and and the control groups . Both training groups increased the time cycled ( 40 - 85s ) and work load ( 10 - 20W ) in the cycle ergometer test . The control group deteriorated in HRQoL according to total score in SGRQ while the training groups remained constant . The water group improved their activity score in SGRQ and their physical health score in SF-36 and those improvements were significant as compared to the l and and the control groups . In conclusion , high intensity physical group training in water is of benefit for patients with COPD . It was in some areas found to be even more effective regarding improvements in physical capacity and experienced physical health compared to the same kind of training on l and L and -based exercise is often difficult for people with chronic obstructive pulmonary disease ( COPD ) who have coexisting obesity or musculoskeletal or neurological conditions . This r and omised controlled trial aim ed to determine the effectiveness of water-based exercise training in improving exercise capacity and quality of life compared to l and -based exercise training and control ( no exercise ) in people with COPD and physical comorbidities . Participants referred to pulmonary rehabilitation were r and omly allocated to a water-based exercise , l and -based exercise or the control group . The two exercise groups trained for 8 weeks , completing three sessions per week . 45 out of 53 participants ( mean±sd age 72±9 years ; forced expiratory volume in 1 s 59±15 % predicted ) completed the study . Compared to controls , water-based exercise training significantly increased 6-min walking distance , incremental and endurance shuttle walk distances , and improved Chronic Respiratory Disease Question naire ( CRDQ ) dyspnoea and fatigue . Compared to l and -based exercise training , water-based exercise training significantly increased incremental shuttle walk distance ( mean difference 39 m , 95 % CI 5–72 m ) , endurance shuttle walk distance ( mean difference 228 m , 95 % CI 19–438 m ) and improved CRDQ fatigue . Water-based exercise training was significantly more effective than l and -based exercise training and control in increasing peak and endurance exercise capacity and improving aspects of quality of life in people with COPD and physical comorbidities Purpose . To investigate effects of decreased training frequency in patients with COPD . Methods . Forty-three COPD patients participated in a controlled study . The intervention group ( 30 patients ) trained 3 times a week during 3 months and once a week during 6 months . Before , after 3 and 9 months all patients performed walking tests , cycle ergometer tests and responded question naires on health-related quality of life ( HRQoL ) ( SGRQ , SF-36 ) . Results . At 9 months compared to 3 months there were no changes in distance walked in the groups . Both groups decreased their VO2peak and the training group deteriorated in HRQoL. At 9 months compared to baseline the training group showed increased distance walked compared to the control group . In the disease-specific SGRQ the training group tended to improve their activity score while the control group tended to deteriorate in total score . In SF-36 the control group decreased their physical component score . Conclusion . Training once a week does not seem to be sufficient to maintain the level achieved after the 3-month period of training in COPD patients . However , training once a week during 6 months preceded by 3 months of high frequency training seems to prevent deterioration in physical capacity and HRQoL compared to baseline . Further studies are needed to investigate how to best sustain the benefits gained after physical training Kurabayashi H , Machida I , H and a H , Akiba T , Kubota K : Comparison of three protocol s for breathing exercises during immersion in 38 ° C water for chronic obstructive pulmonary disease . Am J Phys Med Rehabil 1998;77:145–148 Respiratory function test , arterial blood gas analysis , and ejection fraction were used to compare three protocol s of breathing exercises during immersion in 38 ° C water . Therapy was given for 2 mo to patients with stable chronic obstructive pulmonary disease . Protocol A consisted of a total exercise period of 20 min/wk ( 10 min/day , 2 days/wk ) and was performed by 7 patients ( 5 cases of asthma and 2 cases of emphysema ) . Protocol B consisted of a total exercise period of 120 min/wk ( 20 min x2 per day at 10:00 am and 3:00 pm , 3 days/wk ) and was performed by 9 patients ( 6 asthmas and 3 emphysemas ) . Protocol C consisted of a total exercise period of 120 min/wk ( 20 min/day , 6 days/wk ) and was performed by 8 patients ( 4 asthmas and 4 emphysemas ) . The ratio of forced expired volume in one second to forced vital capacity ( FEV10 % ) was significantly increased in protocol s B and C ( P < 0.01 ) . The ratio of forced vital capacity to the predicted normal value ( % FVC ) was not changed in any of the three protocol s. A significant increase in peak flow was observed in protocol s B and C ( P < 0.05 ) . The maximal expiratory flow at 25 % ( V25 ) was not changed in any of the three protocol s. Pao2 was significantly increased and Paco2 was significantly decreased in protocol B ( P < 0.01 and P < 0.05 , respectively ) , whereas only Paco2 was significantly decreased in protocol C ( P < 0.05 ) . Ejection fraction was increased in protocol s B and C. These results suggest that exercise for a total period of 120 min/wk is preferable to that of 20 min/wk in COPD OBJECTIVE The optimum method for sustaining the benefits gained from pulmonary rehabilitation ( PR ) has not been determined . In this report the authors describe the 4-year referral and uptake patterns to a hospital-based outpatient PR programme , and the sustained benefits of PR in patients with COPD attending a community-based maintenance exercise programme . METHODS Entry and exit data were mapped for all patients referred to the PR service over the review period . All eligible patients were offered a community-based maintenance exercise programme upon completion of PR . A total of 21 patients underwent follow-up assessment of functional exercise capacity , quality of life ( QOL ) and health-care utilization . RESULTS Over a 4-year period , 467 patients ( 80 % with COPD ) were referred to the programme , of whom 230 entered PR . In total , 172 patients completed PR , with attrition ( 25 % ) being mostly due to medical problems . Of the 84 patients who elected for the community-based programme , 46 were still attending at follow up and 21 patients with moderate-to-severe COPD ( 44.9 + /- 12.6 ( mean + /- SD ) FEV(1)% predicted ) were reassessed at 18.4 + /- 11.9 months post PR . Significant improvements ( mean change ( 95 % confidence interval ) ) persisted in 6-min walk distance ( 41.1 m ( 15.7 - 66.5 ) ) , distance walked in 20 min ( 195.1 m ( 82.3 - 308 ) ) and in QOL ( Chronic Respiratory Disease Question naire ) ( 11.0 points ( 4.4 - 17.6 ) ) ( P < 0.01 ) . The QOL improvements exceeded the minimum clinical ly important difference . A trend towards a reduction in COPD -related hospital admissions , bed-days and emergency department presentations was observed in the 12 months following PR . Self-reported adherence with the home exercise programme indicated that 67 % of patients were exercising at least 3 - 5 days each week in addition to attending a class . CONCLUSION For patients with moderate-to-severe COPD , a weekly community-based maintenance exercise class , supervised by a physiotherapist , combined with a home exercise programme is an effective intervention for maintaining improvements following PR OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice AIM To assess the feasibility and acceptability of swimming pool-based exercise as pulmonary rehabilitation ( PR ) for COPD sufferers . METHOD 101 patients with mild or moderate COPD registered with a South London general practice were invited to a swimming pool-based PR programme . Participants completed spirometry , the Chronic Respiratory Question naire ( CRQ-SR ) , and the Incremental Shuttle Walk Test ( ISWT ) before and after the programme . A qualitative interview was used to assess participants ' views . RESULTS 24 patients ( 24 % ) expressed interest ; 18 were recruited and 16 ( 16 % ) completed the PR programme . Their mean age was 69 yrs , seven were female , and mean % predicted FEV1 was 59 % . The mean number of sessions attended was 10.6 out of 12 . Significant improvements in dyspnoea score ( difference 4.9 ; 95 % CI -8.27 to -1.48 ) and walking distance ( difference 32 metres ; 95 % CI -52.63 to -11.36 ) were observed , and all other findings were in the direction of improvement . Most patients enjoyed being in the water , were happy to expose themselves in swimsuits , overcame their fears , valued learning about COPD and socializing with fellow sufferers , and were positive about their physical improvement . CONCLUSION The swimming pool is a feasible and positive alternative venue for PR for COPD patients in primary care OBJECTIVE To determine the importance of a breathing out into water exercise during subtotal immersion for emphysematous patients . DESIGN Results of a respiratory function test and arterial blood gas analysis were examined to compare the programs of breathing exercise with and without the breathing out into water exercise . The breathing exercises in a pool filled with 38 degrees C water were performed 30 min/day , 5 days/wk , for 2 mo in 17 patients with stable chronic emphysema . Patients were r and omly assigned to breathing exercise programs including subtotal water immersion with the nose and mouth either immersed ( 9 patients ) or out of the water ( 8 patients ) during exhalation . RESULTS The ratio of % forced expired volume in 1 sec to forced vital capacity and % forced vital capacity at rest were significantly increased in the program with the breathing out into water exercise , but they did not change in the program without the breathing out into water exercise . A significant increase in peak flow was observed in the former program , although it did not change in the latter program . The maximal expiratory flow at 25 % did not change in either program . Pao2 was significantly increased and Paco2 was significantly decreased in the former program , although a trend for a decrease in Paco2 was observed in the latter program . CONCLUSIONS These results suggest that the breathing out into water exercise enhances the effects of a breathing exercise during immersion and is useful in rehabilitation for chronic pulmonary emphysema |
12,506 | 24,357,869 | 5 A systematic review of 8 controlled trials involving patients with CKD showed that clinical pharmacist interventions improved management of anemia , blood pressure , and lipids , as well as calcium and phosphate parameters .
8 In this patient population , clinical pharmacists ’ interventions reduced hospital admissions , length of hospital stay , and incidence of end-stage renal disease or death .
| Patients with stage 1 to 5 CKD and those undergoing dialysis are at extremely high risk for drug therapy problems ( DTPs ) .
2,3 In controlled trials involving general patient population s , clinical pharmacist interventions have reduced hospital admissions , length of hospital stay , readmis sions , and emergency department visits .
4 - 7 The activities of pharmacists most strongly associated with improved patient outcomes include participating on rounds , interviewing patients , performing medication reconciliation , counselling patients on discharge , and conducting postdischarge followup . | BACKGROUND In patients with chronic kidney disease ( CKD ) , anemia is associated with left ventricular hypertrophy and adverse cardiovascular and clinical outcomes . Moreover , anemia is associated with a reduction in quality of life , particularly when the hemoglobin level drops below 100 g/l . 1 Thus , the goal of treating anemia in iron-replete patients with erythropoietic-stimulating agents ( ESAs ) is to reduce the likelihood of cardiovascular events , improve patients ’ survival , and improve patients ’ quality of life while minimizing any deleterious effects of the drug . Given that ESAs increase blood pressure and have other potential side effects , it is also important to assess whether the quantity of the ESA used might contribute to adverse events such as more rapid deterioration of kidney function , earlier requirement for dialysis , and vascular access failure . It is acknowledged that , if left untreated , patients with severe anemia may require blood transfusions , which have associated risks and costs , and possible implication s for patients awaiting a kidney transplant . In light of this , in most developed countries , the question for CKD patients with significant anemia has often not been whether to use ESAs , but when to use them and what target hemoglobin level to aim for . 2 The earliest anemia correction studies in nondialysischronic kidney disease ( ND-CKD ) and hemodialysis-chronic kidney disease ( HD-CKD ) patients compared the use of erythropoietin a with placebo . 3–5 Most early studies were not design ed and powered to examine clinical outcomes other than quality of life , and no differences were apparent in such other outcomes . Several of the studies showed improvements in quality of life compared with placebo . 3–5 Subsequent r and omized control trials ( RCTs ) have tended to examine the impact of using ESAs to achieve different target hemoglobin level ranges on surrogate endpoints , such as left ventricular ( LV ) mass , where patients with the lower hemoglobin target would be less likely to require the use of an ESA or would require lower doses to maintain the prespecified lower target hemoglobin . Two RCTs 6,7 in HDCKD patients compared with the use of ESAs to achieve intermediate hemoglobin and high hemoglobin targets . Although both studies showed no difference in progression of LV mass , the higher target hemoglobin led to improved quality of life in some of the domains , but the size of BACKGROUND Although recent consensus guidelines proposed more aggressive vancomycin troughs of > 10 or 15 - 20 mg/L for complicated Staphylococcus aureus infections , dosing information to achieve these targets in patients undergoing hemodialysis ( HD ) is scarce . METHODS We used Monte Carlo simulation ( MCS ) methods with a previously published population -pharmacokinetic model and relevant patient demographics to evaluate and revise our existing vancomycin dosing protocol ( 1000-mg load followed by 500-mg maintenance dose , with doses infused during the last hour of dialysis ) . A new protocol ( 1000-mg load followed by 500-mg maintenance dose for patients < 70 kg , 1250-mg followed by 750-mg for those 70 - 100 kg , and 1500-mg followed by 1000-mg for those > 100 kg ) was developed and prospect ively vali date d to achieve therapeutic serum troughs in patients undergoing high-flux HD . RESULTS MCSs predicted that our existing protocol would be suboptimal in more than one-third of patients . Simulations predicted that the new vancomycin dosing protocol would achieve maintenance ( pre-HD ) troughs of 10 - 20 mg/L in 86.0 % of cases including 15 - 20 mg/L in 35.2 % . In prospect i ve validation , the observed postload trough ( pre-HD session 2 ) was 13.5 ± 3.4 mg/L with 76.9 % of levels ( 20 of 26 ) between 10 and 20 mg/L. The observed maintenance trough was 17.3 ± 4.0 mg/L with 65.5 % ( 19 of 29 ) between 10 and 20 mg/L and 89.7 % ( 26 of 29 ) within 10 % of the upper limit ( ie , 10 - 22 mg/L ) . CONCLUSIONS In this study , a practical vancomycin dosing protocol for patients undergoing HD was developed and prospect ively vali date d to achieve therapeutic serum concentrations in the clinical setting BACKGROUND Patients 80 years or older are underrepresented in scientific studies . The objective of this study was to investigate the effectiveness of interventions performed by ward-based pharmacists in reducing morbidity and use of hospital care among older patients . METHODS A r and omized controlled study of patients 80 years or older was conducted at the University Hospital of Uppsala , Uppsala , Sweden . Four hundred patients were recruited consecutively between October 1 , 2005 , and June 30 , 2006 , and were r and omized to control ( n = 201 ) and intervention ( n = 199 ) groups . The interventions were performed by ward-based pharmacists . The control group received st and ard care without direct involvement of pharmacists at the ward level . The primary outcome measure was the frequency of hospital visits ( emergency department and readmissions [ total and drug-related ] ) during the 12-month follow-up period . RESULTS Three hundred sixty-eight patients ( 182 in the intervention group and 186 in the control group ) were analyzed . For the intervention group , there was a 16 % reduction in all visits to the hospital ( quotient , 1.88 vs 2.24 ; estimate , 0.84 ; 95 % confidence interval [ CI ] , 0.72 - 0.99 ) and a 47 % reduction in visits to the emergency department ( quotient , 0.35 vs 0.66 ; estimate , 0.53 ; 95 % CI , 0.37 - 0.75 ) . Drug-related readmissions were reduced by 80 % ( quotient , 0.06 vs 0.32 ; estimate , 0.20 ; 95 % CI , 0.10 - 0.41 ) . After inclusion of the intervention costs , the total cost per patient in the intervention group was $ 230 lower than that in the control group . CONCLUSION If implemented on a population basis , the addition of pharmacists to health care teams would lead to major reductions in morbidity and health care costs Background : Medical in patients are at risk for suboptimal health outcomes from adverse drug events and under-use of evidence -based therapies . We sought to determine whether collaborative care including a team-based clinical pharmacist improves the quality of prescribed drug therapy and reduces hospital readmission . Methods : Multicenter , quasi-r and omized , controlled clinical trial . Consecutive patients admitted to 2 internal and 2 family medicine teams in 3 teaching hospitals between January 30 , 2006 and February 2 , 2007 were included . Team care patients received proactive clinical pharmacist services ( medication history , patient-care round participation , resolution of drug-related issues , and discharge counseling ) . Usual care patients received traditional reactive clinical pharmacist services . The primary outcome was the overall quality score measured retrospectively by a blinded chart review er using 20 indicators targeting 5 conditions . Secondary outcomes included 3- and 6-month readmission . Results : A total of 452 patients ( 220 team care , 231 usual care , mean age : 74 years , 46 % male ) met eligibility criteria . Team care patients were more likely than usual care patients to receive care specified by the indicators overall ( 56.4 % vs. 45.3 % ; adjusted mean difference : 10.4 % ; 95 % confidence interval [ CI ] : 4.9 % , 15.7 % ) and for each targeted disease state except for heart failure . Team care patients experienced fewer readmissions at 3 months ( 36.2 % vs. 45.5 % ; adjusted OR : 0.63 ; 95 % CI : 0.42 , 0.94 ) but not at 6 months ( 50.7 % vs. 56.3 % ; adjusted OR ; 0.78 ; 95 % CI : 0.53 , 1.15 ) . Conclusions : In patients admitted to internal and family medicine teams , team-based care including a clinical pharmacist , improved the overall quality of medication use and reduced rates of readmission BACKGROUND Explicit criteria for judging medication safety and use issues in patients with chronic kidney disease ( CKD ) are lacking . STUDY DESIGN Quality improvement report . SETTING & PARTICIPANTS Nephrologists ( n = 4 ) , primary care physicians ( n = 2 ) , hospital pharmacists with expertise in nephrology ( n = 4 ) , and community pharmacists ( n = 2 ) . The PAIR ( Pharmacotherapy Assessment in Chronic Renal Disease ) criteria were applied retrospectively to 90 patients with CKD in a r and omized study . QUALITY IMPROVEMENT PLAN Development of an explicit set of criteria to enable rapid and systematic detection of drug-related problems ( DRPs ) . Using a R AND method , experts judged the clinical significance of DRPs and the appropriateness of a community pharmacist intervention . The PAIR criteria include 50 DRPs grouped into 6 categories . OUTCOMES DRPs detected using the PAIR criteria compared with implicit clinical judgment by nephrology pharmacists . MEASUREMENTS Prevalence of DRPs and reliability , validity , and responsiveness of the PAIR criteria . RESULTS A mean of 2.5 DRPs/patient ( 95 % CI , 2.0 - 3.1 ) was identified based on the PAIR criteria compared with 3.9 DRPs/patient ( 95 % CI , 3.4 - 4.5 ) based on clinical judgment of nephrology pharmacists . Inter-rater reliability coefficients ( κ ) by PAIR category varied from 0.80 - 1.00 , with an intraclass correlation coefficient ( ICC ) of 0.93 ( 95 % CI , 0.89 - 0.95 ) for total DRPs per patient . Test-retest reliability coefficients by category varied from 0.74 - 1.00 , with an ICC of 0.91 ( 95 % CI , 0.82 - 0.96 ) for total DRPs per patient . During the study , the mean number of DRPs per patient did not change significantly when assessed using the PAIR criteria and clinical judgment . LIMITATION The prevalence of PAIR DRPs may be underestimated due to the retrospective nature of the validation . CONCLUSION The prevalence of DRPs requiring the intervention of community pharmacists is high in patients with CKD . The PAIR criteria are reliable , but their responsiveness remains to be shown |
12,507 | 20,170,770 | Among non-pharmacological therapies , ES for pain relief was unchanged for self-management , education , exercise and acupuncture .
Among pharmacological therapies , the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs , diacerhein and intra-articular ( IA ) corticosteroid was not greatly changed .
ES for pain relief from IA hyaluronic acid , glucosamine sulphate , chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias .
Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo .
CONCLUSION Publication of a large amount of new research evidence has result ed in changes in the calculated risk-benefit ratio for some treatments for OA . | OBJECTIVE To up date evidence for available therapies in the treatment of hip and knee osteoarthritis ( OA ) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009 . | The effect on urine C-telopeptides of type II collagen ( uCTX-II ) of oral and transdermal estradiol treatment was compared using sample s from two r and omized , double-blind , placebo-controlled trials . A total of 171 healthy , Danish postmenopausal women , 45 - 65 years of age completed the 2-year study periods . The uCTX-II marker assessed cartilage degradation , and this response was compared with the effect on urine C-telopeptides of type I collagen ( uCTX-I ) , considered a specific marker of bone resorption . Doses in the oral estradiol treatment groups ( continuous combined therapy ) were 1 mg 17-beta-estradiol+1 mg drosperinone or 1 mg 17-beta-estradiol+2 mg drosperinone or 1 mg 17-beta-estradiol+3 mg drosperinone or placebo . Doses in the transdermal estradiol treatment groups ( continuous combined therapy ) were 45 microg 17-beta-estradiol+30 levonorgestrel or 45 microg 17-beta-estradiol+40 microg levonorgestrel or placebo . The effect of oral and transdermal estradiol therapy on cartilage degradation was reflected as a decrease of 19 - 30 % in uCTX-II ( P=0.02 and P=0.003 vs. placebo ) after 1 year of treatment . uCTX-I decreased 70 % ( P<0.0001 vs. placebo ) reflecting a pronounced effect on bone resorption that was consistent with a 2-year increase in spine and hip BMD of 7 - 8 % and 4 - 6 % , respectively . The results indicate that different regimens of postmenopausal HRT both have an effect on cartilage and bone thus protecting against osteoporosis and osteoarthritis ( OA ) . However , long-term clinical trials are needed to further investigate this issue 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 . ) BACKGROUND Paracetamol is a recommended symptomatic treatment of osteoarthritis ( OA ) , but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used . OBJECTIVES To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment . METHODS A double blind , parallel group , placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee . Patients were r and omly assigned to receive paracetamol 4 g/day ( n = 405 ) or placebo ( n = 374 ) for 6 weeks . Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of > or=30 mm on a 100 mm visual analogue scale . The primary end point was a 30 % decrease of global pain intensity of the knee . Intention to treat analyses were performed . RESULTS The percentage of responders did not differ significantly between groups : 52.6 % and 51.9 % in paracetamol and placebo groups , respectively ( p = 0.840 ) . In a subgroup of patients with chronic mechanical knee pain without signs of inflammation ( n = 123 ) , the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm , in the paracetamol ( n = 63 ) and placebo ( n = 60 ) groups , respectively-mean difference 10.0 mm ; 95 % CI 1.0 to 19.0 ; p = 0.0294 . No serious adverse events were attributable to treatment . CONCLUSION A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found , suggesting that paracetamol use in symptomatic OA of the knee should be further explored . The tolerability and safety of paracetamol , at the recommended maximum dose of 4 g/day , was confirmed over 6 weeks In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life OBJECTIVE Osteoarthritis ( OA ) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States . Methylsulfonylmethane ( MSM ) is a popular dietary supplement used as a single agent and in combination with other nutrients , and purported to be beneficial for arthritis . However , there is paucity of evidence to support the use of MSM . METHODS A r and omized , double-blind , placebo-controlled trial was conducted . Fifty men and women , 40 - 76 years of age with knee OA pain were enrolled in an outpatient medical center . Intervention was MSM 3 g or placebo twice a day for 12 weeks ( 6g/day total ) . Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale ( WOMAC ) , patient and physician global assessment s ( disease status , response to therapy ) , and SF-36 ( overall health-related quality of life ) . RESULTS Compared to placebo , MSM produced significant decreases in WOMAC pain and physical function impairment ( P<0.05 ) . No notable changes were found in WOMAC stiffness and aggregated total symptoms scores . MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation ( P<0.05 ) . CONCLUSION MSM ( 3 g twice a day ) improved symptoms of pain and physical function during the short intervention without major adverse events . The benefits and safety of MSM in managing OA and long-term use can not be confirmed from this pilot trial , but its potential clinical application is examined . Underlying mechanisms of action and need for further investigation of MSM are discussed OBJECTIVE To investigate whether early changes in biochemical markers of bone ( NTX-I ) and cartilage ( CTX-II [ C-terminal crosslinking telopeptide of type II collagen ] ) degradation are associated with radiological progression in patients with knee osteoarthritis ( OA ) receiving risedronate . DESIGN Two thous and four hundred and eighty three patients with medial compartment knee OA were r and omized in two 24-month studies in North America ( NA ) and European Union ( EU ) . Studies evaluated risedronate 5 mg/day , 35 mg/week ( EU ) , 50 mg/week ( NA ) , and 15 mg/day ( NA and EU ) , compared to placebo in reducing signs and symptoms and in slowing radiographic progression . One thous and eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed . RESULTS Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months . Patients who had CTX-II levels returned to low levels ( < 150 ng/mmol creatinine ) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [ odds-ratio ( 95 % confidence interval ) : 0.57 ( 0.39 - 0.85 ) after adjustment for demographics and joint space width ] . The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [ odds-ratio 0.36 ( 0.21 - 0.63 ) ] . No significant association between NTX-I levels and radiological progression was observed . CONCLUSION CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months . Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression Objectives .To estimate cost and outcomes of the Arthritis Foundation aquatic exercise classes from the societal perspective . Design .R and omized trial of 20-week aquatic classes . Cost per quality -adjusted life year ( QALY ) gained was estimated using trial data . Sample size was based on 80 % power to reject the null hypothesis that the cost/QALY gained would not exceed $ 50,000 . Subjects and Methods . Recruited 249 adults from Washington State aged 55 to 75 with a doctor-confirmed diagnosis of osteoarthritis to participate in aquatic classes . The Quality of Well-Being Scale ( QWB ) and Current Health Desirability Rating ( CHDR ) were used for economic evaluation , supplemented by the arthritis-specific Health Assessment Question naire ( HAQ ) , Center for Epidemiologic Studies -Depression Scale ( CES-D ) , and Perceived Quality of Life Scale ( PQOL ) collected at baseline and postclass . Outcome results applied to life expectancy tables were used to estimate QALYs . Use of health care facilities was assessed from diaries/ question naires and Medicare reimbursement rates used to estimate costs . Nonparametric bootstrap sampling of costs/QALY ratios established the 95 % CI around the estimates . Results .Aquatic exercisers reported equal ( QWB ) or better ( CHDR , HAQ , PQOL ) health-related quality of life compared with controls . Outcomes improved with regular class attendance . Costs/QALY gained discounted at 3 % were $ 205,186 using the QWB and $ 32,643 using the CHRD . Conclusion .Aquatic exercise exceeded $ 50,000 per QALY gained using the community-weighted outcome but fell below this arbitrary budget constraint when using the participant-weighted measure . Confidence intervals around these ratios suggested wide variability of cost effectiveness of aquatic exercise BACKGROUND Treatment of osteoarthritis is usually limited to short-term symptom control . We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms . METHODS We did a r and omised , double-blind placebo controlled trial , in which 212 patients with knee osteoarthritis were r and omly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years . Weightbearing , anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years . Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis , whereas minimum joint-space width -- ie , at the narrowest point -- was measured by visual inspection with a magnifying lens . Symptoms were scored by the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index . FINDINGS The 106 patients on placebo had a progressive joint-space narrowing , with a mean joint-space loss after 3 years of -0.31 mm ( 95 % CI -0.48 to -0.13 ) . There was no significant joint-space loss in the 106 patients on glucosamine sulphate : -0.06 mm ( -0.22 to 0.09 ) . Similar results were reported with minimum joint-space narrowing . As assessed by WOMAC scores , symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate . There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups . INTERPRETATION The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis OBJECTIVE Glucosamine products have been used extensively for the management of pain in osteoarthritis ( OA ) . We investigated the efficacy of the hydrochloride salt of glucosamine on pain and disability in knee OA . METHODS At Week -2 , subjects were examined , r and omized , and instructed to take only prescribed acetaminophen for pain . At Week 0 patients were examined , prescribed acetaminophen , and either placebo or glucosamine hydrochloride ( glucosamine ) . At Week 4 the prescriptions for acetaminophen and placebo or glucosamine were renewed . At Weeks 4 and 8 , patients returned diaries and unused medications , and were examined . The WOMAC question naire was administered at Weeks -2 , 0 , and 8 . After completing the r and omized 8 week trial , subjects were offered known glucosamine hydrochloride capsules in an 8 week open label trial , with followup telephone survey after the 8 week open label trial . RESULTS The primary endpoint ( statistically significant difference in WOMAC pain score between Week 0 and Week 8) was not met . However , positive trends were noted for the glucosamine group in 23 of 24 WOMAC questions . A significant difference was noted from Week 5 through Week 8 in the knee examination ( p = 0.026 ) and in the response to a daily diary pain question ( p = 0.018 ) . However , responding to the question , " Are you better than at the start of the trial ? " , 40 % of placebo and only 49 % of glucosamine subjects answered in the affirmative ( p = 0.58 ) . At the end of the r and omized trial , 34 % of placebo and 47 % of glucosamine subjects believed that they had been given glucosamine . After the end of the 8 week open label trial , 77 % of the subjects were still taking glucosamine , although now obliged to pay for commercially available products . CONCLUSION There was no significant difference in pain reduction between the glucosamine hydrochloride and placebo groups as measured by WOMAC . However , the secondary endpoints of cumulative pain reduction as measured by daily diary and knee examination were favorable , suggesting that glucosamine hydrochloride benefits some patients with knee OA BACKGROUND Analgesics are commonly used and may impair kidney function . However , limited prospect i ve information is available on the long-term effects of aspirin , other nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and acetaminophen on renal function . METHODS A total of 1697 women participating in the Nurses ' Health Study provided information on a mailed question naire in 1999 about lifetime use of acetaminophen , aspirin , and NSAIDs and provided blood sample s in 1989 and 2000 . The main outcome was change in estimated glomerular filtration rate ( GFR ) in 11 years . Multivariate logistic regression was used to determine the odds of developing the outcome according to lifetime analgesic intake . RESULTS The mean + /- SD estimated GFR decreased from 88 + /- 17 to 79 + /- 17 mL/min per 1.73 m(2 ) . There were no substantial differences in the unadjusted or estimated GFR levels among the categories of lifetime intake for the 3 analgesic groups at baseline or after 11 years . Acetaminophen use was associated with an increased risk of a GFR decline of at least 30 mL/min per 1.73 m(2 ) ( P trend = .01 ) and a GFR decline of 30 % or greater ( P trend<.001 ) , but aspirin and NSAID use were not . Compared with women consuming less than 100 g of acetaminophen , multivariate-adjusted odds ratio ( 95 % confidence intervals ) for a decline in GFR of at least 30 mL/min per 1.73 m(2 ) for women consuming more than 3000 g was 2.04 ( 1.28 - 3.24 ) . CONCLUSIONS Higher lifetime use of aspirin and NSAIDs is not associated with renal function decline , but high acetaminophen use may increase the risk of loss of renal function . The absolute risk of renal function decline due to even high lifetime analgesic intake seems to be modest OBJECTIVE To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis . DESIGN Ninety patients with knee osteoarthritis were r and omized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline ( treatment group ) or the minimal amount of irrigation ( 250 ml ) required to perform arthroscopy ( placebo group ) . The primary outcome variable was aggregate WOMAC score . RESULTS The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores , the primary outcome variable ; the mean change in aggregate WOMAC score at 12 months was 15.5 ( 95 % CI 7.7 , 23.4 ) for the full irrigation group compared to 8.9 ( 95 % CI 4.9 , 13.0 ) for the minimal irrigation group ( P=0.10 ) . Full irrigation did have a statistically significant effect on patients ' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale ( VAS ) ( the secondary outcome variables ) . Mean change in WOMAC pain scores decreased by 4.2 ( 95 % CI -0.9 , 9.4 ) for the full irrigation group compared with a mean decrease of 2.3 ( 95 % CI -0.1 , 4.7 ) in the minimal irrigation group ( P=0.04 ) . Mean VAS pain scores decreased by 1.47 ( 95 % CI -1.2 , 4.1 ) in the full irrigation group compared to a mean decrease of 0.12 ( 95 % CI 0.0 , 0.3 ) in the minimal irrigation group ( P=0.02 ) . A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessment s and aggregate WOMAC scores at 12 months ; patients with crystals had statistically greater improvements in pain . CONCLUSIONS Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA , particularly in those who have occult intraarticular crystals BACKGROUND Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression . The aim of this r and omized , placebo-controlled trial was to determine whether long-term ( 3-year ) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis , as previously suggested . METHODS Two hundred two patients with knee osteoarthritis ( using American College of Rheumatology criteria ) were r and omized to receive oral glucosamine sulfate , 1500 mg once a day , or placebo . Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint , and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC ( Western Ontario and McMaster Universities ) . RESULTS Osteoarthritis was of mild to moderate severity at enrollment , with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points . Progressive joint space narrowing with placebo use was -0.19 mm ( 95 % confidence interval , -0.29 to -0.09 mm ) after 3 years . Conversely , there was no average change with glucosamine sulfate use ( 0.04 mm ; 95 % confidence interval , -0.06 to 0.14 mm ) , with a significant difference between groups ( P = .001 ) . Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings ( > 0.5 mm ) : 5 % vs 14 % ( P = .05 ) . Symptoms improved modestly with placebo use but as much as 20 % to 25 % with glucosamine sulfate use , with significant final differences on the Lequesne index and the WOMAC total index and pain , function , and stiffness subscales . Safety was good and without differences between groups . CONCLUSION Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis , possibly determining disease modification BACKGROUND Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures , but there is limited evidence to support its use . METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months ' duration and unhealed , as confirmed by magnetic resonance imaging , were r and omly assigned to undergo vertebroplasty or a sham procedure . Participants were stratified according to treatment center , sex , and duration of symptoms ( < 6 weeks or > or = 6 weeks ) . Outcomes were assessed at 1 week and at 1 , 3 , and 6 months . The primary outcome was overall pain ( on a scale of 0 to 10 , with 10 being the maximum imaginable pain ) at 3 months . RESULTS A total of 78 participants were enrolled , and 71 ( 35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group ) completed the 6-month follow-up ( 91 % ) . Vertebroplasty did not result in a significant advantage in any measured outcome at any time point . There were significant reductions in overall pain in both study groups at each follow-up assessment . At 3 months , the mean ( + /-SD ) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3 , respectively ( adjusted between-group difference , 0.6 ; 95 % confidence interval , -0.7 to 1.8 ) . Similar improvements were seen in both groups with respect to pain at night and at rest , physical functioning , quality of life , and perceived improvement . Seven incident vertebral fractures ( three in the vertebroplasty group and four in the placebo group ) occurred during the 6-month follow-up period . CONCLUSIONS We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures , at 1 week or at 1 , 3 , or 6 months after treatment . ( Australian New Zeal and Clinical Trials Registry number , ACTRN012605000079640 . OBJECTIVES Patients with knee osteoarthritis ( OA ) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies . The aim of this study was to compare the benefits of intra-articular corticosteroid injections ( CSIs ) and tidal irrigation ( TI ) in patients with OA of the knee . METHODS We performed a dual-centre , single blind , r and omised , parallel group trial comparing TI and CSI . Patients with knee OA were r and omised to either irrigation using a 3.2 mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1 % lidocaine . Patients were followed for 6 months . The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score ( visual analogue scale , VAS ) . RESULTS One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI . In both treatment groups , over 80 % of patients reported improvement at 2 and 4 weeks . After this time , the benefit of CSI decreased whereas that of TI was maintained : at 26 weeks the pain relief afforded by TI was significantly greater than that of CSI . At 26 weeks 29 % of the CSI group reported improvement vs 64 % of the TI group ( P<0.001 ) . Patients with a knee effusion responded better to both treatments , however , this was most apparent for CSI . Patients with less severe radiographic OA also obtained the greatest improvement from both treatments . CONCLUSION Both procedures lead to significant short-term pain relief of at least 4 weeks , however , TI displayed a significantly greater duration of benefit . Patients with effusions and milder radiographic change obtained the best response to treatment BACKGROUND Vertebroplasty is commonly used to treat painful , osteoporotic vertebral compression fractures . METHODS In this multicenter trial , we r and omly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement ( control group ) . The primary outcomes were scores on the modified Rol and -Morris Disability Question naire ( RDQ ) ( on a scale of 0 to 23 , with higher scores indicating greater disability ) and patients ' ratings of average pain intensity during the preceding 24 hours at 1 month ( on a scale of 0 to 10 , with higher scores indicating more severe pain ) . Patients were allowed to cross over to the other study group after 1 month . RESULTS All patients underwent the assigned intervention ( 68 vertebroplasties and 63 simulated procedures ) . The baseline characteristics were similar in the two groups . At 1 month , there was no significant difference between the vertebroplasty group and the control group in either the RDQ score ( difference , 0.7 ; 95 % confidence interval [ CI ] , -1.3 to 2.8 ; P=0.49 ) or the pain rating ( difference , 0.7 ; 95 % CI , -0.3 to 1.7 ; P=0.19 ) . Both groups had immediate improvement in disability and pain scores after the intervention . Although the two groups did not differ significantly on any secondary outcome measure at 1 month , there was a trend toward a higher rate of clinical ly meaningful improvement in pain ( a 30 % decrease from baseline ) in the vertebroplasty group ( 64 % vs. 48 % , P=0.06 ) . At 3 months , there was a higher crossover rate in the control group than in the vertebroplasty group ( 51 % vs. 13 % , P<0.001 ) [ corrected ] . There was one serious adverse event in each group . CONCLUSIONS Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group . ( Clinical Trials.gov number , NCT00068822 . OBJECTIVE To determine the minimal perceptible clinical improvement ( MPCI ) in patients with osteoarthritis ( OA ) with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) question naire , and patient and investigator global assessment of disease status in r and omized clinical trials for treatment of OA . METHODS Subjects with OA of the knee or hip were r and omized to receive either rofecoxib 12.5 or 25 mg once daily , ibuprofen 800 mg 3 times daily , or placebo for 6 weeks . The WOMAC and global assessment s were completed at baseline and Weeks 2 , 4 , and 6 . A patient global assessment of response to therapy ( 0 to 4 scale ) was used to " anchor " the WOMAC scores . MPCI was defined as the difference in mean change from baseline in WOMAC ( 100 mm normalized visual analog scale , VAS ) between patients with 0 = " None " global response to therapy and patients with 1 = " Poor " global response to therapy . RESULTS MPCI was determined to be 9.7 , 9.3 , and 10.0 mm for the WOMAC pain , physical function and stiffness subscales , respectively , and 11.1 mm for WOMAC question 1 : Pain walking on a flat surface . The MPCI for the investigator was 0.4 with investigator assessment of disease status reported on a 0 to 4 Likert scale . Of note , the estimated MPCI for the WOMAC and investigator globals were similar irrespective of treatment , sex , age , or geographic region . CONCLUSION In this analysis , mean changes of roughly 9 to 12 mm ( 100 mm normalized VAS ) on WOMAC scales were perceptible changes to patients with hip and knee OA . A mean decrease of 0.4 in global disease status ( 0 to 4 Likert scale ) as assessed by the investigator corresponded to the patients ' MPCI . Underst and ing the minimal perceptible differences may permit a better assessment of the clinical relevance of therapeutic interventions in OA Background S-Adenosylmethionine ( SAMe ) is a dietary supplement used in the management of osteoarthritis ( OA ) symptoms . Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs ( NSAIDs ) for comparison . The present study compares the effectiveness of SAMe to a cyclooxygenase-2 ( COX-2 ) inhibitor ( celecoxib ) for pain control , functional improvement and to decrease side effects in people with osteoarthritis of the knee . Methods A r and omized double-blind cross-over study , comparing SAMe ( 1200 mg ) with celecoxib ( Celebrex 200 mg ) for 16 weeks to reduce pain associated with OA of the knee . Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study . Subjects were tested for pain , functional health , mood status , isometric joint function tests , and side effects . Results On the first month of Phase 1 , celecoxib showed significantly more reduction in pain than SAMe ( p = 0.024 ) . By the second month of Phase 1 , there was no significant difference between both groups ( p < 0.01 ) . The duration of treatment and the interaction of duration with type of treatment were statistically significant ( ps ≤ 0.029 ) . On most functional health measures both groups showed a notable improvement from baseline , however no significant difference between SAMe and celecoxib was observed . Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment . ConclusionS AMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis . Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used OBJECTIVE To assess the effects of the prescription formulation of glucosamine sulfate ( 1,500 mg administered once daily ) on the symptoms of knee osteoarthritis ( OA ) during a 6-month treatment course . METHODS Three hundred eighteen patients were enrolled in this r and omized , placebo-controlled , double-blind trial in which acetaminophen , the currently preferred medication for symptomatic treatment of OA , was used as a side comparator . Patients were r and omly assigned to receive oral glucosamine sulfate 1,500 mg once daily ( n = 106 ) , acetaminophen 3 gm/day ( n = 108 ) , or placebo ( n = 104 ) . The primary efficacy outcome measure was the change in the Lequesne index after 6 months . Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and response according to the Osteoarthritis Research Society International criteria . These outcome measures were assessed using an intent-to-treat analysis . RESULTS At baseline , the study patients had moderately severe OA symptoms ( mean Lequesne index approximately 11 points ) . Glucosamine sulfate was more effective than placebo in improving the Lequesne score , with a final decrease of 3.1 points , versus 1.9 with placebo ( difference between glucosamine sulfate and placebo -1.2 [ 95 % confidence interval -2.3 , -0.8 ] ) ( P = 0.032 ) . The 2.7-point decrease with acetaminophen was not significantly different from that with placebo ( difference -0.8 [ 95 % confidence interval -1.9 , 0.3 ] ) ( P = 0.18 ) . Similar results were observed for the WOMAC . There were more responders to glucosamine sulfate ( 39.6 % ) and acetaminophen ( 33.3 % ) than to placebo ( 21.2 % ) ( P = 0.004 and P = 0.047 , respectively , versus placebo ) . Safety was good , and was comparable among groups . CONCLUSION The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms . Although acetaminophen also had a higher responder rate compared with placebo , it failed to show significant effects on the algofunctional indexes OBJECTIVE To determine whether a multimodal physiotherapy programme including taping , exercises , and massage is effective for knee osteoarthritis , and if benefits can be maintained with self management . METHODS R and omised , double blind , placebo controlled trial ; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial . Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practice s for 12 weeks . Physiotherapy included exercise , massage , taping , and mobilisation , followed by 12 weeks of self management . Placebo was sham ultrasound and light application of a non-therapeutic gel , followed by no treatment . Primary outcomes were pain measured by visual analogue scale and patient global change . Secondary measures included WOMAC , knee pain scale , SF-36 , assessment of quality of life index , quadriceps strength , and balance test . RESULTS Using an intention to treat analysis , physiotherapy and placebo groups showed similar pain reductions at 12 weeks : -2.2 cm ( 95 % CI , -2.6 to -1.7 ) and -2.0 cm ( -2.5 to -1.5 ) , respectively . At 24 weeks , pain remained reduced from baseline in both groups : -2.1 ( -2.6 to -1.6 ) and -1.6 ( -2.2 to -1.0 ) , respectively . Global improvement was reported by 70 % of physiotherapy participants ( 51/73 ) at 12 weeks and by 59 % ( 43/73 ) at 24 weeks . Similarly , global improvement was reported by 72 % of placebo participants ( 48/67 ) at 12 weeks and by 49 % ( 33/67 ) at 24 weeks ( all p>0.05 ) . CONCLUSIONS The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . Design R and omised controlled trial and patient preference study . Setting 26 general practice s. Participants People aged ≥50 with knee pain : 282 in r and omised trial and 303 in preference study . Interventions Advice to use topical or oral ibuprofen . Primary outcome measures WOMAC ( Western Ontario and McMaster Universities ) osteoarthritis index , major and minor adverse effects . Results Changes in global WOMAC scores at 12 months were equivalent . In the r and omised trial the difference ( topical minus oral ) was two points ( 95 % confidence interval −2 to 6 ) ; in the preference study , it was one point ( −4 to 6 ) . There were no differences in major adverse effects in the trial or study . The only significant differences in secondary outcomes were in the r and omised trial . The oral group had more respiratory adverse effects ( 17 % v 7%,95 % confidence interval for difference −17 % to −2 % ) , the change in serum creatinine was 3.7 mmol/l less favourable ( 0.9 µmol/l to 6.5 µmol/l ) ; and more participants changed treatments because of adverse effects ( 16 % v 1 % , −16 % to −5 % ) . In the topical group more participants had chronic pain grade III or IV at three months , and more participants changed treatment because of ineffectiveness . Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year , and there are more minor side effects with oral NSAIDs . Topical NSAIDs may be a useful alternative to oral NSAIDs . Trial registration IS RCT N 79353052 OBJECTIVE To examine , in routine practice , the effectiveness and cost-effectiveness of oxycodone ( OxyContin ) compared with st and ard therapy for osteoarthritis pain . STUDY DESIGN Open-label active-controlled r and omized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen ( Percocet ) . METHODS Outcomes and health re source utilization data were collected by telephone interview . Effectiveness was measured among 485 patients as the proportion having at least 20 % improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain score . Quality -adjusted life-years ( QALYs ) were calculated from the Health Utilities Index 3 score . Cost-effectiveness was measured as cost per patient improved and the QALYs gained , using generic oxycodone-acetaminophen in the base case for the healthcare and societal perspectives . Uncertainty was evaluated using multiple 1-way sensitivity analyses and cost-effectiveness acceptability curves . RESULTS Improvement occurred in 62.2 % of patients with oxycodone and in 45.9 % of patients with oxycodone-acetaminophen ( P < .001 ) . After adjustment for baseline differences , 0.0105 QALYs were gained with oxycodone compared with oxycodone-acetaminophen ( P = .17 ) . The mean societal costs per patient during 4 months were 7379 US dollars and 7528 US dollars for oxycodone and oxycodone-acetaminophen , respectively ( P = .33 ) . Oxycodone was more effective and less costly than oxycodone-acetaminophen based on the societal perspective ( including costs associated with time lost ) . Based on the healthcare perspective ( excluding costs associated with time lost ) , the cost-effectiveness of oxycodone was 4883 US dollars per patient improved and 75,810 US dollars per QALY gained . The base-case results were robust . CONCLUSIONS From the societal perspective , oxycodone was more effective and less costly than oxycodone-acetaminophen . From the healthcare perspective , oxycodone ( compared with generic oxycodone-acetaminophen ) fell within the acceptable range of cost-effectiveness between 50,000 US dollars and 100,000 US dollars per QALY gained OBJECTIVES To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs ( NSAIDs ) . DESIGN An equivalence study was design ed to compare the effect of advice to use preferentially oral or topical ibuprofen ( an NSAID ) on knee pain and disability , NSAID-related adverse effects and NHS/societal costs , using a r and omised controlled trial ( RCT ) and a patient preference study ( PPS ) . Reasons for patient preferences for topical or oral preparations , and attitudes to adverse effects , were explored in a qualitative study . SETTING Twenty-six general practice s in the UK . PARTICIPANTS Participants comprised 585 people with knee pain , aged 50 years or over ; 44 % were male , mean age 64 years . The RCT had 282 participants : 144 in the oral group and 138 in the topical group . The PPS had 303 participants : 79 in the oral group and 224 in the topical group . INTERVENTIONS Advice to use preferentially oral or topical NSAIDs for knee pain . OUTCOME MEASURES The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcome measures were the Short Form with 36 Items ( SF-36 ) , perceived troublesomeness of knee pain , satisfaction with health status , major adverse effects ( unplanned hospital admissions and deaths ) and minor adverse events over 12 months . The health economic analysis measured the comparative cost per quality -adjusted life-year ( QALY ) from both an NHS and a societal perspective over 1 and 2 years . RESULTS Changes in the global WOMAC score at 12-months were equivalent in both studies : topical - oral , RCT difference=2 [ 95 % confidence interval ( CI ) -2 to 6 ] , PPS difference=1 ( 95 % CI -4 to 6 ) . There were no differences in the secondary outcomes , except for a suggestion , in the RCT , that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade , and more likely to report changing treatment because of inadequate pain relief . There were no differences in the rate of major adverse effects but some differences in the number of minor ones . In the RCT , 17 % and 10 % in the oral and the topical group , respectively , had a defined respiratory adverse effect ( 95 % CI of difference -17 % to -2.0 % ) ; after 12 months , the change in serum creatinine was 3.7 mmol/l ( 95 % CI 0.9 to 6.5 ) less favourable in the oral than in the topical group , and 11 % of those in the oral group reported changing treatment because of adverse effects compared with 1 % in the topical group ( p=0.02 ) . None of these differences were seen in the PPS . Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively . In the RCT the cost per QALY in the oral group , from an NHS perspective , was in the range 9000 - 12,000 pounds . In the PPS it was 2564 pounds over 1 year , but over 2 years the oral route was more cost-effective . Patient preference for medication type was affected by previous experience of medication ( including adverse reactions ) , other illness , pain elsewhere , anecdotes , convenience , severity of pain and perceived degree of degeneration . Lack of underst and ing about knee pain and the action of medication led to increased tolerance of symptoms . Potentially important symptoms may inadvertently have been disregarded , increasing participants ' risk of suffering a major adverse effect . CONCLUSIONS Advice to use either oral or topical preparations has an equivalent effect on knee pain , but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs . Generally , these results support advising older people with knee pain to use topical rather than oral NSAIDS . However , for patients who prefer oral NSAID preparations rather than a topical NSAID , particularly those with more widespread or severe pain , the oral route is a reasonable treatment option , provided that patients are aware of the risks of potentially serious adverse effects from oral medication . Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs . Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate Abstract Objective : Glucosamine , classified as a slow-acting drug in osteoarthritis ( SADOA ) , is an efficacious chondroprotective agent . Methylsulfonylmethane ( MSM ) , the isoxidised form of dimethyl-sulfoxide ( DSMO ) , is an effective natural analgesic and anti-inflammatory agent . The aim of this study was to compare the efficacy and safety of oral glucosamine ( Glu ) , methylsulfonylmethane ( MSM ) , their combination and placebo in osteoarthritis of the knee . Patients and design : A total of 118 patients of either sex with mild to moderate osteoarthritis were included in the study and r and omised to receive either Glu 500 mg , MSM 500 mg , Glu and MSM or placebo capsules three times daily for 12 weeks . Patients were evaluated at 0 ( before drug administration ) , 2 , 4 , 8 and 12 weeks post-treatment for efficacy and safety . The efficacy parameters studied were the pain index , the swelling index , visual analogue scale pain intensity , 15 m walking time , the Lequesne index , and consumption of rescue medicine . Results : Glu , MSM and their combination significantly improved signs and symptoms of osteoarthritis compared with placebo . There was a statistically significant decrease in mean ( ± SD ) pain index from 1.74 ± 0.47 at baseline to 0.65 ± 0.71 at week 12 with Glu ( p < 0.001 ) . MSM significantly decreased the mean pain index from 1.53 ± 0.51 to 0.74 ± 0.65 , and combination treatment result ed in a more significant decrease in the mean pain index ( 1.7 ± 0.47 to 0.36 ± 0.33 ; p < 0.001 ) . After 12 weeks , the mean swelling index significantly decreased with Glu and MSM , while the decrease in swelling index with combination therapy was greater ( 1.43 ± 0.63 to 0.14 ± 0.35 ; p < 0.05 ) after 12 weeks . The combination produced a statistically significant decrease in the Lequesne index . All treatments were well tolerated . Conclusion : Glu , MSM and their combination produced an analgesic and anti-inflammatory effect in osteoarthritis . Combination therapy showed better efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents . All the treatments were well tolerated . The onset of analgesic and anti-inflammatory activity was found to be more rapid with the combination than with Glu . It can be concluded that the combination of MSM with Glu provides better and more rapid improvement in patients with osteoarthritis BACKGROUND Nonnarcotic analgesics are the most commonly used drugs in the United States . To our knowledge , the association between the use of these analgesics , particularly acetaminophen , and the risk of hypertension among men has not been extensively studied . METHODS The association between analgesic use and risk of incident hypertension was analyzed in a prospect i ve cohort analysis of 16 031 male health professionals without a history of hypertension at baseline . Detailed information about the frequency of use of acetaminophen , nonsteroidal anti-inflammatory drugs , and aspirin was gathered at baseline and up date d 2 years later . The relative risk of incident hypertension during 4 years of follow-up was analyzed using multivariable proportional hazards regression . RESULTS We identified 1968 incident cases of hypertension . After adjusting for multiple potential confounders , men who used acetaminophen 6 to 7 days per week compared with nonusers had a relative risk for incident hypertension of 1.34 ( 95 % confidence interval , 1.00 - 1.79 ; P=.01 for trend ) . This same comparison result ed in relative risks of 1.38 ( 95 % confidence interval , 1.09 - 1.75 ; P=.002 for trend ) for nonsteroidal anti-inflammatory drugs and 1.26 ( 95 % confidence interval , 1.14 - 1.40 ; P<.001 for trend ) for aspirin . We observed similar results when the number of pills per week was analyzed rather than frequency of use in days per week . CONCLUSIONS The frequency of nonnarcotic analgesic use is independently associated with a moderate increase in the risk of incident hypertension . Given the widespread use of these medications and the high prevalence of hypertension , these results may have important public health implication OBJECTIVES To determine the efficacy of community water-based therapy for the management of lower limb osteoarthritis ( OA ) in older patients . DESIGN A pre-experimental matched-control study was used to estimate efficacy of water-based exercise treatment , to check design assumptions and delivery processes . The main study was a r and omised controlled trial of the effectiveness of water-based exercise ( treatment ) compared with usual care ( control ) in older patients with hip and /or knee OA . The latter was accompanied by an economic evaluation comparing societal costs and consequences of the two treatments . SETTING Water exercise was delivered in public swimming pools in the UK . Physical function assessment s were carried out in established laboratory setting s. PARTICIPANTS 106 patients ( 93 women , 13 men ) over the age of 60 years with confirmed hip and /or knee OA took part in the preliminary study . A similar , but larger , group of 312 patients ( 196 women , 116 men ) took part in the main study , r and omised into control ( 159 ) and water exercise ( 153 ) groups . INTERVENTIONS Control group patients received usual care with quarterly semi-structured telephone interview follow-up only . The intervention in the main study lasted for 1 year , with a further follow-up period of 6 months . MAIN OUTCOME MEASURES Pain score on the Western Ontario and McMaster Universities OA index ( WOMAC ) . Additional outcome measures were included to evaluate effects on quality of life , cost-effectiveness and physical function measurements . RESULTS Short-term efficacy of water exercise in the management of lower limb OA was confirmed , with effect sizes ranging from 0.44 [ 95 % confidence interval ( CI ) 0.03 to 0.85 ] on WOMAC pain to 0.76 ( 95 % CI 0.33 to 1.17 ) on WOMAC physical function . Of 153 patients r and omised to treatment , 82 ( 53.5 % ) were estimated to have complied satisfactorily with their treatment at the 1-year point . This had declined to 28 ( 18 % ) by the end of the 6-month follow-up period , during which support for the intervention had been removed and those wishing to continue exercise had to pay their own costs for maintaining their exercise treatment . High levels of co-morbidity were recorded in both groups . Nearly two thirds of all patients had a significant other illness in addition to their OA . Fifty-four control and 53 exercise patients had hospital inpatient episodes during the study period . Water exercise remained effective in the main study but overall effect size was small , on WOMAC pain at 1 year , a reduction of about 10 % in group mean pain score . This had declined , and was non-significant , at 18 months . Mean cost difference estimates showed a saving in the water exercise group of pound123 - -175 per patient per annum and incremental cost-effectiveness ratios ranged from pound3838 to pound5951 per quality -adjusted life-year ( QALY ) . Net reduction in pain was achieved at a net saving of pound135 - -175 per patient per annum and the ceiling valuation of pound580 - -740 per unit of WOMAC pain reduction was favourably low . CONCLUSIONS Group-based exercise in water over 1 year can produce significant reduction in pain and improvement in physical function in older adults with lower limb OA , and may be a useful adjunct in the management of hip and /or knee OA . The water-exercise programme produced a favourable cost -- benefit outcome , using reduction in WOMAC pain as the measure of benefit . Further research is suggested into other similar public health interventions . Investigation is also needed into how general practice can best be supported to facilitate access to participants for research trials in healthcare , as well as an examination of the infrastructure and workforce capacities for physical activity delivery and the potential extent to which healthcare may be supported in this way . More detailed research is required to develop a better underst and ing of the types of exercise that will work for the different biomechanical subtypes of knee and hip OA and investigation is needed on access and environmental issues for physical activity programmes for older people , from both a provider and a participant perspective , the societal costs of the different approaches to the management of OA and longer term trends in outcome measures ( costs and effects ) OBJECTIVE To evaluate the effectiveness of tidal irrigation ( TI ) in comparison with a well-matched sham irrigation ( SI ) procedure as a treatment for knee osteoarthritis ( OA ) . METHODS One hundred eighty subjects with knee OA were r and omized to receive TI or SI , with clinical followup over the ensuing 12 months . The primary outcomes of interest were change in pain and function , as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Subjects and the nurse assessor were blinded , and success of blinding was assessed . RESULTS Although the study groups were otherwise comparable , the baseline WOMAC pain and physical functioning scores were higher ( worse ) in the SI group . After adjustment for baseline , there were no differences between the effects 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 Background Concurrent head-to-head comparisons of healthcare interventions regarding cost-utility are rare . The concept of favorable cost-effectiveness of total hip or knee arthroplasty is thus inadequately verified . Patients and methods In a trial involving several thous and patients from 10 medical specialties , 223 patients who were enrolled for hip or knee replacement surgery were asked to fill in the 15D health-related quality of life ( HRQoL ) survey before and after operation . Results Mean ( SD ) HRQoL score ( on a 0–1 scale ) increased in primary hip replacement patients ( n = 96 ) from 0.81 ( 0.084 ) preoperatively to 0.86 ( 0.12 ) at 12 months ( p < 0.001 ) . In revision hip replacement ( n = 24 ) the corresponding scores were 0.81 ( 0.086 ) and 0.82 ( 0.097 ) respectively ( p = 0.4 ) , and in knee replacement ( n = 103 ) the scores were 0.81 ( 0.093 ) and 0.84 ( 0.11 ) respectively ( p < 0.001 ) . Of 15 health dimensions , there were statistically significant improvements in moving , usual activities , discomfort and symptoms , distress , and vitality in both primary replacement groups . Mean cost per quality -adjusted life year ( QALY ) gained during a 1-year period was € 6,710 for primary hip replacement , € 52,274 for revision hip replacement , and € 13,995 for primary knee replacement . Interpretation Hip and knee replacement both improve HRQoL. The cost per QALY gained from knee replacement is twice that gained from hip replacement BACKGROUND Recommendations state that acetaminophen should be used in preference to nonsteroidal anti-inflammatory drugs in the initial treatment of symptomatic osteoarthritis ( OA ) of the hip or knee , because of lesser toxicity and the pervasive belief that acetaminophen is not only effective in treating OA pain but is of equal analgesic efficacy as nonsteroidal anti-inflammatory drugs . METHODS This was a r and omized , double-blind , placebo-controlled trial of diclofenac sodium , 75 mg twice daily , vs acetaminophen , 1000 mg 4 times daily , in 82 subjects with symptomatic OA of the medial knee . Osteoarthritis was quantitated radiographically , and subjects met stringent baseline pain criteria . The primary evaluation of efficacy used the Western Ontario and McMaster Universities Osteoarthritis Index , with evaluations at screening , baseline , and 2 and 12 weeks after treatment . Intention-to-treat analysis was used . RESULTS Twenty-five subjects were r and omized to diclofenac , 29 to acetaminophen , and 28 to placebo . The groups were closely matched for age , sex , body mass index , prior use of OA medications , baseline pain , and radiographic features . At 2 and 12 weeks , clinical ly and statistically significant ( P<.001 ) improvements were seen in the diclofenac-treated group ; however , no significant improvements were seen in the acetaminophen-treated group ( P = .92 at 2 weeks and .19 at 12 weeks ) . Stratification of subjects according to baseline pain , pre study OA medication , and radiographic grade showed no clear pattern of preferential response to diclofenac , and did not reveal a subset of subjects who responded to acetaminophen . CONCLUSIONS Diclofenac is effective in the symptomatic treatment of OA of the knee , but acetaminophen is not . A review of the literature reveals that there is scanty published evidence for a therapeutic effect of acetaminophen relative to placebo in patients with OA of the knee , because most published studies use active comparators ( ie , nonsteroidal anti-inflammatory drugs ) only . The advocacy of acetaminophen use in subjects with OA of the knee should be reconsidered pending further placebo-controlled studies Objective : Several observational studies indicate that estrogen deficiency increases the incidence of osteoarthritis in postmenopausal women . To vali date this observation , we investigated the effects of ovariectomy ( OVX ) on cartilage erosion in rats using histology and an established bio-assay of cartilage-specific collagen type II degradation products ( CTX-II ) . Furthermore , we investigated whether estrogen and levormeloxifene , a selective estrogen-receptor modulator ( SERM ) , can prevent the OVX-induced changes in cartilage degradation . The clinical relevance was assessed in postmenopausal women by measuring the changes in CTX-II during 12-month treatment with levormeloxifene versus placebo . Design : Sixty 6-month-old rats were divided in five groups . One group was subjected to sham and the others to OVX , followed by treatment with vehicle alone , estradiol or 0.2 mg/kg/day or 5 mg/kg/day of levormeloxifene . The rats were treated for 9 weeks with biweekly blood and urine sampling for measurement of bone resorption and cartilage turnover . After study termination , hind knees were removed for histological analysis of erosions . The effect of levormeloxifene in post-menopausal women was assessed by measuring CTX-II in sample s from 301 women who were participating in a phase II study of this SERM . Results : OVX rats showed significant increases in the urinary excretion of CTX-II . After 9 weeks this was manifested as increased surface erosion of knee articular cartilage compared with sham-operated rats . Treatment with estrogen or levormeloxifene prevented the OVX-induced changes . There was a significant correlation between the 4-week changes in CTX-II and cartilage erosion at week 9 ( r = 0.64 , P < 0.001 ) . In postmenopausal women treated with levormeloxifene , the urinary excretion of CTX-II was decreased by approximately 50 % and restored CTX-II levels to the premenopausal range . Conclusions : This study is the first to demonstrate that a SERM suppresses cartilage degradation in both rodents and humans , suggesting potential therapeutical benefits in the prevention of destructive joint diseases such as osteoarthritis Spa therapy is frequently used in daily rheumatological practice , but its benefit remains to be evaluated . A prospect i ve r and omized controlled study was conducted in 1993 in patients with osteoarthritis of the hip , knee or lumbar spine . Treatment was either spa therapy at Vichy ( France ) of 3 weeks duration ( spa group ) or usual therapy ( control group ) . Assessment criteria were pain ( visual analogue scale ) , functional impairment ( Lequesne 's index for hip or knee disease , Main and Waddell 's for lumbar spinal diseases ) , quality of life index [ revised Arthritis Impact Measurement Scale ( AIMS 2 ) ] , and analgesic and /or non-steroidal anti-inflammatory drug ( NSAID ) consumption . Patients were included by r and omization into one of the two arms ( spa or control ) and assessment criteria were collected before spa therapy or the control period , and 3 and 24 weeks thereafter . A total of 188 patients ( lumbar spine 95 , knee 64 , hip 29 ) were included in the study ( spa group 91 , control group 97 ) . Changes in the assessment criteria after a 6 month follow-up period showed improvement in terms of pain , functional impairment and quality of life , with a reduced intake of symptomatic drugs ( NSAID and analgesic drugs ) in the spa group . This study suggests that spa therapy of 3 weeks duration has a prolonged , beneficial , symptomatic effect in osteoarthritis OBJECTIVE Viscosupplementation with hylan G-F 20 has recently become registered for treatment of patients with osteoarthritis ( OA ) of the knee in most parts of the world . The cost effectiveness and cost utility of this new therapeutic modality were determined as part of a Canadian prospect i ve , r and omized , 1-year , open-label , multicentered trial . DESIGN A total of 255 patients were r and omized to ' Appropriate care with hylan G-F 20 ' ( AC+H ) or ' Appropriate care without hylan G-F 20 ' ( AC ) . Costs ( 1999 Canadian dollars ) were collected from the societal viewpoint and included all costs related to OA of the knee and OA in all joints . Patients completed a number of outcomes question naires including the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and the Health Utilities Index Mark 3 ( HUI3 ) . Data were collected at clinic visits ( baseline , 12 months ) and by telephone ( 1 , 2 , 4 , 6 , 8 , 10 , and 12 months ) . RESULTS The AC+H group over the year had higher costs ( $ 2125-$1415=$710 , P < 0.05 ) , more patients improved ( 69%-40%=29%,P = 0.0001 ) , greater increases in HUI3 ( 0.13 - 0.03=0.10 , P < 0.0001 ) and increased quality -adjusted life years ( QALYs ) ( 0.071 , P < 0.05 ) . The incremental cost-effectiveness ratio was $ 2505/patient improved . The incremental cost-utility ratio was $ 10000/QALY gained . Sensitivity analyses and a second cost perspective gave similar results . CONCLUSION The cost-utility ratio is below the suggested Canadian adoption threshold . The results provide strong evidence for adoption of treatment with hylan G-F 20 in the patients and setting s studied in the trial Context Although many patients use glucosamine to treat osteoarthritis , available studies have reported inconsistent effects of glucosamine on symptoms and joint changes . In addition , previous studies have more often included patients with knee than with hip osteoarthritis . Contribution The investigators r and omly assigned 222 patients with hip osteoarthritis to glucosamine , 1500 mg/d , or placebo . After 2 years of treatment , no clinical ly significant effect on pain , function , or joint space narrowing was found . Caution Twenty of the patients in the trial had joint replacement during the study . The Editors The effectiveness of glucosamine sulfate for treating osteoarthritis is controversial . A 2005 systematic review of 20 trials found evidence to be inconclusive ( 1 ) . In the 15 trials comparing glucosamine with placebo , the overall effect on pain favored glucosamine , but 8 of the trials found no effect on pain . More recent trials ( 24 ) have also yielded inconclusive results . In the Netherl and s and other countries , glucosamine is sold as an over-the-counter dietary supplement and is used by many patients , often on the advice of their physicians . Given the prevalent use of glucosamine , definitive evidence about its effectiveness is needed . Some studies suggest that glucosamine may provide greater benefit to patients with less severe radiographic osteoarthritis than to patients with more severe disease ( 5 , 6 ) . Most previous trials have studied only patients with knee osteoarthritis , with the exception of 3 early trials that included patients with other affected joints ( 79 ) . Trials specifically testing glucosamine in patients with hip osteoarthritis have not been available . Although osteoarthritis of the knee is more common than hip osteoarthritis , hip osteoarthritis is common enough to warrant assessment of glucosamine for this condition . To date , only 2 trials have published data on the effects of glucosamine sulfate on joint structure ( 10 , 11 ) . Some expressed concern about the radiography protocol used in these trials ( 1214 ) , and further study is needed to clarify these findings . To explore some of the uncertainties regarding the effectiveness of glucosamine sulfate , we conducted a 2-year , blinded , r and omized , placebo-controlled trial to evaluate the effect of glucosamine sulfate on the symptomatic and radiographic progression of hip osteoarthritis in patients recruited from primary care setting s. Methods Study Design In this trial , all outcome assessors , patients , data analysts , and research ers were blinded to group assignment . The Medical Ethics Committee of the Erasmus Medical Center , Rotterdam , the Netherl and s , approved the study design , and patients provided written informed consent . We reported the detailed study protocol in 2005 ( 15 ) and summarize it here . Setting and Participants General practitioners in the Rotterdam area recruited study patients . Patients were eligible for inclusion if they met the American College of Rheumatology clinical criteria for hip osteoarthritis ( 16 ) during a screening examination at the research center . Patients who had undergone or were awaiting hip replacement surgery were not eligible . We excluded patients who had a Kellgren and Lawrence score of 4 ( 17 ) , renal disease , liver disease , diabetes mellitus , or a disabling comorbid condition that would make visits to the research center impossible , as well as patients already receiving glucosamine and those unable to fill out Dutch question naires . We encouraged patients who violated study protocol and those who had total hip arthroplasty during the study to complete data collection to limit the loss to follow-up . R and omization and Intervention Eligible patients were r and omly assigned to receive either 1500 mg of oral glucosamine sulfate ( administered once daily as two 750-mg tablets ) or placebo for 2 years . The glucosamine used in this study was provided by Numico Research BV ( Wageningen , the Netherl and s ) but was manufactured by Nutricia Manufacturing USA ( Greenville , South Carolina ) . It contained 2000 mg of D-glucosamine sulfate 2-potassium chloride , which results in a net content of 1500 mg of glucosamine sulfate per 2 pills . The placebo pills were identical in appearance , smell , and taste . We used a computer-generated , blinded r and omization list provided by an independent research er to r and omly assign patients to glucosamine sulfate or placebo . This list , which was r and omized per block of 6 numbers , stratified patients by radiologic findings ( Kellgren and Lawrence score < 2 vs. 2 ) and by local versus generalized osteoarthritis ; patients received a number in chronological order ( 15 ) . Assignment of patients to the right stratum of the r and om assignment list was done by the main research er , who was blinded to therapy . To evaluate blinding , patients had to indicate in the last question naire to which treatment they thought they were r and omly assigned . Outcomes and Follow-up Primary outcome measures were WOMAC 3.1 ( 5-point Likert format ) pain and function over 24 months and joint space narrowing after 24 months ( 18 , 19 ) . Secondary outcome measures were WOMAC pain , function , and stiffness after 3 , 12 , and 24 months ; overall WOMAC stiffness ; a visual analogue scale ( VAS ) to measure pain in the past week ; and pain medication use . The WOMAC subscales are presented as normalized scores ( 0 to 100 , where 0 equals no symptoms ) . We recorded the use of pain medication ; classified patients as never , occasional , or daily users ; and then determined whether people increased , decreased , or did not change their use of pain medication from baseline . In the case of patients with bilateral hip symptoms , we asked patients to indicate their most affected hip for our analyses of joint space narrowing . For patients who were undecided , we used the hip with the highest Kellgren and Lawrence score or the smallest internal rotation during a physical examination . We used QBone Planner 5.4 ( Medis , Leiden , the Netherl and s ) to measure joint space width on calibrated digital radiographs of the hip joints . We read radiographs from both time points ( baseline and 24 months ) side by side . One research er measured joint space width manually on predefined lateral , superior , axial , and medial sites ( 20 ) . In addition to these 4 points , we visually identified and measured the minimal joint space width on both the baseline and 24-month radiograph . We used the smallest of these 6 measurements as the actual minimum joint space width for analyses . A second observer also measured the joint space width in a r and om subset of 28 study patients , and we found high interobserver agreement ( intraclass correlation coefficient of minimal joint space width , 0.98 ) . We collected data for the primary and secondary outcome measures at different time points throughout the study . At baseline and after 24 months , patients came to the Erasmus Medical Center for radiography and to complete study question naires . Weight-bearing , anteroposterior digital radiography of the pelvis was performed according to a highly st and ardized protocol to allow reliable measurement of joint space narrowing ( 15 ) . At baseline and then every 3 months through month 24 , we asked patients to complete the WOMAC instrument , a VAS for pain in the past week ( score range , 0 to 100 ; 0 equals no pain ) , and a checklist for specific adverse events and to answer questions regarding pain medication and adherence . We mailed the intermediate question naires to the patients for completion at home . A research er visited patients every 6 months to deliver a new supply of study medication and evaluate adherence by using the Brief Medication Question naire ( BMQ ) ( 21 ) and a pill count . The BMQ monitors the amount of days per week that patients have taken their study medication . For overall effect , we considered patients to be adherent if they ingested more than 80 % of the total study medication . Statistical Analysis We used the data from all nine 3-month question naires ( at baseline and 3 , 6 , 9 , 12 , 15 , 18 , 21 , and 24 months ) . We also report outcomes for measurements at 3 , 12 , and 24 months and a mean effect of the therapy over 24 months incorporating all scores . We performed the analyses by using SPSS 11.0.1 ( SPSS , Chicago , Illinois ) and SAS 8.2 ( SAS Institute , Cary , North Carolina ) . We used linear mixed models to analyze the data , assuming that data were missing at r and om . We chose an unstructured covariance structure to model the covariance of repeated measures by patients , because this yielded the lowest Akaike information criterion . Fixed effects were time , time by therapy , and the covariates we adjusted for . For patients who had total hip arthroplasty during the trial , we included observed data before surgery in the analysis and assumed data after surgery to be missing . For patients who were lost to follow-up , we included all observed data in the analysis . We adjusted the WOMAC and VAS pain analyses for body mass index , sex , and agefactors that may have influenced symptoms ( 22 , 23 ) . We also adjusted analyses for pain medication use and Kellgren and Lawrence score . The analyses for joint space narrowing were adjusted for Kellgren and Lawrence score ( 24 ) , age , and sex ( 25 ) . We used ordinal regression analysis to assess the effect of glucosamine sulfate on pain medication use by using data from all patients who completed the study and did not have total hip arthroplasty . We performed additional analyses to assess the effect of adherence on the outcome . To explore the validity of the missing-at-r and om data assumption for patients who underwent total hip arthroplasty during the study , we did sensitivity analyses on the WOMAC pain data . In 5 scenarios , the missing data for patients who underwent total hip arthroplasty were imputed with extreme scores : mean of the 5 best scores for the glucosamine sulfate recipients and that of the 5 worst scores for the placebo recipients ( traditional best case ) ; mean of the best scores for placebo recipients OBJECTIVE To evaluate the ability of diacerein , an interleukin-1beta inhibitor , to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis ( OA ) . METHODS In this r and omized , double-blind , placebo-controlled 3-year study , 507 patients with primary OA of the hip ( by the American College of Rheumatology criteria ) received diacerein ( 50 mg twice a day ) or placebo . The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs , using a 0.1-mm-graduated magnifying glass . RESULTS Baseline characteristics were comparable in the 2 treatment groups ( 255 patients receiving diacerein , 252 receiving placebo ) ; 238 patients ( 47 % ) discontinued the study , mainly because of adverse events in the diacerein group ( 25 % versus 12 % with placebo ) and because of inefficacy in the placebo group ( 14 % versus 7 % with diacerein ) . The percentage of patients with radiographic progression , defined by a joint space loss of at least 0.5 mm , was significantly lower in patients receiving diacerein than in patients receiving placebo , both in the intent-to-treat analysis and in the completer analysis ( 50.7 % versus 60.4 % [ P = 0.036 ] and 47.3 % versus 62.3 % [ P = 0.007 ] , respectively ) . In those patients who completed 3 years of treatment , the rate of joint space narrowing was significantly lower with diacerein ( mean + /- SD 0.18 + /- 0.25 mm/year versus 0.23 + /- 0.23 mm/year with placebo ; P = 0.042 ) . Diacerein had no evident effect on the symptoms of OA in this study . However , a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index . Diacerein was well tolerated during the 3-year study . The most frequent adverse events were transient changes in bowel habits . CONCLUSION This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible , and shows , for the first time , that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo , coupled with a good safety profile . The clinical relevance of these findings requires further investigation OBJECTIVE We wanted to assess the effect of rapid diet-induced weight loss on the function of obese , knee osteoarthritis ( OA ) patients . METHODS Eighty patients with knee OA , 89 % women ( n=71 ) , were recruited . Mean ( SD ) body-mass index ( BMI ) was 35.9 ( 5.1 ) kg/m(2 ) and age 62.6 ( 11.1 ) years . Patients were r and omized to either a low-energy diet ( LED 3.4MJ/day ) , or a control diet ( 5MJ/day ) . The LED group had weekly dietary sessions , whereas the control group was given a booklet describing weight loss practice s. Changes in body weight and body composition were examined as independent predictors of changes in knee OA symptoms . Symptoms were monitored by the Western Ontario and McMaster Universities ' ( WOMAC ) OA index . RESULTS The LED and control group lost a mean ( SE ) of 11.1 (0.6)% and 4.3 (0.6)% , respectively , with a mean difference being 6.8 % ( 95 % confidence interval ( CI ) : 5.5 to 8.1 % ; P<0.0001 ) . The decrease in body fat percent was higher in the LED group , 2.2 % ( 1.5 to 3.0 % ; P<0.0001 ) . The total WOMAC index improved in the LED group ( P<0.0001 ) , but not in the control group ( P=0.12 ) , mean difference : -219.3 mm ( -369.2 to -69.4 mm ; P=0.005 ) . The ' Number Needed to Treat ( NNT ) ' to ensure an improvement in WOMAC>/=50 % was 3.4 ( 2.1 to 8.8 ) patients . Changes in total WOMAC index were best predicted by the reduction of body fat percent , with a 9.4 % ( 4.8 to 13.9 % ) improvement in WOMAC for each percent of body fat reduced ( P=0.0005 ) . CONCLUSIONS In our patients with knee OA , a weight reduction of 10 % improved function by 28 % . LED might be of advantage to control diet because of the rapidity of weight loss and a more significant loss of body fat OBJECTIVE Recently we reported that glucosamine sulphate ( GS ) did not have an effect on the symptoms and progression of primary care patients with hip osteoarthritis ( OA ) . The aim of this present study was to investigate whether there are subgroups of patients with hip OA for whom GS might be an effective therapy . METHOD We r and omized 222 patients with hip OA that met one of the American College of Rheumatology criteria to either 1500 mg of oral GS or placebo once daily for 2 years . Subgroup analyses were predefined for radiographic severity ( Kellgren & Lawrence (KL)=1 vs > or=2 ) and for type of OA ( localised vs generalised ) . Additional exploratory subgroup analyses focused on groups based on pain level , pain medication use , baseline joint space width ( JSW ) , and concomitant knee OA at baseline . Primary outcome measures were Western Ontario MacMaster Universities ( WOMAC ) pain and function scores over 24 months , and joint space narrowing ( JSN ) after 24 months . RESULTS In the predefined subgroups based on radiographic severity and type of OA , the outcomes WOMAC pain , function and JSN were similar for the GS and placebo group . CONCLUSION GS was not significantly better than placebo in reducing symptoms and progression of hip OA in subgroups of patients OBJECTIVE Osteoarthritis ( OA ) of the knee causes significant morbidity and current medical treatment is limited to symptom relief , while therapies able to slow structural damage remain elusive . This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate ( CS ) , alone or in combination , as well as celecoxib and placebo on progressive loss of joint space width ( JSW ) in patients with knee OA . METHODS A 24-month , double-blind , placebo-controlled study , conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial ( GAIT ) , enrolled 572 patients with knee OA who satisfied radiographic criteria ( Kellgren/Lawrence [ K/L ] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline ) . Patients with primarily lateral compartment narrowing at any time point were excluded . Patients who had been r and omized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily , CS 400 mg 3 times daily , the combination of glucosamine and CS , celecoxib 200 mg daily , or placebo over 24 months . The minimum medial tibiofemoral JSW was measured at baseline , 12 months , and 24 months . The primary outcome measure was the mean change in JSW from baseline . RESULTS The mean JSW loss at 2 years in knees with OA in the placebo group , adjusted for design and clinical factors , was 0.166 mm . No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group . Treatment effects on K/L grade 2 knees , but not on K/L grade 3 knees , showed a trend toward improvement relative to the placebo group . The power of the study was diminished by the limited sample size , variance of JSW measurement , and a smaller than expected loss in JSW . CONCLUSION At 2 years , no treatment achieved a predefined threshold of clinical ly important difference in JSW loss as compared with placebo . However , knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments OBJECTIVE Strontium ranelate significantly decreases the risk of osteoporotic fractures . The objective of the present study was to investigate whether strontium ranelate ( 2 g/day ) also affects cartilage brakedown as measured by urinary marker of cartilage degradation , design ated CTX-II . METHODS A subgroup of 2617 postmenopausal osteoporotic women ( aged 75.7+/-4.4 years ) were selected from the TROPOS phase III study on the basis of a urinary sampling reported at each visit during the first three years of the study . When included in TROPOS , they were r and omized to strontium ranelate or placebo in a double-blind fashion for 3 years . A calcium and vitamin D supplement was also provided to the subjects during the study . A marker of collagen type II degradation ( CTX-II ) corrected for urinary creatinine ( CTX-II/cr . ) was assessed at regular intervals throughout the study in 1310 patients in strontium ranelate group and 1307 patients in placebo group . RESULTS The response in CTX-II depended on time ( p<0.0001 ) , and this time dependency differed statistically significantly between groups ( time x treatment ) ( p<0.0003 ) . In addition , there was a statistically significant difference between treatments ( p<0.0001 ) . The difference in the response of CTX-II/cr . appeared already after three months , with the strontium ranelate-treated subjects having approximately 15 - 20 % lower values than the placebo-treated subjects for the remaining study period ( p<0.0001 ) . CONCLUSION Treatment with strontium ranelate significantly decreases urinary excretion of CTX-II , a marker of cartilage destruction . Further studies are warranted to investigate an effect on cartilage formation and symptoms of osteoarthritis BACKGROUND Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase ( COX 2 ) inhibitor or a non-steroidal anti-inflammatory drug ( NSAID ) with a proton-pump inhibitor ( PPI ) . These two treatments have similar effectiveness , but they are insufficient for protection of patients at very high risk for ulcer bleeding . We aim ed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs , combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding . METHODS 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre , prospect i ve , r and omised , double-blind trial after admission to hospital with upper-gastrointestinal bleeding . Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative . All patients were given 200 mg celecoxib twice daily . 137 patients were r and omly assigned to receive 20 mg esomeprazole twice daily ( combined-treatment group ) , and 136 to receive a placebo ( control group ) for 12 months . The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00365313 . FINDINGS Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk . The 13-month cumulative incidence of the primary endpoint was 0 % in the combined-treatment group and 12 ( 8.9 % ) in the controls ( 95 % CI difference , 4.1 to 13.7 ; p=0.0004 ) . The median follow-up was 13 months ( range 0.4 - 13.0 ) . Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups . INTERPRETATION Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI . Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding BACKGROUND Oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) are commonly used to relieve the symptoms of osteoarthritis ( OA ) but can produce harmful systemic effects and end-organ damage . A topical NSAID formulation may provide symptom relief with fewer adverse effects . A new topical diclofenac sodium solution-containing the absorption enhancer dimethyl sulfoxide-was evaluated for the relief of the symptoms of primary OA of the knee . METHODS A total of 326 patients met entry criteria ( including abnormal radiographic findings and flare of pain ) and were r and omized to receive 40 drops of topical diclofenac solution or a vehicle-control solution , 4 times daily , for 12 weeks . We evaluated 3 primary outcome measures , the Western Ontario McMaster Universities LK3.1 OA Index ( WOMAC ) pain and physical function subscales and a patient global assessment , and 2 other measures , stiffness and pain on walking , at baseline and after final application . We assessed safety by evaluation of adverse events , vital signs , and irritation at the application site . RESULTS Topical diclofenac solution was significantly more effective than the vehicle-control solution for all outcome measures ; pain , P = .001 ; physical function , P = .002 ; patient global assessment , P = .003 ; stiffness , P = .005 ; and pain on walking , P = .004 . Among patients receiving topical diclofenac , self-limiting minor skin irritation occurred in 68 ( 41.5 % ) of 164 patients , including dryness in 60 ( 36.6 % ) , rash in 18 ( 11.0 % ) , and paresthesia , pruritus , and vesiculobullous rash in 1 ( 0.6 % ) each . There was no significant difference between groups in NSAID-related gastrointestinal tract complaints or in dropouts due to study -related adverse effects . CONCLUSION Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee , with only minor local irritation and no significant systemic adverse events Abstract Objective To evaluate clinical effectiveness of a self management programme for arthritis in patients in primary care with osteoarthritis . Design R and omised controlled trial . Setting 74 general practice s in the United Kingdom . Participants 812 patients aged 50 and over with osteoarthritis of hips or knees ( or both ) and pain or disability ( or both ) . Intervention Participants were r and omised to six sessions of self management of arthritis and an education booklet ( intervention group ) or the education booklet alone ( control group ) . Main outcome measures Primary outcome was quality of life , as assessed by the short form health survey ( SF-36 ) . Several other physical and psychosocial secondary outcomes were assessed . Data were collected at baseline , four months , and 12 months . Results Response rates were 80 % and 76 % at four and 12 months . The two groups showed significant differences at 12 months on the anxiety subscore of the hospital anxiety and depression scale ( mean difference −0.62 , 95 % confidence interval −1.08 to −0.16 ) , arthritis self efficacy scale for pain ( 0.98 , 0.07 to 1.89 ) , and self efficacy for other aspects of management ( 1.58 , 0.25 to 2.90 ) . Results were similar for intention to treat and per protocol analyses . No significant difference was seen in number of visits to the general practitioner at 12 months . Conclusions The self management of arthritis programme reduced anxiety and improved participants ' perceived self efficacy to manage symptoms , but it had no significant effect on pain , physical functioning , or contact with primary care . Trial registration Current Controlled Trials IS RCT N79115352 [ controlled-trials.com ] OBJECTIVE To assess the incidence of Total Joint Replacement ( TJR ) during the long-term follow-up of patients with knee osteoarthritis ( OA ) formerly receiving treatment with glucosamine sulphate or placebo . METHODS Knee OA patients participating in two previous r and omised , placebo-controlled , double-blind , 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months , were systematic ally contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement . RESULTS Out of 340 patients with at least 12 months of treatment , 275 ( i.e. , 81 % ) could be retrieved and interviewed for the present evaluation : 131 formerly on placebo and 144 on glucosamine sulphate . There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up . The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation , making up a total of 2178 patient-years of observation ( including treatment and follow-up ) . Total knee replacement had occurred in over twice as many patients from the placebo group , 19/131 ( 14.5 % ) , than in those formerly receiving glucosamine sulphate , 9/144 ( 6.3 % ) ( P=0.024 , chi-square test ) , with a Relative Risk that was therefore 0.43 ( 95 % confidence interval ( CI ) : 0.20 - 0.92 ) , i.e. , a 57 % decrease compared with placebo . The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased ( P=0.026 ) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate . A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health re sources than those from the placebo group during the last year of follow-up . CONCLUSIONS Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation Background : Treatment of osteoarthritis with oral NSAID therapy provides pain relief but carries a substantial risk of adverse effects . Topical NSAID therapy offers an alternative to oral treatment , with the potential for a reduced risk of side effects . The objective of this trial was to assess the safety and efficacy of a topical diclofenac solution in relieving the symptoms of primary osteoarthritis of the knee . Methods : We identified 248 men and women from southern Ontario with primary osteoarthritis of the knee and at least moderate pain . The patients were r and omly assigned to apply 1 of 3 solutions to their painful knee for 4 weeks : a topical diclofenac solution ( 1.5 % wt/wt diclofenac sodium in a carrier containing dimethyl sulfoxide [ DMSO ] ) ; a vehicle-control solution ( the carrier containing DMSO but no diclofenac ) ; and a placebo solution ( a modified carrier with a token amount of DMSO for blinding purpose s but no diclofenac ) . The primary efficacy end point was pain relief , measured by the Western Ontario and McMaster Universities ( WOMAC ) LK3.0 Osteoarthritis Index pain subscale . Secondary end points were improved physical function and reduced stiffness ( measured by the WOMAC subscales ) , reduced pain on walking and patient global assessment ( PGA ) . Safety was evaluated with clinical and laboratory assessment s. Results : In the intent-to-treat group the mean change ( and 95 % confidence interval [ CI ] ) in pain score from baseline to final assessment was significantly greater for the patients who applied the topical diclofenac solution ( –3.9 [ – 4.8 to –2.9 ] ) than for those who applied the vehicle-control solution ( –2.5 [ – 3.3 to –1.7 ] ; p = 0.023 ) or the placebo solution ( –2.5 [ –3.3 to –1.7 ] ; p = 0.016 ) . For the secondary variables the topical diclofenac solution also revealed superiority to the vehicle-control and placebo solutions , leading to mean changes ( and 95 % CIs ) of –11.6 ( –14.7 to –8.4 ; p = 0.002 and 0.014 , respectively ) in physical function , –1.5 ( –1.9 to –1.1 ; p = 0.015 and 0.002 , respectively ) in stiffness and –0.8 ( –1.1 to –0.6 ; p = 0.003 and 0.015 , respectively ) in pain on walking . The PGA scores were significantly better for the patients who applied the topical diclofenac solution than for those who applied the other 2 solutions ( p = 0.039 and 0.025 , respectively ) . The topical diclofenac solution caused some skin irritation , mostly minor local skin dryness , in 30 ( 36 % ) of the 84 patients , but this led to discontinuation of treatment in only 5 ( 6 % ) of the cases . The incidence of gastrointestinal events did not differ between the treatment groups . No serious gastrointestinal or renal adverse events were reported or detected by means of laboratory testing . Interpretation : This topical diclofenac solution can provide safe , site-specific treatment for osteoarthritic pain , with only minor local skin irritation and minimal systemic side effects BACKGROUND In addition to their antipyretic , anti-inflammatory , and pain-relieving effects , analgesics may interfere with blood pressure regulation . However , little prospect i ve information is available on the association between analgesic use and the risk of hypertension . METHODS We performed a prospect i ve study of 80 020 women aged 31 to 50 years who participated in the Nurses ' Health Study II and had no previous history of hypertension . Frequency of use ( in days per month ) of aspirin , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and acetaminophen was collected by mailed question naire in 1995 . Incident cases of physician-diagnosed hypertension were identified by self-report on the 1997 biennial question naire . RESULTS During 164 090 person-years of follow-up , 1650 incident cases of hypertension were identified . At least 1 d/mo , 51.2 % of the cohort used aspirin , 76.7 % used NSAIDs , and 72.5 % used acetaminophen . After adjusting for age , all 3 classes of analgesics were associated with an increased risk of incident hypertension ( P<.001 for trend ) . After further adjustment for all 3 analgesics and other potential risk factors , only NSAIDs and acetaminophen ( P<.001 for trend for both ) were significantly associated with risk of hypertension . Compared with nonusers , the relative risk of hypertension for women taking NSAIDs 22 d/mo or more was 1.86 ( 95 % confidence interval , 1.51 - 2.28 ) and for those taking acetaminophen 22 d/mo or more was 2.00 ( 95 % confidence interval , 1.52 - 2.62 ) . CONCLUSIONS Use of NSAIDs and use of acetaminophen were significantly associated with increased risk of hypertension , but aspirin use was not . A substantial proportion of hypertension in the United States , and the associated morbidity and mortality , may be due to the use of these medications OBJECTIVE To evaluate the efficacy and safety of diacerein , a drug with interleukin-1beta -- inhibitory activity in vitro , in patients with knee osteoarthritis ( OA ) . METHODS A total of 484 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 16-week , r and omized , double-blind , placebo-controlled , parallel study group with 3 diacerein dosages of 50 mg/day , 100 mg/day , and 150 mg/day ( administered twice daily ) . RESULTS In the intent-to-treat population , 100 mg/day diacerein ( 50 mg twice daily ) was significantly superior ( P < 0.05 ) to placebo using the primary criterion ( visual analog scale [ VAS ] assessment of pain on movement ) . Significant improvement ( P < 0.05 ) was also observed for the secondary criteria , which included the Western Ontario and McMaster Universities OA Index ( WOMAC ) , the WOMAC subscores , and the VAS assessment of h and icap . In patients treated with diacerein dosages of 50 mg/day and 150 mg/day , favorable but not significant results were observed for the primary criterion . The best daily dosage of diacerein , calculated from the effect on the VAS assessment of pain on movement , was 90.1 mg . In the per- protocol population , the analysis of the primary criterion showed significant dose-dependent differences ( P < 0.05 ) between each of the 3 diacerein dosages and the placebo . No differences were observed among the 3 diacerein groups . A significantly higher incidence ( P < 0.05 ) of adverse events ( AEs ) , as well as a higher rate of dropoout due to AEs , was observed in patients treated with 150 mg/day diacerein versus those treated with placebo , 50 mg/day diacerein , or 100 mg/day diacerein . Mild-to-moderate transient changes in bowel habits were the most frequent AEs , increasing with the dosage . CONCLUSION Diacerein , a drug for the treatment of OA , was shown to be an effective treatment for symptoms in patients with knee OA . Taking into account both efficacy and safety , the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day ( 50 mg twice daily ) Objectives To investigate the cost effectiveness of cyclo-oxygenase-2 ( COX 2 ) selective inhibitors and traditional non-steroidal anti-inflammatory drugs ( NSAIDs ) , and the addition of proton pump inhibitors to these treatments , for people with osteoarthritis . Design An economic evaluation using a Markov model and data from a systematic review was conducted . Estimates of cardiovascular and gastrointestinal adverse events were based on data from three large r and omised controlled trials , and observational data were used for sensitivity analyses . Efficacy benefits from treatment were estimated from a meta- analysis of trials reporting total Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index score . Other model inputs were obtained from the relevant literature . The model was run for a hypothetical population of people with osteoarthritis . Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events . Comparators Licensed COX 2 selective inhibitors ( celecoxib and etoricoxib ) and traditional NSAIDs ( diclofenac , ibuprofen , and naproxen ) for which suitable data were available were compared . Paracetamol was also included , as was the possibility of adding a proton pump inhibitor ( omeprazole ) to each treatment . Main outcome measures The main outcome measure was cost effectiveness , which was based on quality adjusted life years gained . Quality adjusted life year scores were calculated from pooled estimates of efficacy and major adverse events ( that is , dyspepsia ; symptomatic ulcer ; complicated gastrointestinal perforation , ulcer , or bleed ; myocardial infa rct ion ; stroke ; and heart failure ) . Results Addition of a proton pump inhibitor to both COX 2 selective inhibitors and traditional NSAIDs was highly cost effective for all patient groups considered ( incremental cost effectiveness ratio less than £ 1000 ( € 1175 , $ 1650 ) ) . This finding was robust across a wide range of effectiveness estimates if the cheapest proton pump inhibitor was used . In our base case analysis , adding a proton pump inhibitor to a COX 2 selective inhibitor ( used at the lowest licensed dose ) was a cost effective option , even for patients at low risk of gastrointestinal adverse events ( incremental cost effectiveness ratio approximately £ 10 000 ) . Uncertainties around relative adverse event rates meant relative cost effectiveness for individual COX 2 selective inhibitors and traditional NSAIDs was difficult to determine . Conclusions Prescribing a proton pump inhibitor for people with osteoarthritis who are taking a traditional NSAID or COX 2 selective inhibitor is cost effective . The cost effectiveness analysis was sensitive to adverse event data and the specific choice of COX 2 selective inhibitor or NSAID agent should , therefore , take into account individual cardiovascular and gastrointestinal risks Objective To evaluate the impact of st and ardised consultations on patients with osteoarthritis of the knee . Design Open pragmatic cluster r and omised controlled trial . Setting Primary care in France . Participants 198 primary care rheumatologists , each of whom had to include two consecutive patients who met the American College of Rheumatology criteria for osteoarthritis of the knee . Interventions St and ardised consultation was provided during three goal oriented visits ( education on osteoarthritis and treatment management ; information on physical exercises ; information on weight loss ) or usual care . Main outcome measures Change in body weight and in time spent on physical exercises ( Baecke index ) at four months . Results 336 patients were included ( 154 allocated to st and ardised consultation and 182 to usual care ) . Nine patients were excluded because of lack of baseline data ( st and ardised consultation , n=8 ; usual care , n=1 ) . At four months , taking into account the clustering effect , the decrease in weight was greater in the st and ardised consultation group than in the usual care group ( mean −1.11 ( SD 2.49 ) kg v −0.37 ( 2.39 ) kg ; P=0.007 ) . The physical activity score was higher for the st and ardised consultation group than for the usual care group ( mean 0.20 ( 0.65 ) v 0.04 ( 0.78 ) ; P=0.013 ) . The st and ardised consultation and usual care groups did not differ in secondary outcomes , except for global assessment of disease activity ( 0 - 10 numeric scale : mean −1.66 ( 2.26 ) v −0.90 ( 2.48 ) ; P=0.003 ) and pain level ( 0 - 10 numeric scale : mean −1.65 ( 2.32 ) v −1.18 ( 2.58 ) ; P=0.04 ) . Conclusions A structured consultation programme for patients with osteoarthritis of the knee result ed in short term improvement in weight loss and time spent on physical activity . Trial registration Clinical trials NCT00462319 PURPOSE To present the safety and effectiveness results of a prototypical 12-week , double-blind , r and omized placebo-controlled trial of glucosamine among subjects with knee osteoarthritis who were recruited and followed entirely over the Internet . METHODS The study comprised 205 subjects aged 45 years or older with symptomatic knee osteoarthritis who were recruited over the Internet ; eligibility was authenticated through medical record review . Participants were assigned r and omly to 1.5 g/d of glucosamine ( n = 101 ) or placebo ( n = 104 ) , of whom 108 completed the intervention ( 93 in each arm ) . The primary outcome measure was the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index ( Likert version ) . Additional outcome measures included the physical function and stiffness subscales and overall score of the question naire , and analgesic use . RESULTS There was no difference between treatment and control groups in terms of change in pain score ( 2.0 + /- 3.4 vs. 2.5 + /- 3.8 , P = 0.41 ) , stiffness ( 0.7 + /- 1.6 vs. 0.8 + /- 1.5 , P = 0.52 ) , physical function ( 5.2 + /- 9.5 vs. 4.6 + /- 9.6 , P = 0.49 ) , overall score ( 7.8 + /- 13.1 vs. 7.8 + /- 13.5 , P = 0.81 ) , and analgesic use ( 133 + /- 553 vs. -88 + /- 755 , P = 0.12 ) . Stratification by osteoarthritis severity , glucosamine product , and use of a nonsteroidal anti-inflammatory drug , as well as exclusion of opiate users , did not alter the results . The number and type of adverse events reported was similar between the groups . CONCLUSION Our results suggest that although glucosamine appears to be safe , it is no more effective than placebo in treating the symptoms of knee osteoarthritis Objective : To evaluate whether exercise treatment based on behavioural grade d activity comprising booster sessions is a cost-effective treatment for patients with osteoarthritis of the hip and /or knee compared with usual care . Methods : An economic evaluation from a societal perspective was carried out alongside a r and omised trial involving 200 patients with osteoarthritis of the hip and /or knee . Outcome measures were pain , physical functioning , self-perceived change and quality of life , assessed at baseline , 13 , 39 and 65 weeks . Costs were measured using cost diaries for the entire follow-up period of 65 weeks . Cost and effect differences were estimated using multilevel analysis . Uncertainty around the cost-effectiveness ratios was estimated by bootstrapping and graphically represented on cost-effectiveness planes . Results : 97 patients received behavioural grade d activity , and 103 patients received usual care . At 65 weeks , no differences were found between the two groups in improvement with respect to baseline on any of the outcome measures . The mean ( 95 % confidence interval ) difference in total costs between the groups was −€773 ( −€2360 to € 772)—that is , behavioural grade d activity result ed in less cost but this difference was non-significant . As effect differences were small , a large incremental cost-effectiveness ratio of € 51 385 per quality adjusted life year was found for grade d activity versus usual care . Conclusions : This study provides no evidence that behavioural grade d activity is either more effective or less costly than usual care . Yielding similar results to usual care , behavioural grade d activity seems an acceptable method for treating patients with osteoarthritis of the hip and /or knee OBJECTIVE Bisphosphonates have slowed the progression of osteoarthritis ( OA ) in animal models and have decreased pain in states of high bone turnover . The Knee OA Structural Arthritis ( KOSTAR ) study , which is the largest study to date investigating a potential structure-modifying OA drug , tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA . METHODS The study group comprised 2,483 patients with medial compartment knee OA and 2 - 4 mm of joint space width ( JSW ) , as determined using fluoroscopically positioned , semiflexed-view radiography . Patients were enrolled in 2 parallel 2-year studies in North America and the European Union . These studies evaluated the efficacy of risedronate at dosages of 5 mg/day , 15 mg/day , 35 mg/week ( in Europe ) , and 50 mg/week ( in North America ) compared with placebo in reducing signs and symptoms , as measured by the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index and patient global assessment ( PGA ) scores , and in slowing radiographic progression . RESULTS A reduction of approximately 20 % in signs and symptoms , as measured by WOMAC subscales and PGA scores , was observed in all groups , with no treatment effect of risedronate demonstrated . Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression ( joint space loss of > or=0.6 mm ) . Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years . A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen , a cartilage degradation marker associated with progressive OA , was seen in patients who received risedronate . No increase in the number of adverse events was demonstrated for risedronate compared with placebo . CONCLUSION Although risedronate ( compared with placebo ) did not improve signs or symptoms of OA , nor did it alter progression of OA , a reduction in the level of a marker of cartilage degradation was observed . A sustained clinical ly relevant improvement in signs and symptoms was observed in all treatment and placebo groups OBJECTIVE To evaluate the efficacy , safety and carry-over effect of diacerein , in comparison to piroxicam , in the treatment of Thai patients with symptomatic knee osteoarthritis ( OA ) . DESIGN This was a double-blind , r and omised , piroxicam-controlled , parallel-group study . A 7-day non-steroidal anti-inflammatory drug washout period was followed by a 16-week treatment period with either diacerein 100mg/day or piroxicam 20mg/day , and an 8-week treatment-free observation period . The primary efficacy criterion was pain on Western Ontario and McMaster University Osteoarthritis ( WOMAC ) A. The secondary criteria included WOMAC B , C and total WOMAC , paracetamol intake , Short Form-36 question naire and global judgements on efficacy and tolerability by patients and investigators . RESULTS Of 171 r and omised patients , 150 completed the study and 161 were analysed in the intent-to-treat population ( diacerein : 82 , piroxicam : 79 ) . Pain ( WOMAC A ) decreased to a similar extent in both groups at Week 16 ( diacerein : -69.7%+/-31.5 % ; piroxicam : -74.1+/-26.2 % ; P = n.s . ) . On treatment discontinuation , pain increased in the piroxicam group at Weeks 20 ( -47%+/-47.8 % ) and 24 ( -26.8%+/-60.6 % ) while improvements persisted in the diacerein group at Weeks 20 ( -66.9%+/-35.9 % ) and 24 ( -69.5%+/-33.7 % ) , with a significant difference in favour of diacerein at Weeks 20 and 24 , demonstrating the carry-over effects of the drug . The incidence of adverse events was similar in both groups but more patients from the piroxicam group dropped out of the study due to these events . CONCLUSIONS Diacerein was as effective as piroxicam in reducing pain and improving function but , unlike piroxicam , displayed a carry-over effect and a better safety profile BACKGROUND Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis , but it is unclear how the procedure achieves this result . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee . METHODS A total of 180 patients with osteoarthritis of the knee were r and omly assigned to receive arthroscopic débridement , arthroscopic lavage , or placebo surgery . Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope . Patients and assessors of outcome were blinded to the treatment-group assignment . Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores -- three on scales for pain and two on scales for function-- and one objective test of walking and stair climbing . A total of 165 patients completed the trial . RESULTS At no point did either of the intervention groups report less pain or better function than the placebo group . For example , mean ( + /-SD ) scores on the Knee-Specific Pain Scale ( range , 0 to 100 , with higher scores indicating more severe pain ) were similar in the placebo , lavage , and débridement groups : 48.9+/-21.9 , 54.8+/-19.8 , and 51.7+/-22.4 , respectively , at one year ( P=0.14 for the comparison between placebo and lavage ; P=0.51 for the comparison between placebo and débridement ) and 51.6+/-23.7 , 53.7+/-23.7 , and 51.4+/-23.2 , respectively , at two years ( P=0.64 and P=0.96 , respectively ) . Furthermore , the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinical ly meaningful difference . CONCLUSIONS In this controlled trial involving patients with osteoarthritis of the knee , the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure Nonprescription doses of naproxen sodium , acetaminophen , and placebo were compared to determine their efficacy and safety in osteoarthritis of the knee . In two identical multicenter , r and omized , double-blind , placebo-controlled , multidose , parallel- design studies , patients with osteoarthritis aged ( mean ± SD ) 60.6 ± 12.8 years were r and omized to daily doses of 660 mg naproxen sodium ( 440 mg naproxen sodium in patients ≥65 years ) , 4000 mg acetaminophen , or placebo for 7 days . Naproxen sodium ( 440/660 mg ) provided significantly greater improvements in pain at rest , on passive motion , on weight-bearing , stiffness after rest ( morning ) , day and night pain compared with placebo , and significantly greater relief from resting pain than acetaminophen ( P < 0.05 ) . Acetaminophen provided significantly greater improvements in day pain compared with placebo . Daily evaluations showed naproxen sodium ( 440/660 mg ) provided superior pain relief to acetaminophen and was significantly better than acetaminophen at reducing difficulties experienced in walking several blocks and difficulties in bending , lifting , and stooping . Naproxen sodium ( 440/660 mg ) and acetaminophen ( 4000 mg ) were significantly more effective than placebo in improving mobility level , household tasks , and walking and bending . Patient and investigator evaluation scores were significantly higher in naproxen sodium and acetaminophen groups compared with placebo ; no differences were observed between active treatments . Naproxen sodium and acetaminophen had similar safety profiles to placebo . Nonprescription doses of naproxen sodium ( 440/660 mg ) effectively relieve pain and other symptoms of osteoarthritis . Naproxen sodium is an alternative in the initial treatment of osteoarthritis and may be preferred to acetaminophen as first-line therapy in patients with moderate or severe pain OBJECTIVE To determine the efficacy and safety of diacerhein , a potential new therapeutic agent with properties differing from those of existing nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and of a combination of diacerhein and an NSAID ( tenoxicam ) in the treatment of osteoarthritis ( OA ) of the hip . METHODS Two hundred eighty-eight patients with painful OA of the hip were enrolled in an 8-week r and omized , double-blind , placebo-controlled , 2 x 2 factorial design study . Four treatment groups were defined : 1 ) diacerhein placebo and tenoxicam placebo , 2 ) tenoxicam and diacerhein placebo , 3 ) diacerhein and tenoxicam placebo , and 4 ) diacerhein and tenoxicam . The daily dosages of diacerhein and tenoxicam were 100 mg and 20 mg , respectively . RESULTS Analyses of efficacy showed no interaction between diacerhein and tenoxicam in terms of efficacy , a clinical ly significant rapid ( < or = 2 weeks ) and persisting effect of tenoxicam during the 8 weeks of the study , and a slow-acting ( 6 weeks ) effect of diacerhein . Moderate , transient diarrhea was the most frequent side effect observed in the diacerhein group ( 37 % ) compared with the placebo group ( 4 % ) . CONCLUSION Both tenoxicam and diacerhein appear to be superior to placebo , and neither agent appears to significantly enhance or detract from the efficacy of the other when they are administered concomitantly . The onset of action of diacerhein appears to be delayed ( > or = 4 weeks ) OBJECTIVE To determine whether the efficacy of diacerein persists at 2 months after the end of a 3-month treatment period , compared with placebo , in patients with painful knee osteoarthritis ( OA ) . METHODS After a 1-week nonsteroidal antiinflammatory drug washout period , patients received either diacerein or placebo for 3 months , followed by an off-treatment period of 3 months to determine the carryover effects of the drug . Although patients were followed up through month 6 , the primary efficacy end point was the percent change from baseline in pain ( Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] A ) at month 5 ( i.e. , 2 months after the end of treatment ) compared with placebo . The co- primary efficacy end point was the percent change from baseline in the total WOMAC score , also at month 5 versus placebo . RESULTS Two hundred three patients were screened , and 168 patients with painful knee OA were r and omized . One hundred sixty-five patients were analyzed in an intent-to-treat analysis . At month 5 , diacerein showed statistically significant superiority versus placebo as assessed with both the WOMAC A ( P < 0.0001 ) and the total WOMAC ( P < 0.0001 ) , demonstrating the carryover effect of the drug . This superiority was already evident from month 2 for pain ( P = 0.001 ) and month 1 for total WOMAC ( P = 0.0021 ) . Diacerein was safe and well tolerated . No serious or previously undocumented adverse events were observed during the study . CONCLUSION This is the first published study of a symptomatic slow-acting OA drug in which the time of assessment of the primary outcome end points was 2 months after the end of a 3-month treatment period . The results show that diacerein is safe and effective for the treatment of knee OA and has a long carryover effect OBJECTIVE To investigate whether oral calcitonin treatment influences the increases in type II collagen ( CII ) degradation and related surface erosions of articular cartilage in ovariectomized rats . METHODS Fifty rats were r and omly allocated into 1 of the 5 following intervention groups : sham-operated , ovariectomy , ovariectomy plus subcutaneously implanted 17beta-estradiol pellet , ovariectomy plus 2 mg/kg salmon calcitonin plus 50 mg/kg 5CNAC ( carrier ) , or ovariectomy plus 50 mg/kg 5CNAC . Each treatment was administered for 9 weeks after the ovariectomy . Blood sample s for biochemical marker analysis were collected from fasting animals at baseline , on day 3 , and after 1 , 2 , 4 , 6 , and 9 weeks . CII degradation was quantified by specific immunoassay , and the changes in severity scores of articular cartilage erosions were visualized and scored in histologic sections of the knees . RESULTS Ovariectomy result ed in a marked increase in serum levels of C-telopeptide of type II collagen ( CTX-II ) ( P < 0.001 ) , which could be effectively reversed by 17beta-estradiol supplementation . Oral administration of calcitonin elicited similar decreases in serum levels of CTX-II ( P < 0.001 ) . Histologic scoring of cartilage erosion showed significantly less cartilage erosion in calcitonin-treated ovariectomized rats versus control ovariectomized rats that were untreated or treated with 5CNAC alone . ( P < 0.01 ) . CONCLUSION The in vivo effects of calcitonin in rats suggest that calcitonin is able to counteract CII degradation and the accompanying structural disintegration of articular cartilage promoted by estrogen deficiency . Clinical assessment of the chondroprotective potential of calcitonin in postmenopausal women seems warranted OBJECTIVE To evaluate long term efficacy of three iterative courses of three weekly intra-articular ( IA ) injections of NRD101 in the treatment of symptomatic knee osteoarthritis ( OA ) . PATIENTS AND METHODS A 1 year prospect i ve , multicentre , r and omised , double blind , placebo controlled study of 301 patients aged > 50 years with painful and radiological medial knee OA . Patients were r and omly assigned into three groups receiving : ( 1 ) three courses of three IA injections of hyaluronic acid ( HA ) + oral placebo ; ( 2 ) IA injections of saline solution + diacerein 100 mg/day ; ( 3 ) IA injections of saline solution + oral placebo . Demographic data and symptomatic criteria -pain , Lequesne 's index , patient 's global assessment of disease activity , percentage of painful days-were obtained during the study ; primary structural criterion was JSW . Efficacy criteria were changes in pain VAS , joint space narrowing ( JSN ) , and percentage of progressors ( JSN > 0.5 mm ) . An intention to treat analysis was used for symptomatic variables , and completer analysis for structural variables . RESULTS Baseline characteristics were similar between the three groups . Mean ( SD ) improvement in pain VAS was clinical ly relevant ( -33.9 ( 27.3 ) , n = 301 ) , but with no difference between the groups ( p = 0.96 ) . JSW deteriorated ( -0.09 ( 0.55 ) mm , n = 277 , p = 0.01 ) , but with no difference between the groups ( p = 0.82 ) . Percentages of progressors were 17.7 , 18.9 , and 20.3 % ( p = 0.90 ) , in groups 1 , 2 , and 3 , respectively . CONCLUSION A weak but statistically significant structural deterioration occurred over 1 year , together with clinical ly relevant symptomatic improvement in patients receiving oral drug and iterative IA injections . Symptomatic and /or structural effects for both this new HA compound and diacerein were not demonstrated BACKGROUND The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown . METHODS We conducted a single-center , r and omized , controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee . Patients were r and omly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone . The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) score ( range , 0 to 2400 ; higher scores indicate more severe symptoms ) at 2 years of follow-up . Secondary outcomes included the Short Form-36 ( SF-36 ) Physical Component Summary score ( range , 0 to 100 ; higher scores indicate better quality of life ) . RESULTS Of the 92 patients assigned to surgery , 6 did not undergo surgery . Of the 86 patients assigned to control treatment , all received only physical and medical therapy . After 2 years , the mean ( + /-SD ) WOMAC score for the surgery group was 874+/-624 , as compared with 897+/-583 for the control group ( absolute difference [ surgery-group score minus control-group score ] , -23+/-605 ; 95 % confidence interval [ CI ] , -208 to 161 ; P=0.22 after adjustment for baseline score and grade of severity ) . The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6 , respectively ( absolute difference , -0.2+/-11.1 ; 95 % CI , -3.6 to 3.2 ; P=0.93 ) . Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery . CONCLUSIONS Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy . ( Clinical Trials.gov number , NCT00158431 . OBJECTIVE Advice to use topical or oral NSAIDs is equally effective for the treatment of knee pain in older people . The ingredient cost of topical preparations is typically more than oral preparations , but could save costs because they have fewer adverse effects . A cost-utility study is needed to decide on their comparative cost effectiveness . METHODS We recruited 585 people aged > or=50 yrs with knee pain ; 282 participated in a r and omized controlled trial and 303 in a patient preference study from 26 MRC General Practice Research Framework practice s in the UK . They received advice to preferentially use topical or oral NSAIDs for knee pain . We calculated the comparative cost per quality -adjusted life year ( QALY ) from both a National Health Service ( NHS ) and a societal perspective over 12 and 24 months . RESULTS Compared with the topical route , oral NSAIDs cost the NHS pound191 and pound72 more over 1 yr in the r and omized trial and preference study , respectively . The cost per QALY , from an NHS perspective , was in the range of pound9000- pound12000 in the r and omized trial . In the preference study , it was pound2564 over 1 yr , but over 2 yrs the oral route was dominant . CONCLUSIONS Our cost-effectiveness analysis supports the use of oral NSAIDs in selected patients . Nevertheless , deciding to recommend oral NSAIDs in preference to topical NSAIDs could have a substantial impact on NHS costs because of the uncertainty in the cost-effectiveness estimate |
12,508 | 15,464,182 | Low- quality trials showed no significant effect of antioxidant supplementation on mortality .
INTERPRETATION We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers ; on the contrary , they seem to increase overall mortality . | BACKGROUND Oxidative stress can cause cancer .
Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality . | The purpose of this study was to evaluate the effect of selenium ( Se ) in the prevention of human primary liver cancer . Three intervention trials were conducted among the residents at high risk to primary liver cancer ( PLC ) in Qidong county , Jiang-su province , the People ’s Republic of China . This area has the second highest rate of PLC in China . One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite ( Se-salt ) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt . The second trial was undertaken among hepatitis B virus surface antigen carriers ( HBVsAg+ ) receiving supplement of 200 μg Se in form of selenized , yeast ( Se-yeast ) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast ( 200 μg of Se daily ) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas BACKGROUND In observational studies , individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer . However , the few r and omized trials of beta-carotene supplementation show no overall benefits ; some even suggest harm . This trial was design ed to test the effects of beta-carotene supplementation in women . METHODS The Women 's Health Study is a r and omized , double-blind , placebo-controlled trial originally testing aspirin , vitamin E , and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older . The beta-carotene component was terminated early after a median treatment duration of 2.1 years ( range = 0.00 - 2 . 72 years ) . Statistical tests were two-sided . RESULTS Among women r and omly assigned to receive beta-carotene ( 50 mg on alternate days ; n = 19 939 ) or placebo ( n = 19 937 ) , there were no statistically significant differences in incidence of cancer , cardiovascular disease , or total mortality after a median of 4.1 years ( 2.1 years ' treatment plus another 2.0 years ' follow-up ) . There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group ( relative risk [ RR ] = 1.03 ; 95 % confidence interval [ CI ] = 0.89 - 1 . 18 ) . There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined . For cardiovascular disease , there were no statistically significant differences for myocardial infa rct ion ( 42 in the beta-carotene group versus 50 in the placebo group ) , stroke ( 61 versus 43 ) , deaths from cardiovascular causes ( 14 versus 12 ) , or the combined end point of these three events ( 116 versus 102 ; among women with more than one event , only the first was counted ) . Deaths from any cause were similar in the two groups ( 59 versus 55 ) . Among smokers at baseline ( 13 % of all women ) , there were no statistically significant differences in overall incidence of cancer ( RR = 1.11 ; 95 % CI = 0.78 - 1.58 ) or cardiovascular disease ( RR = 1.01 ; 95 % CI = 0 . 62 - 1.63 ) . CONCLUSION Among apparently healthy women , there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer . METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers . A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects The association between vegetable and fruit consumption and stomach cancer risk was investigated in the Netherl and s Cohort Study among 120,852 men and women aged 55 - 69 years at the start in September 1986 . Analyses were based on 282 incident stomach cancer cases after 6.3 years of follow-up . Age- and sex-adjusted rate ratios of stomach cancer in increasing quintiles of combined vegetable and fruit consumption were 1.00 , 0.70 , 0.65 , 0.76 , and 0.64 ( p trend = 0.04 ) . Multivariate analysis result ed in rate ratios that were somewhat closer to one ( p trend = 0.14 ) . Furthermore , inverse associations for total vegetables , pulses , raw leafy vegetables , total fruit , citrus fruit , and apples and pears that were observed in crude analyses became weaker or disappeared in multivariate analyses . Total vegetable , but not fruit , consumption was significantly lower in cases diagnosed in the first follow-up year . In analyses limited to first year cases ( resembling a case-control study ) , rate ratios for increasing tertiles of total vegetable consumption were 1.00 , 0.17 , and 0.18 ( p trend = 0.0001 ) , which may indicate the presence of information bias in case-control studies . This prospect i ve study suggests that vegetable and fruit consumption was not clearly associated with stomach cancer risk in the Dutch population . The findings of this study are comparable with findings of other cohort studies , but they do not support the findings of case-control studies High rates of hepatitis B virus ( HBV ) infection and primary liver cancer ( PLC ) are present in Qidong county . Epidemiological surveys demonstrated an inverse association between selenium ( Se ) level and regional cancer incidence , as well as HBV infection . Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2 % and liver precancerous lesion by 75.8 % of ducks , caused by exposure to natural environmental etiologic factors . An intervention trial was undertaken among the general population of 130,471 . Individuals in five townships were involved for observation of the preventive effect of Se . The 8-yr follow-up data showed reduced PLC incidence by 35.1 % in selenized table salt supplemented vs the nonsupplemented population . On withdrawal of Se from the treated group , PLC incidence rate began to increase . However , the inhibitory response to HBV was sustained during the 3-yr cessation of treatment . The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 μg of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group , whereas no incidence of PLC was found in 113 subjects supplemented with Se . Again on cessation of treatment , PLC developed at a rate comparable to that in the control group , demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect Epidemiological and experimental studies have indicated that dietary factors such as vitamin C , vitamin E , and beta-carotene are associated with the risk of colorectal cancer . This study was carried out within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) , whose participants were r and omly assigned to four supplementation groups : ( a ) alpha-tocopherol ( AT ) , 50 mg/day ; ( b ) beta-carotene ( BC ) , 20 mg/day ; ( c ) both AT and BC ; and ( d ) placebo . We included the 15,538 ATBC Study participants who had been r and omized within the areas of three major cities in southern Finl and . Cases of colorectal adenoma ( n = 146 ) were identified by the pathology laboratories in the study areas , and these participants ' medical records were collected and review ed . Alpha-tocopherol supplementation increased the risk for adenomas ( relative risk , 1.66 ; 95 % confidence interval , 1.19 - 2.32 ) , whereas beta-carotene supplementation had no effect on the risk ( relative risk , 0.98 ; 95 % confidence interval , 0.71 - 1.35 ) . Slightly more prediagnosis rectal bleeding and intestinal pain occurred in those adenoma cases who received alpha-tocopherol supplements than in those who did not . Thus , some bias may have result ed , with alpha-tocopherol supplementation leading to more colonoscopies and , thus , to an increased detection of incident polyps in this group . This is further supported by the trial finding that alpha-tocopherol supplementation did not increase the risk of colorectal cancer BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes BACKGROUND Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies . METHODS We prospect ively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts : the Nurses ' Health Study ( 88 764 women ) and the Health Professionals ' Follow-up Study ( 47 325 men ) . Diet was assessed and cumulatively up date d in 1980 , 1984 , 1986 , and 1990 among women and in 1986 and 1990 among men . The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996 , respectively . Relative risk ( RR ) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders . All statistical tests were two-sided . RESULTS With a follow-up including 1 743 645 person-years and 937 cases of colon cancer , we found little association of colon cancer incidence with fruit and vegetable consumption . For women and men combined , a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 ( 95 % confidence interval [ CI ] = 0.98 - 1.05 ) . A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 ( 95 % CI = 0.97 - 1.09 ) . Similar results were obtained for women and men considered separately . A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 ( 95 % CI = 0.89 - 1.03 ) among women and 1 . 08 ( 95 % CI = 1.00 - 1.16 ) among men . For rectal cancer ( total , 244 cases ) , a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 ( 95 % CI = 0.95 - 1.09 ) in men and women combined . None of these associations was modified by vitamin supplement use or smoking habits . CONCLUSIONS Although fruits and vegetables may confer protection against some chronic diseases , their frequent consumption does not appear to confer protection from colon or rectal cancer Background : Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer . This has been supported by animal experimental studies , case control and cohort studies . Material s and Methods : In a prospect i ve intervention study of colorectal adenomas , and intermediary stage in colorectal carcinogenesis , 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg , vitamin C 150 mg , vitamin E 75 mg , selenium 101 µg , and calcium ( 1.6 g daily ) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence . All polyps of < 10 mm at enrolment or follow-up were left unresected until the end of the study . Results : 87–91 % of the patients attended the annual endoscopic follow-up investigations , and 19 % of the patients dropped out of the medical intervention . The rest consumed 85 % of the total amount of tablets over the 3 years . The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group . Diet registration showed that , when adding the intake of antioxidants and calcium from diet and intervention , there was a significant difference between the intake of these substances in the active and the placebo group . No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period . Moreover , there was no effect on polyps of < 5 or 5–9 mm , or on polyps in the different colonic segments analyzed separately . A reduced growth of adenomas was found in patients < 60 years of age taking active medication ( n = 8) compared to those taking placebo ( n = 6 ; mean difference 2.3 mm ; 95 % CI 0.26–4.36 ) . There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis ( log-rank test p value 0.035 ) . Subgroup analysis showed that only the group of patients with no family history of colorectal cancer , those with only one adenoma at inclusion , and those < 65 years benefitted from the intervention medication . Conclusion : The study did not find an overall effect on polyp growth . Our data , however , may support a protective role of calcium and antioxidants on new adenoma formation Because supplements of vitamins C and E had been associated with reduction of fecal mutagen levels , a double-blind r and omized trial was design ed to examine the effects of these vitamins on the rate of recurrence of colorectal polyps , presumed precursors for colorectal cancer . Two hundred patients believed to be free of polyps after removal of at least one colorectal polyp were r and omized to receive a supplement of 400 mg each of ascorbic acid and alpha-tocopherol , or a placebo . Fifteen patients had to be excluded because a review of pathology indicated that their polyps were not adenomatous . A second colonoscopic examination was planned after 2 yr of supplementation . One hundred thirty-seven people ( 75 % of eligible subjects ) completed the study ; polyps were observed in the second colonoscopy in 41.4 % of 70 subjects on vitamin supplements and in 50.7 % of 67 subjects on placebos . After adjustment for differences between groups in demographic and dietary factors before study entry , the relative risk of polyp occurrence was 0.86 , with 95 % confidence limits from 0.51 to 1.45 , in an analysis of 129 subjects with complete information on demographic and dietary factors who had completed the trial . Of the 48 patients who had not completed the study , 7 had died , 33 had not returned to their physician for an examination , and 8 had had a follow-up colonoscopy or sigmoidoscopy . Inclusion of the three polyps found in these eight examinations led to an estimate of relative risk of 0.86 ( 95 % confidence limits , 0.51 to 1.43 ) . The findings of this investigation suggest that any reduction in the rate of polyp recurrence associated with vitamin supplementation is small , and a larger study would be required to ensure that an effect of this size was not a chance finding Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Colonic adenomas represent the natural precursor lesions of most colorectal cancers . The treatment of choice is endoscopic polypectomy . However , after endoscopic removal , polyps recur in a large fraction of cases . Thus , we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps . After polypectomy , 255 individuals were r and omized into three groups . Group 1 was given vitamin A ( 30,000 IU/ day ) , vitamin C ( 1 g/day ) , and vitamin E ( 70 mg/day ) ; Group 2 was given lactulose ( 20 g/day ) ; Group 3 received no treatment . Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma . The remaining 209 individuals were included in the analysis according to the “ intention to treat ” criterion , though 34 did not adhere to the scheduled treatment or were lost during the follow-up . Subjects were followed at regular intervals for an average of 18 months . Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist . In the 209 evaluable subjects , the percentages of recurrence of adenomas were 5.7 percent , 14.7 percent , and 35.9 percent in the vitamins , lactulose , and untreated groups , respectively . The fraction of subjects remaining free of adenomas , estimated by Kaplan-Meier survival curves , was significantly different among the three groups ( log-rank chisquared = 17.138;P < 0.001 ) . Using Cox 's regression analysis , treatment was the only variable that significantly contributed to the model ( regression coefficient=0.905;P<0.001 ) . In conclusion , either antioxidant vitamins or , to a lesser extent , lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents , at least in high-risk individuals The " SUpplementation en VItamines et Minéraux AntioXydants " ( SU.VI.MAX ) Study is a r and omized double-blind , placebo-controlled , primary -prevention trial which started in 1994 in France . This epidemiologic study is design ed to test the efficacy of a daily supplementation with antioxidant vitamins ( vitamin C , 120 mg , vitamin E , 30 mg , and beta-carotene , 6 mg ) and minerals ( selenium , 100 microg , and zinc , 20 mg ) at nutritional doses , in reducing the main causes of premature death ( cancers and cardiovascular diseases ) ; 12,735 eligible subjects ( women aged 35 to 60 years , and men aged 45 to 60 years ) were included in 1994 and and will be followed up for 8 years . Participants undergo a yearly visit consisting , every other year , of either biological sampling or clinical examination . They also regularly provide information on health events and dietary intake by filling out computerized question naires using the Minitel Telematic Network . After 2 years of supplementation , biochemical indicators of vitamin and trace element status reach reasonable level without reaching concentrations as high as those observed in intervention studies , which tested relatively high doses of antioxidants , and ended up with higher risk of pathology BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States . It has been proposed that carotenoids and retinoids are agents that may prevent these disorders . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers , former smokers , and workers exposed to asbestos . The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol ( vitamin A ) in the form of retinyl palmitate per day on the primary end point , the incidence of lung cancer , were compared with those of placebo . RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up ( mean length of follow-up , 4.0 years ) . The active-treatment group had a relative risk of lung cancer of 1.28 ( 95 percent confidence interval , 1.04 to 1.57 ; P=0.02 ) , as compared with the placebo group . There were no statistically significant differences in the risks of other types of cancer . In the active-treatment group , the relative risk of death from any cause was 1.17 ( 95 percent confidence interval , 1.03 to 1.33 ) ; of death from lung cancer , 1.46 ( 95 percent confidence interval , 1.07 to 2.00 ) ; and of death from cardiovascular disease , 1.26 ( 95 percent confidence interval , 0.99 to 1.61 ) . On the basis of these findings , the r and omized trial was stopped 21 months earlier than planned ; follow-up will continue for another 5 years . CONCLUSIONS After an average of four years of supplementation , the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer , cardiovascular disease , and any cause in smokers and workers exposed to asbestos Evidence from both epidemiological and experimental observations have fueled the belief that the high consumption of fruits and vegetables rich in carotenoids may help prevent cancer and heart disease in humans . Because of its well-documented antioxidant and antigenotoxic properties , the carotenoid beta-carotene ( betaCT ) gained most of the attention in the early 1980s and became one of the most extensively studied cancer chemopreventive agents in population -based trials supported by the National Cancer Institute . However , the results of three r and omized lung cancer chemoprevention trials on betaCT supplementation unexpectedly contradicted the large body of epidemiological evidence relating to the potential benefits of dietary carotenoids . Not only did betaCT show no benefit , it was associated with significant increases in lung cancer incidence , cardiovascular diseases , and total mortality . These findings aroused widespread scientific debate that is still ongoing . It also raised the suspicion that betaCT may even possess co-carcinogenic properties . In this review , we summarize the current data on the co-carcinogenic properties of betaCT that is attributed to its role in the induction of carcinogen metabolizing enzymes and the over-generation of oxidative stress . The data presented provide convincing evidence of the harmful properties of this compound if given alone to smokers , or to individuals exposed to environmental carcinogens , as a micronutrient supplement . This has now been directly verified in a medium-term cancer transformation bioassay . In the context of public health policies , while the benefits of a diet rich in a variety of fruits and vegetables should continue to be emphasized , the data presented here point to the need for consideration of the possible detrimental effects of certain isolated dietary supplements , before mass cancer chemoprevention clinical trials are conducted on human subjects . This is especially important for genetically predisposed individuals who are environmentally or occupationally exposed to mutagens and carcinogens , such as those found in tobacco smoke and in industrial setting OBJECTIVE To study the preventive effects of selenium on primary liver cancer . METHODS After screening of blood sample s in 18,000 males from 20 to 65 years-old in Qidong , Jiangsu province ( a high risk area for liver cancer ) , 2,065 cases of HBsAg positive , AFP negative and normal liver function ( normal ALT values ) were found . The subjects were r and omly divided into two groups , based on their residence areas ; 1,112 subjects ( experimental group ) received one tablet of sodium selenite ( 0.5 mg Se ) every day and 953 subjects ( control group ) received one placebo tablet every day . RESULTS During three years of intervention and follow up , the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group ( P < 0.01 ) . At the same time , the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group ( P < 0.01 ) , and the incidence of new liver cancer in the experimental group ( 3 057.55/10(6 ) , 34 cases out of 1,112 subjects ) was significantly lower than the control group ( 5 981.11/10(6 ) ; 57 cases out of 953 subjects ) ( P < 0.01 ) . CONCLUSION The results confirms that selenium supplementation in general population s lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible BACKGROUND People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel . Antioxidant vitamins , which are present in vegetables and fruits , have been associated with a diminished risk of cancers at various anatomical sites . We conducted a r and omized , controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma , a precursor of invasive cancer . METHODS We r and omly assigned 864 patients , using a two-by-two factorial design , to four treatment groups , which received placebo ; beta carotene ( 25 mg daily ) ; vitamin C ( 1 g daily ) and vitamin E ( 400 mg daily ) ; or the beta carotene plus vitamins C and E. In order to identify new adenomas , we performed complete colonoscopic examinations in the patients one year and four years after they entered the study . The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations . RESULTS Patients adhered well to the prescribed regimen , and 751 completed the four-year clinical trial . There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas ; the relative risk for beta carotene was 1.01 ( 95 percent confidence interval , 0.85 to 1.20 ) ; for vitamins C and E , it was 1.08 ( 95 percent confidence interval , 0.91 to 1.29 ) . Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location . CONCLUSIONS The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer . Although our data do not prove definitively that these antioxidants have no anticancer effect , other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits BACKGROUND A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals . In humans , epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian , China , have persistently low intake of multiple nutrients and exhibit one of the world 's highest rates of esophageal/gastric cardia cancer , with an exceptionally high risk of esophageal dysplasia . PURPOSE To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia , we conducted a 6-year prospect i ve intervention trial in Linxian . METHODS Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were r and omly assigned to receive , throughout that period , daily supplementation with 14 vitamins and 12 minerals or placebo . Doses were typically two to three times U.S. Recommended Daily Allowances . Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from sample s of individuals r and omly selected without replacement every 3 months throughout the trial . Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years . RESULTS A total of 324 deaths occurred during the 6-year intervention period ; 167 occurred in the control ( placebo ) group and 157 occurred in the supplement group . Cancer was the leading cause of death ( 54 % of all deaths ) ; 18 % were due to cerebrovascular diseases and 29 % to other causes . Cumulative esophageal/gastric cardia death rates were 8 % lower ( relative risk [ RR ] = 0.92 ; 95 % confidence interval [ CI ] = 0.67 - 1.28 ) among individuals receiving supplements rather than placebo , a nonsignificant ( P > .10 ) difference . Risk of total mortality was 7 % lower ( RR = 0.93 ; 95 % CI = 0.75 - 1.16 ; P > .10 ) , total cancer 4 % lower ( RR = 0.96 ; 95 % CI = 0.71 - 1.29 ; P > .10 ) , cerebrovascular disease 38 % lower ( RR = 0.62 ; 95 % CI = 0.37 - 1.06 ; P = .08 ) , and other diseases 12 % higher ( RR = 1.12 ; 95 % CI = 0.74 - 1.69 ; P > .10 ) among the treated group . Cumulative cancer incidence rates were nearly the same in the two groups . CONCLUSIONS No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus . IMPLICATION S Although no statistically significant short-term benefits were observed , longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia BACKGROUND Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber , beta carotene , and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans . PURPOSE We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25 % of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene ( 20 mg daily ) . METHODS We performed a r and omized , partially double-blinded , placebo-controlled factorial trial in which half the patients were assigned to each intervention , result ing in seven intervention groups and one control group . Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed . Dietary changes were individually initiated and monitored by dietitians and research nurses . At surveillance colonoscopy , the size and location of all polyps were recorded , and their histology was later central ly review ed . Among 424 patients who were r and omly assigned in the trial , 13 were found to be ineligible upon histologic review . Among the remaining 411 , complete outcome data were collected from 390 at 24 months and from 306 at 48 months . All P values are from two-sided tests of statistical significance . RESULTS There was no statistically significant prevention of total new adenomas with any of the interventions . We found a statistically non-significant reduced risk of large adenomas ( > or = 10 mm ) with the low-fat intervention : At 24 months , the odds ratio ( OR ) adjusted for potential confounders = 0.4 and 95 % confidence interval ( CI ) = 0.1 - 1.1 ; at 48 months , OR = 0.3 and 95 % CI = 0.1 - 1.0 . Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran : At 24 months , OR = 0.8 and 95 % CI = 0.3 - 2.2 ; at 48 months , OR = 0.8 and 95 % CI = 0.3 - 2.5 . Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months , a statistically significant finding ( P = .03 ) . CONCLUSIONS Because only small numbers of patients were studied , our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this r and omized , controlled trial must be treated with caution . The results do suggest , however , that these interventions may reduce the transition from smaller to larger adenomas , a step that may critically define those adenomas most likely to progress to malignancy BACKGROUND Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural population s living in the province of Nariño , Colombia , in the And es Mountains . METHODS A r and omized , controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and /or intestinal metaplasia , two precancerous lesions . Individuals were assigned to receive anti-Helicobacter pylori triple therapy and /or dietary supplementation with ascorbic acid , beta-carotene , or their corresponding placebos . Gastric biopsy specimens taken at baseline were compared with those taken at 72 months . Relative risks of progression , no change , and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects . All statistical tests were two-sided . RESULTS All three basic interventions result ed in statistically significant increases in the rates of regression : Relative risks were 4.8 ( 95 % confidence interval [ CI ] = 1.6 - 14.2 ) for anti-H. pylori treatment , 5 . 1 ( 95 % CI = 1.7 - 15.0 ) for beta-carotene treatment , and 5.0 ( 95 % CI = 1.7 - 14.4 ) for ascorbic acid treatment in subjects with atrophy . Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 ( 95 % CI = 1.0 - 9.3 ) , 3.4 ( 95 % CI = 1.1 - 9.8 ) , and 3.3 ( 95 % CI = 1.1 - 9.5 ) . Combinations of treatments did not statistically significantly increase the regression rates . Curing the H. pylori infection ( which occurred in 74 % of the treated subjects ) produced a marked and statistically significant increase in the rate of regression of the precursor lesions ( relative risks = 8.7 [ 95 % CI = 2.7 - 28.2 ] for subjects with atrophy and 5.4 [ 95 % CI = 1.7 - 17.6 ] for subjects with intestinal metaplasia ) . CONCLUSIONS In the very high-risk population studied , effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process , mostly by increasing the rate of regression of cancer precursor lesions , and may be an effective strategy to prevent gastric carcinoma BACKGROUND It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease , cancer , and other adverse outcomes . METHODS 20,536 UK adults ( aged 40 - 80 ) with coronary disease , other occlusive arterial disease , or diabetes were r and omly allocated to receive antioxidant vitamin supplementation ( 600 mg vitamin E , 250 mg vitamin C , and 20 mg beta-carotene daily ) or matching placebo . Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants . An average of 83 % of participants in each treatment group remained compliant during the scheduled 5-year treatment period . Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol , increased that of vitamin C by one-third , and quadrupled that of beta-carotene . Primary outcomes were major coronary events ( for overall analyses ) and fatal or non-fatal vascular events ( for subcategory analyses ) , with subsidiary assessment s of cancer and of other major morbidity . FINDINGS There were no significant differences in all-cause mortality ( 1446 [ 14.1 % ] vitamin-allocated vs 1389 [ 13.5 % ] placebo-allocated ) , or in deaths due to vascular ( 878 [ 8.6 % ] vs 840 [ 8.2 % ] ) or non-vascular ( 568 [ 5.5 % ] vs 549 [ 5.3 % ] ) causes . Nor were there any significant differences in the numbers of participants having non-fatal myocardial infa rct ion or coronary death ( 1063 [ 10.4 % ] vs 1047 [ 10.2 % ] ) , non-fatal or fatal stroke ( 511 [ 5.0 % ] vs 518 [ 5.0 % ] ) , or coronary or non-coronary revascularisation ( 1058 [ 10.3 % ] vs 1086 [ 10.6 % ] ) . For the first occurrence of any of these " major vascular events " , there were no material differences either overall ( 2306 [ 22.5 % ] vs 2312 [ 22.5 % ] ; event rate ratio 1.00 [ 95 % CI 0.94 - 1.06 ] ) or in any of the various subcategories considered . There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause . INTERPRETATION Among the high-risk individuals that were studied , these antioxidant vitamins appeared to be safe . But , although this regimen increased blood vitamin concentrations substantially , it did not produce any significant reductions in the 5-year mortality from , or incidence of , any type of vascular disease , cancer , or other major outcome BACKGROUND Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers , including cancers of the esophagus and stomach . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian County , China , have one of the world 's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients . PURPOSE We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian . METHODS Individuals of ages 40 - 69 were recruited in 1985 from four Linxian communes . Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period . The subjects were r and omly assigned to intervention groups according to a one-half replicate of a 2(4 ) factorial experimental design . This design enabled testing for the effects of four combinations of nutrients : ( A ) retinol and zinc ; ( B ) riboflavin and niacin ; ( C ) vitamin C and molybdenum ; and ( D ) beta carotene , vitamin E , and selenium . Doses ranged from one to two times U.S. Recommended Daily Allowances . RESULTS A total of 2127 deaths occurred among trial participants during the intervention period . Cancer was the leading cause of death , with 32 % of all deaths due to esophageal or stomach cancer , followed by cerebrovascular disease ( 25 % ) . Significantly ( P = .03 ) lower total mortality ( relative risk [ RR ] = 0.91 ; 95 % confidence interval [ CI ] = 0.84 - 0.99 ) occurred among those receiving supplementation with beta carotene , vitamin E , and selenium . The reduction was mainly due to lower cancer rates ( RR = 0.87 ; 95 % CI = 0.75 - 1.00 ) , especially stomach cancer ( RR = 0.79 ; 95 % CI = 0.64 - 0.99 ) , with the reduced risk beginning to arise about 1 - 2 years after the start of supplementation with these vitamins and minerals . No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc , riboflavin and niacin , or vitamin C and molybdenum . Patterns of cancer incidence , on the basis of 1298 cases , generally resembled those for cancer mortality . CONCLUSIONS The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults , particularly with the combination of beta carotene , vitamin E , and selenium , may effect a reduction in cancer risk in this population . IMPLICATION S The results on their own are not definitive , but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements A r and omised double-blind intervention trial was carried out in Huixian , Henan Province , People 's Republic of China , to determine whether combined treatment with retinol , riboflavine , and zinc could lower the prevalence of precancerous lesions of the oesophagus . 610 subjects in the age group 35 - 64 were r and omised to receive once a week the active treatment ( 15 mg [ 50 000 IU ] retinol , 200 mg riboflavine , and 50 mg zinc ) or placebo . Both at entry to the study and at the end of the treatment , 13.5 months later , the subjects were examined , with an emphasis on signs of vitamin A and riboflavine deficiences , and riboflavine , retinol , beta-carotene , and zinc levels were measured . Compliance was excellent . The final examination , on 567 ( 93 % ) subjects , included oesophagoscopy and at least two biopsies . The intervention did not affect the prevalence of oesophageal lesions : after one year , the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3 % in the placebo group and 48.9 % in the vitamin/zinc treated group |
12,509 | 30,372,514 | We found no clear beneficial or harmful effects of carvedilol versus traditional , non-selective beta-blockers on mortality , upper gastrointestinal bleeding , serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient . | BACKGROUND Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis , portal hypertension and gastroesophageal varices .
Carvedilol is a non-selective beta-blocker with additional intrinsic alpha1-blocking effects , which may be superior to traditional , non-selective beta-blockers in reducing portal pressure and , therefore , in reducing the risk of upper gastrointestinal bleeding .
OBJECTIVES To assess the beneficial and harmful effects of carvedilol compared with traditional , non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices . | Carvedilol is a non‐selective vasodilating β‐blocker with weak α1 receptor antagonism . Recent studies have demonstrated its potential as a portal hypotensive agent . Objective Non-selective β-blockers or endoscopic b and ligation ( EBL ) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices . Additional α-adrenergic blockade ( as by carvedilol ) may increase the number of patients with haemodynamic response ( reduction in hepatic venous pressure gradient ( HVPG ) of ≥20 % or to values < 12 mm Hg ) . Design Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment ( 80–160 mg/day ) were included . HVPG responders were kept on propranolol ( PROP group ) , while non-responders were placed on carvedilol ( 6.25–50 mg/day ) . Carvedilol responders continued treatment ( CARV group ) , while non-responders to carvedilol underwent EBL . The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders . Results 36 % ( 37/104 ) of patients showed a HVPG response to propranolol . Among the propranolol non-responders 56 % ( 38/67 ) eventually achieved a haemodynamic response with carvedilol , while 44 % ( 29/67 ) patients were finally treated with EBL . The decrease in HVPG was significantly greater with carvedilol ( median 12.5 mg/day ) than with propranolol ( median 100 mg/day ) : −19±10 % versus −12±11 % ( p<0.001 ) . During a 2 year follow-up bleeding rates for PROP were 11 % versus CARV 5 % versus EBL 25 % ( p=0.0429 ) . Fewer episodes of hepatic decompensation ( PROP 38%/CARV 26 % vs EBL 55 % ; p=0.0789 ) and significantly lower mortality ( PROP 14%/CARV 11 % vs EBL 31 % ; p=0.0455 ) were observed in haemodynamic responders compared to the EBL group . Conclusions Carvedilol leads to a significantly greater decrease in HVPG than propranolol . Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response , which is associated with improved outcome with regard to prevention of variceal bleeding , hepatic decompensation and death Background and aims B and ligation and propranolol are the current therapies for primary prevention of variceal bleeding . Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome . The aim of this study to assess the efficacy of carvedilol , propranolol , and b and ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year . Methods The study included 264 cirrhotic patients with medium/large-sized varices who were c and i date s for primary prophylaxis of variceal bleeding . Patients were r and omly divided into three groups : group I : b and ligation ; group II : propranolol ; group III : carvedilol . Results Group I showed higher success rate of 75 % , followed by group III with 70.2 % and group II with 65.2 % . Risk of bleeding was comparable between the three groups , with group II carrying the highest rate of complications ( 34.7 % ) followed by group III ( 14.2 % ) and finally group I ( 5.7 % ) . After 1 year of follow-up , Child score did not improve in any of the studied groups , while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III . Conclusions B and ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications . Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects . Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens , although medical treatment reduces portal hypertensive gastropathy . Choice of treatment depends on patient will , compliance with treatment , and endoscopist competence OBJECTIVES : Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis . More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient ( HVPG ) than propranolol . The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol . METHODS : A total of 110 patients with a baseline HVPG value > 12 mm Hg were allocated r and omly to receive either carvedilol or propranolol . The HVPG measurement was repeated after 6 weeks of daily medication . The primary end point was a ≥20 % fall in HVPG compared with baseline or < 12 mm Hg . RESULTS : The difference in the proportion of responders in the carvedilol ( 49.1 % ) vs. propranolol ( 30.9 % ) groups did not reach statistical significance in the intention-to-treat analysis ( P=0.08 ) . However , among patients with a model for end-stage liver disease ( MELD ) score ≥15 , carvedilol result ed in a significantly greater response than that of propranolol ( 7/12 , 58.3 % vs. 0/10 , 0 % ; P=0.005 ) . Similarly , carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 ( 46.2 vs. 0 % ; P=0.046 ) . The presence of ascites also had a significant influence on the response rate ( 51.5 vs. 24.2 % ; P=0.042 ) . A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons ( P=0.005 ) . Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different . CONCLUSIONS : Overall , carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient . However , this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to underst and the relative risk benefit BACKGROUND Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage . Their effectiveness in preventing varices is unknown . METHODS We r and omly assigned 213 patients with cirrhosis and portal hypertension ( minimal hepatic venous pressure gradient [ HVPG ] of 6 mm Hg ) to receive timolol , a nonselective beta-blocker ( 108 patients ) , or placebo ( 105 patients ) . The primary end point was the development of gastroesophageal varices or variceal hemorrhage . Endoscopy and HVPG measurements were repeated yearly . RESULTS During a median follow-up of 54.9 months , the rate of the primary end point did not differ significantly between the timolol group and the placebo group ( 39 percent and 40 percent , respectively ; P=0.89 ) , nor were there significant differences in the rates of ascites , encephalopathy , liver transplantation , or death . Serious adverse events were more common among patients in the timolol group than among those in the placebo group ( 18 percent vs. 6 percent , P=0.006 ) . Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year . CONCLUSIONS Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events . ( Clinical Trials.gov number , NCT00006398 . Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis . The aim of this multicenter , prospect i ve , cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis . A training set of 291 and a test set of 174 bleeding cirrhotic patients were included . Treatment was according to the preferences of each center and the follow-up period was 6 weeks . Predictive rules for 5-day failure ( uncontrolled bleeding , rebleeding , or death ) and 6-week mortality were developed by the logistic model in the training set and vali date d in the test set . Initial treatment controlled bleeding in 90 % of patients , including vasoactive drugs in 27 % , endoscopic therapy in 10 % , combined ( endoscopic and vasoactive ) in 45 % , balloon tamponade alone in 1 % , and none in 17 % . The 5-day failure rate was 13 % , 6-week rebleeding was 17 % , and mortality was 20 % . Corresponding findings for variceal versus nonvariceal bleeding were 15 % versus 7 % ( P = .034 ) , 19 % versus 10 % ( P = .019 ) , and 20 % versus 15 % ( P = .22 ) . Active bleeding on endoscopy , hematocrit levels , aminotransferase levels , Child-Pugh class , and portal vein thrombosis were significant predictors of 5-day failure ; alcohol-induced etiology , bilirubin , albumin , encephalopathy , and hepatocarcinoma were predictors of 6-week mortality . Prognostic re assessment including blood transfusions improved the predictive accuracy . All the developed prognostic models were superior to the Child-Pugh score . In conclusion , prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades . Initial treatment stops bleeding in 90 % of patients . Accurate predictive rules are provided for early recognition of high-risk patients OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND AND AIMS Newer studies suggest that carvedilol , a beta-blocker with a moderate anti-alpha-1 activity , is superior to propranolol in reducing the portal pressure and risk of variceal bleeding . The effect on arterial blood pressure is a matter of concern especially in decompensated patients . AIMS to assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic , humoral , and respiratory characteristics in cirrhosis . METHODS Patients with cirrhosis and portal hypertension were r and omised to receive carvedilol ( n=16 ) or propranolol ( n=13 ) . Cardiac , systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months . RESULTS Arterial blood pressure , heart rate , and cardiac output decreased equally , central circulation time and systemic vascular resistance increased significantly but similarly . Central blood volume , plasma volume and arterial compliance were unaltered . The QTc interval and renin levels decreased in the carvedilol group , however not significantly different from the propranolol group . Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups . Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups ( -17 % and -20 % , non significant ) . CONCLUSIONS Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could not demonstrate any significant difference between the two treatments BACKGROUND / AIMS The incidence and natural history of small esophageal varices ( EV ) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients . METHODS We prospect ively evaluated 206 cirrhotics , 113 without varices and 93 with small EV , during a mean follow-up of 37+/-22 months . Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded . Endoscopy was performed every 12 months . RESULTS The rate of incidence of EV was 5 % ( 95%CI : 0.8 - 8.2 % ) at 1 year and 28 % ( 21.0 - 35.0 % ) at 3 years . The rate of EV progression was 12 % ( 5.6 - 18.4 % ) at 1 year and 31 % ( 21.2 - 40.8 % ) at 3 years . Post-alcoholic origin of cirrhosis , Child-Pugh 's class ( B or C ) and the finding of red wale marks at first examination were predictors for the variceal progression . The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices : 12 % ( 95 % CI : 5.2 - 18.8 % ) vs. 2 % ( 0.1 - 4.1 % ) ; ( P<0.01 ) . Predictor for bleeding was the presence of red wale marks at first endoscopy . CONCLUSIONS In patients with no or small EV , endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction Abstract Background and aims Endoscopic variceal ligation ( EVL ) plus beta blocker is the mainstay treatment after index bleed to prevent rebleed . Primary objective of this study was to compare EVL plus propranolol versus EVL plus carvedilol on reduction of HVPG after 1 month of therapy . Methods Patients of cirrhosis presenting with index esophageal variceal bleed received st and ard treatment ( Somatostatin therapy f/b EVL ) following which HVPG was measured and patients were r and omized to propranolol or carvedilol group if HVPG was > 12 mmHg . St and ard endotherapy protocol was continued in both groups . HVPG was again measured at 1 month of treatment . Results Out of 129 patients of index esophageal variceal bleed , 59 patients were eligible and r and omized into carvedilol ( n = 30 ) and propranolol ( n = 29 ) . At 1 month of treatment , decrease in heart rate , mean arterial blood pressure ( MAP ) and HVPG was significant within each group ( p = 0.001 ) . Percentage decrease in MAP was significantly more in carvedilol group as compared to propranolol group ( p = 0.04 ) . Number of HVPG responders ( HVPG decrease > 20 % or below 12 mmHg ) was significantly more in carvedilol group ( 22/29 ) as compared to propranolol group ( 14/28 ) , p = 0.04 . Conclusion Carvedilol is more effective in reducing portal pressure in patients with cirrhosis with esophageal bleed . Though a larger study is required to substantiate this , the results in this study are promising for carvedilol . Clinical trials online government registry ( CTRI/2013/10/004119 ) . Trial registration number OBJECTIVE : Propranolol is known to decrease portal pressure in cirrhotic patients with portal hypertension ; however , a substantial number of patients do not respond to propranolol administration . The addition of isosorbide-5-mononitrate may enhance portal pressure reduction in patients receiving propranolol . Carvedilol is a nonselective β-blocker with α1-adrenergic blocking activity . It has been shown to decrease portal pressure in cirrhotic patients . Additionally , carvedilol has a greater portal hypotensive effect than propranolol alone in patients with cirrhosis . The current study is aim ed at comparing the acute hemodynamic effects of carvedilol with the effects of propranolol plus isosorbide-5-mononitrate in patients with viral cirrhosis . METHODS : Patients with viral cirrhosis were r and omly assigned to receive an oral administration of carvedilol of 25 mg ( n = 11 ) or an oral administration of propranolol 40 mg plus isosorbide-5-mononitrate 20 mg ( n = 11 ) . Hemodynamic values were measured at basal and 90 min after drugs administration . RESULTS : Both carvedilol and propranolol plus isosorbide-5-mononitrate significantly decreased cardiac index , heart rate , and HVPG . The magnitude of changes in HVPG observed between the basal and after drugs administration was greater in patients receiving carvedilol than in those receiving propranolol plus isosorbide-5-mononitrate ( −18.6 ± 3.6 % vs−10.1 ± 3.6 % , p < 0.05 ) . Hepatic blood flow increased following carvedilol administration but remained unchanged in patients receiving propranolol plus isosorbide-5-mononitrate . The magnitude of decrease in mean arterial pressure ( MAP ) did not differ between the two groups of patients . CONCLUSION : In our patients with viral cirrhosis , carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of HVPG . Carvedilol administration causes an increase in hepatic blood flow , but its systemic effects were similar to those of propranolol plus isosorbide-5-mononitrate Only some patients show a substantial hepatic venous pressure gradient ( HVPG ) reduction after propranolol , which makes it desirable to investigate drugs with greater portal hypotensive effect . The aim of this study was to investigate whether carvedilol , a nonselective beta-blocker with anti-alpha1-adrenergic activity , may cause a greater HVPG reduction than propranolol . Thirty-five cirrhotic patients had hemodynamic measurements before and after the r and om administration of carvedilol ( n = 14 ) , propranolol ( n = 14 ) , or placebo ( n = 7 ) . Carvedilol markedly reduced HVPG , from 19.5 + /- 1.3 to 15.4 + /- 1 mm Hg ( P < .0001 ) . This HVPG reduction was greater than after propranolol ( -20.4 + /- 2 vs. -12.7 + /- 2 % , P < .05 ) . Moreover , carvedilol decreased HVPG greater than 20 % of baseline values or to < /=12 mm Hg in a greater proportion of patients ( 64 % vs. 14 % , P < .05 ) . Both drugs caused similar reductions in hepatic and azygos blood flows , suggesting that the greater HVPG decrease by carvedilol was because of reduced hepatic and portocollateral resistance . Propranolol caused greater reductions in heart rate and cardiac output than carvedilol , whereas carvedilol caused a greater decrease in mean arterial pressure ( -23.1 vs. -11 % , P < .05 ) . Thus , carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis , suggesting a greater therapeutic potential . However , it causes arterial hypotension , which calls for careful evaluation before its long-term use BACKGROUND Systematic review s may be compromised by selective inclusion and reporting of outcomes and analyses . Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta- analysis ( e.g. from multiple measurement scales and time points ) and the choice of effect estimate to include in the meta- analysis is based on the results ( e.g. statistical significance , magnitude or direction of effect ) . Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results ( e.g. a protocol -defined outcome is omitted from the published systematic review ) . OBJECTIVES To summarise the characteristics and synthesis e the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic review s of r and omised controlled trials ( RCTs ) , investigated the factors ( e.g. statistical significance or direction of effect ) associated with the prevalence and quantified the bias . SEARCH METHODS We search ed the Cochrane Methodology Register ( to July 2012 ) , Ovid MEDLINE , Ovid EMBASE , Ovid PsycINFO and ISI Web of Science ( each up to May 2013 ) , and the US Agency for Healthcare Research and Quality ( AHRQ ) Effective Healthcare Program 's Scientific Re source Center ( SRC ) Methods Library ( to June 2013 ) . We also search ed the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for method ological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods . SELECTION CRITERIA We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting , or both , in systematic review s of RCTs of healthcare interventions . We included empirical studies assessing any type of selective inclusion or reporting , such as investigations of how frequently RCT outcome data is selectively included in systematic review s based on the results , outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic review s. DATA COLLECTION AND ANALYSIS Two review authors independently selected empirical studies for inclusion , extracted the data and performed a risk of bias assessment . A third review author resolved any disagreements about inclusion or exclusion of empirical studies , data extraction and risk of bias . We contacted authors of included studies for additional unpublished data . Primary outcomes included overall prevalence of selective inclusion or reporting , association between selective inclusion or reporting and the statistical significance of the effect estimate , and association between selective inclusion or reporting and the direction of the effect estimate . We combined prevalence estimates and risk ratios ( RRs ) using a r and om-effects meta- analysis model . MAIN RESULTS Seven studies met the inclusion criteria . No studies had investigated selective inclusion of results in systematic review s , or discrepancies in outcomes and analyses between systematic review registry entries and published systematic review s. Based on a meta- analysis of four studies ( including 485 Cochrane Review s ) , 38 % ( 95 % confidence interval ( CI ) 23 % to 54 % ) of systematic review s added , omitted , up grade d or down grade d at least one outcome between the protocol and published systematic review . The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain . The meta-analytic estimate suggested an increased risk of adding or upgrading ( i.e. changing a secondary outcome to primary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.43 , 95 % CI 0.71 to 2.85 ; two studies , n = 552 meta-analyses ) . Also , the meta-analytic estimate suggested an increased risk of downgrading ( i.e. changing a primary outcome to secondary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.26 , 95 % CI 0.60 to 2.62 ; two studies , n = 484 meta-analyses ) . None of the included studies had investigated whether the association between statistical significance and adding , upgrading or downgrading of outcomes was modified by the type of comparison , direction of effect or type of outcome ; or whether there is an association between direction of the effect estimate and discrepant outcome reporting . Several secondary outcomes were reported in the included studies . Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic review s ( 6 % in one study and 22 % in the other ) . One study ( including 62 Cochrane Review s ) found that 32 % ( 95 % CI 21 % to 45 % ) of systematic review s did not report all primary outcomes in the abstract . Another study ( including 64 Cochrane and 118 non-Cochrane review s ) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes ( RR 2.66 , 95 % CI 1.81 to 3.90 ) . None of the studies included systematic review s published after 2009 when reporting st and ards for systematic review s ( Preferred Reporting Items for Systematic review s and Meta-Analyses ( PRISMA ) Statement , and Method ological Expectations of Cochrane Intervention Review s ( MECIR ) ) were disseminated , so the results might not be generalisable to more recent systematic review s. AUTHORS ' CONCLUSIONS Discrepant outcome reporting between the protocol and published systematic review is fairly common , although the association between statistical significance and discrepant outcome reporting is uncertain . Complete reporting of outcomes in systematic review abstract s is associated with statistical significance of the results for those outcomes . Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results . Modifications that occur once the review has commenced , along with their justification , should be clearly reported . Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results . The lack of research on selective inclusion of results in systematic review s needs to be addressed and studies that avoid the method ological weaknesses of existing research are also needed BACKGROUND Carvedilol , a non-selective beta- and alpha-1 blocking agent , has portal hypotensive action . This study evaluates the acute and 7-day response to carvedilol , and compares it to that of propranolol . METHODS Thirty-six cirrhotics were r and omized into two groups of 18 each , and treated with carvedilol or propranolol . Hepatic venous pressure gradient ( HVPG ) was measured before and 90 min after either 25 mg carvedilol or 80 mg propranolol was administered orally , and again 7 days after 12.5 mg carvedilol daily or 80 mg propranolol daily , respectively . ' Responders ' were defined as those with HVPG reduction of > or = 20 % . RESULTS With carvedilol , 11/18(61.1 % ) and 11/17(64.7 % ) patients responded acutely and after 7 days , respectively , while 9/18(50 % ) and 10/16(62.5 % ) did so to propranolol . However , HVPG reduction ( percent ) by carvedilol was not superior to that by propranolol either acutely ( 27.67 + /- 31.49 compared to 22.98 + /- 27.40 , P = 0.6 ) or after 7 days ( 28.2 + /- 29.05 compared to 23.25 + /- 20.15 , P = 0.6 ) . With carvedilol , the acute HVPG response ( P < 0.001 ) and responder status ( P = 0.018 ) were good predictors of the response after 7 days , but were weak predictors in the case of propranolol ( 0.1 > P > 0.05 and P = 0.059 , respectively ) . On carvedilol , only one patient ( with ascites ) developed symptomatic systemic hypotension with oliguria . CONCLUSION Carvedilol is a relatively safe , effective portal hypotensive agent , both acutely and over 7 days , but not superior to propranolol , at least in Indians . The acute hemodynamic response seems promising in predicting long-term response BACKGROUND AND AIMS Our aim was to identify predictors of clinical decompensation ( defined as the development of ascites , variceal hemorrhage [ VH ] , or hepatic encephalopathy [ HE ] ) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient ( HVPG ) . METHODS We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices . All had baseline laboratory tests and HVPG . Patients were followed prospect ively every 3 months until development of varices or VH or end of study . To have complete information , until study termination , about clinical decompensation , medical record review was done . Patients who underwent liver transplantation without decompensation were censored at transplantation . Cox regression models were developed to identify predictors of clinical decompensation . Receiver operating characteristic ( ROC ) curves were constructed to evaluate diagnostic capacity of HVPG . RESULTS Median follow-up time of 51.1 months . Sixty-two ( 29 % ) of 213 patients developed decompensation : 46 ( 21.6 % ) ascites , 6 ( 3 % ) VH , 17 ( 8 % ) HE . Ten patients received a transplant and 12 died without clinical decompensation . Median HVPG at baseline was 11 mm Hg ( range , 6 - 25 mm Hg ) . On multivariate analysis , 3 predictors of decompensation were identified : HVPG ( hazard ratio [ HR ] , 1.11 ; 95 % confidence interval [ CI ] , 1.05 - 1.17 ) , model of end-stage liver disease ( MELD ) ( HR , 1.15 ; 95 % CI , 1.03 - 1.29 ) , and albumin ( HR , 0.37 ; 95 % CI , 0.22 - 0.62 ) . Diagnostic capacity of HVPG was greater than for MELD or Child-Pugh score . CONCLUSIONS HVPG , MELD , and albumin independently predict clinical decompensation in patients with compensated cirrhosis . Patients with an HVPG < 10 mm Hg have a 90 % probability of not developing clinical decompensation in a median follow-up of 4 years BACKGROUND / AIMS Recent reports have suggested that the vasodilating beta-blocker carvedilol may have beneficial acute haemodynamic effects in cirrhotic portal hypertension . However , no data exist on chronic use or renal effects in this patient group . The aim of this study was to assess the acute and chronic haemodynamic and renal effects of carvedilol in cirrhotic patients . METHODS Seventeen cirrhotic patients ( mean age 55.2+/-2.8 , mean Child-Pugh score 7.4+/-0.5 ) were studied . Hepatic venous pressure gradient , cardiac output , systemic vascular resistance , mean arterial pressure , heart rate and hepatic blood flow were measured before and 1 h after 25 mg carvedilol . After 4 weeks of therapy with carvedilol 25 mg daily , these measurements were repeated before and after rechallenge with carvedilol . Urine volume , sodium excretion and creatinine clearance were also measured before and after 4 weeks of therapy . RESULTS Seven patients did not complete the 4-week carvedilol therapy due to hypotension or poor compliance . Hepatic venous pressure gradient fell by 20.8 % acutely ( p<0.001 ) and by 16.3 % after 4 weeks of therapy ( p<0.002 ) . Heart rate , mean arterial pressure and cardiac output fell after acute administration of carvedilol , but only heart rate fell significantly after 4 weeks of treatment . Hepatic blood flow , urine volume , sodium excretion and creatinine clearance remained unchanged after therapy . CONCLUSION Carvedilol has beneficial effects on splanchnic haemodynamics following acute and chronic administration in cirrhosis , without compromising hepatic blood flow or renal function . However , a substantial number of patients can not tolerate 25 mg daily To enhance the portal hypotensive effect of nonselective beta-blockers , combinations of vasoactive agents with different mechanisms should be considered . The effect of carvedilol ( CAS 72956 - 09 - 3 , Artist ) , and alpha-/beta-blocking agent , on hepatic and systemic hemodynamics in 10 patients with portal hypertension was evaluated . After administration of carvedilol , the hepatic venous pressure gradient ( HVPG ) decreased from 15.9 + /- 3.2 mmHg to 13.3 + /- 4.0 mmHg ( mean + /- SD ) at 60 min ( -15 % ) and to 12.9 + /- 3.0 mmHg at 90 min ( -17 % , p < 0.05 ) . However , only 5 patients showed a decrease of HVPG by more than 20 % at 60 or 90 min . The estimated hepatic blood flow ( EHBF ) was not significantly reduced . In contrast , heart rate ( -8 % , p < 0.05 ) , mean arterial pressure ( -10 % , p < 0.01 ) , and cardiac index ( CI ) ( -8 % , p < 0.05 ) were all reduced at 90 min , while total systemic vascular resistance was not altered . The reduction of HVPG was significantly correlated with the decrease of CI ( r = 0.6415 , p < 0.05 ) . The portal hypotensive effect of carvedilol may mainly result from a reduction of CI . However , because of the greater reduction of HVPG than that of CI , other additive actions were suggested Nonselective beta-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis . Treatment with isosorbide-5-mononitrate ( IS-MN ) plus propranolol achieves a greater reduction in portal pressure than propranolol alone . The present multicenter , prospect i ve , double-blind , r and omized , controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding . A total of 349 consecutive cirrhotic patients with gastroesophageal varices were r and omized to receive propranolol + placebo ( n = 174 ) or propranolol + IS-MN ( n = 175 ) . There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups ( propranolol + placebo , 8.3 % and 10.6 % ; propranolol + IS-MN , 5 % and 12.5 % ) . The only independent predictor of variceal bleeding was a variceal size greater than 5 mm . However , among patients with varices greater than 5 mm ( n = 196 ) , there were no significant differences in the incidence of variceal bleeding between the 2 groups . Survival was also similar . Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache . There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function . In conclusion , propranolol effectively prevents variceal bleeding . Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol . However , the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding BACKGROUND AND AIM Carvedilol has been shown to be more effective than propranolol in decreasing portal pressure . Sufficient data from controlled trials remains limited . This trial compared the relative safety and efficacy between carvedilol and nadolol plus isosorbide mononitrate in preventing variceal rebleeding . METHODS After successful control of acute esophageal variceal bleeding , eligible patients were r and omized to the carvedilol group , 61 patients , using carvedilol 6.25 - 12.5 mg daily or the N + I group , 60 patients , using nadolol 40 - 80 mg plus isorsorbide-5-mononitrate 20 mg daily . The end points were rebleeding from varices , adverse events or death . RESULTS After a median follow up of 30 months , recurrent upper gastrointestinal bleeding developed in 37 patients ( 61 % ) in the carvedilol group and 37 patients ( 62 % ) in the N + I group ( P = 0.90 ) . Recurrent bleeding from esophageal varices occurred in 31 patients ( 51 % ) in the carvedilol group and in 26 patients ( 43 % ) in the N + I group ( P = 0.46 ) . Recurrent bleeding from gastric varices occurred in two patients ( 3 % ) in the carvedilol group and in eight patients ( 13 % ) in the N + I group ( P = 0.05 ) . Severe adverse events occurred in one patient in the carvedilol group and 17 patients in the N + I group ( P < 0.0001 ) . Fifteen patients of the carvedilol group and 17 patients in the N + I group died ( P = 0.83 ) . Two patients in the carvedilol group and three patients in the N + I group died of variceal bleeding . CONCLUSIONS Carvedilol was as effective as nadolol plus isorsorbide-5 -mononitrate mononitrate in the prevention of gastroesophageal variceal rebleeding with fewer severe adverse events and similar survival Abstract Objectives . Carvedilol is a non-selective β-blocker with intrinsic anti-α1-adrenergic activity , potentially more effective than propranolol in reducing hepatic venous pressure gradient ( HVPG ) . We compared the long-term effect of carvedilol and propranolol on HVPG and assessed whether the acute response to oral propranolol predicted the long-term HVPG response on either drug . Material and methods . HVPG was measured in 38 patients with cirrhosis and HVPG ≥ 12 mm Hg at baseline and then again 90 min after an oral dose of 80 mg propranolol . Patients were double-blinded r and omized to either carvedilol ( 21 patients ) or propranolol ( 17 patients ) and after 90 days of treatment HVPG measurements were repeated . Results . HVPG decreased by 19.3 ± 16.1 % ( p < 0.01 ) and by 12.5 ± 16.7 % ( p < 0.01 ) in the carvedilol and propranolol groups , respectively , with no significant difference between treatment regimens ( p = 0.21 ) . Although insignificant , an acute decrease in HVPG of ≥12 % was the best cut-off value to predict long-term HVPG response to propranolol when using ROC curve analysis . Conclusions . This r and omized study showed that carvedilol is at least as effective as propranolol on HVPG after long-term administration . Furthermore , a predictive value of an acute propranolol test on HVPG could not be confirmed In a double-blind r and omized trial , the hemodynamic events following the administration of propranolol ( n = 51 ) or a placebo ( n = 51 ) were prospect ively studied in cirrhotic patients with esophageal varices . The hepatic venous pressure gradient , heart rate , and variceal size were determined at the baseline and 3 , 12 , and 24 months after the beginning of therapy . Baseline values were similar in both groups . At 3 months , the hepatic venous pressure gradient decreased significantly in propranolol-treated patients ( from 18.1 + /- 4.2 to 15.7 + /- 3.4 mm Hg ; P less than 0.05 ) but not in patients receiving the placebo ( 19.6 + /- 6.8 to 17.5 + /- 5.3 mm Hg ; NS ) . At subsequent time intervals this gradient decreased significantly from the baseline value in both groups . Heart rate decreased significantly in the propranolol-treated group at all times ( P less than 0.001 ) . Variceal hemorrhage occurred in 13 patients ( 11 placebo- , 2 propranolol-treated ; P less than 0.01 ) , all of whom had a hepatic venous pressure gradient greater than 12 mm Hg . In 21 patients ( 14 propranolol- , 7 placebo-treated ) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg ; none of them bled from esophageal varices , and their mortality rate also decreased . Because most of the bleeding events occurred during the first year ( 10 placebo- , 1 propranolol-treated ; P less than 0.01 ) , propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient . Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival , this should be the aim of the pharmacological therapy of portal hypertension Short‐term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient ( HVPG ) in cirrhotic patients , but induces arterial hypotension that may prevent its long‐term use in portal hypertensive patients . This study compared the HVPG reduction and safety of long‐term carvedilol and propranolol . Fifty‐one cirrhotic patients were r and omly assigned to receive carvedilol ( n = 26 ) and propranolol ( n = 25 ) . Hemodynamic measurements and renal function were assessed at baseline and after 11.1 ± 4.1 weeks . Carvedilol caused a greater decrease in HVPG than popranolol ( − 19 ± 2 % vs. − 12 ± 2 % ; P < 0.001 ) . The proportion of patients achieving an HVPG reduction ⩾20 % or ⩽ 20 mm Hg was greater after carvedilol ( 54 % vs. 23 % ; P < 0.05 ) . Carvedilol , but not propranolol caused a significant decrease in mean arterial pressure ( MAP ) ( – 11 ± 1 % vs. – 5 ± 3 % ; P = 0.05 ) and a significant increase in plasma volume ( PV ) and body weight ( 11 ± 5 % and 2 ± 1 % , respectively ; P < 0.05 ) . Glomerular filtration rate ( GFR ) was unchanged with either drug , but the dose of diuretics was increased more frequently after carvedilol ( 27 % vs. 8 % P = 0.07 ) . Adverse events requiring discontinuation of treatment occurred in 2 patients receiving carvedilol and in 3 receiving propranolol . In conclusion , carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis . However , its clinical applicability may be limited by its systemic hypotensive effects . Further trials are needed to confirm the therapeutic potential of carvedilol . ( HEPATOLOGY2002;36:1367–1373 ) OBJECTIVE Beta-blockers have been shown to reduce portal pressure in patients with cirrhosis and limit the development of portosystemic shunts in portal hypertensive animals . Thus , a r and omized double-blind trial was conducted to evaluate propranolol in the prevention of the development of large oesophageal varices in patients with cirrhosis without varices or with small varices . METHODS One hundred and two patients received long-acting propranolol ( 160 mg/day ) and 104 patients received a placebo . At inclusion , there was no significant difference between the two groups in terms of clinical characteristics or biochemical tests . At 2 years , the size of varices was estimated on video recordings . RESULTS One-third of the patients were lost to follow-up , and 95%/97 % of the remaining patients were compliant in the propranolol and placebo groups , respectively . At 2 years , the proportion of patients with large varices was 31 % in the propranolol group and 14 % in the placebo group ( P < 0.05 ) . Three and four patients bled in the propranolol and placebo groups , respectively , and nine and ten died , respectively . CONCLUSION This trial suggests that propranolol administration can not be recommended for the prevention of the development of large oesophageal varices in patients with cirrhosis ; thus other studies are needed in selected subgroups of patients Endoscopic b and ligation ( EBL ) and nonselective β-blockade are two effective strategies in the primary prevention of variceal bleeding . Meta-analyses have shown an advantage of EBL over propranolol with regard to bleeding rates but not mortality . By contrast , a recent r and omized , controlled trial shows less bleeding associated with the use of carvedilol compared with EBL BACKGROUND & AIMS Nonselective beta-blockers ( beta-blockers ) are very effective in preventing first variceal bleeding ( FVB ) in patients with cirrhosis . However , 15%-25 % of patients have contraindications or develop severe side effects precluding its use . The present study evaluates whether isosorbide-5-mononitrate ( Is-MN ) effectively prevents variceal bleeding in patients with contraindications or who could not tolerate beta-blockers . METHODS One hundred thirty-three consecutive cirrhotic patients with gastro-esophageal varices and contraindications or intolerance to beta-blockers were included in a multicenter , prospect i ve , double-blind r and omized controlled trial . Sixty-seven were r and omized to receive Is-MN , and 66 to receive placebo . RESULTS There were no significant differences in the 1- and 2-year actuarial probability of experiencing a FVB between the 2 treatment groups . Presence of variceal red signs at endoscopy was the only variable independently associated with an increased risk of variceal bleeding on follow-up ( relative risk 3.4 ; P < 0.01 ) . Survival and adverse events were similar in the 2 groups . There were no significant differences in the incidence of ascites or changes in renal function . CONCLUSIONS Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who can not be treated with beta-blockers because contraindications or intolerance to these drugs , suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding Placebo or propranolol was given r and omly of two groups of 12 adults with cirrhosis who had recently held from oesophageal or gastric varices or from acute gastric erosions . During three months ' follow-up 5 patients in the placebo and none in the propranolol group had recurrent gastrointestinal bleeding BACKGROUND AND OBJECTIVE Alternative drug therapies are needed for the treatment of portal hypertension . The aim of this r and omized study was to evaluate and compare the effects of carvedilol and nebivolol on the hepatic venous pressure gradient ( HVPG ) response in the patients with liver cirrhosis . MATERIAL AND METHODS In total , 20 cirrhotic patients were r and omized into 2 groups and treated with carvedilol ( n=10 ) or nebivolol ( n=10 ) . HVPG was measured at baseline , 60 minutes after the administration of carvedilol ( 25 mg ) or nebivolol ( 5 mg ) , and after 14 days of carvedilol ( 25 mg ) or nebivolol ( 5 mg ) administered daily . RESULTS . Carvedilol significantly reduced HVPG from 22.2 mm Hg ( SD , 4.4 ) to 15.2 mm Hg ( SD , 3.7 ) after 60 minutes and to 16.4 mm Hg ( SD , 2.9 ) after 14 days ( P<0.01 ) . Nebivolol reduced HVPG from 19.7 mm Hg ( SD , 2.5 ) to 15.7 mm Hg ( SD , 2.6 ) and 16.7 mm Hg ( SD , 3.2 ) , respectively ( P<0.02 ) . Carvedilol effectively decreased HVPG in a greater proportion of the patients after an acute probe ( 88 % vs. 57 % ) and after 14 days of the treatment ( 88 % vs. 28 % , P<0.05 ) in comparison with nebivolol . CONCLUSION Carvedilol and nebivolol reduce HVPG in cirrhotic patients ; however , the effect of carvedilol on the HVPG reduction might be superior to that of nebivolol , especially after 14 days of treatment Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
12,510 | 21,549,642 | These findings highlight the current deficiency in the literature and suggest that evidence is insufficient to draw any conclusions regarding the effect of intramural fibroids on reproductive outcomes | Intramural fibroids when encountered in women undergoing fertility treatment present a clinical dilemma .
Despite recent studies that have suggested a negative outcome for intramural fibroids on fertility outcomes , the evidence remains far from conclusive .
The current study presents a systematic review and meta- analysis of the currently available evidence . | BACKGROUND Several studies have reported that the presence of intramural fibroids affects conception following IVF . We attempted to corroborate or refute the conclusions relating to IVF and leiomyomas of the aforementioned studies . METHODS Women with small intramural leiomyomata ( < or = 5 cm ) discovered on initial pelvic sonographic studies performed in preparation for IVF were prospect ively matched by age , with the next patient of the same age undergoing IVF who did not demonstrate fibroids ( controls ) . RESULTS Though no significant differences were found in outcome when comparing these two groups , there was a distinct trend for lower live delivery rates and higher miscarriage rates . CONCLUSIONS These data support the conclusions of the only other prospect i ve matched control study evaluating similar factors , i.e. that small intramural fibroids can negatively affect IVF outcome . Nevertheless , we think that a multicentre study should be conducted first before evaluating whether myomectomy improves outcome or not BACKGROUND There is no consensus as to whether uterine fibroids have any adverse effects on the outcomes of assisted reproduction treatment . This prospect i ve study compared implantation/pregnancy rates of women with and without fibroids undergoing IVF-embryo transfer and measured uterine blood flow indices of the fibroid group . METHODS Patients who had fibroids that , during transvaginal scanning , were found to be not distorting the endometrial lining were placed in the fibroid group , while patients with normal uteri were controls . Those with previous myomectomy or pedunculated subserosal fibroids only were excluded . All received a st and ard ovarian stimulation regimen . Doppler ultrasound examinations of uterine arteries were carried out in the fibroid group prior to oocyte retrieval . RESULTS Similar implantation/pregnancy rates , multiple pregnancy rates and pregnancy outcomes were noted in both groups . In the fibroid group , significantly lower pulsatility index ( PI ) and resistance index ( RI ) of the right uterine artery and the average of right and left uterine arteries were found in those failing to conceive than in those patients who subsequently conceived ( P < 0.001 ) . CONCLUSION The presence of fibroids not distorting the endometrial lining does not adversely affect implantation and pregnancy rates during IVF-embryo transfer . Significantly lower uterine artery PI and RI were found in non-pregnant women with fibroids than in their pregnant counterparts BACKGROUND The impact of intramural fibroids on the success of IVF treatment is controversial and the mechanisms leading to poor treatment outcomes remain unknown . We compared endometrial and subendometrial blood flow between women with and without intramural fibroids during IVF treatment . METHODS Three-dimensional ( 3D ) ultrasound examination with power Doppler was performed on the day of oocyte retrieval in 50 patients with intramural fibroids not distorting the uterine cavity and in 50 matched controls to measure endometrial thickness , uterine pulsatility index (PI)/resistance index ( RI ) , endometrial volume and vascularization index (VI)/flow index (FI)/vascularization flow index ( VFI ) of endometrial and subendometrial regions . Smokers , patients with serum estradiol concentrations > or = 20,000 pmol/l on the day of HCG and previous history of myomectomy were excluded . RESULTS Endometrial thickness and pattern , averaged uterine PI and RI and endometrial and subendometrial VI/FI/VFI were similar between the fibroid group and the control group . There was no correlation between the total volume of fibroids and endometrial and subendometrial 3D power Doppler flow indices in the fibroid group . CONCLUSION Endometrial and subendometrial 3D power Doppler flow indices were similar in patients with and without small intramural fibroids BACKGROUND Although uterine fibroids occur in 30 % of women and are associated with a degree of subfertility , the effect of intramural fibroids on the outcome of IVF or ICSI treatment has not been prospect ively studied . METHODS Data were prospect ively collected on 434 women undergoing IVF/ICSI in the assisted conception unit of an inner London teaching hospital . Patients were assessed for the presence of fibroids by transvaginal ultrasound and hysterosonography or hysteroscopy where appropriate . RESULTS During the study period , 112 women with ( study ) , and 322 women without ( controls ) , intramural fibroids were treated . Patients were similar regarding the cause and duration of their infertility , number of previous treatments , and basal serum FSH concentration . Women in the study group were on average 2 years older ( 36.4 versus 34.6 years ; P < 0.01 ) . There was no significant difference in the duration of ovarian stimulation or gonadotrophin requirement , number of follicles developed , oocytes collected , embryos available for transfer or replaced . When analysing only women with intramural fibroids of < or = 5 cm in size ( n = 106 ) pregnancy , implantation and ongoing pregnancy rates were significantly reduced : 23.3 , 11.9 and 15.1 respectively compared with 34.1 , 20.2 and 28.3 % in the control group ( P = 0.016 , P = 0.018 and P = 0.003 ) . The mean size of the largest fibroids was 2.3 cm ( 90 % range 2.1 - 2.5 cm ) . Logistic regression analysis demonstrated that the presence of intramural fibroids was one of the significant variables affecting the chance of an ongoing pregnancy , even after controlling for the number of embryos available for replacement and increasing age , particularly age > or = 40 years , odds ratio 0.46 ( CI 0.24 - 0.88 ; P = 0.019 ) . CONCLUSION This study demonstrated that an intramural fibroid halves the chances of an ongoing pregnancy following assisted conception OBJECTIVES To examine total pregnancy rate , pregnancy rate in relation to pretreatment with GnRH-analogues , the frequency of myoma recurrencies and the influence of size , number and localization of removed myomata on pregnancy rate and outcome in infertility patients after myomectomy . STUDY DESIGN A comparative , retrospective non-r and omized clinical study involving 67 patients with desire for children and no other recognizable infertility factor . Myomectomy had been performed between 1985 and 1993 . Most patients had been operated by laparotomy using microsurgical instruments and techniques . Thirty-three patients had been treated with a GnRH agonist for usually 3 months , and in 34 patients the operation was performed without pretreatment . Patients were followed up to June , 1994 . All patients were mailed a question naire and invited to an ultrasound examination . RESULTS Thirty-nine of the 67 patients ( 58.2 % ) became pregnant , and a total of 51 pregnancies were observed . Of the women who actually conceived , 61.5 % did so within the first year . There was no significant difference in pregnancy rates between patients who had been pretreated with GnRH agonists and those who had not . However , 1 year after the operation the group of GnRH-treated women was significantly overrepresented among those already pregnant ( P = 0.02 ) . Sonografical examination revealed in 31 out of the 67 patients ( 46.3 % ) recurrent myomata > 1 cm in diameter . There was no statistically significant difference in the pregnancy rates between patients with and without recurrencies . However , there was a significant tendency toward a loss or short duration of the pregnancy due to spontaneous abortion and premature delivery in patients with recurrent or persistent myomata ( P < 0.01 ) . Pregnancy rate was significantly lower in patients with more than five myomata removed ( P < 0.001 ) . In the group with a larger myoma volume the pregnancy rate was significantly higher than in the group with the smaller one ( P < 0.01 ) , possibly indicating that the size on removal of myomata is an important factor for infertility patients . Concerning the localization of the removed myomata , no statistically significant difference was found in the pregnancy rates between various localizations . Of the 51 pregnancies , 31 ( 60.8 % ) led to a delivery , vaginal in 13 cases ( 41.9 % ) and 18 times by Caesarean section ( 58.1 % ) . Of the pregnancies that were lost , 39.2 % were due to spontaneous abortion or ectopic pregnancy . CONCLUSIONS Our study supports reports on the benefits of myomectomy , performed with the appropriate technique , in patients with otherwise unknown cause of infertility . It shows , additionally , that characteristics of myomata , such as number and size , may influence postmyomectomy pregnancy rates This prospect i ve , controlled study was performed in order to evaluate whether the location of uterine fibroids may influence reproductive function in women and whether removal of the fibroid prior to conception may improve pregnancy rate and pregnancy maintenance . We examined 181 women affected by uterine fibroids who had been trying to conceive for at least 1 year without success . The main outcome measures were the pregnancy rate and the miscarriage rate . Among the patients who underwent myomectomy , the pregnancy rates obtained were 43.3 % in cases of submucosal , 56.5 % in cases of intramural , 40.0 % in cases of submucosal – intramural and 35.5 % in cases of intramural – subserosal uterine fibroids , respectively . Among the patients who did not undergo surgical treatment , the pregnancy rates obtained were 27.2 % in women with submucosal , 41.0 % in women with intramural , 15.0 % in women with submucosal – intramural and 21.43 % in women with intramural – subserosal uterine fibroids , respectively . Although the results were not statistically significant in the group of women with intramural and intramural – subserosal fibroids , this study confirms the important role of the position of the uterine fibroid in infertility as well as the importance of fibroids removal before the achievement of a pregnancy , to improve both the chances of fertilization and pregnancy maintenance Twenty to fifty per cent of women are estimated to have fibroids , and the incidence increases with age until menopause.1 Whether fibroids cause infertility is the subject of considerable speculation ; fibroids are estimated to be the sole cause of infertility in less than 3 % of cases.2 The impression that fibroids contribute to infertility has arisen from several case series , mostly without controls , where a varying proportion of previously infertile women conceived after their fibroids had been removed.3 4 However , case series are generally not considered strong evidence of causation , so whether fibroids do cause infertility , and therefore whether they should be removed , is still uncertain.5 A systematic review of 22 observational studies and one r and omised controlled trial has recently reported reduced fertility in women with fibroids , mostly in association with assisted reproductive technology cycles.6 The review suggests that the location of the fibroids may matter : women with subserosal fibroids do not seem to be less fertile than women with no fibroids ; however , women with submucosal fibroids ( with or without intramural fibroids ) had decreased fertility and increased pregnancy loss compared with women with no fibroids . There are several reasons to be |
12,511 | 18,090,580 | Of these , only one trial found a significant difference in QOL between the comparator arms : paclitaxel plus cisplatin was better than teniposide plus cisplatin .
CONCLUSION Based on our review , it seems unlikely that a major difference exists in the global QOL associated with st and ard chemotherapy regimens for advanced NSCLC . | PURPOSE Systemic chemotherapy is accepted as a st and ard of care for patients with advanced non-small cell lung cancer ( NSCLC ) .
Although survival outcomes are equivalent among st and ard chemotherapy regimens , it is unknown whether the quality of life ( QOL ) outcomes are also comparable .
We evaluated available literature s to summarize the state of current knowledge and provide suggestions for future studies . | BACKGROUND It is increasingly important to have timely information about the economic impact of new cancer therapies in today 's cost-conscious environment . Nearly 170 000 people are diagnosed with lung cancer annually in the United States . We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer . There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms . METHODS Use of both protocol and non protocol lung cancer-related health care was tracked for 24 months from the initiation of therapy . To determine expenditures , nationally st and ardized costs were applied to each type of health care service used , and these were summed over time . Lifetime expenditures and 95 % confidence intervals ( CIs ) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring . Student 's t tests were used to compare the difference in costs between the arms . All statistical tests were two-sided . RESULTS Cancer-related health care costs over the period of observation averaged 40,292 dollars ( 95 % CI = 36,226 dollars to 44,359 dollars ) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars ( 95 % CI = 44,674 dollars to 53,208 dollars ) for patients in the carboplatin plus paclitaxel arm ( P = .004 ) , with a mean difference of 8648 dollars ( 95 % CI = 2634 dollars to 14,662 dollars ) . Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm ( P = .0003 and P<.0001 , respectively ) , whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm ( P<.0001 ) . There was no difference between the arms in costs for blood products , supportive care medications , non protocol -related inpatient or outpatient care , and non protocol chemotherapy . CONCLUSIONS Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine . The majority of the cost difference is due to the additional cost of the protocol chemotherapy ( approximately 12,000 dollars ) . Notable differences in costs of downstream health care were not apparent PURPOSE To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 332 patients with advanced NSCLC were r and omized to receive cisplatin 80 mg/m2 on day 1 either in combination with teniposide 100 mg/m2 on days 1 , 3 , and 5 ( arm A ) or paclitaxel 175 mg/m2 by 3-hour infusion on day 1 ( arm B ) ; cycles were repeated every 3 weeks . RESULTS Fifteen patients were ineligible ; patient characteristics were well balanced between the two arms : 71 % were male , 71 % had less than 5 % weight loss , 89 % had a World Health Organization ( WHO ) performance status of 0 to 1 , 51 % had adenocarcinoma , and 61 % had stage IV disease . Hematologic toxicity was significantly more severe in arm A ( leukopenia , neutropenia , and thrombocytopenia grade 3 or 4 : 66 % v 19 % , 83 % v 55 % , 36 % v 2 % in arms A and B , respectively ) , which result ed in more febrile neutropenia ( 27 % v 3 % in arms A and B , respectively ) , dose reductions , and treatment delays . There were a total of nine toxic deaths , six due to neutropenic sepsis : five in arm A and one in arm B. In contrast , arthralgia/myalgia ( grade 2 or 3 , 4 % v 17 % ) , peripheral neurotoxicity ( grade 2 or 3 , 6 % v 29 % ) , and hypersensitivity reactions ( 1 % v 7 % , all grade s ) were significantly more frequent in arm B. The frequency and severity of other toxicities were comparable between the two arms . Responses were one complete and 44 partial on arm A ( 28 % ) and two complete and 61 partial ( 41 % ) on arm B ( P = .018 ) . There was no significant difference in survival , with median and 1-year survivals 9.9 versus 9.7 months and 41 % versus 43 % , respectively in arm A and B. Progression-free survival was 4.9 and 5.4 months in arm A and B , respectively . Selected centers participated in a quality -of-life ( QoL ) assessment , which was performed by the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter . Arm B achieved a better score at week 6 for emotional , cognitive and social functioning , global health status , fatigue , and appetite loss , which was lost at 12 weeks . In conclusion , arm B appears superior to arm A with regard to response rate , side effects , and QoL. CONCLUSION Although survival was not improved , arm B offers a better palliation for advanced NSCLC patients than arm PURPOSE Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non-small-cell lung cancer ( NSCLC ) . To determine whether a new agent , paclitaxel , would further improve survival in NSCLC , the Eastern Cooperative Oncology Group conducted a r and omized trial comparing paclitaxel plus cisplatin to a st and ard chemotherapy regimen consisting of cisplatin and etoposide . PATIENTS AND METHODS The study was carried out by a multi-institutional cooperative group in chemotherapy-naive stage IIIB to IV NSCLC patients r and omized to receive paclitaxel plus cisplatin or etoposide plus cisplatin . Paclitaxel was administered at two different dose levels ( 135 mg/m(2 ) and 250 mg/m(2 ) ) , and etoposide was given at a dose of 100 mg/m(2 ) daily on days 1 to 3 . Each regimen was repeated every 21 days and each included cisplatin ( 75 mg/m(2 ) ) . RESULTS The characteristics of the 599 patients were well-balanced across the three treatment groups . Superior survival was observed with the combined paclitaxel regimens ( median survival time , 9.9 months ; 1-year survival rate , 38.9 % ) compared with etoposide plus cisplatin ( median survival time , 7.6 months ; 1-year survival rate , 31.8 % ; P = . 048 ) . Comparing survival for the two dose levels of paclitaxel revealed no significant difference . The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients ( P = .152 ) . For the stage IV subgroup , the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel ( P = .246 ) . With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias , neurotoxicity , and , possibly , increased treatment-related cardiac events with high-dose paclitaxel , toxicity was similar across all three arms . Quality of life ( QOL ) declined significantly over the 6 months . However , QOL scores were not significantly different among the regimens . CONCLUSION As a result of these observations , paclitaxel ( 135 mg/m(2 ) ) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial Purpose : The main purpose of this paper is to present the results of a r and omized trial comparing the effects of two chemotherapy regimens on the Quality of life ( QOL ) of patients with advanced non-small-cell lung cancer ( NSCLC ) . Trials in advanced stage disease represent an important treatment context for QOL assessment . A second purpose of this paper is to examine methods for h and ling the level of missing data commonly observed in the advanced stage disease context . Methods : Patients were r and omized to receive cisplatin plus vinorelbine or carboplatin plus paclitaxel . The QOL of 222 patients was assessed with the Functional Assessment of Cancer Therapy – Lung ( FACT-L ) prior to r and omization ; follow-up assessment s occurred at 13 and 25 weeks . Three methods were used to analyze the QOL data : ( 1 ) cross-sectional analysis of four patient categories ( improved , stable , missing , and declined ) based on changes in the FACT-L score , ( 2 ) a mixed linear model , and ( 3 ) a pattern mixture model . The longitudinal analyses addressed two potential data biases . Results : Question naire su bmi ssion rates were 91 % at baseline , 68 % at 13 weeks , and 47 % at 25 weeks . The cross-sectional and mixed linear model analyses did not show significant differences by treatment arm in patient-reported QOL . The pattern mixture model analysis , more appropriate given non-ignorable missing data , also found no statistically significant effect of treatment on patient QOL . Conclusion : We present a sensitivity analysis approach with multiple methods for analyzing treatment effects on patient QOL in the presence of substantial , non-ignorable missing data in an advanced stage disease clinical trial . We conclude that the two treatment arms did not differ statistically in their effects on patient QOL over a 25-week treatment period PURPOSE To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin ( reference regimen ) in response rate for patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Chemotherapy-naive patients were r and omized to receive gemcitabine 1,250 mg/m(2 ) days 1 and 8 plus cisplatin 75 mg/m(2 ) day 2 every 21 days ( GC arm ) , or paclitaxel 225 mg/m(2 ) ( 3-hour infusion ) then carboplatin ( area under the concentration-time curve of 6 mg/mL x min ) , both on day 1 every 21 days ( PCb arm ) , or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2 ) day 1 every 28 days ( VC arm ) . RESULTS Six hundred twelve patients were r and omized to treatment ( 205 GC , 204 PCb , and 203 VC ) . Overall response rates for the GC ( 30 % ) and PCb ( 32 % ) arms were not significantly different from that of the VC arm ( 30 % ) . There were no differences in overall survival , time to disease progression , or time to treatment failure . Median survival for the GC , PCb , and VC groups was 9.8 , 9.9 , and 9.5 months , respectively . Neutropenia was significantly higher on the VC arm ( GC 17 % or PCb 35 % v VC 43 % of cycles , P < .001 ) , as was thrombocytopenia on the GC arm ( GC 16 % v VC 0.1 % of cycles , P < .001 ) . Alopecia and peripheral neurotoxicity were most common on the PCb arm , as was nausea/vomiting on the VC arm ( P < .05 ) . CONCLUSION Efficacy end points were not significantly different between experimental and reference arms , although toxicities showed differences . These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine ( DG ) and vinorelbine/cisplatin ( VC ) combinations in chemotherapy-naive non-small-cell lung cancer ( NSCLC ) patients . PATIENTS AND METHODS Patients with advanced NSCLC were r and omly assigned to receive either DG ( gemcitabine 1,000 mg/m(2 ) [ days 1 and 8 ] plus docetaxel 100 mg/m(2 ) [ day 8 ] ) or VC ( vinorelbine 30 mg/m(2 ) [ days 1 and 8 ] plus cisplatin 80 mg/m(2 ) [ day 8 ] ) and prophylactic recombinant human granulocyte colony-stimulating factor ( 150 microg/m(2 ) subcutaneously [ day 9 through 15 ] ) every 3 weeks . Results A total of 413 r and omly assigned patients were analyzed for response and toxicity ( DG , n = 197 ; VC , n = 192 ) . Median survival was 9.0 and 9.7 months ( P = .965 ) for DG and VC arms , respectively ; the corresponding 1-year survival rates were 34.3 % and 40.8 % , respectively . Overall response rate was 30 % ( 95 % CI , 23.9 % to 36.3 % ) and 39.2 % ( 95 % CI , 32.5 % to 45.9 % ; P = .053 ) for DG and VC , respectively . Toxicity was as follows ( DG v VC ) : grade 2 to 4 anemia , 34 % v 55 % ( P = .0001 ) ; grade 3 to 4 neutropenia , 16 % v 37 % ( P = .0001 ) ; febrile neutropenia , 6 % v 11 % ( P = .009 ) ; and grade 3 to 4 nausea and vomiting , 1 % v 15 % ( P = .003 ) . Nephrotoxicity occurred in 8 % and ototoxicity in 2 % of VC-treated patients . There were five and six treatment-related deaths in the DG and VC arms , respectively . Quality of life was improved in DG but not in VC patients . CONCLUSION Although the two regimens produced comparable overall survival , the DG regimen had a better toxicity profile . Therefore , DG could be used in the first-line setting of advanced NSCLC , especially for patients who can not tolerate cisplatin PURPOSE This r and omized trial was design ed to determine whether paclitaxel plus carboplatin ( PC ) offered a survival advantage over vinorelbine plus cisplatin ( VC ) for patients with advanced non -- small-cell lung cancer . Secondary objectives were to compare toxicity , tolerability , quality of life ( QOL ) , and re source utilization . PATIENTS AND METHODS Two hundred two patients received VC ( vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d , day 1 every 28 days ) and 206 patients received PC ( paclitaxel 225 mg/m(2 ) over 3 hours with carboplatin area under the curve of 6 , day 1 every 21 days ) . Patients completed QOL question naires at baseline , 13 weeks , and 25 weeks . Re source utilization forms were completed at five time points through 24 months . RESULTS Patient characteristics were similar between the groups . The objective response rate was 28 % in the VC arm and 25 % in the PC arm . Median survival was 8 months in both arms , with 1-year survival rates of 36 % and 38 % , respectively . Grade 3 and 4 leukopenia ( P = .002 ) and neutropenia ( P = .008 ) occurred more frequently on the VC arm . Grade 3 nausea and vomiting were higher on the VC arm ( P = .001 , P = .007 ) , and grade 3 peripheral neuropathy was higher on the PC arm ( P < .001 ) . More patients on the VC arm discontinued therapy because of toxicity ( P = .001 ) . No difference in QOL was observed . Overall costs on the PC arm were higher than on the VC arm because of drug costs . CONCLUSION PC is equally efficacious as VC for the treatment of advanced non -- small-cell lung cancer . PC is less toxic and better tolerated but more expensive than VC . New treatment strategies should be pursued PURPOSE To compare the variability and sample size requirements of the global quality -of-life ( QOL ) scores of the following three major QOL instruments : the Functional Assessment of Cancer Therapy-General ( FACT-G ) , Functional Living Index-Cancer ( FLIC ) , and European Organisation for Research and Treatment of Cancer Core Quality of Life Question naire C30 ( EORTC QLQ-C30 ) . PATIENTS AND METHODS Cancer patients were r and omly assigned to answer two of the three instruments using an incomplete block design ( n = 1,268 ) . The instruments were compared in terms of coefficient of variation , effect size in detecting a difference between patients with different performance status , and correlation coefficient between scores at baseline and follow-up . RESULTS The FACT-G and FLIC had significantly smaller coefficients of variation than the EORTC QLQ-C30 ( both P < .05 ) . The FLIC also had significantly larger correlation coefficients between scores at baseline and follow-up than the EORTC QLQ-C30 ( P < .05 ) . The FACT-G and the FLIC had a larger effect size in a cross-sectional and longitudinal setting , respectively , than the EORTC QLQ-C30 in differentiating patients with different performance status ( both P < .05 ) . CONCLUSION In some aspects , the FACT-G and FLIC global QOL scores had smaller variability and larger discriminative ability than the EORTC QLQ-C30 . Further research using other criteria to compare the three instruments is recommended PURPOSE Few r and omized trials have demonstrated survival benefit of combination chemotherapy involving new agents plus cisplatin compared with classic combination chemotherapy in advanced non-small-cell lung cancer ( NSCLC ) . The primary aim of this study was to test whether docetaxel plus cisplatin ( DC ) improves survival compared with vindesine plus cisplatin ( VdsC ) in patients with previously untreated stage IV NSCLC . PATIENTS AND METHODS Eligible , stage IV , chemotherapy-naive patients ( n = 311 ) were r and omly assigned to receive docetaxel 60 mg/m(2 ) intravenously on day 1 plus cisplatin 80 mg/m(2 ) intravenously on day 1 of a 3- or 4-week cycle , or vindesine 3 mg/m(2 ) intravenously on days 1 , 8 , and 15 plus cisplatin 80 mg/m(2 ) intravenously on day 1 of a 4-week cycle . Cross-over administration of docetaxel and vindesine was prohibited for both treatment groups . RESULTS Overall , 302 patients were eligible for evaluation . The DC arm demonstrated significant improvements compared with the VdsC arm in overall response rates ( 37 % v 21 % , respectively ; P < .01 ) and median survival times ( 11.3 v 9.6 months , respectively ; P = .014 ) . Two-year survival rates were 24 % for the DC arm compared with 12 % for the VdsC arm . The physical domain of the Quality of Life for Cancer Patients Treated with Anticancer Drugs measure was significantly better in the DC arm than in the VdsC arm ( P = .020 ) . Toxicity was predominantly hematologic and was more severe in the VdsC arm . CONCLUSION As first-line treatment for stage IV NSCLC , DC result ed in greater clinical benefit in terms of response rate ( with marked improvements in overall and 2-year survival rates ) and quality of life than did treatment with PURPOSE To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life ( QoL ) in advanced non-small-cell lung cancer ( NSCLC ) compared with vinorelbine plus cisplatin as first-line chemotherapy . PATIENTS AND METHODS Patients ( n = 1,218 ) with stage IIIB to IV NSCLC were r and omly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks ( VC ) . RESULTS Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients ( P = .044 ; hazard ratio , 1.183 [ 97.2 % confidence interval , 0.989 to 1.416 ] ) . The 2-year survival rate was 21 % for DC-treated patients and 14 % for VC-treated patients . Overall response rate was 31.6 % for DC-treated patients v 24.5 % for VC-treated patients ( P = .029 ) . Median survival ( 9.4 v 9.9 months [ for VC ] ; P = .657 ; hazard ratio , 1.048 [ 97.2 confidence interval , 0.877 to 1.253 ] ) and response ( 23.9 % ) with DCb were similar to those results for VC . Neutropenia , thrombocytopenia , infection , and febrile neutropenia were similar with all three regimens . Grade 3 to 4 anemia , nausea , and vomiting were more common ( P < .01 ) with VC than with DC or DCb . Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients , who experienced deterioration in QoL. CONCLUSION DC result ed in a more favorable overall response and survival rate than VC . Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC . These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer ( NSCLC ) , we set out to determine a clinical ly meaningful change ( CMC ) on the Lung Cancer Subscale ( LCS ) and the Trial Outcome Index ( TOI ) of the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire . We used data from Eastern Cooperative Oncology Group study 5592 ( E5592 ) , a r and omized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients . Patients completed the FACT-L at baseline ( pretreatment ) , 6 weeks , 12 weeks , and 6 months . Comparing across baseline performance status ( 0 vs. 1 ) , prior weight loss ( < 5 % vs. > or = 5 % ) , and primary disease symptoms ( < or = 1 vs. > 1 ) , LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2 , respectively ( all Ps < .001 ) . Mean improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease . Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later ( mean = -1.2 vs.1.9 , respectively ) . Similarly , the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment . Twelve-week TOI change scores for patients progressing early ( mean = -8.1 ) were 5.7 points worse than those of patients progressing later ( mean = -8.1 vs. -2.4 , respectively ) . Analyses assuming nonr and om missing data result ed in slightly larger differences . Clinical ly relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI , setting upper limits for minimal CMCs . These values were comparable to suggested distribution-based criteria of a minimally important difference . These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC , and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials PURPOSE Platinum-containing chemotherapy regimens are the st and ard treatment for patients with advanced non-small-cell lung cancer ( NSCLC ) , although toxicity is common and may significantly affect the patient 's quality of life ( QoL ) . This trial aim ed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL , without influencing negatively on survival , compared with cisplatin-containing regimens . PATIENTS AND METHODS Patients with stage IIIB ( effusion and supraclavicular nodes ) or IV documented NSCLC who were younger than 70 years of age were r and omly assigned gemcitabine plus vinorelbine ( GemVin ) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin ( cisplatin-based ) . European Organization for Research and Treatment of Cancer scales were used for QoL analysis . RESULTS Five hundred one patients were r and omly assigned to treatment . The median age was 62 years . There were no significant differences in global QoL scores between the two arms after 2 months of treatment . However , worsening scores for appetite , vomiting , and alopecia were significantly more common in the cisplatin-based arm . Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms , respectively . For the GemVin arm the hazard ratio for death was 1.15 ( 90 % confidence interval [ CI ] , 0.96 to 1.37 ) and the hazard ratio for progression was 1.29 ( 90 % CI , 1.10 to 1.52 ) . Grade 3 or 4 myelosuppression , vomiting , alopecia , and ototoxicity were significantly more frequent with cisplatin-based treatment . CONCLUSION Global QoL is not improved with GemVin , although advantages in some components of QoL were apparent . GemVin is less toxic than st and ard cisplatin-based chemotherapy . There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy . GemVin could be offered to advanced NSCLC patients who express concern about toxicity BACKGROUND The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer ( NSCLC ) . This phase III study of chemotherapy-naïve advanced NSCLC patients was design ed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination . Paclitaxel was given at a dose of 200 mg/m(2 ) ( 3-h intravenous infusion ) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2 ) , all repeated every 3 weeks . Survival , toxicity and quality of life were also compared . PATIENTS AND METHODS Patients were r and omised to receive one of the two combinations , stratified according to centre , performance status , disease stage and histology . The primary analyses of response rate and survival were carried out on response-evaluable patients . Survival was also analysed for all r and omised patients . Toxicity analyses were carried out on all treated patients . RESULTS A total of 618 patients were r and omised . The two treatment arms were well balanced with regard to gender ( 83 % male ) , age ( median 58 years ) , performance status ( 83 % ECOG 0 - 1 ) , stage ( 68 % IV , 32 % IIIB ) and histology ( 38 % squamous cell carcinoma ) . In the paclitaxel/carboplatin arm , 306 patients received a total of 1311 courses ( median four courses , range 1 - 10 courses ) while in the paclitaxel/cisplatin arm , 302 patients received a total of 1321 courses ( median four courses , range 1 - 10 courses ) . In only 76 % of courses , carboplatin was administered as planned at an AUC of 6 , while in 96 % of courses , cisplatin was given at the planned dose of 80 mg/m(2 ) . The response rate was 25 % ( 70 of 279 ) in the paclitaxel/carboplatin arm and 28 % ( 80 of 284 ) in the paclitaxel/cisplatin arm ( P = 0.45 ) . Responses were review ed by an independent radiological committee . For all r and omised patients , median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [ hazard ratio 1.20 , 90 % confidence interval ( CI ) 1.03 - 1.40 ] ; the 1-year survival rates were 33 % and 38 % , respectively . On the same data set , a survival up date after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm ( hazard ratio 1.22 , 90 % CI 1.06 - 1.40 ; P = 0.019 ) ; the 2-year survival rates were 9 % and 15 % , respectively . Excluding neutropenia and thrombocytopenia , which were more frequent in the paclitaxel/carboplatin arm , and nausea/vomiting and nephrotoxicity , which were more frequent in the paclitaxel/cisplatin arm , the rate of severe toxicities was generally low and comparable between the two arms . Overall quality of life ( EORTC QLQ-C30 and LC-13 ) was also similar between the two arms . CONCLUSIONS This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC . Although paclitaxel/carboplatin yielded a similar response rate , the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option PURPOSE To compare the therapeutic efficacy of paclitaxel plus cisplatin ( arm A ) versus gemcitabine plus cisplatin ( arm B ) and arm A versus paclitaxel plus gemcitabine ( arm C ) in chemotherapy-naive patients with advanced non-small-cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Patients were r and omly assigned to receive either paclitaxel 175 mg/m2 ( 3-hour infusion , day 1 ) or gemcitabine 1,250 mg/m2 ( days 1 and 8) both combined with cisplatin 80 mg/m2 ( day 1 ) or paclitaxel 175 mg/m2 ( 3-hour infusion , day 1 ) combined with gemcitabine 1,250 mg/m2 ( days 1 and 8) . Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration , progression-free survival , toxicities , quality of life [ QoL ] , and cost of treatment . RESULTS Four hundred eighty patients ( arm A , 159 ; arm B , 160 ; arm C , 161 patients ) were enrolled ; all baseline characteristics were balanced . Median survival times were as follows : arm A , 8.1 months ; arm B , 8.9 months ; arm C , 6.7 months . Response rates were 31.8 % for arm A , 36.6 % for arm B , and 27.7 % for arm C. Other than myelosuppression ( B v A , P < .005 ) , no statistically or clinical ly significant differences were observed for secondary end points . The average treatment costs were 25 % higher in arm C as compared with arms A and B. CONCLUSION Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin . Treatment was well tolerated , and most QoL parameters were similar , but costs associated with the nonplatinum arm were highest BACKGROUND Vinorelbine , a semisynthetic vinca alkaloid , represents a well-tolerated treatment for elderly patients with advanced non-small-cell lung cancer ( NSCLC ) . We explored the quality of life ( QoL ) of such patients in a multicenter r and omized trial that compared vinorelbine treatment with supportive care alone . METHODS Eligible patients were 70 years of age or older , had stage IV or IIIB NSCLC that was ineligible for radiotherapy , and had a performance status of 0 - 2 ( a status of fully active to a status of capable of all self-care but unable to work ) . Vinorelbine was given intravenously on days 1 and 8 of a 21-day treatment cycle , for a total of six cycles . QoL was evaluated with European Organization for Research and Treatment of Cancer question naires QLQ-C30 and QLQ-LC13 , and the QoL data were analyzed by fitting a linear mixed model for each QoL scale . Survival curves were plotted and were compared with the Mantel-Haenszel test . Relative hazards of death and 95 % confidence intervals ( CIs ) were estimated by the Cox model . RESULTS Investigators , blinded to the results , stopped the trial early because of a low enrollment rate . ( From April 1996 to November 1997 , 191 of the 350 targeted patients were r and omly assigned . ) Data from 161 patients have been analyzed . Vinorelbine-treated patients scored better than control patients on QoL functioning scales , and they reported fewer lung cancer-related symptoms but reported worse toxicity-related symptoms . There was a statistically significant ( two-sided P = .03 ) survival advantage for patients receiving vinorelbine ; median survival increased from 21 to 28 weeks in the vinorelbine-treated group . The relative hazard of death for vinorelbine-treated patients was 0.65 ( 95 % CI = 0.45 - 0.93 ) . CONCLUSION Vinorelbine improves survival of elderly patients with advanced NSCLC and possibly improves overall |
12,512 | 27,212,123 | With regard to the effectiveness of Enz following AA or AA following Enz , recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy . | This study was design ed to evaluate the efficacy , tolerability , and sequential administration of abiraterone acetate ( AA ) and enzalutamide ( Enz ) for metastatic castration-resistant prostate cancer ( mCRPC ) . | BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND In the AFFIRM trial of patients with metastatic castration-resistant prostate cancer after progression with docetaxel treatment , enzalutamide significantly increased overall survival compared with placebo . Here we present the prospect ively defined analyses of some secondary endpoints , including occurrence of skeletal-related events , measures of pain control , and patient-reported health-related quality of life ( HRQoL ) . METHODS In this phase 3 , double-blind trial , patients were r and omly assigned ( 2:1 ) to receive enzalutamide 160 mg/day or placebo orally , stratified by ECOG baseline performance status ( 0 or 1 vs 2 ) and mean pain score ( Brief Pain Inventory-Short Form [ BPI-SF ] question 3 worst pain , score ≤3 vs ≥4 ) . Secondary endpoints were time to first skeletal-related event ( defined as radiation therapy or surgery to bone ) ; change from baseline to week 13 in pain severity and interference ; pain palliation and progression at week 13 ; time to pain progression ; overall improvement in HRQoL ; improvements in HRQoL domains ; and time to HRQoL deterioration . Analysis was done on the intention-to-treat population for each endpoint . AFFIRM is registered with Clinical Trials.gov , number NCT00974311 . FINDINGS Median time to first skeletal-related event in the enzalutamide ( n=800 ) and placebo ( n=399 ) groups was 16·7 months ( 95 % CI 14·6 to 19·1 ) and 13·3 months ( 95 % CI 9·9 to not yet reached ) , respectively ( hazard ratio [ HR ] 0·69 [ 95 % CI 0·57 - 0·84 ] ; p=0·0001 ) . Pain progression at week 13 occurred in 174 ( 28 % ) of 625 evaluable patients in the enzalutamide group versus 101 ( 39 % ) of 259 patients in the placebo group ( difference -11·2 % , 95 % CI -18·1 to -4·3 ; p=0·0018 ) . Median time to pain progression was not yet reached in the enzalutamide group ( 95 % CI not yet reached to not yet reached ) versus 13·8 ( 13·8 to not yet reached ) months in the placebo group ( HR 0·56 [ 95 % CI 0·41 to 0·78 ] ; p=0·0004 ) . Mean treatment effects for pain severity ( mean change from baseline in the enzalutamide group -0·15 , 95 % CI -0·28 to -0·02 , vs placebo 0·50 , 0·29 to 0·70 ; difference -0·65 , 95 % CI -0·89 to -0·41 ; p<0·0001 ) and interference ( -0·01 , -0·18 to 0·16 , vs 0·74 , 0·47 to 1·00 ; respectively , difference -0·74 , 95 % -1·06 to -0·43 ; p<0·0001 ) were significantly better with enzalutamide than with placebo . 22 ( 45 % ) of 49 evaluable patients in the enzalutamide group reported pain palliation at week 13 versus one ( 7 % ) of 15 in the placebo group ( difference 38·2 % , 95 % CI 19·4 - 57·0 ; p=0·0079 ) . Overall improvement in HRQoL was reported in more patients receiving enzalutamide ( 275 [ 42 % ] of 652 ) than in those receiving placebo ( 36 [ 15 % ] of 248 ; p<0·0001 ) . Patients in the enzalutamide group had longer median time to HRQoL deterioration than did those in the placebo group ( 9·0 months , 95 % CI 8·3 - 11·1 , vs 3·7 months , 95 % CI 3·0 - 4·2 ; HR 0·45 , 95 % CI 0·37 - 0·55 ; p<0·0001 ) in risk of deterioration . INTERPRETATION Our results show that , in addition to improving overall survival , enzalutamide improves wellbeing and everyday functioning of patients with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation |
12,513 | 29,497,608 | Study outcomes included improved knowledge , attitude , and behaviors . | Background Youth peer-led interventions have become a popular way of sharing health information with young people and appear well suited to Indigenous community context s. However , no systematic review s focusing on Indigenous youth have been published .
We conducted a systematic review to underst and the range and characteristics of Indigenous youth-led health promotion projects implemented and their effectiveness . | OBJECTIVE : The goal of this study was to assess the efficacy of an after-school , peer-led , healthy living program on adiposity , self-efficacy , and knowledge of healthy living behaviors in children living in a remote isolated First Nation . METHODS : A quasi-experimental trial with a parallel nonequivalent control arm was performed with 151 children in Garden Hill First Nation during the 2010–2011 and 2011–2012 school years . Fourth grade students were offered a 5-month , peer-led intervention facilitated by high school mentors between January and May of each school year ; students in the control arm received st and ard curriculum . The main outcome measures were waist circumference ( WC ) and BMI z score . Secondary outcome measures included healthy living knowledge and self-efficacy . RESULTS : Fifty-one children ( mean ± SD age : 9.7 ± 0.4 years ; BMI z score : 1.46 ± 0.84 ) received the intervention , and 100 children were in the control arm . At baseline , WC ( 79.8 vs 83.9 cm ) , BMI z score ( 1.46 vs 1.48 ) , and rates of overweight/obesity ( 75 % vs 72 % ) did not differ between arms . After the intervention , the change in WC ( adjusted treatment effect : –2.5 cm [ 95 % confidence interval ( CI ) : –4.1 to –0.90 ] ; P = .002 ) and BMI z score ( adjusted treatment effect : –0.09 [ 95 % CI : –0.16 to –0.03 ] ; P = .007 ) were significantly lower in the intervention arm compared to the control arm . The intervention arm also experienced improvements in knowledge of healthy dietary choices ( 2.25 % [ 95 % CI : –0.01 to 6.25 ] ; P = .02 ) . Self-efficacy was associated with the change in WC after the intervention ( β = –7.9 , P = .03 ) . CONCLUSIONS : An after-school , peer-led , healthy living program attenuated weight gain and improved healthy living knowledge in children living in a remote isolated First Nation The Solihull Approach is a psychotherapeutic and behavioural model for health visitors and other professionals working with children and families to address sleeping , toileting , feeding and behavioural difficulties in young children . This pilot study used quantitative methods to assess the effectiveness of the Solihull Approach compared to st and ard health visitor practice . At assessment , the parent completed the short form Parenting Stress Index and a visual analogue scale rating how severe the problem was . The health visitor also completed a visual analogue scale rating their perception of the severity of the problem . This process was repeated at the end of the intervention and again at three months follow-up . Results showed statistically significant better outcome on five out of six measures for the experimental group . Results are discussed in context of a small sample size We conducted a school-based parallel cluster r and omized controlled trial with 36-month follow-up of children aged 7 to 8 years . Primary schools were r and omly assigned to 2 groups : 3 applications of fluoride varnish ( 22,600 ppm ) each year or no intervention . The primary outcome was DFS increment in the first permanent molars , with the hypothesis that 9 applications of varnish over 3 years would result in a lower increment in the test group . Follow-up measurements were recorded by examiners blind to the allocation . Ninety-five schools were r and omized to the test and 95 to the reference groups ; 1473 ( test ) and 1494 ( reference ) children participated in the trial . An intention-to-treat analysis was carried out with r and om effects models . The DFS increment was 0.65 ( SD 2.15 ) in the test and 0.67 ( SD 2.10 ) in the reference groups , respectively . There was no statistically significant difference between the groups . We were unable to demonstrate an effect for fluoride varnish when it was used as a public health intervention to prevent caries in the first permanent molar teeth ( Inter-national St and ard R and omized Controlled Trial Registration : IS RCT N : # 72589426 IMPORTANCE Schools are considered an attractive setting to promote healthy living behaviors in children , but previous school-based interventions aim ed at preventing weight gain in children have yielded mixed results . Novel school-based approaches are needed to modify healthy living behaviors and attenuate weight gain in children . OBJECTIVE To assess the effectiveness of a peer-led healthy living program called Healthy Buddies on weight gain and its determinants when disseminated at the provincial level to elementary school students . DESIGN , SETTING , AND PARTICIPANTS Cluster-r and omized effectiveness trial performed during the 2009 - 2010 school year . Baseline and follow-up measurements were made in October 2009 and May 2010 , respectively . The study was performed in 19 elementary schools in Manitoba , Canada , and included 647 elementary school students aged 6 to 12 years ( 48 % girls ) . INTERVENTION Schools were r and omized to receive regular curriculum or Healthy Buddies lesson plans . Lesson plans were delivered by older ( 9- to 12-year-old ) elementary school students to the younger ( 6- to 8-year-old ) peers and targeted 3 components of health : physical activity , healthy eating , and self-esteem and body image . MAIN OUTCOMES AND MEASURES The primary outcome measures were the change in waist circumference and body mass index z score . Secondary outcomes included physical activity ( steps per day ) , cardiorespiratory fitness , self-efficacy , healthy living knowledge , and self-reported dietary intake . RESULTS At baseline , 36 % of children were overweight or obese and 11 % achieved the recommended 13,500 steps per day . Intention-to-treat analyses showed that waist circumference declined significantly in the intervention group relative to controls : -1.42 cm ( -2.68 to -0.17 ; P = .03 ) . Reductions in waist circumference were particularly significant for children who were younger , overweight or obese , or attending First Nations schools . No difference in body mass index z score was observed between groups . Self-efficacy , healthy living knowledge , and dietary intake significantly improved in younger peers who received the intervention compared with students from control schools . No differences were observed in daily step counts or cardiorespiratory fitness between the groups . CONCLUSIONS AND RELEVANCE The implementation of Healthy Buddies lesson plans delivered by older peers within an elementary school setting is an effective method for attenuating increases in central adiposity and improving knowledge of healthy living behaviors among elementary school students . Improvements were achieved with parallel improvements in diet quality , self-efficacy , and knowledge of healthy living . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01979978 A peer-managed self-control program to teach responsible drinking was tested with 30 American Indian teenagers at high risk for problem drinking . Students were r and omly assigned to three groups incorporating combinations of self-monitoring , peer-assisted self-control training , and alcohol education . Significant decreases were observed in quantity and frequency of drinking and in peak blood alcohol levels . These improvements were maintained at follow-ups of 4 , 9 , and 12 months posttreatment . Self-report data were corroborated by breath tests and official records . No group differences were found , indicating that minimal and full program interventions had comparable effects |
12,514 | 25,461,441 | The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer | Smoking is estimated to cause about half of all bladder cancer cases .
Case – control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk .
As part of the World Cancer Research /American Institute for Cancer Research Continuous Up date Project , we conducted a systematic review and meta- analysis of prospect i ve studies to assess the dose – response relationship between fruit and vegetables and incidence and mortality of bladder cancer . | Data derived from laboratory investigations suggest that a number of dietary variables may contribute to bladder carcinogenesis . Although bladder cancer is the fourth leading cause of cancer in men in the United States , dietary studies are few . The authors examined the relations between intakes of macro- and micronutrients and the risk of bladder cancer among men in the prospect i ve Health Professionals Follow-Up Study . Each participant completed a 131-item food frequency question naire in 1986 and in 1990 , from which nutrient intakes were calculated . During 12 years of follow-up , 320 cases of bladder cancer were diagnosed . No association was observed for total caloric or macronutrient intake and bladder cancer risk . Similarly , we found no relation for dietary intake of potassium , sodium , calcium , magnesium , phosphorus , iron , or water-soluble vitamins and bladder cancer risk . Total vitamin E intake and vitamin E supplements were inversely associated with risk . In addition , a dose-response relation was observed for duration of vitamin E supplement use . A suggestive inverse association was seen with dose of vitamin C supplement use . More studies are needed to determine the role of vitamins E and C supplement intake in bladder carcinogenesis We examined the relation between dietary fruit and vegetables , carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospect i ve cohort study . Over a median of 11 years , we followed 27 111 male smokers aged 50–69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study . During this period , 344 men developed bladder cancer . All of these men had completed a 276-food item dietary question naire at baseline . Cox proportional hazards models were used to estimate the relative risks and 95 % confidence intervals and to simultaneously adjust for age , smoking history , energy intake and intervention group . Consumption of fruits and vegetables was not associated with the risk of bladder cancer ( relative risk=1.28 ; 95 % confidence intervals CI : 0.89–1.84 , for highest vs lowest quintile ) . Similarly , no associations were observed for groups of fruits or vegetables ( berries and cruciferous vegetables ) , or for specific fruits and vegetables . Dietary intakes of alpha-carotene , beta-carotene , lycopene , lutein/zeaxanthin , beta-cryptoxanthin , vitamins A , E , and C , and folate were not related to the risk of bladder cancer . These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk . However , these results may not be generalisable to non-smokers BACKGROUND There is probable evidence that some types of fruit and vegetables provide protection against many cancers . OBJECTIVE We hypothesized that fruit and vegetable intakes are inversely related to the incidence of total cancers among women and men aged > 50 y. DESIGN We performed a prospect i ve study among the cohort of the National Institutes of Health-AARP Diet and Health Study . We merged the MyPyramid Equivalents Data base ( version 1.0 ) with food-frequency- question naire data to calculate cup equivalents for fruit and vegetables . From 1995 to 2003 , we identified 15,792 and 35,071 cancer cases in 195,229 women and 288,109 men , respectively . We used Cox proportional hazards models to estimate multivariate relative risks ( RRs ) and 95 % CIs associated with the highest compared with the lowest quintile ( Q ) of fruit and vegetable intakes . RESULTS Fruit intake was not associated with the risk of total cancer among women ( RR(Q5 vs Q1 ) = 0.99 ; 95 % CI : 0.94 , 1.05 ; P trend = 0.059 ) or men ( RR(Q5 vs Q1 ) = 0.98 ; 95 % CI : 0.95 , 1.02 ; P for trend = 0.17 ) . Vegetable intake was not associated with risk of total cancer among women ( RR(Q5 vs Q1 ) = 1.04 ; 95 % CI : 0.98 , 1.09 ; P for trend = 0.084 ) , but was associated with a significant decrease in risk in men ( RR(Q5 vs Q1 ) = 0.94 ; 95 % CI : 0.91 , 0.97 ; P trend = 0.004 ) . This significant finding among men was no longer evident when we limited the analysis to men who never smoked ( RR(Q5 vs Q1 ) = 0.97 ; 95 % CI : 0.91 , 1.04 ; P for trend = 0.474 ) . CONCLUSIONS Intake of fruit and vegetables was generally unrelated to total cancer incidence in this cohort . Residual confounding by smoking is a likely explanation for the observed inverse association with vegetable intake among men BACKGROUND Previous epidemiologic studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results , especially with regard to the types of fruits and vegetables consumed . We examined total fruit and vegetable intake , as well as intakes of subtypes of fruits and vegetables , in relation to bladder cancer risk in a large male prospect i ve cohort study . METHODS Two hundred fifty-two cases of incident bladder cancer were diagnosed from 1986 through January 31 , 1996 , among 47,909 men enrolled in the Health Professionals Follow-up Study . Each participant in this cohort completed a 131-item food-frequency question naire in 1986 and subsequently in 1990 and 1994 . We used logistic regression analyses to examine fruit and vegetable intake in relation to bladder cancer risk , after adjusting for age , history of cigarette smoking , current smoking status , geographic region , total fluid intake , and caloric intake . RESULTS We observed a weak , inverse association that was not statistically significant between total fruit and vegetable intake and bladder cancer risk . Intake of cruciferous vegetables was inversely associated with risk ( relative risk = 0.49 ; 95 % confidence interval = 0.32 - 0.75 , for the highest category of cruciferous vegetable intake compared with the lowest ) , but intakes of yellow or green leafy vegetables or carotenoid-rich vegetables were not associated with risk . Individual cruciferous vegetables , except for coleslaw , were all inversely related to bladder cancer risk , but only the associations for broccoli and cabbage were statistically significant . CONCLUSIONS Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk , but other vegetables and fruits may not confer appreciable benefits against this cancer CONTEXT Previous studies indicate that the population attributable risk ( PAR ) of bladder cancer for tobacco smoking is 50 % to 65 % in men and 20 % to 30 % in women and that current cigarette smoking triples bladder cancer risk relative to never smoking . During the last 30 years , incidence rates have remained stable in the United States in men ( 123.8 per 100,000 person-years to 142.2 per 100,000 person-years ) and women ( 32.5 per 100,000 person-years to 33.2 per 100,000 person-years ) ; however , changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer . OBJECTIVE To evaluate the association between tobacco smoking and bladder cancer . DESIGN , SETTING , AND PARTICIPANTS Men ( n = 281,394 ) and women ( n = 186,134 ) of the National Institutes of Health-AARP ( NIH-AARP ) Diet and Health Study cohort completed a lifestyle question naire and were followed up between October 25 , 1995 , and December 31 , 2006 . Previous prospect i ve cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2 ) statistic . MAIN OUTCOME MEASURES Hazard ratios ( HRs ) , PARs , and number needed to harm ( NNH ) . RESULTS During 4,518,941 person-years of follow-up , incident bladder cancer occurred in 3896 men ( 144.0 per 100,000 person-years ) and 627 women ( 34.5 per 100,000 person-years ) . Former smokers ( 119.8 per 100,000 person-years ; HR , 2.22 ; 95 % confidence interval [ CI ] , 2.03 - 2.44 ; NNH , 1250 ) and current smokers ( 177.3 per 100,000 person-years ; HR , 4.06 ; 95 % CI , 3.66 - 4.50 ; NNH , 727 ) had higher risks of bladder cancer than never smokers ( 39.8 per 100,000 person-years ) . In contrast , the summary risk estimate for current smoking in 7 previous studies ( initiated between 1963 and 1987 ) was 2.94 ( 95 % CI , 2.45 - 3.54 ; I(2 ) = 0.0 % ) . The PAR for ever smoking in our study was 0.50 ( 95 % CI , 0.45 - 0.54 ) in men and 0.52 ( 95 % CI , 0.45 - 0.59 ) in women . CONCLUSION Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987 , relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher , with PARs for women comparable with those for men Objective : To examine the relation between fruits and vegetables , carotenoids , folate , and vitamins A , C , E and the risk of bladder cancer in a prospect i ve study of women Methods : A total of 237 incident bladder cancer cases were documented during 20 years of follow-up among 88,796 women enrolled in the Nurses ’ Health Study . Dietary intake was assessed by food-frequency question naires every two to four years and incident diagnosis of bladder cancer was ascertained every two years . Cox proportional hazard models were used to estimate incidence rate ratios ( RR ) and 95 % confidence intervals ( CI ) for bladder cancer risk , adjusting for age , pack-years of smoking , current smoking , and total caloric intake . Results : Consumption of total fruits and vegetables was not associated with bladder cancer risk ( RR = 1.08 , 95 % CI = 0.70–1.65 , for > 5.5 compared to < 2.5 servings per day ) . Similarly , dietary intakes of carotenoids , folate , and vitamins A , C , E , were not related to bladder cancer risk . No association was observed between supplemental intake of multivitamins , vitamins A , C , E and bladder cancer risk . Conclusions : We did not observe any association for fruit and vegetable consumption or vitamin intake and bladder cancer risk among women Fruit and vegetable consumption has been inconsistently associated with risk of bladder cancer . We used data from a prospect i ve population -based cohort study of 82,002 Swedish women and men to examine the association between fruit and vegetable consumption and bladder cancer incidence . Diet was assessed with a vali date d food frequency question naire . During a mean follow-up of 9.4 years , 485 incident cases of bladder cancer were identified in the Swedish cancer registries . We found no statistically significant association between intakes of total fruits and vegetables , total fruits , or total vegetables and bladder cancer risk after adjustment for age , sex , education , and cigarette smoking . The multivariate rate ratios ( 95 % confidence intervals ) comparing the highest with the lowest quartile of intake were 0.80 ( 0.60 - 1.05 ) for total fruits and vegetables , 0.93 ( 0.69 - 1.25 ) for fruits , and 0.89 ( 0.67 - 1.19 ) for vegetables . Likewise , no associations were observed for citrus fruits , cruciferous vegetables , or green leafy vegetables . The associations did not differ by sex or smoking status . In conclusion , findings from this prospect i ve study suggest that fruit and vegetable intakes are not likely to be appreciably associated with the risk of bladder cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(9):2519–22 BACKGROUND Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent . Biomarkers may provide more accurate measures of nutrient status . OBJECTIVE We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma ( UCC ) in a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition . DESIGN A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex , age at baseline , study center , date and time of blood collection , and fasting status . Plasma carotenoids ( α- and β-carotene , β-cryptoxanthin , lycopene , lutein , and zeaxanthin ) were measured by using reverse-phase HPLC , and plasma vitamin C was measured by using a colorimetric assay . Incidence rate ratios ( IRRs ) were estimated by using conditional logistic regression with adjustment for smoking status , duration , and intensity . RESULTS UCC risk decreased with higher concentrations of the sum of plasma carotenoids ( IRR for the highest compared with the lowest quartile : 0.64 ; 95 % CI : 0.44 , 0.93 ; P-trend = 0.04 ) . Plasma β-carotene was inversely associated with aggressive UCC ( IRR : 0.51 ; 95 % CI : 0.30 , 0.88 ; P-trend = 0.02 ) . Plasma lutein was inversely associated with risk of nonaggressive UCC ( IRR : 0.56 ; 95 % CI : 0.32 , 0.98 ; P-trend = 0.05 ) . No association was observed between plasma vitamin C and risk of UCC . CONCLUSIONS Although residual confounding by smoking or other factors can not be excluded , higher concentrations of plasma carotenoids may reduce risk of UCC , in particular aggressive UCC . Plasma lutein may reduce risk of nonaggressive UCC Basic research and case – control studies have suggested that citrus consumption may protect against cancer . However , the protective effect has been observed from few prospect i ve studies . This study investigated the association of citrus consumption with cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort , which covered an age range of 40–79 years , and was followed up from 1995 to 2003 for all‐cancer and individual cancer incidence . Citrus consumption was assessed using a self‐administered question naire . The Cox proportional hazard model was applied to estimate relative risks ( RRs ) and 95 % CIs . During the 323,204 person‐years of follow‐up , 3,398 cases were identified totally . Citrus consumption , especially daily consumption , was correlated with reduced all‐cancer incidence , the RRs were 0.89 ( 95 % CI = 0.80–0.98 ) for total participants , 0.86 ( 0.76–0.98 ) for males and 0.93 ( 0.79–1.09 ) for females , as well as multiple cancers at individual sites , especially pancreatic ( RR = 0.62 , 95 % CI = 0.38–1.00 ) and prostate cancer ( RR = 0.63 , 95 % CI = 0.41–0.97 ) . Joint effect analysis showed a reduced risk of overall cancer existed only for subjects who consumed ≥1 cup green tea/day ( RR = 0.83 , 95 % CI = 0.73–0.93 ) as well as for males ( RR = 0.83 , 95 % CI = 0.71–0.97 ) or females ( RR = 0.82 , 95 % CI = 0.68–0.99 ) . These findings suggest that citrus consumption is associated with reduced all‐cancer incidence , especially for subjects having simultaneously high green tea consumption . Further work on the specific citrus constituents is warranted , and clinical trials are ultimately necessary to confirm the protective effect BACKGROUND Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma ( UCC ) of the bladder , but results are inconsistent . The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness . Therefore , we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . METHODS After 8.9 years of follow-up , 947UCC were diagnosed among 468,656 EPIC participants . Of these , 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases . At recruitment , fruit and vegetable consumption was assessed by vali date d dietary question naires . Multivariable hazard ratios were estimated using Cox regression stratified by age , sex and center and adjusted for smoking status , duration and intensity of smoking , and energy intake . RESULTS Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC . A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC ( hazard ratio ( HR ) 0.88 ; 95%confidence interval ( CI ) 0.78 - 1.00 and HR 0.87 ; 95%CI 0.77 - 0.98 , respectively ) , while the intake of root vegetables was inversely associated with risk of aggressive UCC ( HR 0.87 ; 95%CI 0.77 - 0.98 ) . CONCLUSION Our study did not confirm a protective effect of total fruit and /or vegetable consumption on aggressive or non-aggressive UCC . High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC ; however chance findings can not be excluded Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer . We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Data on food consumption and complete follow‐up for cancer occurrence was available for a total of 478,533 participants , who were recruited in 10 European countries . Estimates of rate ratios were obtained by Cox proportional hazard models , stratified by age at recruitment , gender and study centre , and adjusted for total energy intake , smoking status , duration of smoking and lifetime intensity of smoking . A calibration study in a sub sample was used to control for dietary measurement errors . After a mean follow‐up of 8.7 years , 1015 participants were newly diagnosed with bladder cancer . Increments of 100 g/day in fruit and vegetable consumption combined did not affect bladder cancer risk ( i.e. , calibrated HR = 0.98 ; 95%CI : 0.95–1.01 ) . Borderline statistically significant lower bladder cancer risks were found among never smokers with increased consumption of fruit and vegetables combined ( HR = 0.94 95%CI : 0.87–1.00 with increments of 100 g/day ; calibrated HR = 0.92 95%CI 0.79–1.06 ) and increased consumption of apples and pears ( hard fruit ; calibrated HR = 0.90 95%CI : 0.82–0.98 with increments of 25 g/day ) . For none of the associations a statistically significant interaction with smoking status was found . Our findings do not support an effect of fruit and vegetable consumption , combined or separately , on bladder cancer risk . © 2009 Geographic variations in bladder cancer risk , observed in the United States and other countries , have been ecologically related to soil selenium levels . Evidence from clinical trials , observational , and animal studies suggests that selenium is anticarcinogenic and can affect the risk of Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer , as they contain numerous nutrients , phytochemicals , and antioxidants with potentially anticarcinogenic properties . In a prospect i ve analysis of 185,885 older adults participating in the Multiethnic Cohort Study , we examined whether the consumption of fruits and vegetables , or of nutrients concentrated in fruits and vegetables , was associated with bladder cancer risk . Cox proportional hazards models were used to calculate HRs and 95 % CIs for bladder cancer in relation to dietary intakes . A total of 581 invasive bladder cancer cases ( 429 men and 152 women ) were diagnosed over a mean follow-up period of 12.5 y. In women , total fruits and vegetables [ HR = 0.35 ( 95 % CI : 0.22 , 0.56 ) ; highest vs. lowest quartile ] , total vegetables [ HR = 0.49 ( 95 % CI : 0.29 , 0.83 ) ] , yellow-orange vegetables [ HR = 0.48 ( 95 % CI : 0.30 , 0.77 ) ] , total fruits [ HR = 0.54 ( 95 % CI : 0.34 , 0.85 ) ] , and citrus fruits [ HR = 0.56 ( 95 % CI : 0.34 , 0.90 ) ] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models . In addition , women with the highest intakes of vitamins A , C , and E ; the carotenoids α-carotene , β-carotene , and β-cryptoxanthin ; and folate had a lower risk of bladder cancer . For men , no associations for fruits , vegetables , or nutrients were found overall , although inverse associations were observed for vegetable intake among current smokers , and in ethnic-specific analyses , for fruit and vegetable intake among Latinos specifically . Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies |
12,515 | 23,594,621 | Findings were less consistent for lower-than-referent values . | Background Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients .
Several studies have demonstrated non-linear ( U-shaped or J-shaped ) associations between these minerals and mortality , though many research ers have assumed linear relationships in their statistical modeling .
This analysis synthesizes the non-linear relationships across studies . | Background Progression of coronary artery calcification ( CAC ) has been described in hemodialysis patients , and severe CAC has been associated with the occurrence of cardiovascular events in this population . Little information is available regarding peritoneal patients . Aim To prospect ively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression , as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period . Methods Using multislice coronary tomography , calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients . Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables , including lipid profile , parameters of mineral metabolism , and markers of inflammation . Cardiovascular events , hospitalizations , and all-cause mortality were recorded . Results At baseline , 29 patients ( 59 % ) presented CAC and a median calcium score of 234.7 ( range 10.3 – 2351 ) Agatston units . Progression of CAC was observed in 13 patients ( 43 % ) who , in comparison with those presenting no CAC progression , were older , presented higher baseline calcium scores , and had higher mean glucose levels , lower mean high density lipoprotein cholesterol levels , and more months using low calcium peritoneal solution . We also observed a trend toward more often presenting with a history of hypertension , exhibiting more hyperphosphatemic and hyperglycemic events , and having lower albumin levels . In multiple logistic regression , only baseline calcium score was independently associated with progression of CAC . A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC . Hospitalization event-free time did not differ between the groups . Conclusion Determining CAC provides important prognostic data in peritoneal dialysis patients . Baseline calcium score and disturbances in glucose , mineral , and lipid metabolism were indicative of higher risk of CAC progression in this population BACKGROUND AND OBJECTIVES Vascular calcification is increasingly recognized as an important component of cardiovascular disease in chronic kidney disease . The objective of this study was to investigate prospect ively the determinants , cardiovascular functional consequences , and survival associated with vascular calcification over 24 mo . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A total of 134 patients ( 60 on hemodialysis , 28 on peritoneal dialysis , and 46 with stage 4 chronic kidney disease ) were studied . Vascular calcification of the superficial femoral artery was assessed using multislice spiral computed tomography ; pulse wave velocity ; all medications and time-averaged biochemical parameters were recorded at baseline and 12 and 24 mo . RESULTS A total of 101 patients remained at 24 mo . Progressive calcification was seen in 58 of 101 patients . Most ( 31 of 46 ) patients with an initial calcification score of zero did not develop calcification . The hemodialysis group demonstrated a greater degree of progression than patients who were on peritoneal dialysis or had stage 4 chronic kidney disease . Progressive calcification was associated with age , male gender , serum alkaline phosphatase , beta blockers , and lipid-lowering agents . Increases in vascular calcification correlated with increased arterial stiffness . Vascular calcification was present in 20 of 21 patients who died . Cox proportional hazard analysis identified change in calcification score , calcium intake from phosphate binders , and low albumin as risk factors for death . CONCLUSIONS Patients with stages 4 and 5 chronic kidney disease and preexisting vascular calcification exhibit significantly increased calcification over 24 mo . Rapid progression of calcification is associated with arterial stiffness and mortality BACKGROUND Dietary restrictions to control serum phosphorus , which are routinely recommended to persons with chronic kidney disease , are usually associated with a reduction in protein intake . This may lead to protein-energy wasting and poor survival . OBJECTIVE We aim ed to ascertain whether a decline in serum phosphorus and a concomitant decline in protein intake are associated with an increase in the risk of death . DESIGN In a 3-y study ( 7/2001 - 6/2004 ) of 30 075 prevalent maintenance hemodialysis ( MHD ) patients , we examined changes in serum phosphorus and in normalized protein nitrogen appearance ( nPNA ) , a surrogate of dietary protein intake , during the first 6 mo and the subsequent mortality . Four groups of MHD patients were defined on the basis of the direction of the changes in serum phosphorus and nPNA . RESULTS Baseline phosphorus had a J-shaped association with mortality , whereas higher baseline nPNA was linearly associated with greater survival . Compared with MHD patients whose serum phosphorus and nPNA both rose over 6 mo , those whose serum phosphorus decreased but whose nPNA increased had greater survival , with a case mix-adjusted death risk ratio of 0.90 ( 95 % confidence limits : 0.86 , 0.95 ; P < 0.001 ) , whereas those whose phosphorus increased but whose nPNA decreased or those whose phosphorus and nPNA both decreased had worse mortality with a risk ratio of 1.11 ( 1.05,1.17 ; P < 0.001 ) and 1.06 ( 1.01,1.12 ; P = 0.02 ) , respectively . CONCLUSIONS The risk of controlling serum phosphorus by restricting dietary protein intake may outweigh the benefit of controlled phosphorus and may lead to greater mortality . Additional studies including r and omized controlled trials should examine whether nondietary control of phosphorus or restriction of nonprotein sources of phosphorus is safer and more effective BACKGROUND Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease ( ESRD ) . Although calcium levels critically affect almost all cellular processes , the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown . METHODS An inception cohort of 433 patients starting ESRD therapy was followed prospect ively for an average of 41 months . Serum calcium and other parameters were measured monthly . The mean calcium levels were 9.4 + /- 0.7 mg/dl . 23 % of the patients had mean calcium levels < 8.8 mg/dl . After adjusting for baseline age , diabetes mellitus , ischemic heart disease , smoking and cholesterol levels , as well as serial albumin , hemoglobin , mean arterial blood pressure , phosphate and alkaline phosphatase levels , chronic hypocalcemia was strongly associated with mortality ( RR 2.10 , p = 0.006 for a mean calcium level < 8.8 mg/dl ) . The association with mortality was similar in hemodialysis ( RR 2.10 , p = 0.006 ) and peritoneal dialysis patients ( 2.67 , p = 0.034 ) . Using similar covariate adjustment , chronic hypocalcemia was associated with de novo ischemic heart disease ( RR 5.23 , p < 0.001 ) , recurrent ischemic heart disease ( RR 2.46 , p = 0.006 ) , de novo cardiac failure ( RR 2.64 , p < 0.001 ) , and recurrent cardiac failure ( RR 3.30 , p < 0.001 ) . Hypocalcemia retained its independent impact on morbidity and mortality when analyzed as a time-dependent covariate . CONCLUSIONS Chronic hypocalcemia , a very common , reversible feature of chronic uremia , is independently associated with morbidity and mortality in ESRD patients BACKGROUND Obesity is associated with secondary hyperparathyroidism in the general population . It is unknown whether body mass index ( BMI ) affects parathyroid hormone ( PTH ) level and its association with mortality in dialysis patients . METHODS From a prospect i ve cohort study of incident dialysis patients in the Netherl and s ( NECOSAD ) , we selected all patients with recorded BMI and PTH at 3 months ( baseline ) after the start of dialysis [ n = 1628 , age 59 ± 15 years , BMI 24.7 ± 4.1 kg/m(2 ) , median PTH 13.0 ( interquartile range 5.3 - 29.0 ) pmol/L ] . We assessed associations between BMI and PTH at baseline and between their changes over 3 months by correlation and linear regression analyses . The effect of the changes in PTH on all-cause mortality during a subsequent mean follow-up of 3.2 ± 2 years was assessed by Cox regression analyses . RESULTS Median PTH levels at baseline were lowest in underweight patients ( 10.2 pmol/L ) , followed by normal weight ( 12.1 pmol/L ) , overweight ( 14.0 pmol/L ) and obese patients ( 17.5 pmol/L ) . The associations were similar in diabetic and non-diabetic patients . A ≥ 5 % decrease in BMI ( n = 101 ) over 3 months was accompanied by a 26 % decrease in PTH ( PTH(ratio ) 0.74 ; P = 0.039 ) , whereas a ≥ 5 % increase in BMI ( n = 143 ) was associated with an 11 % increase in PTH ( PTH(ratio ) 1.11 ; P = 0.026 ) . Compared to patients with stable PTH levels , patients with decreasing PTH in the presence of weight loss showed a 2-fold higher mortality ( hazard ratio 2.02 , 95 % confidence interval 1.45 - 2.83 ; P < 0.001 ) , in contrast to those with decreasing PTH in the absence of weight loss . Additional analyses showed that the weight loss was responsible for increased deaths . CONCLUSIONS PTH is associated with BMI and its longitudinal changes in dialysis patients , both in patients with and without diabetes mellitus . An increased mortality seen for patients with concurrent decreases in PTH and BMI was explained by the weight loss , representing an important confounder for outcome analyses according to levels of PTH . Low and decreasing PTH levels may be symptoms of wasting , which should be taken into account in the care of dialysis patients BACKGROUND Abnormalities in bone mineral metabolism parameters are common in patients with end-stage kidney disease on dialysis therapy . The National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative ( KDOQI ) guidelines propose targets for calcium , phosphate , and intact parathyroid hormone ( iPTH ) levels in patients undergoing dialysis . However , whether achievement of these targets improves survival is unknown . STUDY DESIGN Retrospective cohort study . SETTING & PARTICIPANTS Incident patients on hemodialysis or peritoneal dialysis therapy in the United Kingdom from 2000 - 2004 who survived at least 12 months . PREDICTOR Achievement of KDOQI calcium , phosphate , and iPTH guideline targets during the first year of dialysis therapy . OUTCOMES All-cause mortality in the subsequent 2 years . MEASUREMENTS Calcium , phosphate , and iPTH at quarterly intervals , demographic and comorbid condition data at baseline . RESULTS We included 7,076 incident patients ( 4,947 hemodialysis , 2,129 peritoneal dialysis ) in our analysis . Approximately two thirds of patients were men and 21 % had diabetes as the cause of kidney failure . Guideline target achievement for each quarter varied from 23%-26 % for iPTH level , 43%-47 % for calcium level , and 54%-62 % for phosphate level targets . In adjusted Cox proportional hazards models , patients who achieved guideline targets in all 4 quarters did not have a survival advantage over patients who never achieved target ( P > 0.1 for calcium , phosphate , and iPTH ) . LIMITATIONS Missing information about medication use , vitamin D and alkaline phosphatase levels , and dialysate calcium content . CONCLUSIONS Our findings do not support the use of KDOQI bone mineral guideline achievement as a quality measure for dialysis care . Prospect i ve studies with longer term follow-up are needed to define the optimal cutoff values for calcium , phosphate , and iPTH and assess the effect of guideline implementation on patient survival Hyperphosphatemia is highly prevalent among patients with end-stage renal disease ( ESRD ) and is associated with increased mortality risk in hemodialysis ( HD ) patients . The mechanism through which this mortality risk is mediated is unclear . Data from two national r and om sample s of HD patients ( n = 12,833 ) was used to test the hypothesis that elevated serum PO(4 ) contributes mainly to cardiac causes of death . During a 2-yr follow-up , the cause-specific relative risk ( RR ) of death for patients was analyzed separately for several categories of cause of death , including coronary artery disease ( CAD ) , sudden death , and other cardiac causes , cerebrovascular and infection . Cox regression models were fit for each of the eight cause of death categories , adjusting for patient demographics and non-cardiovascular comorbid conditions . Time at risk for each cause-specific model was censored at death that result ed from any of the other causes . Higher mortality risk was seen for patients in the high PO(4 ) group ( > 6.5mg/dl ) compared with the lower PO(4 ) group ( < or = 6.5mg/dl ) for death result ing from CAD ( RR 1.41 ; P < 0.0005 ) , sudden death ( RR 1.20 ; P < 0.01 ) , infection ( RR 1.20 ; P < 0.05 ) , and unknown causes ( RR 1.25 ; P < 0.05 ) . Patients in the high PO(4 ) group also had non-significantly increased RR of death from other cardiac and cerebrovascular causes of death . The RR of sudden death was also strongly associated with elevated Ca x PO(4 ) product ( RR 1.07 per 10 mg(2)/dl(2 ) ; P < 0.005 ) and serum parathyroid hormone levels greater than 495 pg/ml ( RR 1.25 ; P < 0.05 ) . This study identifies strong relationships between elevated serum PO(4 ) , Ca x PO(4 ) product , and parathyroid hormone and cardiac causes of death in HD patients , especially deaths result ing from CAD and sudden death . More vigorous measures to reduce the prevalence of these factors in HD patients may result in improved survival Although hyperphosphatemia is a risk factor for mortality , there are limited data on whether therapy with phosphorus binders affects survival . We analyzed a prospect i ve cohort study of 10,044 incident hemodialysis patients using Cox proportional hazards analyses to compare 1-yr all-cause mortality among patients who were or were not treated with phosphorus binders . We performed intention-to-treat analyses to compare patients who began treatment with phosphorus binders during the first 90 d after initiating hemodialysis ( n = 3555 ) with those who remained untreated during that period ( n = 5055 ) . We also performed as-treated analyses that modeled phosphorus binder treatment as a time-dependent exposure . We compared survival in a subcohort of treated ( n = 3186 ) and untreated ( n = 3186 ) patients matched by their baseline serum phosphate levels and propensity score of receiving phosphorus binders during the first 90 d. One-year mortality was 191 deaths/1000 patient-years at risk . Treatment with phosphorus binders was independently associated with decreased mortality compared with no treatment in the intention-to-treat , as-treated , and matched analyses . The results were independent of baseline and follow-up serum phosphate levels and persisted in analyses that excluded deaths during the first 90 d of hemodialysis . In summary , treatment with phosphorus binders is independently associated with improved survival among incident hemodialysis patients . Although confirmatory studies are needed in the dialysis setting , future placebo-controlled , r and omized trials of phosphorus binders might focus on predialysis patients with chronic kidney disease and normal serum phosphate levels The most frequent cause of death in hemodialysis patients is cardiovascular disease with chronic inflammation being an epidemiologically proved risk factor . Many studies have shown C-reactive protein ( CRP ) as the strongest predictor of long-term mortality of hemodialysis patients , while other reports have indicated acute phase proteins as potential predictors of the mortality . The present study therefore aim ed to evaluate the prevalence of chronic inflammation in hemodialysis patients and the role of acute phase proteins together with lipids and divalent ions for predicting mortality in hemodialysis patients . Chronic inflammation was defined , based on the serum level of high sensitive CRP > 8.4 mg/L and /or serum amyloid-A ( SAA ) > 8.9 mg/L. Acute phase proteins are defined as one whose plasma concentration increase ( positive ) or decreases ( negative ) by at least 25 % during inflammation . High sensitive CRP and SAA were positive acute phase proteins measured , while albumin and fetuin-A , a calcification inhibitor , were selected as negative acute phase proteins . This prospect i ve 36-month follow-up study included 130 patients ( 60 males and 70 females , aged 55.1 + /- 12.9 years ) maintained by hemodialysis for 107.2 + /- 54.72 months at a Nephrology Clinic in Bel grade . The prevalence of chronic inflammation was 35.4 % ( 46 patients ) . During the follow-up period , 24 patients ( 18.5 % ) died and 2 patients received transplants . In multivariate analysis , potential independent predictors of mortality in hemodialysis patients are hyperphosphatemia , hypoalbuminemia , and high SAA . Considering that assays for SAA are widely used , we propose that SAA is the best predictor for outcomes of end-stage renal disease BACKGROUND Haemodialysis patients are ageing and have with a high rate of comorbidities . The impact of this novel clinical setting on intact parathyroid hormone ( iPTH ) is not well established . METHODS For this observational , prospect i ve multicentre cohort study , incident haemodialysis patients were recruited in 40 Italian centres and followed up for a mean period of 18 + /- 6.7 months . Clinical characteristics and biochemistry were recorded at baseline . Comorbid conditions were scored by the Charlson comorbidity index ( CCI ) . RESULTS Data of 411 patients ( mean age : 66.5 + /- 14.8 years ; 17.3 % > 80 years old ) were recorded . The mean CCI was 4.17 + /- 2.8 . In patients with CCI > 0 , an inverse correlation was observed between CCI ( excluding age ) and iPTH ( P = 0.00002 ) . Independently of CCI , patients with iPTH < 150 pg/ml had 76 % as high as the risk of all-cause mortality . After multivariable adjustment , the combination of the first tertile of iPTH with second and third tertiles of CCI was significantly associated with all-cause mortality ( RR = 3.83 , P = 0.02 ; RR = 3.79 , P = 0.01 , respectively ) . CONCLUSIONS Incident haemodialysis patients suffer from a high rate of clinical complications . In these patients , low iPTH and high CCI are often associated and very likely responsible for an adverse outcome BACKGROUND The clinical significance of blood lead levels ( BLLs ) in chronic peritoneal dialysis ( CPD ) patients was undetermined prior to this study . METHODS A total of 315 patients on CPD were included in this 18-month prospect i ve study . BLLs measured at baseline were categorized according to a BLL tertile of high ( > 8.66 microg/dL ) , middle ( 5.62 - 8.66 microg/dL ) and low ( < 5.62 microg/dL ) for cross-sectional analyses . Mortality and cause of death were recorded for longitudinal analyses . RESULTS At baseline , patients with high BLLs had a trend of higher parathyroid hormone and lower residual renal function than patients in other groups . Stepwise multiple regression analysis found that parathyroid hormone positively correlated and residual renal function negatively correlated with logarithmic-transformed BLLs in CPD patients after other confounders were adjusted . At the end of follow-up , 37 ( 11.7 % ) patients had died . Kaplan-Meier analysis showed that patients with high BLLs had greater mortality than those with middle and low BLLs ( P = 0.008 ) . Cox multivariate analysis showed that , using the low BLL group as the reference , basal high BLLs ( hazard ratio [ HR ] = 3.745 , 95 % confidence interval [ 95 % CI ] = 1.218 - 11.494 , P = 0.001 ) and middle BLLs ( HR = 1.867 , 95 % CI = 1.618 - 2.567 , P = 0.001 ) were associated with increased HR for all-cause mortality for CPD patients . There is a significant trend ( P < 0.001 ) of HR for mortality trend tests among the three study groups . CONCLUSIONS BLLs are associated with residual renal function and hyperparathyroidism and are related to increased HR for all-cause 18-month mortality in CPD patients AIMS Mortality of maintenance haemodialysis ( HD ) patients is very high due to polymorbidity , mostly from metabolic and cardiovascular disease . In order to identify patients with high risk for life-threatening complications , reliable prognostic markers would be helpful . Pregnancy-associated plasma protein-A ( PAPP-A ) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function . It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD . METHODS AND RESULTS PAPP-A serum levels were measured in 170 patients participating in the monitor ! trial , a prospect i ve dynamic dialysis cohort multicenter study in Switzerl and . Patients were followed up for a median time of 17 months after measuring PAPP-A , and evaluated for death of any cause . Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations . A multivariate logistic regression analysis for death was performed including PAPP-A , age , sex , number of comorbidities , dialysis vintage , Kt/V , IL-6 , C-reactive protein , parathyroid hormone ( PTH ) , Ca x PO(4 ) product , and total serum cholesterol . A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk , respectively . A total of 23 deaths occurred during follow-up , equalling an incidence rate of 0.1 . Baseline median PAPP-A levels were 40 % higher in non-survivors vs. survivors ( P = 0.023 ) . In a multivariate analysis , only PAPP-A , age , and Ca x PO(4 ) product were independent predictors of mortality . A cut-off value of 24 mIU/L discriminates significantly ( P = 0.015 ) between patients at low or high risk for death with a negative predictive value of 91 % . CONCLUSION PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population . The pathogenetic relevance of PAPP-A , particularly in the development of cardiovascular disease , remains to be further eluci date BACKGROUND The majority of dialysis patients suffer from vitamin D deficiency , which might contribute to an adverse health outcome . We aim ed to eluci date whether European dialysis patients with low 25-hydroxyvitamin D ( 25(OH)D ) levels are at increased risk of mortality and specific fatal events . METHODS This was a prospect i ve cohort study of incident dialysis patients in the Netherl and s ( the NECOSAD ) . We selected all patients with measured 25(OH)D at 12 months after the start of dialysis , the baseline for our study . By Cox regression analyses , we assessed the impact of 25(OH)D levels on short-term ( 6 months of follow-up ) as well as longer-term mortality ( 3 years of follow-up ) . Associations of 25(OH)D levels with cardiovascular and non-cardiovascular mortality were also determined . RESULTS The data from 762 patients ( 39 % females , age 59 ± 15 years , 25(OH)D = 18 ± 11 ng/mL ) were available . Fifty-one and 213 patients died during a follow-up of 6 months and 3 years , respectively . After adjustments for possible confounders , the hazard ratio ( HR ) ( with 95 % CI ) for mortality was 2.0 ( 1.0 - 3.8 ) for short-term and 1.5 ( 1.0 - 2.1 ) for longer-term mortality when comparing patients with 25(OH)D levels ≤ 10 ng/mL with those presenting with 25(OH)D levels > 10 ng/mL. Adjusted HRs for cardiovascular mortality were 2.7 ( 1.1 - 6.5 ) and 1.7 ( 1.1 - 2.7 ) for short- and longer-term mortality , respectively . For non-cardiovascular mortality , we observed no relevant association overall . The impact of 25(OH)D levels on clinical events was modified by parathyroid hormone ( PTH ) status , with low 25(OH)D levels meaningfully affecting outcomes only in patients with PTH levels above the median of 123 pmol/L. CONCLUSIONS Vitamin D deficiency in dialysis patients is associated with an adverse health outcome , in particular with short-term cardiovascular mortality . Intervention studies are urgently needed to evaluate whether vitamin D supplementation improves health outcomes of dialysis patients Data from the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) allow estimation of the percentage of patients outside published hemodialysis guidelines and their associated mortality risk . We estimated the number of life years that could be gained from adherence to four of these guidelines and two other modifiable practice s , i.e. dialysis dose , phosphate control , improved anemia , partial correction of serum albumin , reduced interdialytic weight gain and less use of catheters for vascular access . We extrapolated DOPPS data on these practice s and guidelines to the US hemodialysis population for a 5-year projected period . Of the practice s we examined , the highest relative risk of mortality was associated with having albumin < 3.5 g/dl ( relative risk = 1.38 , p < 0.0001 ) ; 20.5 % of the patients in the study fell outside the target range . The adjusted sum of the patient years attributable to all six practice patterns was 143,617 ; a more conservative estimate , modeling life years potentially gained by bringing half of all patients outside targets within them , is 69,367 . The magnitude of potential savings in life years should encourage greater adherence to guidelines and practice s that are significantly associated with better survival We evaluated risks associated with elevated alkaline phosphatase in hemodialysis patients using longitudinal data from the Dialysis Outcomes and Practice Patterns Study , a prospect i ve observational study of hemodialysis patients in 12 countries . Alkaline phosphatase levels were normalized by the upper limit of the laboratory-reported reference range . Cause-specific hospitalization and mortality risks were evaluated using Cox proportional hazards models , stratified by region and adjusted for phosphorus , calcium , albumin , parathyroid hormone , case mix , and numerous comorbidities . The odds of high normalized alkaline phosphatase were increased twofold in the United States in comparison to Japan . Elevations of normalized alkaline phosphatase were significantly associated with several comorbid conditions , increased fractures , parathyroidectomy , risk of hospitalization due to major adverse cardiac events , higher all-cause cardiovascular , and infection-related mortality risk . Our results also show that elevated serum normalized alkaline phosphatase was associated with higher risks of hospitalization and death in hemodialysis patients , independent of calcium , phosphorus , and parathyroid hormone levels Secondary hyperparathyroidism ( SHPT ) affects a significant number of hemodialysis patients , and metabolic disturbances associated with it may contribute to their high mortality rate . As patients with lower serum calcium , phosphorus , and parathyroid hormone are reported to have improved survival , we tested whether prescription of the calcimimetic cinacalcet to hemodialysis patients with SHPT improved their survival . We prospect ively collected data on hemodialysis patients from a large provider beginning in 2004 , a time coincident with the commercial availability of cinacalcet hydrochloride . This information was merged with data in the United States Renal Data System to determine all-cause and cardiovascular mortality . Patients included in the study received intravenous ( i.v . ) vitamin D therapy ( a surrogate for the diagnosis of SHPT ) . Of 19,186 patients , 5976 received cinacalcet and all were followed from November 2004 for up to 26 months . Unadjusted and adjusted time-dependent Cox proportional hazards modeling found that all-cause and cardiovascular mortality rates were significantly lower for those treated with cinacalcet than for those without calcimimetic . Hence , this observational study found a significant survival benefit associated with cinacalcet prescription in patients receiving i.v . vitamin D. Definitive proof , however , of a survival advantage awaits the performance of r and omized clinical trials Atherosclerotic vascular diseases are a major cause of morbidity and mortality for end-stage renal disease patients . We followed prospect ively 226 hemodialysis patients by carotid ultrasonography to determine if ultrasonographic markers are predictive of the prognosis of these patients . The end-point was death or completion of the five-year follow-up period . Fatal cerebrovascular and cardiovascular events were the most common cause of death . By multivariate analysis , diabetes mellitus ( DM ) ( P=0.005 ) , plaque number ( PN ) by ultrasonography ( P=0.023 ) , age ( P=0.001 ) , calcium-phosphate product ( P=0.049 ) , and serum albumin ( P=0.009 ) were extracted as independent risk factors . The five-year increase of PN was significantly greater for DM patients than for non-DM patients . Moreover , PN was an independent marker of a fatal event , irrespective of DM status . Our results suggest that PN may be a useful predictor of the long-term prognosis of hemodialysis patients BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism BACKGROUND Hyperhomocysteinemia , cardiovascular disease ( CVD ) , and malnutrition are common in patients with end-stage renal disease ( ESRD ) . This study was design ed to assess possible relationships between total plasma homocysteine ( tHcy ) , nutritional status , and ischemic CVD . METHODS We performed a cross-sectional study in 117 unselected patients on maintenance hemodialysis ( HD ) treatment , among whom there was a high prevalence of malnutrition ( 56 % ) , as assessed by the subjective global nutritional assessment ( SGNA ) , and a high prevalence of CVD ( 60 % ) , and prospect ively , we followed-up the overall mortality for four years . RESULTS The level of tHcy was elevated in 95 % of the HD patients , and that of total plasma cysteine ( tCys ) was also significantly elevated , while the plasma concentrations of methionine ( Met ) , serine ( Ser ) , and taurine ( Tau ) were significantly lower than those in healthy controls . The 65 patients who were malnourished according to the SGNA score had significantly lower levels of serum albumin ( SAlb ) , plasma IFG-1 ( p-IGF-1 ) , tHcy , tCys , and Met than the 52 patients with normal nutritional status , whereas the levels of Ser , Tau , plasma folate , and vitamin B12 were similar in the two groups . The prevalence of malnutrition was 30 % in the 47 patients without CVD and was significantly higher ( 70 % , P < 0.001 ) in the 70 patients with CVD , who also had lower tHcy , SAlb , plasma IGF-1 , serum creatinine ( SCr ) , and blood hemoglobin . The tHcy levels were positively correlated with SAlb , Met , tCys , and SCr . Stepwise , multiple-regression analysis showed that tCys , SAlb , and normalized protein equivalent of nitrogen appearance ( nPNA ) , an indicator of protein intake , were independent predictors of tHcy . The patients with tHcy < 24 micromol/L ( median value ) had a significantly worse four-year survival than those with a higher tHcy ( > or = 24 micromol/L ) . CONCLUSIONS Our results demonstrate that most of HD patients have grossly elevated tHcy levels , but that the absolute level appears to be dependent on nutritional status , protein intake , and SAlb . The results also suggest that the lower tHcy levels in patients with CVD than in those without CVD may be related to the higher prevalence of malnutrition and hypoalbuminemia in the CVD patients . This is also in accordance with our observation that the patients with lower tHcy had a worse survival rate than those with higher tHcy , considering that malnutrition is a strong risk factor for mortality and that CVD is the most common cause of death in ESRD patients Elevated serum phosphorus is a predictable accompaniment of end-stage renal disease ( ESRD ) in the absence of dietary phosphate restriction or supplemental phosphate binders . The consequences of hyperphosphatemia include the development and progression of secondary hyperparathyroidism and a predisposition to metastatic calcification when the product of serum calcium and phosphorus ( Ca x PO4 ) is elevated . Both of these conditions may contribute to the substantial morbidity and mortality seen in patients with ESRD . We have analyzed the distribution of serum phosphorus in two large national , r and om , cross-sectional sample s of hemodialysis patients who have been receiving dialysis for at least 1 year . Data were obtained from two special studies of the United States Renal Data System , the Case Mix Adequacy Study ( 1990 ) and the Dialysis Morbidity and Mortality Study Wave 1 ( 1993 ) . The relative risk of death by serum phosphorus quintiles is described after adjusting for age at onset of ESRD , race , sex , smoking status , and the presence of diabetes , the acquired immunodeficiency syndrome , and /or neoplasm . Logistic regression analysis is then used to describe the demographic , comorbid , and laboratory parameters associated with high serum phosphorus . Serum phosphorus was similar in these two study population s and averaged 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL and at least 30 % of each group had serum phosphorus levels greater than 7 mg/dL. The adjusted relative risk of death by serum phosphorus level was not uniform across all quintiles , being constant below a level of 6.5 mg/dL and increasing significantly above this level . The relative risk of death for those with a serum phosphorus greater than 6.5 mg/dL was 1.27 relative to those with a serum phosphorus of 2.4 to 6.5 mg/dL. This increased risk was not diminished by statistical adjustment for coexisting medical conditions , delivered dose of dialysis , nutritional parameters , or markers of noncompliance . Evaluation of predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate analysis that younger age at onset of ESRD , female sex , white race , diabetes , active smoking , and higher serum creatinine levels were all significant predictors . Analysis of serum calcium revealed no correlation with relative risk of death . The Ca x PO4 product , however , showed a mortality risk trend similar to that seen with serum phosphorus alone . Those in the highest quintile of the Ca x PO4 product ( > 72 mg2/dL2 ) had a relative mortality risk of 1.34 relative to those with products of 42 to 52 mg2/dL2 . The relative mortality risk by log parathyroid hormone ( PTH ) level was elevated for patients with higher levels , but the mortality risk associated with hyperphosphatemia was independent of PTH . For hemodialysis patients who have been receiving dialysis for at least 1 year , we conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL and that this places them at increased risk of death . This increased risk is independent of PTH . The mechanism(s ) responsible for death is unknown , but may be related to an abnormally high Ca x PO4 product . Although mechanisms are not clearly established , this study supports the need for vigorous control of hyperphosphatemia to improve patient survival BACKGROUND Severe hyperphosphatemia ( serum phosphate level > 6.5 mg/dL [ > 2.10 mmol/L ] ) has been associated directly with increased overall and cardiovascular mortality in hemodialysis ( HD ) patients . Currently , clinical guidelines recommend maintaining phosphate levels within normal range ( 3.0 to 5.0 mg/dL [ 0.97 to 1.61 mmol/L ] ) . However , mild hyperphosphatemia ( phosphate , 5.01 to 6.5 mg/dL [ 1.62 to 2.10 mmol/L ] ) is still to be addressed as an independent mortality risk factor in HD patients . METHODS The association between serum phosphate level and survival in maintenance HD patients was explored prospect ively in 385 incident patients from 1990 to 2001 . Cox regression was performed using phosphate level as : ( 1 ) a continuous variable ; ( 2 ) stratified as low phosphate level ( <3 mg/dL [ < 0.97 mmol/L ] ) , normal phosphate level ( 3.0 to 5.0 mg/dL [ 0.97 to 1.61 mmol/L ] ) , mild hyperphosphatemia ( phosphate , 5.01 to 6.5 mg/dL [ 1.62 to 2.10 mmol/L ] ) , or severe hyperphosphatemia ( phosphate > 6.5 mg/dL [ > 2.10 mmol/L ] ) ; and ( 3 ) phosphate level greater or less than 5.0 mg/dL ( > or < 1.61 mmol/L ) . RESULTS As a continuous variable , relative risk ( RR ) for mortality for serum phosphate level was 1.26 ( confidence interval [ CI ] , 1.09 to 1.47 ) after adjusting for age , sex , diabetes , Kt/V , albumin level , hemoglobin level , serum calcium level , normalized protein catabolic rate , and parathyroid hormone level . Compared with a normal phosphate level , mild hyperphosphatemia showed an adjusted mortality RR of 1.94 ( CI , 1.17 to 3.19 ) , and severe hyperphosphatemia , an RR of 2.02 ( CI , 1.10 to 3.73 ) . Patients with a phosphate level cutoff value greater than 5.0 mg/dL ( > 1.61 mmol/L ) showed a 2-fold increase in adjusted RR for mortality compared with those with a phosphate level of 5.0 mg/dL or less ( < or = 1.61 mmol/L ; RR , 2.11 ; CI , 1.44 to 3.08 ) . CONCLUSION A serum phosphate level greater than 5.0 mg/dL ( > 1.61 mmol/L ) is independently associated with an increased risk for death in HD patients Elevated bone mineral parameters have been associated with mortality in dialysis patients . There are conflicting data about calcium , parathyroid hormone ( PTH ) , and mortality and few data about changes in bone mineral parameters over time . We conducted a prospect i ve cohort study of 1007 incident hemodialysis and peritoneal dialysis patients . We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis , inflammation , and comorbidity . Serum calcium , phosphate , and calcium-phosphate product ( CaP ) increased in these patients between baseline and 6 months ( P<0.001 ) and then remained stable . Serum PTH decreased over the first year ( P<0.001 ) . In Cox proportional hazards models adjusting for inflammation , comorbidity , and other confounders , the highest quartile of phosphate was associated with a hazard ratio ( HR ) of 1.57 ( 1.07 - 2.30 ) using both baseline and time-dependent values . The highest quartiles of calcium , CaP , and PTH were associated with mortality in time-dependent models but not in those using baseline values . The lowest quartile of PTH was associated with an HR of 0.65 ( 0.44 - 0.98 ) in the time-dependent model with 6-month lag analysis . We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients . High levels of calcium , CaP , and PTH are associated with mortality immediately preceding an event . Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients Although the National Kidney Foundation ( NKF ) has published clinical practice guidelines for the management of risk factors for cardiovascular disease , these guidelines have not been tested rigorously for their effectiveness . We conducted an observational study among patients with end‐stage kidney disease to examine the prognostic impact of threshold levels recommended by the NKF for blood pressure , hemoglobin , calcium‐phosphate product , parathyroid hormone , low‐density lipoprotein , and glycosylated hemoglobin . The study population ( N=197 ) was assembled from a previously completed r and omized trial examining arteriovenous graft thrombosis . Cox proportional hazard analysis was used to calculate hazard ratios for the association of levels outside guideline recommended targets and death , adjusting for age , comorbidity , race , and albumin . The proportion of patients outside guideline targets ranged from 33 % to 81 % , and the impact of levels outside guideline targets on mortality varied substantially . Elevated calcium‐phosphate product and glycosylated hemoglobin had harmful effects , with adjusted hazard ratios of 1.58 ( 95 % CI 1.00–2.50 ; p=0.050 ) and 2.21 ( 95 % CI 0.99–4.97 ; p=0.054 ) , respectively . Nontarget levels for blood pressure , hemoglobin , and parathyroid hormone had little effect , with adjusted hazard ratios of 1.15 ( 95 % CI 0.74–1.78 ; p=0.542 ) , 1.04 ( 95 % CI 0.65–1.68 ; p=0.866 ) , and 0.90 ( 95 % CI 0.50–1.61 ; p=0.722 ) , respectively . Elevated low‐density lipoprotein had a paradoxically beneficial effect , with an adjusted hazard ratio of 0.48 ( 95 % CI 0.23–1.00 ; p=0.049 ) . These results suggest that the prognostic impact of current threshold levels recommended by select NKF guidelines on mortality is variable . Accordingly , the development and implementation of clinical practice guidelines should be accompanied by corresponding efforts to confirm their impact on patient outcomes . Such efforts are essential for the improvement of guidelines and to inform health policy optimally Excess parathyroid hormone ( PTH ) has long been considered detrimental to the health of patients with end-stage renal disease . PTH has been implicated as a multisystem uremic toxin , and hyperparathyroidism can be a debilitating complication in dialyzed patients . We have studied prospect ively the relationship of enrollment serum intact PTH and various demographic characteristics and other biochemical parameters to all-cause mortality in 345 hemodialysis ( HD ) and 277 peritoneal dialysis ( PD ) patients . We monitored the patients for 14 years . Observed survival and survival after adjustment for age , race , gender , months on dialysis at enrollment , diabetic status , and nutritional markers were significantly better for patients with enrollment PTH greater than 200 pg/mL than for patients with PTH 65 to 199 pg/mL and patients with PTH less than 65 pg/mL. Enrollment serum PTH was an independent predictor of survival in HD and PD patients . For HD patients , age and months on HD at enrollment were associated inversely with PTH level , whereas black race , creatinine , and phosphorus were associated directly with PTH . For PD patients , age , diabetes , and months on PD at enrollment were inverse predictors , whereas black race , albumin , creatinine , and phosphorus were associated positively with PTH . Lower than expected levels of PTH in uremic patients is associated with increased mortality . We hypothesize that inadequate protein intake or phosphorus intake or both result in impaired development of the expected secondary hyperparathyroidism and in the excess mortality risk inherent with malnutrition BACKGROUND Nonadherence among hemodialysis patients compromises dialysis delivery , which could influence patient morbidity and mortality . The Dialysis Outcomes and Practice Patterns Study ( DOPPS ) provides a unique opportunity to review this problem and its determinants on a global level . METHODS Nonadherence was studied using data from the DOPPS , an international , observational , prospect i ve hemodialysis study . Patients were considered nonadherent if they skipped one or more sessions per month , shortened one or more sessions by more than 10 minutes per month , had a serum potassium level openface>6.0 mEq/L , a serum phosphate level openface>7.5 mg/dL ( > 2.4 mmol/L ) , or interdialytic weight gain (IDWG)>5.7 % of body weight . Predictors of nonadherence were identified using logistic regression . Survival analysis used the Cox proportional hazards model adjusting for case-mix . RESULTS Skipping treatment was associated with increased mortality [ relative risk ( RR ) = 1.30 , P = 0.01 ] , as were excessive IDWG ( RR = 1.12 , P = 0.047 ) and high phosphate levels ( RR = 1.17 , P = 0.001 ) . Skipping also was associated with increased hospitalization ( RR = 1.13 , P = 0.04 ) , as were high phosphate levels ( RR = 1.07 , P = 0.05 ) . Larger facility size ( per 10 patients ) was associated with higher odds ratios ( OR ) of skipping ( OR = 1.03 , P = 0.06 ) , shortening ( OR = 1.03 , P = 0.05 ) , and IDWG ( OR = 1.02 , P = 0.07 ) . An increased percentage of highly trained staff hours was associated with lower OR of skipping ( OR = 0.84 per 10 % , P = 0.02 ) ; presence of a dietitian was associated with lower OR of excessive IDWG ( OR = 0.75 , P = 0.08 ) . CONCLUSION Nonadherence was associated with increased mortality risk ( skipping treatment , excessive IDWG , and high phosphate ) and with hospitalization risk ( skipping , high phosphate ) . Certain patient/facility characteristics also were associated with nonadherence |
12,516 | 15,106,169 | There was no consistent evidence that written plans produced better patient outcomes than no written plan .
For some outcomes , there appeared to be an advantage of one type of plan over the other , but there was no consistency - one type of plan was not consistently more effective than another .
REVIEW ERS ' CONCLUSIONS The available trials are too small and the results too few and inconsistent to form any firm conclusions as to the contribution of written self management plans in the known beneficial effects of a comprehensive asthma care programme | BACKGROUND Non-adherence to treatment advice is a common phenomenon in asthma and may account for a significant proportion of the morbidity .
Comprehensive care that includes asthma education , a written self-management plan and regular review has been shown to improve asthma outcomes , but the contribution of these components has not been established .
OBJECTIVES To determine whether the provision of a written asthma self-management plan increases adherence and improves outcome . | A prospect i ve r and omised trial was performed to evaluate the effectiveness of an asthma education programme administered by an asthma nurse specialist in an out-patient setting . Sixty asthmatic patients ( mean age 28.5 years ) were enrolled , 30 to a usual care control group and 30 to an education group . The education group underwent an individual education programme lasting at least one hour . The following variables were measured at baseline , one month after the education programme and at one year follow-up : asthma knowledge by MCQ ( 36 point question naire ) , inhaler technique ( 7 point scale ) , peak expiratory flow rate ( PEFR ) and symptomatology by visual analogue score ( 0 to 10 score ) . The education group 's inhaler technique and MCQ score both improved significantly at one month , from 5.4 ( 0.3 ) ( mean [ SEM ] ) to 6.5 ( 0.3 ) , p < 0.001 , and from 7.5 ( 2.4 ) to 22 ( 1.8 ) , p < 0.0001 respectively . Both of these improvements were significantly greater than in the control group , and both were maintained at one year follow-up . The symptom score improved over one year in the education group , from 5.4 ( 0.6 ) to 7.6 ( 0.5 ) , p < 0.05 , and was unchanged in the control group . There was no change in the PEFR in either group . This study shows clear objective benefits to an out-patient asthma education programme conducted by an asthma nurse specialist Self-report is a frequently-used method of assessing compliance with prescribed medications in patients with chronic illnesses . Most research ers agree , however , that self-report misrepresents patient adherence to regimen prescription . In this r and omized , controlled study evaluating inhaler medication compliance , diary data was compared to electronic monitoring in 55 adults with asthma . Subjects r and omized to the treatment group received a six-week self-management program . An electronic monitor , the MDI Chronolog , was used in this study to assess inhaler use . The MDI Chronolog records the date and time of each inhaled activation . The self-report measure used was a daily asthma diary . Subjects were asked to use their inhaled medications as usual and record the date and time they administered their medication over a one-week period . Moderate correlations ( rs=.55 , Mdnd=95.8 , Mdnc=91.6 ) were found when comparing the number of administrations calculated using the MDI Chronolog to the number of administrations reported in the subject ’s diary . When the dosing interval was examined , however , the correlation was weaker ( rs=.44 , Mdndiary=92.8 , Mdnchronolog=37.5 ) . In each case , self-reported compliance was higher than monitored adherence A prospect i ve controlled trial of home monitoring of peak expiratory flow rate ( PEFR ) was conducted to determine the usefulness of an objective measure of lung function in association with an education program and a medication self-management plan in reducing morbidity in adult patients with asthma . Thirty-five patients managed themselves , using peak flow readings as the basis for the therapeutic plan coupled with educational intervention , whereas 35 control patients used symptoms and spirometric data for following physicians ' treatment plans . After a 6-mo study period , patients in the experimental group showed statistically significant improvements in morbidity parameters ( days lost from work , acute asthma attacks , days on antibiotic therapy , physician consultations , and emergency room admissions for asthma ) , increases in FVC , FEV1 , and FEV1/FVC , mean PEFR and mean morning PEFR , decrease in percentage of the mean PEFR amplitude , and a reduction in the use of inhaled beta-agonists , oral theophylline , and oral prednisone . Although improvements in some of these parameters were also found in the control group , they did not reach the levels of significance obtained in the experimental group . The personal use of an objective measure of lung function in association with a medication self-management plan leads to improvement in the patient 's condition BACKGROUND --A hospital based , community service asthma education programme for adults to improve asthma knowledge , promote compliance with medication , and reduce morbidity was evaluated . METHODS --The programme was evaluated using a r and omised experimental and control group design with repeated measurements over 12 months . A volunteer community sample of 192 respondents was recruited of whom 116 satisfied the inclusion criteria . At the 12 month follow up some data were obtained for all subjects . Intervention subjects attended four 2.5 hour education sessions at weekly intervals . An asthma knowledge question naire was administered and compliance was assessed from diary records . Morbidity was assessed retrospectively by question naire , prospect ively by diary , and objective ly by spirometry and serial peak expiratory flow rate monitoring . The adequacy of medical treatment was also assessed . Data were collected at baseline , immediately after the intervention , and at three , six , nine , and 12 months after intervention . RESULTS --Improvements occurred in knowledge and compliance in the intervention group but the impact on morbidity was modest ; this was due , at least in part , to the inadequacy of medical treatment . CONCLUSIONS --Treatment of asthma should be review ed and optimised in conjunction with self-management programmes in order to improve health outcomes Abstract Objectives To assess the feasibility and effectiveness of a general practice based , proactive system of asthma care in children . Design R and omised controlled trial with cluster sampling by general practice . Setting General practice s in the northern region of the Australian Capital Territory . Participants 174 children with moderate to severe asthma who attended 24 general practitioners . Intervention System of structured asthma care ( the 3 + visit plan ) , with participating families reminded to attend the general practitioner . Main outcome measures Process measures : rates for asthma consultations with general practitioner , written asthma plans , completion of the 3 + visit plan ; clinical measures : rates for emergency department visits for asthma , days absent from school , symptom-free days , symptoms over the past year , activity limitation over the past year , and asthma drug use over the past year ; spirometric lung function measures before and after cold air challenge . Results Intervention group children had significantly more asthma related consultations ( odds ratio for three or more asthma related consultations 3.8 ( 95 % confidence interval 1.9 to 7.6 ; P = 0.0001 ) , written asthma plans ( 2.2 ( 1.2 to 4.1 ) ; P = 0.01 ) , and completed 3 + visit plans ( 24.2 ( 5.7 to 103.2 ) ; P = 0.0001 ) than control children and a mean reduction in measurements of forced expiratory volume in one second after cold air challenge of 2.6 % ( 1.7 to 3.5 ) ; P = 0.0001 ) less than control children . The number needed to treat ( benefit ) for one additional written asthma action plan was 5 ( 3 to 41 ) children . Intervention group children had lower emergency department attendance rates for asthma ( odds ratio 0.4 ( 0.2 to 1.04 ) ; P = 0.06 ) and less speech limiting wheeze ( 0.2 ( 0.1 to 0.4 ) ; P = 0.0001 ) than control children and were more likely to use a spacer ( 2.8 ( 1.6 to 4.7 ) ; P = 0.0001 ) . No differences occurred in number of days absent from school or symptom-free day scores . Conclusions Proactive care with active recall for children with moderate to severe asthma is feasible in general practice and seems to be beneficial To assess the efficacy of self-management programs it is important to know what behavioural changes take place . This paper assesses whether including self-treatment guidelines ( action plans ) in a self-management program for adult asthmatics , leads to greater behavioural changes than a program without these guidelines . Patients were r and omised into a self-treatment group ( n=123 ) or an active control group ( n=122 ) . All subjects received self-management training . Discussed topics included the pathophysiology of asthma , medication and side-effects , triggers , symptoms , smoking , physical exercise , and compliance . The only difference was that the self-treatment group received instructions about self-treatment of exacerbations and the control group did not . At 1 year of follow-up asthma-specific self-efficacy expectancies , outcome expectancies , and asthma-specific knowledge improved significantly in all patients . Only self-treatment group patients demonstrated favourable changes in generalised self-efficacy , social support , and self-treatment and self-management behaviour , in case of a hypothetical scenario of a slow-onset exacerbation . We conclude that our self-management program is effective in changing the behavioural variables , and including self-treatment guidelines ( action plans ) has added benefit Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms . The use of peak flow meters ( PFM ) has been recommended as an important part of self-management plans . We studied 92 ( 47 F ) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management . Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse . Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician . Forty-four patients were r and omized to the PFM group and 48 to the symptoms group . Spirometry , symptom scores , quality of life , medication use , and measures of health care utilization and morbidity ( emergency department visits , hospitalizations , unscheduled doctor visits , and days lost from work or school ) were recorded at baseline and throughout the study period . PC20 methacholine was measured at the first and at the final visits . There were significant improvements within groups for FEV1 , symptoms score , PC20 methacholine , and quality of life , but no between-group differences . A significant shift from higher to lower daily use of beta-agonists ( p < 0.008 for both groups ) and significant shifts to higher daily doses of inhaled steroids ( p < 0.001 ) occurred in each group . Adherence to the self-management plans was only 65 % in the PFM group and 52 % in the symptoms group . Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group . Our findings show that education , regular follow-up , and an action plan are effective in improving asthma control and quality of life , but the routine use of PFM to guide interventions is not the only way to accomplish these objectives The purpose of the AIR/Kaiser-Permanente asthma project is to evaluate various approaches to the education of adults with asthma , identifying those types of patients for whom particular approaches are most cost effective . Critical self-management prac tices for adults with asthma were identified using the critical incident technique . An individualized and a group administered educational program are being developed to teach the identified critical skills , using the instructional models previously employed in AIR WISE and AIR POWER programs for children with asthma . Three hundred patients with moderate to severe asthma from Northern California Kaiser-Permanente Medical Group clinics will participate in a trial of these programs . Patients will be r and omly assigned to one of four conditions : One of two educational programs , an information/attention control , or a data -only control condition . Data will be collected on all patients for 15 months ; health care utilization data covering a two-year period will be available from medical records . Program effectiveness will be evaluated in terms of pre-post changes in the patients ' knowledge , attitudes , self-man agement practice s , medical condition , daily functioning , and utilization of services . Cost effectiveness will be evaluated , paying specific attention to the cost effectiveness of different educational approaches for different types of patients Two different patient education programmes for asthma in general practice were evaluated in a controlled trial . Knowledge , self management , and morbidity due to asthma were assessed in 339 patients by means of a question naire . One group then received a maximum education programme , a second group received a limited education programme , and a third acted as a control group . 274 patients were reassessed after one 1 year . In both the intervention groups , underst and ing of asthma was greater after the trial . Only in the maximum intervention group was a significant improvement in knowledge of asthma shown . Neither group showed any change in self-management ability or asthma morbidity that differed significantly from changes in the control group . These simple informational education programmes were ineffective when applied to a general practice population . Further studies of factors affecting attitudes , beliefs , and actions are needed to improve the advice and support given to asthma patients The purpose of this study was to evaluate the impact of a self-management program for adults with moderate to severe asthma on compliance with inhaled , prescribed , nonemergency medications ; asthma symptoms ; and airway obstruction . In this controlled experimental study , 55 subjects from a rural community were r and omized to one of two groups . Self-efficacy theory served as the framework for this study . Primary measures included the Metered Dose Inhaler ( MDI ) Chronolog , a journal of daily asthma concerns , and a peak-flow meter to appraise airway obstruction . Secondary measures included the Asthma Self-Management Assessment Tool ( ASMAT ) and the Self-Efficacy for Asthma Management Scale ( SEAMS ) . These measures were completed pre- and post-intervention . Data analysis using descriptive and inferential statistics revealed that subjects receiving the self-management program increased compliance with inhaled medications ( U = 271 , p = .043 ) Our aim was to assess the efficacy of budesonide ( Pulmicort Turbohaler Astra ) used as part of a self-management plan in a group of patients with chronic asthma . One hundred and twenty five patients with nocturnal asthma symptoms , despite the use of inhaled prophylactic and beta 2-agonist therapy , were r and omized to inhaled budesonide 200 , 400 or 800 micrograms b.i.d . either with dose adjustments made by the physician , i.e. doctor-managed ( DM ; n = 64 ) , or as part of a self-management plan ( SM ; n = 61 ) . The SM group were allowed to adjust their dose according to written guidelines based on morning peak flow . At the end of the 6 month treatment period , there were no significant differences detected between the DM and the SM groups either from the clinic or diary card data . Both groups demonstrated a significant reduction in the number of sleep-disturbed nights , by 75 % in the DM group and 77 % in the SM group , at the end of the study . In conclusion , for patients with mild-to-moderate asthma , either a doctor-adjusted dose regimen or a peak flow based self-management plan involving budesonide is equally efficacious . For some patients , a simple regimen , adjusted by the physician at clinic visits , may be easier to follow BACKGROUND During the past 15 years , programs to improve self-management practice s in adults with asthma have reported improvement in functional status and reduction of inappropriate use of health care services . However , these programs usually represent an ideal approach , applying multiple patient education methods . Consequently , when these programs are found to be efficacious , it is important to replicate the programs as well as to evaluate less complex methods that may be more appropriate for nonacademic health care setting s. METHODS We compared the following 3 st and ardized self-management treatments in a r and omized , controlled trial : ( 1 ) a replication of the self-management program developed at a university medical center that was previously shown to be efficacious ; ( 2 ) a modified version of this program including only the core elements ; and ( 3 ) a usual-care program . Outcome measures included medication and inhaler regimen adherence , asthma symptoms , respiratory illness , functional status , and use of health care re sources . RESULTS All 3 groups improved on measures of respiratory illnesses , use of health care services , and functional status . Patients in both education groups did no better than the usual-care group . CONCLUSIONS The results are inconsistent with the results of the first asthma self-management study at this institution and with those of efficacy studies of similar programs . Two factors , selection of the patient population and historical changes in asthma treatment , most likely contributed to the lack of impact of the self-management programs . As a result of the improved st and ards for usual care due to both factors , the opportunity to effect patient outcomes was substantially reduced STUDY OBJECTIVE To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma . DESIGN A r and omized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan , a symptom-based plan , or a peak flow-based action plan . SETTING A university hospital asthma clinic . POPULATION One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma . INTERVENTIONS All subjects received evaluation and education for asthma before being r and omly allocated to receive no action plan , a symptom-based action plan , or a peak flowmeter and a peak flow-based action plan . MEASUREMENTS Subjects were assessed by question naire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma . RESULTS At 6 months after enrollment , although all three intervention groups experienced improvement in their asthma control , there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group ( p=0.006 ) . No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups . CONCLUSIONS We conclude that a peak flow-based action plan is effective , at least in the short term , in protecting patients with asthma against severe exacerbations of their disease BACKGROUND --Peak flow based asthma self-management plans have been strongly advocated in consensus statements , but convincing evidence for the effectiveness of this approach has been largely lacking . METHODS --A r and omised controlled trial was conducted in 25 general practice s comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period . RESULTS --Seventy two subjects ( 33 in the self-management group and 39 in the planned visit group ) completed the study protocol , but diary card data for at least three months were available on a total of 84 ( 39 in the self-management group and 45 in the planned visit group ) . Teaching self-management took longer than the planned visit review . In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 ( 85 % ) and 27 ( 82 % ) cases , respectively . There were no between group differences during the study period in terms of lung function , symptoms , quality of life , and prescribing costs . Only within the self-management group were improvements noted in disturbance of daily activities and quality of life . Possible explanations for these negative results include small numbers of subjects , the mild nature of their asthma , and inappropriate self-management strategies for such patients . CONCLUSIONS -- Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes . Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma . In this prospect i ve r and omized controlled trial , 245 patients with stable , moderate to severe asthma were included . They were r and omized into a self-treatment group ( group S ) and a control group ( group C ) . Both groups received self-management education . Additionally , group S received self-treatment guidelines based on peak expiratory flow ( PEF ) and symptoms . Outcome parameters included : asthma symptoms , quality of life , pulmonary function , and exacerbation rate . The 2-yr study was completed by 174 patients . Both groups showed an improvement in the quality of life of 7 % . PEF variability decreased by 32 % and 29 % , and the number of outpatient visits by 25 % and 18 % in groups S and C , respectively . No significant differences in these parameters were found between the two groups . After 1 yr , patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma . The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups . Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma . However , patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group BACKGROUND --To improve asthma control and reduce readmission rates through increased knowledge and the development of self management skills , a brief ( three hour ) adult education programme was developed . METHODS --The course was design ed to improve inhaler skills and to teach how to adjust drug doses according to peak flow ( PEF ) measurements and a treatment plan . It was evaluated in a r and omised controlled trial in 76 patients admitted to hospital for asthma by using question naires , spirometry , and home monitoring of PEF at entry and at five and 10 months after intervention . The question naire provided measures of knowledge about asthma , self management behaviour appropriate to asthma control , asthma symptom frequency and severity , and psychosocial disturbance attributable to asthma . RESULTS --During the 10 months observation period the readmission rate for the educated group was one seventh that of the control group and attendance at accident and emergency departments also decreased . No consistent differential improvements were observed in spirometric results , average PEF , or mean daily variability of PEF . Both groups showed improvements in measures of asthma knowledge , behaviour , symptoms , and psychosocial disturbances . However , the intervention group showed a significantly greater improvement in some measures of asthma knowledge and self management skills . CONCLUSION --Despite minimal effect on measures of airway function , substantial changes in illness behaviour and use of health care facilities can be achieved by a brief asthma education programme We assessed whether peak expiratory flow monitoring added to a self-management education programme reduced morbidity and improved pulmonary function and adherence to treatment in 100 asthma patients ( aged 17 - 65 years ) with adequate treatment and regular 1-year follow-up . Patients r and omized to the experimental group used peak expiratory flow readings as the basis for their therapeutic plan coupled with educational intervention , whereas patients in the control group received the same educational intervention and used symptoms only to guide self-management . Morbidity parameters , functional status and adherence to medical regimens improved in both groups , although the percentage of patients with satisfactory adherence was significantly better in the group with peak expiratory flow monitoring ( 83 % ) than in controls ( 52 % ) ( P = 0.05 ) . The multivariate analysis showed that severity of asthma ( odds ratio 9.28 , 95 % confidence interval 1.87 - 45.96 , P = 0.006 for moderate asthma ) and type of self-management education programme ( odds ratio : 6.19 ; 95 % confidence interval : 2.04 - 18.81 ; P = 0.001 for the use of peak expiratory flow readings ) were the only independent predictors of adherence to treatment . However , a statistically significant association between adherence and use of peak expiratory flow monitoring was only found in patients with moderate asthma ( P = 0.0009 ) . We conclude that peak expiratory flow monitorization in optimal conditions ( adequate medical regimen , individualized self-management education and regular follow-up ) showed a beneficial effect on adherence to prescribed regimens only in patients with moderate asthma Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma . However , it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention . A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited ; 98 completed the study . The first 45 patients were assigned to Group C ( control ; usual treatment ) . Thereafter , patients were r and omized to either Group LE ( limited education ; teaching of the inhaler technique plus self- action plan given by the on call physician ) or Group SE ( same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations ) . At baseline , there was no difference between groups in asthma morbidity , medication needs , or pulmonary function . After 12 mo , only Group SE showed a significant improvement in knowledge , willingness to adjust medications , quality of life scores , and peak expiratory flows . In the last 6 mo , the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE ( p = 0.03 ) . The number ( % ) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE ( p = 0.02 ) . We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment The aims of the present study were as follows : We compared the effectiveness of personalized asthma self-management recommendations with that of a group self-management program . We assigned each of 34 asthma patients r and omly to one of three conditions : individualized asthma self-management , group asthma self-management , and control . We derived individualized self-management recommendations from patient recordings of asthma occurrence , asthma precipitants , and peak expiratory flow rate made during a 3-month period . The group program we used was the Wheezers Anonymous program . As compared to a control group of patients who received no self-management training , the patients in both the individualized and group condition evidence d improvement of pulmonary function , as measured daily with a home peak flow meter . The improvement was equivalent for patients in the two conditions . Patients in the individualized condition also exhibited a drop in frequency of asthma attacks , but patients in the group condition did not . We concluded that individualized asthma self-management is effective in reducing symptoms of asthma The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age . Patients were r and omly assigned to an education or noneducation group . A st and ard education program regarding asthma and asthma medications was provided to the education group during four monthly visits . At each visit , all patients were assessed in terms of knowledge of asthma and medications , asthma-related symptoms , and pulmonary function . Patients were also asked to self-rate their compliance . The education program increased the patients ' knowledge of cromolyn , and appeared to result in increased cromolyn compliance . Post-hoc analyses , however , suggested that increased compliance did not correspond to improved medical status unless the quality of management ( by physician and parents ) of the child 's asthma was taken into account . These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance OBJECTIVE To compare the use of patient-performed peak expiratory flow ( PEFR ) and symptom monitoring as asthma self-management tools initiated from community pharmacies . DESIGN AND SETTING 110 patients over 6 years of age were recruited from five private-sector community pharmacies . Patients were identified from pharmacist recall as having ' asthma ' . Information on the frequency of their asthma symptoms , medication use , level of physical activity , school or work attendance and lung function was obtained using a question naire to classify patients as either mild , moderate or severe . Each patient was alternately assigned to either the symptom or PEFR monitoring procedure in the order they were recruited . Patients performing symptom monitoring used a visual analogue scale to assess symptoms , whereas those in the PEFR monitoring group assessed symptoms and used a pocket-size peak flow meter to measure lung function . Both self-monitoring groups were required to adhere to an individualized management plan based on guideline recommendations and to record their monitored data in a diary card for 2 months . Data from the diary cards were review ed , collated , transcribed and analysed using the Student t and Mann-Whitney tests . OUTCOME MEASURES The average monthly frequency of appropriate patient responses determined from their adherence to the self-management plan was used to compare the usefulness of symptom and PEFR self-monitoring . In particular , appropriate use of medication and need for medical consultation was compared . RESULTS 21 symptom and 40 PEFR-assigned patients completed 2 months ' monitoring . The average monthly frequency of appropriate responses in patients using PEFR ( 0.76 ) was significantly higher than that of patients using symptom monitoring ( 0.53 , P < 0.006 ) . Patients applying symptom monitoring had a higher monthly frequency ( 0.39 ) of inappropriate medication use compared to the PEFR group ( 0.14 ) . Furthermore , the patients ' mean daily symptom scores ( 2.85 ) were significantly lower than that estimated by the research er ( 4.12 , P < 0.03 ) . For all three asthma severity groups a higher monthly average of appropriate responses was observed in patients using PEFR monitoring compared to those who used symptom monitoring . CONCLUSION PEFR self-monitoring proved to be a more useful asthma tool than symptom self-monitoring . Patients applying symptom monitoring tend to underestimate the severity of their condition and use medication inappropriately . Active involvement of community pharmacists in facilitating and reinforcing out-patient self-monitoring would help to optimize asthma management OBJECTIVE --To compare a peak flow self management plan for asthma with a symptoms only plan . DESIGN --R and omisation to one of the self management plans and follow up for a year . SETTING --Four partner , rural training practice in Norfolk . SUBJECTS--115 Patients ( 46 children and 69 adults ) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic . MAIN OUTCOME MEASURES --The number of doctor consultations , courses of oral steroids , and short term nebulised salbutamol treatments and the number of patients who required doctor consultations , courses of oral steroids , and short term nebulised salbutamol . RESULTS --Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups . The results were similar for children and adults . The proportions of patients requiring a doctor consultation fell from 98 % ( 50/51 ) to 66 % ( 34/51 ) in the peak flow group and from 97 % ( 62/64 ) to 53 % ( 34/64 ) in the symptoms only group and the proportions requiring oral steroids from 73 % ( 34/46 ) to 47 % ( 21/46 ) and 52 % ( 31/60 ) to 12 % ( 7/60 ) . The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group . CONCLUSIONS --The peak flow meter was not the crucial ingredient in the improved illness of the two groups . Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma . Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care STUDY OBJECTIVE To determine the effect of an outpatient program design ed to reduce readmissions for asthma exacerbations among adults with asthma . DESIGN R and omized patient selection with crossover . SETTING Bellevue Hospital , New York City , New York . PATIENTS We identified 104 adult asthmatics who had previously required multiple hospitalizations for asthma attacks . Forty-seven patients were r and omly assigned to an intensive outpatient treatment clinic and 57 patients continued to receive their previous outpatient care . Nineteen patients from this latter group were then crossed to the intensive outpatient therapy clinic . INTERVENTIONS Attenders of the intensive outpatient treatment program were treated with a vigorous medical regimen and educational program . Emphasis was placed on teaching patients aggressive self-management strategies in case of marked asthma exacerbation . MEASUREMENTS AND MAIN RESULTS The main measurement used to determine efficacy of the study program was readmission rate and hospital days used . Prospect i ve comparison of treated compared with untreated patients indicated that program enrollment result ed in a threefold reduction in readmission rate and a twofold reduction in hospital day use rate ( P less than 0.004 and P less than 0.02 , respectively ) . Using retrospective data with patients serving as their own controls , we found a threefold reduction in readmission rate and in hospital day use ( P less than 0.003 ) during a 32-month follow-up period . A similar magnitude of reduction in hospital utilization was found when patients were crossed over to the intensive treatment group ( P less than 0.004 ) . CONCLUSIONS By using a vigorous medical regimen and intensive educational program , we were able to decrease hospital use among a group of adult asthmatics who had previously required repeated readmissions for acute asthma exacerbations BACKGROUND --Previous work has indicated a high rate of non-attendance at hospital based clinics among young , multiracial asthmatic patients of lower socioeconomic class . The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated . METHODS --A prospect i ve controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were r and omised to the usual follow up or the education centre plus usual follow up . Measurements were taken at entry into the study and again nine months later . RESULTS --At nine months patients r and omised to the education centre had more preventive medications , more peak expiratory flow meters and better flow meter technique , more self-management plans , better knowledge of appropriate action to take when confronted with worsening asthma , less nocturnal awakening , and better self-reported asthma control than the control group . There was no difference between the study groups in measurements of compliance , hospital admission , days lost from school or work , or emergency room use . CONCLUSIONS --The main effects of education were on asthma knowledge and self-management skills , whilst improvements in asthma morbidity were small . Potential reasons for this include heterogeneous study population ( in terms of baseline self-management skills , asthma severity , ethnicity and age ) , pragmatic study design , insensitivity of many of the measurements of morbidity , the modest effectiveness of a single time limited education programme , and inability to limit the effects of such a large community based study to the intervention group ( there was a 67 % reduction in asthma admissions during the study period from the geographical area targeted compared with a 22 % reduction for the rest of Auckl and ) BACKGROUND We developed and evaluated a self-management program for adult asthma . In developing the program , we considered questions of format and behavior control . The format we selected included components known to be effective in educational setting s. We regulated asthma management behavior through the introduction of environmental cues . METHODS Seventy-six subjects , whose asthma was generally under medical control , were assigned r and omly to either a treatment group or a waiting-list control group . Those in the treatment group were exposed to a 7-week program that incorporated proven features of providing effective training and establishing behavioral control . Subsequently , subjects in the control group received the treatment . Short-term evaluation of the treatment was made after the subjects in the experimental group were trained but before the control subjects were trained . Long-term evaluation was conducted after both groups of subjects were trained . RESULTS Over the short term , self-management training led to fewer asthma symptoms and physician visits and improvement in asthma management skills and cognitive abilities . Over the long term , self-management training was related to lower asthma attack frequency , reduced medication use , improvement in cognitive measures , and increased use of self-management skills . CONCLUSIONS The program improved asthma management in patients whose conditions were already under good medical control . The effects of the program were apparent a year after the conclusion of self-management training The efficacy of an adult asthma self-management program , Wheezers Anonymous ( WA ) , was tested utilizing 79 adult asthmatic patients . Subjects were r and omly assigned to a treatment or waiting-list control group . Baseline data gathered included measures of symptom severity , health-care utilization , knowledge of asthma , attitudes about asthma , and self-efficacy . All subjects completed the same measures 1 , 2 , and 3 months following the WA intervention . Knowledge about asthma increased in the treatment group relative to the waiting-list controls ; the number of attacks decreased in the treatment group only , thus demonstrating the efficacy of the WA program There is evidence that educational programmes may improve patient 's compliance with asthma treatment and control symptoms . Whilst medical parameters have been thoroughly studied , few data are available concerning psychological intervention . The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group ( ARG ) and in a Control Group ( CG ) . Forty consecutive asthmatics were r and omly enrolled , all of whom were diagnosed , treated and followed-up according to the International Guidelines . Both groups underwent a psychological assessment at baseline and after one year . A battery of question naires was used to obtain data relating to baseline characteristics ( anxiety , depression , psychophysiological disorders ) , emotional reactions to asthma attacks ( panic-fear , etc , ) and cognitive variables ( external control , psychological stigma , internal beliefs , external chance , etc . ) involved in the perceived illness . In addition , the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention . In both groups , a reduction of anxiety and depression scores was observed , as well as a significant improvement of the medical parameters evaluated . Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Question naire and on the External Control Subscale after 1 year . The Control Group reported higher score on the External Chance Scale . The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma . Larger scale studies on this topic are suggested Abstract Objective : To evaluate integrated care for asthma in clinical , social , and economic terms . Design : Pragmatic r and omised trial . Setting : Hospital outpatient clinics and general practice s throughout the north east of Scotl and . Patients : 712 adults attending hospital outpatient clinics with a diagnosis of asthma confirmed by a chest physician and pulmonary function reversibility of at least 20 % . Main outcome measures : Use of bronchodilators and inhaled and oral steroids ; number of general practice consultations and hospital admissions for asthma ; sleep disturbance and other restrictions on normal activity ; pyschological aspects of health including perceived asthma control ; patient satisfaction ; and financial costs . Results : After one year there were no significant overall differences between those patients receiving integrated asthma care and those receiving conventional outpatient care for any clinical or psycho-social outcome . For pulmonary function , forced expiratory volume was 76 % of predicted for integrated care patients and 75 % for conventional out patients ( 95 % confidence interval for difference -3.6 % to 5.0 % ) . Patients who had experienced integrated care were more likely to select it as their preferred course of future management ( 75 % ( 251/ 333 ) v 62 % ( 207/333 ) ( 6 % to 20 % ) ; they saved pounds sterling 39.52 a year . This was largely because patients in conventional outpatient care consulted their general practioner as many times as those in integrated care , who were not also visiting hospital . Conclusion : Integrated care for moderately severe asthma patients is clinical ly as effective as conventional outpatient care , cost effective , and an attractive management option for patients , general practioners , and hospital consultants Patient education and self-management programmes have proved effective in many studies with short follow-up periods . We studied the 3-year cost-effectiveness of an intensive programme of patient education and supervision for self-management . The study consisted of 162 consecutive newly diagnosed asthmatics who were r and omized either into an intervention group ( IG ) receiving intensive patient education and supervision for self-management at an outpatient clinic during the first year , or a control group ( CG ) receiving conventional education at the baseline visits only . Both groups had 2 additional years of follow-up . Lung functions and health-related quality of life ( HRQOL ) were measured . Extra direct and indirect costs were recorded . At 3 years the differences in forced expiratory volume in 1 s ( FEV1 ) and in peak expiratory flow ( PEF ) were significantly better in the IG being in ( % predicted ) respectively 5.3 ( 95 % CI 0.6 - 10.0 ) and 4.4 ( 95 % CI 0.1 - 8.7 ) , ( P < 0.05 ) . The airway responsiveness ( PD15 ) did not differ significantly , but the improvement from baseline to 3 years was significantly greater in the IG , being 0.40 dose steps ( 95 % CI 0.05 - 0.75 ) ( P < 0.05 ) . HRQOL scores did not differ significantly . The risk for sickness day was less in the IG with a RR of 0.6 ( 95 % CI 0.50 - 0.69 ) ( P = 0.000 ) and among patients who used the PEF meter . The compliance was similar in both groups when measured by the PEF-based self-management . There was no statistically significant difference in costs , although there was a consistent tendency for lower costs in the intensive programme . The intensive programme was more effective in terms of FEV1 , PEF and improvement in PD15 and equally effective in terms of other lung functions and HRQOL , but there was no clear difference in the costs The effect of patient education on steroid inhaler compliance and rescue medication utilization in patients with asthma or chronic obstructive pulmonary disease ( COPD ) has not been previously investigated in a single study . We r and omized 78 asthmatics and 62 patients with COPD after ordinary outpatient management . Intervention consisted of two 2-h group sessions and 1 to 2 individual sessions by a trained nurse and physiotherapist . A self-management plan was developed . We registered for 12 mo medication dispensed from pharmacies according to the Anatomical Therapeutic Chemical ( ATC ) classification index . Steroid inhaler compliance ( SIC ) was defined as ( dispensed/prescribed ) x 100 and being compliant as SIC > 75 % . Among asthmatics 32 % and 57 % were compliant ( p = 0.04 ) with a median ( 25th/75th percentiles ) SIC of 55 % ( 27/96 ) and 82 % ( 44/127 ) ( p = 0.08 ) in the control and intervention groups , respectively . Patient education did not seem to change SIC in the COPD group . Uneducated patients with COPD were dispensed double the amount of short-acting inhaled beta(2)-agonists compared with the educated group ( p = 0.03 ) . We conclude that patient education can change medication habits by reducing the amount of short-acting inhaled beta(2)-agonists being dispensed among patients with COPD . Educated asthmatics showed improved steroid inhaler compliance compared with the uneducated patients , whereas this seemed unaffected by education in the COPD group The prevalence and impact of adult asthma are substantial , and poor self-management practice s , especially failures to adhere to treatment regimens , appear to be a significant problem . Desirable characteristics of an intervention program to improve self-management were identified through needs assessment and review of existing patient education re sources . A comprehensive program was developed that integrated a workbook with one-to-one counseling and adherence-enhancing strategies . A longitudinal 1-year study compared patients receiving this self-management program with " usual care " patients receiving st and ard asthma pamphlets . Patients were r and omly assigned to conditions . Baseline score and asthma severity were statistically controlled . Self-management patients had substantially better adherence than usual care patients , as well as improved functional status , at follow-up . Hospital and emergency department visits decreased in both groups but did not differ between groups The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity , knowledge , and compliance with inhaled corticosteroid treatment using a prospect i ve , r and omized , controlled , one-year-before/one-year-after protocol . After rigorous optimization of asthma therapy under the care of respirologists , patients were assigned to one of three groups : Group C ( control group : no formal education ) , Group P ( education and action plan based on peak-flow monitoring ) , and Group S ( education with action plan based on monitoring of asthma symptoms ) . A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study . Asthma morbidity decreased significantly in all groups ( p = 0.001 ) . Mean values one-year-before/one-year-after in Groups C , P , and S were : unscheduled medical visits , 2.4/0.8 , 2.3/0.7 , and 1.9/ 0.7 ; hospitalizations , 0.21/0.04 , 0.24/0.04 , and 0.40/0.09 ; oral steroid treatments ; 1.3/0.5 , 1.2/0.7 , and 1.3/0.9 ; absenteeism from work/school , 9.6/5.2 , 8.8/2.2 , and 6.3/2.9 . Between-group differences did not reach statistical significance ( p > 0.05 ) . Asthma knowledge increased in both educated groups compared with the control group ( p < 0.001 ) as did short-term compliance with inhaled corticosteroids . These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity . In such clinical setting s , structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma , although it could not add extra benefit with regard to morbidity . Nevertheless , this study does not refute the potential benefit of educational interventions aim ed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors PURPOSE Excess morbidity and mortality due to asthma , aggravated by demonstrably poor patient self-management practice s , suggest the need for formal patient education programs . Individual and group asthma education programs were developed and evaluated to determine their cognitive , behavioral , and clinical effects . PATIENTS AND METHODS We compared changes in asthma symptoms , utilization of medical services , knowledge about asthma , metered-dose inhaler ( MDI ) technique , and self-management behaviors for 323 adult Kaiser Permanente patients with moderate to severe asthma who were r and omly assigned to small-group education , individual teaching , or 1 of 2 control conditions -- an information ( workbook ) control or usual control ( no formal asthma education ) . Data were collected from patients by question naire , diary , and physical examination at enrollment and at 5 months and 1 year after intervention . Medical record data on these patients were abstract ed for a total 3-year period , from 1 year before to 2 years after enrollment . RESULTS Compared with the usual control , the self-management education programs were associated with significant improvements in control of asthma symptoms ( reduced " bother " due to asthma and increased symptom-free days ) , MDI technique , and environmental control practice s. Small-group education also was associated with significant improvements in physician evaluation of the patients ' asthma status and in patients ' level of physical activity . For both group and individual education recipients , improvement in MDI technique was positively correlated with improved control of symptoms ; however , the degree of improvement in symptoms was greater than that which could be accounted for on the basis of improvement in MDI technique alone . The time course over which changes occurred in the various outcome measures suggests the mechanism by which education result ed in improvement in the patient 's status . Significant improvements in MDI technique and environmental control practice s were manifest immediately following education ( 5-month follow-up ) and at the 1-year follow-up . Significant improvements in symptom measures were not apparent until the 1-year follow-up . The rate of utilization of medical care for acute exacerbations decreased between baseline and the 2-year follow-up period , but this decrease did not differ significantly among treatment conditions . However , there was a trend toward greater reduction in patients receiving small-group education . An ad hoc finding of a significant difference favoring small-group education between the baseline and the second follow-up year acute visit rates was observed . This result must be regarded as tentative , since it is not clear that unambiguous statistical significance is attained in the light of multiplicity issues . However , this trend is consistent with the antecedent benefits of the small-group education , and appears to warrant further investigation . CONCLUSIONS Carefully design ed asthma education programs for adults can improve patients ' underst and ing of their condition and its treatment and increase their motivation and confidence that the condition can be controlled , thereby increasing their adherence to the treatment regimen and management of symptoms , and , in turn , improving control of symptoms . Both small-group education and individual education were associated with significant benefits , but the group program was simpler to administer , better received by patients and educators , and more cost-effective . The results show promise for improving clinical outcomes , through well- design ed educational programs , for patients with asthma and other chronic health problems Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes . In order to evaluate two training programs for asthmatic children aged 7 - 14 , 81 patients were r and omly assigned to three groups . Group 1 consisted of 27 patients and their parents who participated in a five-day st and ardized family-oriented clinical asthma training program . They had monthly follow-up meetings with the training team for a period of six months . Group 2 ( n = 29 ) had the same clinical training without follow-up interventions ; a control group ( n = 25 ) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group . Question naires regarding self-management aspects , coping and anxiety were filled out by patients , parents , family doctors and the training team prior to as well as twelve months after the training . The results indicate that Training group 1 benefitted most with respect to active asthma self-management , Training group 2 to some degree while the control group showed no significant effects . The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance . Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions The effectiveness of small group education of general practitioners in the management of asthma was evaluated by r and omized controlled trial . The outcome measure was the asthma morbidity of the general practitioners ' own patients . Following r and om selection from the list of one family practitioner committee in suburban London , the 27 participating general practitioners were allocated r and omly to one of two educational groups or to a control group . The educational intervention comprised eight meetings at which the management of chronic asthma was discussed and attempts made to devise agreed strategies for care . The two educational groups devised different strategies . Asthma morbidity was assessed by postal question naires to patients before the intervention and on five further occasions at six-monthly intervals over two and a half years . Of 454 patients who entered the study 338 completed the sixth and final assessment . The degree of morbidity experienced by the patients and their reported use of asthma specific drugs was considerable and was notably constant over the period of study . There was no difference in morbidity between the three groups at the outset and no effect of the intervention could be demonstrated . In this educational intervention the participating general practitioners were not informed about the morbidity and drug use reported by their patients . This information may be crucial if small groups are to be used to design and implement effective strategies for care . It would appear that small group education of general practitioners in the form reported here is not effective in reducing morbidity from chronic asthma Abstract Objective : To compare the efficacy of self management of asthma with traditional treatment . Design : 12 month prospect i ve r and omised trial . Setting : Outpatient clinics in Finl and . Subjects : 115 patients with mild to moderately severe asthma . Interventions : Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements . Main outcome measures : Unscheduled admissions to hospital and outpatient visits , days off work , courses of antibiotics and prednisolone , lung function , and quality of life . Results : The mean number of unscheduled visits to ambulatory care facilities ( 0.5 v 1.0 ) , days off work ( 2.8 v 4.8 ) , and courses of antibiotics ( 0.4 v 0.9 ) and prednisolone ( 0.4 v 1.0 ) per patient were lower and the quality of life score ( 16.6 v 8.4 at 12 months ) higher in the self management group than in the traditionally treated group . In both groups admissions for asthma were rare . Conclusions : Self management reduces incidents caused by asthma and improves quality of life . Key messages Key messages This trial of 115 patients with mild to moderately severe disease r and omised half to a traditional care and half to a self management programme consisting of education about asthma and daily peak flow readings Intervention thresholds of < 85 % of the optimal peak flow for doubling the dose of inhaled steroid for two weeks and of < 70 % of the optimal peak flow for starting a course of oral steroids worked well The self management group had fewer incidents ( consultations , days off work , courses of prednisolone or antibiotics ) than the traditionally treated group and better quality of life scores Adherence of patients to the self management instructions was better than Most asthma self-management programs have focused on children , but the preva lence and impact , both personal and economic , of adult asthma is substantial . More over , failure to adhere to treatment regimens appears to be a significant problem in adult asthma . It appears important , therefore , to develop asthma self-management programs for adults . The UAB program is based on the Health Belief Model for health behavior and on the PRECEDE Model for patient education . A needs assessment and a review of existing educational material s were used to specify the content of a self- care workbook . This workbook seeks to increase cognitive skills , encourage daily self- assessment of asthma , demonstrate success in asthma self-management , and promote effective social support . The overall intervention integrates this workbook with sys tematic reinforcement of self-monitoring and self-management . A prospect i ve con trolled study is comparing patients receiving this " special intervention " with " usual care " patients who receive only routinely available pamphlets providing information about asthma . Patients are r and omly assigned to treatments by the closed envelope technique . Sample sizes were determined on the basis of statistical power . Outcomes in five areas are assessed : ( 1 ) health care utilization , ( 2 ) functional status , ( 3 ) knowl edge , ( 4 ) adherence , and ( 5 ) psychological reactions We hypothesized that an educational intervention based on a readiness model would lead to improved health outcomes among patients with asthma . Within a r and omized control design in an urban Latino and African-American community , we conducted an intensive three-month pediatric intervention . A Family Coordinator provided patient education based on a readiness-to-learn model , and facilitated improved interactions between the patient and the doctor . Family education addressed the most basic learning needs of patients with asthma by improving their perception of asthma symptom persistence using asthma diaries and peak flow measures . The physician intervention focused clinicians ’ attention on patients ’ diary records and peak flow measures , and encouraged physicians to use stepped action plans . Patients were also tested for allergic sensitization and provided strategies to reduce contact with allergens and other asthma triggers . The results showed significant improvements by intervention group families on measures of knowledge , health beliefs , self-efficacy , self- regulatory skill , and adherence ; decreases in symptom persistence and activity restriction ; and increased prescription of anti-inflammatory medication by the physicians of the intervention group families Facilitated asthma-specialist care delivered by allergists was compared to generalist care on the rate of relapse of asthma emergency room ( ER ) visits and hospitalizations and on asthma control in a prospect i ve , controlled study of San Diego Kaiser Health Plan members with asthma . Subjects with asthma between the ages of 6 and 59 years presenting for acute ER care for asthma were systematic ally assigned by alternating , consecutively , the day of their ER visit to receive either ( 1 ) facilitated referral to an asthma specialist within the allergy department and concomitant comprehensive ongoing asthma care ( intervention group , n = 149 ) or ( 2 ) continued outpatient management from generalist physicians ( control group , n = 160 ) . The course of their asthma was evaluated blindly during the subsequent 6 months by review of medical records , initial and follow-up question naires , and spirometry . Compared to the control group , the intervention group noted ( 1 ) a 75 % reduction in the number of , and percent of , subjects with asthma awakenings per night ( p less than or equal to 0.0001 ) , ( 2 ) an almost 50 % reduction in asthma ER relapses ( p = 0.017 ) result ing from a reduction in the frequency of multiple relapse ( p = 0.005 ) , and ( 3 ) a greater use of inhaled corticosteroids ( p less than 0.00001 ) and cromolyn ( p = 0.002 ) . Thus , facilitated referral of subjects with asthma to specialists in asthma therapy after acute ER therapy appears to reduce asthma ER relapses and to improve asthma outcome Asthma , a chronic inflammatory condition of the airways , is a major health problem in the United States , affecting about 12 million people ( Bailey et al. , 1992 ; British Thoracic Society , 1990 ; Huss et al. , 1992 ) . People with asthma experience on average more than 100 days of restricted activity annually ( Bailey et al. , 1992 ) . Mortality and morbidity due to asthma are increasing , particularly among African Americans ( Buist & Vollmer , 1990 ; Wilson , 1993 ) . The costs for treating asthma in African Americans are exceptionally high because members of this population tend to use the emergency department as a primary source of care ( Baker , Stevens , & Brooks , 1994 ; Kellerman , 1994 ) . It is important that African Americans learn , through asthma self-management programs , what they need to manage their asthma and how to meet these needs through the health care system and increase their access to health services . As African Americans with asthma increase their access to and use of primary care and their use of inhaled corticosteroids as appropriate , they will better manage their asthma , thus maintaining their activity levels and reducing asthma-related mortality and morbidity and emergency department use ( Bauman et al. , 1989 ; Clark & Starr-Schneidkraut , 1994 ; Sly , Cahill , Willet , & Burton , 1994 ) . ASTHMA SELF-MANAGEMENT Two central components of most asthma education programs are asthma attack prevention and attack management ( Clark & Starr-Schneidkraut , 1994 ) . Asthma education and skills training in self-management help individuals draw from a base of asthma knowledge and make appropriate decisions and take corrective actions ( Bauman et al. , 1989 ; Clark & Starr-Schneidkraut , 1994 ) . The knowledge gained by participants in educational programs , such as accurate use of peak flow meters and asthma inhalers , may positively affect their perceptions of asthma ; these perceptions have been found to play a major role in how well patients adhere to medical treatment regimens ( Acker , 1992 ; Taytard , 1992 ) . As individuals become more proficient at managing their asthma and are able to function better in their daily lives , their asthma-related quality of life should improve ( Juniper , Guyatt , Ferrie , & Griffith , 1993 ; Rowe & Oxman , 1993 ) . Research ers agree that for behavioral changes to be long lasting , they must become sufficiently integrated into aspects of individuals ' daily lives ( Bauman et al. , 1989 ; Bolton , Tilley , Kuder , Reeves , & Schultz , 1991 ) . Empowerment Principles To help individuals integrate asthma management into their daily lives , asthma self-management courses must teach principles of empowerment . Empowerment refers to the development of the personal re sources ( social , psychological , intellectual , and spiritual ) individuals need to give them control and mastery over their lives ( Feste , 1992 ; Kalyanpur & Rao , 1991 ) . Developing these personal re sources is especially critical for African Americans with asthma , a disease in which much of the burden of day-to-day management and recognition of symptoms rests with the individual . In addition , African Americans have traditionally held a disempowered political , economic , and social position in U.S. society and have thus been prevented from exercising control and mastery over their environments ( McKinney , Harel , & Williams , 1990 ; Thomas & Quinn , 1991 ) . Empowerment-centered asthma education can help African Americans with asthma better manage this chronic condition . Church Setting Asthma education programs can be offered in the local church , a context central to many African Americans . Taylor and Chatters ( 1986 ) described the African American church as functioning as an " omnipresent and important institution " ( p. 637 ) for African Americans of all ages . Historically , churches have provided for the educational , nutritional , psychological , and employment needs of African Americans and been focal points for community activities ( Taylor , Thornton , & Chatters , 1987 ; Walls & Zarit , 1991 ) . We r and omized 135 adult asthma patients to a control group , and 132 patients to an experimental group which received a special health education intervention . Four adherence measures were documented at baseline and 12-month follow-up : correct inhaler use , inhaler adherence , medication adherence , and total adherence rating . Costs to routinely deliver the intervention were $ 32.03/patient . Experimental group patients exhibited a significantly higher level of improvement in adherence ( 44 percent ) than control group patients ( 2 percent ) Patients need to underst and their asthma to be able to react appropriately . At least 30 minutes is needed by a trained asthma professional to teach asthma self-management effectively . Many patients accept symptoms and attacks unnecessarily through insufficient knowledge of their condition and treatment . In this small study , those who were educated by a trained asthma nurse had a significantly higher knowledge of their condition and management . Most of those who were educated by a trained asthma nurse had symptoms less frequently . Those who were educated by a trained asthma nurse had no time off work whereas 49 % of the control group had time off work Aims To evaluate postal prompts to increase patients ' underst and ing and use of self-management plans ( SMP ) . Methods A single-blinded r and omised controlled trial in 545 adults with asthma prescribed an inhaled corticosteroid . The control group were mailed an invitation for a medical review . The second and third groups were mailed invitations with a blank or a personalised written action plan respectively . Outcomes were whether patients had a review , felt they knew how to use SMP , and the self reported ' Royal College of Physicians three questions ' score of current morbidity ( ' RCP score ' ) . Results Compared to the control group , prompts with a personalised written action plan result ed in more patients having a review of their care ( odds ratio 2.33 , 95 % CI 1.37 to 3.93 ) and underst and ing how to use their SMP ( odds ratio 2.20 , 95 % CI 1.13 to 4.30 ) . Prompts with a blank written action plan result ed in more review s ( odds ratio 1.92 , 95 % CI 1.18 to 3.11 ) but no difference in underst and ing how to use their SMP ( odds ratio 1.28 95 % CI 0.66 to 2.45 ) . Review s carried out : 70 % vs 82 % vs 84 % for groups 1 , 2 and 3 respectively ; underst and ing how to use a SMP : 40 % vs 46 % vs 59 % for groups 1 , 2 and 3 respectively . There was no difference in reported ' RCP scores ' between the three groups . Conclusions Personalised prompts increased frequency of review and patients underst and ing of SMPs but SMPs remain underused |
12,517 | 26,383,108 | RESULTS Meta-analyses showed that Tai Chi improved or showed a tendency to improve physical performance outcomes , including 6-min walking distance ( 6MWD ) and knee extensor strength , in most or all four chronic conditions .
Tai Chi also improved disease-specific symptoms of pain and stiffness in OA .
CONCLUSIONS The results demonstrated a favourable effect or tendency of Tai Chi to improve physical performance and showed that this type of exercise could be performed by individuals with different chronic conditions , including COPD , HF and OA | BACKGROUND Many middle-aged and older persons have more than one chronic condition .
Thus , it is important to synthesis e the effectiveness of interventions across several comorbidities .
The aim of this systematic review was to summarise current evidence regarding the effectiveness of Tai Chi in individuals with four common chronic conditions-cancer , osteoarthritis ( OA ) , heart failure ( HF ) and chronic obstructive pulmonary disease ( COPD ) . | Background —Tai Chi Chuan ( TTC ) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls . Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test . There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test . Methods —In this cross sectional study , 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group . Another 30 sedentary men aged 66.2 were selected to serve as the control group . Measurements included resting heart rate , left and right single leg stance with eyes closed , modified sit and reach test , total body rotation test ( left and right ) , and a three minute step test . Results —Compared with the sedentary group , the TCC group had significantly better scores in resting heart rate , three minute step test heart rate , modified sit and reach , total body rotation test on both right and left side ( p<0.01 ) , and both right and left leg st and ing with eyes closed ( p<0.05 ) . According to the American Fitness St and ards , the TCC group attained the 90th percentile rank for sit and reach and total body rotation test , right and left . Conclusion —Long term regular TCC exercise has favourable effects on the promotion of balance control , flexibility , and cardiovascular fitness in older adults BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 PURPOSE Individuals with osteoarthritis can experience difficulty walking and poor strength , possibly leading to falls and fractures . Exercise has been found to increase strength and bone mineral density . The purpose of this study was to determine the effects of 6 months of t'ai chi on knee muscle strength , bone mineral density , and fear of falling in older women with osteoarthritis . METHODS Eighty-two ( 82 ) women with osteoarthritis , recruited from outpatient clinics and community health centers , were r and omly assigned to either a t'ai chi group and took part in a t'ai chi program , or a control group . Of these , 30 subjects ( mean age = 63 years ) in the t'ai chi group and 35 ( mean age = 61 years ) in the control group completed post-test measures at 6 months . RESULTS After the 6-month study period , subjects in the t'ai chi program had significantly greater knee extensor endurance ( pre- to post-test mean increase = 36.4 W/kg , versus 1.1 W/kg for the controls ) , and significantly greater bone mineral density in the neck of the proximal femur ( mean change = 0.09 , versus -0.10 for the controls ) , Ward 's triangle ( mean change = 0.04 , versus -0.04 for the controls ) , and trochanter ( mean change = 0.07 , versus -0.05 for the controls ) than the controls . However , knee extensor and flexor strength did not differ significantly between the groups . The fear of falling during daily activities reduced significantly more in the t'ai chi group ( mean change = -2.40 , versus 0.66 for the controls ) . CONCLUSIONS T'ai chi increased knee extensor muscle endurance and bone mineral density in older women with osteoarthritis , and decreased their fear of falling during daily activities . Further study with long-term follow-up is needed to substantiate the role of t'ai chi exercise in the prevention of fall and its related fracture PURPOSE Tai Chi exercise , an ancient Chinese martial art , has drawn more and more attention for its health benefits . The purpose of the study was to identify the effects of a Sun-style Tai Chi exercise on arthritic symptoms ( joint pain and stiffness ) , motivation for performing health behaviors , and the performance of health behaviors among older women with osteoarthritis . METHODS Total of 72 women with the mean age of 63 years old were recruited from out patients clinic or public health centers according to the inclusion criteria and assigned r and omly to either the Tai Chi exercise group or the control . A Sun-style Tai Chi exercise has been provided three times a week for the first two weeks , and then once a week for another 10 weeks . In 12 weeks of study period , 22 subjects in the Tai Chi exercise group and 21 subjects in the control group completed the posttest measure with the dropout rate of 41 % . Outcome variables included arthritic symptoms measured by K-WOMAC , motivation for health behavior , and health behaviors . RESULTS At the completion of the 12 week Tai Chi exercise , the Tai Chi group perceived significantly less joint pain ( t=-2.19 , p=0.03 ) and stiffness ( t=-2.24 , p=0.03 ) , perceived more health benefits ( t=2.67 , p=0.01 ) , and performed better health behaviors ( t=2.35 , p=0.02 ) , specifically for diet behavior ( t=2.06 , p=0.04 ) and stress management ( t=2.97 , p=0.005 ) . CONCLUSION A Sun-style Tai Chi exercise was found as beneficial for women with osteoarthritis to reduce their perceived arthritic symptoms , improve their perception of health benefits to perform better health behaviors BACKGROUND Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease ( COPD ) have been widely reported , the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD . This study reported a r and omised controlled trial , which investigated the effects of Tai Chi on lung function , exercise capacity , and diaphragm strength in patients with COPD . TRIAL DESIGN Single blind r and omised controlled study . SETTING Department of Respiratory Medicine , Xiangya Hospital , Central South University . METHODS Forty patients with COPD were r and omised into either a control group or Tai Chi intervention group . Participants in the control group received only routine care , while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program . OUTCOMES Lung function parameters , blood gas parameters , 6-min walking distance ( 6MWD ) , and diaphragm strength parameters . RESULTS Lung function parameters ( FEV1 : 1.43 ± 0.08 and FEV1 ( % ) predicted : 47.6 ± 4.76 ) , 6MWD ( 476 ± 15 ) and diaphragm strength parameters ( TwPes : 1.17 ± 0.07 , TwPga : -1.12 ± 0.06 , and TwPdi : 1.81 ± 0.09 ) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care ( p<0.05 ) . These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline ( p<0.05 ) . In contrast , no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group ( p>0.05 ) . CONCLUSIONS Tai Chi enhances lung function , exercise capacity , and diaphragm strength . However , this is only preliminary research data and a larger trial is needed for more detailed results OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation Objective . In a r and omized trial of women with early stage breast cancer undergoing adjuvant chemotherapy , two stress management interventions , tai chi training and spiritual growth groups , were compared to a usual care control group , to evaluate psychosocial functioning , quality of life ( QOL ) , and biological markers thought to reflect cancer- and treatment-specific mechanisms . Method . The sample consisted of 145 women aged 27–75 years ; 75 % were Caucasian and 25 % African American . A total of 109 participants completed the study , yielding a 75 % retention rate . Grounded in a psychoneuroimmunology framework , the overarching hypothesis was that both interventions would reduce perceived stress , enhance QOL and psychosocial functioning , normalize levels of stress-related neuroendocrine mediators , and attenuate immunosuppression . Results . While interesting patterns were seen across the sample and over time , the interventions had no appreciable effects when delivered during the period of chemotherapy . Conclusions . Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes . Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period . It may be that interventions requiring less activity and /or group attendance would have enhanced therapeutic effects , and more active interventions need to be tested prior to and following recovery from chemotherapy Objectives . To evaluate the sustaining effects of Tai Chi Qigong ( TCQ ) in improving the psychosocial health in chronic obstructive pulmonary disease ( COPD ) patients in the sixth month . Background . COPD affects both physical and emotional aspects of life . Measures to minimize patients ' suffering need to be implemented . Methods . 206 COPD patients were r and omly assigned into three groups : TCQ group , exercise group , and control group . The TCQ group completed a three-month TCQ program , the exercise group practice d breathing and walking exercise , and the control group received usual care . Results . Significant group-by-time interactions in quality of life ( QOL ) using St. George 's respiratory question naire ( P = 0.002 ) and the perceived social support from friends using multidimensional scale of perceived social support ( P = 0.04 ) were noted . Improvements were observed in the TCQ group only . Conclusions . TCQ has sustaining effects in improving psychosocial health ; it is also a useful and appropriate exercise for COPD patients OBJECTIVE To assess the effects of a 12-week Tai Chi exercise program on sleep using the sleep spectrogram , a method based on a single channel electrocardiogram (ECG)-derived estimation of cardiopulmonary coupling , previously shown to identify stable and unstable sleep states . METHODS We retrospectively analyzed 24-h continuous ECG data obtained in a clinical trial of Tai Chi exercise in patients with heart failure . Eighteen patients with chronic stable heart failure , left ventricular ejection fraction < or= 40 % ( mean [ + /-st and ard deviation ] age , 59+/-14 years , mean baseline ejection fraction 24%+/-8 % , mean ) were r and omly assigned to receive usual care ( N=10 ) , which included pharmacological therapy and dietary and exercise counseling , or 12 weeks of Tai Chi training ( N=8 ) in addition to usual care . Using the ECG-based sleep spectrogram , we compared intervention and control groups by evaluating baseline and 12-week high ( stable ) and low ( unstable ) frequency coupling ( HFC & LFC , respectively ) as a percentage of estimated total sleep time ( ETST ) . RESULTS At 12 weeks , those who participated in Tai Chi showed a significant increase in HFC ( + 0.05+/-0.10 vs. -0.06+/-0.09 % ETST , p=0.04 ) and significant reduction in LFC ( -0.09+/-0.09 vs. + 0.13+/-0.13 % ETST , p<0.01 ) , compared to patients in the control group . Correlations were seen between improved sleep stability and better disease-specific quality of life . CONCLUSIONS Tai Chi exercise may enhance sleep stability in patients with chronic heart failure . This sleep effect may have a beneficial impact on blood pressure , arrhythmogenesis and quality of life Purpose . To assess if Tai Chi added to endurance training ( ET ) is more effective than ET alone in improving exercise tolerance and quality of life ( QOL ) of elderly patients with chronic heart failure ( CHF ) . Design . Sixty CHF patients , age 73.8 ± 6 years , M/F 51/9 , were enlisted . Thirty pts were r and omized to combined training ( CT ) performing Tai Chi + ET and 30 patients to ET ( ET only ) . Methods . At baseline and after 12 weeks all patients underwent 6-minute walking test ( 6MWT ) , assessment of amino terminal probrain natriuretic peptide ( NT-pro BNP ) , quadriceps maximal voluntary contraction ( MVC ) and peak torque ( PT ) , QOL question naire ( MacNewQLMI ) , blood pressure ( BP ) , and heart rate ( HR ) . All patients performed 4 sessions of exercise/week . Results . Distance at 6mwt improved in both groups with significant between-groups differences ( P = .031 ) . Systolic BP and NT-proBNP decreased significant in the CT group compared to ET ( P = .025 ) and P = .015 ) , resp . ) . CT group had a greater significant improvement in physical perception ( P = .026 ) and a significant increase of PT compared to ET group . Conclusions . The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET Goals Health-related quality of life ( HRQL ) and self-esteem are often diminished among women diagnosed and treated for breast cancer . Tai Chi is a moderate form of exercise that may be an effective therapy for improving HRQL and self-esteem among these women . We sought to compare the efficacy of Tai Chi Chuan ( TCC ) and psychosocial support ( PST ) for improving HRQL and self-esteem among breast cancer survivors . Patients and methods A group of 21 women diagnosed with breast cancer , who had completed treatment within the last 30 months were r and omized to receive 12 weeks of TCC or PST . Participants in both groups met three times a week for 60 minutes . HRQL and self-esteem were assessed at baseline , 6 weeks , and 12 weeks . Results The TCC group demonstrated significant improvements in HRQL , while the PST group reported declines in HRQL , with the differences between the two groups approaching significance at week 12 . Additionally , the TCC group exhibited improvements in self-esteem , while the PST group reported declines in self-esteem , with the differences between groups reaching statistical significance at week 12 . These findings , coupled with a visual inspection of the raw change scores , support the plausibility of a dose-response relationship concerning Tai Chi . Conclusions In this pilot investigation , the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks , while the support group exhibited declines . R and omized , controlled clinical trials with larger sample sizes are needed Osteoarthritis of the knee is the most common cause of chronic disability among older persons in the United States [ 1 ] . In persons with symptomatic osteoarthritis of the knee , quadriceps muscle weakness is common and is widely believed to result from disuse atrophy secondary to joint pain . Although exercises to strengthen the quadriceps may relieve joint pain in persons with osteoarthritis of the knee [ 2 - 6 ] , the role of periarticular muscle weakness in the pathogenesis of joint pain and disability in these persons is poorly understood . The basis for the beneficial effect of strengthening exercises is unclear , and the duration of the improvement has not been studied . Furthermore , the possibility that muscle weakness is an etiologic factor underlying the pathologic changes of osteoarthritis has seldom been considered . Elucidation of the role of muscle weakness in osteoarthritis is particularly important given our growing underst and ing of safe and effective methods for increasing strength in elderly persons [ 7 , 8 ] . A substantial proportion of persons who have radiographic evidence of osteoarthritis of the knee have no joint pain [ 9 ] . Because asymptomatic persons with radiographic changes seldom seek medical attention for osteoarthritis , muscle weakness has not been studied previously in this group . Thus , it is not known whether quadriceps weakness precedes or follows joint pain or ( if it follows joint pain ) whether it is mediated by disuse atrophy or by physiologic mechanisms that may inhibit muscle contraction [ 10 ] . To address this issue , we studied the relation among lower-extremity muscle strength , lower-extremity lean tissue mass , and osteoarthritis of the knee in men and women 65 years of age and older . Methods Study Group To obtain a sample of elderly persons living in the community , we conducted brief telephone interviews with residents of households in central Indiana . Potential participants were selected through modified r and om-digit dialing to increase the sample d proportion of persons 65 years of age and older . Persons were eligible if they met the minimal criteria for participation : They were willing and able to provide informed consent and to undergo the necessary strength assessment s and other evaluations . Persons were excluded if they had had amputations of both lower extremities , had undergone total knee arthroplasty , or had recently had a cerebrovascular accident or myocardial infa rct ion . A total of 462 persons ( approximately 55 % of all who were eligible ) agreed to participate and completed the following evaluations . Evaluations Radiography of the Knee St and ing anteroposterior and lateral radiographs of both knees of each study participant were obtained , and the severity of osteoarthritis in the tibiofemoral compartment was grade d by a musculoskeletal radiologist according to the criteria of Kellgren and Lawrence . Similar criteria , based on the presence of osteophytes and joint space narrowing , were used for the patellofemoral compartment [ 11 ] . The radiologist was blinded to the clinical status and characteristics of all patients . A participant had to have a Kellgren and Lawrence grade of 2 or more in either knee to be classified as having osteoarthritis . Knee Pain and Function The Western Ontario and McMaster Universities Arthritis Index was used to evaluate knee pain and function [ 12 ] . This index assesses the severity of knee pain during 5 activities or situations ( walking on a flat surface , going up or down stairs , at night while in bed , sitting or lying , and st and ing upright ) and the severity of impairment of lower-extremity function during 17 activities . Pain and functional impairment were assessed in each knee separately . Responses to each question about the severity of knee pain and level of impairment were recorded on a categorical scale as none , mild , moderate , severe , or extreme . Each category was assigned a corresponding numeric score from 1 to 5 ( 5 = extreme ) . Hence , the range on the pain scale was 5 to 25 and the range on the physical impairment scale was 17 to 85 ( 85 = greatest functional limitation ) . For the purpose s of analysis , participants who rated the severity of their knee pain as moderate or greater ( 3 ) with any of the 5 activities on more than half of the days in the month preceding the evaluation were considered to have knee pain . Thus , pain in the more distant past that had resolved was not included . Participants were also question ed about current and previous regular ( 5 times per week ) or occasional use of over-the-counter and prescription analgesics and nonsteroidal anti-inflammatory drugs ( NSAIDs ) in the past year . Lower-Extremity Muscle Strength The strength of each leg was evaluated by using an isokinetic dynamometer ( KIN-COM 500H , Chattecx Corp. , Hixson , Tennessee ) . Peak torque was recorded in both the concentric ( contractions during muscle shortening ) and eccentric ( contractions during muscle lengthening ) modes . Participants were allowed several submaximal or maximal practice efforts to familiarize themselves with the operation of the dynamometer . Once formal testing began , the best of three maximal efforts was recorded for flexion and extension at both 60 degrees per second and 120 degrees per second . Aborted efforts were repeated in order to obtain the best possible representation of strength for each participant . Concentric and eccentric testing yielded similar results , but because of greater variability in eccentric testing , only the concentric test results are shown . Lower-Extremity Lean Tissue Mass Total-body dual-energy x-ray absorptiometry was done in all participants by using a Lunar-DPX-L instrument ( Lunar Corp. , Madison , Wisconsin ) . Results were analyzed for total and regional body composition , including body fat , mineral , and lean components ( lean components were components other than fat or mineral ) . The right and left lower extremities were analyzed separately . The lower extremity was defined as all tissue below a diagonal line drawn outward and upward from the groin area through the femoral neck . Statistical Analysis Participants were divided into four groups on the basis of presence or absence of radiographic evidence of osteoarthritis of the knee and presence or absence of knee pain , as defined above . Men and women were compared by using the t-test . Comparisons of Arthritis Index pain and functional impairment scores were done by using nonparametric approaches . For analyses of continuous data involving more than two groups of participants ( for example , osteoarthritis with or without knee pain ) , analysis of variance was used to determine whether an overall difference was present . The Fisher protected least-significant-difference procedure was used for pairwise comparisons . Comparisons within participants ( for example , comparison of the two legs in a person with unilateral osteoarthritis of the knee ) were done by using paired t-tests . Regression models were constructed with the generalized estimating equations approach of Zeger and Liang [ 13 ] . This approach inflates the st and ard errors to adjust for correlations in both independent variables ( such as strength ) and dependent variables ( such as radiographic grade ) within participants . Statistically significant differences ( P < 0.05 ) in the above analyses are specifically noted below . Results The characteristics of the 462 men and women in the cohort are shown in Table 1 . As expected , men were taller , were heavier , and had greater lower-extremity strength and lean tissue mass in the lower extremities compared with women ( P < 0.001 for all comparisons ) . Table 1 . Age , Height , Weight , and Lower-Extremity Strength and Lean Tissue Mass * One hundred forty-five participants ( 31 % ; 33 % of the women and 30 % of the men ) had radiographic evidence of osteoarthritis involving the tibiofemoral compartment , the patellofemoral compartment , or both . In 62 participants ( 43 % ) , the radiographic changes were unilateral . Table 2 shows the association between osteoarthritis and obesity [ 14 - 16 ] . Women in the cohort who had osteoarthritis were approximately 15 % heavier than women with normal radiographs and no knee pain . Men with osteoarthritis were also slightly heavier than men without osteoarthritis . Table 2 . Body Weight and Summed Arthritis Index Scores for Recent Pain and Function in the Left Knee in Participants with and without Radiographic Evidence of Osteoarthritis * Among those with radiographic evidence of tibiofemoral osteoarthritis , women were slightly more likely than men to report knee pain ( P = 0.10 ; Table 3 ) . Table 3 . Radiography and Recent Pain in the Left Knee Table 2 also shows the mean summed and the distribution of scores for left knee pain and functional impairment ( data for the right knee were similar ) . Among men and women with radiographic evidence of osteoarthritis who reported having knee pain , the mean summed pain score for the knee with osteoarthritis was approximately 12 ( median score , 2 of 5 ) . In comparison , the mean pain score of participants who reported knee pain but did not have radiographic evidence of osteoarthritis in the painful knee was approximately 10 ( median score , 2 of 5)-only slightly lower than the mean pain score of participants with radiographic changes . Consistent with their relatively low pain scores , these community-dwelling participants with osteoarthritis reported moderately low use of NSAIDs ( Table 4 ) . Table 4 . Participants Reporting Regular Current or Previous Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs Related to the Presence of Radiographic Evidence of Osteoarthritis of the Knee and Recent Knee Pain * Arthritis Index scores for functional impairment paralleled those for pain ( Table 2 ) . Participants with osteoarthritis had the greatest functional impairment ( P < 0.001 for the comparison with patients who did not have pain or radiographic evidence of osteoarthritis ) . Functional impairment in participants who had pain but no radiographic evidence of Objective : To evaluate the effects of tai chi consisting of group and home-based sessions in elderly subjects with knee osteoarthritis . Design : A r and omized , controlled , single-blinded 12-week trial with stratification by age and sex , and six weeks of follow-up . Setting : General community . Participants : Forty-one adults ( 709 / 9.2 years ) with knee osteoarthritis . Interventions : The tai chi programme featured six weeks of group tai chi sessions , 40 min/session , three times a week , followed by another six weeks ( weeks 7 -12 ) of home-based tai chi training . Subjects were requested to discontinue tai chi training during a six-week follow-up detraining period ( weeks 13 - 18 ) . Subjects in the attention control group attended six weeks of health lectures following the same schedule as the group-based tai chi intervention ( weeks 0 -6 ) , followed by 12 weeks of no activity ( weeks 7 - 18 ) . Main outcome measures : Knee pain measured by visual analogue scale , knee range of motion and physical function measured by Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) were recorded at baseline and every three weeks throughout the 18-week study period . Data were analysed using a mixed model ANOVA . Results : The six weeks of group tai chi followed by another six weeks of home tai chi training showed significant improvements in mean overall knee pain ( P = 0.0078 ) , maximum knee pain ( P = 0.0035 ) and the WOMAC subscales of physical function ( P = 0.0075 ) and stiffness ( P = 0.0206 ) compared to the baseline . No significant change of any outcome measure was noted in the attention control group throughout the study . The tai chi group reported lower overall pain and better WOMAC physical function than the attention control group at weeks 9 and 12 . All improvements disappeared after detraining BACKGROUND / AIMS Treatment for breast cancer produces side effects that diminish functional capacity and quality of life ( QOL ) among survivors . Tai Chi Chuan ( TCC ) is a moderate form of exercise that may improve functional capacity and QOL in these individuals . Women who completed treatment for breast cancer were r and omized to receive TCC or psychosocial support therapy for 12 weeks ( 60 min ; three times weekly ) . RESULTS The TCC group demonstrated significant improvements in functional capacity , including aerobic capacity , muscular strength , and flexibility , as well as QOL ; the psychosocial support therapy group showed significant improvements only in flexibility , with declines in aerobic capacity , muscular strength , and QOL . CONCLUSIONS The TCC group exhibited significant improvements in functional capacity and QOL . These data suggest that TCC may enhance functional capacity and QOL among breast cancer survivors Objective : To evaluate the effects of Tai Chi Qigong training on the quality of life and physical function of patients with osteoarthritis of the knee . Design : A preliminary , single-blind , r and omized controlled trial . Setting : General community , performed at Hwaseong City Health Center . Participants : Forty-four elderly subjects ( mean age , 69.1 ± 5.4 years ) with knee osteoarthritis . Intervention : The patients were r and omized ( 2:1 ) to : ( 1 ) an eight-week Tai Chi Qigong training programme or ( 2 ) a waiting list control group . The programme involved eight weeks of group Tai Chi Qigong sessions , with 60 minutes per session twice a week . Main outcome measures : The primary outcome was quality of life measured with the Short Form 36 ( SF-36 ) at baseline and week 8 . Secondary outcomes included the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and 6-m walking time . Results : The training group had statistically significant improvements in the quality of life ( changes of SF-36 , Qigong versus control : 21.6 ± 16.8 versus 9.8 ± 13.6 , P<0.05 ) and 6-m walking test ( change in walking time , Qigong versus control : —1.6 ± 1.7 versus —0.2 ± 0.8 s , P<0.01 ) . The WOMAC scores in the training group were markedly improved , although the differences were not statistically significant . Conclusions : Tai Chi Qigong training appears to have beneficial effects in terms of the quality of life and physical functioning of elderly subjects with knee osteoarthritis . However , more rigorous trials are needed to confirm the efficacy of this training for patients with osteoarthritis of the knee OBJECTIVE To determine the effects of T'ai Chi training on arthritis self-efficacy , quality of life indicators , and lower extremity functional mobility in older adults with osteoarthritis . DESIGN A prospect i ve , r and omized , controlled clinical trial . Intervention length was 12 weeks , with outcomes measured before and after intervention using blinded testers . Group ( T'ai Chi vs Control ) x time ( 2 x 2 ) mixed factorial ANOVA . SETTING Allied Health Sciences Center at Springfield College , Springfield , MA PARTICIPANTS : A total of 33 community-dwelling participants ( mean age 68 ) diagnosed with lower extremity osteoarthritis and having no prior T'ai Chi training longer than 2 weeks . INTERVENTION T'ai Chi training included two 1-hour T'ai Chi classes per week for 12 weeks . MEASUREMENTS Arthritis self-efficacy ( Arthritis Self-Efficacy Scale ) , quality of life indicators ( Arthritis Impact Measurement Scale ) , functional outcomes ( one-leg st and ing balance , 50-foot walking speed , time to rise from a chair ) . RESULTS T'ai Chi participants experienced significant ( P < .05 ) improvements in self-efficacy for arthritis symptoms , total arthritis self-efficacy , level of tension , and satisfaction with general health status . CONCLUSIONS A moderate T'ai Chi intervention can enhance arthritis self-efficacy , quality of life , and functional mobility among older adults with osteoarthritis . T'ai Chi training is a safe and effective complementary therapy in the medical management of lower extremity osteoarthritis Purpose This paper evaluates the effectiveness of a 3-month Tai chi Qigong ( TCQ ) program in promoting the psychosocial functional health of clients with chronic obstructive pulmonary disease ( COPD ) in Hong Kong . Methods This study employed a single-blind , r and omized controlled trial . Two hundred and six COPD clients were r and omly assigned into three groups , namely , TCQ group , exercise group , and control group . Subjects in the TCQ group received a TCQ program , consisting of two 60-min sessions each week for 3 months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group received their usual care . Data collection s were performed at baseline , on the sixth week and on the third month . The primary outcomes were health-related quality of life using St. George Respiratory Question naire-Hong Kong Chinese version and perceived social support using the Multidimensional Scale of Perceived Social Support-Chinese version . Results The TCQ group showed greater improvements in the symptom ( F4 , 404 = 3.351 , P = 0.010 ) and activity domains ( F4 , 404 = 2.611 , P = 0.035 ) . No differences were detected in perceived social support among the three groups . Conclusions Tai chi Qigong promoted health outcomes with respect to clients ’ perception of their respiratory symptoms . Moreover , TCQ decreased disturbances to their physical activities OBJECTIVE To evaluate the effectiveness of Tai Chi in the treatment of knee osteoarthritis ( OA ) symptoms . METHODS We conducted a prospect i ve , single-blind , r and omized controlled trial of 40 individuals with symptomatic tibiofemoral OA . Patients were r and omly assigned to 60 minutes of Tai Chi ( 10 modified forms from classic Yang style ) or attention control ( wellness education and stretching ) twice weekly for 12 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain score at 12 weeks . Secondary outcomes included WOMAC function , patient and physician global assessment s , timed chair st and , depression index , self-efficacy scale , and quality of life . We repeated these assessment s at 24 and 48 weeks . Analyses were compared by intent-to-treat principles . RESULTS The 40 patients had a mean age of 65 years and a mean body mass index of 30.0 kg/m(2 ) . Compared with the controls , patients assigned to Tai Chi exhibited significantly greater improvement in WOMAC pain ( mean difference at 12 weeks -118.80 mm [ 95 % confidence interval ( 95 % CI ) -183.66 , -53.94 ; P = 0.0005 ] ) , WOMAC physical function ( -324.60 mm [ 95 % CI -513.98 , -135.22 ; P = 0.001 ] ) , patient global visual analog scale ( VAS ; -2.15 cm [ 95 % CI -3.82 , -0.49 ; P = 0.01 ] ) , physician global VAS ( -1.71 cm [ 95 % CI -2.75 , -0.66 ; P = 0.002 ] ) , chair st and time ( -10.88 seconds [ 95 % CI -15.91 , -5.84 ; P = 0.00005 ] ) , Center for Epidemiologic Studies Depression Scale ( -6.70 [ 95 % CI -11.63 , -1.77 ; P = 0.009 ] ) , self-efficacy score ( 0.71 [ 95 % CI 0.03 , 1.39 ; P = 0.04 ] ) , and Short Form 36 physical component summary ( 7.43 [ 95 % CI 2.50 , 12.36 ; P = 0.004 ] ) . No severe adverse events were observed . CONCLUSION Tai Chi reduces pain and improves physical function , self-efficacy , depression , and health-related quality of life for knee OA CONTEXT Because Tai Chi ( TC ) is beneficial to elders without cognitive impairment ( CI ) , it also may benefit elders with CI . But elders with CI have generally been excluded from TC studies because many measurement tools require verbal reports that some elders with CI are unable to provide . OBJECTIVES To test the efficacy of a TC program in improving pain and other health outcomes in community-dwelling elders with knee osteoarthritis ( OA ) and CI . METHODS This pilot cluster-r and omized trial was conducted between January 2008 and June 2010 ( Clinical Trials.gov Identifier : NCT01528566 ) . The TC group attended Sun style TC classes , three sessions a week for 20 weeks ; the control group attended classes providing health and cultural information for the same length of time . Measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain , physical function and stiffness subscales ; the Get Up and Go test ; the Sit-to-St and test ; and the Mini-Mental State Examination ( MMSE ) , administered at baseline , every four weeks during the intervention and at the end of the study ( post-test ) . RESULTS Eight sites participated in either the TC group ( four sites , 28 participants ) or control group ( four sites , 27 participants ) . The WOMAC pain ( P = 0.006 ) and stiffness scores ( P = 0.010 ) differed significantly between the two groups at post-test , whereas differences between the two groups in the WOMAC physical function score ( P = 0.071 ) and the MMSE ( P = 0.096 ) showed borderline significance at the post-test . WOMAC pain ( P = 0.001 ) , physical function ( P = 0.021 ) , and stiffness ( P ≤ 0.001 ) scores improved significantly more over time in the TC group than in controls . No adverse events were found in either group . CONCLUSION Practicing TC can be efficacious in reducing pain and stiffness in elders with knee OA and CI Although exercise is an important component of heart failure management , optimal regimens , particularly in heart failure with preserved ejection fraction ( HFPEF ) , are uncertain . Tai chi ( TC ) is a mind-body exercise that may have potential benefits but has not been studied in this population . The authors r and omized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise . Assessment s included peak oxygen uptake , 6-minute walk , quality of life , echocardiography , mood , and self-efficacy at baseline and at 12 weeks . Cardiorespiratory measures during exercise were obtained to characterize training intensities . Baseline characteristics were as follows : age 66±12 years , E/A ratio 1.3±0.7 , and E/e ' ratio 15.9±4.8 . Overall , adherence was excellent ( 89 % attendance ) . Change in peak oxygen uptake was similar between groups after 12 weeks , but 6-minute walk distance increased more after TC ( 69±46 m vs 10±31 m , P=.02 ) . While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy , Profile of Mood States (POMS)-Depression scores improved more with TC ( -1.7±2.8 vs 1.6±3 , P=.05 ) . Cardiorespiratory assessment during TC showed lower oxygen uptake ( 4.3 mL/kg/min vs 9.4 mL/kg/min , P<.01 ) , respiratory rate , and heart rate . TC is feasible and safe in HFPEF . Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload OBJECTIVES To evaluate the sustaining effects of Tai chi Qigong in improving the physiological health for COPD patients at sixth month . DESIGN A r and omized controlled trial . Subjects were in three r and omly assigned groups : Tai chi Qigong group , exercise group , and control group . SETTING The 206 subjects were recruited from five general outpatient clinics . INTERVENTIONS Tai chi Qigong group completed a 3-month Tai chi Qigong program . Exercise group practice d breathing and walking as an exercise . Control group received usual care . MAIN OUTCOME MEASURES Primary outcomes included six-minute walking distance and lung functions . Secondary outcomes were dyspnea and fatigue levels , number of exacerbations and hospital admissions . RESULTS Tai chi Qigong group showed a steady improvement in exercise capacity ( P<.001 ) from baseline to the sixth month . The mean walking distance increased from 298 to 349 meters ( + 17 % ) . No significant changes were noted in the other two groups . Tai chi Qigong group also showed improvement in lung functions ( P<.001 ) . Mean forced expiratory volume in 1s increased from .89 to .99l ( + 11 % ) . No significant change was noted in the exercise group . Deterioration was found in the control group , with mean volume decreased from .89 to .84l ( -5.67 % ) . Significant decreased in the number of exacerbations was observed in the Tai chi Qigong group . No changes in dyspnea and fatigue levels were noted among the three groups . CONCLUSIONS Tai chi Qigong has sustaining effects in improving the physiological health and is a useful and appropriate exercise for COPD patients Background : Cardiac rehabilitation improves physical , cognitive and psychosocial functioning , yet services are greatly underutilized with increasing patterns of attrition over time . Tai Chi has been suggested as a possible adjunct to cardiac rehabilitation exercise training . Aim : To describe differences in physical , cognitive and psychosocial functioning among adults ≥ 45 years old attending phase III cardiac rehabilitation , who have or have not self-selected Tai Chi exercise as an adjunct physical activity . Methods : A cross-sectional design compared subjects attending group-based Wu style Tai Chi classes plus cardiac rehabilitation , with cardiac rehabilitation only . Subjects had a battery of physical and cognitive functioning tests administered to examine aerobic endurance , balance , strength , and flexibility , verbal retrieval/recall , attention , concentration and tracking . Subjects completed a health survey to ascertain cardiac event information , medical history , and psychosocial functioning ( i.e. health-related quality of life , stress , depressive symptoms , social support , and Tai Chi self-efficacy ) . Results : A total of 51 subjects ( 75 % married , 84 % college-educated , 96 % White/European-American ) participated . Subjects were on average 70 ( ± 8) years old and had attended cardiac rehabilitation for 45 ( ± 37 ) months . Approximately 45 % ( n = 23 ) attended Tai Chi classes plus cardiac rehabilitation , while 55 % ( n = 28 ) attended cardiac rehabilitation only . Subjects attending Tai Chi plus cardiac rehabilitation had better balance , perceived physical health , and Tai Chi self-efficacy compared to those attending cardiac rehabilitation only ( p ≤ 0.03 ) . Conclusion : Tai Chi can be easily implemented in any community/cardiac rehabilitation facility , and may offer adults additional options after a cardiac event Objective : To study the effect of Tai Chi on exercise tolerance in patients with moderate heart failure . Design : R and omised parallel group study balanced for baseline variables . Setting : Cardiology Department , Royal Hallamshire Hospital . Patients and methods : 52 patients 42 men , mean age 68.9 years , range 4690 years , and 10 women , mean age 70.0 years , range 5882 with chronic heart failure New York Heart Association symptom class IIIII were studied . Patients were r and omised to Tai Chi Chuan twice a week for 16 weeks or to st and ard medical care without exercise rehabilitation . Main outcome measures : The primary outcome measure was the change in the distance walked in the shuttle walk test . Secondary outcome measures were changes in symptom scores and quality of life indices . Results : Objective measures of exercise tolerance did not improve significantly with Tai Chi , but patients having Tai Chi exercise had an improvement in symptom scores of heart failure measured by the Minnesota Living with Heart Failure Question naire comparison of deltas , 2.4 control vs 14.9 ; p0.01 , and depression scores measured by the SCL-90-R question naire 2.9 vs 6.8 ; p0.12 compared with those patients in the control group . Conclusion : In patients with chronic heart failure , 16 weeks of Tai Chi training was safe , with no adverse exercise related problems . It was enjoyed by all taking part and led to significant improvements in symptoms and quality of life BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA OBJECTIVE To evaluate the effectiveness of a Tai chi Qigong ( TCQ ) program in enhancing respiratory functions and activity tolerance in clients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A single-blind , r and omized controlled trial . SETTING Five general outpatient clinics in Hong Kong . INTERVENTION In total , 206 COPD clients were r and omly assigned into one of the three groups , namely , TCQ , exercise , and control group . Subjects in the TCQ group received a TCQ program consisting of two 60-min sessions each week for three months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group were instructed to maintain their usual activities . Data collection was performed at baseline and at the 6-week and 3-month marks . OUTCOMES Lung functions , 6-min walk test , and COPD exacerbation rate . RESULTS Results of repeated measures of analysis of covariance demonstrated that there were significant interaction effects between time and group in forced vital capacity ( p=.002 , η(2)=.06 ) , forced expiratory volume in 1s ( p<.001 , η(2)=.02 ) , walking distance ( p<.001 ) , and exacerbation rate ( p=.006 , η(2)=.06 ) at 3 months . Improvements were noted in the TCQ group . No changes were observed in the exercise group , while a decline in lung functions was noticed in the control group . CONCLUSION Tai chi Qigong was able to improve respiratory functions and activity tolerance level in COPD clients . The breathing and walking exercise helped maintain lung functions and slow down disease progression OBJECTIVE Twelve forms of Sun-style tai chi exercise have been developed specifically to reduce the symptoms and improve the physical functioning of arthritic patients , and this r and omized study examined the changes in symptoms and physical characteristics in older women with osteoarthritis ( OA ) at the completion of a 12-week tai chi exercise program . METHODS Seventy-two patients with OA were r and omly assigned into 2 groups . Due to a 41 % overall dropout rate , 22 experimental subjects and 21 controls completed pre- and post-test measures over a 12 week interval . Outcome variables were physical symptoms and fitness , body mass index , cardiovascular functioning , and perceived difficulties in physical functioning . The independent t test was used to examine group differences . RESULTS The homogeneity test confirmed that there were no significant group differences in demographic data and pretest measures . Mean comparisons of the change scores revealed that the experimental group perceived significantly less pain ( t = -2.19 , p = 0.034 ) and stiffness ( t = -2.13 , p = 0.039 ) in their joints , and reported fewer perceived difficulties in physical functioning ( t = -2.81 , p = 0.008 ) , while the control group showed no change or even deterioration in physical functioning after 12 weeks . In the physical fitness test , there were significant improvements in balance ( t = 3.34 , p = 0.002 ) and abdominal muscle strength ( t = 2.74 , p = 0.009 ) for the tai chi exercise group . No significant group differences were found in flexibility and upper-body or knee muscle strength in the post-test scores . CONCLUSION Older women with OA were able to safely perform the 12 forms of Sun-style tai chi exercise for 12 weeks , and this was effective in improving their arthritic symptoms , balance , and physical functioning . A longitudinal study with a larger sample size is now needed to confirm the potential use of tai chi exercise in arthritis management Treatment of breast cancer can significantly diminish functional capacity in patients months and even years after the completion of treatments . Tai chi chuan ( TCC ) is a moderate form of exercise that may be an effective therapy for improving functional capacity among breast cancer survivors . We sought to provide pilot data comparing the efficacy of TCC and psychosocial therapy ( PST ; physical activity control ) for improving functional capacity among breast cancer survivors post treatment . Twenty-one women who had completed treatment of breast cancer were r and omized to receive TCC or PST 3 times/wk for 12 weeks . Functional capacity was assessed at baseline and at 12 weeks . The TCC group demonstrated significant improvement in functional capacity ( specifically aerobic capacity , muscular strength , and flexibility ) whereas the PST group showed significant improvement in flexibility only . These data suggest that TCC may be an efficacious intervention for enhancing functional capacity among breast cancer survivors and may support the need for larger r and omized , controlled clinical trials to further eluci date these relationships BACKGROUND Alternative strategies for exercises that provide both training and relaxation benefits are optimal for persons with very low functional capacities who also are at high risk for complications . T'ai Chi C'hih , a modified form of traditional T'ai Chi , is a series of slow balanced movements and breathing promoted to increase energy levels and induce relaxation . OBJECTIVES To estimate the energy costs and cardiovascular effects of T'ai Chi C'hih . Measured energy costs of specific activities can assist with safe exercise prescription for individuals with very low energy reserves . METHODS A convenience sample ( n = 26 ) of healthy adults participated in this study , which involved completion of surveys to estimate functional capacity and exercise participation , training in a select series of nine T'ai Chi C'hih movements , and oxygen consumption testing while movements are performed . Movements involving front to back and lateral moves of the lower extremity , full shoulder range of motion of upper extremity , and deep forced inhalation and stepped exhalations were performed at slow to fast cadences in sitting and st and ing positions . The Human Activity Profile was used to estimate lifestyle energy consumption . Exercise participation was quantified as Kcal/Kg(1 ) expended per week . RESULTS Metabolic equivalents ( METs ) for sitting T'ai Chi C'hih movements were estimated to be 1.5 + /- 0.17 and 2.3 + /- 0.34 for slow st and ing , and 2.6 + /- 0.47 for fast st and ing . Mean maximum heart rates ranged from 43 % to 49 % of predicted maximum heart rates . Mean increases in both systolic and diastolic blood pressures over resting were 8 % . Mean METs of breathing exercises ranged from 3 to 3.6 . There were no differences in responses to the movements by gender or experience with T'ai Chi exercise . CONCLUSION The movements used to perform T'ai Chi C'hih require energy expenditure comparable with that for activities of daily living and for low level exercises currently recommended for persons with low exercise tolerance . Therefore , T'ai Chi C'hih may be an alternative approach to health promotion in many population s with chronic disease Introduction Breast cancer survivors experience diminished health-related quality of life ( HRQOL ) . We report on the influence of tai chi chuan exercise ( TCC ) on HRQOL and explore associations between changes in HRQOL and biomarkers . Methods Breast cancer survivors ( N = 21 ) were r and omly assigned to TCC or st and ard support therapy ( SST ) for 12 weeks ( three times/week ; 60 min/session ) . Interleukin-6 , interleukin-8 ( IL-8 ) , insulin-like growth factor-1 ( IGF-1 ) , insulin-like growth factor-binding protein (IBFBP)-1 , IGFBP-3 , glucose , insulin , and cortisol were measured pre- and postintervention . Overall HRQOL and subdomains were assessed at preintervention ( T1 ) , midintervention ( T2 ) and postintervention ( T3 ) and biomarkers at T1 and T3 . Results The TCC group improved in total HRQOL ( T1–T2:CS = 8.54 , P = 0.045 ) , physical functioning ( T1–T2:CS = 1.89 , P = 0.030 ) , physical role limitations ( T1–T2 CS = 1.55 , P = 0.023 ) , social functioning ( T1–T3:CS = 1.50 , P = 0.020 ) , and general mental health ( T1–T2:CS = 2.67 , P = 0.014 ; T1–T3:CS = 2.44 , P = 0.019 ) . The SST improved in social functioning ( T1–T2:CS = 0.64 , P = 0.043 ) and vitality ( T1–T2:CS = 0.90 , P = 0.01 ) . There were relationships between changes in IGF-1 and overall HRQOL ( r = −0.56 ; P < 0.05 ) , physical role limitation ( r = −0.68 ; P < 0.05 ) , and social functioning ( r = −0.56 ; P < 0.05 ) . IGFBP-1 changes were associated with physical role limitations changes ( r = 0.60 ; P < 0.05 ) . IGFBP-3 changes were associated with physical functioning changes ( r = 0.46 ; P ≤ 0.05 ) . Cortisol changes were associated with changes in physical role limitations ( r = 0.74 ; P < 0.05 ) and health perceptions ( r = 0.46 ; P < 0.05 ) . Glucose changes were associated with emotional role limitation changes ( r = −0.70 ; P < 0.001 ) . IL-8 changes were associated with emotional role limitation changes ( r = 0.59 ; P < 0.05 ) . Discussion / conclusions TCC may improve HRQOL by regulating inflammatory responses and other biomarkers associated with side effects from cancer and its treatments . Implication s for cancer survivorsTCC may be an intervention capable of improving HRQOL in breast cancer survivors The aim of this report is to investigate the effects of 8 weeks of intensive Tai Chi Chuan ( TCC ) training on physiological function and fear of falling ( FOF ) in the less-robust elderly . Forty-nine community-dwelling elderly , aged 60 or older , were classified r and omly into a TCC training or control group . Physical performance measures ( including one-leg stance , trunk flexion , and walking speed ) and interviews were conducted before and after the intervention . The TCC group showed significant improvements in balance and flexibility , and a reduced FOF , when compared with the control group after the intervention . However , walking speed did not change significantly . The results suggest that a high-frequency , short-term TCC training program can improve balance , flexibility , and increase the confidence of less-robust elderly . These suggest the effectiveness of TCC for intervention as a means to prevent falling among high-risk elderly population This study examines the effects of a 16-week Tai Chi ( TC ) training program on the muscle strength , endurance , and reaction time of the lower extremities of elderly people . A total of 40 elderly individuals ( aged 60 years ) completed the study . They were divided into two groups : the TC group ( 11 men and 11 women ) underwent a supervised TC exercise program for 16 weeks , while the control group ( 9 men and 9 women ) received general education for a comparable time period . Pre- and post-intervention measurements were conducted . An isokinetic dynamometer was used to measure the maximum concentric strength and dynamic endurance of the knee flexors and the extensors , and the maximum concentric strength of the ankle plantarflexors and dorsiflexors . The neuromuscular response of the rectus femoris , semitendinosus , gastrocnemius , and anterior tibialis muscles was measured by the onset latency to sudden perturbations using an electromyography system . After 16 weeks , the TC group showed a 19.9 % increase in muscle strength of the knee flexors ( p<.000 ) that was significantly greater than that in the control group ( p=.046 ) . There was also a significant decrease in semitendinosus muscle latency ( 6.6 % , p=.014 ) that was significantly shorter than that in the control group ( p=.042 ) . No significant training effects were found in other measures . These results suggest that improving biomechanical characteristics of lower extremity muscles may need longer TC intervention for elderly people Objective . The purpose of this r and omized controlled trial ( RCT ) was to examine the feasibility and acceptability of a Tai Chi Chih ( TCC ) intervention in senior female cancer survivors with physical functioning limitations , and its effects on health-related quality of life ( QOL ) . Design . This was a two-armed , parallel group , RCT with 12-weeks of Tai Chi Chih or Health Education Control . Methods . Sixty-three senior ( M age = 67 years , SD = 7.15 ) female cancer survivors ( 83 % breast cancer , stages I-III ) with physical functioning limitations ( SF-12 Health Survey role-physical & physical functioning subscales ) were r and omized to 12-weeks of TCC or Health Education control ( HEC ) . Primary outcomes were feasibility and acceptability . Secondary outcomes included health-related QOL ( SF-36 Health Survey ) , and participants ’ qualitative feedback on the intervention . Results . Retention ( TCC = 91 % ; HEC = 81 % ) and class attendance ( TCC = 79 % ; HEC = 83 % ) rates , and satisfaction levels for both study arms were high , but did not significantly differ from one another . At one-week post-intervention , none of the SF-36 scores differed between the TCC and HEC groups . Within-group analyses revealed significant improvements in the mental component summary score in TCC ( p = 0.01 ) , but not in HEC . Qualitative analyses indicated that the TCC group felt they received mental and physical benefits , whereas HEC group reported on social support benefits and information received . Conclusion . The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors . Future , larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population |
12,518 | 27,254,313 | Reduction in UAE under antihypertensive treatment is associated with reduced risk of clinical cardiovascular events .
Our findings suggest that UAE changes may represent a valuable intermediate end point for cardiovascular events in primary hypertension | BACKGROUND Increased urine albumin excretion ( UAE ) is a well known predictor of cardiovascular events in patients with primary hypertension .
Whether a reduction in UAE is associated to an improvement in cardiovascular risk is at present unclear .
We performed a systematic review and meta-regression analysis of available trials to investigate whether treatment-induced changes in UAE are related to cardiovascular outcome . | BACKGROUND Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme ( ACE ) inhibitors in persons with type 2 diabetes . METHODS In this prospect i ve , multicenter , double-blind , five-year study , we r and omly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan ( 80 mg daily , in 120 subjects ) or the ACE inhibitor enalapril ( 20 mg daily , in 130 subjects ) . The primary end point was the change in the glomerular filtration rate ( determined by measuring the plasma clearance of iohexol ) between the baseline value and the last available value during the five-year treatment period . Secondary end points included the annual changes in the glomerular filtration rate , serum creatinine level , urinary albumin excretion , and blood pressure ; the rates of end-stage renal disease and cardiovascular events ; and the rate of death from all causes . RESULTS After five years , the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 ( where the minus sign denotes a decrement ) in the telmisartan-treated subjects , as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects ; the treatment difference was thus -2.6 ml per minute per 1.73 m2 ( 95 percent confidence interval , -7.1 to 2.0 ml per minute per 1.73 m2)[corrected ] The lower boundary of the confidence interval , in favor of enalapril , was greater than the predefined margin of -10.0 ml per minute per 1.73 m2 , indicating that telmisartan was not inferior to enalapril . The effects of the two agents on the secondary end points were not significantly different after five years . CONCLUSIONS Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes . These findings do not necessarily apply to persons with more advanced nephropathy , but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P<0.001 ) and angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P<0.001 ) ; the rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P<0.001 ) , syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P<0.001 ) . CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . ) OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism . The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events R and omized Trial ( FACET ) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension . Prospect ively defined cardiovascular events were assessed as secondary outcomes . RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension ( systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg ) . Exclusion criteria included a history of coronary heart disease or stroke , serum creatinine > 1.5 mg/dl , albuminuria > 40 μg/min , and use of lipid-lowering drugs , aspirin , or antihypertensive agents other than beta-blockers or diuretics . A total of 380 hypertensive diabetics were r and omly assigned to open-label fosinopril ( 20 mg/day ) or amlodipine ( 10 mg/day ) and followed for up to 3.5 years . If blood pressure was not controlled , the other study drug was added . RESULTS Both treatments were effective in lowering blood pressure . At the end of followup , between the two groups there was no significant difference in total serum cholesterol , HDL cholesterol , HbA1c , fasting serum glucose , or plasma insulin . The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infa rct ion , stroke , or hospitalized angina than those receiving amlodipine ( 14/189 vs. 27/191 ; hazards ratio = 0.49 , 95 % CI = 0.26–0.95 ) . CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures , but the patients r and omized to fosinopril had a significantly lower risk of major vascular events , compared with the patients r and omized to amlodipine Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk . The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study . Urinary albumin/creatinine ratio ( UACR ) was measured at baseline and annually . Time-varying albuminuria was closely related to risk for the primary composite end point ( ie , when UACR decreased during treatment , risk was reduced accordingly ) . When the population was divided according to median baseline value ( 1.21 mg/mmol ) and median year 1 UACR ( 0.67 mg/mmol ) , risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 ( 5.5 % ) , to low baseline/high year 1 ( 8.6 % ) , to high baseline/low year 1 ( 9.4 % ) , and to high baseline/high year 1 ( 13.5 % ) values . Similar significant , stepwise increases in risk were seen for the components of the primary composite end point ( cardiovascular mortality , stroke , and myocardial infa rct ion ) . The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure . We propose that monitoring of albuminuria should be an integrated part of the management of hypertension . If albuminuria is not decreased by the patient ’s current antihypertensive and other treatment , further intervention directed toward blood pressure control and other modifiable risks should be considered Background The R and omized Olmesartan and Diabetes Microalbuminuria Prevention ( ROADMAP ) study showed that 40 mg Olmesartan medoxomil ( OM ) versus placebo delayed microalbuminuria onset in patients with type 2 diabetes and normoalbuminuria . Methods and Results One thous and seven hundred and fifty‐eight ROADMAP patients ( placebo arm : 877 ; OM arm : 881 ) participated in the observational follow up ( OFU ) with an average of 3.3 years . They received st and ard medical care and micro‐ and macrovascular events were documented . During observational follow‐up 62.9 % and 60.1 % in the former OM and placebo group , respectively , received treatment with a RAS blocking agent . During the OFU period the systolic blood pressure ( SBP ) increased to mean values of 135 mm Hg in both groups . Patients who had developed microalbuminuria during ROADMAP had a higher incidence of cardio‐ and cerebrovascular events ( OR 1.77 , CI 1.03 to 3.03 , P=0.039 ) during the OFU period compared with patients in whom this was not the case . Diabetic retinopathy was significantly reduced in the former OM group ( 8 [ 0.9 % ] versus 23 [ 2.6 % ] , OR : 0.34 , CI 0.15 to 0.78 , P=0.011 ) and the rate of microalbuminuria was numerically reduced . Congestive heart failure requiring hospitalization ( 3 [ 0.3 % ] versus 12 [ 1.4 % ] , OR : 0.23 , CI 0.06 to 0.85 , P=0.027 ) was reduced and there was a trend of reduced cardio‐/cerebrovascular events ( OM versus Pb : 73 [ 8.3 % ] versus 86 [ 9.8 % ] patients ) . Seven ( 0.8 % ) deaths ( including 2 CV events ) were reported in former placebo patients versus 3 ( 0.3 % ) ( non‐CV events ) in former OM patients . Conclusions Development of microalbuminuria is a valid marker for future CV events . RAS blockade with Olmesartan might cause sustained reduction ( legacy effect ) of micro‐ and macrovascular events The degree of albuminuria predicts cardiovascular and renal outcomes , but it is not known whether changes in albuminuria also predict similar outcomes . In two multicenter , multinational , prospect i ve observational studies , a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes . We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months . A greater than or equal to twofold increase in albuminuria from baseline to 2 years , observed in 28 % , associated with nearly 50 % higher mortality ( HR 1.48 ; 95 % CI 1.32 to 1.66 ) , and a greater than or equal to twofold decrease in albuminuria , observed in 21 % , associated with 15 % lower mortality ( HR 0.85 ; 95 % CI 0.74 to 0.98 ) compared with those with lesser changes in albuminuria , after adjustment for baseline albuminuria , BP , and other potential confounders . Increases in albuminuria also significantly associated with cardiovascular death , composite cardiovascular outcomes ( cardiovascular death , myocardial infa rct ion , stroke , and hospitalization for heart failure ) , and renal outcomes including dialysis or doubling of serum creatinine ( adjusted HR 1.40 ; 95 % CI 1.11 to 1.78 ) . In conclusion , in patients with vascular disease , changes in albuminuria predict mortality and cardiovascular and renal outcomes , independent of baseline albuminuria . This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk BACKGROUND Angiotensin receptor blockers ( ARB ) and angiotensin converting enzyme ( ACE ) inhibitors are known to reduce proteinuria . Their combination might be more effective than either treatment alone , but long-term data for comparative changes in renal function are not available . We investigated the renal effects of ramipril ( an ACE inhibitor ) , telmisartan ( an ARB ) , and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage . METHODS The trial ran from 2001 to 2007 . After a 3-week run-in period , 25 620 participants were r and omly assigned to ramipril 10 mg a day ( n=8576 ) , telmisartan 80 mg a day ( n=8542 ) , or to a combination of both drugs ( n=8502 ; median follow-up was 56 months ) , and renal function and proteinuria were measured . The primary renal outcome was a composite of dialysis , doubling of serum creatinine , and death . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00153101 . FINDINGS 784 patients permanently discontinued r and omised therapy during the trial because of hypotensive symptoms ( 406 on combination therapy , 149 on ramipril , and 229 on telmisartan ) . The number of events for the composite primary outcome was similar for telmisartan ( n=1147 [ 13.4 % ] ) and ramipril ( 1150 [ 13.5 % ] ; hazard ratio [ HR ] 1.00 , 95 % CI 0.92 - 1.09 ) , but was increased with combination therapy ( 1233 [ 14.5 % ] ; HR 1.09 , 1.01 - 1.18 , p=0.037 ) . The secondary renal outcome , dialysis or doubling of serum creatinine , was similar with telmisartan ( 189 [ 2.21 % ] ) and ramipril ( 174 [ 2.03 % ] ; HR 1.09 , 0.89 - 1.34 ) and more frequent with combination therapy ( 212 [ 2.49 % ] : HR 1.24 , 1.01 - 1.51 , p=0.038 ) . Estimated glomerular filtration rate ( eGFR ) declined least with ramipril compared with telmisartan ( -2.82 [ SD 17.2 ] mL/min/1.73 m(2)vs -4.12 [ 17.4 ] , p<0.0001 ) or combination therapy ( -6.11 [ 17.9 ] , p<0.0001 ) . The increase in urinary albumin excretion was less with telmisartan ( p=0.004 ) or with combination therapy ( p=0.001 ) than with ramipril . INTERPRETATION In people at high vascular risk , telmisartan 's effects on major renal outcomes are similar to ramipril . Although combination therapy reduces proteinuria to a greater extent than monotherapy , overall it worsens major renal outcomes The Japan Multicenter Investigation of Antihypertensive Treatment for Nephropathy in Diabetics ( J-MIND ) study was conducted to evaluate the effect of nifedipine retard or enalapril on nephropathy in hypertensive patients with type 2 diabetes . A total of 436 patients with normoalbuminuria [ urinary albumin excretion rate ( AER ) < 30 mg/day ] or microalbuminuria [ AER : 30 - 300 mg/day ] were r and omized to receive nifedipine retard or enalapril and were followed for 24 months . There were no differences in baseline characteristics between the two groups ( the mean AER was 45 and 42 mg/day , respectively ) . Intent-to-treat analysis showed no significant difference in AER after 2 years , although the mean AER increased to 64 and 74 mg/day in the nifedipine retard and enalapril groups , respectively . The AER increased in patients with normoalbuminuria , whereas it did not change in those with microalbuminuria . There were no differences between the two groups with respect to progression from normoalbuminuria to microalbuminuria , progression from microalbuminuria to overt proteinuria , and regression from microalbuminuria to normoalbuminuria . The incidence of cardiovascular events was also similar in both groups . In conclusion , nifedipine retard and enalapril had a similar effect on nephropathy in hypertensive type 2 diabetic patients without overt proteinuria Objectives To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients . Design The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre , prospect i ve , double-blind , parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria r and omized to at least 2-year VeraTran ( verapamil/tr and olapril 180 mg/2 mg daily ) or tr and olapril ( 2 mg daily , identical image ) treatment . Main outcome was persistent macroalbuminuria ( albuminuria > 200 μg/min in two consecutive visits ) . Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7 % . Results Over a median follow-up of 4.5 years , 18 patients ( 13 % ) on VeraTran vs. 15 ( 10.5 % ) on tr and olapril [ unadjusted hazard ratio ( 95 % confidence interval [ CI ] ) 1.07 ( 0.54–2.12 ) , P = 0.852 ] progressed to macroalbuminuria , respectively ; 62 ( 44.9 % ) vs. 71 ( 49.7 % ) [ 0.80 ( 0.57–1.12 ) , P = 0.198 ] regressed to normoalbuminuria ( urinary albumin excretion < 20 μg/min ) , and 20 ( 14.5 % ) vs. 21 ( 14.7 % ) [ hazard ratio 0.93 ( 0.50–1.72 ) , P = 0.816 ] had major cardiovascular events . BP and metabolic control were similar between groups . Patients with cardiovascular events were significantly less [ 13 ( 9.8 % ) vs. 28 ( 18.9 % ) , hazard ratio : 0.37 ( 0.19–0.71 ) , P = 0.003 ] among those regressing to normoalbuminuria than those without regression . Difference was independent of treatment allocation and was significant also after adjusting for baseline characteristics [ 0.40 ( 0.20–0.79 ) , P = 0.009 ] , follow-up SBP [ 0.40 ( 0.20–0.80 ) , P = 0.010 ] or DBP [ 0.36 ( 0.18–0.73 ) , P = 0.004 ] BP or HbA1C [ 0.43 ( 0.21–0.88 ) , P = 0.021 ] . Conclusion In hypertensive type 2 diabetes patients with microalbuminuria , verapamil added-on tr and olapril did not improve renal or cardiovascular outcomes . Independent of verapamil , tr and olapril normalized albuminuria in half of patients and this translated into significant cardioprotection BACKGROUND Although several important studies have been performed in hypertensive type 2 diabetic patients , it is not known whether lowering blood pressure in normotensive ( BP < 140/90 mm Hg ) patients offers any beneficial results on vascular complications . The current study evaluated the effect of intensive versus moderate diastolic blood pressure ( DBP ) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients . METHODS The current study was a prospect i ve , r and omized controlled trial in normotensive type 2 diabetic subjects . The subjects were r and omized to intensive ( 10 mm Hg below the baseline DBP ) versus moderate ( 80 to 89 mm Hg ) DBP control . Patients in the moderate therapy group were given placebo , while the patients r and omized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication . The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion , progression of retinopathy and neuropathy and the incidence of cardiovascular disease . RESULTS The mean follow-up was 5.3 years . Mean BP in the intensive group was 128 + /- 0.8/75 + /- 0.3 mm Hg versus 137 + /- 0.7/81 + /- 0.3 mm Hg in the moderate group , P < 0.0001 . Although no difference was demonstrated in creatinine clearance ( P = 0.43 ) , a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria ( P = 0.012 ) and microalbuminuria to overt albuminuria ( P = 0.028 ) . The intensive BP control group also demonstrated less progression of diabetic retinopathy ( P = 0.019 ) and a lower incidence of strokes ( P = 0.03 ) . The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent . CONCLUSION Over a five-year follow-up period , intensive ( approximately 128/75 mm Hg ) BP control in normotensive type 2 diabetic patients : ( 1 ) slowed the progression to incipient and overt diabetic nephropathy ; ( 2 ) decreased the progression of diabetic retinopathy ; and ( 3 ) diminished the incidence of stroke BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation . Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent BACKGROUND The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion ( UAE ) in hypertensive diabetic patients . METHODS We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and r and omized them to amlodipine ( 5 to 15 mg/day ) , fosinopril ( 10 to 30 mg/day ) , or amlodipine plus fosinopril ( 5/10 to 15/30 mg/day ) for a 3-month titration period . The nonresponder patients or those complaining of side effects during the titration period were discontinued ( n = 144 ) ; the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years . Every 6 months , blood pressure ( BP ) , heart rate ( HR ) , UAE , creatinine clearance , and glycosylated hemoglobin ( HbA1c ) were evaluated . RESULTS The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis . All three treatments provided a significant decrease in UAE during the 48-month study period . However , this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy ( after 3 v 18 months of therapy ) . In addition , the combination therapy provided a greater antialbuminuric effect than the single drugs . This could be due to the greater antihypertensive effects , although other drug-specific effects can not be excluded . The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group , but they were lower in the combination group . CONCLUSIONS These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes |
12,519 | 30,116,896 | However , this review did not find evidence identifying the most effective intervention for preventing postpartum depression symptoms in adolescent mothers | Postpartum depression ( PPD ) is a major public health problem affecting 10–57 % of adolescent mothers which can affect not only adolescent mothers but also their infants .
Thus , there is a need for interventions to prevent PPD in adolescent mothers .
However , recent systematic review s have been focused on effective interventions to prevent PPD in adult mothers .
These interventions may not necessarily be applicable for adolescent mothers .
Therefore , the purpose of this review was to examine the effectiveness of the existing interventions to prevent PPD in adolescent mothers . | OBJECTIVE To evaluate the efficacy of a paraprofessional-delivered , home-visiting intervention among young , reservation-based American Indian ( AI ) mothers on parenting knowledge , involvement , and maternal and infant outcomes . METHOD From 2002 to 2004 , expectant AI women aged 12 to 22 years ( n = 167 ) were r and omized ( 1:1 ) to one of two paraprofessional-delivered , home-visiting interventions : the 25-visit " Family Spirit " intervention addressing prenatal and newborn care and maternal life skills ( treatment ) or a 23-visit breast-feeding/nutrition education intervention ( active control ) . The interventions began during pregnancy and continued to 6 months postpartum . Mothers and children were evaluated at baseline and 2 , 6 , and 12 months postpartum . Primary outcomes included changes in mothers ' parenting knowledge and involvement . Secondary outcomes included infants ' social and emotional behavior ; the home environment ; and mothers ' stress , social support , depression , and substance use . RESULTS Participants were mostly teenaged , first-time , unmarried mothers living in reservation communities . At 6 and 12 months postpartum , treatment mothers compared with control mothers had greater parenting knowledge gains , 13.5 ( p < .0001 ) and 13.9 ( p < .0001 ) points higher , respectively ( 100-point scale ) . At 12 months postpartum , treatment mothers reported their infants to have significantly lower scores on the externalizing domain ( beta = -.17 , p < .05 ) and less separation distress in the internalizing domain ( beta = -.17 , p < .05 ) . No between-group differences were found for maternal involvement , home environment , or mothers ' stress , social support , depression , or substance use . CONCLUSIONS This study supports the efficacy of the paraprofessional-delivered Family Spirit home-visiting intervention for young AI mothers on maternal knowledge and infant behavior outcomes . A longer , larger study is needed to replicate results and evaluate the durability of child behavior outcomes BACKGROUND Children of adolescent mothers may suffer because of parenting inadequacies . The use of volunteer home visitors to enhance parenting skills has not been well studied . OBJECTIVE To evaluate the effect of a volunteer model home visitation program on adolescent parenting outcomes . DESIGN R and omized trial with assignment to home visitation or control group . SETTING Urban , African American community . PARTICIPANTS Adolescents aged 12 to 18 years at 28 or more weeks ' gestation or who had delivered a baby in the past 6 months were recruited between February 1996 and August 1999 . INTERVENTION Volunteers were recruited from the community and trained to implement a parenting curriculum during weekly home visits . Each volunteer was paired with one teenager . MAIN OUTCOME MEASURE Vali date d instruments measuring parenting stress , parenting behaviors , and mental health . RESULTS A total of 232 teenagers were successfully r and omized to home visitation and control groups . At baseline , the groups were comparable on demographic , social support , and mental health measures . Almost half the teenagers had poor mental health at baseline , and high rates persisted at follow-up in both groups . In multivariate models , the home visitation group demonstrated significantly better parenting behavior scores at follow-up than did the control group ( P = .01 ) but showed no differences in parenting stress or mental health . CONCLUSIONS The volunteer home visitation program significantly improved some parenting outcomes but not parental distress or poor mental health . Volunteers may be an effective means of providing parenting education , but interventions that include specific means of addressing poor mental health are likely to have greater effects PURPOSE To compare effects of an early intervention program ( EIP ) of intense home visitation by public health nurses ( PHNs ) with effects of traditional public health nursing care ( TPHN ) on infant health and selected maternal outcomes of adolescent mothers . METHODS EIP adolescents ( N = 102 ) received preparation-for-motherhood classes and individual home visits ( from pregnancy through 1 year postpartum ) from PHNs employed in a county health department . Participants were predominantly Latina ( 64 % ) and African-American ( 11 % ) and from impoverished background s. Infant health outcomes were determined based on medical record data ; interviews and st and ardized question naires evaluated other program effects ( e.g. , maternal educational achievement and psychological status ) . Data were analyzed using Chi-square and repeated measures ANOVA . RESULTS Infants of EIP mothers experienced significantly fewer total days ( n = 74 ) and actual episodes ( n = 14 ) of hospitalization during the first year of life than those receiving TPHN ( n = 154 , n = 24 , respectively ) . Similarly , positive program effects were found for immunization rates . There were no group differences in emergency room visits or repeat pregnancy rates . Alcohol , tobacco , and marijuana use significantly increased from pregnancy through 1 year postpartum in both groups but remained markedly lower than rates prior to pregnancy ( lifetime rates ) . CONCLUSIONS These findings demonstrate the positive effects of a PHN home visitation program on health outcomes for children of adolescent mothers . Days of infant hospitalization were substantially reduced and immunization rates increased during the first year of life for children of EIP mothers . Greater efforts need to be directed toward preventing repeat pregnancy and return to substance use following childbirth in at-risk adolescent mothers OBJECTIVE To assess the impact of a paraprofessional-delivered home-visiting intervention to promote child care knowledge , skills , and involvement among pregnant American Indian adolescents . DESIGN R and omized controlled trial comparing a family-strengthening intervention with a breastfeeding education program . SETTING One Apache and 3 Navajo communities . PARTICIPANTS Fifty-three pregnant American Indian adolescents were r and omly assigned to intervention ( n = 28 ) or control ( n = 25 ) groups . Follow-up data were available for 19 intervention and 22 control participants . Intervention Paraprofessionals delivered 41 prenatal and infant care lessons in participants ' homes from 28 weeks ' gestation to 6 months post partum . MAIN OUTCOME MEASURES Child care knowledge , skills , and involvement . RESULTS Mothers in the intervention compared with the control group had significantly higher parent knowledge scores at 2 months ( adjusted mean difference [ AMD ] , + 14.9 [ 95 % confidence interval ( CI ) , + 7.5 to + 22.4 ] ) and 6 months post partum ( AMD , + 15.3 [ 95 % CI , + 5.9 to + 24.7 ] ) . Intervention group mothers scored significantly higher on maternal involvement scales at 2 months post partum ( AMD , + 1.5 [ 95 % CI , -0.02 to + 3.02 ] ) , and scores approached significance at 6 months post partum ( AMD , + 1.1 [ 95 % CI , -0.06 to + 2.2 ] ) . No between-group differences were found for child care skills . CONCLUSIONS A paraprofessional-delivered , family-strengthening home-visiting program significantly increased mothers ' child care knowledge and involvement . A longer and larger trial is needed to underst and the intervention 's potential to improve adolescent parenting and related child outcomes in American Indian communities The prevalence of postnatal depression ( 10%-15 % ) renders it a major public health problem not only for the depressed mother but also for the infant , who may suffer from behavioral disturbances and cognitive delays in later years . This study aim ed at evaluating an educational intervention to alleviate postnatal depression and at generally measuring the prenatal and postnatal mood of primiparous women . A prospect i ve , r and omized controlled trial of an education intervention to reduce postnatal depression was conducted at three sites in Australia enrolling a total of 184 primiparous women . The intervention consisted of an information booklet on postnatal depression and an audiotape of one woman 's journey through clinical postnatal depression . Mood was assessed once prenatally ( 12 - 28 weeks ) and twice postnatally ( 8 - 12 weeks and 16 - 24 weeks ) using the Scale for Assessment of Depression and Schizophrenia modified for pregnant and postnatal women ( SADS-M ) . Demographic and social support data were also collected at enrollment . Comparisons between the control group and the intervention group revealed no differences ; the educational intervention did not show any effect when women 's mood was measured by the SADS-M. Overall , a general , significant , steady decrease of depressive tendencies was observed when the two postnatal assessment s were compared to the prenatal measurements . Women were less depressed postnatally than prenatally . This overall improvement of mood was significant in most SADS-M items . The exceptions were discouragement , anxiety , anger , and irritability , which did not reach significance . Additional multivariate analyses revealed no relevant influence of social support or demographic variables on the changes in mood . The main results that the education intervention had no effect and women , overall , were more depressed prenatally than postnatally contributes further evidence to the view that the prenatal period is a separate entity from the postnatal period , with distinctive psychoneuro-endocrine pathways and , thus , suggesting different profiles of women 's experience . This evidence indicates the necessity to screen , refer , and manage prenatal maternal mood as an entity in its own right , rather than as a window on the postnatal period PURPOSE Adolescent mothers are at risk for rapidly becoming pregnant again and for depression , school dropout , and poor parenting . We evaluated the impact of a community-based home-visiting program on these outcomes and on linking the adolescents with primary care . METHODS Pregnant adolescents aged 12 to 18 years , predominantly with low incomes and of African American race , were recruited from urban prenatal care sites and r and omly assigned to home visiting or usual care . Trained home visitors , recruited from local communities , were paired with each adolescent and provided services through the child ’s second birthday . They delivered a parenting curriculum , encouraged contraceptive use , connected the teen with primary care , and promoted school continuation . Research assistants collected data via structured interviews at baseline and at 1 and 2 years of follow-up using vali date d instruments to measure parenting ( Adult-Adolescent Parenting Inventory ) and depression ( Center for Epidemiologic Studies Depression ) . School status and repeat pregnancy were self-reported . We measured program impact over time with intention-to-treat analyses using generalized estimating equations ( GEE ) . RESULTS Of 122 eligible pregnant adolescents , 84 consented , completed baseline assessment s , and were r and omized to a home-visited group ( n = 44 ) or a control group ( n = 40 ) . Eighty-three percent completed year 1 or year 2 follow-up assessment s , or both . With GEE , controlling for baseline differences , follow-up parenting scores for home-visited teens were 5.5 points higher than those for control teens ( 95 % confidence interval , 0.5–10.4 points ; P = .03 ) and their adjusted odds of school continuation were 3.5 times greater ( 95 % confidence interval , 1.1–11.8 ; P < .05 ) . The program did not have any impact on repeat pregnancy , depression , or linkage with primary care . CONCLUSIONS This community-based home-visiting program improved adolescent mothers ’ parenting attitudes and school continuation , but it did not reduce their odds of repeat pregnancy or depression or achieve coordination with primary care . Coordinated care may require explicit mechanisms to promote communication between the community program and primary care Background Postpartum depression is a devastating condition that affects a significant number of women and their offspring . Few preventive interventions have targeted high risk youth , such as American Indians ( AIs ) . Objective To evaluate the feasibility of a depression prevention program for AI adolescents and young adults . Methods Expectant AI women ( mean age = 18.15 ; N = 47 ) were r and omized ( 1:1 ) to either the Living in Harmony program ( LIH , an 8 lesson cognitive-behaviorally based program ) or an Educational – Support program ( ES , an 8 lesson education program ) . Both interventions were delivered by AI paraprofessionals . Adolescents were evaluated during their pregnancy at baseline , at post-intervention , and at 4 , 12 , and 24 weeks postpartum . The primary outcome measure was the Center for Epidemiological Studies –Depression scale ( CES-D ) . Additional measures of depression included the onset of major depressive disorder ( MDD ; assessed via computerized diagnostic interview ) and the Edinburgh Postpartum Depression Scale ( EPDS ) . Secondary outcomes included changes in mothers ’ global functioning and social support . Results At all post intervention assessment s , mothers in both groups showed similar reductions in depressive symptoms and similar rates of MDD ( 0 and 6 % in LIH and ES respectively ) . Both groups of participants also showed similar improvements in global functioning . No changes in either group were found on the measure of social support . Conclusions Findings suggest that both paraprofessional-delivered interventions may reduce symptoms of depression among AIs . Replication with a larger sample , a usual care control condition , blinded evaluators , and a longer follow-up is needed OBJECTIVE The Affordable Care Act provides funding for home-visiting programs to reduce health care disparities , despite limited evidence that existing programs can overcome implementation and evaluation challenges with at-risk population s. The authors report 36-month outcomes of the paraprofessional-delivered Family Spirit home-visiting intervention for American Indian teen mothers and children . METHOD Expectant American Indian teens ( N=322 , mean age=18.1 years ) from four southwestern reservation communities were r and omly assigned to the Family Spirit intervention plus optimized st and ard care or optimized st and ard care alone . Maternal and child outcomes were evaluated at 28 and 36 weeks gestation and 2 , 6 , 12 , 18 , 24 , 30 , and 36 months postpartum . RESULTS At baseline the mothers had high rates of substance use ( > 84 % ) , depressive symptoms ( > 32 % ) , dropping out of school ( > 57 % ) , and residential instability ( 51 % ) . Study retention was ≥83 % . From pregnancy to 36 months postpartum , mothers in the intervention group had significantly greater parenting knowledge ( effect size=0.42 ) and parental locus of control ( effect size=0.17 ) , fewer depressive symptoms ( effect size=0.16 ) and externalizing problems ( effect size=0.14 ) , and lower past month use of marijuana ( odds ratio=0.65 ) and illegal drugs ( odds ratio=0.67 ) . Children in the intervention group had fewer externalizing ( effect size=0.23 ) , internalizing ( effect size=0.23 ) , and dysregulation ( effect size=0.27 ) problems . CONCLUSIONS The paraprofessional home-visiting intervention promoted effective parenting , reduced maternal risks , and improved child developmental outcomes in the U.S. population subgroup with the fewest re sources and highest behavioral health disparities . The methods and results can inform federal efforts to disseminate and sustain evidence -based home-visiting interventions in at-risk population Abstract Given the high co-occurrence of depression and parental stress among adolescent mothers , we evaluated the relationship between parental stress and postpartum depression among primiparous adolescent mothers . We conducted an observational analysis among a cohort of 106 adolescent mothers at 289 postpartum visits who were enrolled in a r and omized controlled trial to prevent postpartum depression . Parental stress was measured using the Parenting Stress Index , short form . The Structured Clinical Interview for DSM-IV Childhood Diagnoses was administered to assess for postpartum depression ; subthreshold depression was assessed using the Children ’s Depression Rating Scale , revised version . Generalized estimating equations were utilized to assess the relationship of parental stress on postpartum depression during the first 6 months postpartum . We present adjusted odds ratios ( AOR ) controlling for study arm , age , born in the United States , prior history of depression , and number of study visits . The median age was 16 years , 53 % were Latina , and 16 % reported a past history of depression . Nineteen adolescents ( 19 % ) were diagnosed with postpartum depression and 25 % experienced high levels of parental stress through 6 months postpartum . Adolescent mothers who reported higher levels of parental stress were at significantly increased risk for postpartum depression [ AOR 1.06 ( 95 % CI 1.04–1.09 ) ; p < 0.0001 ] . High levels of parental stress predicted subsequent postpartum depression when assessing parental stress at visits prior to a depression diagnosis to determine whether we could establish a temporal association [ AOR 1.06 ( 95 % CI 1.02–1.09 ) ; p < 0.01 ] . Parental stress was also a risk factor for subthreshold depression [ AOR 1.04 ( 95 % CI 1.01–1.07 ) ; p < 0.01 ] . Parental stress was a significant risk factor for developing both postpartum depression as well as subthreshold depression among adolescent mothers . Interventions that target a reduction in parental stress may lead to less depression severity among primiparous adolescent mothers OBJECTIVE Adolescent pregnancy is common and minority adolescents are at high risk . We sought the following : ( 1 ) to prospect ively assess prevalence of antenatal depression ( AND ) and postpartum depression ( PPD ) in minority adolescents and ( 2 ) to examine the association of social support and adjustment , trauma , and stress on depression status . STUDY DESIGN A total of 212 pregnant adolescents were recruited from public prenatal clinics and administered a prospect i ve research survey during pregnancy and 6 weeks ' postpartum . Depression was measured using the Edinburgh Postnatal Depression Scale . Univariate , bivariate , and multivariable analyses were performed using logistic regression to assess predictors of AND and PPD . RESULTS In our cohort , 20 % screened positive for AND and 10 % for PPD . The strongest predictor of PPD was AND ( odds ratio [ OR ] , 4.89 ; P < .001 ) . Among adolescents with trauma history , there was a 5-fold increase ( OR , 5.01 ) in the odds of AND and a 4-fold increase ( OR , 3.76 ) in the odds of PPD . AND was associated with the adolescent 's poor social adjustment ( P < .001 ) , perceived maternal stress ( P < .001 ) , less social support ( P < .001 ) , and a less positive view of pregnancy ( P < .001 ) . PPD was significantly associated with primiparity ( P = .002 ) , poor social adjustment ( P < .001 ) , less social support and involvement of the baby 's father ( P < .001 ) , and less positive view of pregnancy ( P < .001 ) . CONCLUSION Significant independent risk factors for PPD include AND , view of pregnancy , and social support . Trauma history was highly prevalent and strongly predicted AND and PPD . Point prevalence decreased postpartum , and this may be due to transient increased social support following the birth , warranting longer follow-up and development of appropriate interventions in future work Thirty-two depressed adolescent mothers received ten 30-minute sessions of massage therapy or relaxation therapy over a five-week period . Subjects were r and omly assigned to each group . Although both groups reported lower anxiety following their first and last therapy sessions , only the massage therapy group showed behavioral and stress hormone changes including a decrease in anxious behavior , pulse , and salivary cortisol levels . A decrease in urine cortisol levels suggested lower stress following the five-week period for the massage therapy group The difficulties that adolescent mothers encounter as a result of the combined stress of adolescence , parenthood , maintaining peer relationships , and establishing positive relationships with their infants have been identified in the literature , and these characteristics are often associated with poor infant outcomes . This study was design ed to examine the effects of an infant massage intervention on adolescent mothers ' attitudes and perceptions of their infants . Twenty-five African-American adolescent mothers ( mean age 16.13 years ) , who were enrolled in a parent training program for high school students in a southern state , participated in the project . The mothers were assigned r and omly to an intervention ( 9 ) or control group ( 16 ) . After a brief training session , participants in the intervention group practice d massage with their infants for approximately 2 months . Data analysis was based on the 15 participants who completed both baseline and 2-month follow-up measures ( 8 in the control group and 7 in the intervention group ) . This study found some support for teaching infant massage to adolescent mothers as a way of enhancing maternal-infant physical contact and lowering depression , as well as positively influencing mothers ' perceptions of infant temperament . Results indicate that infant massage training may lead to improvements beyond those achieved with a typical parent education curriculum and shows potential as a low-cost supplement to current teen mother education in high schools BACKGROUND Adolescent pregnancy and parenting remain a major public concern because of their impact on maternal-child health and on the social and economic well-being of the nation . Federal welfare reform legislation has created an urgent need for community-based nursing intervention programs to improve health and social outcomes for disadvantaged adolescent mothers and to promote their self-sufficiency . OBJECTIVE To evaluate the effects of an early intervention program ( EIP ) that uses a public health nursing model on health and social outcomes of adolescent mothers and their children and on the quality of mother-child interaction . METHODS Pregnant adolescents referred to a county health department were r and omly assigned to an experimental ( EIP ) or control ( traditional public health nursing [ TPHN ] ) group . The sample included 121 adolescents from predominantly minority and impoverished background s who were followed from pregnancy through 6 weeks postpartum . Intense and comprehensive home visitation by public health nurses and preparation-for-motherhood classes were provided to adolescents in the EIP . Health outcomes were determined on the basis of medical record data . Other measures included maternal self-report on selected behaviors , nurse interviews , and the Nursing Child Assessment Teaching Scale ( NCATS ) . RESULTS Early findings indicate reduced premature birth and low-birth-weight ( LBW ) rates for young mothers receiving both forms of public health nursing care . No significant differences between groups were found for infant birth weight or type of delivery . Infants in the EIP had significantly fewer total days of birth-related hospitalization and rehospitalization than those in the TPHN group during the first 6 weeks of life ( chi2(1 ) = 6.41 ; p = 0.01 ) . Adolescents in the EIP demonstrated significantly more positive educational outcomes ( e.g. , lower school dropout rates ) than those in the TPHN group ( chi2(1 ) = 6.76 ; p < 0.009 ) . CONCLUSIONS The early findings of this study demonstrate that pregnant adolescents benefit from both traditional and more intense public health nursing care in terms of prenatal and perinatal outcomes . The EIP was associated with decreased infant morbidity during the first 6 weeks of life and decreased maternal school dropout . Long-term outcomes for the EIP are being evaluated PROBLEM Little is known about the rates , correlates , and consequences of depression among a sample of first-time mothers . METHODS Four-site prospect i ve study of the first 3 years of life among first children born to first-time mothers , including adolescent ( N= 396 ) , lower- ( N= 169 ) , and higher-re source adult ( N= 117 ) . Mothers were administered the Beck Depression Inventory prenatally and 6 months postpartum . Measures of maternal and infant behaviors were taken at 8 months . FINDINGS Adolescent mothers displayed higher prenatal and 6-month rates of depression than lower- and higher-re source adult mothers , with significantly more adolescent mothers " consistently " depressed at the two time points than lower- and higher-re source adult mothers . Further , adolescent mothers were significantly more likely to become depressed after their babies were born than lower- or higher-re source adult mothers . Depression was negatively related to parenting practice s and babies ' behavior . As depression increased , mothers scored less favorably in maternal warmth and sensitivity , contingent responsiveness , and general verbalness ; children scored less favorably in warmth seeking toward their mothers . CONCLUSION Findings signify the need for counseling and nurse-based intervention and prevention services geared at preparing pregnant adolescents for motherhood OBJECTIVE The purpose of the study was to determine the effectiveness of a social support intervention delivered to pregnant adolescent girls between 32 and 36 weeks of gestation in preventing symptoms of depression at 6 weeks postpartum . DESIGN The study used a repeated measures design . SETTING Data were collected at a teenage parenting program , an educational option of the public school system . PARTICIPANTS Participants ( n = 128 ) were pregnant and postpartum adolescents . MAIN OUTCOME MEASURE Symptoms of depression at 6 weeks postpartum . INTERVENTION Participants completed the Postpartum Support Question naire , Rosenberg 's Self-Esteem instrument , and the Center for Epidemiological Studies of Depression instrument at baseline , then were r and omly assigned to one of three intervention groups ( pamphlet , video , or pamphlet plus video ) or the control group . The content of the intervention was based on a synthesis of the literature describing social support needed and desired by postpartum adolescents . RESULTS No significant differences were found in Center for Epidemiological Studies of Depression instrument scores among the groups at 6 weeks postpartum . Using path analysis , the authors found that predictors of symptoms of depression at 6 weeks postpartum were ( a ) receiving more support from friends , family , and others and ( b ) having low self-esteem . CONCLUSION These findings differ from earlier studies , and both research and clinical implication s are discussed BACKGROUND Postnatal depression can have long term adverse consequences for the mother-infant relationship and the infant 's development . Improving a mother 's depression per se has been found to have little impact on mother-infant interaction . The aims of this study were to determine whether attending regular massage classes could reduce maternal depression and also improve the quality of mother-infant interaction . METHOD Thirty-four primiparous depressed mothers , median 9 weeks postpartum , identified as being depressed following completion of the Edinburgh Postnatal Depression Scale ( EPDS ) at 4 weeks postpartum , were r and omly allocated either to an infant massage class and a support group ( massage group ) or to a support group ( control group ) . Each group attended for five weekly sessions . Changes in maternal depression and mother-infant interaction were assessed at the beginning and the end of the study by comparing EPDS scores and ratings of videotaped mother-infant interaction . RESULTS The EPDS scores fell in both groups . Significant improvement of mother-infant interaction was seen only in the massage group . LIMITATION The sample size was small and had relatively high dropout . It was not possible to distinguish which aspects of the infant massage class contributed to the benefit . CONCLUSION This study suggests that learning the practice of infant massage by mothers is an effective treatment for facilitating mother-infant interaction in mothers with postnatal depression OBJECTIVE The purpose of this study was to estimate the effect of an interpersonally oriented intervention on the reduction of the risk of postpartum depression in primiparous adolescents . STUDY DESIGN We conducted a r and omized controlled trial of 106 pregnant primiparous adolescents who were ≤17 years old at their first prenatal visit . Participants were assigned r and omly to the intervention program ( n = 54 ) or the attention and dose-matched control program ( n = 52 ) . Each program included 5 sessions that were delivered during the prenatal period . A structured diagnostic interview was administered to assess for the primary outcome and depression at 6 weeks , 3 months , and 6 months after delivery . RESULTS Participants included Hispanic ( 53 % ) , non-Hispanic black ( 17 % ) , and non-Hispanic white ( 16 % ) adolescents . The overall rate of depression in the intervention group ( 12.5 % ) was lower than the control group ( 25 % ) with a hazard rate ratio of 0.44 ( 95 % confidence interval , 0.17 - 1.15 ) at 6 months after delivery . CONCLUSION An intervention that is delivered during the prenatal period has the potential to reduce the risk for postpartum depression in primiparous adolescent mothers PURPOSE To examine race/ethnic differences in depressive symptoms among adolescent mothers during the first four years postpartum . METHODS A prospect i ve study of 623 adolescent mothers , 18 years or younger followed four years after delivery . Depressive symptoms were measured using the Beck Depression Inventory ( BDI ) . These analyses focused on data collected at 3 , 12 , 24 and 48 months postpartum . RESULTS Overall , 57 % of the sample reported moderate to severe depressive ( MSD ) symptoms during the four-year period . The steepest increase in the percent reporting new MSD symptoms occurred during the first 12 months after delivery . The prevalence of MSD symptoms was highest at three months ( 36.7 % ) and steadily declined through 48 months ( 21.1 % ) for all race/ethnic groups with one exception : a slightly higher percentage of African-Americans reported MSD symptoms at 48 ( 20.0 % ) than at 24 months ( 16.9 % ) . Logistic regression analysis used to calculate the relative odds of experiencing MSD symptoms revealed higher odds of depressive symptoms for Caucasians ( adjusted odds ratio [ AOR ] 2.0 ; 95 % confidence interval [ CI ] 1.2 - 3.4 ) at three months , and for Mexican-Americans at both 12 ( AOR 2.6 ; 95 % CI 1.4 - 4.8 ) and 24 ( AOR 2.2 ; 95 % CI 1.1 - 4.4 ) months . MSD symptoms at three months were significantly related to MSD symptoms at 48 months for all race/ethnic groups ( p < .001 ) . CONCLUSIONS More than 50 % of adolescent mothers experience MSD symptoms during the first postpartum year . As a group , African-American adolescent mothers appear to have the lowest rates of MSD symptoms , but higher rates of recurrence , when compared with Mexican-Americans and Caucasians OBJECTIVE The authors sought to examine the effectiveness of Family Spirit , a paraprofessional-delivered , home-visiting pregnancy and early childhood intervention , in improving American Indian teen mothers ’ parenting outcomes and mothers ’ and children ’s emotional and behavioral functioning 12 months postpartum . METHOD Pregnant American Indian teens(N=322 ) from four southwestern tribal reservation communities were r and omlyassigned in equal numbers to the Family Spirit intervention plus optimized st and ard care or to optimized st and ard care alone . Parent and child emotional and behavioral outcome data were collected at baseline and at 2 , 6 , and 12 months postpartum using self-reports , interviews , and observational measures . RESULTS At 12 months postpartum , mothers in the intervention group had significantly greater parenting knowledge parenting self-efficacy , and home safety attitudes and fewer externalizing behaviors , and their children had fewer externalizing problems . In a sub sample of mothers with any lifetime substance use at baseline ( N=285 ; 88.5 % ) , children in the intervention group had fewer externalizing and dysregulation problems than those in the st and ard care group , and fewer scored in the clinical ly “ at risk ” range ( $ 10th percentile ) for externalizing and internalizing problems . No between-group differences were observed for outcomes measured by the Home Observation for Measurement of the Environment scale . CONCLUSIONS Outcomes 12 months postpartum suggest that the Family Spirit intervention improves parenting and infant outcomes that predict lower lifetime behavioral and drug use risk for participating teen mothers and children Few interventions have succeeded in reducing psychosocial risk among pregnant women . The objective of this study was to determine whether an integrated group prenatal care intervention already shown to improve perinatal and sexual risk outcomes can also improve psychosocial outcomes compared to st and ard individual care . This r and omised controlled trial included pregnant women ages 14–25 from two public hospitals ( N = 1047 ) who were r and omly assigned to st and ard individual care , group prenatal care or integrated group prenatal care intervention ( CenteringPregnancy Plus , CP+ ) . Timing and content of visits followed obstetrical guidelines , from 18-week gestation through birth . Each 2-h group prenatal care session included physical assessment , education/skills building and support via facilitated discussion . Using intention-to-treat models , there were no significant differences in psychosocial function ; yet , women in the top tertile of psychosocial stress at study entry did benefit from integrated group care . High-stress women r and omly assigned to CP+ reported significantly increased self-esteem , decreased stress and social conflict in the third trimester of pregnancy ; social conflict and depression were significantly lower 1-year postpartum ( all p-values < 0.02 ) . CP+ improved psychosocial outcomes for high-stress women . This ‘ bundled ’ intervention has promise for improving psychosocial outcomes , especially for young pregnant women who are traditionally more vulnerable and underserved |
12,520 | 30,133,690 | AUTHORS ' CONCLUSIONS Glucocorticoids reduced symptoms of croup at two hours , shortened hospital stays , and reduced the rate of return visits to care .
Our conclusions have changed , as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours | BACKGROUND Glucocorticoids are commonly used for croup in children .
This is an up date of a Cochrane Review published in 1999 and previously up date d in 2004 and 2011 .
OBJECTIVES To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years . | OBJECTIVE To determine whether dexamethasone prevents postextubation airway obstruction in young children . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Pediatric intensive care unit of a university teaching hospital . PATIENTS Sixty-six children , < 5 yrs of age , intubated and mechanically ventilated for > 48 hrs . INTERVENTIONS Patients were r and omized to receive intravenous dexamethasone ( 0.5 mg/kg , maximum dose 10 mg ) or saline , every 6 hrs for six doses , beginning 6 to 12 hrs before elective extubation . MEASUREMENTS AND MAIN RESULTS Dependent variables included the presence of stridor , Croup Score , and pulsus paradoxus at 10 mins , 6 , 12 , and 24 hrs after extubation ; need for aerosolized racemic epinephrine and reintubation . The dexamethasone and placebo groups were similar in age ( median 3 months [ range 1 to 57 ] vs. 4 months [ range 1 to 59 ] , p = .6 ) , frequency of underlying airway anomalies ( 3/33 vs. 3/33 , p = 1.0 ) , and duration of mechanical ventilation ( median 3.3 days [ range 2.1 to 39 ] vs. 3.5 days [ range 2.1 to 15 ] , p = .7 ) . The dexamethasone group had a lower frequency of stridor , Croup Score , and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation . Fewer dexamethasone-treated patients required epinephrine aerosol ( 4/31 vs. 22/32 , p < .0001 ) and reintubation ( 0/31 vs. 7/32 , p < .01 ) . Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension . CONCLUSION Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children STUDY OBJECTIVE To identify patients with croup who after treatment with nebulized racemic epinephrine , oral dexamethasone , and mist may be safely discharged home after a period of observation . DESIGN Prospect i ve interventional . SETTING Urban children 's hospital emergency department . PARTICIPANTS Children with croup who received racemic epinephrine for the treatment of stridor at rest . INTERVENTIONS After treatment with .5 mL racemic epinephrine , .6 mg/kg dexamethasone PO , and mist , patients who were assessed as being safe for discharge after 3 hours of observation were discharged home and contacted for 48-hour follow-up . RESULTS Fifty-five patients with croup were treated with racemic epinephrine . Thirty patients ( 55 % ) had sustained responses and were discharged home after 3 hours of observation . No recurrence of respiratory distress and no return visits for medical care were reported ( 95 % confidence interval , 0 % to 8.0 % ) . CONCLUSION Patients with croup who are treated with racemic epinephrine , oral dexamethasone , and mist may be safely discharged home if the patient is assessed as ready for discharge after 3 hours of observation BACKGROUND Although previous studies have shown that dexamethasone is useful in croup , the optimal dosage has not been clarified yet . The aim of this study was to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared with the recommended dose of 0.6 mg/kg for treatment of hospitalized children with moderate to severe croup . METHOD Forty-one children aged 6 months to 5 years admitted from March 2001 to October 2003 at the pediatric ward of Hatyai Hospital with moderate to severe croup were recruited for the study . After r and om allocation , each child received a single intravenous injection of either dexamethasone 0.6 mg/kg ( maximum dose 12 mg ) or 0.15 mg/kg ( maximum dose 3 mg ) . All children were given a single dose of epinephrine nebulization at the beginning of the study . The croup scores were measured at 0 , 1 , 2 , 3 , 4 , 6 , 8 , 10 and 12 h after the dexamethasone injection . RESULTS One hour following the injection , the mean croup scores were significantly reduced from baseline values in both groups ( p<0.01 ) . There was no difference in the mean croup scores between the two groups at any time . Median times to croup scores equal or less than two in both high- and low-dose groups were 8 and 7.9 h , respectively . No patient required intubation or was removed from the study because of a rising croup score after enrollment . There was no significant adverse reaction from dexamethasone treatment in either group . CONCLUSION Dexamethasone 0.15 and 0.6 mg/kg are equally effective in the treatment of moderate to severe croup Abstract Objective : To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital . Design : Double blind , r and omised , placebo controlled clinical trial . Setting : The emergency department of a tertiary paediatric hospital . Subjects : 100 children aged 4 - 122 months presenting with mild croup . Intervention : A single oral dose of dexamethasone 0.15 mg/kg or placebo . Main outcome measure : Return to medical care with ongoing croup . Results : Baseline characteristics of the two treatment groups were similar . Eight children ( all from the placebo group ) returned to medical care with ongoing croup , one being admitted . There was no reported difference in duration of croup symptoms , duration of viral symptoms , or rate of return to medical care for other reasons . Conclusion : Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup . Key messages The benefits of steroids for children admitted to hospital are now well estab- lished Most children with croup may be sent home , though up to one fifth may return with croup A small single dose of oral dexamethasone ( 0.15 mg/kg ) dramatically reduces the chance of reattending All children presenting with croup should be considered for The objective of this study was to compare the efficacy of a single dose of oral dexamethasone of varying sizes in 120 children hospitalized with croup in two sequential double blind , r and omized , controlled clinical trials ( Trials A and B ) . The study was conducted in the Emergency Department Observation Ward of a tertiary pediatric hospital . One hundred and twenty children ( age range 6 to 160 months ) hospitalized with croup participated . Baseline characteristics for the two groups in each trial were similar . In Trial A 60 children received either 0.6 or 0.3 mg/kg dexamethasone syrup ; in Trial B 60 children received either 0.3 or 0.15 mg/ kg dexamethasone syrup . Duration of hospitalization , reduction in croup scores , and adrenaline usage were evaluated . Median duration of hospitalization was similar for children in Trial A ( 7 and 8 hr ) , and in Trial B ( 9 and 9 hr ) . Croup scores following treatment did not differ and were significantly lower than initial scores for all groups and in each trial . Other outcome measures were similar for the two groups in each trial , including need for nebulized adrenaline , numbers of patients admitted to intensive care , rate of return to medical care with reoccurrence of croup , and readmission to hospital with croup following discharge from hospital . We conclude that oral dexamethasone in a dose of 0.15 mg/kg is as effective as 0.3 or 0.6 mg/kg in relieving symptoms and results in a similar duration of hospitalization in children with croup AIMS Croup is a clinical syndrome which included inspiratory stridor , coughing with a dog-like sound , noise obstruction and respiratory distress symptoms . This present study was conducted to compare the effects of cold drink and dexamethasone , and the effects of their co-administration on children 's croup . MATERIAL S AND METHODS In this study , all patients with croup admitted to the emergency ward of Madani Hospital Khorramabad were divided through the simple r and omized method into 3 groups after informed consents were taken from their parents . The first group was given cold drink , second group with dexamethasone ( DM ) , and the third group were given the combined treatment simultaneously . The patients in the first and second groups who did not show signs of improvement received the simultaneous treatment similar to the third group . The data were analyzed using the SPSS software through descriptive statistics and inferential statistics including multi-field variance analysis and co-variance analysis . RESULT The results of the study indicated a statistically significant between the 3 group in terms of improvement time-scale of croup clinical symptoms ( P=0.001 ) . There was no significant difference observed between the effects of other variables on improvement time-scale of croup clinical symptoms . CONCLUSION The cold drink has less treating effect than DM and combined simultaneous treatment method . Also , DM had more influence than simultaneous treatment method . In addition , other variables including age , sex , birth weight , BMI , respiratory allergy and previous croup history did not influenced improvement time-scale and only type of intervention influenced improvement time-scale of croup clinical symptoms Objective : To evaluate the effect of adding inhaled budesonide ( 2 mg ) to oral dexamethasone 0.15 mg/kg in children hospitalized with croup . Setting : Observation ward of a Tertiary Paediatric Hospital Emergency Department . Subjects : Seventy-two children ( age range 3 to 126 months ) hospitalized with croup . Intervention : Children r and omized to receive either 2 mg of nebulized budesonide or placebo , with all children receiving a single oral dose of 0.15 mg/kg dexamethasone . Outcome measures : Primary outcome was duration of hospital stay . Other measures included croup scores from 0 to 12 hours , use of nebulized epinephrine , duration of croup symptoms , duration of viral symptoms , and return to medical care for croup or for any other reason following discharge from hospital . Results : Baseline characteristics for the 2 groups were similar . There was no difference in time to discharge for the 2 groups or for other outcome measures with a risk ratio of 1.3 ( 95 % confidence intervals of 0.82 and 2.1 ) . Conclusions : The addition of inhaled budesonide ( 2 mg ) to oral dexamethasone ( 0.15 mg/kg ) offers no advantage in the treatment of children hospitalized with croup OBJECTIVE To investigate the efficacy and tolerance of 12-hourly dosing with 2 mg 4 mL-1 of inhaled budesonide versus placebo in patients admitted to hospital with moderate/severe croup . METHOD Eighty-two children hospitalised with croup received either 2 mg 4 mL-1 of budesonide or placebo 12 hourly ( maximum four doses ) via Ventstream nebuliser in a r and omised , double-blind manner . Croup scores were performed at 0 , 2 , 6 , 12 , 24 , 36 and 48 h from initial nebulisation whilst the patient remained hospitalised . Follow-up assessment s were made 1 and 3 days after discharge . RESULTS Improvement was observed in the budesonide group over the 12-h dosing interval when compared to placebo ( P = 0.04 ) . Time to attain a significant clinical improvement was superior in the budesonide group ( P = 0.01 ) . Three days after discharge seven of 32 placebo-treated patients and one of 34 budesonide-treated patients had sought further medical follow-up ( P = 0.02 ) . CONCLUSION Twelve-hourly dosing with inhaled budesonide significantly improved symptoms of croup as well as decreased relapse rates when compared with placebo OBJECTIVES Croup or acute laryngotracheobronchitis is the most common cause of the upper airway obstruction . Cool mist , nebulized racemic epinephrine and steroids are commonly used for therapy . Although steroid treatment can be applied orally , in nebulized form , or parenterally , no study has compared these three regimens yet . In this study , the efficacy of nebulized budesonide , and oral and intramuscular dexamethasone are compared for treatment of croup . STUDY DESIGN Sixty children aged 6 - 36 months were r and omly allocated into four groups . The first three study groups ( 15 children in each ) took nebulized budesonide , oral dexamethasone and intramuscular dexamethasone , respectively , in addition to salbutamol and other supportive measures and these were compared with the placebo group . All patients were evaluated with " Westley Croup Score " on admission to pediatric emergency department ( 0h ) and at 24 , 48 and 72h . RESULTS At the end of the study , the croup scores of all steroid treatment groups were significantly lower than the placebo group , but there was no statistical difference among them . CONCLUSIONS Nebulized budesonide , oral and parenteral dexamethasone have the same effectiveness for treatment of croup and the choice depends on conditions of the patient and the physician ABSTRACT . Seventy‐two children hospitalized for croup received on admission a single dose of either 0.6 mg/kg dexamethasone or an equivalent placebo intramuscularly from r and omized ampules ; subsequently the same patients were r and omized to receive either nebulized racemic epinephrine or saline by intermittent positive pressure breathing . Of the four treatment groups those receiving a placebo injection and nebulized saline had the slowest recovery by all criteria . Dexamethasone and nebulized epinephrine reduced the symptoms and hastened recovery , but dexamethasone was more effective by clinical evaluation at 6 and 12 hours post admission . The patients given dexamethasone had a significantly shorter hospital stay than those receiving placebo . We conclude that a single injection of a potent corticosteroid is beneficial in acute spasmodic croup . Nebulized racemic epinephrine given with an appropriate device is also effective , but the effect of epinephrine is less remarkable in patients treated with dexamethasone This prospect i ve cohort study evaluated the effectiveness and safety of a selective discharge policy for patients treated with racemic epinephrine ( RE ) and intramuscular ( IM ) dexamethasone ( DEX ) in the emergency department ( ED ) . Children younger than 13 years of age presenting to the ED with croup who were treated with RE and IM DEX and discharged home were enrolled in the study . Patients were discharged home if they were free of intercostal retractions and stridor at rest , following a 2 h observation period . Telephone follow up determined whether further medical attention for croup was required within 48 h of discharge from the ED . Eighty-two patients were enrolled in the study over a one year period . Six of these patients ( 7 % ) required follow up for croup within 48 h of discharge and 2 ( 2 % ) required admission . We conclude that a subset of patients with croup treated with RE and IM DEX in the ED can be safely discharged home Aerosolized racemic epinephrine , but not L-epinephrine , is commonly used in treating croup . The efficacy and adverse effects of nebulized racemic and L-epinephrine in the treatment of laryngotracheitis were compared . Children 6 months to 6 years of age with a croup score of 6 or above were assigned in a r and omized double-blind fashion to receive either racemic ( n = 16 ) or L-epinephrine ( n = 15 ) aerosols . Croup score , heart rate , blood pressure , respiratory rate , fraction of inspired oxygen , and oxygen saturation were recorded before treatment and at 5 , 15 , 30 , 60 , 90 , and 120 minutes after the aerosol . Patients in both groups showed significant transient reduction of the croup score and respiratory rate following the aerosol ( P less than .001 ) , but there were no differences between treatment groups when croup score , heart rate , blood pressure , and respiratory rate were assessed over time . It is concluded that L-epinephrine is at least as effective as racemic epinephrine in the treatment of laryngotracheitis and does not carry the risk of additional adverse effects . L-Epinephrine is also more readily available worldwide , is less expensive , and can be recommended for this purpose Many studies have attempted to find out whether steroid treatment is beneficial in children with croup , but the results have been inconclusive . We have done a prospect i ve placebo-controlled study of the effect of prednisolone on two clinical endpoints -- the duration of intubation and the need for reintubation . Reasons for exclusion were age under 6 months , congenital airway anomalies , and previous intubation . 70 eligible children were r and omly assigned treatment with prednisolone 1 mg/kg ( n = 38 ) or placebo ( n = 32 ) every 12 h given by nasogastric tube until 24 h after extubation . 11 ( 34 % ) placebo-treated and only 2 ( 5 % ) prednisolone-treated patients required reintubation after accidental or elective extubation ( p = 0.004 , Fisher 's exact test ; odds ratio 8.9 , 95 % confidence interval 1.7 - 59.3 ) . Survival analysis with log-normal regression showed that the duration of intubation was shorter with steroid therapy ( p less than 0.003 ) and increasing age ( p less than 0.02 ) , but was not influenced by endotracheal tube size or abnormality on chest radiograph . The median duration of intubation was 138 ( 95 % CI 118 - 160 ) h in children who received placebo and 98 ( 85 - 113 ) h in the prednisolone group . Steroid therapy reduces the duration of intubation and the need for reintubation in children intubated for croup 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 . Although common practice , evidence to support treatment of croup with prednisolone is scant . Methods . We conducted a community-based r and omized trial to compare the effectiveness of prednisolone ( 2 mg/kg/d for 3 days , n = 41 ) versus 1 dose of dexamethasone ( 0.6 mg/kg ) and 2 doses of placebo ( n = 46 ) . Participants were children 1 to 8 years old with croup symptoms ≤48 hours , categorized as mild ( 42 % ) or moderate ( 58 % ) . Results . There were no differences for those treated with dexamethasone or prednisolone for additional health care for croup ( 2 % vs 7 % , P = .34 ) , duration of croup symptoms ( 2.8 vs 2.2 days , P = .63 ) , nonbarky cough ( 6.1 vs 5.9 days , P = .81 ) , nights with disturbed sleep for the parent ( 0.68 vs 1.21 nights , P = .55 ) , and days with stress ( 1.39 vs 1.56 days , P = .51 ) . Conclusion . There were no detected differences in outcomes between the 2 croup treatments for either child or parent The aim of this prospect i ve , r and omised , double blind study was to evaluate whether nebulised local steroid treatment is effective in the treatment of croup . Thirty six infants and children ( 0.4 - 4.9 years of age ) admitted to hospital with moderate to severe croup were allocated to receive either 2 mg nebulised budesonide ( 20 children ) or saline ( 16 children ) . Disease severity was assessed by a clinical total croup score based on stridor , cough , retractions , dyspnoea , and cyanosis . In addition the overall clinical impression was evaluated ( 0 - 100 ) . Two hours after treatment there was a significant improvement in the total croup score in the group treated with budesonide ( 8 to 4.5 ) , but not in the group treated with saline ( 8 to 8) . Furthermore , the overall clinical impression assessment score decreased significantly ( 50 to 25 ) in the group treated with budesonide , whereas it remained constant in the placebo group ( 60 to 62 ) . The total croup score and overall clinical severity were significantly better in the group treated with budesonide than in the placebo group . No side effects were observed . The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children and infants with moderate to severe croup In a r and omized , controlled investigation , 349 children with pseudo-croup stage I or II were given 6 mg of dexamethasone or placebo . Although the rate of recovery was similar in both groups , there was a significant difference when only the more seriously affected children were considered : steroid treated patients recovered quicker . Steroids appear to be useful in the routine treatment of simple , uncomplicated pseudo-croup , even if their effect apparently is not very impressive . Thus , close supervision remains the most important measure in this nearly always benign but potentially dangerous condition Objectives Dexamethasone is associated with adrenal insufficiency in adults and children with chronic disease . This association has not been studied after single-dose oral dexamethasone , the st and ard of care for children with croup . We hypothesized that single-dose oral dexamethasone in children with croup is associated with a transient decrease in endogenous glucocorticoids . Methods We conducted a prospect i ve , 2-arm , pharmacodynamic study of single-dose oral dexamethasone 0.6 mg/kg ( maximum , 12 mg ) in children older than 2 years with croup compared with controls ( children with febrile upper respiratory tract infections who did not receive dexamethasone ) . Primary outcome was urinary 6β-hydroxycortisol – cortisol ratio . Results Twenty-seven children were analyzed ( 22 with croup and 5 with upper respiratory tract infections ) . Median 6β-hydroxycortisol – cortisol ratios before dexamethasone , the following morning , and on days 1 , 3 , and 7 were 2.8 , 2.2 , 2.0 , 2.8 , and 2.6 , respectively . Among controls , the median 6β-hydroxycortisol – cortisol ratios at the same time intervals was 1.9 , 1.5 , 1.8 , 2.5 , and 1.7 , respectively . There were no significant differences in the change from time 0 between groups at any time point . There were no serious adverse events or infectious complications . Conclusions Single-dose oral dexamethasone is not associated with decreased endogenous corticosteroid levels in children with croup . Future studies should use criterion st and ard tests to rule out suppression of the hypothalamic-pituitary-adrenal axis and be powered sufficiently to identify adverse clinical outcomes BACKGROUND The benefits of dexamethasone treatment for moderate-to-severe croup are well established . However , most children with croup have mild symptoms , and it is unknown whether they would derive the same degree of benefit from dexamethasone treatment as children with more severe disease . METHODS We conducted a double-blind trial at four pediatric emergency departments in which 720 children with mild croup were r and omly assigned to receive one oral dose of either dexamethasone ( 0.6 mg per kilogram of body weight ) or placebo . The children had mild croup , as defined by a score of < or = 2 on the croup scoring system of Westley et al. The primary outcome was a return to a medical care provider for croup within seven days after treatment . The secondary outcome was the presence of ongoing symptoms of croup on days 1 , 2 , and 3 after treatment . Other outcomes included economic costs , hours of sleep lost by the child , and stress on the part of the parent in relation to the child 's illness . RESULTS Baseline clinical characteristics were similar in the two groups . Return to medical care was significantly lower in the dexamethasone group ( 7.3 percent vs. 15.3 percent , P<0.001 ) . In the dexamethasone group , there was quicker resolution of croup symptoms ( P=0.003 ) , less lost sleep ( P<0.001 ) , and less stress on the part of the parent ( P<0.001 ) . CONCLUSIONS For children with mild croup , dexamethasone is an effective treatment that results in consistent and small but important clinical and economic benefits . Although the long-term effects of this treatment are not known , our data support the use of dexamethasone in most , if not all , children with croup We compared the efficacy of high-dose dexamethasone sodium phosphate ( 0.6 mg/kg ) in laryngotracheitis ( LT ) v spasmodic croup ( SC ) in 72 children ( age range , 8 months to 8 years ) using a double-blind r and omized protocol that measured the individual change in respirations as an objective variable to evaluate the outcome . Administration of dexamethasone did not change the respirations in the patients with LT and significantly decreased the respirations in the patients with SC , compared with the placebo group . Since , in most cases , the pediatrician will be able to differentiate between LT and SC at admission by history and clinical signs , it seems that steroid treatment should be avoided in cases of LT and may be of benefit in some cases of SC This study aims to determine whether a sub population of children with croup , given mist and dexamethasone , can be treated with nebulized racemic epinephrine and safely discharged after observation in the emergency department . A prospect i ve study was design ed , enrolling children aged three months to six years with a clinical diagnosis of croup . Croup scores were assigned on arrival , after 30 minutes of saline mist , and 30 , 120 , and 240 minutes after nebulized racemic epinephrine . All children received mist ; those with a croup score > 3 after mist were given nebulized racemic epinephrine . All patients received intramuscular dexamethasone . Patients were discharged if they were significantly improved after four hours of observation . Phone follow-up occurred 24 to 48 hours after discharge . Sixty children received racemic epinephrine for croup . The median croup score on arrival was 5 , and there was no difference in arrival croup score by disposition . The two-hour croup score was significantly higher for admitted patients ( P < 0.05 by the Mann-Whitney U test ) . Forty children ( 66 % ) were discharged after nebulized racemic epinephrine and four hours of observation . No patients returned to the emergency department within 24 hours for further treatment . Two patients could not be contacted . The 95 % confidence interval for 0/38 patients with a negative outcome is ( 0–9.3 % ) . We conclude that children with croup treated with dexamethasone and mist , receiving one nebulized racemic epinephrine treatment , can be discharged after a four-hour period of observation if they appear clinical ly well to an experienced physician , and if close follow-up can be established It was the objective of this study to compare the efficacy of oral dexamethasone and inhaled budesonide in children hospitalized with croup , using a three-way , double blind , r and omized , placebo-controlled clinical trial design . The trial was carried out in the Emergency Department Observation Ward of a tertiary pediatric hospital . The subjects for the study were 80 children ( age range 5 to 158 months ) who were hospitalized with croup . Children received either 2 mg of nebulised budesonide , dexamethasone syrup ( 0.6 mg/kg ) or a placebo . Median duration of hospitalization was shorter for children treated with dexamethasone ( 12 hr ) and budesonide ( 13 hr ) compared to placebo ( 20 hr ) ( P < 0.03 ) . There was no significant difference in hospitalization time between children treated with dexamethasone and budesonide . Median time to a croup score of < or = 1 was shorter for children treated with dexamethasone ( 2 hr ) or budesonide ( 3 hr ) compared to those who received placebo ( 8 hr ) ( P < 0.01 ) . Croup scores for both steroid groups were significantly lower than the placebo group by 1 hr and remained so subsequently . The croup scores did not differ significantly in the 2 steroid treated groups . Six of the 30 children ( 20 % ) in the placebo group required adrenaline after the first hour compared to none of the 50 children in the steroid treated groups ( P < 0.02 ) . We conclude that oral dexamethasone and inhaled budesonide are both effective in reducing symptoms and duration of hospitalization in children with croup OBJECTIVE To assess the efficacy of oral dexamethasone or nebulized dexamethasone sodium phosphate in children with mild croup . METHODS Double-blind , placebo-controlled study of 264 children between 6 months and 6 years of age with symptoms of croup for fewer than 48 hours . Patients were excluded if they received racemic epinephrine or corticosteroid treatment . Other exclusion criteria included corticosteroid treatment during the 14 days prior to enrollment or complicating medical condition . Subjects r and omly received oral dexamethasone ( 0.6 mg/kg ) , nebulized dexamethasone sodium phosphate ( 160 microg ) , or placebo . Telephone follow-up was obtained on days 1 , 2 , 3 , 4 , and 7 . MAIN OUTCOME MEASURES The primary outcome measure was treatment failure , defined as receiving corticosteroid or racemic epinephrine treatment during the 7 days after enrollment in the study . Secondary outcome measures included seeking additional care and the parental assessment s of the patients ' condition obtained during follow-up ( worse , same , better , or gone ) . RESULTS Eighty-five patients received oral dexamethasone , 91 received nebulized dexamethasone , and 88 received placebo . There were 3 treatment failures in the oral dexamethasone-treated group , 12 in the nebulized dexamethasone-treated group , and 10 in the placebo-treated group ( P = .05 ) . Ten children in the oral dexamethasone-treated group sought additional care compared with 27 and 29 in the nebulized dexamethasone-treated and placebo-treated groups , respectively ( P = .002 ) . Parents of children in the oral dexamethasone-treated group reported greater improvement on day 1 ( P<.001 ) compared with the nebulized dexamethasone-treated and placebo-treated groups . CONCLUSIONS Children with mild croup who receive oral dexamethasone treatment are less likely to seek subsequent medical care and demonstrate more rapid symptom resolution compared with children who receive nebulized dexamethasone or placebo treatment CONTEXT Children with croup are often treated with humidity even though this is not scientifically based , consumes time , and can be harmful . Although humidity using the traditional blow-by technique is similar to room air and no water droplets reach the nasopharynx , particles sized for laryngeal deposition ( 5 - 10 microm ) could be beneficial . OBJECTIVE To determine whether a significant difference in the clinical Westley croup score exists in children with moderate to severe croup who were admitted to the emergency department and who received either 100 % humidity or 40 % humidity via nebulizer or blow-by humidity . DESIGN AND SETTING A r and omized , single-blind , controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department . PARTICIPANTS A convenience sample of 140 previously healthy children 3 months to 10 years of age with Westley croup score of more than 1 or 2 or higher ( scoring system range , 0 - 17 ) ; 21 families refused participation . INTERVENTION Thirty-minute administration of humidity using traditional blow-by technique ( commonly used placebo , n = 48 ) , controlled delivery of 40 % humidity ( optimally delivered placebo , n = 46 ) , or 100 % humidity ( n = 46 ) with water particles of mass median diameter 6.21 microm . MAIN OUTCOME MEASURE A priori defined change in the Westley croup score from baseline to 30 and 60 minutes in the 3 groups . RESULTS Groups were comparable before treatment . At 30 minutes the difference in the improvement in the croup score between the blow-by and low-humidity groups was 0.03 ( 95 % confidence interval [ CI ] , -0.72 to 0.66 ) , between low- and high-humidity groups , 0.16 ( 95 % CI , -0.86 to 0.53 ) , and between blow-by and high-humidity groups , 0.19 ( 95 % CI , -0.87 to 0.49 ) . Results were similar at 60 minutes . Differences between groups in pulse and respiratory rates and oxygen saturation changes were insignificant , as were proportions of excellent responders ; proportions with croup score of 0 at study conclusion ; and proportions receiving dexamethasone , epinephrine , or requiring additional medical care or hospitalization . CONCLUSIONS One hundred percent humidity with particles specifically sized to deposit in the larynx failed to result in greater improvement than 40 % humidity or humidity by blow-by technique . This study does not support the use of humidity for moderate croup for patients treated in the emergency department . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00230841 AIMS To determine whether nebulised budesonide improves the symptoms or shortens the duration of stay of children admitted to hospital with a clinical diagnosis of croup . METHODS A prospect i ve , r and omised , double blind placebo controlled trial . Patients received either nebulised budesonide or placebo every 12 hours . The main outcome measures were duration of inpatient stay and croup scores at 30 minutes , one , two , four , 12 , and 24 hours . RESULTS 87 patients ( 89 admissions ) aged 7–116 months entered the trial . Nebulised budesonide was associated with a significant improvement in symptoms at 12 hours ( 95 % confidence interval ( CI ) 1 to 3 ) and 24 hours ( 95 % CI 0 to 3 ) . Patients with an initial croup score above 3 demonstrated a significant improvement in symptoms at two hours ( 95 % CI 1 to 3 ) . Nebulised budesonide was also associated with a 33 % reduction in the length of stay ( 95 % CI 2 % to 63 % ) when the confounding variables of age , initial croup score , and coryzal symptoms were taken into consideration . CONCLUSIONS Nebulised budesonide is an effective treatment for children admitted to hospital with a clinical diagnosis of croup OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with GRADE and other experts . RESULTS Up date d guidance continues to be conceptually similar to GRADE . Review ers are to evaluate SOE separately for each major treatment comparison for each major outcome . We added reporting bias as a required domain and retained study limitations ( risk of bias ) , consistency , directness , and precision ( and three optional domains ) . Additional guidance covers scoring consistency , precision , and reporting bias , grading bodies of evidence with r and omized controlled trials and observational studies , evaluating single study bodies of evidence , using studies with high risk of bias , and presenting findings with greater clarity and transparency . SOE is grade d high , moderate , low , or insufficient , reflecting review ers ' confidence in the findings for a specific treatment comparison and outcome . CONCLUSION No single approach for grading SOE suits all review s , but a more consistent and transparent approach to reporting summary information will make review s more useful to the broad range of audiences that AHRQ 's work aims to reach . EPC working groups will consider ongoing challenges and modify guidance as needed , on issues such as combining trials and observational studies in bodies of evidence , weighting domains , and combining qualitative and quantitative syntheses CONTEXT The effectiveness of glucocorticoids for patients with croup is well established but it remains uncertain which glucocorticoid regimen is most effective . OBJECTIVE To determine the effectiveness of 3 glucocorticoid regimens in patients with croup . DESIGN R and omized controlled trial with parallel design . SETTING Emergency departments of 2 Canadian pediatric tertiary care hospitals . PARTICIPANTS Children with a clinical syndrome consistent with croup , aged 3 months to 5 years , with a croup score of 2 or greater following at least 15 minutes of mist therapy . INTERVENTIONS Oral dexamethasone , 0.6 mg/kg , and nebulized placebo ; oral placebo and nebulized budesonide , 2 mg ; or oral dexamethasone , 0.6 mg/kg , and nebulized budesonide , 2 mg . MAIN OUTCOME MEASURES Westley croup score ( primary outcome ) , hospital admission rates , time spent in the emergency department , return visits to the emergency department , or ongoing symptoms at 1 week . RESULTS The mean change in the croup score from baseline to the final study assessment was -2.3 ( 95 % confidence interval [ CI ] , -2.6 to -2.0 ) in the budesonide group ( n = 65 ) , -2.4 ( 95 % CI , -2.6 to -2.2 ) in the dexamethasone group ( n = 69 ) , and -2.4 ( 95 % CI , -2.7 to -2.1 ) in the budesonide and dexamethasone group ( n = 64 , P = .70 ) . CONCLUSIONS Based on the similar outcomes in the 3 groups , oral dexamethasone is the preferred intervention because of its ease of administration , lower cost , and more widespread availability The authors examined 85 children who had serious recurrent pseudogroup syndrome , and re-examined them 1 - 3 years later . 1/3 of the patients was also allergic , mostly to mites and grasspollens . The patients got either regular , daily two inhalation , or their parents were taught to inspire the drug in the case of stenotic cough of hoarseness . Half of the patients did not answer to our letter . The parents of 43 patients answered and described their observations according to the inquiry letter . 2/3 of treated children either amolioreted definitely of became symptom free . 12 patients had 30 laryngeal attacks before the budesonide treatment whereas only 3 attacks , needing hospitalisation , occurred after the budesonide treatment . 6 patients experienced definite amelioration and two children 's state worsened . Budesonide therapy seemed to be useful in the prevention and therapy of recurrent laryngitic children . Further experiences using turbo-inhaler and placebo would be important for more definite statement . Nevertheless inhalative budesonide is the first drug promising fast remission of laryngeal edema Objective The objective was to derive a simple clinical scoring instrument for assessing children with croup by telephone for use in clinical research studies . Methods We review ed published literature on croup scores , surveyed experienced pediatric emergency nurses and physicians , and conducted a prospect i ve cohort study . Score items were derived from published literature and surveys of experienced clinicians . We enrolled children with croup attending an urban pediatric emergency department . Families of children enrolled were contacted daily by telephone and asked st and ardized questions about their child ’s clinical symptoms and family functioning . Data from this survey were used to derive the clinical score . Results We identified 11 unique croup scores from the literature and interviewed 6 experienced clinicians . We enrolled 330 children and achieved complete follow-up for 301 . Of the various groupings of items and duration of assessment , the 2-item score ( barky cough and stridor ) was the simplest and most reliable . Three days of follow-up yielded optimal correlations . Conclusions We derived a 2-item Telephone Out Patient score assessed daily for 3 days after an emergency department visit . Validation of this score in a future , independent prospect i ve cohort is needed UNLABELLED Glucocorticoids are an effective treatment for croup , although the most beneficial route of administration remains unclear . Recent studies have concluded that both intramuscular dexamethasone and oral dexamethasone are effective treatments , but there are few data directly comparing the two for moderate-to-severe croup . OBJECTIVES The authors ' primary objective was to determine whether there is a difference in proportion of children with resolution of symptoms attributable to croup at 24 hours , when treated with oral or intramuscular dexamethasone . Secondarily , the authors sought to estimate whether there is a difference in proportion of children with resolution of symptoms attributable to croup at 10 days and to estimate the interval to complete resolution of symptoms between these two routes . METHODS The authors performed a prospect i ve , r and omized , double-blind trial involving children aged 3 - 84 months with moderate-to-severe croup , presenting to a suburban teaching emergency department ( ED ) . Patients were eligible for enrollment if they had inspiratory stridor or a barky cough and a croup score of 2 or greater after 10 - 15 minutes of cool mist therapy . The patients were r and omized to one of two intervention groups . In both groups , the parents were not present in the treatment room during study drug administration . One group received 0.6 mg/kg of intramuscular dexamethasone and an oral placebo , while the other group received 0.6 mg/kg of oral dexamethasone and direct pressure on their thigh with the hub of a syringe . A nurse placed a B and -Aid on the site of the real or mock injection . Parents were contacted by telephone approximately 1 and 10 days after the index visit to ask about their child 's symptoms using a st and ardized question naire . Data were analyzed using an intention-to-treat approach . RESULTS Of 126 patients eligible , 96 were recruited , with complete follow-up on 95 . The groups were similar in all baseline characteristics , treatments received in the ED , and disposition . At 24 hours and 10 days after the visit , there were no statistical differences between the groups for the proportion with stridor , expiratory sounds , barky cough , sleep pattern , the degree of improvement , or the proportion with complete resolution of symptoms at one day . CONCLUSIONS No statistical differences for any parameters were observed between intramuscular and oral dexamethasone treatments for children with moderate-to-severe croup at 24 hours or at any time the week after treatment . The duration s of symptoms were similar between the treatment groups BACKGROUND Although recent evidence has strongly supported the use of glucocorticoid therapy in children hospitalized with croup , the benefit of this therapy in children with less severe croup has not been documented . This r and omized , double-blind trial compared a nebulized glucocorticoid , budesonide , with placebo in out patients with mild-to-moderate croup . METHODS Children three months to five years of age were eligible for the study if their croup scores fell in the mild-to-moderate range ( scores of 2 to 7 out of a possible 17 ) . The patients were r and omly assigned to receive either 2 mg ( 4 ml ) of nebulized budesonide ( 27 children ) or 4 ml of nebulized normal saline ( 27 children ) ; they were then assessed hourly for up to four hours by investigators who were unaware of the assigned treatments . RESULTS The median croup score at entry into the study was 4 in both groups . At the final study assessment , the median score was significantly lower in the budesonide group than in the placebo group ( 1 vs. 3 , P = 0.005 ) . The patients in the budesonide group were discharged from the emergency department significantly earlier than those in the placebo group ( P = 0.002 ) . One week after enrollment , 21 patients assigned to placebo had received dexamethasone , as compared with 15 patients assigned to budesonide ( P = 0.10 ) , and 7 patients assigned to placebo had been admitted to the hospital , as compared with 1 patient assigned to budesonide ( P = 0.05 ) . CONCLUSIONS We conclude that nebulized budesonide leads to a prompt and important clinical improvement in children with mild-to-moderate croup who come to the emergency department OBJECTIVE To determine the added clinical benefit of nebulized budesonide in children with mild to moderate croup treated with 0.6 mg/kg oral dexamethasone . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Emergency department of a tertiary-care pediatric hospital with 47,000 visits per year . PARTICIPANTS Children 3 months to 5 years of age with a syndrome consisting of hoarseness , inspiratory stridor , and barking cough and a croup score of 3 or greater after at least 15 minutes of mist therapy . Patients were excluded from the study if they had diagnoses of epiglottitis , chronic upper or lower airway disease ( not including asthma ) , or severe croup or had received corticosteroids within the preceding 2 weeks . INTERVENTION All patients received 0.6 mg/kg oral dexamethasone and were r and omly assigned to receive 4 mL ( 2 mg ) of budesonide solution ( n=25 ) or 4 mL of 0.9 % saline solution ( n=25 ) by updraft nebulizer with a continuous flow of oxygen at 5 to 6 L/min . MAIN OUTCOME MEASURES The primary outcome measure was the proportion of patients in each group who had clinical ly important changes ( two points ) in the croup score during the 4 hours after treatment . RESULTS Eighty-four percent ( n=21 ) of the patients who received budesonide had clinical ly important responses , compared with 56 % ( n=14 ) in the placebo group . The number of patients who would need to be treated with nebulized budesonide for one patient to have a clinical ly important response is four patients . CONCLUSIONS Despite receiving simultaneous oral dexamethasone , pediatric out patients with mild to moderate croup have added , clinical ly important improvement in respiratory symptoms after treatment with budesonide Objective : For children with croup controversy remains over dosage and time to onset of action of oral steroids . The Cochrane Collaboration and other review s have suggested 0.6 mg/kg dexamethasone be used ( despite some evidence that 0.15 mg/kg is effective ) with no expectation of benefit before 4–6 h. This r and omized double‐blinded clinical trial examines whether 0.15 mg/kg dexamethasone works by 30 min OBJECTIVE Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup . However , there has been no direct comparison of these therapies . We undertook a multicenter , r and omized , double-blind , parallel group study in 66 hospitalized children with viral or spasmodic croup . METHODS Children 0.5 to 6 years of age were assessed using a vali date d croup symptom score ( stridor , 0 through 4 ; cough , 0 through 3 ; retractions , 0 through 3 ; dyspnea , 0 through 3 ; and color , 0 through 4 ) at 0.5 , 1 , 1.5 , 2 , 12 , and 24 hours after nebulization . Patients received either budesonide ( 2 mg/4 mL ) or L-adrenaline ( 4 mg/4 mL ) via nebulization . The primary outcome measure was change in the total croup symptom score . RESULTS Thirty-five children received budesonide and 31 received adrenaline . There was no significant difference in baseline features , including croup score ( mean [ 95 % confidence interval ] : budesonide , 7.1 [ 6.7 - 7.5 ] ; adrenaline , 7.7 [ 7.3 - 8.1 ] ) . All patients had significant improvement from baseline , and there was not significant difference between the two treatments , as measured by change in croup scores , change in oxygen saturation , duration of hospitalization , number of subsequent treatments with systemic steroids or adrenaline , and adverse events . No child required intubation . CONCLUSION This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup The value of corticosteroids in the treatment of acute croup remains in doubt . Support for their use comes primarily from the otolaryngology literature . Martensson , et al , 1 Novik , 2 and Davison 3 maintain that the course of the illness is shortened by the antiinflammatory effect of steroid therapy . Morse 4 stated that this form of treatment has reduced the incidence of tracheostomy . Leegaard 5 does not agree with this concept . In a recent study , Eden and Larkin 6 could not demonstrate any difference between the control and corticosteroidtreated groups . In a further attempt to help resolve this question , a controlled , double-blind study was carried out on 50 hospital patients with acute croup . Material s and Methods Fifty consecutive patients admitted to the hospital with acute croup were included in this study . Children presenting with acute respiratory infections characterized by barking cough , hoarseness , sternal retractions , and respiratory stridor were included . One PURPOSE To determine if treating children who have acute , moderate croup with nebulized dexamethasone sodium phosphate in the emergency department results in clinical improvement by 4 hours and a decrease in the hospitalization rate . DESIGN R and omized , double-blind , placebo controlled trial . SETTING Emergency department , children 's hospital . PATIENTS Fifty-five children with croup who were in moderate respiratory distress after treatment with mist for 30 minutes who met inclusion and exclusion criteria . MEASUREMENTS Croup score , respiratory rate , heart rate , and oxygen saturation were assessed by one of us ( D.W.J. or S.S. ) before treatment and 2 and 4 hours after treatment . A staff pediatrician or senior pediatric resident , also " blind " to treatment , decided on admission to or discharge from the hospital . The differences between groups for change in croup score and hospitalization rate after treatment were analyzed . RESULTS Evaluation of the croup scores disclosed a significant improvement in the dexamethasone-treated group compared with the placebo group at 4 hours ( P=.005 , Mann-Whitney U ) . However , the hospitalization rate was not statistically different at the end of treatment ( 33 % vs 52 % , P=.28 ) or after 24 hours ( 48 % vs 60 % , P=.56 , Yates corrected chi(2 ) ) . Our study has 80 % power to detect a two-thirds reduction in hospitalization rate . Two patients with neutropenia treated with dexamethasone had a clinical course consistent with bacterial tracheitis . CONCLUSIONS Treatment of moderate croup with nebulized dexamethasone results in clinical improvement within 4 hours . We did not show a decrease in hospitalization rates , although our sample size was only large enough to detect a 67 % reduction in the rate of hospitalization . Given the infectious complications and the absence of evidence for a sustained clinical effect , we do not recommend that patients with croup be treated with nebulized dexamethasone Beneficial effects of treatment of viral croup with inhaled corticosteroids and administered with a jet-nebulizer have been reported in recent years . To facilitate such therapy at home and avoid hospitalization , the administration of inhaled corticosteroids with a metered dose inhaler ( MDI ) with a holding-chamber was studied as a potential alternative . In a hospital-based prospect i ve , double-blind , r and omized study , 17 children admitted with croup were treated with either fluticasone propionate MDI ( 2,000 microg with the Babyhaler spacer ) or placebo . The primary outcome variable was the croup symptom score recorded from 0 up to 24 hours . Secondary outcome variables were the need for administration of nebulized corticosteroids with a nebulizer , the need for intubation , and the duration of hospitalization . The administration of the drug with an MDI and spacer was well tolerated in each child . In all children the clinical course was favorable , without any significant differences between the actively treated and placebo-treated group . One child needed additional use of inhaled corticosteroids with a jet nebulizer , despite treatment with fluticasone . Mean duration of hospitalization was 2.6 ( 1 - 4 ) and 2.4 ( 1 - 4 ) days for treatment with fluticasone and placebo , respectively . No undesirable side effects of treatment were reported . In conclusion , this study did not demonstrate therapeutic benefits of fluticasone propionate when administered with an MDI and a spacer compared with placebo . We hypothesize that the lack of effect is probably due to the inadequate deposition of adequate inhaled corticosteroids in the upper airways BACKGROUND In children with croup , treatment with nebulized budesonide decreases symptoms , but it is uncertain how budesonide compares with dexamethasone , the conventional therapy for croup , and whether either reduces the rate of hospitalization . METHODS We performed a double-blind , r and omized trial involving 144 children with moderately severe croup . The children were treated with racepinephrine and a single dose of 4 mg of nebulized budesonide ( 48 children ) , 0.6 mg of intramuscular dexamethasone per kilogram of body weight ( 47 children ) , or placebo ( 49 children ) . The children were assessed before treatment and then hourly for five hours after treatment . Physicians who were unaware of the treatment assignments determined the children 's need for further treatment and hospitalization . RESULTS The characteristics of the groups were similar at base line , including the types of viruses identified , the types of croup , and the clinical severity of the illness . The overall rates of hospitalization were 71 percent in the placebo group ( 35 of 49 children ) , 38 percent in the budesonide group ( 18 of 48 children ) , and 23 percent in the dexamethasone group ( 11 of 47 children ) ( unadjusted P=0.001 for the comparison of budesonide with placebo , P<0.001 for the comparison of dexamethasone with placebo , and P=0.18 for the comparison of budesonide with dexamethasone ) . Children treated with budesonide or dexamethasone had a greater improvement in croup scores than those given placebo ( P=0.03 and P<0.001 , respectively ) , and those treated with dexamethasone had a greater improvement than those treated with budesonide ( P=0.003 ) . CONCLUSIONS In children with moderately severe croup , treatment with intramuscular dexamethasone or nebulized budesonide result ed in more rapid clinical improvement than did the administration of placebo , with dexamethasone offering the greatest improvement . Treatment with either glucocorticoid result ed in fewer hospitalizations OBJECTIVE Recent studies have demonstrated that a single intramuscular injection of dexamethasone ( 0.6 mg/kg ) shortens the duration and severity of illness in hospitalized patients with acute viral laryngotracheitis ( croup ) . Our objective was to determine if dexamethasone has a role in the outpatient management of patients with acute viral croup of moderate severity . METHODS Patients , 6 months to 5 years of age , who came to the emergency department ( ED ) with acute viral croup , a croup score of at least 2 ( range 0 to 17 ) , and a disposition of discharge were r and omized in a double-blind fashion to receive a single intramuscular injection of dexamethasone , 0.6 mg/kg , or an equal volume of normal saline before discharge from the ED . Patients were excluded if they had any structural abnormalities , had received any steroids in the preceding 24 hours , or if they required beta-agonist therapy , more than one racemic epinephrine treatment , or hospitalization . Patients were followed up by telephone 24 hours and 7 to 10 days after discharge to determine whether additional medical attention was sought for perceived lack of improvement or worsening of symptoms . Secondary outcome included the parents ' perception of how the child was doing at 24 hours , based on a 4-point ordinal scale : worse ( 1 ) , same ( 2 ) , improved ( 3 ) , symptoms resolved ( 4 ) , and the number of days it took for complete recovery . RESULTS Of the 38 patients comprising the study group , 19 received dexamethasone . The median age was 19 months ( range 6 to 66 months ) , and median pretreatment croup score was 3 ( range 2 to 5 ) for both groups . The number of patients requiring racemic epinephrine was similar in both groups . Five patients sought additional medical attention within 48 hours . Four of the five patients had received placebo ( 21 % of the placebo group ) and one had received dexamethasone ( 5 % of the steroid group ) ( not statistically significant ) . At the 24-hour telephone follow-up , significantly more patients in the dexamethasone group had a score consistent with improvement compared with placebo ( 84 % vs 42 % , P = .003 ) . There was no difference in the number of days for symptoms to completely resolve between the two groups . CONCLUSION The use of dexamethasone in the outpatient management of viral croup was associated with a reduction in severity of illness within 24 hours after treatment . Patients with viral croup of moderate severity should be considered as c and i date s for the use of dexamethasone before discharge from the ED We studied 50 preterm infants who had multiple or traumatic endotracheal intubations , or whose duration of endotracheal intubation was > or = to 14 days , and who were considered at high risk for airway edema . These infants were enrolled in a prospect i ve , r and omized , controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress . At study entry , both groups had similar weights , postnatal ages , methylxanthine use , ventilator setting s , blood gas values , and pulmonary function test results ( dynamic compliance , total respiratory resistance , tidal volume , peak-to-peak transpulmonary pressure , minute ventilation , and peak inspiratory and expiratory flow rates ) . Patients underwent blood gas studies , physical examinations , and pulmonary function testing at baseline ( 4 hours before extubation ) and again 2 to 4 hours and 18 to 24 hours after extubation . Twenty-seven infants received dexamethasone , 0.25 mg/kg per dose , at baseline , and then every 8 hours for a total of three doses ; 23 infants received saline solution at corresponding times . Eighteen to twenty-four hours after extubation , total pulmonary resistance increased by 225 % from baseline in the control group compared with 33 % in the dexamethasone group ( p < 0.006 ) , and the dexamethasone group had a greater tidal volume , a greater dynamic compliance , and a lower arterial carbon dioxide pressure . Of 23 control infants , 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients ( p < 0.006 ) . Of the 23 control patients , 4 required reintubation compared with none of the treated group ( p < 0.05 ) . We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight , high-risk preterm infants The objective of this study was to compare the effect of L-epinephrine plus dexamethasone vs. dexamethasone for treatment of croup in children . A r and omized , double-blind clinical trial was implemented on 174 patients with croup , aged from 6 months to 6 years , and admitted to the Amir Kabir Pediatric Hospital ( Arak , Iran ) . After r and omized allocation , patients were administered dexamethasone , and then , they received either saline or L-epinephrine . Westley croup scores , heart rate , respiratory rate , and blood pressure were recorded every half an hour for a total of 120 min . There was a significant difference in mean of croup scores between two groups ( P < 0.009 ) . In addition , a significant difference was seen on mean of heart rate between two groups ( P < 0.026 ) . Our results showed a considerable difference in reduction of velocity of croup scores in patients who received nebulized L-epinephrine compared to patients who received placebo To determine whether a single dose of dexamethasone ( 0.6 mg/kg ) is useful in the treatment of acute laryngotracheitis ( croup ) , 29 hospitalized patients with acute laryngotracheitis were r and omly assigned in a double-blind fashion to receive either parenterally administered dexamethasone ( n = 16 ) or a saline placebo ( n = 13 ) . Severity of the illness was assessed by a clinical croup score based on retractions , stridor , air entry , cyanosis , and level of consciousness . Twelve hours from the time of injection , the patients receiving the dexamethasone had a statistically significant decline in median croup score from 4.5 to 1.0 ( p less than 0.001 ) , whereas the patients receiving the placebo did not . By 24 hours , a decline of two or more points in the total croup score was noted in 85 % of the patients in the dexamethasone group compared with 33 % of the patients in the placebo group ( p = 0.027 ) . During this same period , only 19 % of patients receiving dexamethasone required two or more racemic epinephrine treatments in comparison with 62 % of patients who received the placebo ( p less than 0.05 ) . There was no statistical difference between the two groups in improvement in oxygen saturation , respiratory rates , or duration of hospitalization . We conclude that dexamethasone is beneficial in reducing the overall severity of moderate to severe acute laryngotracheitis during the first 24 hours after injection N 1950 Wyliel reported that 70 of 100 I unselected adult patients intubated under ether or cyclopropane anesthesia complained postoperatively of either mild or severe sore throat . Baron and Kohlmoos2 in 1951 found that 80 consecutive adults noted a mild degree of discomfort during the first 24 hours following intubation ; none , however , developed important sequelae . In 1958 Wolfson2 question ed 521 adult patients directly and observed that 18.4 per cent complained of postintubation soreness ; 4.5 per cent of these patients also had objective findings of hoarseness or loss of voice . Conway and associates4 in 1960 found a 38.2 per cent incidence of postintubation sore throat in a series of 642 adult patients interrogated directly . In 1964 Hartsell and Stephen ? revealed that 5.7 per cent of 400 adult patients question ed indirectly complained of postintubation sore throat . Deming and OechG in 1961 described the use of dexamethosone and diphenhydramine in the treatment of severe postintubation subglottic edema in children . Jafle7 in 1964 reported the effectiveness of dexamethasone in reducing and eliminating postoperative laryngeal edema in children 5 years old and under who were intubated nasotracheally for dental procedures BACKGROUND Viral laryngotracheobronchitis croup is the most common cause of acute upper airway obstruction in young children . Clinical assessment of children with croup is often performed using ' croup scores ' ; however , these scores have not been vali date d outside of the research setting . OBJECTIVE To determine the reliability of clinical observation items in croup scores in a paediatric emergency department ( ED ) setting . DESIGN Literature review identified 12 observation items ( level of consciousness or mental status , inspiratory breath sounds , air entry , stridor , cough , cyanosis or colour , anxiety or air hunger , retractions and /or flaring , respiratory rate and heart rate , oxygen saturation and respiratory distress ) ; overlapping items were combined , yielding 10 variables . In a prospect i ve cohort study over 13 months , patients presenting with croup were observed independently , and croup scores were assigned by the triage nurse , ED nurse and the ED physician before treatment . Agreement among observers for clinical observations was analysed using Cohen 's quadratic weighted kappa . SETTING University-affiliated , paediatric hospital ED providing primary care to an urban area ( population 330,000 ) . PATIENTS Children aged three months to five years presenting with viral croup ( preceding history of at least one day of upper respiratory tract symptoms associated with barking cough and /or hoarseness and /or stridor ) . RESULTS One hundred fifty-eight children meeting inclusion criteria for croup were assessed by three observers within 1 h of each other 's assesments and before treatment . Interobserver agreement among the three observers using weighted kappa was greater than chance for all clinical observation items and ranged from fair to moderate ( 0.2 to 0.4 and 0.4 to 0.6 , respectively ) . CONCLUSIONS In the busy practice setting of a paediatric ED , substantial interobserver variability exists among health care providers in the measurement of respiratory signs associated with croup in young children . Based on the present study in a practice setting and two research studies , the most reliable items of all of the published items included in croup scoring systems were stridor and retractions OBJECTIVES To compare speed and accuracy of graphical data extraction using manual estimation and open source software . STUDY DESIGN AND SETTING Data points from eligible graphs/figures published in r and omized controlled trials ( RCTs ) from 2009 to 2014 were extracted by two authors independently , both by manual estimation and with the Plot Digitizer , open source software . Corresponding authors of each RCT were contacted up to four times via e-mail to obtain exact numbers that were used to create graphs . Accuracy of each method was compared against the source data from which the original graphs were produced . RESULTS Software data extraction was significantly faster , reducing time for extraction for 47 % . Percent agreement between the two raters was 51 % for manual and 53.5 % for software data extraction . Percent agreement between the raters and original data was 66 % vs. 75 % for the first rater and 69 % vs. 73 % for the second rater , for manual and software extraction , respectively . CONCLUSIONS Data extraction from figures should be conducted using software , whereas manual estimation should be avoided . Using software for data extraction of data presented only in figures is faster and enables higher interrater reliability We evaluated the use of dexamethasone in the management of acute laryngotracheobronchitis ( croup ) . Thirty patients , ranging in age from eight to 60 months , were evaluated in a prospect i ve , double-blind study . Patients received dexamethasone , 0.3 mg/kg at the time of admission and a similar dose 2 hours later , and were compared with a placebo group receiving saline . Sixteen patients received dexamethasone and 14 patients received the placebo . Severity of each group was scored by a st and ardized system . Patients receiving dexamethasone had a mean admission score of 8.46 points ; patients receiving placebo , 8.14 . Twenty-four hours after admission the patients in the treatment group had a mean score of 1.19 as contrasted with a score of 5.58 for the placebo group ( P less than 0.01 ) . We concluded that dexamethasone when administered in adequate dosage by an intramuscular route hastens the recovery of infants and children with acute uncomplicated croup OBJECTIVE Steroid use for the treatment of croup has been supported by several studies , although few have addressed the use of oral dexamethasone for outpatient management . The efficacy of oral ( PO ) versus intramuscular ( IM ) dosing of dexamethasone in the outpatient treatment of moderate croup are compared in this study . METHODS Patients between the ages of 3 months and 12 years with moderate croup ( history or presence of stridor , cyanosis , or retractions ) were eligible for enrollment in this single-blind , prospect i ve study . Patients were r and omized to receive a single dose ( 0.6 mg/kg , maximum 8 mg ) of IM or PO dexamethasone . Parents were contacted by phone to assess resolution of symptoms and need for further evaluation . RESULTS Two hundred seventy-seven patients were enrolled ( median age : 2.1 years ) . One hundred thirty-nine patients received IM dexamethasone , and 138 received PO . At phone follow-up , 141 ( 51 % ) had total resolution of symptoms ( 75 in IM , 66 in PO ) . Eighty patients ( 29 % ) returned for further evaluation ( 45 in IM , 35 in PO ) . Twenty-three ( 8 % ) received either more steroids , racemic epinephrine , or admission ( 11 in IM , 12 in PO ) . CONCLUSION No statistically significant difference was found in the need for subsequent interventions after a single dose of either IM or PO dexamethasone . A single PO dose of dexamethasone can be effectively and safely used for the outpatient treatment of moderate croup Background : Croup remains a common respiratory problem presenting to emergency departments . A single oral treatment of oral dexamethasone results in improved outcome . Prednisolone has similar pharmacokinetic properties and has a significant advantage in that it is commercially available in liquid preparations . Objective : To ascertain whether a single oral dose of prednisolone was equivalent to a single oral dose of dexamethasone ( matched for potency ) in children with mild to moderate croup . Design : A double blind , r and omised , controlled equivalence trial Setting : Tertiary paediatric emergency department . Patients : 133 children aged 3 to 142 months presenting with mild to moderate croup . Interventions : Children received either a single oral dose of dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg . Outcome : The main outcome measure was unscheduled re-presentation to medical care as determined by telephone follow up at 7 to 10 days . Croup score , adrenaline ( epinephrine ) use , time spent in the emergency department , and duration of croup and viral symptoms were secondary outcome measures . Results : Children treated with prednisolone were more likely to re-present : 19 of 65 children ( 29 % ) reattended medical care compared with 5 of 68 ( 7 % ) from the dexamethasone group . The confidence intervals around this 22 % difference in outcome were 8 % to 35 % , outside the 0 % to 7.5 % range of equivalence . There were no significant differences in other outcome measures . Conclusion : A single oral dose of prednisolone is less effective than a single oral dose of dexamethasone in reducing unscheduled re-presentation to medical care in children with mild to moderate croup Thirty-two infants , aged 1 to 12 months , hospitalized with acute wheezing , were studied . They were r and omly divided into four treatment groups of eight patients each . The treatments were intramuscular dexamethasone or placebo ( double-blind ) , and salbutamol ( oral and inhaled ) , or none ( open ) , in all four possible combinations . The study was carried out as a r and omized block design with eight blocks of four infants each , matched by age and clinical score . Average daily improvements , as reflected by changes in the clinical score and length of hospital stay , was essentially the same for infants treated with placebo , salbutamol alone , and dexamethasone alone . However , combined salbutamol-dexamethasone treatment result ed in more than twice the rate of improvement of the other treatments . The difference was statistically highly significant ( P less than .01 ) . Furthermore , the response of this combined treatment was observed within 24 hours ; none of the ten infants in whom there was no significant improvement within 48 hours and neither of the two patients who developed respiratory failure received the combined salbutamol-dexamethasone treatment . A potentiating effect of corticosteroids on the beta-adrenergic responsiveness is a possible explanation for the advantage of this combined treatment in the management of acute wheezing in infancy AIM The purpose of this study was to determine whether local anti-inflammatory therapy with inhaled beclomethasone dipropionate is effective in the outpatient management of acute viral croup . METHODS Children six months to five years of age , presenting to the Emergency Department ( ED ) with a croup score of at least 2 participated in the study . All children were assigned in a r and omised double-blind fashion to receive either nebulized L-epinephrine ( LE ) , a single intramuscular injection of dexamethasone ( D ) 0.6 mg/kg , or inhaled beclomethasone dipropionate ( BD ) 200 mg , via aerochamber . Croup score ( CS ) , heart rate ( HR ) , blood pressure , respiratory rate ( RR ) and oxygen saturation were recorded at study entry and at 15 , 30 , 60 , 90 and 120 minutes after treatment . RESULTS Sixty-four patients were enrolled into the study . Significant improvement of the croup score was noticed at the end of observation time in all groups . The LE group showed significant improvements of CS , HR and RR in comparison to the other two groups . Inhaled BD was as effective as intramuscular D in the treatment of mild to moderate croup in the ED . CONCLUSION The use of inhaled beclomethasone in the outpatient management of croup was associated with a significant reduction in the severity of illness within 24 h after treatment THE VALUE of corticosteroids in the treatment of croup has not been convincingly established . Some authors have cl aim ed that corticosteroid therapy reduced or shortened the duration of airway obstruction so that fewer patients required tracheostomy.1,2Skowron and his associates3were able to demonstrate in a controlled study that the duration of fever , stridor , sternal retractions , and hospital stay were significantly reduced in corticosteroid treated patients , but concluded that the potential risk of serious side effects outweighed these advantages . Other workers have been unable to show measurable benefit from steroid therapy.4 - 6 Croup is a common disorder in young children , and therapy may occasionally include tracheostomy . It therefore seemed important to determine in a carefully controlled study whether the course of the disease could in fact be alleviated by the administration of corticosteroids . A preliminary pilot study carried out during 1964 and 1965 by D. Kaufman , MD , and We r and omised 59 children hospitalized for croup to treatment with either inhaled budesonide or injected dexamethasone . Group A were treated with two inhalations of 1000 micrograms budesonide and group B received dexamethasone 0.6 mg/kg intramuscularly . We used a modified Westley-score , based on chest-wall retractions , barking cough , respiratory frequency and stridor . The children was aged three months to six years ( mean 20 months ) . Three hours after the first treatment there was significant improvement in score amongst all children ( p < 0.001 ) , but no difference between the two groups ( p < 0.20 ) . Six and 12 hours after the first treatment there were significantly better clinical scores in group B ( p = 0.001 , p = 0.0004 ) . Based on this study we recommend dexamethasone 0.6 mg/kg intramuscularly for children to be treated for croup Objective : Intramuscular dexamethasone is an effective , but painful , treatment for croup . The effectiveness of betamethasone , an oral , palatable , and equally potent glucocorticoid has not been studied . The purpose of this study was to compare the effectiveness of a single oral dose of betamethasone with intramuscular dexamethasone in the outpatient treatment of mild to moderate croup . Methods : Children aged 6 months to 6 years presenting to a tertiary care pediatric emergency department ( ED ) with a modified Westley croup score of 0 to 11 were r and omized to receive either 0.6 mg/kg IM dexamethasone or 0.4 mg/kg PO betamethasone . Croup score , heart rate , respiratory rate , pulse oximetry , and need for supplemental treatments were recorded at study entry and at 1 , 2 , and 4 hours after treatment . Follow-up data were collected by daily telephone follow-up on persistence of symptoms and the need for additional treatment or physician visits up to 7 days after the ED visit . Results : Each study group contained 26 patients . Despite r and omization , the mean baseline croup score was higher in the dexamethasone group ( 3.6 ± 2.6 vs. 2.0 ± 2.4 , P = 0.03 ) . Patients in both groups showed a significant reduction in the croup score after treatment , and there were no significant differences between croup scores at 4 hours ( P = 0.18 ) . Similarly , there were no differences between groups in the hospital admission rate , time to resolution of symptoms , need for additional treatments , or number of return ED visits . Conclusion : There is no difference between oral betamethasone and intramuscular dexamethasonein the management of mild to moderate viral croup . It is palatable and does not require a nurse for administration , making it a good alternative for ambulatory management Abstract Objective : To compare the effectiveness of nebulised L-epinephrine in combination with systemic or nebulised corticosteroid with that of cool mist and systemic corticosteroids in the treatment of moderate to severe croup . Patients and methods : Children were eligible for study if they presented to the emergency department with a moderate to severe croup . Patients were r and omly assigned to three groups : group 1 , cool mist and intramuscular dexamethasone ( n = 26 ) ; group 2 , nebulised L-epinephrine and intramuscular dexamethasone ( n = 31 ) ; group 3 , nebulised L-epinephrine and nebulised budesonide ( n = 19 ) . The croup score , vital signs and oxygen saturation were assessed before and after medication . Adverse events , additional L-epinephrine and hospitalisation were recorded . Results : Age , sex , initial croup score and vital signs were similar in all groups . Croup scores were significantly decreased over time in all treatment groups and this decrease was very evident at 30 minutes ( p < 0.05 ) . Croup scores of groups 2 and 3 were significantly lower than those of group 1 at 30 and 60 minutes but no difference was observed between groups 2 and 3 at these timepoints . The numbers of patients who had croup scores < 2 at 30 and 60 minutes were higher in groups 2 and 3 than group 1 ( p = 0.004 and p = 0.032 , respectively ) . More patients in group 1 received additional L-epinephrine treatments ( p = 0.014 ) . Changes in vital signs were not different among groups when assessed over time ( p > 0.05 ) . Conclusions : This study demonstrated that with early combination treatment , croup scores improved rapidly and hospitalisation rates were low . Patients with moderate to severe croup presenting to the emergency department should receive nebulised L-epinephrine in combination with intramuscular dexamethasone or nebulised budesonide . No significant adverse effects were observed with L-epinephrine . The use of L-epinephrine has been proposed instead of racemic epinephrine in patients with moderate to severe croup because it is efficacious , well tolerated , less expensive and more readily available in many countries A double blind trial of prednisolone treatment was carried out on 95 children with clinical evidence of epidemic bronchiolitis . The trial showed that there was no difference between the prednisoIone and the placebo group in the duration of symptoms and signs OBJECTIVE To determine whether the use of mist improves clinical symptoms in children presenting to the emergency department ( ED ) with moderate croup . METHODS Children 3 months to 6 years of age were eligible for the study if they presented to the ED with moderate croup . Moderate croup was defined as a croup score of 2 - 7 . The patients were r and omly assigned to receive either mist ( humidified oxygen ) via mist stick or no mist . The patients had croup scores measured at baseline and every 30 minutes for up to two hours . At these intervals the following parameters were also measured : heart rate , respiratory rate , oxygen saturation , and patient comfort score . The patients were treated until the croup score was less than 2 or until two hours had elapsed . All patients initially received a dose of oral dexamethasone ( 0.6 mg/kg ) . Other treatments , such as racemic epinephrine or inhaled budesonide , were given at the discretion of the treating physician . The research assistants were unaware of the assigned treatments . RESULTS There were 71 patients enrolled in the study ; 35 received mist and 36 received no mist . The two treatment groups had similar characteristics at baseline . The median baseline croup score was 4 in both groups . The outcomes were measured as the change from baseline at 30 , 60 , 90 , and 120 minutes . The change in the croup score from baseline in the mist group was not statistically different from the croup score change in the group that did not receive mist ( p = 0.39 ) . There was also no significant difference in improvement of oxygen saturation , heart rate , or respiratory rate at any of the assessment times . There was no adverse effect from the mist therapy . CONCLUSIONS Mist therapy is not effective in improving clinical symptoms in children presenting to the ED with moderate croup The aim of this prospect i ve , r and omised , double blind study was to evaluate whether inhaled nebulized corticosteroid is effective in the treatment of croup . Thirty-seven children ( aged 0.4 - 4.9 years ) admitted to hospital with moderate to severe croup were allocated to treatment with either 2 mg nebulized budesonide ( 20 ) or saline ( 17 ) . Disease severity was assessed by a clinical croup score based on stridor , cough , retractions , dyspnoea and cyanosis , and the overall clinical assessment was scored on a visual log scale ( 0 - 100 ) . Two hours after treatment there was a significant improvement in croup score in the group treated with budesonide ( 8 to 4.5 ) , but not in the group treated with saline ( 8 to 8) . Furthermore , the overall clinical assessment score decreased significantly ( 50 to 25 ) in the group treated with budesonide , whereas it remained constant in the placebo group ( 60 to 62 ) . The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children with moderate to severe croup Many practitioners have considered that steroids , with their anti-inflammatory properties , should be efficacious in the treatment of acute laryngotracheitis . To examine this theory , 200 consecutive cases of acute laryngotracheitis admitted to The Hospital for Sick Children , Toronto , were included in a double-blind study using dexamethasone-21-phosphate and placebo according to a r and om selection code . All other therapy was kept constant . Each patient was assessed by one observer according to seven clinical parameters . The results of this study were subjected to statistical analysis and significantly favoured the steroid-treated group in four parameters only . In view of the risks inherent in steroid therapy , this degree of difference is not sufficient to warrant routine use of this drug for patients with acute laryngotracheitis The purpose of this study was to identify a cohort of children with laryngotracheitis ( croup ) who may be safely discharged from the emergency department ( ED ) after treatment with nebulized racemic epinephrine ( RE ) , corticosteroids , and prolonged observation . Consecutive children ( younger than 13 years of age ) presenting to the ED with the diagnosis of laryngotracheitis were evaluated prospect ively according to a croup scoring system . Sixty-one patients ( 4 to 108 months of age ) with persistent inspiratory stridor at rest after 20 minutes of mist therapy who received nebulized RE ( 0.05 ) mL/kg of a 2.25 % solution ) and intramuscular dexamethasone ( 0.6 mg/kg ) were enrolled in the study . Patients were observed in the ED while croup scores were assessed at 15 , 60 , 120 , and 180 minutes . Croup scores were significantly improved ( analysis of variance , P < .01 ) throughout the observation period in 31 patients ( 51 % ) who were discharged from the ED . Only one patient returned within 48 hours for further cool mist therapy . The maximum benefit from RE therapy was seen at 60 minutes . If a child had persistent resting stridor or a croup score greater than 2 at that time , hospitalization was inevitable . The 30 patients admitted to the hospital were younger ( 19.1 v 27.8 months ) and had higher pretreatment croup scores ( 5.7 v 4.1 ) . This was the first prospect i ve study to identify a subset of children who have received RE to be safely discharged home after observation in the ED |
12,521 | 30,178,881 | There is no clear evidence of an association between PPI monotherapy and increased cardiovascular risk | BACKGROUND Clopidogrel 's anti-platelet effects may be attenuated by a pharmacokinetic interaction with co-prescribed proton pump inhibitors , which inhibit oxidative pathways that convert clopidogrel into its active metabolites .
Despite this , the impact of PPIs on cardiovascular risk in the absence of clopidogrel is not well defined .
AIM To report on a systematic review and meta- analysis of the association between PPIs and cardiovascular risk , independent of clopidogrel . | BACKGROUND Few epidemiological studies have investigated the relative importance of major coronary risk factors in the two sexes within the same study population . In particular , it is not clear whether smoking carries a similar risk of coronary heart disease in men and women . METHODS AND RESULTS The associations between smoking , serum lipids , blood pressure , and myocardial infa rct ion were examined in a population -based prospect i ve study of 11,843 men and women aged 35 to 52 years at entry . During 12 years , 495 cases of first myocardial infa rct ion among men and 103 cases among women were identified . Myocardial infa rct ion incidence was 4.6 times higher among men . The incidence was increased sixfold in women and threefold in men who smoked at least 20 cigarettes per day compared with never-smokers , and the rate in female heavy smokers exceeded that of never-smoking men . Multivariate analysis identified current smoking as a stronger risk factor in women ( relative risk , 3.3 ; 95 % confidence interval [ CI ] , 2.1 to 5.1 ) than in men ( relative risk , 1.9 ; 95 % CI , 1.6 to 2.3 ) . Among those under 45 years old at entry , the smoking-related sex difference was more pronounced ( in women : relative risk , 7.1 ; 95 % CI , 2.6 to 19.1 ) ( in men : relative risk , 2.3 ; 95 % CI , 1.6 to 3.2 ) . Serum total cholesterol , HDL cholesterol , and systolic blood pressure were also highly significant predictors in both sexes . CONCLUSIONS Smoking was a stronger risk factor for myocardial infa rct ion in middle-aged women than in men . Relative risks associated with serum lipids and blood pressure were similar despite large sex differences in myocardial infa rct ion incidence rates BACKGROUND Up to three quarters of patients with gastroesophageal reflux disease ( GERD ) have symptoms , such as heartburn , but no macroscopic evidence of erosive esophagitis , making symptomatic GERD a common clinical problem in the primary care setting . OBJECTIVE To compare the efficacy and safety of omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; and placebo in the treatment of symptomatic GERD without erosive esophagitis . METHODS Patients with a history of heartburn ( > or = 12 months ) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week , r and omized , double-blind , placebo-controlled trial . The absence of erosive esophagitis was established through endoscopy . Eligible patients were r and omized to 1 of 3 treatment groups : omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; or placebo . Patients were assessed at weeks 2 and 4 . The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data : daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment . The efficacy of omeprazole for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea was also assessed . RESULTS Of 359 r and omized patients , 355 were included in the statistical analysis ( intention-to-treat population ) . Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group ( 62 % , day 7 ; 74 % , day 27 ) than in the 10-mg omeprazole group ( 41 % , day 7 ; 49 % , day 27 ) or the placebo group ( 14 % , day 7 ; 23 % ; day 27 ) . Complete resolution of heartburn every day during the last treatment week was significantly ( P < or = .002 ) higher in the 20-mg omeprazole group ( 48 % ) than in the 10-mg omeprazole ( 27 % ) or placebo ( 5 % ) group . Omeprazole was significantly ( P < or = .003 ) more effective than placebo for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea . CONCLUSIONS Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief . Omeprazole , 20 mg once daily , was superior to omeprazole , 10 mg once daily , and to placebo in providing early and sustained resolution of heartburn , as well as treatment of other troublesome GERD symptoms Peptic ulcer bleeding is a serious medical problem with significant morbidity and mortality . Endoscopic therapy significantly reduces further bleeding , surgery and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients . The efficacy of large-dose proton pump inhibitor ( PPI ) therapy in reducing re-bleeding after endoscopic therapy has been supported by evidence derived from r and omized controlled trials . It may be premature to recommend small-dose intravenous injection PPI after endoscopic hemostasis in patients with bleeding ulcers . An up date d systematic review shows that PPI therapy before endoscopy significantly reduces the proportion with major stigmata and requirement for endoscopic therapy at index endoscopy . Some studies show that there is no significant difference between oral and intravenous PPIs in raising intragastric pH. However , clinical data is lacking in patients with peptic ulcer bleeding to date Background Dexlansoprazole MR , a modified‐release formulation of dexlansoprazole , an enantiomer of lansoprazole , effectively heals erosive oesophagitis Abstract In this study , we aim ed to determine the association between gastroesophageal reflux disease ( GERD ) and subsequent coronary heart disease ( CHD ) development , if any , and to evaluate whether longer use of proton pump inhibitors ( PPIs ) increases the risk of CHD . Patients diagnosed with GERD between 2000 and 2011 were identified as the study cohort ( n = 12,960 ) . Patients without GERD were r and omly selected from the general population , frequency-matched with the study group according to age , sex , and index year , and evaluated as the comparison cohort ( n = 51,840 ) . Both cohorts were followed up until the end of 2011 to determine the incidence of CHD . The risk of CHD was evaluated in both groups by using Cox proportional hazards regression models . The GERD patients had a greater probability of CHD than the cohort without GERD did ( log-rank test , P < 0.001 and 11.8 vs 6.5 per 1000 person-years ) . The GERD cohort had a higher risk of CHD than the comparison cohort did after adjustment for age , sex , hypertension , diabetes , hyperlipidemia , alcohol-related illness , stroke , chronic obstructive pulmonary disease , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis ( adjusted hazard ratio [ aHR ] : 1.49 , 95 % confidence interval [ CI ] : 1.34–1.66 ) . The risk of CHD was greater for the patients treated with PPIs for more than 1 year ( aHR = 1.67 , 95 % CI = 1.34–2.08 ) than for those treated with PPIs for < 1 year ( aHR = 1.56 , 95 % CI = 1.39–1.74).Our population -based cohort study results indicate that GERD was associated with an increased risk of developing CHD , and that PPI use for more than 1 year might increase the risk of CHD Background — The clinical significance of the interaction between clopidogrel and proton pump inhibitors ( PPIs ) remains unclear . Methods and Results — We examined the relationship between PPI use and 1-year cardiovascular events ( cardiovascular death , myocardial infa rct ion , or stroke ) in patients with acute coronary syndrome r and omized to clopidogrel or ticagrelor in a prespecified , nonr and omized subgroup analysis of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial . The primary end point rates were higher for individuals on a PPI ( n=6539 ) compared with those not on a PPI ( n=12 060 ) at r and omization in both the clopidogrel ( 13.0 % versus 10.9 % ; adjusted hazard ratio [ HR ] , 1.20 ; 95 % confidence interval [ CI ] , 1.04–1.38 ) and ticagrelor ( 11.0 % versus 9.2 % ; HR , 1.24 ; 95 % CI , 1.07–1.45 ) groups . Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI ( PPI versus non-PPI gastrointestinal treatment : clopidogrel , HR , 0.98 ; 95 % CI , 0.79–1.23 ; ticagrelor , HR , 0.89 ; 95 % CI , 0.73–1.10 ) . In contrast , patients on no gastric therapy had a significantly lower primary end point rate ( PPI versus no gastrointestinal treatment : clopidogrel , HR , 1.29 ; 95 % CI , 1.12–1.49 ; ticagrelor , HR , 1.30 ; 95 % CI , 1.14–1.49 ) . Conclusions — The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel . However , a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment . Therefore , in the PLATO trial , the association between PPI use and adverse events may be due to confounding , with PPI use more of a marker for , than a cause of , higher rates of cardiovascular events . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00391872 BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) Objective Gastroesophageal reflux disease ( GERD ) is a common disease which can cause troublesome symptoms and affect quality of life . In addition to esophageal complications , GERD may also be a risk factor for extra-esophageal complications . Both GERD and coronary artery disease ( CAD ) can cause chest pain and frequently co-exist . However , the association between GERD and acute myocardial infa rct ion ( AMI ) remain unclear . The purpose of the study was to compare the incidence of acute myocardial infa rct ion in GERD patients with an age- , gender- , and comorbidity matched population free of GERD . We also examine the association of the risk of AMI and the use of acid suppressing agents in GERD patients . Methods We identified patients with GERD from the Taiwan National Health Insurance Research Data base . The study cohort comprised 54,422 newly diagnosed GERD patients ; 269,572 r and omly selected age- , gender- , comorbidity-matched subjects comprised the comparison cohort . Patients with any prior CAD , AMI or peripheral arterial disease were excluded . Incidence of new AMI was studied in both groups . Results A total 1,236 ( 0.5 % ) of the patients from the control group and 371 ( 0.7 % ) patients from the GERD group experienced AMI during a mean follow-up period of 3.3 years . Based on Cox proportional-hazard model analysis , GERD was independently associated with increased risk of developing AMI ( hazard ratio ( HR ) = 1.48 ; 95 % confidence interval ( CI ) : 1.31–1.66 , P < 0.001 ) . Within the GERD group , patients who were prescribed proton pump inhibitors ( PPIs ) for more than one year had slightly decreased the risk of developing AMI , compared with those without taking PPIs ( HR = 0.57 ; 95 % CI : 0.31–1.04 , P = 0.066 ) . Conclusions This large population -based study demonstrates an association between GERD and future development of AMI , however , PPIs use only achieved marginal significance in reducing the occurrence of AMI in GERD patients . Further prospect i ve studies are needed to evaluate whether anti-reflux medication may reduce the occurrence of acute ischemic event in GERD patients Background Recent evidence suggests that proton pump inhibitors ( PPIs ) might be linked with adverse cardiac events , but a causal relationship is unproven . Methods We applied the self-matched case series method to two studies using population -based health care data from Ontario , Canada between 1996 and 2008 . The first included subjects aged 66 years or older hospitalized for acute myocardial infa rct ion within 12 weeks following initiation of PPI , while the second included subjects hospitalized for heart failure . In both studies we design ated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks . To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines , drugs with no plausible causal link to adverse cardiac events . Results During the 13-year study period , we identified 5550 hospital admissions for acute myocardial infa rct ion and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy . In the main analyses , we found that initiation of a PPI was associated with a higher risk of acute myocardial infa rct ion ( odds ratio 1.8 ; 95 % confidence interval 1.7 to 1.9 ) and heart failure ( odds ratio 1.8 ; 95 % confidence interval 1.7 to 1.9 ) . However , secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines , drugs with no known or suspected association with adverse cardiac events . Conclusion PPIs are associated with a short-term risk of adverse cardiac events , but similar associations are seen with other drugs exhibiting no known cardiac toxicity . Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause- and -effect OBJECTIVES : High- quality data regarding the efficacy of acid-suppressive treatment for unexplained chest pain are lacking . The aim of this study was to evaluate the efficacy of esomeprazole in primary -care treatment of patients with unexplained chest pain stratified for frequency of reflux/regurgitation symptoms . METHODS : Patients with a ≥2-week history of unexplained chest pain ( unrelated to gastroesophageal reflux ) who had at least moderate pain on ≥2 of the last 7 days were stratified by heartburn/regurgitation frequency ( ≤1 day/week ( stratum 1 ) vs. ≥2 days/week ( stratum 2 ) ) and r and omized to 4 weeks of double-blind treatment with twice-daily esomeprazole 40 mg or placebo . Chest pain relief during the last 7 days of treatment ( ≤1 day with minimal symptoms assessed daily using a 7-point scale ) was analyzed by stratum in keeping with the predetermined analysis plan . RESULTS : Overall , 599 patients ( esomeprazole : 297 , placebo : 302 ) were r and omized . In stratum 1 , more esomeprazole than placebo recipients achieved chest pain relief ( 38.7 % vs. 25.5 % ; P=0.018 ) ; no between-treatment difference was observed in stratum 2 ( 27.2 % vs. 24.2 % ; P=0.54 ) . However , esomeprazole was superior to placebo in a post-hoc analysis of the whole study population ( combined strata ; 33.1 % vs. 24.9 % ; P=0.035 ) . CONCLUSIONS : A 4-week course of high-dose esomeprazole provided statistically significant relief of unexplained chest pain in primary -care patients who experienced infrequent or no heartburn/regurgitation , but there was no such significant reduction in patients with more frequent reflux symptoms Background and Aims Proton pump inhibitors ( PPIs ) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome . Recent pre- clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease . We explore this potential risk in the general population via data -mining approaches . Methods Using a novel approach for mining clinical data for pharmacovigilance , we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population . Results In multiple data sources , we found gastroesophageal reflux disease ( GERD ) patients exposed to PPIs to have a 1.16 fold increased association ( 95 % CI 1.09–1.24 ) with myocardial infa rct ion ( MI ) . Survival analysis in a prospect i ve cohort found a two-fold ( HR = 2.00 ; 95 % CI 1.07–3.78 ; P = 0.031 ) increase in association with cardiovascular mortality . We found that this association exists regardless of clopidogrel use . We also found that H2 blockers , an alternate treatment for GERD , were not associated with increased cardiovascular risk ; had they been in place , such pharmacovigilance algorithms could have flagged this risk as early as the year 2000 . Conclusions Consistent with our pre- clinical findings that PPIs may adversely impact vascular function , our data -mining study supports the association of PPI exposure with risk for MI in the general population . These data provide an example of how a combination of experimental studies and data -mining approaches can be applied to prioritize drug safety signals for further investigation Proton pump inhibitors ( PPIs ) are commonly used drugs for the treatment of gastric reflux . Recent retrospective cohorts and large data base studies have raised concern that the use of PPIs is associated with increased cardiovascular ( CV ) risk . However , there is no prospect i ve clinical study evaluating whether the use of PPIs directly causes CV harm . We conducted a controlled , open-label , cross-over pilot study among 21 adults aged 18 and older who are healthy ( n=11 ) or have established clinical cardiovascular disease ( n=10 ) . Study subjects were assigned to receive a PPI ( Prevacid ; 30 mg ) or a placebo pill once daily for 4 weeks . After a 2-week washout period , participants were crossed over to receive the alternate treatment for the ensuing 4 weeks . Subjects underwent evaluation of vascular function ( by the EndoPAT technique ) and had plasma levels of asymmetric dimethylarginine ( ADMA , an endogenous inhibitor of endothelial function previously implicated in PPI-mediated risk ) measured prior to and after each treatment interval . We observed a marginal inverse correlation between the EndoPAT score and plasma levels of ADMA ( r = −0.364 ) . Subjects experienced a greater worsening in plasma ADMA levels while on PPI than on placebo , and this trend was more pronounced amongst those subjects with a history of vascular disease . However , these trends did not reach statistical significance , and PPI use was also not associated with an impairment in flow-mediated vasodilation during the course of this study . In conclusion , in this open-label , cross-over pilot study conducted among healthy subjects and coronary disease patients , PPI use did not significantly influence vascular endothelial function . Larger , long-term and blinded trials are needed to mechanistically explain the correlation between PPI use and adverse clinical outcomes , which has recently been reported in retrospective cohort studies Objectives : To determine if an educational intervention initiated in secondary care can influence prescribing of proton pump inhibitors ( PPIs ) in the community . Methods : A prospect i ve study of PPI use in patients admitted to medical wards in a university hospital . A simple educational intervention was employed to reduce inappropriate prescribing of PPIs in the community . Results : In the pre-intervention analysis 66/271 ( 24 % ) patients were receiving treatment with a PPI prescribed in the community . In 36/66 ( 54 % ) patients the PPI had been prescribed inappropriately . Six months after the intervention 91/344 ( 26 % ) patients were prescribed a PPI in the community . In only 45 of these 91 ( 49 % ) patients was there a recommended indication . Conclusion : The intervention used in this study had no effect on the proportion of patients taking a PPI at the time of hospital admission or on the appropriateness of prescribing in the community OBJECTIVES To determine the prevalence and economic effect of inappropriate proton pump inhibitor ( PPI ) use in an ambulatory care setting . STUDY DESIGN Retrospective medical record review of r and om sample with subgroup analysis . METHODS Patients were categorized according to appropriateness of pharmacotherapy based on documented upper gastrointestinal tract diagnoses , gastrointestinal or extraesophageal symptoms , or gastroprotection . Adverse events potentially associated with PPI use were identified . RESULTS Of 946 patients in an ambulatory care setting , 35.4 % were given PPI therapy for an appropriately documented upper gastrointestinal tract diagnosis , 10.1 % received PPIs empirically for symptomatic treatment based on extraesophageal symptoms , 18.4 % received PPIs for gastroprotection , and 36.1 % had no documented appropriate indication for PPI therapy . In a subgroup analysis , 48.6 % of patients across all 4 categories received PPIs without documentation of reevaluation of upper gastrointestinal tract symptoms , accounting for 1034 patient-years of PPI use . The total cost of inappropriate PPI use was $ 233,994 based on over-the-counter PPI costs and $ 1,566,252 based on average wholesale price costs . Potentially related adverse events in this cohort included Clostridium difficile – associated diarrhea ( 6 cases ) and community-acquired pneumonia ( 1 case ) , but no cases of hip fracture or vitamin B12 deficiency were identified . CONCLUSIONS Proton pump inhibitors are often overused in the ambulatory care setting without documented valid indications . Inappropriate use of PPIs is associated with substantial cost expenditure and with the potential for adverse events Most patients with gastro‐oesophageal reflux disease ( GERD ) , regardless of endoscopic status , suffer symptomatic relapse within 6 months of stopping acid suppressant therapy RATIONALE Gastroesophageal reflux disease ( GERD ) is common among patients with asthma ; however , studies investigating the effect of proton pump inhibitors on asthma outcomes report conflicting results . OBJECTIVES To investigate the effect of esomeprazole 40 mg once or twice daily on asthma outcomes in patients with concomitant symptoms of GERD . METHODS This 26-week , r and omized , double-blind , placebo-controlled study ( NCT00317044 ) included adult patients ( 18 - 70 yr ) with moderate-to-severe asthma and symptomatic GERD . The change in morning peak expiratory flow ( primary variable ) , evening peak expiratory flow , FEV(1 ) , asthma symptoms , Asthma Quality of Life Question naire , Reflux Disease Question naire , and tolerability were assessed . MEASUREMENTS AND MAIN RESULTS A total of 961 patients were r and omized and 828 completed the study . Relative to baseline , improvement in morning peak expiratory flow was observed for both esomeprazole 40 mg once daily ( + 3.5 L/min ; 95 % CI , -3.2 to 10.2 ) and 40 mg twice daily ( + 5.5 L/min ; 95 % CI , -1.2 to 12.2 ) , although no statistically significant between-treatment differences were apparent . At treatment end , both doses of esomeprazole significantly improved FEV(1 ) versus placebo ( + 0.09 L and + 0.12 L ; P = 0.0039 and P < 0.0001 , respectively ) . However , only esomeprazole 40 mg twice daily demonstrated a significant improvement when FEV(1 ) was calculated over the entire 26-week period ( + 0.07 L ; P = 0.0042 ) . Significant improvements in Asthma Quality of Life Question naire total score were demonstrated for both esomeprazole doses compared with placebo ( + 0.28 and + 0.41 ; P = 0.0006 and P < 0.0001 , respectively ) . CONCLUSIONS Esomeprazole may improve pulmonary function and asthma-related quality of life . However , the improvements were minor and of small clinical significance Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure . The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure . Twenty-two symptomatic chronic heart failure patients were r and omized to receive 800 mg oral magnesium oxide daily or placebo for 3 months . Data collected included large and small arterial elasticity/compliance , hemodynamic parameters , exercise capacity , and quality -of-life score at baseline , 1 week , and 3 months . Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo . This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients |
12,522 | 21,143,545 | Community-based models of care are not inherently more costly than institutions , once account is taken of individuals ' needs and the quality of care .
New community-based care arrangements could be more expensive than long-stay hospital care but may still be seen as more cost-effective because , when properly set up and managed , they deliver better outcomes . | Many European mental health systems are undergoing change as community-centred care replaces large-scale institutions .
We review empirical evidence from three countries ( UK , Germany , Italy ) that have made good progress with this rebalancing of care .
We focus particularly on the economic consequences of deinstitutionalisation . | BACKGROUND Intensive case management is commonly advocated for the care of the severely mentally ill , but evidence of its cost-effectiveness is lacking . AIMS To investigate the cost-effectiveness of intensive compared with st and ard case management for patients with severe psychosis . METHOD 708 patients with psychosis and a history of repeated hospital admissions were r and omly allocated to st and ard ( case-loads 30 - 35 ) or intensive ( case-loads 10 - 15 ) case management . Clinical and re source use data were assessed over two years . RESULTS No statistically significant difference was found between intensive and st and ard case management in the total two-year costs of care per patient ( means 24,550 Pounds and 22,700 Pounds , respectively , difference 1850 Pounds , 95 % CI--1600 Pounds to 5300 Pounds ) . There was no evidence of differential effects in African-Caribbean patients or in the most disabled . Psychiatric in-patient hospital stay accounted for 47 % of the total costs , but neither such hospitalisation nor other clinical outcomes differed between the r and omised groups . CONCLUSION Reduced case-loads have no clear beneficial effect on costs , clinical outcome or cost-effectiveness . The policy of advocating intensive case management for patients with severe psychosis is not supported by these results Objective : To compare the clinical outcome and costs of care of psychiatric patients allocated to community multidisciplinary teams or to hospital based care programmes after discharge from inpatient care . Design : R and omised controlled trial . Setting : Inner London ( Paddington and North Kensington ) and outer London ( Brent ) psychiatric services . Subjects : 155 patients with severe mental illness with a previous admission within the past 2 years . Main outcome measures : Ratings of clinical psychopathology , depression , anxiety , and social functioning ; comprehensive costs of health care . Results : Clinical outcomes were available for 133 patients and cost data for 144 patients after 1 year . The clinical outcomes of the two models of care were essentially similar , but admission to hospital was more likely in the hospital based care group and the costs of health care were 14 % greater per patient than in the community group . This difference , however , was dwarfed by a twofold difference in the costs of care in the outer London services compared with those in inner London . This was explained largely by greater inpatient care for outer London patients ( 58 median bed days v 18 for inner London patients ) , more of which was provided by extracontractual referrals to other psychiatric hospitals as Brent had only 0.28/1000 beds available for acute adult patients compared with 0.82/1000 in Paddington and North Kensington over the period of the study . Conclusion : Aftercare by community teams for psychiatric patients with severe mental illness has a similar outcome to hospital based aftercare but with fewer admissions to hospital . When psychiatric bed requirements are insufficient for a population , however , neither form of aftercare is effective as greater use of hospital beds elsewhere swamps any advantage of community care programmes , with disintegration and discontinuity of psychiatric services leading to escalating costs . Key messages Community psychiatric care has generally been shown to require fewer beds than more hospital focused care Clinical outcomes in psychiatric patients with recurrent psychotic illness r and omised to community focused or hospital focused care after discharge from hospital and followed up for 1 year were similar Costs were lower for patients in the community group , which had fewer admissions to hospital Costs were twice as high in one of the areas covered by the study , mainly because of the insufficient number of beds in the area , with great reliance on psychiatric beds outside the catchment area When the number of psychiatric beds in an area becomes too low there is no advantage in providing better community care because the impact of this is swamped by the disintegrating effects of inpatient care outside the catchment Background : This paper presents the quality of life ( QOL ) outcome results from the UK700 r and omised controlled trial of case management . Method : A total of 708 patients with severe mental illness were r and omly assigned to intensive and st and ard forms of case management in four sites in the UK . QOL was assessed using the Lancashire Quality of Life Profile , which provides a self-reported objective and subjective appraisal of eight life domains ( finances , work , leisure , family , social relations , living situation , safety and health ) . The outcome after 2 years was examined using univariate and multivariate analyses . Results : Significant improvements in QOL over the 2 years were observed . The QOL outcome did not differ significantly by case management treatment conditions or by diagnosis . A better outcome was associated with improvements in depression and with the location ( site ) of treatment . In one site there were significant improvements in all eight domains and overall QOL , with moderate or better effect sizes ( > 0.4 ) in three domains and overall QOL . Conclusions : Depression should be assessed when subjective QOL measures are used . Better means for describing service organisations and the context /place in which they operate should be developed in order to explain more of the variance in QOL outcomes BACKGROUND Part of the community psychiatric nurse ( CPN ) service was reorganised into a community support team ( CST ) , with staff acting as case managers . An economic evaluation ran parallel to the comparison with generic CPN care . METHOD Eighty-two clients were r and omly allocated to experimental and control groups . Costs were comprehensively measured over a pre-referral period ( three months ) , and then at 6 , 12 , and 18 months . RESULTS The economic evaluation found a cost difference between the groups . Generic group costs averaged 89 pounds per patient per week more than CST group costs . The difference was only significant for the first six months . Changes in the burden of cost across agencies were observed . CONCLUSIONS Although CPN inputs and costs were higher for the CST group , there was a significant short-term reduction in total cost . Beyond the short term , the CST did not confer cost or cost-effectiveness advantages BACKGROUND In Italy , Residential Facilities ( RFs ) have completely replaced Mental Hospitals ( MHs ) for the residential care of mentally ill patients . We studied all patients resident in 265 r and omly sample d Italian RFs ( 20 % of the total ) . METHOD Structured interviews focusing on each patient were conducted by trained research assistants with the manager and staff of each RF . Patients were rated with the HoNOS and the GAF , and comprehensive information about their sociodemographic and clinical status and care history were gathered . RESULTS Of the 2962 patients living in the sample d facilities , most were males ( 63.2 % ) who had never married , more than 70 % were over 40 years ; 85 % on a pension , most commonly because of psychiatric disability . A substantial proportion ( 39.8 % ) had never worked and very few were currently employed ( 2.5 % ) ; 45 % of the sample was totally inactive , not even assisting with domestic activities in the facility . Two-thirds had a diagnosis of schizophrenia ; co-morbid or primary substance abuse were uncommon . Twenty-one per cent had a history of severe interpersonal violence , but violent episodes in the RFs were infrequent . The managers judged almost three-quarters appropriately placed in their facilities and considered that very few had short-term prospect s of discharge . CONCLUSIONS Italian RFs cater for a large patient population of severely mentally ill requiring residential care . Discharge to independent accommodation is uncommon . Future studies should attempt to clarify how to match residential programmes with patients ' disabilities BACKGROUND The Daily Living Programme ( DLP ) offered intensive home-based care with problem-centred case management for seriously mentally ill people facing crisis admission to the Maudsley Hospital , London . The cost-effectiveness of the DLP was examined over four years . METHOD A r and omised controlled study examined cost-effectiveness of DLP versus st and ard in/out-patient hospital care over 20 months , followed by a r and omised controlled withdrawal of half the DLP patients into st and ard care . Three patient groups were compared over 45 months : DLP throughout the period , DLP for 20 months followed by st and ard care , and st and ard care throughout . Bivariate and multivariate analyses were conducted ( the latter to st and ardise for possible inter- sample differences stemming from sample attrition and to explore sources of within- sample variation ) . RESULTS The DLP was more cost-effective than control care over months 1 - 20 , and also over the full 45-month period , but the difference between groups may have disappeared by the end of month 45 . CONCLUSIONS The reduction of the cost-effectiveness advantage for home-based care was perhaps partly due to the attenuation of DLP care , although sample attrition left some comparisons under-powered BACKGROUND A controlled study tested whether the superior outcome of community care for serious mental illness ( SMI ) in Madison and in Sydney would also be found in inner London . METHOD Patients from an inner London catchment area who faced emergency admission for SMI ( many were violent or suicidal ) were r and omised to 20 months or more of either home-based care ( Daily Living Programme , DLP ; n = 92 ) , or st and ard in-patient and later out-patient care ( controls , n = 97 ) . Most DLP patients had brief in-patient stays at some time . Measures included number and duration of in-patient admissions , independent ratings of clinical and social function , and patients ' and relatives ' satisfaction . RESULTS Outcome was superior with home-based care . Until month 20 , DLP care improved symptoms and social adjustment slightly more , and enhanced patients ' and relatives ' satisfaction . From 3 to 18 months DLP care greatly reduced the number of in-patient bed days as long as the DLP team was responsible for any in-patient phase its patients had . Cost was less . DLP care did not reduce the number of admissions , nor of deaths from self-harm ( 3 DLP , 2 control ) . One DLP patient killed a child . Even at 20 months many DLP and control patients still had severe symptoms , poor social adjustment , no job , and need for assertive follow-up and heavy staff input . ( Beyond 20 months most gains were lost apart from satisfaction . ) CONCLUSIONS It is unclear how much the gain until 20 months from home-based care was due to its site of care , its being problem-centred , its teaching of daily living skills , its assertive follow-up , the home care team 's keeping responsibility for any in-patient phase , its coordination of total care ( case management ) , or to other care components . Home-based care is hard to organise and vulnerable to many factors , and needs careful training and clinical audit if gains are to be sustained Treatment records of 94 patients treated in an experimental home-based psychiatric service and 78 control patients in st and ard care were collected over one year . There was a substantial reduction in in-patient care in the experimental group , both in terms of proportion admitted and duration of admissions , despite similar out-patient and general practice care . The total treatment costs were significantly larger ( > 50 % ) for st and ard care when controlled for by diagnostic grouping . Costs were further examined by including all specialist psychiatric care , and by excluding patients with primary diagnoses of brain damage or alcoholism . Sensitivity analysis explored the effects of increasing the cost of home visits . The relative cost effectiveness of the experimental service persisted . Clinical and social outcome was similar in control and experimental groups BACKGROUND This study evaluated whether a community psychiatric nurse ( CPN ) team providing a comprehensive aftercare service , using a case management approach , improves psychopathology and social functioning of the long-term mentally ill , and reduces hospital use compared with a generic CPN team . METHOD Patients suffering from severe and persistent mental health problems were r and omised to intensive aftercare or generic care after referral to the CPN manager . Each group contained 41 patients who were assessed at baseline and at 6 , 12 and 18 months by an independent research psychologist . Outcome measures included the GAS , PSE , SAS , patient and relatives ' satisfaction , number of admissions , and length of stay . RESULTS No difference between the groups was found on any of the outcome measures , despite the much higher number of contacts of the intensive ( n = 52 ) versus generic CPNs ( n = 13 ) and the much greater range of interventions . CONCLUSIONS Intensive aftercare for people with persistent mental health problems was not found to be of greater benefit than generic CPN care . Many factors need to be considered for aftercare to be effective , including community re sources , process of care , and staff training BACKGROUND The Daily Living Programme ( DLP ) offered problem-oriented , home-based care for people aged 17 - 64 with severe mental illness facing emergency admission to the Bethlem-Maudsley Hospital . The multidisciplinary DLP team acted as direct provider and link with other services . Each patient had a key worker . Cost-effectiveness was assessed . METHOD The comprehensive costs of DLP and st and ard in-patient care were compared within a r and omised controlled trial . Cost measures ranged over all service inputs and living expenses . The costs of informal care and lost employment were also considered . Assessment s of service use , costs and outcomes were conducted at referral , 4 , 11 and 20 months . RESULTS The DLP was significantly less costly than st and ard treatment in both short and medium term ( P = 0.000 ) . Cost savings accrued almost exclusively to the NHS , with no other agency 's costs being higher . CONCLUSIONS Coupled with mildly encouraging outcome results over the 20 month period , the DLP was clearly cost-effective in this medium term BACKGROUND There has been a widespread development of community multi-disciplinary teams aim ed to deliver coordinated comprehensive mental health care , yet there is little published evidence on the quality of care and economics of providing such care for people with severe mental illness . METHOD This is a clustered r and omized controlled economic comparison of the quality of care for patients with chronic schizophrenia by a multi-disciplinary community team with close links with primary care , and a traditional psychiatric service in a district general hospital psychiatric unit . RESULTS Two years after it was established , patients with access to the community team had more of their needs met ; they had fewer unmet needs ; and they were more satisfied with the care they had received . They had more service contacts and received more interventions . The community team result ed in savings in the use of some hospital re sources but these were not sufficient to offset the cost of the new service . The community team successfully directed care to patients with more needs , whereas no such relationship was evident for the traditional hospital-based service . Four years after the team was established , it met a greater proportion of needs for underactivity , daily living skills , use of public amenities and managing finances . CONCLUSIONS Better quality care was provided at 2 and 4 years after its establishment by the multi-disciplinary community service than the traditional hospital-based service . Re sources were targeted more efficiently by the community service |
12,523 | 26,192,405 | Meta-regression found differences between study outcomes may be attributable to length of breastfeeding recall , study design , country income and date of study inception .
Some of the protective effect of breastfeeding for asthma may be related to recall bias in studies of lesser method ological quality .
There is some evidence that breastfeeding is protective for asthma ( 5 - 18 years ) .
There is weaker evidence for a protective effect for eczema ≤2 years and allergic rhinitis ≤5 years of age , with greater protection for asthma and eczema in low-income countries | AIM To systematic ally review the association between breastfeeding and childhood allergic disease . | Abstract Objectives : To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years . Design : Prospect i ve cohort study . Setting : Western Australia . Subjects : 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years . Main outcome measures : Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age , allowing for several important confounders : sex , gestational age , smoking in the household , and early childcare . Results : After adjustment for confounders , the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years : asthma diagnosed by a doctor ( odds ratio 1.25 , 95 % confidence interval 1.02 to 1.52 ) ; wheeze three or more times since 1 year of age ( 1.41 , 1.14 to 1.76 ) ; wheeze in the past year ( 1.31 , 1.05 to 1.64 ) ; sleep disturbance due to wheeze within the past year ( 1.42 , 1.07 to 1.89 ) ; age when doctor diagnosed asthma ( hazard ratio 1.22 , 1.03 to 1.43 ) ; age at first wheeze ( 1.36 , 1.17 to 1.59 ) ; and positive skin prick test reaction to at least one common aeroallergen ( 1.30 , 1.04 to 1.61 ) . Conclusion : A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth . These findings are important for our underst and ing of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits . Key messages Asthma is the leading cause of admission to hospital in Australian children and its prevalence is increasing Whether breast feeding protects against asthma or atopy , or both , is controversial Asthma is a complex disease , and the relative risks between breast feeding and asthma or atopy are unlikely to be large ; this suggests the need for investigation in a large prospect i ve birth cohort with timely assessment of atopic outcomes and all relevant exposures Exclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctor Public health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and BACKGROUND Breast-feeding clearly protects against early wheezing , but recent data suggest that it might increase later risk of atopic disease and asthma . OBJECTIVE We sought to examine the relationship between breast-feeding and later asthma and allergy outcomes by using data from the Avon Longitudinal Study of Parents and Children , a large birth cohort in the United Kingdom . METHODS We used adjusted logistic regression models to evaluate the association between breast-feeding and atopy at age 7 years , bronchial responsiveness to methacholine at age 8 years , and wheeze at ages 3 and 7 1/2 years . Bayesian methods were used to assess the possibility of bias caused by an influence of early wheezing on the duration of breast-feeding , as well as selection bias . RESULTS Breast-feeding was protective for wheeze in the first 3 years of life ( odds ratio [ OR ] of 0.80 [ 95 % CI , 0.70 - 0.90 ] for > or = 6 months relative to never ) but not wheeze ( OR , 0.98 ; 95 % CI , 0.79 - 1.22 ) , atopy ( OR , 1.12 ; 95 % CI , 0.92 - 1.35 ) , or bronchial hyperresponsiveness ( OR , 1.07 ; 95 % CI , 0.82 - 1.40 ) at ages 7 to 8 years . Bayesian models adjusting for the longer duration of breast-feeding among children with wheezing in early infancy produced virtually identical results . CONCLUSIONS We did not find consistent evidence for either a deleterious effect or a protective effect of breast-feeding on later risk of allergic disease in a large prospect i ve birth cohort of children with objective outcome measures and extensive data on potential confounders and effect modifiers . Neither reverse causation nor loss to follow-up appears to have material ly biased our results BACKGROUND Opinions and recommendations about the optimal duration of exclusive breastfeeding have been strongly divided , but few published studies have provided direct evidence on the relative risks and benefits of different breastfeeding duration s in recipient infants . OBJECTIVE We examined the effects on infant growth and health of 3 compared with 6 mo of exclusive breastfeeding . DESIGN We conducted an observational cohort study nested within a large r and omized trial in Belarus by comparing 2862 infants exclusively breastfed for 3 mo ( with continued mixed breastfeeding through > /= 6 mo ) with 621 infants who were exclusively breastfed for > /= 6 mo . Regression to the mean , within-cluster correlation , and cluster- and individual-level confounding variables were accounted for by using multilevel regression analyses . RESULTS From 3 to 6 mo , weight gain was slightly greater in the 3-mo group [ difference : 29 g/mo ( 95 % CI : 13 , 45 g/mo ) ] , as was length gain [ difference : 1.1 mm ( 0.5 , 1.6 mm ) ] , but the 6-mo group had a faster length gain from 9 to 12 mo [ difference : 0.9 mm/mo ( 0.3 , 1.5 mm/mo ) ] and a larger head circumference at 12 mo [ difference : 0.19 cm ( 0.07 , 0.31 cm ) ] . A significant reduction in the incidence density of gastrointestinal infection was observed during the period from 3 to 6 mo in the 6-mo group [ adjusted incidence density ratio : 0.35 ( 0.13 , 0.96 ) ] , but no significant differences in risk of respiratory infectious outcomes or atopic eczema were apparent . CONCLUSIONS Exclusive breastfeeding for 6 mo is associated with a lower risk of gastrointestinal infection and no demonstrable adverse health effects in the first year of life OBJECTIVE To estimate the prevalence of wheezing in the chest among adults , and to explore the effect of some variables on the prevalence of this condition . METHODS This was a prospect i ve cohort study on individuals born in the city of Pelotas ( Southern Brazil ) in 1982 . A total of 4,297 subjects was traced in 2004 - 5 , representing 77.4 % of the original cohort . Data were collected by means of interviews using the ISAAC ( International Study of Asthma and Allergies in Childhood Steering Committee ) question naire . Associations between the outcome ' occurrence of wheezing in the chest within the 12 months prior to the interview ' and the variables of socioeconomic , demographic and birth characteristics were tested by means of multivariable analyses , using Poisson regression . RESULTS The prevalence of wheezing over the preceding year was 24.9 % . Among the individuals reporting wheezing , 54.6 % reported difficulty in sleeping , and 12.9 % reported difficulty in speaking due to wheezing . The prevalence of wheezing in the chest was significantly higher among women . This association was maintained in analyses adjusted for non-white skin color , family history of asthma and low socioeconomic level . Among men , there was no significant association in the analyses adjusted for skin color and family income at birth . Family histories of asthma and poverty throughout life presented significant associations with wheezing in the chest . For both sexes , there were no associations with the variables of birth weight and breastfeeding duration . CONCLUSIONS The prevalence of wheezing in the chest was high , and subjects with low family income at birth were more likely to have had wheezing in the chest over the preceding year The aim of this study was to assess the preventive effect of exclusive breast-feeding and early solid food avoidance on atopic dermatitis ( AD ) in infancy . This study is part of a dietary clinical trial in a prospect i ve cohort of healthy term newborns at risk of atopy . It was recommended to breast-feed for at least 4 months and to avoid solid food in the same time-period . Eight hundred and sixty-five infants exclusively breast-fed , and 256 infants partially or exclusively formula-fed , were followed-up until the end of the first year following birth . AD and sensitization to milk and egg were considered as study end-points . The 1-year incidence of AD was compared between the two study groups . Adjusted odds ratios ( OR ) with 95 % confidence intervals ( CI ) were calculated by multiple logistic regression . The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given . In the breast-fed group , the adjusted OR for AD was 0.47 ( 95 % CI 0.30 - 0.74 ) . The strongest risk factor was the occurrence of AD in the subject 's core family . The risk of infants with AD to be sensitized to milk was four times higher , and to egg eight times higher , than in infants without AD . Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence . We conclude that in infants at atopic risk , exclusive breast-feeding for at least 4 months is effective in preventing AD in the first year of life The relationship between breastfeeding , respiratory and other allergic disorders has been controversial . Our aim was to investigate the relationships between breastfeeding , respiratory outcomes , eczema and atopy at 15 months of age in a prospect i ve birth cohort in New Zeal and . A total of 1105 children were enrolled at birth , and 1011 ( 91.2 % ) were followed up at 15 months . Logistic regression was used to model associations between breastfeeding duration and respiratory outcomes , eczema and atopy after adjusting for relevant confounding variables : ethnicity , socio-economic status , parity , body mass index , smoking in pregnancy , gender and respiratory infections in the first 3 months of life . Breastfeeding was associated with a significant reduction in the risk of adverse respiratory outcomes at 15 months . After adjustment for confounders , each month of exclusive breastfeeding reduced the risk of doctor-diagnosed asthma by 20 % ( odds ratio 0.80 , 95 % confidence interval 0.71 to 0.90 ) , wheezing by 12 % ( 0.88 , 0.82 to 0.94 ) and inhaler use by 14 % ( 0.86 , 0.78 to 0.93 ) . Associations for both exclusive and additional breastfeeding duration s , and respiratory outcomes remained independently significant when modelled simultaneously . Although independently associated with all respiratory outcomes , adjusting for parental history of allergic disease or maternal history of asthma did not alter our findings . Breastfeeding was not associated with eczema or atopy at 15 months . In conclusion , there was a significant protective effect of breastfeeding on infant wheezing and other adverse respiratory outcomes that may be early indicators of asthma in New Zeal and children RATIONALE Virus-induced wheezing episodes in infancy often precede the development of asthma . Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood . OBJECTIVES To define the relationship between specific viral illnesses and early childhood asthma development . METHODS A total of 259 children were followed prospect ively from birth to 6 years of age . The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage , culture , and multiplex reverse transcriptase-polymerase chain reaction . The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed . MEASUREMENTS AND MAIN RESULTS Viral etiologies were identified in 90 % of wheezing illnesses . From birth to age 3 years , wheezing with respiratory syncytial virus ( RSV ) ( odds ratio [ OR ] , 2.6 ) , rhinovirus ( RV ) ( OR , 9.8 ) , or both RV and RSV ( OR , 10 ) was associated with increased asthma risk at age 6 years . In Year 1 , both RV wheezing ( OR , 2.8 ) and aeroallergen sensitization ( OR , 3.6 ) independently increased asthma risk at age 6 years . By age 3 years , wheezing with RV ( OR , 25.6 ) was more strongly associated with asthma at age 6 years than aeroallergen sensitization ( OR , 3.4 ) . Nearly 90 % ( 26 of 30 ) of children who wheezed with RV in Year 3 had asthma at 6 years of age . CONCLUSIONS Among outpatient viral wheezing illnesses in infancy and early childhood , those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort OBJECTIVE Previous studies of predictors of atopic dermatitis have had limited sample size , small numbers of variables , or retrospective data collection . The purpose of this prospect i ve study was to investigate several perinatal predictors of atopic dermatitis occurring in the first 6 months of life . DESIGN We report findings from 1005 mothers and their infants participating in Project Viva , a US cohort study of pregnant women and their offspring . The main outcome measure was maternal report of a provider 's diagnosis of eczema or atopic dermatitis in the first 6 months of life . We used multiple logistic regression models to assess the associations between several simultaneous predictors and incidence of atopic dermatitis . RESULTS Cumulative incidence of atopic dermatitis in the first 6 months of life was 17.1 % . Compared with infants born to white mothers , the adjusted odds ratio ( OR ) for risk of atopic dermatitis among infants born to black mothers was 2.41 ( 95 % confidence interval [ CI ] : 1.47 , 3.94 ) and was 2.58 among infants born to Asian mothers ( 95 % CI : 1.27 , 5.24 ) . Male infants had an OR of 1.76 ( 95 % CI : 1.24 , 2.51 ) . Increased gestational age at birth was a predictor ( OR : 1.14 ; 95 % CI : 1.02 , 1.27 , for each 1-week increment ) , but birth weight for gestational age was not . Infants born to mothers with a history of eczema had an OR of 2.67 ( 95 % CI : 1.74 , 4.10 ) ; paternal history of eczema also was predictive , although maternal atopic history was more predictive than paternal history . Several other perinatal , social , feeding , and environmental variables were not related to risk of atopic dermatitis . CONCLUSIONS Black and Asian race/ethnicity , male gender , higher gestational age at birth , and family history of atopy , particularly maternal history of eczema , were associated with increased risk of atopic dermatitis in the first 6 months of life . These findings suggest that genetic and pre- and perinatal influences are important in the early presentation of this condition The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease . A r and omised controlled trial examined the effects of withholding cows ' milk protein during the first three months of life and replacing cows ' milk with soya milk . The children were followed up to the age of 7 years . Withholding cows ' milk did not reduce the incidence of allergy or wheezing . Children who had ever been breast fed had a lower incidence of wheeze than those who had not ( 59 % and 74 % respectively ) . The effect persisted to age 7 years in the non-atopics only , the risk of wheeze being halved in the breast fed children after allowing for employment status , sex passive smoking , and overcrowding . Allergic disease was not associated with exposure to tobacco smoke , house dust mite antigen , or cats . Breast feeding may confer long term protection against respiratory infection The association between breastfeeding and wheezing , lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood ( ISAAC ) Phase II . Cross-sectional studies were performed in 27 centres in 20 countries . Information on disease and exposure factors was collected by parental question naires . Data from 54,000 r and omly selected school children ( aged 8–12 yrs , 31,759 with skin prick testing ) and a stratified sub sample ( n = 4,888 ) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function . R and om effect models for meta- analysis were applied to calculate combined odds ratios ( ORs ) . Any breastfeeding was associated with less wheeze both in affluent ( adjusted OR ( ORadj ) 0.87 , 95 % confidence interval ( CI ) 0.78–0.97 ) and nonaffluent countries ( ORadj 0.80 , 95 % CI 0.68–0.94 ) . Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries ( ORadj 0.69 , 95 % CI 0.53–0.90 ) . Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries . In contrast , breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only ( mean ratio 1.11 , 95 % CI 1.02–1.20 ) . Breastfeeding is associated with protection against nonatopic wheeze , which becomes particularly evident in nonaffluent countries . Overall , breastfeeding was not related to any measure of allergy . These findings may explain some of the controversy regarding breastfeeding , since the direction of the association with breastfeeding depends on the predominating wheeze phenotype ( e.g. atopic , nonatopic ) Early feeding with cows ' milk ( CM ) may cause cows ' milk allergy ( CMA ) . Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant . We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA , the effects of formula and breast feeding on the subsequent immunologic types of CMA , and the importance of immune factors present in colostrum in the immune responses of infants with CMA . In a cohort of 6209 infants , 824 were exclusively breast-fed and 87 % required supplementary milk while in the maternity hospital : 1789 received CM formula , 1859 pasteurized human milk , and 1737 whey hydrolysate formula . The cumulative incidence of CMA , verified by a CM elimination-challenge test , was 2.4 % in the CM , 1.7 % in the pasteurized human milk and 1.5 % in the whey hydrolysate group . Among these infants , exposure to CM at hospital and a positive atopic heredity increased the risk of CMA . Of the exclusively breast-fed infants , 2.1 % had CMA . Risk factors for the development of IgE-mediated CMA were : exposure to CM at hospital , breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding . The content of transforming growth factor-beta1 ( TGF-beta1 ) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA . In infants with CMA , TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM , but positively with infants ' IgA and IgG antibodies to CM proteins . Feeding of CM formula at maternity hospital increases the risk of CMA , but exclusive breast-feeding does not eliminate the risk . Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA . Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA ABSTRACT A prospect i ve case‐control study is presented to assess an allergy prevention programme in children up to 36 months of age . Infants born at three maternity hospitals were followed from birth : 279 infants with high atopic risk ( intervention group ) were compared with 80 infants with similar atopic risk but no intervention ( non‐intervention group ) . The intervention programme included dietary measures ( exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet ) and environmental measures ( avoidance of parental smoking in the presence of the babies , day care > 2 years of life ) . Mothers in this group who had insufficient breast milk were r and omly assigned to one of two coded formulas : either a hydrolysed milk formula ( Nidina HA , Nestlé ) or a conventional adapted formula ( Nan , Nestlé ) . Other environmental measures remained the same as for the breastfeeding mothers . The non‐intervention group were either breastfed or received the usual Italian milk feeding and weaning diet , without environmental advice . The main outcome measures were anthropometric measurements and allergic disease manifestations . Normal anthropometric data were observed both in the intervention group and in the nonintervention group . The incidence of allergic manifestations was much lower in the intervention group than in the nonintervention group at 1 year ( 11.5 versus 54.4 % , respectively ) and at 2 years ( 14.9 versus 65.6 % ) and 3 years ( 20.6 versus 74.1 % ) . Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non‐intervention group from birth up to the second year of life , while urticaria and gastrointestinal disorders were only present in the non‐intervention group in the first year of life . Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non‐intervention group . Relapse of the same allergic symptom was less in the intervention group ( 13.0 % ) than in the non‐intervention group ( 36.9 % ) . In comparison to the non‐intervention group , there were fewer intervention group cases with two or more different allergic symptoms ( 8.7 versus 32.6 % ) , and they were more likely to avoid steroid treatment ( 0 versus 10.8 % ) and hospital admission ( 0 versus 6.5 % ) . Babies in the non‐intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group . In the intervention group the breastfed infants had the lowest incidence of allergic symptoms , followed by the infants fed the hydrolysed formula ( ns ) . Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants , although less than their counterparts in the non‐intervention group . Of the affected subjects in the intervention group , 80.4 % were RAST and /or Prick positive to food or inhalant allergens . Total serum IgE values detected at birth in the intervention group were not predictive , but at 1 and 2 years of age , IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy . In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups . Of the various factors tested in the non‐intervention group , the following were the most important in the pathogenesis of allergic symptoms : ( i ) formula implementation begun in the first week of life ; ( ii ) early weaning ( < 4 months ) ; ( iii ) feeding beef ( < 6 months ) ; ( iv ) early introduction of cow 's milk ( < 6 months ) ; and ( v ) parental smoking in the presence of the babies and early day care admission ( < 2 years of life ) . All the preventive measures used in this study ( exclusive breastfeeding and /or hydrolysed milk feeding , delayed and selective introduction of solid foods , and environmental advice ) were effective at the third year of follow‐up , greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma , and exclusive breastfeeding with respiratory illness , atopy and asthma in children . A cohort study of 2,602 children enrolled prior to birth and followed prospect ively , provided data on respiratory illness , the method of feeding in the first year of life , as reported on a prospect i ve diary card , and current asthma at the age of 6 yrs ( defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold , and currently taking either preventer or reliever asthma medication ) , as reported by parental question naire . Atopy was defined by a positive skin-prick test assessed at the age of 6 yrs . Wheezing lower respiratory illness ( LRI ) in the first year of life , particularly multiple episodes of wheezing LRI , increased the risk for current asthma in both nonatopic ( odds ratio ( OR ) 4.10 , p⪕0.0005 ) and atopic children ( OR 9.00 , p⪕0.0005 ) , but did not increase the risk for atopy . In contrast , up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted ( p=0.006 ) and adjusted ( p=0.057 ) analysis . Following adjustment , exclusive breastfeeding for < 4 months was associated with an increased risk for current asthma ( OR 1.36 , 95 % confidence interval 1.00–1.85 , p=0.047 ) . Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs , suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within individual children . Exclusive breastfeeding protects against asthma via effects on both these pathways , as well as through other as yet undefined mechanisms OBJECTIVES We investigated the relationship between breastfeeding , asthma and atopy , and child body mass index ( BMI ) . METHODS From a prospect i ve birth cohort ( n = 2860 ) in Perth , Western Australia , 2195 children were followed up to age 6 years . Asthma was defined as doctor-diagnosed asthma and wheeze in the last year , and atopy was determined by skin prick test of 1596 children . Breastfeeding , BMI , asthma , and atopy were regressed allowing for confounders and the propensity score for overweight . RESULTS Using fractional polynomials , we found no association between breastfeeding and overweight . Less exclusive breastfeeding was associated with increased asthma and atopy , and BMI increased with asthma . CONCLUSIONS Less exclusive breastfeeding leads to increases in child asthma and atopy and a higher BMI is a risk factor for asthma The evidence of the effect of the age at introduction of new foods during infancy on the development of asthma and allergic rhinitis is inconsistent and scarce . We set out to study these associations . A prospect i ve birth cohort of infants with increased HLA-DQB1-conferred risk for type 1 diabetes was recruited in 1996 - 2000 . The families completed at home a record on the age at introduction of new foods . Persistent asthma and allergic rhinitis were assessed at the age of 5 years with an International Study of Asthma and Allergies in Childhood-type question naire . The Cox proportional hazards regression analyses were adjusted for parental asthma and allergic diseases , and several perinatal and sociodemographical factors . Out of the 1293 children , 77 ( 6.0 % ) developed persistent asthma ; and out of the 1288 children , 185 ( 14.4 % ) developed allergic rhinitis by the age of 5 years . Early age at introduction of oats was associated with a reduced risk of persistent asthma ( hazard ratio ( HR ; 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.36 ( 0.15 , 0.85 ) and 0.37 ( 0.22 , 0.62 ) , respectively , P < 0.001 ) . Early age at introduction of fish was dose dependently associated with a decreased risk of allergic rhinitis ( HR ( 95 % CI ) for the first and mid-tertiles compared with the latest tertile was 0.34 ( 0.22 , 0.54 ) and 0.45 ( 0.28 , 0.70 ) , respectively , P < 0.001 ) . The present finding that age at introduction of oats is inversely and independently associated with development of persistent asthma is novel . We confirmed the earlier observation that the age at introduction of fish is inversely related to the risk of allergic rhinitis . Clinical implication s remain to be determined 54 babies who had been solely breast-fed for more than 6 months , 77 babies who had been breast-fed for 2 - -6 months , and 105 babies who had been weaned to cow's-milk-based formulas at less than 2 months were followed for the first 3 years of life . All the babies had the same pattern of solid food intake until 1 year of age . Compared with formula feeding , prolonged breast-feeding result ed in a lower incidence of severe or obvious atopic disease particularly in babies with family history of atopy BACKGROUND The relationship between infant feeding and childhood asthma is controversial . This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma . METHODS Healthy non-selected newborn infants ( n=1246 ) were enrolled at birth . Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on ⩾2 question naires at 6 , 9 , 11 or 13 years . Recurrent wheeze ( ⩾4 episodes in the past year ) was reported by question naire at seven ages in the first 13 years of life . Duration of exclusive breast feeding was based on prospect i ve physician reports or parental question naires completed at 18 months . Atopy was assessed by skin test responses at the age of 6 years . RESULTS The relationship between breast feeding , asthma , and wheeze differed with the presence or absence of maternal asthma and atopy in the child . After adjusting for confounders , children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed ( OR 8.7 , 95 % CI 3.4 to 22.2 ) . This relationship was only evident for atopic children and persisted after adjusting for confounders . In contrast , the relation between recurrent wheeze and breast feeding was age dependent . In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze ( OR 0.45 , 95 % CI 0.2 to 0.9 ) , regardless of the presence or absence of maternal asthma or atopy in the child . Beginning at the age of 6 years , exclusive breast feeding was unrelated to prevalence of recurrent wheeze , except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze ( OR 5.7 , 95 % CI 2.3 to 14.1 ) , especially if the child was atopic . CONCLUSION The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child . While associated with protection against recurrent wheeze early in life , breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years , but only for atopic children with asthmatic mothers BACKGROUND Predictive models have rarely been used in allergy research and practice . However , they might support physicians in advising patients . OBJECTIVE The aim of this study was to create predictive models for the incidence and persistence of allergic rhinitis ( AR ) during adolescence . METHODS A prospect i ve population -based cohort study was conducted starting at age 9 to 11 years . Potential risk factors for atopic diseases obtained at baseline in 2810 subjects were used to create predictive logistic regression models for the incidence and persistence of physician-diagnosed AR with current symptoms at age 15 to 18 years . RESULTS Positive skin prick test responses to outdoor allergens at baseline were the most important determinant for both the incidence and persistence of AR until follow-up . For the incidence of AR , positive skin prick test responses to indoor allergens , parental history of asthma , female sex , and not having been breast-fed exclusively for 2 or more months were additional statistically significant independent risk factors . Depending on the number of risk factors present , the probability of the incidence of AR increased from 2 % ( no risk factors present ) to 72 % ( full model ; 95 % CI , 58 % to 85 % ) . The probability of persistence of AR ranged from 33 % ( no risk factors present ) to 83 % ( full model ; 95 % CI , 70 % to 97 % ) . CONCLUSION The course of AR over puberty can be predicted using risk factors that are easy to determine in childhood . Sensitization to outdoor allergens seems to play a much greater role for disease development than sensitization to indoor allergens . This might help pediatricians in advising patients Background Wheezing is the most common symptom of childhood respiratory tract illnesses . It is important not only for its associated acute morbidity , but also for the fact that early childhood wheezing confers a high risk for asthma . Epidemiological studies from various countries show that 10–15 % of children < 1 year of age and 25 % of children < 5 years of age have wheezing-associated respiratory tract illness , and one-third of these children develop asthma later in life . Methods In this retrospective study , we evaluated the association between a history of wheezing and prenatal , postnatal , familial , and environmental risk factors in 858 7-year-old children , r and omly selected from seven primary schools in Bursa , Turkey , by means of an easy-to-underst and question naire form . Among these children , 12.4 % had a history of early transient wheezing , 7.1 % had persistent wheezing , and 7.7 % had late onset wheezing ; 72.8 % had no wheezing symptoms and 33.3 % of children who experienced wheezing during the first 3 years of life had physician-diagnosed asthma . Results Notable risk factors associated with wheezing were as follows : male gender , lower socioeconomic status , premature birth , maternal smoking during pregnancy , bottle-feeding before 2 months of age , dampness and mold at home , hospitalization due to any respiratory illness in infancy , history of croup between 6 months and 5 years of age , frequent upper respiratory infections during the first 3 years of life , allergic eczema in the child , and any allergic disease in the mother or siblings . Conclusion This study shows that the high rates of reported wheezing in the 858 primary school children in Bursa are clearly attributable to important risk factors that have long been recognized and discussed by research ers worldwide , and this suggests that all efforts at primary prevention may be insufficient Controversy surrounds the issue of whether children with asthmatic mothers should be breast-fed . The aim of this study was to investigate whether maternal asthma status alters the association between asthma and breast-feeding . In a cohort study of 2602 West Australian children enrolled before birth and followed prospect ively , we collected data on method of infant feeding , maternal asthma ( as reported by parental question naire ) , atopy ( as measured by skin prick test ) , and current asthma ( defined as a physician 's diagnosis of asthma and wheeze in the last year ) at 6 years of age . The risk of childhood asthma increased if exclusive breast-feeding was stopped ( other milk was introduced ) before 4 months ( odds ratio , 1.28 ; 95 % CI , 1.01 - 1.62 ; P = .038 ) , and this risk was not altered by atopy or maternal asthma status . After adjusting for covariates , exclusive breast-feeding for less than 4 months was a significant risk factor for current asthma ( odds ratio , 1.35 ; 95 % CI , 1.00 - 1.82 ; P = .049 ) . There was no formal statistical interaction between breast-feeding and maternal asthma status ( P = .970 ) . In this study maternal asthma status did not modify the association between asthma and breast-feeding duration . We recommend that infants with or without a maternal history of asthma be exclusively breast-fed for 4 months and beyond BACKGROUND In Phase Three of the International Study of Asthma and Allergies in Childhood ( ISAAC ) , we investigated the relationship between breast feeding in infancy and symptoms of asthma , rhinoconjunctivitis and eczema in 6 - 7 year old children . METHODS Parents or guardians of 6 - 7 year old children completed written question naires on current symptoms of asthma , rhinoconjunctivitis and eczema , and on a range of possible asthma risk factors including a history of breast feeding ever . Prevalence odds ratios were estimated using logistic regression , adjusted for gender , region of the world , language , per capita gross national income , and other risk factors . RESULTS In all 206,453 children from 72 centres in 31 countries participated in the study . Reported breast feeding ever was not associated with current wheeze , with an odds ratio ( adjusted for gender , region of the world , language , per capita gross national income , and factors encountered in infancy ) of 0.99 ( 95 % CI 0.92 - 1.05 ) , current rhinoconjunctivitis ( OR 1.00 , 95 % CI 0.93 - 1.08 ) , current eczema ( OR 1.05 , 95 % CI 0.97 - 1.12 ) , or symptoms of severe asthma ( OR 0.95 , 95 % CI 0.87 - 1.05 ) . Breast feeding was however associated with a reduced risk of severe rhinoconjunctivitis ( OR 0.74 , 95 % CI 0.59 - 0.94 ) and severe eczema ( OR 0.79 , 95 % CI 0.66 - 0.95 ) . CONCLUSIONS There was no consistent association between breast feeding use in the first year of life and either a history or current symptoms of wheezing , rhinoconjunctivitis or eczema in 6 - 7 year old children , but possibly an effect on severe symptoms of the latter two conditions OBJECTIVE To analyze the effects of pregnancy and early events in the newborn on the risk of subsequent atopic dermatitis ( AD ) during the first year of life . PATIENTS AND METHODS This is a prospect i ve multicenter cohort study of newborns during the first year of life . Newborns identified on r and om days in three obstetrics departments in the area of Bergamo , Lombardy , Northern Italy , were eligible . At baseline , the mothers were interviewed by medical staff during their stay in hospital after delivery . At 6 and 12 months after delivery , a postal question naire was sent to the parents . Relative risks were calculated with and without adjustment by multiple regression analysis . RESULTS A total of 1081 newborns entered the study : 796 ( 74 % ) parents answered the 12-month question naire . Hundred and thirty-eight ( 17 % ) reported a diagnosis of AD at 6 months and 222 ( 28 % ) at 12 months . Parental history of AD and /or asthma was associated with an increased risk of AD ( RR 1.5 , 95%CI 1.1 - 2.0 ) . Birth weight was slightly associated with an increased risk of AD : RR 1.04 , 95%CI 1.001 - 1.08 ( continuous variable , increment of 100 grams ) . No association emerged between breast feeding , smoking , and risk of AD . CONCLUSIONS This study in an Italian offspring cohort points to family history of atopic diseases and body weight at birth as relevant risk factors . The study was unable to document associations with other perinatal factors particularly breast feeding and parental smoking in the perinatal period BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders BACKGROUND Most infants developing atopic dermatitis have a low risk for atopy . Primary prevention of atopic dermatitis is difficult . OBJECTIVE To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life . METHODS Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks , either having started with formula feeding or being on full breast-feeding ( breast-feeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . RESULTS A total of 414 infants were r and omized to the prebiotic group and 416 infants to the control group . A total of 300 infants were followed in the breast-feeding group . Up to the first birthday , atopic dermatitis occurred in significantly fewer infants from the prebiotic group ( 5.7 % ) than from the control group ( 9.7 % ; P = .04 ) . The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group ( 7.3 % ) . In a Cox regression model , the rate of atopic dermatitis was significantly lower by 44 % in the prebiotic group versus the control group ( P = .04 ) . The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants . CONCLUSION Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants BACKGROUND The literature regarding the association between breast-feeding and atopic diseases has been contradictory . OBJECTIVE We have assessed the relationship between breast-feeding and atopic disorders in a cohort followed into middle age . METHODS The Tasmanian Asthma Study is a population -based prospect i ve cohort study that has followed participants from the age of 7 to 44 years . Exclusive breast-feeding in the first 3 months of life was examined as a risk factor for atopic diseases by using multiple logistic regression and generalized estimating equation analyses . RESULTS At age 7 years , exclusively breast-fed children with a maternal history of atopy had a marginally lesser risk of current asthma than those not exclusively breast-fed ( odds ratio [ OR ] , 0.8 ; 95 % CI , 0.6 - 1.0 ) . However , after age 7 years , the risk reversed , and exclusively breast-fed children had an increased risk of current asthma at 14 ( OR , 1.46 ; 95 % CI , 1.02 - 2.07 ) , 32 ( OR , 1.84 ; 95 % CI , 1.06 - 3.3 ) , and 44 ( OR , 1.57 ; 95 % CI , 1.15 - 2.14 ) years . Exclusively breast-fed children also had a reduced risk of food allergy at age 7 years but an increased risk of food allergy ( OR , 1.26 ; 95 % CI , 1.1 - 1.5 ) and allergic rhinitis ( OR , 1.2 ; 95 % CI , 1.0 - 1.3 ) at 44 years . CONCLUSION Exclusively breast-fed babies with a maternal history of atopy were less likely to develop asthma before the age of 7 years , but more likely to develop asthma after the age of 7 years . CLINICAL IMPLICATION S The current recommendation to breast-feed high-risk infants for protection against early wheezing illness can be confirmed . However , the recommendation should be reconsidered for protection against allergic asthma and atopy in the longer term Background Preschool rhinovirus ( RV ) wheezing illnesses predict an increased risk of childhood asthma ; however , it is not clear how specific viral illnesses in early life relate to lung function later on in childhood . Objective To determine the relationship of virus-specific wheezing illnesses and lung function in a longitudinal cohort of children at risk for asthma . Methods Two hundred thirty-eight children were followed prospect ively from birth to 8 years of age . Early life viral wheezing respiratory illnesses were assessed by using st and ard techniques , and lung function was assessed annually by using spirometry and impulse oscillometry . The relationships of these virus-specific wheezing illnesses and lung function were assessed by using mixed-effect linear regression . Results Children with RV wheezing illness demonstrated significantly decreased spirometry values , FEV1 ( P = .001 ) , FEV0.5 ( P < .001 ) , FEF25 - 75 ( P < .001 ) , and also had abnormal impulse oscillometry measures —more negative reactance at 5 Hz ( P < .001)—compared with those who did not wheeze with RV . Children who wheezed with respiratory syncytial virus or other viral illnesses did not have any significant differences in spirometric or impulse oscillometry indices when compared with children who did not . Children diagnosed with asthma at ages 6 or 8 years had significantly decreased FEF25 - 75 ( P = .05 ) compared with children without asthma . Conclusion Among outpatient viral wheezing illnesses in early childhood , those caused by RV infections are the most significant predictors of decreased lung function up to age 8 years in a high-risk birth cohort . Whether low lung function is a cause and /or effect of RV wheezing illnesses is yet to be determined Aims : To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age . Methods : A birth cohort of 4089 infants was followed prospect ively in Stockholm , Sweden . Information about various exposures was obtained by parental question naires when the infants were 2 months old , and about allergic symptoms and feeding at 1 and 2 years of age . Duration of exclusive and partial breast feeding was assessed separately . Symptom related definitions of various allergic diseases were used . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) were estimated in a multiple logistic regression model . Adjustments were made for potential confounders . Results : Children exclusively breast fed during four months or more exhibited less asthma ( 7.7 % v 12 % , ORadj = 0.7 , 95 % CI 0.5 to 0.8 ) , less atopic dermatitis ( 24 % v 27 % , ORadj = 0.8 , 95 % CI 0.7 to 1.0 ) , and less suspected allergic rhinitis ( 6.5 % v 9 % , ORadj = 0.7 , 95 % CI 0.5 to 1.0 ) by 2 years of age . There was a significant risk reduction for asthma related to partial breast feeding during six months or more ( ORadj = 0.7 , 95 % CI 0.5 to 0.9 ) . Three or more of five possible allergic disorders — asthma , suspected allergic rhinitis , atopic dermatitis , food allergy related symptoms , and suspected allergic respiratory symptoms after exposure to pets or pollen — were found in 6.5 % of the children . Exclusive breast feeding prevented children from having multiple allergic disease ( ORadj = 0.7 , 95 % CI 0.5 to 0.9 ) during the first two years of life . Conclusion : Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease — that is , asthma , atopic dermatitis , and suspected allergic rhinitis , up to 2 years of age . This protective effect was also evident for multiple allergic disease OBJECTIVE To investigate the effects of breastfeeding on wheezing and current asthma in children 2 to 6 years of age . STUDY DESIGN Infants ( n=1105 ) were enrolled in a prospect i ve birth cohort in New Zeal and . Detailed information about infant feeding was collected using question naires administered at birth and at 3 , 6 , and 15 months . From this , duration s of exclusive and any breastfeeding were calculated . Information about wheezing and current asthma was collected at 2 , 3 , 4 , 5 , and 6 years . Logistic regression was used to model associations between breastfeeding and outcomes with and without adjustment for confounders . RESULTS After adjustment for confounders , each month of exclusive breastfeeding was associated with significant reductions in current asthma from 2 to 6 years ( all , P<.03 ) . Current asthma at 2 , 3 , and 4 years was also reduced by each month of any breastfeeding ( all , P<.005 ) . In atopic children , exclusive breastfeeding for ≥ 3 months reduced current asthma at ages 4 , 5 , and 6 by 62 % , 55 % , and 59 % , respectively . CONCLUSION Breastfeeding , particularly exclusive breastfeeding , protects against current asthma up to 6 years . Although exclusive breastfeeding reduced risk of current asthma in all children to age 6 , the degree of protection beyond 3 years was more pronounced in atopic children Epidemiological studies associated with breastfeeding have provided conflicting results about whether it is preventive or a risk factor for atopic eczema in children . The current prospect i ve study investigated the relationship between breastfeeding and the risk of atopic eczema in Japan . A birth cohort of 763 infants was followed . The first survey during pregnancy and the second survey between 2 and 9 months postpartum collected information on potential confounding factors and atopic eczema status . Data on breastfeeding and symptoms of atopic eczema were obtained from question naires in the third survey from 16 to 24 months postpartum . The following variables were a priori selected as potential confounders : maternal age , maternal and paternal history of asthma , atopic eczema , and allergic rhinitis , indoor domestic pets ( cats , dogs , birds , or hamsters ) , family income , maternal and paternal education , maternal smoking during pregnancy , baby 's sex , baby 's birth weight , baby 's older siblings , household smoking in the same room as the infant , and time of delivery before the third survey . In the third survey , 142 infants ( 18.6 % ) were revealed to have developed atopic eczema based on criteria of the International Study of Asthma and Allergies in Childhood . In an overall analysis , neither exclusive nor partial breastfeeding was significantly related to the risk of atopic eczema . After excluding 64 infants identified with suspected atopic eczema in the second survey , both exclusive breastfeeding for 4 months or more and partial breastfeeding for 6 months or more were independently associated with an increased risk of atopic eczema only among infants with no parental history of allergic disorders [ multivariate odds ratios were 2.41 ( 95 % confidence interval , 1.10 - 5.55 ) and 3.39 ( 95 % confidence interval , 1.20 - 12.36 ) , respectively ] . The authors found that , overall , neither exclusive nor partial breastfeeding had a strong impact on the risk of atopic eczema . However , a parental allergic history may affect the risk Abstract Objective : To investigate whether changes in certain perinatal and social factors explain the increased prevalence of hay fever and eczema among British adolescents between 1974 and 1986 . Design : Two prospect i ve birth cohort studies . Setting : Engl and , Wales , and Scotl and . Subjects : 11 195 children born 3 - 9 March 1958 and 9387 born 5 - 11 April 1970 . Main outcome measures : Parental reports of eczematous rashes and of hay fever or allergic rhinitis in the previous 12 months at age 16 . Results : The prevalence of the conditions over the 12 month period increased between 1974 and 1986 from 3.1 % to 6.4 % ( prevalence ratio 2.04 ( 95 % confidence interval 1.79 to 2.32 ) for eczema and from 12.0 % to 23.3 % ( prevalence ratio 1.93 ( 1.82 to 2.06 ) ) for hay fever . Both conditions were more commonly reported among children of higher birth order and those who were breast fed for longer than 1 month . Eczema was more commonly reported among girls and hay fever among boys . The prevalence of hay fever decreased sharply between social classes I and V , increased with maternal age up to the early 30s , and was lower in children whose mothers smoked during pregnancy . Neither condition varied significantly with birth weight . When adjusted for these factors , the relative odds of hay fever ( 1986 v 1974 ) increased from 2.23 ( 2.05 to 2.43 ) to 2.40 ( 2.19 to 2.63 ) . Similarly , the relative odds of eczema rose from 2.02 ( 1.73 to 2.36 ) to 2.14 ( 1.81 to 2.52 ) . Conclusions : Taken together , changes between cohorts in sex , birth weight , birth order , maternal age , breast feeding , maternal smoking during pregnancy , and father 's social class at birth did not seem to explain any of the observed rise in the prevalence of hay fever and eczema . However , correlates of these factors which have changed over time may still underlie recent increases in allergic disease . Key messages Between 1974 and 1986 there was an apparent doubling in the 12 month period prevalence of both hay fever and eczema among British 16 year olds The prevalence of hay fever increased significantly with higher social class and decreasing birth order , both trends being steeper for children born in 1958 than for those born in 1970 Hay fever was less common if the mother smoked during pregnancy and more common with increasing maternal age up to the early 30s . The prevalences of hay fever and eczema were slightly higher among children breast fed for more than one month When taken together , differences in sex , birth weight , birth order , maternal age , breast feeding , maternal smoking during pregnancy , and father 's social class at birth between children born in 1958 and those born in 1970 did not seem to explain any of the observed increases in prevalence of hay fever and eczema at age 16 Factors related to father 's social class at birth , birth order , maternal age , smoking during pregnancy , and breast feeding deserve further investigation as possible explanations of the increase in atopic disease in Britain and Infantile atopic eczema ( AE ) is a risk marker for future asthma . This study assesses the contribution of modifiable exposures to infantile AE . If modifiable exposures contribute substantially to infantile AE , its prevention might be a sensible approach to asthma prevention . Pregnant women ( n = 1978 ) were systematic ally recruited from maternity hospitals of the Slovak Republic ; their birthed cohort of 1990 children were prospect ively followed for 1 yr . Children 's exposures to selected environmental and dietary factors were assessed via maternal question naires administered at delivery and 1 yr of age . A child was considered to have AE , based on physical examination ( SCORAD index > 2 ) or mother 's report of a previous physician diagnosis . Multivariate logistic regression was used to calculate adjusted odds ratios and percent total regression scores ( TRS ) for each variable . At 1 yr of age 1326 ( 67 % ) of the children remained in the cohort and 207 ( 15.6 % ) developed AE . Various modifiable environmental and dietary exposures increased the likelihood of AE ( ownership of cats ; consumption of infant formula , eggs , and fish ) while others decreased the likelihood of AE ( ownership of livestock ; exclusive breast feeding for > or = 4 months ) . Overall , modifiable exposures contributed less to the TRS than did non-modifiable exposures ( 38 % vs. 62 % , respectively ) . The modifiable exposure category that contributed most to the TRS was infant feeding practice s ( 27.5 % TRS ) . Modifiable exposures -- especially those related to infant feeding practice s -- significantly contribute to infantile AE , although modifiable factors contribute less overall than do non-modifiable exposures Breast feeding ( BF ) provides many advantages to the offspring ; however , at present there is an ongoing debate as to whether or not it prevents allergic diseases . The aim of the current study was to investigate the effect of duration of BF on eczema in the first year of life . A birth cohort of 1128 infants was followed prospect ively from 5 months of pregnancy . Data were collected using question naires , a medical examination and blood tests for allergy at the age of 1 yr . Breast feeding was not statistically significant associated with eczema in the first year of life [ adj ORs with 95 % CIs : 0.8 ( 0.4 - 1.3 ) , 0.8 ( 0.5 - 1.3 ) and 1.0 ( 0.6 - 1.5 ) for BF duration of 1 - 6 wk , 7 - 12 wk and > or = 13 wk , respectively ] . Eczema was positively associated with atopy and educational level of the mother , use of antibiotics in pregnancy and passive smoking by the child during the first 12 months . Regular postnatal contact of the infants with dogs was inversely associated with eczema . Breast feeding was positively associated with eczema among children with non-atopic parents [ adj ORs with 95 % CIs : 2.1 ( 0.4 - 10.6 ) , 2.2 ( 0.4 - 11.3 ) and 1.9 ( 0.4 - 8.5 ) for BF duration of 1 - 6 wk , 7 - 12 wk and > or = 13 wk , respectively ] , whereas an inverse association was found among children with atopic parents [ adj ORs with 95 % CIs : 0.6 ( 0.3 - 1.3 ) , 0.7 ( 0.3 - 1.4 ) and 0.9 ( 0.5 - 1.7 ) for the same BF duration s ] . However , these associations were not statistically significant . Breast feeding has no significant effect on the prevalence of eczema in the first year of life . The effect of BF on eczema in children depends on parental atopy BACKGROUND A number of studies have observed an association between breast-feeding and increased risk of development of asthma and eczema . It has been proposed that these results might be due to early signs of atopic disease in the infant causing mothers to prolong breast-feeding . OBJECTIVE We sought to determine whether early symptoms of atopic disease ( eczema , food reaction , or asthma ) or positive skin prick test responses reduce the likelihood of ceasing breast-feeding . METHODS A prospect i ve birth cohort of 620 infants from Melbourne , Australia , was used . Telephone interviews every 4 weeks were conducted until 64 weeks and then again at 78 and 104 weeks to determine duration of breast-feeding ( both exclusive and total ) and evidence of atopic disease . Because of the varying time of onset of atopic symptoms , they were modeled as time-varying covariates in Cox models . RESULTS Only 52 ( 8.4 % ) infants did not establish breast-feeding , whereas an additional 103 ( 25.0 % ) did not establish exclusive breast-feeding . Early signs of atopic disease or sensitization were independently associated with an approximately 28 % reduction in risk of ceasing exclusive breast-feeding ( adjusted hazard ratio , 0.72 ; 95 % CI , 0.53 - 0.97 ) ; P=.029 ) , but there was no evidence for a relationship with risk of ceasing breast-feeding completely ( adjusted hazard ratio , 1.12 ; 95 % CI , 0.92 - 1.37 ; P=.262 ) . CONCLUSION Early signs of atopic disease might prolong the duration of exclusive breast-feeding . This could mask a protective effect of breast-feeding or even result in breast-feeding appearing to be a risk factor for the development of atopic diseases . Future investigation of the relationship between breast-feeding and atopic diseases should consider this possibility The present study aim ed to investigate the prevalence of atopic dermatitis in primary schoolchildren in Denizli , Turkey , and to determine the possible risk factors for atopic dermatitis in home environment . A self-administered question naire was h and led to the parents of 2,100 children aged 7 to 15 years , from three r and omized primary schools and 1,644 ( 78.9 % ) completed and returned the question naire . The question naire included the United Kingdom Working Party diagnostic criteria and asked about conditions that could affect the course of atopic dermatitis . The prevalence of atopic dermatitis and coexisting factors that may affect the course of the disease were evaluated in 1,644 children ( 825 girls and 819 boys ) . The prevalence of atopic dermatitis was detected as 4.9 % . Passive smoking , heating systems either in the house or in the child 's bedroom , and the number of people living in the house had no significant effect ( p > 0.005 ) . The difference in prevalence of atopic dermatitis between developed and developing countries is striking . The determination of the factors that have an influence in this issue will probably enable us to change the course and frequency of atopic dermatitis |
12,524 | 31,739,647 | The groups receiving most SL were healthy older adults and older adult population s with aging disabilities and illnesses .
The articles in the present review highlight that SL can have a positive effect on older adults ' health promotion and can enhance their community participation | Service-Learning ( SL ) has become a teaching methodology that promotes social and personal skills while helping groups in need and at risk of social exclusion .
This paper is a systematic review of the literature on SL experiences and research on college subjects in the area of health-care promotion in setting s for older adults . | Abstract Service-Learning can be a rewarding and challenging experience for students . One of the rewards for students can be the connection between their course work and real life experience . However , students interacting with population s with which they have limited prior experience face unique challenges . We developed a training program design ed to facilitate comfort with older adults who have dementia for service-learners in a gerontology course who were serving at an Adult Day Services ( ADS ) program . Students in the course completed pre- and post-surveys assessing level of contact with older adults and attitudes on aging . Service-learners serving at the ADS comprised the treatment group ( n = 5 ) while those serving at other S-L sites made up the control group ( n = 11 ) . Independent and paired sample t-tests indicated that the training program contributed to intra-individual and group differences in comfort working with older adults and with adults who are cognitively impaired . Differences in attitudes about older adults were also identified . Implication s for adult development courses involving S-L at dementia care programs are discussed Background Health-related fitness has been reported to be associated with improved quality of life ( QoL ) in the elderly . Health-related fitness is comprised of several dimensions that could be enhanced by specific training regimens . It has remained unclear how various dimensions of health-related fitness interact with QoL in postmenopausal women . Objective The purpose of the current study was to investigate the relationship between the dimensions of health-related fitness and QoL in elderly women . Methods A cohort of 408 postmenopausal women in a rural area of Taiwan was prospect ively collected . Dimensions of health-related fitness , consisting of muscular strength , balance , cardiorespiratory endurance , flexibility , muscle endurance , and agility , were assessed . QoL was determined using the Short Form Health Survey ( SF-36 ) . Differences between age groups ( stratified by decades ) were calculated using a one-way analysis of variance ( ANOVA ) and multiple comparisons using a Scheffé test . A Spearman ’s correlation analysis was performed to examine differences between QoL and each dimension of fitness . Multiple linear regression with forced-entry procedure was performed to evaluate the effects of health-related fitness . A P-value of < 0.05 was considered statistically significant . Results Age-related decreases in health-related fitness were shown for sit-ups , back strength , grip strength , side steps , trunk extension , and agility ( P<0.05 ) . An age-related decrease in QoL , specifically in physical functioning , role limitation due to physical problems , and physical component score , was also demonstrated ( P<0.05 ) . Multiple linear regression analyses demonstrated that back strength significantly contributed to the physical component of QoL ( adjusted beta of 0.268 [ P<0.05 ] ) . Conclusion Back strength was positively correlated with the physical component of QoL among the examined dimensions of health-related fitness . Health-related fitness , as well as the physical component of QoL , declined with increasing age ABSTRACT The major purpose of this study was to identify the knowledge , misconceptions , and bias regarding aging among graduate physical therapy students and to determine whether service-learning modified any of these variables . A cohort of 40 students in a graduate physical therapy program was r and omly divided into an experimental ( service-learning ) or control ( no service-learning ) group . General knowledge and attitudes about aging were measured by Palmore 's Facts on Aging Quiz I. The Wilson Student Evaluation of Faculty tool measured student evaluations of a faculty member at the end of the semester . Two-way analyses of variance with repeated measures revealed that all students increased their knowledge about aging , p < .05 . However , students who initially had negative attitudes toward older adults significantly improved their attitudes only after the service-learning experience , p < .05 . A t-test revealed that teaching evaluation scores were significantly lower in the service-learning course , p < .05 . The results suggest that service-learning effectively enhanced both the knowledge and attitudes of physical therapy students toward the older adult . Although service-learning imparted better learning for the student , there was some risk to the faculty member as evidence d by lower teaching evaluations BACKGROUND As the population ages , the effects of Alzheimer 's disease will be felt by all nurses . Providing proper care for people with Alzheimer 's disease is difficult and requires specific skills , attitudes , and knowledge . Limited data exists regarding nursing students ' attitudes and knowledge toward people with Alzheimer 's disease , whether undergraduate education prepares students to care for this population , or the best methods to support students in learning in an innovative and interactive environment . OBJECTIVES The aim of this study was to determine the effect of different educational experiences on nursing students ' knowledge and attitudes toward people with Alzheimer 's disease and to explore nursing students ' knowledge and attitudes surrounding the care of people with Alzheimer 's disease . DESIGN A convergent mixed method design . A three group ( Alzheimer 's disease clinical experience , online learning module , and no dementia-specific intervention ) , pretest and posttest design served as the quantitative arm of the study . A focus group discussion with themes extracted served as the qualitative piece of the study . SETTING College of Nursing in North Texas . PARTICIPANTS Convenience sample of 94 senior level nursing students enrolled in the undergraduate nursing program 's Community Health course . METHOD Students completed pre and posttest surveys which included Alzheimer 's Disease Knowledge Scale , Dementia Attitudes Scale , and demographic question naire . Content analysis was conducted on focus group responses to qualitative interview questions . RESULTS The Alzheimer 's disease clinical group experienced increased knowledge and improved attitudes toward people with Alzheimer 's disease compared with students who completed the online module or had no dementia-specific intervention . Four themes emerged from focus group data : Basic Alzheimer 's disease knowledge , need for Alzheimer 's disease experiential learning , negative feelings related to behaviors , and appropriate responses to behavioral and psychological symptoms of dementia . CONCLUSION Experiential learning in the form of clinical placements increased knowledge and improved attitudes about Alzheimer 's disease compared with an online module and no dementia-specific intervention |
12,525 | 28,625,077 | Teeth with periodontitis , healthy implants , or implants with peri-implantitis were colonized by periodontal microorganisms .
Porphyromonas gingivalis and especially Prevotella intermedius/nigrescens were often identified at peri-implantitis sites .
Peri-implantitis sites were also colonized by uncultivable asaccharolytic anaerobic Gram-positive rods and anaerobic Gram-negative rods , which were not frequently identified in teeth with periodontitis or healthy implants .
Opportunistic microorganisms were not found very frequently in peri-implantitis sites .
Peri-implantitis represents a heterogeneous mixed infection that includes periodontopathic microorganisms , uncultivable asaccharolytic anaerobic Gram-positive rods and other uncultivable Gram-negative rods , and , rarely , opportunistic microorganisms such as enteric rods and Staphylococcus aureus .
Sequencing methods that evaluate the entire microbiome improve identification of microorganisms associated with peri-implantitis | BACKGROUND This systematic review assesses microbiologic profiles of peri-implantitis , periodontitis , and healthy implants based on studies that evaluated microbial biofilms and entire microbiomes to establish their similarities and differences . | BACKGROUND The aim of the present prospect i ve longitudinal study of periodontally diseased and periodontally healthy patients was a clinical , microbiological , and radiographic comparison of teeth and implants and an assessment of the implant success rate . METHODS Thirty-nine partially edentulous patients provided with a total of 150 implants were enrolled in the study . Oral rehabilitation was undertaken in 15 patients treated for generalized aggressive periodontitis ( GAgP ) , 12 patients treated for generalized chronic periodontitis ( GCP ) , and 12 periodontally healthy patients . The examinations of the teeth and implants were carried out within the framework of a 3-month recall schedule over a 3-year period . At each session , clinical parameters for probing depth ( PD ) , gingival recession ( GR ) , attachment level ( AL ) , gingival index ( GI ) , and plaque index ( PI ) were recorded , and the composition of the subgingival microflora determined by dark-field microscopy . In the periodontally diseased patients , Actinobacillus actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , and Prevotella intermedia ( P.i . ) were detected at teeth and implants by DNA analysis in the first and third years after insertion of the superstructure . Intraoral radiographs of the teeth and implants were taken at baseline , immediately after insertion of the superstructure , and then 1 and 3 years later . RESULTS The GI and PI at implants and teeth remained below 0.25 and 0.6 , respectively , in all patient groups throughout the study period . At the implants and teeth , a slight increase in PD and a continuous attachment loss was recorded in the GAgP patients . The attachment loss was greater at the implants than at the teeth in all groups . The morphological distribution of the microorganisms revealed virtually healthy conditions in all groups . A.a . was detected in two GAgP patients , whereas P.g . and P.i . were found more frequently both in the GAgP and in the GCP patients . Radiographically detected bone loss was higher after 3 years at implants and teeth in the GAgP patients than in the other two groups . The implant success rates recorded were 100 % in the periodontally healthy and GCP patients , and 95.7 % in the maxilla and 100 % in the m and ible of the GAgP patients . CONCLUSIONS The results show that oral rehabilitation can be performed with implants in patients treated for generalized aggressive and chronic periodontitis . However , slight attachment loss and bone loss were registered at the implants and teeth in the patients with aggressive periodontitis BACKGROUND Two systematic review s have evaluated the quality of research and reporting of observational studies investigating the prevalence of , the incidence of and the risk factors for peri-implant diseases and of experimental clinical studies evaluating the efficacy of preventive and therapeutic interventions . MATERIAL S AND METHODS For the improvement of the quality of reporting for both observational and experimental studies , the STROBE and the Modified CONSORT recommendations were encouraged . RESULTS To improve the quality of research in peri-implant diseases , the following were recommended : the use of unequivocal case definitions ; the expression of outcomes at the subject rather than the implant level ; the implementation of study validation tools ; the reporting of potential sources of bias ; and the use of appropriate statistical methods . CONCLUSIONS In observational studies , case definitions for peri-implantitis were agreed . For risk factor determination , the progressive use of cross-sectional and case-control studies ( univariate analyses ) , to prospect i ve cohorts ( multilevel modelling for confounding ) , and ultimately to intervention studies were recommended . For preventive and interventional studies of peri-implant disease management , parallel arm RCTs of at least 6-months were encouraged . For studies of non-surgical and surgical management of peri-implantitis , the use of a composite therapeutic end point was advocated . The development of st and ard control therapies was deemed essential BACKGROUND Periodontitis and peri-implantitis are linked to the presence of several key pathogens . The treatment of these infectious processes therefore involves the reduction/eradication of bacteria associated with periodontitis . METHODS This prospect i ve , split-mouth , single-blind study followed the colonization of ' pristine ' sulci created in 42 partially edentulous patients during implant surgery ( e.g. abutment connection ) . The hypothesis was that the composition of the maturing subgingival plaque in these ' fresh ' peri-implant pockets would soon ( within 2 weeks ) be comparable to the subgingival microbiota of teeth with similar clinical parameters ( reference sites ) , including the presence of bacteria associated with periodontitis . Per patient , four subgingival plaque sample s were taken from shallow and medium pockets around implants ( test sites ) , and teeth within the same quadrant ( undisturbed microbiota as control sites ) , 1 , 2 , 4 , 13 , 26 and 78 weeks after abutment connection , respectively . The sample s were analysed by either checkerboard DNA-DNA hybridization , or cultural techniques , or real-time polymerase chain reaction ( PCR ) for intra-subject comparisons ( teeth vs. implant , for comparable probing depths ) . RESULTS Checkerboard DNA-DNA hybridization and real-time PCR revealed a complex microbiota ( including several pathogenic species ) in the peri-implant pockets within 2 weeks after abutment connection . After 7 days , the detection frequency for most species ( including the bacteria associated with periodontitis ) was already nearly identical in sample s from the fresh peri-implant pockets ( 5 % and 20 % of the microbiota belonging to red and orange complex , respectively ) when compared with sample s from the reference teeth . Afterwards ( e.g. between weeks 2 and 13 ) , the number of bacteria in peri-implant pockets only slightly increased ( + /-0.1 log value ) , with minor changes in the relative proportions of bacteria associated with periodontitis ( 8 % and 33 % of the microbiota belonging to red and orange complex , respectively ) . Although small differences were seen between teeth and implants at week 2 with cultural techniques , a striking similarity in subgingival microbiota was found with this technique from month 3 on , with nearly identical detection frequencies for bacteria associated with periodontitis for both abutment types . CONCLUSIONS This study indicates that the initial colonization of peri-implant pockets with bacteria associated with periodontitis occurs within 2 weeks Background Due to the world-wide increase in treatments involving implant placement , the incidence of peri-implant disease is increasing . Late implant failure is the result of the inability to maintain osseointegration , whose most important cause is peri-implantitis . The aim of this study was to analyze the clinical , microbiological , and immunological aspects in the peri-implant sulcus fluid ( PISF ) of patients with healthy dental implants and patients with peri-implantitis . Methods PISF sample s were obtained from 24 peri-implantitis sites and 54 healthy peri-implant sites in this prospect i ve cross-sectional study . The clinical parameters recorded were : modified gingival index ( mGI ) , modified plaque index ( mPI ) and probing pocket depth ( PPD ) . The periodontopathogenic bacteria Tannerella forsythia , Treponema denticola and Porphyromonas gingivalis were evaluated , together with the total bacterial load ( TBL ) . PISF sample s were analyzed for the quantification of Interleukin (IL)-8 , IL-1β , IL-6 , IL-10 and Tumor Necrosis Factor (TNF)-α using flow cytometry ( FACS ) . Results The mGI and PPD scores in the peri-implantitis group were significantly higher than the healthy group ( p < 0.001 ) . A total of 61.5 % of the patients with peri-implantitis had both arches rehabilitated , compared with 22.7 % of patients with healthy peri-implant tissues ; there was no implant with peri-implantitis in cases that received m and ibular treatment exclusively ( p < 0.05 ) . Concentrations of Porphyromonas gingivalis ( p < 0.01 ) , association with bacteria Porphyromonas gingivalis and Treponema denticola ( p < 0.05 ) , as well as the TBL ( p < 0.05 ) are significantly higher in the peri-implantitis group . IL-1β ( p < 0.01 ) , IL-6 ( p < 0.01 ) , IL-10 ( p < 0.05 ) and TNF-α ( p < 0.01 ) are significantly higher at the sites with peri-implantitis compared to healthy peri-implant tissue , while IL-8 did not increase significantly . Conclusion The results of the present study involving a limited patient sample suggest that the peri-implant microbiota and which dental arch was rehabilitated involved could contribute to bone loss in peri-implantitis . A significant relationship is observed between the concentration of cytokines ( interleukins 1β , 6 and 10 and TNF-α ) and the inflammatory response in peri-implantitis tissue The aim of this study was to longitudinally follow up osseointegrated titanium implants in partially dentate patients by clinical , radiographic and microbiological parameters in order to evaluate possible changes in the peri-implant health over time . Fifteen individuals treated with titanium implants , ad modum Brånemark , and followed for ten years were included in the study . Before implant placement ten years previously , the individuals had been treated for advanced periodontal disease and thereafter been included in a maintenance care program . The survival rate of the implants after ten years was 94.7 % . The bone loss was 1.7 mm when using the abutment-fixture junction as a reference point . Of the individuals , 50 % were positive for plaque at the implants . Bleeding on sulcus probing was present at 61 % of the implant surfaces . Ten years previously , the individuals had been carriers of putative periodontal pathogens , such as Porphyromonas gingivalis , Prevotella intermedia , Actinobacillus actinomycetemcomitans , Capnocytophaga spp . and Campylobacter rectus , and were also carriers of these species at the current examination . The results of the present study suggest that the presence of these putative periodontal pathogens at implants may not be associated with an impaired implant treatment . These species are most likely part of the normal resident microbiota of most individuals and may therefore be found at r and om at both stable and progressing peri-implant sites |
12,526 | 19,191,981 | There is at present not enough evidence to recommend a specific pressure ulcer classification system for use in daily practice . | AIMS To review systematic ally the interrater reliability of pressure ulcer classification systems to find out which classification should be used in daily practice .
BACKGROUND Pressure ulcer classification systems are important tools in research and practice .
They aim at providing accurate and precise communication , documentation and treatment decisions .
Pressure ulcer classifications are criticised for their low degree of interrater reliability . | The predictive validity of the Braden Scale and the timing of assessment for optimal prediction of pressure sore development ( PS ) were studied in a nursing home population . Subjects ( N = 102 ) over age 19 , free of PS and admitted within the previous 72 hr , were r and omly selected from consecutive admissions to a skilled nursing facility . Subjects were assessed for risk and skin condition every 48 to 72 hr for 4 weeks . Twenty-eight subjects ( 27.5 % ) developed a PS . A cut score of 18 used at the observation prior to the first recorded PS maximized prediction , producing a sensitivity of 79 % , a specificity of 74 % , a 54 % predictive value of a positive test , 90 % predictive value of a negative test , and 75 % correct classification rate BACKGROUND There have been no studies that have tested the Braden Scale for predictive validity and established cutoff points for assessing risk specific to different setting s. OBJECTIVES To evaluate the predictive validity of the Braden Scale in a variety of setting s ( tertiary care hospitals , Veterans Administration Medical Centers [ VAMCs ] , and skilled nursing facilities [ SNFs ] ) . To determine the critical cutoff point for classifying risk in these setting s and whether this cutoff point differs between setting s. To determine the optimal timing for assessing risk across setting s. METHOD R and omly selected subjects ( N= 843 ) older than 19 years of age from a variety of care setting s who did not have pressure ulcers on admission were included . Subjects were 63 % men , 79 % Caucasian , and had a mean age of 63 ( + /-16 ) years . Subjects were assessed for pressure ulcers using the Braden Scale every 48 to 72 hours for 1 to 4 weeks . The Braden Scale score and skin assessment were independently rated , and the data collectors were blind to the findings of the other measures . RESULTS One hundred eight of 843 ( 12.8 % ) subjects developed pressure ulcers . The incidence was 8.5 % , 7.4 % , and 23.9 % in tertiary care hospitals , VAMCs , and SNFs , respectively . Subjects who developed pressure ulcers were older and more likely to be female than those who did not develop ulcers . Braden Scale scores were significantly ( p = .0001 ) lower in those who developed ulcers than in those who did not develop ulcers . Overall , the critical cutoff score for predicting risk was 18 . Risk assessment on admission is highly predictive of pressure ulcer development in all setting s but not as predictive as the assessment completed 48 to 72 hours after admission . CONCLUSIONS Risk assessment on admission is important for timely planning of preventive strategies . Ongoing assessment in SNFs and VAMCs improves prediction and permits fine-tuning of the risk-based prevention protocol s. In tertiary care the most accurate prediction occurs at 48 to 72 hours after admission and at this time the care plan can be refined The purpose of this study was to examine the predictive validity of the Braden scale in predicting pressure sore risk and to determine the physiological and nonphysiological variables associated with the prediction of pressure ulcers in Black and Latino/Hispanic elders . A prospect i ve clinical design ws used to conduct the study . Among 74 patients aged 60 years or older , 24 patients ( 32 % ) developed either a stage 1 or stage 2 pressure ulcer . Black elders had a higher incidence rate ( 21 % ) than Latino/Hispanic elders ( 11 % ) . A 2-tailed Fisher 's exact test revealed that the Braden scale with a cutoff score of 18 was highly associated with predicting Black elders aged 75 years and older who were at risk of developing pressure ulcers ( p < or = .011 ) . Sensitivity was 81 % and specificity was 100 % . The female gender was also a highly significant factor in the development of pressure ulcers ( chi 2(1 , N = 49 ) = 6.4 , p < or = .011 ) . Overall , the Braden scale was found to be a valid tool in predicting pressure ulcer risk in Black elders aged 75 years or older when a cutoff score of 18 is used OBJECTIVE To identify specific demographic , medical , functional status , and nutritional characteristics that predict the development of stage 2 or greater pressure ulcers among patients whose activity is limited to bed or chair . DESIGN Prospect i ve inception cohort study . SETTING Tertiary care , urban , university teaching hospital . PATIENTS A total of 286 patients fulfilling the following criteria : admitted to the hospital within the previous 3 days , age 55 years or more , expected to be confined to bed or chair for at least 5 days or had a hip fracture , and without a stage 2 or greater pressure ulcer . MAIN OUTCOME MEASURE Time to in-hospital development of a stage 2 or greater pressure ulcer . RESULTS Total cumulative incidence of pressure ulcers was 12.9 % ( n = 37 ) after a median time of 9 days from admission to final skin examination . Age of 75 years or more , dry skin , nonblanchable erythema ( a stage 1 pressure ulcer ) , previous pressure ulcer history , immobility , fecal incontinence , depleted triceps skinfold , lymphopenia ( lymphocyte count < 1.50 x 10(9)/L ) , and decreased body weight ( < 58 kg ) were significantly associated with pressure ulcer development by univariate Kaplan-Meier survival analyses ( P < .05 by log-rank test ) . Risk ratios ( and 95 % confidence intervals ) for predictors ( P < or = .05 ) of pressure ulcer development after multivariable Cox regression analysis included the following : nonblanchable erythema , 7.52 ( 1.00 to 59.12 ) ; lymphopenia , 4.86 ( 1.70 to 13.89 ) ; immobility , 2.36 ( 1.14 to 4.85 ) ; dry skin , 2.31 ( 1.02 to 5.21 ) ; and decreased body weight , 2.18 ( 1.05 to 4.52 ) . The 3-week cumulative incidence of pressure ulcers with none , one , two , or three or more of these characteristics was 0 % , 11.4 % , 39.6 % , and 67.9 % , respectively ( P < .001 by log-rank test ) . CONCLUSIONS These results suggest that nonblanchable erythema , lymphopenia , immobility , dry skin , and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair This article describes a method for estimating the inter-rater reliability of pressure ulcer ( PU ) staging ( stages I-IV ) from raters in National Data base of Nursing Quality Indicators ( NDNQI ) participating hospitals . The method models ordinal spanning data utilizing an ordinal probit Bayesian hierarchical model ( BHM ) across several hospitals in which raters monitor patient 's PUs . An ulcer that can not be accurately assessed because the base of the wound can not be seen is defined as unstageable . Our novel approach allows for an unstageable PU rating to be included in the analysis . We compare the ordinal probit BHM to an approximate r and om-effects ( st and ard approach in the literature ) model that assumes that the raw ordinal data are continuous OBJECTIVE To determine the incidence of pressure ulcers in varied population s , and whether demographic characteristics ( age , gender , race ) and primary diagnosis are factors in pressure ulcer development when the level of risk for developing ulcers is considered . To determine if there is a difference in the type of preventive services prescribed for persons who do or do not develop pressure ulcers when risk is controlled and whether differences can be related to demographic characteristics . DESIGN Cohort study . SETTING Two skilled nursing homes , two university operated tertiary care hospitals , and two Veteran 's Administration Medical Centers ( VAMCs ) in Omaha , NE , Durham , NC , and Chicago , IL . PATIENTS A total of 843 r and omly selected patients more than 19 years of age who did not have pressure ulcers on admission to their place of care . Subjects were 63 % male , 79 % white , and had a mean age of 63 ( + /- 16 ) years . MEASURES A head-to-toe skin assessment for pressure ulcers recording site and stage of ulcers , scores for the Braden Scale for Predicting Pressure Sore Risk , demographic characteristics ( age , sex , race ) , and primary diagnosis and preventive interventions ( turning or repositioning orders and pressure reduction surface ) were documented on the patient record . Observations were made every 48 to 72 hours for a minimum of 1 to a maximum of 4 weeks . MAIN OUTCOME MEASURES Presence/absence and stage of pressure ulcers . MAIN RESULTS One hundred eight of 843 ( 12.8 % ) subjects developed pressure ulcers . The incidence was 8.5 % , 7.4 % , and 23.9 % in tertiary care , VAMCs , and nursing homes , respectively . Logistic regression demonstrated that lower Braden Scale scores , older age and white race predicted pressure ulcers ; gender was not predictive . Primary diagnoses were not significant predictors of pressure ulcer risk when the Braden Scale score was entered into the regression . Prescription of turning was predicted by Braden Scale scores and by white race , whereas prescription of pressure reduction was predicted by Braden Scale scores , white race , and female sex . CONCLUSIONS Risk assessment , rather than diagnoses or demographic characteristics , is recommended as the basis for prescriptive decisions . Risk assessment should cue health care providers to make more judicious use of turning and support surfaces to prevent pressure ulcers . Persons who are at risk for pressure ulcers should have turning and pressure reduction surfaces consistently prescribed and implemented . The costs and goals of preventive prescription for those not at risk for pressure ulcers should be considered AIMS AND OBJECTIVES In this experimental study , a 4-cm thermoactive viscoelastic foam overlay and a heating source on the operating room table was compared with the st and ard operating room table with a heating source for the effect on the postoperative pressure ulcer incidence in cardiac surgery patients . BACKGROUND Pressure ulcer incidence in the cardiac surgery population is reported to be up to 29.5 % . The prolonged compressive forces from lying on the operating room table are one source of pressure ulcer development in this population . Pressure-reducing devices on the operating room (OR)-table should reduce the patients ' interface pressure and thus the hazard of skin breakdown . METHODS A r and omized controlled trial was performed to test the effect of a 4-cm thermoactive viscoelastic foam overlay with a water-filled warming mattress on the OR-table ( test OR-table ) compared with the st and ard OR-table ( a water-filled warming mattress , no pressure-reducing device ) on the postoperative pressure ulcer incidence in cardiac surgery patients . INSTRUMENTS The pressure ulcer classification system of the European Pressure Ulcer Advisory Panel ( EPUAP ) was used for pressure ulcer grading . RESULTS The results show that patients lying on the 4-cm thermoactive viscoelastic foam overlay suffer slightly more pressure ulcer ( 17.6 % ) than patients on the st and ard OR-table without the foam overlay ( 11.1 % ) . Because of the clinical relevance of the results , the r and omized controlled trial was terminated after 175 patients at the interim analysis although the power calculation stated 350 patients . CONCLUSIONS The combination of a 4-cm viscoelastic foam overlay and a warming source can not be recommended for pressure ulcer prevention on the operating room table . RELEVANCE TO CLINICAL PRACTICE Foam overlays are used to prevent pressure ulcers in patients . It is necessary to use such devices according to patient safety and use of re sources Stage 1 pressure ulcers are difficult to diagnose . Several prevalence studies have shown that almost half of the pressure ulcers identified are stage 1 . The present study investigated the importance of stage 1 . The following research questions were formulated : Is there a difference between the prevalence of stage 1 pressure ulcers identified in the institutions participating in the present study and that found in the other institutions participating in the Dutch National Prevalence Survey ? What percentage of stage 1 pressure ulcers are reversible within a few hours ? What is the clinical course of stage 1 pressure ulcers ? Which patient characteristics and preventive interventions are related to the clinical course of stage 1 ? The study used a prospect i ve , descriptive and comparative design . All patients of six long-term care hospitals and six acute care hospitals in whom stage 1 pressure ulcers were identified during the 1999 National Prevalence Survey in the Netherl and s were followed for 1 week ( acute care hospitals ; n = 68 patients ) or 2 weeks ( long-term care hospitals ; n = 115 patients ) . The patients were reassessed using the question naire developed for the National Prevalence Survey ( patient characteristics , assessment of risk of pressure ulcers , characteristics of the pressure ulcers and use of preventive methods ) on the same day as the national survey itself , and again after 3 days , after 7 days and after 14 days ( only long-term care hospitals ) . The results showed fewer stage 1 pressure ulcers in the institutions participating in the present study than in the National Prevalence Survey , the difference being almost 50 % . The first re assessment found the prevalence of stage 1 to be further reduced by an average of almost 50 % , a reduction which was greater for the long-term care hospitals than for the acute care hospitals . However , some of the ulcers that had disappeared reappeared in subsequent re assessment s. In the long-term care hospitals , 8.7 % of the stage 1 pressure ulcers deteriorated to a higher stage , vs. 22.1 % in acute care hospitals . No significant patient characteristics were found to affect the course of stage 1 , except that women in acute care hospitals more often had a stage 1 pressure ulcer at the first re assessment than men . In general , patients whose stage 1 ulcer deteriorated were undergoing more preventive interventions ; not all differences were significant . We conclude that , although stage 1 is reversible in most cases , it can be interpreted as an important warning sign for nurses and patients to act . If no adequate interventions are applied , the pressure ulcer may deteriorate AIM To assess the inter-rater reliability of the PRESSURE Trial pressure ulcer diagnosis ( > /= Grade 2 ) and skin classification for all grade s between the clinical research nurse ( CRN ) team leader and CRNs working across different hospital sites ; and CRNs and ward-based nurses . BACKGROUND The United Kingdom National Health Service Health Technology Assessment Programme has funded a multi-centre , r and omized controlled trial to compare the clinical and cost-effectiveness of alternating pressure mattress overlays and mattress replacements - PRESSURE Trial . Outcome skin assessment s were recorded by qualified ward-based nurses daily , and expert CRNs twice weekly . METHOD Paired assessment s were undertaken and skin assessed on seven body sites . The per cent agreement between nurses in the diagnosis of a pressure ulcer was determined and the Kappa statistic and confidence intervals calculated . Per cent agreement between nurses in classifying skin for all grade s was also determined . RESULTS Assessment s were undertaken by 378 pairs : 16 paired patient assessment s ( 107 site comparisons ) by the CRN team leader and CRNs , and 362 paired patient assessment s ( 2396 site comparisons ) between CRNs and ward-based nurses . There was 100 % agreement between the CRN team leader and CRNs in the diagnosis of a pressure ulcer , and the Kappa statistics indicated ' very good ' agreement . There were only two ( 1.9 % ) disagreements in classifying skin for all grade s between these nurses . The agreement in the diagnosis of a pressure ulcer between CRNs and ward-based nurses varied by skin site , ranging from 93.6 % to 100 % , with the Kappa statistics indicating ' good ' and ' very good ' agreement . However , there were 508 ( 21.2 % ) disagreements in classifying skin for all grade s. CONCLUSIONS Overall agreement and Kappa statistics indicated ' very good ' and ' good ' agreement between expert nurses , and between expert nurses and qualified ward-based staff , respectively . However , the high prevalence of normal skin concealed clinical ly important disagreements in both the diagnosis of pressure ulcers and skin classification for all grade BACKGROUND Pressure ulcers frequently occur in hospitalised patients . The prevalence of pressure ulcers grade 2 or worse varies from 3 % to 12 % in hospitalised patients . Incidence figures are not frequently reported . While incidence and prevalence are both measures of disease frequency , they provide different perspectives on pressure ulcers . OBJECTIVES To describe the incidence rate and prevalence of pressure ulcers in hospitalised patients . DESIGN Prospect i ve inception cohort study . SETTING Two large hospitals , one general ( 530-beds ) and one teaching ( 1042-beds ) , in The Netherl and s. PARTICIPANTS A non-selected , though not strictly r and om , sample of 1536 patients was eligible for inclusion in the study . One thous and four hundred and thirty one patients ( 93.2 % ) consented to participate . Eventually , 1229 patients ( 80 % ) had a complete follow-up . The sample consisted of patients admitted to the surgical , internal , neurological and geriatric wards for more than 5 days between January 1999 and June 2000 . METHODS Follow-up once a week until pressure ulcer occurrence , discharge or length of stay over 12 weeks . MAIN OUTCOME MEASURES Occurrence of a pressure ulcer grade 2 or worse during admission to hospital , according to the classification of the European Pressure Ulcer Advisory Panel . RESULTS One hundred and thirty four patients developed 172 pressure ulcers during follow-up . The overall weekly incidence rate was 0.06 per week ( 95 % confidence interval 0.05 - 0.07 per week ) . Highest rates were observed for surgical patients and lowest for geriatric and neurologic patients ( 0.08 and 0.02 , respectively ) . The week specific prevalence varied between 12.8 % and 20.3 % . CONCLUSIONS Among patients hospitalised for more than 5 days overall one may expect 6 % per week to develop pressure ulcers . It would appear that any preventive measures can only be effective if taken timely . Accordingly , preventive measures should be considered early , because pressure ulcers were observed already within the first week of admission AIM This paper reports a study examining the interrater and intrarater reliability of classifying pressure ulcers according to the European Pressure Ulcer Advisory Panel classification system when using photographs of pressure ulcers and incontinence lesions . BACKGROUND Pressure ulcer classification is an essential tool for assessing ulcers and their severity and determining which preventive or therapeutic action is needed . Many classification systems are described in the literature . There are only a limited number of studies that evaluate the interrater reliability of pressure ulcer grading scales . The intrarater reliability is seldom studied . METHODS The study consisted of two phases . In the first phase 56 photographs , together with a r and om selection of nine photographs from the same set , were presented to 473 nurses . In the second phase , the 56 photographs were presented twice to 86 other nurses with an interval of one month and in a different order . All the nurses were familiar with the European Pressure Ulcer Advisory Panel classification . They did not receive any additional training on classification , and were asked to classify the lesions as normal skin , blanchable erythema , pressure ulcers ( four grade s , European Pressure Ulcer Advisory Panel classification ) or incontinence lesions . RESULTS In the first phase , the multirater-Kappa for the 473 participating nurses was 0.37 ( P < 0.001 ) . Non-blanchable erythema was often confused with blanchable erythema and incontinence lesions . Also incontinence lesions were frequently not correctly classified . The intrarater agreement was low ( kappa = 0.38 ) . In the second phase , the interrater agreement was not significantly different in both sessions . The intrarater agreement was 0.52 . CONCLUSION Both the interrater and intrarater reliability of the European Pressure Ulcer Advisory Panel classification of lesion photographs by nurses was very low . Differentiation between pressure ulcers and incontinence lesions seems to be difficult AIM This paper reports a study investigating whether repositioning patients lying on a pressure-reducing mattress alternately for 2 hours in a lateral position and 4 hours in a supine position reduces the incidence of pressure ulcers in comparison with repositioning every 4 hours . BACKGROUND Repositioning is commonly recognized as an effective preventive measure . Almost no research has been carried out so far on the necessary turning frequencies to prevent pressure ulcer lesions . The pressure is higher in a lateral than in a supine position . METHOD A two-arm r and omized controlled trial was conducted in 16 Belgian elder care nursing homes . Patients with non-blanchable erythema were r and omly assigned to either an experimental or a control group . In the experimental group ( n = 122 ) , patients were repositioned alternately 2 hours in a lateral position and 4 hours in a supine position . In the control group ( n = 113 ) , patients were repositioned every 4 hours . The sitting protocol was identical in both groups . Pressure areas were observed daily and classified according to the four grade s of the European Pressure Ulcer Advisory Panel . RESULTS In the experimental group , 16.4 % patients developed a pressure ulcer lesion ( grade 2 - 4 ) , while 21.2 % did so in the control group . The incidence was not statistically significantly different between the two groups ( P = 0.40 ) . The severity ( P = 0.65 ) and location ( P = 0.19 ) of pressure ulcer lesions , and the time to developing them ( P = 0.29 ) were also similar in both groups . No patient developed a pressure ulcer at the hips . A considerable number of patients changed from a lateral to a supine position between the turning intervals . CONCLUSION More frequent repositioning on a pressure-reducing mattress does not necessarily lead to fewer pressure ulcer lesions and consequently can not be considered as a more effective preventive measure AIMS AND OBJECTIVES To evaluate whether postponing preventive measures until non-blanchable erythema appears will actually lead to an increase in incidence of pressure ulcers ( grade s 2 - 4 ) when compared with the st and ard risk assessment method . BACKGROUND To distinguish patients at risk for pressure ulcers from those not at risk , risk assessment scales are recommended . These scales have limited predictive validity . The prevention of further deterioration of non-blanchable erythema ( grade 1 pressure ulcer ) instead of the st and ard way of assigning prevention could be a possible new approach . DESIGN R and omized-controlled trial . METHODS Patients admitted to surgical , internal or geriatric wards ( n = 1617 ) were included . They were r and omly assigned to an experimental and a control group . In the experimental group ( n = 826 ) , prevention was started when non-blanchable erythema appeared , in the control group ( n = 791 ) when the Braden score was < 17 or when non-blanchable erythema appeared . In both groups , patients received identical prevention , either by using a polyethylene-urethane mattress in combination with turning every four hours or by using an alternating pressure air mattress . Pressure points were observed daily and classified according to the four grade s of the European Pressure Ulcer Advisory Panel . The Braden scale was scored every three days . RESULTS In the experimental group , 16 % of patients received preventive measures , in the control group 32 % . The pressure ulcer incidence ( grade s 2 - 4 ) was not significantly different between the experimental ( 6.8 % ) and control group ( 6.7 % ) . CONCLUSION Significantly fewer patients need preventive measures when prevention is postponed until non-blanchable erythema appears and those patients did not develop more pressure ulcers than patients who received prevention based on the st and ard risk assessment method . RELEVANCE TO CLINICAL PRACTICE Using the appearance of non-blanchable erythema to allocate preventive measures leads to a considerable reduction of patients in need of prevention without result ing in an increase in pressure ulcers A criterion-referenced Web-based test was design ed and administered to 256 individuals at 48 r and omly sample d National Data base of Nursing Quality Indicators ( NDNQI ) member hospitals to determine the reliability of the NDNQI pressure ulcer indicator . Overall κ values for pressure ulcer identification , staging , and sourcing indicate moderate to near perfect reliability . Findings suggest that nurses can accurately differentiate pressure ulcers from other ulcerous wounds in Web-based photographs , reliably stage pressure ulcers , and reliably identify community versus nosocomial pressure ulcers OBJECTIVE This study investigated whether a decision tree can aid pressure ulcer management . It hypothesised that nurses who use a decision tree in pressure ulcer care assess wound grade more accurately and select more appropriate dressings . METHOD Sixty-six nurses were r and omly assigned to two groups . Each nurse review ed written information and pictures of three cases of pressure ulceration , and then grade d and selected a dressing for the lesions . The absence or presence of a decision tree was used as an independent variable . Measurements included : mean and st and ard deviation ; confidence intervals ; percentages ; Chi-square test , Pearson 's correlation and Kruskal-Wallis test . RESULTS Baseline characteristics were comparable for both groups . There was no statically significant difference between the grade s selected by the two groups . But significantly more of the decision tree users selected an appropriate dressing ( p < 0.02 ) . Joint scores ( ranging from 0 to 6 ) were assigned for each accurate decision . The mean score for the experimental group was 4.47 + /- 1.14 ( 95 % CI : 0.95 [ 4.06 - 4.88 ] ) and for the control group , 3.35 + /- 1.30 ( 95 % CI : 0.95 [ 2.90 - 3.81 ] ) . CONCLUSION Decision trees could help nurses to make complex clinical decisions . Further studies undertaken in a clinical setting are needed BACKGROUND studies of the effectiveness of alternating pressure air mattresses ( APAMs ) for the prevention of pressure ulcers are scarce and in conflict . OBJECTIVE evaluating whether an APAM is more or equally effective as the st and ard prevention . DESIGN r and omised controlled trial . SETTING AND SUBJECTS patients admitted to 19 surgical , internal , or geriatric wards in seven Belgian hospitals were included if they were in need of prevention of pressure ulcers . To define this need , two methods were used r and omly : the Braden Scale or the presence of non-blanchable erythema ( NBE ) . METHODS 447 patients were r and omised into either an experimental or a control group . In the experimental group , 222 patients were lying on an APAM ( Alpha-X-Cell , Huntleigh Healthcare , UK ) . In the control group , 225 patients were lying on a visco-elastic foam mattress ( Tempur , Tempur-World Inc. , USA ) in combination with turning every 4 hours . Both groups had identical sitting protocol s. RESULTS there was no significant difference in incidence of pressure ulcers ( grade 2 - 4 ) between the experimental ( 15.6 % ) and control group ( 15.3 % ) ( P = 1 ) . There were significantly more heel pressure ulcers in the control group ( P = 0.006 ) . There was an interaction effect between the risk assessment method and preventive measures for the development of all pressure ulcers and sacral pressure ulcers . CONCLUSION fewer patients developed heel pressure ulcers on an APAM . Patients identified as being in need of prevention based on the presence of NBE had a tendency to develop fewer pressure ulcers on an APAM . Patients identified as being in need of prevention , based on the Braden Scale , appeared to develop more sacral pressure ulcers on an APAM |
12,527 | 12,202,327 | Stretching produced small and statistically non-significant reductions in muscle soreness .
Stretching before or after exercising does not confer protection from muscle soreness .
Insufficient research has been done with which to determine the effects of stretching on sporting performance | OBJECTIVE To determine the effects of stretching before and after exercising on muscle soreness after exercise , risk of injury , and athletic performance . | To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked Abstract The effects of an 8-week unilateral contract-relax ( CR ) stretching training program ( passive stretch after isometric contraction ) on muscular performance were investigated in a group of 16 athletes . The flexibility , maximum torque and angular position as well as contraction work in movements of the knee joint were determined before training and after 4 and 8 weeks of training . The torque measurements were performed under isokinetic conditions , eccentrically at angular velocities of 60 ° · s−1 and 120 ° · s−1 , isometrically at five different joint positions , and concentrically at angular velocities of 60 , 120 , 180 and 240 ° · s−1 using an isokinetic dynamometer . A surface electromyogram ( EMG ) of the thigh muscles ( quadriceps and hamstrings ) was recorded simultaneously . As compared to untrained control limbs , significant improvements in active and passive flexibility ( up to 6.3 ° in range of motion ) , maximum torque ( up to 21.6 % ) and work ( up to 12.9 % ) were observed , and these were especially pronounced under eccentric load conditions . A comparison between integrated EMG recordings during eccentric and concentric loads , as well as the interpretation of the training-induced changes in the EMG , suggest that muscular activity under eccentric loads may be impaired by mental processes Eccentric activities are an important component of physical conditioning and everyday activities . Delayed onset muscle soreness ( DOMS ) can result from strenuous eccentric tasks and can be a limiting factor in motor performance for several days after exercise . An efficacious method of treatment for DOMS would enhance athletic performance and hasten the return to activities of daily living . The purpose of this study was to identify a treatment method which could assist in the recovery of DOMS . In the selection of treatment methods , emphasis was directed toward treatments that could be rendered independently by an individual , therefore making the treatment valuable to an athletic trainer in team setting . DOMS was induced in 70 untrained volunteers via 15 sets of 15 eccentric contractions of the forearm extensor muscles on a Lido isokinetic dynamometer . All subjects performed a pilot exercise bout for a minimum of 9 weeks before data collection to assure that DOMS would be produced . Data were collected on 15 dependent variables : active and passive wrist flexion and extension , forearm girth , limb volume , visual analogue pain scale , muscle soreness index , isometric strength , concentric and eccentric wrist total work , concentric and eccentric angle of peak torque . Data were collected on six occasions : pre- and post-induced DOMS , 20 minutes after treatment , and 24 , 48 , and 72 hours after treatment . Subjects were r and omly assigned to 1 of 7 groups ( 6 treatment and 1 control ) . Treatments included a nonsteroidal anti-inflammatory drug , high velocity concentric muscle contractions on an upper extremity ergometer , ice massage , 10-minute static stretching , topical Amica montana ointment , and sublingual A. montana pellets . A 7 x 6 ANOVA with repeated measures on time was performed on the delta values of each of the 15 dependent variables . Significant main effects ( p < .05 ) were found for all of the dependent variables on time only . There were no significant differences between treatments . Therefore , we conclude that none of the treatments were effective in abating the signs and symptoms of DOMS . In fact , the NSAID and A. montana treatments appeared to impede recovery of muscle function Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees . Two different companies going through basic training at the same time were used . Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course . The control company ( N 148 ) proceeded through normal basic training . The intervention company ( N 150 ) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program . All subsequent lower extremity overuse injuries were recorded through the troop medical clinic . Hamstring flexibility increased significantly in the intervention group compared with the control group . The number of injuries was also significantly lower in the intervention group . Forty-three injuries occurred in the control group for an incidence rate of 29.1 % , compared with 25 injuries in the intervention group for an incidence rate of 16.7 % . Thus , in this study , the number of lower extremity overuse injuries was significantly lower in infantry basic trainees with increased hamstring flexibility This paper discusses statistical techniques for the analysis of dichotomous data arising from a design in which the investigator r and omly assigns each of two clusters of possibly varying size to interventions within strata . The problem addressed is that of assessing the statistical significance of the intervention effect over all strata . We propose a weighted paired t-test based on the empirical logistic transform for design s that r and omize large aggregate clusters in each of several strata The present study sought to investigate the effects of preexercise stretching on delayed onset muscle soreness ( DOMS ) , i.e. soreness , tenderness and loss of muscle force , that usually occurs after strenuous or unaccustomed eccentric exercise . Ten female volunteers performed 10 sets of 10 maximal isokinetic eccentric contractions for knee flexion with both legs after a 5-min ergometer cycling warm-up . Prior to the exercise for one leg , r and omly chosen , 4 x 20 s of static stretching for the hamstring muscle group was implemented . Rated soreness , tenderness on algometer pressure and loss of maximal eccentric contractile force was evaluated preexercise and 24 , 48 and 96 h postexercise . The exercise bout produced severe DOMS , with parameters peaking and troughing at 48 h postexercise . However , no significant differences were found , regarding any of the parameters , when comparing stretched and nonstretched legs . The present study thus suggests that preexercise static stretching has no preventive effect on the muscular soreness , tenderness and force loss that follows heavy eccentric exercise Thirty-six male subjects aged 18 to 26 years were assigned at r and om to one of three treatment groups : biofeedback , static stretch , and control . Muscle soreness was produced in all subjects by an 80 % maximal eccentric contraction of the biceps brachii . The subjects in the biofeedback group applied auditory electromyographic ( EMG ) feedback at 6 , 25 , 30 , 49 , and 54 hours after the exercise , and the stretch group applied static stretch to the exercised arm at the same time periods . Observations of EMG activity and perceived pain level were made immediately before and after exercise , and at 24 , 48 , and 72 hours following exercise . When compared with a control group , both auditory biofeedback and static stretching significantly reduced EMG muscle activity but had no significant effect on perceived pain . The EMG activity and perceived pain of the subjects in each treatment group significantly differed across observations This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training . Prior to training , ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-r and om procedure . The stretch group stretched calf muscles under supervision prior to all intense exercise . The control group stretched upper limb muscles instead . Forty-eight injuries were recorded . Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury ( p = 0.03 ) . Definitive evidence of an effect of stretching on injury risk was not found ( p = 0.76 ) , but the sample size may have been insufficient to detect such an effect It has been suggested in the lay literature that static stretching and /or warm-up will prevent the occurrence of Delayed-Onset Muscle Soreness ( DOMS ) . The primary purpose of this study was to determine the effects of static stretching and /or warm-up on the level of pain associated with DOMS . Sixty-two healthy male and female volunteers were r and omly assigned to four groups : ( a ) subjects who statically stretched the quadriceps muscle group before a step , ( b ) subjects who only performed a stepping warm-up , ( c ) subjects who both stretched and performed a stepping warm-up prior to a step test , and ( d ) subjects who only performed a step test . The step test ( Asmussen , 1956 ) required subjects to do concentric work with their right leg and eccentric work with their left leg to voluntary exhaustion . Subjects rated their muscle soreness on a ratio scale from zero to six at 24-hour intervals for 5 days following the step test . A 4x2x2 ANOVA with repeated measures on legs and Duncan 's New Multiple Range post-hoc test found no difference in peak muscle soreness among the groups doing the step test or for gender ( p greater than .05 ) . There was the expected significant difference in peak muscle soreness between eccentrically and concentrically worked legs , with the eccentrically worked leg experiencing greater muscle soreness . We concluded that static stretching and /or warm-up does not prevent DOMS result ing from exhaustive exercise PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor |
12,528 | 23,563,080 | The prevalence of child sexual abuse was 24 % ( 23 % without outliers ) ; however , such prevalence rate might be underestimated , because many studies restricted definitions to the most severe forms of abuse .
Child sexual abuse was a common experience for both males and females , while it was more frequent for adults than for youths .
Compared to healthy individuals , patients with bipolar disorder reported higher rates of child sexual abuse ; compared to population s with other mental disorders , participants with bipolar disorder reported similar or lower rates of such abuse .
Individuals with bipolar disorder are at risk of having a history of child sexual abuse , although such risk seems to be neither more specific to nor stronger for these individuals , compared to people with other psychiatric disorders | null | null |
12,529 | 26,334,842 | No evidence of bias was found for : ( 1 ) paper versus electronic self-complete ; and ( 2 ) self-complete versus assisted MOA .
Heterogeneity for paper versus electronic comparison was explained by type of construct ( i.e. physical vs. psychological ) .
Heterogeneity for self-completion versus assisted modes was in part explained by setting ( clinic vs. home ) ; the largest bias was introduced when assisted completion occurred in the clinic and follow-up was by self-completion ( either electronic or paper ) in the home .
Conclusions Self-complete paper and electronic MOA can be used interchangeably for research in clinic and home setting s. Self-completion and assisted completion produce equivalent scores overall , although heterogeneity may be induced by setting . | Purpose Technological advances in recent decades have led to the availability of new modes to administer patient-reported outcomes ( PROs ) .
To aid selecting optimal modes of administration ( MOA ) , we undertook a systematic review to determine whether differences in bias ( both size and direction ) exist among modes . | Background The use of Internet-based question naires for collection of data to evaluate patient education and other interventions has increased in recent years . Many self-report instruments have been vali date d using paper- and -pencil versions , but we can not assume that the psychometric properties of an Internet-based version will be identical . Objectives To look at similarities and differences between the Internet versions and the paper- and -pencil versions of 16 existing self-report instruments useful in evaluation of patient interventions . Methods Participants were recruited via the Internet and volunteered to participate ( N=397 ) , after which they were r and omly assigned to fill out question naires online or via mailed paper- and -pencil versions . The self-report instruments measured were overall health , health distress , practice mental stress management , Health Assessment Question naire ( HAQ ) disability , illness intrusiveness , activity limitations , visual numeric for pain , visual numeric for shortness of breath , visual numeric for fatigue , self-efficacy for managing disease , aerobic exercise , stretching and strengthening exercise , visits to MD , hospitalizations , hospital days , and emergency room visits . Means , ranges , and confidence intervals are given for each instrument within each type of question naire . The results from the two question naires were compared using both parametric and non-parametric tests . Reliability tests were given for multi-item instruments . A separate sample ( N=30 ) filled out identical question naires over the Internet within a few days and correlations were used to assess test-retest reliability . Results Out of 16 instruments , none showed significant differences when the appropriate tests were used . Construct reliability was similar within each type of question naire , and Internet test-retest reliability was high . Internet question naires required less follow-up to achieve a slightly ( non-significant ) higher completion rate compared to mailed question naires . Conclusions Among a convenience sample recruited via the Internet , results from those r and omly assigned to Internet participation were at least as good as , if not better than , among those assigned mailed question naires , with less recruitment effort required . The instruments administered via the Internet appear to be reliable , and to be answered similarly to the way they are answered when they are administered via traditional mailed paper question naires & NA ; Electronic question naires for pain assessment are becoming increasingly popular . There have been no published reports to establish the equivalence or psychometric properties of common pain question naires administered via desktop computers . This study compared responses to paper ( P ) and touch screen electronic ( E ) versions of the Short‐Form McGill Pain Question naire ( SF‐MPQ ) and Pain Disability Index ( PDI ) , while examining the role of computer anxiety and experience , and evaluating patient acceptance . In a r and omized , crossover design 189 chronic pain patients completed P and E versions of the SF‐MPQ and PDI , and self‐ratings of anxiety , experience , relative ease and preference . Psychometric properties were highly similar for P and E question naires . For the SF‐MPQ , 60 % or more of subjects gave equivalent responses on individual descriptors and PPI scale , with 80 % rating within ±1 point for an 11‐point VAS . Correlations for the SF‐MPQ scales ranged from 0.68 to 0.84 . For the PDI , 60 % or more of subjects responded within ±1 point on individual questions , and the total score correlation was 0.67 . Comparison of mean difference scores revealed no significant differences between modes for any of the question naire items or scores . Anxiety and experience scores showed no significant associations through correlations and high/low comparisons . Although nearly half of subjects reported no computer training , anxiety ratings were low , and considerably more subjects rated the E question naires as easier and preferred . Findings are consistent with test‐retest reliability data , and support the validity and acceptance of electronic versions of the SF‐MPQ and PDI Background While modern electronic data collection methods ( e.g. , computer touch-screen or web-based ) hold much promise , most current studies continue to make use of more traditional data collection techniques , including paper- and -pencil administration and telephone interviews . The present r and omized trial investigated the measurement properties of the EORTC QLQ-C30 under three different modes of administration ( MOA 's ) . Methods A heterogeneous sample of 314 cancer patients undergoing treatment at a specialized treatment center in Amsterdam were r and omized to one of three MOA 's for the QLQ-C30 : paper- and -pencil at home via the mail , telephone interview , and paper- and -pencil at the hospital clinic . Group differences in internal consistency reliabilities ( Cronbach 's alpha coefficient ) for the scale scores were compared . Differences in mean scale scores were also compared by means of ANOVA , with adjustment for potential confounders . Results Only one statistically significant , yet minor , difference in Cronbach 's alpha between the MOA groups was observed for the Role Functioning scale ( all 3 alphas > 0.80 ) . Significant differences in group means -after adjustment- were found for the Emotional Functioning ( EF ) scale . Patients completing the written question naire at home had significantly lower levels of EF as compared to those interviewed via the telephone ; EF scores of those completing the question naire at the clinic fell in-between those of the other two groups . These differences , however , were small in magnitude . Conclusions MOA had little effect on the reliability or the mean scores of the EORTC QLQ-C30 , with the possible exception of the EF scale Background The most commonly used survey methods are self-administered question naires , telephone interviews , and a mixture of both . But until now evidence out of r and omised controlled trials as to whether patient responses differ depending on the survey mode is lacking . Therefore this study assessed whether patient responses to surveys depend on the mode of survey administration . The comparison was between mailed , self-administered question naires and telephone interviews . Methods A four-armed , r and omised controlled two-period change-over design . Each patient responded to the same survey twice , once in written form and once by telephone interview , separated by at least a fortnight . The study was conducted in 2003/2004 in Germany . 1087 patients taking part in the German Acupuncture Trials ( GERAC cohort study ) , who agreed to participate in a survey after completing acupuncture treatment from an acupuncture-certified family physician for headache , were r and omised . Of these , 823 ( 664 women ) from the ages of 18 to 83 ( mean 51.7 ) completed both parts of the study . The main outcome measure was the comparison of the scores on the 12-Item Short-Form Health Survey ( SF-12 ) and the Grade d Chronic Pain Scale ( GCPS ) question naire for the two survey modes . Results Computer-aided telephone interviews ( CATI ) result ed in significantly fewer missing data ( 0.5 % ) than did mailed question naires ( 2.8 % ; p < 0.001 ) . The analysis of equivalence revealed a difference between the survey modes only for the SF-12 mental scales . On average , reported mental status score was 3.5 score points ( 2.9 to 4.0 ) lower on the self-administered question naire compared to the telephone interview . The order of administration affected results . Patients who responded to the telephone interview first reported better mental health in the subsequent paper question naire ( mean difference 2.8 score points ) compared to those who responded to the paper question naire first ( mean difference 4.1 score points ) . Conclusion Despite the comparatively high cost of telephone interviews , they offer clear advantages over mailed self-administered question naires as regards completeness of data . Only items concerning mental status were dependent on the survey mode and sequence of administration . Items on physical status were not affected . Normative data for st and ardized telephone question naires could contribute to a better comparability with the results of the corresponding st and ardized paper question naires Background Research in quality of life traditionally relies on paper- and -pencil question naires . Easy access to the Internet has inspired a number of studies that use the Internet to collect question naire data . However , Internet-based data collection may differ from traditional methods with respect to response rate and data quality as well as the validity and reliability of the involved scales . Objective We used a r and omized design to compare a paper- and -pencil question naire with an Internet version of the same question naire with respect to differences in response rate and completeness of data . Methods Women referred for mammography at a Danish public hospital from September 2004 to April 2005 , aged less than 67 years and without a history of breast cancer , were eligible for the study . The women received the invitation to participate along with the usual letter from the Department of Radiology . A total of 533 women were invited to participate . They were r and omized to receive either a paper question naire , with a prepaid return envelope , or a guideline on how to fill in the Internet-based version online . The question naire consisted of 17 pages with a total of 119 items , including the Short Form-36 , Multidimensional Fatigue Inventory-20 , Hospital Anxiety and Depression Scale , and questions regarding social status , education level , occupation , and access to the Internet . Nonrespondents received a postal reminder giving them the option of filling out the other version of the question naire . Results The response rate before the reminder was 17.9 % for the Internet group compared to 73.2 % for the paper- and -pencil group ( risk difference 55.3 % , P < .001 ) . After the reminder , when the participant could chose between versions of the question naire , the total response rate for the Internet and paper- and -pencil group was 64.2 % and 76.5 % , respectively ( risk difference 12.2 % , P = .002 ) . For the Internet version , 97.8 % filled in a complete question naire without missing data , while 63.4 % filled in a complete question naire for the paper- and -pencil version ( risk difference 34.5 % , P < .001 ) . Conclusions The Internet version of the question naire was superior with respect to completeness of data , but the response rate in this population of unselected patients was low . The general population has yet to become more familiar with the Internet before an online survey can be the first choice of research ers , although it is worthwhile considering within selected population s of patients as it saves re sources and provides more complete answers . An Internet version may be combined with the traditional version of a question naire , and in follow-up studies of patients it may be more feasible to offer Internet versions OBJECTIVE To compare participants ' responses to Web-based and paper- and -pencil versions of an ophthalmic , patient-reported outcome ( PRO ) question naire . DESIGN Question naire development . PARTICIPANTS Matched subjects with ocular surface disease ( OSD ) ( n = 68 ) and without OSD ( controls , n = 50 ) . METHODS Subjects completed a st and ard , paper- and -pencil and a Web-based version of the same question naire in r and omized order . The administered question naire included several ophthalmic PRO subscales : the National Eye Institute 's ( NEI 's ) Refractive Error Quality of Life Instrument 's Clarity of Vision , Near Vision , Far Vision , Glare , Symptoms , Worry , and Satisfaction with Correction subscales ; the Ocular Surface Disease Index 's ( OSDI 's ) Symptoms subscale ; and the NEI 's Visual Function Question naire 's Driving subscale . Possible scores for each subscale ranged from 0 ( no difficulty ) to 100 ( most difficulty ) . Agreement of subscale scores between modes of administration was assessed using the Bl and -Altman approach and multivariable logistic regression . MAIN OUTCOME MEASURES Subscale scores and an unweighted average total score for each mode of administration . RESULTS Mean differences in scores between modes of administration ranged from -2.1 to + 2.3 units . Although no differences were found to be statistically significant , the Worry and Satisfaction with Correction subscales approached statistical significance ( P = 0.07 and 0.08 , respectively ) . Although most subscale mean differences in score did not differ significantly by gender , age ( ≥40 vs. < 40 years ) , disease status ( OSD vs. control ) , order of administration , or time between completion of the question naires , women had slightly greater score differences than men for the Driving ( P = 0.04 ) and Clarity of Vision ( P = 0.03 ) subscales ; those with OSD had greater score differences for Clarity of Vision than did controls ( P = 0.0006 ) ; and those aged ≥40 years had slightly greater differences in OSDI Symptoms subscale than those aged < 40 years ( P = 0.04 ) . CONCLUSIONS To our knowledge , this Food and Drug Administration and NEI collaboration is the first study to evaluate the equivalence of Web-based and paper versions of ophthalmic PRO question naires . We found no evidence of clinical ly significant differences between scores obtained by the 2 modes for any of the examined subscales . A Web-based instrument should yield scores equivalent to those obtained by st and ard methods , providing a useful tool that may facilitate ophthalmic innovation . FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article Background In clinical and research practice linked to prostate cancer treatment , frequent monitoring of patient health-related quality of life ( HRQOL ) is essential . Practical and analytic limitations of paper question naire data capture may be overcome with the use of self-administered personal digital assistant ( PDA ) data collection . The objective of this study was to assess the reliability , validity , and feasibility of using PDA in place of paper versions of the International Prostate Symptom Score ( IPSS ) , the Patient Oriented Prostate Cancer Utility Survey ( PORPUS ) , and the International Index of Erectile Function-5 ( IIEF-5 ) in a prostate cancer clinic setting . Methods 152 participants were r and omly assigned to one of three conditions : 1 ) paper followed by PDA survey ; 2 ) PDA followed by paper survey ; or 3 ) PDA followed by PDA survey . Evaluation included an assessment of data quality ( internal consistency , test-retest reliability , response correlation , completeness of data ) , and feasibility ( participation rates , time to completion , preference and difficultly/ease of using PDA ) . Results Internal consistency was similar for both PDA and paper applications . Test-retest reliability was confirmed for PDA repeated administration . Data from paper and PDA question naires were strongly correlated . Lower missed item rates were found in PDA administration . 82.8 % of participants preferred using the PDA or had no preference . Mean difficulty/ease ratings indicated that participants found the PDA easy to use . Age did not significantly correlate with preference or difficulty . Conclusion The results confirm the adaptability of the IPSS , IIEF-5 , and the PORPUS to PDA administration . Similarly , the findings of this study support the feasibility of using PDA technology for HRQOL serial data capture in the prostate cancer patient population OBJECTIVE To explore the response rate benefits and data limitations of mixing telephone and web survey modes in a health-related research study . DATA SOURCES / STUDY SETTING We conducted a survey of salaried employees from one large employer in the manufacturing sector in the summer of 2005 . STUDY DESIGN We r and omized 751 subjects , all of whom had previously completed a web survey , to complete a health-related survey either by telephone ( with web follow-up for nonrespondents ) or over the web ( with telephone follow-up ) . PRINCIPAL FINDINGS Survey response rates were significantly higher for the mixed mode survey than they would have been if we fielded either an exclusively telephone or web survey ( 25 and 12 percent higher , respectively ) . Telephone respondents were more likely to provide socially desirable responses to personal lifestyle questions and web respondents provided more missing data when questions were difficult or did not relate to their circumstances . Telephone respondents were also more likely to " agree " to knowledge statements and provide the same response across a series of items with similar response scales than were web respondents . CONCLUSIONS Mixed mode telephone/web surveys can substantially boost response rates over single-mode surveys . Modal differences in responses can be minimized by h and ling missing data options consistently in the two modes , avoiding agree/disagree formats , and not including questions on personal lifestyle or other sensitive issues Background When developing new measuring instruments or deciding upon one for research , consideration of the ‘ best ’ method of administration for the target population should be made . Current evidence is inconsistent in differentiating superiority of any one method in terms of quantity and quality of response . We trialed a novel mixed methods approach in early scale development to determine the best administration method for a new patient-reported outcome instrument for people with pressure ulcers ( the PU-QOL ) . Methods Cognitive interviews were undertaken with 35 people with pressure ulcers to determine appropriateness of a self-completed version of the PU-QOL instrument . Quantitative analysis , including Rasch analysis , was carried out on PU-QOL data from 70 patients with pressure ulcers , r and omised to self-completed or interview-administered groups , to examine data quality and differential item functioning ( DIF ) . Results Cognitive interviews identified issues with PU-QOL self-completion . Quantitative analysis supported these findings with a large proportion of self-completed PU-QOLs returned with missing data . DIF analysis indicated administration methods did not impact the way patients from community care setting s responded , supporting the equivalence of both administration versions . Conclusions Obtaining the best possible health outcomes data requires use of appropriate methods to ensure high quality data with minimal bias . Mixed methods , with the inclusion of Rasch , provided valuable evidence to support selection of the ‘ best ’ administration method for people with PUs during early PRO instrument development . We consider our approach to be generic and widely applicable to other elderly or chronically ill population s or suitable for use in limited sample s where recruitment to large field tests is often difficult Background In the context of a r and omized controlled trial ( RCT ) on HIV testing in the emergency department ( ED ) setting , we evaluated preferences for survey modality and data quality arising from each modality . Methods Enrolled participants were offered the choice of answering a survey via audio computer assisted self-interview ( ACASI ) or pen and paper self-administered question naire ( SAQ ) . We evaluated factors influencing choice of survey modality . We defined unusable data for a particular survey domain as answering fewer than 75 % of the questions in the domain . We then compared ACASI and SAQ with respect to unusable data for domains that address sensitive topics . Results Of 758 enrolled ED patients , 218 ( 29 % ) chose ACASI , 343 chose SAQ ( 45 % ) and 197 ( 26 % ) opted not to complete either . Results of the log-binomial regression indicated that older ( RR = 1.08 per decade ) and less educated participants ( RR = 1.25 ) were more likely to choose SAQ over ACASI . ACASI yielded substantially less unusable data than SAQ . Conclusions In the ED setting there may be a tradeoff between increased participation with SAQ versus better data quality with ACASI . Future studies of novel approaches to maximize the use of ACASI in the ED setting are needed This study examines whether the Internet-based question naire is psychometrically equivalent to the paper-based question naire . A r and om sample of 2,400 teachers in Taiwan was divided into experimental and control groups . The experimental group was invited to complete the electronic form of the Chinese version of Center for Epidemiologic Studies Depression Scale ( CES-D ) placed on the Internet , whereas the control group was invited to complete the paper-based CES-D , which they received by mail . The multi sample invariance approach , derived from structural equation modeling ( SEM ) , was applied to analyze the collected data . The analytical results show that the two groups have equivalent factor structures in the CES-D. That is , the items in CES-D function equivalently in the two groups . Then the e quality of latent mean test was performed . The latent means of " depressed mood , " " positive affect , " and " interpersonal problems " in CES-D are not significantly different between these two groups . However , the difference in the " somatic symptoms " latent means between these two groups is statistically significant at alpha = 0.01 . But the Cohen 's d statistics indicates that such differences in latent means do not apparently lead to a meaningful effect size in practice . Both CES-D question naires exhibit equal validity , reliability , and factor structures and exhibit a little difference in latent means . Therefore , the Internet-based question naire represents a promising alternative to the paper-based question naire OBJECTIVE Follow-up data were collected using postal question naires and if participants did not respond , then data was collected using telephone interviews . The objectives of this study were to examine , for the two methods , how respondents differed in characteristics and whether the observed treatment difference varied . STUDY DESIGN AND SETTING A large clinical trial of lower back pain . RESULTS About 60 % ( 98/163 ) of the nonresponders to postal question naire provided data by telephone , which increased the overall response rate by 14 % ( from 71 % to 85 % ) . A consistent treatment difference was found across the methods for the outcome measures at 12 months , implying that the observed treatment effect had not been modified . There were some differences between the participants : responders of postal question naire were older , likely to be female , white ( ethnic origin ) , not working , with less disability of back pain , compared with those who responded by a telephone interview . At 12 months , there was greater improvement in back pain , disability , and general health for those who responded by postal question naires . CONCLUSION Research ers should consider the use of more than one method of collecting data as this increases response rate , participant representativeness , and enhances precision of effect estimates Background The majority of Internet-mediated studies use measures developed as paper- and -pencil measures or face-to-face-delivered material . Previous research suggests that the equivalence between online and offline measures must be demonstrated rather than assumed . Objective The objective of this study was to explore the equivalence 4 measures completed in an online or offline setting . Methods A sample of students ( n = 1969 ) was r and omly assigned to complete 4 popular scales ( the SF-12v2 , the Hospital Anxiety and Depression Scale ( HADS ) , the Fatigue Symptom Inventory , and a single-item fatigue measure ) either online or by mail survey ( pencil and paper ) . The response rate was 52.51 % ( n = 1034 ) and comparable between the online and offline groups . Results Significant differences were noted in fatigue levels between the online and offline group ( P = .01 ) as measured by the Fatigue Symptom Inventory , with the online sample demonstrating higher levels of fatigue . Equivalency was noted for the SF-12v2 , the Hospital Anxiety and Depression Scale , and the single-item fatigue measure . Internal consistency was high except for the SF-12v2 . The SF-12v2 may not be an ideal measure to use for remote administration . Conclusions Equivalency of the Hospital Anxiety and Depression Scale ( HADS ) and the Physical Component Score and Mental Component Score of the SF-12v2 for online and offline data were demonstrated . Equivalency was not demonstrated for the Fatigue Symptom Inventory . Explanations for the difference in fatigue score between the online and offline sample s are unclear . Research that seeks to match sample s and control for extraneous online and offline variables is called for , along with exploration of factors that may mediate the completion of question naires or alter the respondents ’ relationship with the same , to enhance progress in this area Background : There is increasing interest in measuring patients ’ experiences with individual physicians , and empirical evidence supports this area of measurement . However , the high cost of data collection remains a significant barrier . Survey modes with the potential to lower costs , such as Internet and interactive voice response ( IVR ) telephone , are attractive alternatives to mail , but their comparative response rates and data quality have not been tested . Methods : We r and omly assigned adult patients from the panels of 62 primary care physicians in California to complete a brief , vali date d patient question naire by mail , Internet ( web ) , or IVR . After 2 invitations , web and IVR nonrespondents were mailed a paper copy of the survey ( “ crossover ” to mail ) . We analyzed and compared ( n = 9126 ) the response rates , respondent characteristics , substantive responses , and costs by mode ( mail , web and IVR ) and evaluated the impact of “ crossover ” respondents . Results : Response rates were higher by mail ( 50.8 % ) than web ( 18.4 % ) or IVR ( 34.7 % ) , but after crossover mailings , response rates in each arm were approximately 50 % . Mail and web produced identical scores for individual physicians , but IVR scores were significantly lower even after adjusting for respondent characteristics . There were no significant physician-mode interactions , indicating that statistical adjustment for mode resolves the IVR effect . Web and IVR costs were higher than mail . Conclusions : The equivalence of individual physician results in mail and web modes is noteworthy , as is evidence that IVR results are comparable after adjustment for mode . However , the higher overall cost of web and IVR , as the result of the need for mailings to support these modes , suggests that they do not presently solve cost concerns related to obtaining physician-specific information from patients Objectives This study examined the measurement equivalence of the original paper-based vertical format of the EQ-5D visual analog scale ( EQ VAS ) with a touch-screen computer-based horizontal format . Methods A total of 314 subjects were administered two modes of the EQ VAS in a r and omized crossover design . One mode was the original paper-based 20 cm vertical EQ VAS ; the other mode was touch-screen-based . Measurement equivalence was assessed by testing the 95 % confidence interval of the mean differences from an equivalence threshold of −3 to + 3 points on the VAS and evaluating the intraclass correlation coefficient ( ICC ) . Results The adjusted mean ( SE ) EQ VAS score was 80.96 ( 0.87 ) on the paper and 79.59 ( 0.85 ) on the touch-screen . The mean ( CI ) difference between scores on the two formats was 1.37 with a confidence interval of 0.175–2.559 , wholly contained within the equivalence interval . The ICC was 0.75 , indicating acceptable agreement between the two modes . Almost a third ( 30.1 % ) of the respondents reported identical scores on both formats . Conclusion These results provide evidence for the measurement equivalence of this EQ VAS touch-screen administration mode with the original paper mode Background Self-report measures can guide clinical decisions and are useful when evaluating treatment outcomes . However , many clinicians do not use self-report measures systematic ally in their clinical practice . Internet-based question naires could facilitate administration , but the psychometric properties of the online version of an instrument should be explored before implementation . The recommendation from the International Test Commission is to test the psychometric properties of each question naire separately . Objective Our objective was to compare the psychometric properties of paper- and -pencil versions and Internet versions of two question naires measuring depressive symptoms . Methods The 87 participating patients were recruited from primary care and psychiatric care within the public health care system in Sweden . Participants completed the Beck Depression Inventory ( BDI-II ) and the Montgomery-Åsberg Depression Rating Scale — Self-rated ( MADRS-S ) , both on paper and on the Internet . The order was r and omized to control for order effects . Symptom severity in the sample ranged from mild to severe depressive symptoms . Results Psychometric properties of the two administration formats were mostly equivalent . The internal consistency was similar for the Internet and paper versions , and significant correlations were found between the formats for both MADRS-S ( r = .84 ) and the BDI-II ( r = .89 ) . Differences between paper and Internet total scores were not statistically significant for either question naire nor for the MADRS-S question dealing with suicidality ( item 9 ) when analyzed separately . The score on the BDI-II question about suicidality ( item 9 ) was significantly lower when administered via the Internet compared with the paper score , but the difference was small ( effect size , Cohen ’s [ d ] = 0.14 ) . There were significant main effects for order of administration on both question naires and significant interaction effects between format and order . This should not , however , pose a problem in clinical use as long as the administration format is not changed when repeated measurements are made . Conclusions The MADRS-S can be transferred to online use without affecting the psychometric properties in a clinical ly meaningful way . The full BDI-II also seems to retain its properties when transferred ; however , the item measuring suicidality in the Internet version needs further investigation since it was associated with a lower score in this study . The use of online question naires offers clinicians a more practical way of measuring depressive symptoms and has the potential to save re sources OBJECTIVE To compare the efficiency and differential costs of telephone- vs. mail-based assessment s of outcome in patients registered in a national clinical quality of care registry , the Australian Stroke Clinical Registry ( AuSCR ) . STUDY DESIGN AND SETTING The participants admitted to hospital with stroke or transient ischemic attack were r and omly assigned to complete a health question naire by mail or telephone interview at 3 - 6 months postevent . Response rate , research er burden , and costs of each method were compared . RESULTS Compared with the participants in the mail question naire arm ( n=277 ; 50 % female ; mean age : 70 years ) , those in the telephone arm ( n=282 ; 45 % female ; mean age : 68 years ) required a shorter time to complete the follow-up ( mean difference : 24.2 days ; 95 % confidence interval [ CI ] : 15.0 , 33.5 days ) . However , the average cost of completing a telephone follow-up was greater ( US$ 20.87 vs. US$ 13.86 ) and had a similar overall response to the mail method ( absolute difference : 0.57 % ; 95 % CI : -4.8 % , 6 % ) . CONCLUSION Posthospital stroke outcome data were slower to collect by mail , but the method achieved a similar completion rate and was significantly cheaper to conduct than follow-up telephone interview . Findings are informative for planning outcome data collection in large numbers of patients with acute stroke OBJECTIVES To test the impact of the method of administration ( MOA ) on score level , reliability , and validity of scales developed in the Patient Reported Outcomes Measurement Information System ( PROMIS ) . STUDY DESIGN AND SETTING Two nonoverlapping parallel forms each containing eight items from each of three PROMIS item banks ( Physical Function , Fatigue , and Depression ) were completed by 923 adults with chronic obstructive pulmonary disease , depression , or rheumatoid arthritis . In a r and omized crossover design , subjects answered one form by interactive voice response ( IVR ) technology , paper question naire ( PQ ) , personal digital assistant ( PDA ) , or personal computer ( PC ) and a second form by PC , in the same administration . Method equivalence was evaluated through analyses of difference scores , intraclass correlations ( ICCs ) , and convergent/discriminant validity . RESULTS In difference score analyses , no significant mode differences were found and all confidence intervals were within the prespecified minimal important difference of 0.2 st and ard deviation . Parallel-forms reliabilities were very high ( ICC = 0.85 - 0.93 ) . Only one across-mode ICC was significantly lower than the same-mode ICC . Tests of validity showed no differential effect by MOA . Participants preferred screen interface over PQ and IVR . CONCLUSION We found no statistically or clinical ly significant differences in score levels or psychometric properties of IVR , PQ , or PDA administration compared with PC OBJECTIVE Chronic pain is a common and costly syndrome which affects approximately one in three US adults . Factors such as shortened length of the medical visit , increased availability of technological approaches to care , and a more informed patient all suggest that a new paradigm is required for chronic pain management . Although much has been written about the use of electronic diaries in clinical trials , little has been presented about the use of these diaries in clinic practice and their potential for changing pain behavior . The intent of this preliminary study is to measure accessibility and usability of a software program design ed for use on a personal digital assistant and to discuss how the software program may impact clinic practice and patient behavior . METHODS We present the results of a preliminary , r and omized , comparison , crossover trial of 36 chronic pain patients who were asked to monitor their pain , mood , activity interference , medication use , and pain location on either a paper or electronic diary for 2 weeks . Patients in the electronic diary condition were able to observe changes in their ratings over time and view them on a secure web site . RESULTS No differences were found between paper and electronic tracking on pain descriptors , pain interference , mood , or helpfulness of medication . Similar to past findings , patients found the electronic diary easier to use ( P < 0.0001 ) and would continue using it ( P < 0.05 ) over paper if given the choice . Importantly , patients using the electronic diary reported more frequently that a provider suggested medication change ( P < 0.05 ) based on feedback from the electronic diary . One trend requiring further investigation is that electronic diary users reported that the diary enabled them and their doctor to make care adjustments according to changes in pain status . CONCLUSION This study goes beyond previous research on preference and data quality to investigate how the information provided may affect patient and physician perspectives toward pain management . Although not the initial intent of this study , findings indicate that electronic tracking may provide information which can affect management decisions . A follow-up study is ongoing to investigate these initial results . If found to be true , electronic monitoring may have broad implication s for health care , policy , and improvement in quality of care for chronic pain sufferers in the future Purpose The Social Difficulties Inventory ( SDI-21 ) assesses everyday problems experienced by cancer patients , including difficulties with self-care , work and relationships . Early development and psychometric evaluation studies have vali date d the SDI-21 for computer administration . However , several recent studies have administered the SDI-21 on paper . We sought to test the score equivalence of electronic and paper versions of the SDI-21 . Methods A r and omised two-arm crossover trial in a sample of cancer patients with varied diagnoses . Patients completed electronic ( via the internet ) and paper versions of the SDI-21 , with half r and omly assigned to complete the electronic version first ( n = 51 ) and half the paper version first ( n = 60 ) . Patients were asked to complete both versions at home , within 2 weeks . Analyses were performed for the SDI-21 summary score and three subscales . Results Score distributions and internal reliabilities for the paper and electronic versions were highly similar . There were no significant differences between mean summary or subscale scores for the two administration modes . All mean score differences ( all < 0.25 of a scale point ) were well below the SDI-21 ’s established minimally important differences , and all 95 % confidence intervals were narrow and included zero . Intraclass correlations between paper and electronic scores were uniformly high and significant ( all ≥0.85 ) and above the st and ard acceptable level of reliability . Conclusions Paper and electronic versions of the SDI-21 can be considered equivalent and used interchangeably . This is important because , despite the growth of electronic formats , paper versions are currently still necessary to ensure inclusive use of the SDI-21 with representative sample OBJECTIVE To compare responses to print versions of the Consumer Assessment of Healthcare Providers and Systems 2.0 survey ( CAHPS ) to those for an illustration enhanced format and a telephone based interactive voice response format . METHODS First , 2015 adult patients awaiting primary care visits completed : demographic information , Test of Functional Health Literacy ( S-TOFHLA ) , CAHPS in one of three formats : print , illustrated , or interactive voice . A second sample of 4800 active patients was r and omized to receive alternative formats . RESULTS Response rates for the illustrated ( 31.3 % ) and print ( 30.4 % ) formats were significantly higher than for the interactive voice format ( 18.1 % ) . The results of the illustrated format were comparable to the traditional text version , but required about 2 min more to complete by both low and high literacy groups . There were almost no invalid responses for the interactive voice format , but the format was associated with lower CAHPS satisfaction scores . CONCLUSION Despite extensive efforts to produce formats tailored to individuals with limited literacy , surprisingly we found no consistent advantages to either alternative format . In fact , the interactive voice format yielded lower satisfaction scores and lower response rates . PRACTICE IMPLICATION S Practitioners need to ensure the health instruments they use are aligned with literacy skills and delivery preferences of their consumers . The lack of benefit of the illustrated form does not support investment of re sources in these formats to measure satisfaction . The interactive voice response deserves more study --do lower scores register limited access to or use of telephones , irritation or true signal OBJECTIVE To assess the measurement equivalence of an interactive voice response ( IVR ) version of the EQ-5D with the original paper version . METHODS Subjects were r and omly assigned to : 1 ) paper then IVR , or 2 ) IVR then paper and asked to complete the question naire two days apart . The analyses tested mean differences ( repeated measures analysis of variance ) and reliability ( intraclass correlation coefficient [ ICC ] ) . Equivalence of the means was established if the 95 % confidence interval ( CI ) of the mean difference was within the minimally important difference interval : -0.035 to 0.035 for the EQ-5D index and -3 to 3 for the visual analog scale ( EQ VAS ) . ICC adequacy was tested by comparing the ICC 95 % lower CI with a critical value of 0.70 . RESULTS The analyses included 113 subjects for the index and 109 subjects for the EQ VAS . For the index , the adjusted means of the paper and IVR versions were 0.789 ± 0.016 and 0.798 ± 0 . 017 , respectively . The 95 % CI of the mean difference was -0.024 to 0.006 , within the equivalence interval . The ICC was 0.894 ( 95 % lower CI 0.857 ) , significantly greater than 0.70 . For the EQ VAS , the adjusted means were 71.94 ± 1.87 for paper and 74.63 ± 1.79 for IVR . The 95 % CI of the mean difference was -4.347 to -1.049 , partially within the equivalence interval . The ICC was 0.887 ( 95 % lower CI 0.840 ) , significantly greater than 0.70 . CONCLUSIONS The results provide evidence that the EQ-5D scores on the IVR version were sufficiently equivalent to those obtained on the paper version Background : Automated voice response ( AVR ) systems have been used to collect patient-reported outcome data . Mode of administration of the assessment may affect patient reporting . Objective : To evaluate if there is a differential reporting of symptoms by the mode of assessment : AVR versus a live telephone interview among cancer patients with solid tumors undergoing chemotherapy . Research Design : R and omized clinical trial comparing a nurse-assisted symptom management with an automated telephone symptom management . After completing intake telephone interview administered by a person , patients were r and omized to either nurse arm or AVR arm to receive a 6-contact 8-week symptom management intervention . Patients in the nurse arm were called by specially trained nurses , and patients in the AVR arm were contacted via automated system to assess their symptoms and deliver symptom management strategies . Subjects : Two hundred patients in nurse arm , and 186 patients in the AVR arm completed the first intervention contact . Measures : Severities of 14 cancer-related symptoms were rated by patients at intake interview and at first intervention contact before the receipt of any interventions . Results : When compared with patients contacted by a nurse , patients contacted by the AVR reported higher severity of nausea and vomiting , diarrhea , poor appetite , constipation , diarrhea , pain , and alopecia controlling for prior intake symptom assessment that was free of mode effect . Symptom reporting varied by age , with the oldest group of patients reporting higher severity to the nurse . Conclusion : Mode effect needs to be considered in design ing trials for symptom management and in symptom monitoring in clinical practice BACKGROUND The Internet and telephone are valuable re sources for mental health practitioners when access to face-to-face assessment or therapy is difficult . However , despite the high stakes ( such as access to medication or financial compensation ) often involved in psychological testing , little is known about how test administration mode influences test scores when patients are malingering . The aim of this research was to examine for the first time the equivalence of a malingered measure of depression when administered over the Internet , over the telephone , and with pen and paper . SUBJECTS AND METHODS A mixed experimental design was used with participants ( n=91 ) r and omly allocated to Internet , telephone , or pen- and -paper groups . Participants completed the Edinburgh Depression Scale , first under st and ard instructions and then under instructions to fake as if experiencing severe depression . A manipulation check was included to ensure participants had understood and followed instructions to fake . RESULTS As predicted , participants were able to significantly increase their depression scores when asked to fake depression . Participants reported significantly lower faked depression scores over the telephone than in pen- and -paper format . Faked depression scores in the online group did not differ significantly from those in the telephone and pen- and -paper groups . However , participants in all groups met criteria indicative of a provisional diagnosis of depression . CONCLUSIONS Overall , the results indicate that there may be no meaningful difference between malingering across administration modes . If an individual is malingering depression , administration mode has minimal influence . These findings provide preliminary support for the use of online/telephone technologies in the assessment of depression The influence of the administration method used to collect oral health-related quality of life ( OHRQoL ) data is largely unknown . Therefore , the aim of this study was to determine whether OHRQoL information obtained using the Oral Health Impact Profile ( OHIP ) differed with different methods of collection ( personal interview , via telephone or as a self-administered question naire ) . The OHRQoL was measured using the German version of the OHIP . The instrument was administered to each of 42 patients using three different methods , in a r and omized order , about 1 wk apart . The test-retest reliability coefficient for the repeated OHIP assessment across the three methods of administration , and the magnitude of the variance component for administration method , were determined , characterizing the degree of OHIP score variation that is caused by this factor . Whereas OHIP mean score differences of 3.9 points were present between administration methods , the reliability coefficient of 0.90 ( 95 % CI , 0.85 - 0.95 ) indicated that 90 % of the OHIP score variation was caused by differences between subjects ( and not by the administration method or measurement error ) . The variance component for administration method explained 0.5 % of the OHIP score variation . In conclusion , the method of administration ( personal interview , telephone interview or self-administered question naire ) did not influence substantially OHIP scores in prosthodontic patients |
12,530 | 21,072,277 | While there is a potential beneficial effect in the use of progesterone for some women considered to be at increased risk of preterm birth , primarily in the reduction in the risk of preterm birth before 34 weeks gestation , it remains unclear if the observed prolongation of pregnancy translates into improved health outcomes for the infant | Preterm birth continues to provide an enormous challenge in the delivery of perinatal health care , and is associated with considerable short and long-term health consequences for surviving infants .
Progesterone has a role in maintaining pregnancy , by suppression of the calcium-calmodulin-myosin light chain kinase system .
Additionally , progesterone has recognized anti-inflammatory properties , raising a possible link between inflammatory processes , alterations in progesterone receptor expression and the onset of preterm labor . | Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants . Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence . Two recent double blind r and omized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate ( IM 17OHP-C ) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery . However , it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural , racial and genetic differences play a role in patient ’s response to supplemental progesterone . In addition the patient ’s acceptance of such recommendation is also in question . More research is still required on identification of at risk group , the optimal gestational age at initiation , mode of administration , dose of progesterone and long-term safety OBJECTIVE : A multicenter , r and omized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate ( 17P ) , initiated between 16 and 20 weeks of gestation , reduced preterm birth by 33 % . The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate . METHODS : Using 2002 national birth certificate data , augmented by vital statistics from 2 states , we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy . The number and rate of recurrent spontaneous preterm births were estimated . To predict effect , the reported 33 % reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates . RESULTS : In 2002 , approximately 30,000 recurrent preterm births occurred to women eligible for 17P , having had a recurrent preterm birth rate of 22.5 % . If 17P therapy were delivered to these women , nearly 10,000 spontaneous preterm births would have been prevented , thereby reducing the overall United States preterm birth rate by approximately 2 % , from 12.1 % to 11.8 % ( P < .001 ) , with higher reductions in targeted groups of eligible pregnant women . CONCLUSION : Use of 17P could reduce preterm birth among eligible women , but would likely have a modest effect on the national preterm birth rate . Additional research is urgently needed to identify other population s who might benefit from 17P , evaluate new methods for early detection of women at risk , and develop additional prevention strategies . LEVEL OF EVIDENCE : 11 mg natural progesterone ( P ) was administered to 20 healthy menopausal women by means of a nasal spray or intramuscular injection . Circulating P levels were calculated at various times after administration . The spray formulation yielded a CMax of 3.75 ng/ml at TMax = 60 min , the area under the curve (AUC)0 - 720 being 1,481.6 + /- 343 . Intramuscular administration yielded a mean CMax of 4.137 ng/ml at TMax = 240 min , the AUC0 - 720 being 2,491.2 + /- 540 . P absorption was faster through the nasal than through the intramuscular route , but intramuscular administration led to high serum levels for a much longer period Progesterone was administered to postmenopausal women in a form of vaginal suppositories containing 100 and 200 mg active substance in Butyrum cacao ( BC ) and Massa estarinum ( ME ) , a base with emulsifying properties . In the case of single doses , blood sample s were taken at 2 , 4 , 6 , 24 , 48 and 72 h. Another group of patients received vaginal suppositories ( 100 mg progesterone ) once a day for a 6 day period , with blood sample s taken 12 h after each administration . The plasma levels of progesterone were evaluated by radioimmunoassay . The time of maximum concentration ( tmax ) was 4 h in most cases , and 6 h in the others . The plasma levels were not dose-proportional . Peak plasma concentrations were in the range of 10 - 15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 mg doses . The ratio of the mean area under the curve ( AUC ) for 200 mg and the mean AUC for the 100 mg dose was found to be 1.37 . Replacing BC with ME result ed in the lowering of cmax and AUC , and an increase in tmax following a reducing in the rate and extent of adsorption . In the case of ME suppositories , the variability in AUC , cmax and tmax was greater compared to that observed with the BC suppositories . Elimination half-time was in the range of 9 - 10 h for BC and 14 h for ME suppositories . In vitro assessment of the release kinetics from a hydrophobic and an emulsion type base confirmed previous findings : the latter base assured better pharmaceutical availability . The repeated doses did not seem to produce an accumulation of progesterone in the plasma . On the contrary , a small decrease in plasma levels over time appeared during the 6 day period . Numerical analysis revealed an excellent goodness of fit for the in vivo experimental data via biexponential curves , i.e. a pseudomonocompartmental model Whilst only about a third of all cerebral palsy occurs in children who had been of low birthweight , recent increases in the survival of low and very low birthweight infants have coincided with significant increases in the numbers of cerebral palsy children amongst them . This paper analyses data from the Western Australian Cerebral Palsy Register and from the Maternal and Child Health Research Data Base for stillbirths , neonatal deaths and survivors to address the issues of increased survival , cerebral palsy and timing of brain damage . The analysis is inconclusive but suggestive that both antenatal and postnatal complications are important in the increases in cerebral palsy in low birthweight infants . The good news is that this means that a certain proportion of postnatally damaged low birthweight survivors could possibly be prevented by better neonatal care . The bad news is that the remaining proportion have probably received their damage well before delivery and the possibilities for prevention are still remote . Further studies of low birthweight infants with cerebral palsy are urgently required . They should include antenatal factors , investigating the various aetiological pathways to preterm birth , r and omised controlled trials of neonatal interventions and search ing for better neonatal predictors of brain damage OBJECTIVE This study was undertaken to determine whether progestational agents can prevent inflammation-induced preterm parturition and fetal demise . STUDY DESIGN The activation of contractile and inflammatory pathways in response to localized intrauterine inflammation was investigated by using quantitative polymerase chain reaction ( PCR ) . Serum progesterone ( P4 ) levels and alterations in progesterone receptor-B ( PR-B ) were determined with radioimmunoassay and quantitative PCR , respectively . With our in vivo model of intrauterine inflammation , animals were r and omly assigned to pretreatment with P4 or medroxyprogesterone acetate ( MPA ) before intrauterine lipopolysaccharide ( LPS ) . Animals were observed for preterm delivery . The number of live pups 48 hours after intrauterine LPS was recorded for each treatment group . The ability of MPA to alter signal transduction pathways leading to preterm parturition were investigated by quantitative PCR and histochemical studies . RESULTS Intrauterine inflammation is associated with decreased serum progesterone levels and decreased transcription of PR-B. Preterm delivery rates were 100 % for LPS alone , 63 % for LPS+P4 , and 0 % for LPS+MPA . No live pups remained at 48 hours in the LPS or LPS+P4 groups . Pretreatment with MPA significantly preserved fetal viability . MPA suppressed activation of contraction-associated genes and inflammatory mediators and prevented cervical ripening in response to intrauterine inflammation . CONCLUSION MPA , with its progestational and anti-inflammatory properties , prevented inflammation-induced preterm parturition and significantly preserved fetal viability OBJECTIVE Our purpose was to determine gestational age-specific outcomes of infants born in a period of surfactant use . STUDY DESIGN All 465 consecutive births between 23 and 28 weeks ' gestation in a tertiary center from 1987 to 1992 were analyzed prospect ively . At 18 months ' corrected age , 217 of 254 ( 85 % ) survivors were evaluated . RESULTS From 1987 and 1988 to 1991 and 1992 there was an increase in survival for infants born at 24 weeks ( from 0 % to 33 % p = 0.17 ) , 25 to 26 weeks ( 38 % to 71 % , p < 0.005 ) , and 27 to 28 weeks ( 66 % to 84 % , p < 0.05 ) . At each weekly interval from 24 to 28 weeks of gestation the respective incidence of normality was 44 % , 71 % , 57 % , 76 % and 72 % ( not significant ) and the respective mean developmental quotient was 91 + /- 17 , 89 + /- 25 , 90 + /- 24 , 96 + /- 15 and 96 + /- 14 ( not significant ) . CONCLUSIONS Gestational age was strongly associated with outcome in terms of survival . Overall , 70 % of children followed up were developing within the normal range A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate . The present double-blind investigation was design ed to prospect ively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications . Three groups of active-duty women were studied , beginning between 16 and 20 weeks ' gestation . They were similar for parity , previous abortion , race , cigarette smoking , and marital status . Of these , 80 were given 17 alpha-hydroxyprogesterone caproate , 88 received placebo , and 78 declined to participate in the protocol . There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality . However , when comparison was made to a military dependent population , they had a significantly worse outcome with regard to both perinatal mortality ( p = 0.001 ) and infants with a birth weight less than 2,500 gm ( p = 0.01 ) . We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome , but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate OBJECTIVE On the basis of the recent Maternal Fetal Medicine Unit Networks clinical trial , the American College of Obstetricians and Gynecologists supports the administration of 17-alpha hydroxyprogesterone caproate to high-risk patients . Because inflammation/infection is believed to be a contributing factor in many cases of preterm birth , it is imperative to underst and the effect of 17-alpha hydroxyprogesterone caproate treatment in this clinical situation . STUDY DESIGN Using a mouse model of localized intrauterine inflammation , we investigated the ability of progestational agents to prevent preterm birth . On gestational day 15 ( E15 ) , dams were assigned r and omly to treatment with 17-alpha hydroxyprogesterone caproate , medroxyprogesterone acetate , or vehicle before intrauterine infusion of lipopolysaccharide . All dams were monitored for morbidity and preterm birth . Three separate sets of experiments were performed to assess different outcomes at 6 , 24 , and 96 hours . At 6 and 24 hours , C-reactive protein , interleukin-6 , and interleukin-10 levels were measured in maternal serum by enzyme-linked immunosorbent assay . RESULTS Pretreatment with 17-alpha hydroxyprogesterone caproate or medroxyprogesterone acetate before intrauterine lipopolysaccharide treatment significantly decreased the preterm birth rate , compared with lipopolysaccharide treatment alone . Medroxyprogesterone acetate treatment was more effective than 17-alpha hydroxyprogesterone caproate treatment in the prevention of preterm birth and result ed in live pups at term . Treatment with 17-alpha hydroxyprogesterone caproate was associated with significant maternal morbidity . CONCLUSION In the setting of intrauterine inflammation , progestational agents decrease the preterm birth rate but can result in maternal morbidity . 17-Alpha hydroxyprogesterone caproate should not be used in patients who are suspected of having sub clinical infection and /or acute preterm labor . The mechanisms by which progestational agents inhibit preterm birth warrants further investigations so that the use of this drug to appropriate population s could be pursued without undue fetal or maternal harm OBJECTIVE The purpose of this study was to evaluate whether 17-alpha-hydroxyprogesterone caproate ( 17P ) treatment affect changes in cervical length . STUDY DESIGN Women with singleton pregnancy , between 25 and 33 + 6 weeks of gestation , who were hospitalized for preterm labor were included . Patients with rupture of membranes and /or signs of chorioamnionitis were excluded . Sixty undelivered patients were allocated r and omly to either observation or to receive 341 mg of 17P intramuscularly , twice each week until gestational week 36 . Cervical length was measured by transvaginal ultrasound scanning at discharge and at day 7 and 21 after discharge . Statistical comparisons were done with analysis of variance and chi-square test . RESULTS Shortening of the cervix in the observation group ( 30 cases ) was higher than in the 17P group ( 30 cases ) both at day 7 ( 2.37 + /- 2.0 mm vs 0.83 + /- 1.74 mm ; P = .002 ) and day 21 ( 4.60 + /- 2.73 mm vs 2.40 + /- 2.46 mm ; P = .002 ) . Treatment with 17P was associated with both a reduction in the risk of cervical shortening of > or = 4 mm ( odds ratio , 0.18 ; 95 % CI , 0.04 - 0.66 ) and in the risk of preterm delivery ( odds ratio , 0.15 ; 95 % CI , 0.04 - 0.58 ) . CONCLUSION Undelivered patients after preterm labor undergo progressive shortening of the cervix , which is attenuated by 17P treatment BACKGROUND Previous r and omized trials have shown that progesterone administration in women who previously delivered prematurely reduces the risk of recurrent premature delivery . Asymptomatic women found at midgestation to have a short cervix are at greatly increased risk for spontaneous early preterm delivery , and it is unknown whether progesterone reduces this risk in such women . METHODS Cervical length was measured by transvaginal ultrasonography at a median of 22 weeks of gestation ( range , 20 to 25 ) in 24,620 pregnant women seen for routine prenatal care . Cervical length was 15 mm or less in 413 of the women ( 1.7 % ) , and 250 ( 60.5 % ) of these 413 women were r and omly assigned to receive vaginal progesterone ( 200 mg each night ) or placebo from 24 to 34 weeks of gestation . The primary outcome was spontaneous delivery before 34 weeks . RESULTS Spontaneous delivery before 34 weeks of gestation was less frequent in the progesterone group than in the placebo group ( 19.2 % vs. 34.4 % ; relative risk , 0.56 ; 95 % confidence interval [ CI ] , 0.36 to 0.86 ) . Progesterone was associated with a nonsignificant reduction in neonatal morbidity ( 8.1 % vs. 13.8 % ; relative risk , 0.59 ; 95 % CI , 0.26 to 1.25 ; P=0.17 ) . There were no serious adverse events associated with the use of progesterone . CONCLUSIONS In women with a short cervix , treatment with progesterone reduces the rate of spontaneous early preterm delivery . ( Clinical Trials.gov number , NCT00422526 [ Clinical Trials.gov ] . ) OBJECTIVE The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population . STUDY DESIGN A r and omized , double-blind , placebo-controlled study included 142 high-risk singleton pregnancies . Progesterone ( 100 mg ) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes , between 24 and 34 weeks of gestation . Progesterone ( n = 72 ) and placebo ( n = 70 ) groups were compared for epidemiologic characteristics , uterine contraction frequency , and incidence of preterm birth . Data were compared by chi(2 ) analysis and Fisher exact test . RESULTS The preterm birth rate was 21.1 % ( 30/142 ) . Differences in uterine activity were found between the progesterone and placebo groups ( 23.6 % vs 54.3 % , respectively ; P < .05 ) and in preterm birth between progesterone and placebo ( 13.8 % vs 28.5 % , respectively ; P < .05 ) . More women were delivered before 34 weeks in the placebo group ( 18.5 % ) than in the progesterone group ( 2.7 % ) ( P < .05 ) . CONCLUSION Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients . Premature delivery did not occur in 18 patients receiving the progestational agent , whereas 41 per cent of the 22 receiving the palcebo had premature delivery ( P less than 0.01 ) . The mean duration of pregnancy and the mean birth weight in the former group ( 38.6 weeks + /- 1.6 S.D. , and 2836 g + /- 412 S.D. ) were both significantly greater ( P less than 0.025 ) than that in the latter ( 35.2 weeks + /- 6.7 S.D. ; 2361 g + /- 1085 S.D. ) . The perinatal mortality rate in the group given the progestational agent ( O per cent ) was significantly less than that observed in the placebo group ( 27 per cent ) ( P less than 0.05 ) . Although there were no complications attributable to the progestational drug , the study population was too small for assessment of immediate or long term safety . However , the results indicate a possible obstetric use for this drug OBJECTIVE Activation of the innate immune receptors , Toll-like receptors 2 and 4 , are critical for a host inflammatory response to both Gram-positive and Gram-negative organisms . These receptors can initiate and modulate the inflammatory response . Differential regulation of Toll-like receptors may be one of the mechanisms by which intrauterine inflammation signals parturition . Likewise , progestational agents may have the ability to modify this effect . These studies were performed to eluci date the effect of intrauterine inflammation and medroxyprogesterone acetate on Toll-like receptor expression in the uterus , cervix , and placenta in a mouse model of intrauterine inflammation . STUDY DESIGN On day 15 of gestation , CD-1 mice were r and omized to pretreatment with medroxyprogesterone acetate or vehicle before intrauterine infusion with lipopolysaccharide or sterile saline solution . Six hours after intrauterine infusion , uterine , cervical , and placental tissues were harvested . RNA and protein were extracted . Quantitative polymerase chain reaction was performed for Toll-like receptor 2 and 4 messenger RNA . Western blot analysis was performed with Toll-like receptor 4-specific antibodies . RESULTS Intrauterine inflammation up-regulated Toll-like receptor 2 and 4 messenger RNA in uterus , cervix , and placenta . Pretreatment with medroxyprogesterone acetate decreased the lipopolysaccharide-induced up-regulation of Toll-like receptor 2 and 4 messenger RNA in the cervix and placenta . Medroxyprogesterone acetate treatment , in the presence of lipopolysaccharide , was unable to prevent the lipopolysaccharide-induced increase in Toll-like receptor 4 messenger RNA and protein in the uterus . Medroxyprogesterone acetate treatment alone in pregnant mice significantly increased Toll-like receptor 4 messenger RNA expression in the uterus . CONCLUSION Intrauterine inflammation has a differential effect on Toll-like receptor 2 and 4 expression . The observed up-regulation of Toll-like receptor 2 in the uterus in response to intrauterine lipopolysaccharide may be a mechanism to augment the inflammatory response and may serve to promote parturition in the setting of inflammation . Consequently , the ability of medroxyprogesterone acetate to suppress lipopolysaccharide-induced up-regulation of Toll-like receptor 2 messenger RNA may be one of the mechanisms by which progestins are able to decrease preterm birth BACKGROUND In singleton gestations , 17 alpha-hydroxyprogesterone caproate ( 17P ) has been shown to reduce the rate of recurrent preterm birth . This study was undertaken to evaluate whether 17P would reduce the rate of preterm birth in twin gestations . METHODS We performed a r and omized , double-blind , placebo-controlled trial in 14 centers . Healthy women with twin gestations were assigned to weekly intramuscular injections of 250 mg of 17P or matching placebo , starting at 16 to 20 weeks of gestation and ending at 35 weeks . The primary study outcome was delivery or fetal death before 35 weeks of gestation . RESULTS Six hundred sixty-one women were r and omly assigned to treatment . Baseline demographic data were similar in the two study groups . Six women were lost to follow-up ; data from 655 were analyzed ( 325 in the 17P group and 330 in the placebo group ) . Delivery or fetal death before 35 weeks occurred in 41.5 % of pregnancies in the 17P group and 37.3 % of those in the placebo group ( relative risk , 1.1 ; 95 % confidence interval [ CI ] , 0.9 to 1.3 ) . The rate of the prespecified composite outcome of serious adverse fetal or neonatal events was 20.2 % in the 17P group and 18.0 % in the placebo group ( relative risk , 1.1 ; 95 % CI , 0.9 to 1.5 ) . Side effects of the injections were frequent in both groups , occurring in 65.9 % and 64.4 % of subjects , respectively ( P=0.69 ) , but were generally mild and limited to the injection site . CONCLUSIONS Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with twin gestations . ( Clinical Trials.gov number , NCT00099164 [ Clinical Trials.gov ] . ) The use of luteal phase support has been demonstrated in patients undergoing an IVF/ET procedure . This study was design ed to compare the absorption and the efficacy of two different luteal supports : 17-alpha-hydroxyprogesterone caproate ( Lentogest , AMSA , Italy ) and natural Progesterone ( Prontogest , AMSA , Italy ) . A total of 80 patients received luteal supplementation with 50 mg of natural P/day intramuscularly , until beta-hCG evaluation . Then , in case of positive beta-hCG , patients were r and omly divided into two groups ( A and B ) in order to compare two different protocol s : Group A , 17-OHPc ( 341 mg once a week ) and Group B , natural P ( 50 mg/day ) both intramuscularly and extended for 10 - 12 weeks . Our study showed that the treatment with 17-OHPc results in a higher percentage of pregnancy rate compared to natural P , but the differences are not statistically significant . Thus , we emphasize that 17-OHPc preparation for better acceptance appears to be the most suitable and comfortable method for luteal phase support There are indications that prophylactic administration of 17α-hydroxyprogesterone caproate ( 17α-OHP-C ) could be beneficial in the treatment of women at risk for preterm delivery . Since twin pregnancy is commonly associated with prematurity , 77 women with twin pregnancy were treated during the last trimester until the 37th gestational week with weekly injections of either 17α-OHP-C or a placebo , following double-blind principles . The gestational length and birth weight and the outcome of the neonates were similar in both groups . The administration of 17α-OHP-C thus seems ineffective in the prevention of prematurity risks associated with twin pregnancy . ( Obstet Gynecol 56:692 , 1980 The purpose of this study was to assess the impact of extreme prematurity on three global measures of school outcomes . Using a matched cohort design , exposed infants comprised all surviving singleton infants < or = 28 weeks gestation born at one regional neonatal intensive care hospital between 1983 and 1986 ( n = 132 ) . Unexposed infants comprised r and omly selected full-term infants ( > or = 37 weeks gestation ) frequency matched on date of birth , zip code and health insurance . All children were selected from a regional tertiary children 's centre serving western New York population . St and ardised telephone interviews elicited information on grade repetition , special education placement and use of school-based services . Unconditional logistic regression was used to estimate odds ratios ( OR ) and corresponding 95 % confidence intervals ( CI ) adjusted for potential confounders for children without major h and icaps . Extreme prematurity was associated with a significant increase in risk of grade repetition ( OR = 3.22 ; 95 % CI = 1.63 , 6.34 ) , special education placement ( OR = 3.16 ; 95 % CI = 1.14 , 8.76 ) and use of school-based services ( OR = 4.56 ; 95 % CI = 1.82 , 11.42 ) in comparison with children born at term , even after controlling for age , race , maternal education , foster care placement and the matching factors . These findings suggest that survivors of extreme prematurity remain at risk of educational underachievement OBJECTIVE Preterm birth is the leading cause of perinatal morbidity and mortality worldwide . Treatment of preterm labor with tocolysis has not been successful in improving infant outcome . The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth . The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth . METHODS This r and omized , double-blind , placebo- controlled , multinational trial enrolled and r and omized 659 pregnant women with a history of spontaneous preterm birth . Between 18 + 0 and 22 + 6 weeks of gestation , patients were assigned r and omly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery , 37 weeks ' gestation or development of preterm rupture of membranes . The primary outcome was preterm birth at < /= 32 weeks of gestation . The trial was analyzed using an intent-to-treat strategy . RESULTS Baseline characteristics were similar in the two treatment groups . Progesterone did not decrease the frequency of preterm birth at < /= 32 weeks . There was no difference between the groups with respect to the mean gestational age at delivery , infant morbidity or mortality or other maternal or neonatal outcome measures . Adverse events during the course of treatment were similar for the two groups . CONCLUSION Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth ( < /= 32 weeks ) in women with a history of spontaneous preterm birth . The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone ( e.g. sonographic cervical length ) requires further investigation OBJECTIVE : Our aim was to document the differential neonatal morbidity and intrapartum and neonatal mortality of subgroups of preterm delivery . METHODS : This analysis included 38,319 singleton pregnancies , of which 3,304 ( 8.6 % ) were preterm deliveries ( less than 37 completed weeks ) enrolled in the World Health Organization r and omized trial of a new antenatal care model . We classified them as preterm deliveries after spontaneous initiation of labor , either with or without maternal obstetric and medical complications ; preterm deliveries after prelabor spontaneous rupture of amniotic membranes ( PROM ) , either with or without obstetric and medical complications ; and medically indicated preterm deliveries with maternal obstetric and medical complications . Severe neonatal morbidity and neonatal mortality were the primary outcomes . RESULTS : Fifty-six percent of all preterm deliveries were spontaneous , without maternal complications . Small for gestational age was increased only among the medically indicated preterm delivery group ( 22.3 % ) . Very early preterm delivery ( less than 32 weeks of gestation ) was highest among PROM with complications ( 37 % ) . For intrapartum fetal death and neonatal death , after adjusting by gestational age and other confounding variables , we found that the obstetric and medical complications preceding preterm delivery predicted the different risk levels . Conversely , for severe neonatal morbidity the clinical presentation , ie , PROM or medically indicated , predicted the increased risk . CONCLUSION : There are differential neonatal outcomes among preterm deliveries according to clinical presentation , pregnancy complications , gestational age at delivery , and its association with small for gestational age . This syndromic nature of the condition should be considered if preterm delivery is to be fully understood and thus reduced . LEVEL OF EVIDENCE : International comparison of perinatal mortality rates is subject to various problems in methods of reporting . The main difficulties are differences in the definition of livebirth and the variation in policies on the elective delivery of very preterm fetuses at risk of intrauterine death . This study , based on geographically defined population s within the European Community , set out to compare survival rates in very low birthweight infants ( below 1500 g ) . The first phase of the study in seven population s showed pronounced differences in survival and in the proportion of liveborn infants who weighed less than 1000 g. A further phase studied the outcome of all pregnancies from 22 to 28 weeks ' gestation in four population s. There was no significant difference between the four population s in crude survival rates per 1000 livebirths among infants born at 22 to 28 weeks ' gestation , but more babies were born alive at the earlier gestations in the United Kingdom . Survival rates were higher in Scotl and and Engl and when gestational age at birth was controlled for . Future comparisons of the outcome of perinatal care for extremely immature infants would be more meaningful if data on the outcome of all pregnancies ending after 22 weeks ' gestation were routinely collected through the registration system OBJECTIVE To analyse hospital readmissions to 1 year in infants < 33 weeks ' gestation . STUDY DESIGN Cohort of very preterm infants born in Western Australia . METHODS Parental social class , history of asthma , race , gestational age , birthweight , sex , severity of respiratory disease and oxygen requirement at 28 days chronic lung disease ( CLD ) , 36 weeks and term , maternal smoking , cohabitation with siblings , breast-feeding duration and hospital readmissions were recorded prospect ively . RESULTS Data were available for 538 of 560 ( 96 % ) infants discharged . Eight died in the first year . Two hundred and twenty-five infants ( 42 % ) had 443 readmissions , of which 370 were medical and 73 surgical . Risk factors for medical readmission were Aboriginal race , male sex and CLD . Breast-feeding was protective . Risk factors for surgical admission were male sex , lower gestation , severe hyaline membrane disease , severe CLD and birthweight < 10th centile . CONCLUSIONS Readmission is common after very preterm birth . Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission |
12,531 | 24,942,480 | Though there was support for the effectiveness of cognitive rehabilitation for some cognitive impairments , significant gaps were found in the current evidence base . | Background : Although cognitive impairments are common following stroke , there is considerable uncertainty about the types of interventions that can reduce activity restrictions and improve quality of life .
Indeed , a recent project to identify priorities for research into life after stroke determined that the top priority for patients , carers and health professionals was how to improve cognitive impairments .
Objective : To provide an overview of the evidence for the effectiveness of cognitive rehabilitation for patients with stroke and to determine the main gaps in the current evidence base . | BACKGROUND In a r and omized controlled type Ib study , the effectiveness of three different forms of therapy for the treatment of visual neglect was assessed by comparing therapy outcomes in three groups of patients after cerebrovascular accidents . METHODS A control group received only st and ard exploration training , whilst the second and third group received exploration training combined with either contralateral transcutaneous electrical nerve stimulation ( TENS ) or optokinetic stimulation ( OKS ) respectively . RESULTS It was found that exploration training alone result ed in no improvement on both st and ard neglect tests ( NTs ) and everyday-relevant measures of reading and writing performance . In contrast , the groups receiving TENS or OKS showed significant improvements in both sets of measures with the difference that for the TENS group the improvement in NT scores at the end of therapy had disappeared 1-week later . However , both treatments result ed in significant improvements in reading and writing which were still present upon retesting 1-week after the end of therapy . CONCLUSION Both methods can be recommended for neglect therapy and are superior to exploration therapy alone OBJECTIVE To assess the effectiveness of a rehabilitative training program for patients with limb apraxia . DESIGN R and omized , controlled trial . SETTING Neurologic rehabilitation unit of a university hospital . PATIENTS Thirteen patients with acquired brain injury and limb apraxia ( lasting more than 2 months ) as a result of lesions involving the left cerebral hemisphere . Patients were assigned to a study group or to a control group following a r and omization scheme . The study group underwent an experimental training for limb apraxia . The control group received conventional treatment for aphasia . INTERVENTION A behavioral training program consisting of gesture-production exercises . The rehabilitative program was made up of 3 sections dedicated to the treatment of gestures with or without symbolic value and related or nonrelated to the use of objects . Thirty-five experimental sessions , each lasting 50 minutes , were given . MAIN OUTCOME MEASURES Neuropsychologic tests for assessment of aphasia , verbal comprehension , " general intelligence , " oral apraxia , constructional apraxia , and 3 tests concerning limb praxic function ( ideational apraxia , ideomotor apraxia , gesture recognition ) . Scores related to each test were used to measure the outcome . Video recordings of ideational and ideomotor apraxia tests allowed us to register type and number of praxic errors . All outcome measures , except the aphasia test , were recorded before and after the experimental ( or control ) treatment time interval . RESULTS The patients in the study group achieved a significant improvement of performance in both ideational ( p = .039 ) and ideomotor ( p = .043 ) apraxia tests . They also showed a significant reduction of errors in ideational ( p = .001 ) and ideomotor ( p < .001 ) apraxia tests . A trend toward improvement was found in the gesture comprehension test ( p = .058 ) , while other outcome measures did not show any significant amelioration . Control patients did not show any significant change in performance . CONCLUSIONS The results show the possible effectiveness of a specific training program for the treatment of limb apraxia Aim : To examine the effects of working memory ( WM ) training in adult patients with stroke . Methods : A r and omized pilot study with a treatment group and a passive control group ; 18 participants ( 12 males ) in a vocational age group ( mean age 54 years ) were r and omized to either the treatment or the control condition . The intervention consisted of computerized training on various WM tasks for five weeks . A neuropsychological test battery and self-rating on cognitive functioning in daily life ( the CFQ ) were administered both before and after the treatment . Results : Statistically significant training effects were found on the non-trainedtests for WM and attention , i.e. , tests that measure related cognitive functions but are not identical to tasks in the training programme ( Span board p < 0.05 ; PASAT p < 0.001 ; Ruff 2&7 p < 0.005 ) . There was a significant decrease in symptoms of cognitive problems as measured by the CFQ ( p < 0.005 ) . Conclusion : More than one year after a stroke , systematic WM training can significantly improve WM and attention Prism adaptation has been shown to alleviate the symptoms of unilateral spatial neglect following stroke in single case and small group studies . The purpose s of this single blinded pilot r and omised controlled trial were to determine the feasibility of delivering prism adaptation treatment in a clinical ly valid sample and to assess its impact on self-care . Thirty seven right hemisphere stroke patients with unilateral spatial neglect were r and omised into either prism adaptation ( using 10 dioptre , 6 degree prisms ) or sham treatment ( using plain glasses ) groups . Treatment was delivered each weekday for two weeks . Pointing accuracy , without vision of the finger , was recorded each day before treatment . Outcome was measured , by blinded assessors , four days and eight weeks after the end of treatment using the Catherine Bergego Scale ( CBS ) and the conventional neuropsychological tests from the Behavioural Inattention Test ( BIT ) . Thirty four patients received treatment : 16 with prisms , 18 sham . Mean compliance was 99 % and 97 % , respectively . Over the treatment days only the prism treated group showed increased leftward bias in open loop pointing to targets on a touch screen . However , despite the group level changes in pointing behaviour no overall effect of the treatment on self-care or BIT were found Feedback of eye movements was evaluated as a treatment for visual neglect in right hemisphere stroke patients . Patients with visual neglect identified on the Behavioural Inattention Test ( BIT ) were r and omly allocated to two groups . One group ( n = 9 ) was treated for 2 h 40 min a week for 4 weeks , by wearing glasses which provided a reminder bleep if patients failed to move their eyes to the left in a 15 s interval . The control group ( n = 9 ) received no treatment for their visual inattention . Comparison of the groups after 4 weeks treatment and a further 4 weeks follow-up showed no significant difference either in eye movements or on the BIT . However , there was a trend towards a difference between eye movements in the two groups at 8 weeks , suggesting treatment may have influenced eye movements without changing neglect Background Many interventions delivered within the stroke rehabilitation setting could be considered complex , though some are more complex than others . The degree of complexity might be based on the number of and interactions between levels , components and actions targeted within the intervention . The number of ( and variation within ) participant groups and the context s in which it is delivered might also reflect the extent of complexity . Similarly , design ing the evaluation of a complex intervention can be challenging . Considerations include the necessity for intervention st and ardisation , the multiplicity of outcome measures employed to capture the impact of a multifaceted intervention and the delivery of the intervention across different clinical setting s operating within varying healthcare context s. Our aim was to develop and evaluate the implementation of a complex , multidimensional oral health care ( OHC ) intervention for people in stroke rehabilitation setting s which would inform the development of a r and omised controlled trial . Methods After review ing the evidence for the provision of OHC following stroke , multi-disciplinary experts informed the development of our intervention . Using both quantitative and qualitative methods we evaluated the implementation of the complex OHC intervention across patients , staff and service levels of care . We also adopted a pragmatic approach to patient recruitment , the completion of assessment tools and delivery of OHC , alongside an attention to the context in which it was delivered . Results We demonstrated the feasibility of implementing a complex OHC intervention across three levels of care . The complementary nature of the mixed methods approach to data gathering provided a complete picture of the implementation of the intervention and a detailed underst and ing of the variations within and interactions between the components of the intervention . Information on the feasibility of the outcome measures used to capture impact across a range of components was also collected , though some process orientated uncertainties including eligibility and recruitment rates remain to be further explored within a Phase II exploratory trial . Conclusions Complex interventions can be captured and described in a manner which facilitates evaluation in the form of exploratory and subsequently definitive clinical trials . If effective , the evidence captured relating to the intervention context will facilitate translation into clinical practice BACKGROUND AND PURPOSE Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion . Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy . We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial . METHODS Patients with major ( n=33 ) or minor ( n=14 ) depression participated in a double-blind treatment study with nortriptyline or placebo . They were examined for change in depressive mood , measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and change in cognitive impairment , assessed by the Mini-Mental State Examination ( MMSE ) , after treatment with nortriptyline or placebo . Cognitive treatment response , as measured by the MMSE , was compared between patients whose depression did and did not respond to treatment . RESULTS Patients whose poststroke depression remitted ( predominantly associated with nortriptyline treatment ) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit ( predominantly associated with placebo treatment ) . CONCLUSIONS Our findings support the contention that poststroke major depression leads to a " dementia of depression . " Prior studies failed to show an effect of treatment because the effect size was too small . Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke The aim of this r and omised , double-blind study was to investigate the therapeutic effectiveness of left-h and electrical stimulation for patients with post-stroke left visuo-spatial neglect . This approach was hypothesised to enhance activation of the right hemisphere attention system and to improve visual exploration of extrapersonal space . Participants ( n = 40 ) in the study were in a relatively early stage of recovery from their first right hemisphere stroke , and were r and omly assigned to the experimental ( E ) or control ( C ) group . Group E received conventional visual scanning training combined with electrostimulation of the left h and , while Group C received scanning training with sham stimulation . Their visuo-spatial neglect was assessed twice , prior to the rehabilitation programme and on its completion , using cancellation tests and a letter-reading task . The effect of electrostimulation on hemineglect was assessed following a single administration and after a month-long rehabilitation programme . Although the immediate effect of stimulation was poor , after a month-long rehabilitation period we found significantly greater improvement in Group E patients than in Group C patients . Interestingly , the presence of hemisensory loss did not weaken the observed effect . Therefore , we cl aim that contralesional h and stimulation combined with visual scanning was a more effective treatment for hemineglect rehabilitation than scanning training alone CONTEXT Adjunctive restorative therapies administered during the first few months after stroke , the period with the greatest degree of spontaneous recovery , reduce the number of stroke patients with significant disability . OBJECTIVE To examine the effect of escitalopram on cognitive outcome . We hypothesized that patients who received escitalopram would show improved performance in neuropsychological tests assessing memory and executive functions than patients who received placebo or underwent Problem Solving Therapy . DESIGN R and omized trial . SETTING Stroke center . PARTICIPANTS One hundred twenty-nine patients were treated within 3 months following stroke . The 12-month trial included 3 arms : a double-blind placebo-controlled comparison of escitalopram ( n = 43 ) with placebo ( n = 45 ) , and a nonblinded arm of Problem Solving Therapy ( n = 41 ) . OUTCOME MEASURES Change in scores from baseline to the end of treatment for the Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) and Trail-Making , Controlled Oral Word Association , Wechsler Adult Intelligence Scale-III Similarities , and Stroop tests . RESULTS We found a difference among the 3 treatment groups in change in RBANS total score ( P < .01 ) and RBANS delayed memory score ( P < .01 ) . After adjusting for possible confounders , there was a significant effect of escitalopram treatment on the change in RBANS total score ( P < .01 , adjusted mean change in score : escitalopram group , 10.0 ; nonescitalopram group , 3.1 ) and the change in RBANS delayed memory score ( P < .01 , adjusted mean change in score : escitalopram group , 11.3 ; nonescitalopram group , 2.5 ) . We did not observe treatment effects in other neuropsychological measures . CONCLUSIONS When compared with patients who received placebo or underwent Problem Solving Therapy , stroke patients who received escitalopram showed improvement in global cognitive functioning , specifically in verbal and visual memory functions . This beneficial effect of escitalopram was independent of its effect on depression . The utility of antidepressants in the process of poststroke recovery should be further investigated . Trial Registration clinical trials.gov Identifier : NCT00071643 Objective : To investigate the effectiveness of voluntary trunk rotation and half-field eye-patching to treat patients with unilateral neglect in stroke . Design : Pre — post , day 60 follow-up , single-blinded r and omized controlled trial . Setting : Single-centre inpatient rehabilitation hospital . Subjects : Sixty subacute patients with right hemisphere stroke having unilateral neglect within eight weeks post stroke consented to participate between November 2003 and July 2005 . They were r and omly assigned to three comparison groups . Interventions : Nineteen patients received daily experimental training in voluntary trunk rotation ( TR ) for 1 hour five times a week for 30 days . Twenty patients received the same kind of treatment together with half-field eye-patching ( TR + EP ) . Fifteen patients in the control group received conventional training with the same contact time . Main outcome measures : Patients were assessed on days 0 , 30 and 60 using the Behavioural Inattention Test , the Clock Drawing Test , and the Functional Independence Measure . Results : No significant differences between voluntary trunk rotation ( TR ) , voluntary trunk rotation and half-field eye-patching ( TR + EP ) and controls were found in functional performance and neglect measures at day 30 ( P = 0.042—0.994 ) and follow-up ( P = 0.052—0.911 ) at P = 0.005 using Bonferroni correction . Conclusions : The results of this study do not support the use of voluntary trunk rotation alone or with half-field eye-patching to improve functional performance or reduce unilateral neglect in subacute patients with stroke Background and Purpose — Impaired attention contributes to poor stroke outcomes . Attention process training ( APT ) reduces attention deficits after traumatic brain injury . There was no evidence for effectiveness of APT in stroke patients . This trial evaluated effectiveness of APT in improving attention and broader outcomes in stroke survivors 6 months after stroke . Methods — Participants in this prospect i ve , single-blinded , r and omized , clinical trial were 78 incident stroke survivors admitted over 18 months and identified via neuropsychological assessment as having attention deficit . Participants were r and omly allocated to st and ard care plus up to 30 hours of APT or st and ard care alone . Both groups were impaired ( z≤−2.0 ) across measures of attention at baseline , with the exception of Paced Auditory Serial Addition Test , which was below average ( z≤−1.0 ) . Outcome assessment occurred at 5 weeks and 6 months after r and omization . The primary outcome was Integrated Visual Auditory Continuous Performance Test Full-Scale Attention Quotient . Results — APT result ed in a significantly greater ( P<0.01 ) improvement on the primary outcome than st and ard care . Difference in change on the Cognitive Failures Question naire approached significance ( P=0.07 ) . Differences on other measures of attention and broader outcomes were not significant . Conclusion — APT is a viable and effective means of improving attention deficits after incident stroke Purpose . The right half-field eye-patching technique has been reported to be effective in reducing unilateral neglect ( UN ) and improving functional ability in stroke patients . This study investigated the efficacy of conventional treatment with right half-field eye patching in treating subacute stroke patients with UN , using a r and omised controlled trial . Method . Thirty-five in patients with subacute stroke were recruited and r and omised into intervention and control groups . The patients in the intervention group received 4 weeks of conventional occupational therapy with modified right half-field eye-patching . Those in the control group received 4 weeks of conventional treatment only . Assessors , who were blind to the treatments , assessed the groups using the Behavioural Inattention Test ( BIT ) and the Functional Independence Measure ( FIM ) on admission and at 4 weeks . Results . Patients treated with right half-field eye-patching had significantly ( p = 0.046 ) higher BIT gain ( mean = 25.06 , SD = 30.81 ) than those treated with the conventional treatment ( mean = 8.29 , SD = 10.35 ) . There was no significant difference ( p = 0.467 ) in FIM gain between patients in both groups . Conclusions . Right half-field eye-patching improved stroke patients ' impairment level in terms of UN , but the potential benefits in impairment tests were not confirmed by improvements in function Abstract Objective : We compared visual scanning and mental practice and explored the effects of these techniques on specific hemispatial neglect tests and activities of daily living in chronic hemispatial neglect patients . Methods : Ten right-h and ed patients with hemispatial neglect caused by right hemisphere ischemic strokes were r and omly allocated to 1 of 2 study groups : visual scanning ( n = 5 ) , mental practice ( n = 5 ) . Five additional patients were included in a control group . Three evaluations for hemispatial neglect and the FIM were carried out in the intervention groups : pretreatment , at the end of the intervention period , and 3 months after that intervention period . Control patients were evaluated twice within a 2-month interval . Results : There was a significant difference among the 3 groups in Behavioral Inattention Test ( BIT ) score changes ( P = .047 ) and in FIM self-care item score changes ( P = .035 ) , the visual scanning protocol being responsible for these differences both in BIT ( P = .008 ) and in FIM self-care item scores ( P = .016 ) . The positive functional effects of visual scanning were partially retained at the end of the follow-up period . Conclusions : Visual scanning should probably be considered preferable to mental practice protocol s in the treatment of hemispatial neglect patients Optokinetic stimulation ( OKS ) modulates many facets of the neglect syndrome . This sensory stimulation technique is known to activate multiple brain regions ( temporo-parietal cortex , basal ganglia , brain stem , cerebellum ) some of which are involved in auditory and visual space coding . Here , we evaluated whether OKS modulates auditory neglect transiently and induces a sustained effect ( Study 1 ) , and whether repetitive OKS permanently recovers auditory neglect ( Study 2 ) . In Study 1 , 20 patients with visuospatial neglect and auditory neglect in an auditory midline task following rightsided stroke were r and omly allocated to an experimental and a control group matched for neglect severity and socio-demographic factors . Both groups showed a stable , pathological shift of their auditory subjective median plane ( ASMP ) in front space to the right side . During leftward OKS the experimental group showed a complete normalization of the shift of the ASMP , which endured until 30 min poststimulation , and returned almost to baseline values 24h after OKS . In contrast , the control group who viewed the identical but static dot pattern , showed neither change in their ASMP during this condition , nor any significant change at 30 min or 24h poststimulation . In Study 2 , we show in two sample s of neglect patients ( N = 3 each ) that repetitive leftward OKS with smooth pursuit eye movements as a therapy induces lasting improvements in auditory ( the ASMP ) and visual neglect while visual scanning therapy yielded no measurable effects on auditory and significantly smaller effects on visual neglect . In conclusion , the experiments show that a single session of OKS induces rapid though transient recovery from auditory neglect including a sustained effect after termination of stimulation , while repetitive OKS therapy yields enduring and multimodal recovery from auditory and visual neglect . OKS therapy with pursuit eye movements therefore represents a multimodally effective and easily applicable technique for the treatment of auditory and visual neglect OBJECTIVE To propose a tool to assist trialists in making design decisions that are consistent with their trial 's stated purpose . STUDY DESIGN AND SETTING R and omized trials have been broadly categorized as either having a pragmatic or explanatory attitude . Pragmatic trials seek to answer the question , " Does this intervention work under usual conditions ? , " whereas explanatory trials are focused on the question , " Can this intervention work under ideal conditions ? " Design decisions make a trial more ( or less ) pragmatic or explanatory , but no tool currently exists to help research ers make the best decisions possible in accordance with their trial 's primary goal . During the course of two international meetings , participants with experience in clinical care , research commissioning , health care financing , trial methodology , and reporting defined and refined aspects of trial design that distinguish pragmatic attitudes from explanatory . RESULTS We have developed a tool ( called PRECIS ) with 10 key domains and which identifies criteria to help research ers determine how pragmatic or explanatory their trial is . The assessment is summarized graphically . CONCLUSION We believe that PRECIS is a useful first step toward a tool that can help trialists to ensure that their design decisions are consistent with the stated purpose of the trial PURPOSE At present , prism adaptation is probably the most promising rehabilitation procedure for hemi-neglect . However , r and omised controlled trials are lacking and no data are available on the effectiveness of prism adaptation in the treatment of acute neglect . METHODS We followed sixteen neglect patients using a r and omised controlled design in which six patients received four-day-in-a-row placebo treatment ( CG ) and ten patients received four-day-in-a row experimental treatment with 10 degrees rightward deviating prisms ( EG ) during their stay on the stroke unit . We examined whether patients in the EG improved faster than the CG by administering three neglect tasks ( Schenkenberg Line Bisection , Letter Cancellation , Gainotti Scene Copying ) immediately before and after each treatment . Second , we examined whether patients in the EG demonstrated a better long-term outcome at one month post-treatment ( Behavioural Inattention Test ) . RESULTS Patients in the EG improved faster on spatial tasks ( line bisection , cancellation ) than the CG but not on visuo-construction . Patients in the EG showed no differences with the CG in neglect outcome at one month post-treatment . CONCLUSIONS Four consecutive prism sessions produced beneficial effects in patients with acute neglect . However , prism effects were either short-term , or placebo treatment with repeated pointing and /or repeated neglect testing was more helpful than we anticipated . Our results emphasize the importance of a placebo condition and a follow-up in rehabilitation studies Background : Previous studies have demonstrated the effectiveness of paging systems in compensating for everyday memory and planning problems after brain injury , including in individuals with traumatic brain injury ( TBI ) . Methods : Here , in addition to further analyses of the TBI data from a previous r and omised control crossover trial , results are reported from a sub-group of 36 participants with brain injury from cerebrovascular accident ( CVA ) . Results : Results indicate that , as with the TBI group , the pager was effective . However , the pattern of results following cessation of treatment differed . At a group level , TBI participants demonstrated maintenance of pager-related benefits , whereas CVA participants ’ performance returned to baseline levels . Comparisons of demographic and neuropsychological characteristics of the groups showed that the CVA group was older , had a shorter interval post-injury , and had poorer executive function than the TBI group . Furthermore , within the TBI group , maintenance was associated with executive functioning , such that executive dysfunction impeded maintenance . This correlation remained after controlling for demographic differences between groups . Conclusions : Together , these findings suggest that executive dysfunction may affect treatment — for example , whether or not temporary use of the pager is sufficient to establish a subsequently self-sustaining routine Little is known about the pattern of subacute cognitive domain impairments after ischaemic stroke , nor the temporal evolution of such impairments . Our objective was to investigate the pattern of cognitive impairment in different neuropsychological domains up to a year after ischaemic stroke . We included prospect ively collected data from an observational data base of stroke patients at the National Hospital for Neurology and Neurosurgery , Queen Square , London , UK . Patients were categorised into temporal groups according to the time between the index stroke and neuropsychological profiling . The prevalence of impairment in different cognitive domains was then compared between these categories . The final cohort consisted of 209 patients . Frontal executive function , perceptual and nominal skills all showed a strong trend , with levels of impairment of approximately 30 % at < 1 month and less than half this at > 3 months ( p < 0.05 ) . Speed and attention was the most impaired domain , but had the greatest trend for decreasing impairment , from 72.4 % acutely to 37.9 % after 3 months ( p < 0.01 ) . By contrast , we found that impairment in visual and verbal memory showed no statistically significant change over time . Our results suggest a domain-specific improvement in cognition after ischaemic stroke . Early assessment s may overestimate longer term cognitive deficits , particularly in speed and attention and perceptual functions . The domain-specific improvement patterns may help to inform long-term rehabilitation plans , which should not be based solely on cognitive assessment s undertaken within the first month after stroke UNLABELLED Winkens I , Van Heugten CM , Wade DT , Habets EJ , Fasotti L. Efficacy of Time Pressure Management in stroke patients with slowed information processing : a r and omized controlled trial . OBJECTIVE To examine the effects of a Time Pressure Management ( TPM ) strategy taught to stroke patients with mental slowness , compared with the effects of care as usual . DESIGN R and omized controlled trial with outcome assessment s conducted at baseline , at the end of treatment ( at 5 - 10wk ) , and at 3 months . SETTING Eight Dutch rehabilitation centers . PARTICIPANTS Stroke patients ( N=37 ; mean age + /- SD , 51.5+/-9.7y ) in rehabilitation programs who had a mean Barthel score + /- SD at baseline of 19.6+/-1.1 . INTERVENTION Ten hours of treatment teaching patients a TPM strategy to compensate for mental slowness in real-life tasks . MAIN OUTCOME MEASURES Mental Slowness Observation Test and Mental Slowness Question naire . RESULTS Patients were r and omly assigned to the experimental treatment ( n=20 ) and to care as usual ( n=17 ) . After 10 hours of treatment , both groups showed a significant decline in number of complaints on the Mental Slowness Question naire . This decline was still present at 3 months . At 3 months , the Mental Slowness Observation Test revealed significantly higher increases in speed of performance of the TPM group in comparison with the care-as-usual group ( t=-2.7 , P=.01 ) . CONCLUSIONS Although the TPM group and the care-as-usual group both showed fewer complaints after a 3-month follow-up period , only the TPM group showed improved speed of performance on everyday tasks . Use of TPM treatment therefore is recommended when treating stroke patients with mental slowness BACKGROUND AND PURPOSE The poor outcome observed in stroke patients with visual neglect may be due to greater stroke severity or nonspecialist management . METHODS The effects of visual neglect were studied prospect ively in 150 consecutive stroke patients with comparable stroke pathology and motor severity managed on a stroke unit . A r and omized study was subsequently undertaken in 50 stroke patients with visual neglect to evaluate the effectiveness of spatial cueing during motor activity on functional outcome and re source use in these patients . RESULTS Visual neglect was present in 47 ( 32 % ) of a selected group of 146 patients ( mean age , 77.0 + /- 8.2 years ; 42 % men ) with moderate stroke severity . There were no differences in demography , prestroke function , or motor power in the arm ( 2.6 + /- 1.7 versus 2.3 + /- 2.1 ) or the leg ( 3.2 + /- 1.4 versus 3.0 + /- 1.6 ) on the affected side compared with 99 patients with no visual neglect . Although patients with visual neglect had lower median initial ( 4 versus 5 , P < .01 ) and discharge ( 14 versus 16 , P < .01 ) Barthel Index scores , equal proportions of patients were discharged home ( 60 % versus 65 % ) or to institutions ( 34 % versus 33 % ) in both groups . The duration s of hospitalization ( 64 versus 36 days , P < .001 ) and therapy input ( 47.7 versus 27.8 hours ; P < .01 ) , however , were significantly greater in patients with visual neglect . The r and omized controlled study showed a trend toward higher Barthel scores at 12 weeks ( 14 versus 12.5 , P = NS ) and significant reduction in median length of hospital stay ( 42 versus 66 days ) in patients receiving spatiomotor cueing and early emphasis on functional rehabilitation . CONCLUSIONS Patients with visual neglect managed on a stroke unit have similar destination of discharge despite lower Barthel Index scores compared with patients of equal stroke severity who do not have this deficit . Spatiomotor cueing and early emphasis on function can improve outcome and reduce re source use in these patients OBJECTIVE To compare the effectiveness of a visual attention retraining program using the Useful Field of View ( UFOV ) with a traditional visuoperception treatment program on the driving performance of clients with stroke . DESIGN R and omized controlled trial . SETTING Rehabilitation hospital located in Quebec , Canada . PARTICIPANTS Ninety-seven individuals referred for driving evaluation after a stroke . INTERVENTIONS Participants were r and omized to receive 20 sessions of either UFOV training of visual processing speed , divided attention , and selective attention or traditional computerized visuoperception retraining . MAIN OUTCOME MEASURES Subjects were evaluated with an on-road driving evaluation , visuoperception tests , and the Test of Everyday Attention . An occupational therapist unaware of group assignment conducted all evaluations . RESULTS Eighty-four participants completed the outcome evaluation . There were no significant differences between groups on any of the outcome measures . There was , however , almost a 2-fold increase ( 52.4 % vs 28.6 % ) in the rate of success on the on-road driving evaluation after UFOV training for subjects with right-sided lesions . CONCLUSIONS Rehabilitation that targets visual attention skills was not significantly more beneficial than traditional perceptual training in improving the outcome of an on-road driving evaluation . However , results suggest a potential improvement for subjects with right-sided lesions , indicating that training must target specific skills A group of head injury and stroke patients with impairment of visual perception were r and omly allocated to receive either perceptual retraining or conventional occupational therapy . No significant differences were found between the groups , either before or after 4 weeks of treatment , on measures of visual perception or on activities of daily living scale OBJECTIVE Assessment of a new rehabilitation method for unilateral neglect syndrome ( UNS ) , using a specific device ( Bon Saint Come 's device ) that associates exploratory reconditioning with voluntary trunk rotation . DESIGN Study 1 , r and omized control trial during 2 months ; study 2 , nonr and omized control trial during 2 months . SETTING Neurorehabilitation units in private and public center . PATIENTS In study 1 , 22 consecutive patients with UNS result ing from recent stroke ( < 3 months ) were r and omly assigned to an Experimental Group ( 11 patients ) or to a Control Group ( 11 patients ) . The 2 groups were very similar in terms of general and neurological data . In study 2 , 5 consecutive patients with chronic UNS result ing from an old stroke ( > 6 months ) showing the same characteristics were included . INTERVENTION In study 1 , patients in Group E followed the experimental program 1 hour a day for 1 month ( 20 hours ) and Group C followed usual neurorehabilitation during the same time . In study 2 , every patient followed the experimental program 1 hour a day for 1 month ( 20 hours ) . MAIN OUTCOME MEASURES Assessment in both studies was done at day 0 , day 30 , and day 60 using a battery of UNS tests ( Albert , Scheckenberg , bell ) and an activities of daily living ( ADL ) test ( the Functional Independence Measure [ FIM ] ) . Mean scores of each test were compared between the 2 groups with the Wilcoxon nonparametric test . RESULTS In study 1 all UNS test results and the FIM improved significantly more in Group E than in Group C. In Group E , UNS disappeared in 5 patients and improved in 6 . In Group C , UNS disappeared in 1 patient , improved in 4 , and was unchanged in 6 . In Study 2 , UNS remitted in 2 patients , improved in 2 patients , and was unchanged in 1 . CONCLUSION The Bon Saint Come method seems to significantly improve recent and chronic UNS , as well as ADL function . These encouraging results could have result ed from a synergistic effect of spatial reconditioning and voluntary trunk rotation . It must be assessed by a new study with more patients General insight into the frequency and gravity of cognitive dysfunctions following stroke and its influencing factors is still lacking . With an extensive neuropsychological battery 229 patients who had suffered a stroke were assessed . More than 70 % of the patients showed a marked slowness of information processing , whereas at least 40 % of all patients had difficulty with memory , visuospatial and constructive tasks , language skills , and arithmetic . A significant effect was found for side and type of stroke , gender , and the presence of aphasia . No significant effect was found for cortical versus subcortical lesions , having one versus multiple strokes , having lowered consciousness on admission , the presence of risk factors , a paresis of the h and , or the interval between the stroke and the neuropsychological assessment Objective : To compare the effectiveness of the transfer of training and functional approaches in improving perceptual and functional abilities after stroke . Design : Patients identified as having perceptual problems were r and omly allocated to either the transfer of training approach or the functional approach for perceptual treatment . On completion of six weeks of treatment , each patient was reassessed for perceptual and functional abilities . Subjects and setting : Eighty in patients on the Nottingham Stroke Unit . Interventions y : Perceptual treatment was given for 2.5 hours per week for six weeks . Main outcome measures : Rivermead Perceptual Assessment Battery , Barthel ADL Index and Edmans ADL index . Results : There was no significant difference between the treatment groups on patient characteristics or impairments . The results also showed no significant difference between the treatment groups before and after treatment on perceptual ability total scores , individual perceptual subtest scores , or functional ability total scores ( Mann – Whitney U 642.5–798.0 , p > 0.05 ) . Wilcoxon matched pairs signed ranks tests showed a significant improvement in both groups after treatment on perceptual and functional abilities ( perceptual z = 6.02 , p < 0.001 , functional z = 6.72 , p < 0.001 ) . Conclusions : These results indicated that the improvement in perceptual abilities was equivalent using either of the two approaches . This could be due to spontaneous recovery or the effects of the Stroke Unit We r and omly assigned 39 patients with stroke and homonymous hemianopia or unilateral visual neglect to treatment with 15-diopter plastic press-on Fresnel prisms ( n = 18 ) or to serve as controls ( n = 21 ) . Baseline evaluations of visual perception and activities-of-daily-living ( ADL ) function were similar for both groups . After 4 weeks , the prism-treated group performed significantly better than controls on the following : ( 1 ) Motor Free Visual Perception Test ; ( 2 ) Line Bisection Task ; ( 3 ) Line Cancellation Task ; ( 4 ) Harrington Flocks Visual Field Screener ; and ( 5 ) Tangent Screen Examination . There was no significant difference in Barthel ADL assessment at 4 weeks . Thus , treatment with 15-diopter Fresnel prisms improves visual perception test scores but not ADL function in stroke patients with homonymous hemianopia or unilateral visual neglect OBJECTIVE To examine the effects of a compensatory intervention versus a remedial intervention for deficits in visual processing of adults with acquired brain injuries ( ABI ) . SETTING A cognitive rehabilitation program at a large comprehensive rehabilitation hospital in the New York City metropolitan area . PATIENTS Thirty adults with ABI were matched according to severity of injury , gender , age , and time post-injury , and r and omly assigned to the remedial or compensatory group . INTERVENTIONS The remedial intervention consisted of four 45-minute sessions ( once weekly ) of participation in computer tasks without instruction in compensatory strategies . The compensatory intervention consisted of four 45-minute sessions of instruction in the use of three internal compensatory strategies , including verbalization , chunking , and pacing . MAIN OUTCOME MEASURES Pretest/posttest measures included three functional computer tasks . Weekly measures included a computerized version of the Paced Auditory Serial Addition Task ( PASAT ) and two computerized matching tasks . RESULTS Both groups exhibited statistically significant improvement of comparable degree on posttests and weekly measures . Further analysis revealed that 80 % of both groups used compensatory strategies , regardless of intervention method . Those who used strategies demonstrated better performance than those who did not . CONCLUSION The ability to use internal compensatory strategies may be a significant confound in research examining the effects of the various cognitive rehabilitation intervention methods Microcomputers are widely used in cognitive rehabilitation of brain damage . Unilateral neglect is commonly a target of cognitive rehabilitation , both computer-based and non-computer-based . This study reports the results of a r and omized controlled trial of computer-based rehabilitation with blind follow-up for six months . Thirty-six patients with unilateral neglect , as defined by the behavioral subtests of the Behavioural Inattention Test , were r and omized into two groups . One group of 20 subjects received a mean of 15.5 ( SD = 1.8 ) hours of computerized scanning and attentional training ; the second group of 16 subjects received a mean of 11.4 ( SD = 5.2 ) hours of recreational computing ( selected to minimize scanning and timed attentional tasks ) . Blind follow-up at the end of training and six months after revealed no statistically or clinical ly significant results between groups . These findings argue against routine clinical use of this type of computerized training until further studies establish what type , frequency , and duration of training produces clinical ly significant changes in unilateral visual neglect if , indeed , computerized training can have an effect with this type of disorder PURPOSE Hemispatial neglect , a failure to orient to the contralateral side of the lesion , is a disabling disorder after stroke . Previously arm activation combined with visual training or visual scanning training were found effective in rehabilitation of hemispatial neglect . The aim of this study was to determine whether left arm activation alone could be sufficient to produce a long lasting amelioration of neglect comparable to the effect obtained with traditional visual scanning training . METHODS Twelve neglect patients less than six months from stroke were r and omized either into 20 - 30 hours of left arm activation training or 10 hours of traditional visual scanning training as a part of a comprehensive rehabilitation program . All patients received 48~hours of therapy during the 3-week rehabilitation . RESULTS Visual neglect of the arm activation group recovered significantly in the conventional subtests of the Behavioural Inattention Test both post-rehabilitation and at 6-months follow-up . The improvement of the visual scanning training group was almost significant at the end of the rehabilitation and significant by the follow-up . The behavioural neglect observed in the Catherine Bergego Scale was alleviated nearly significantly at the post-rehabilitation in both groups . The effect was maintained in the arm activation group at 6-months . CONCLUSION The arm activation training appears beneficial even without supplementary visual neglect rehabilitation , although the traditional visual scanning training may have further effects in cognition This study presents a method for analyzing and remediating the visual perceptual deficits often found in persons with acquired right brain injury due to stroke . A total of 57 patients were r and omly assigned to experimental ( N=25 ) or control ( N=32 ) groups . All patients were administered the same test battery prior to assignment . Experimentals received the specific training program and the controls received st and ard rehabilitation . Both groups were retested after a period of one month . Analysis revealed the superior performance of the experimental group . The results suggest that the academic disorders found in right brain damage can be treated as secondary to a primary disturbance in visual scanning behavior |
12,532 | 17,059,433 | Results are generally the same in the meta- analysis and in the comparative trials , with some exceptions . | null | null |
12,533 | 29,977,532 | Conclusions The prevalence of cataract and cataract blindness in China was unmasked . | Background Cataract is the second leading cause of visual impairment and the first of blindness globally .
However , for the most populous country , China , much remains to be understood about the scale of cataract and cataract blindness .
We aim ed to investigate the prevalence of cataract and cataract blindness in China at both the national and subnational levels , with projections till 2050 .
In the coming decades , cataract and cataract blindness will continue to be a leading public-health issue in China due to the ageing population . | PURPOSE To assess blindness prevalence and that caused specifically by cataract in rural southern China . DESIGN Population -based , cross-sectional study . PARTICIPANTS A total of 5342 persons older than 50 years of age . METHODS Visual acuity and eye examinations were performed in the summer of 1997 in a r and om sample of villages in Doumen County . Differences in blindness prevalence associated with age , gender , and education were explored using logistic regression . The survey was preceded by a pilot study in which operational methods were refined and quality assurance measures were performed . MAIN OUTCOME MEASURES Distance visual acuity and lens status . RESULTS Bilateral blindness ( presenting visual acuity < 0.10 ) was found in 4.37 % ( 95 % confidence interval , 3.67%-5.06 % ) . Blindness was associated with increasing age ( P < 0.001 ) and with the lack of education ( P < 0.01 ) . Cataract was the principal cause of blindness in at least one eye in 61.5 % of blind people , with refractive error responsible for another 10 % . An estimated 40 % of the cataract blind were operated on ; surgical coverage was lowest among the elderly , women , and those without schooling , although not at statistically significant levels . CONCLUSIONS Despite the increased attention given to eye care in Doumen County , blindness remains a major public health problem . Cataract surgery is reaching fewer than half of those who could benefit from it OBJECTIVE To perform a reference case cost-utility analysis of second-eye cataract surgery by using the current literature on cataract outcomes and complications . DESIGN Computer-based econometric modeling . METHODS Visual acuity data of patients treated and observed over a 4-month postoperative period were obtained from the U.S. National Cataract Patient Outcomes Research Team report . The results from this prospect i ve study were combined with those of other studies that investigated the complication rates of cataract surgery to complete the cohort of patients and outcomes . These synthesized data were incorporated with time trade-off utility values , which accounted for prior successful cataract surgery in the fellow eye . Cost-utility determinations were made with decision analysis , and present value modeling was used to account for the time value of money and health state consequences . MAIN OUTCOME MEASURES The number of quality -adjusted life-years ( QALYs ) gained was calculated for the study group undergoing second-eye cataract surgery , assuming that the postoperative vision in the second eye was equivalent to the vision in the first eye after surgery ( 20/27 ) . This was divided into the cost of the procedure to find the number of year 2001 nominal U.S. dollars spent per QALY gained . RESULTS Second-eye cataract surgery , as compared with unilateral pseudophakia , result ed in a mean gain of 1.31 undiscounted QALYs per patient treated . A 3 % annual discount rate , dependent on the duration of benefit , was used , yielding 0.92 discounted QALYs gained over a 12-year life expectancy . The mean discounted cost of treatment for each patient totaled 2509 US dollars . The cost divided by the QALYs gained ( benefit ) result ed in 2727 US dollars per QALY gained for this procedure . Sensitivity analysis varying costs and utility values revealed a range from 2045 US dollars to 3649 US dollars per QALY gained . CONCLUSIONS Second-eye cataract surgery is an extremely cost-effective procedure when compared with other interventions across medical specialties . The cost-effectiveness of second-eye surgery diminishes only slightly from the 2023 US dollars per QALY gained from first-eye cataract surgery . This suggests that patients with good vision in one eye and visual loss from cataract in the fellow eye derive substantial benefit from cataract extraction R and om sample s of people aged 40 years and over were drawn from lists of patients registered with two neighbouring inner-city general practice s : one predominantly with Asian patients and the other predominantly with European patients . The people selected were invited to attend specially arranged eye clinics for examination by an ophthalmologist and an optician . We examined 377 people and found that , compared to people of European descent , Asians had a significantly higher prevalence of age-related cataract : 30 % compared to 3 % in people aged under 60 years and 78 % compared to 54 % in those aged 60 years and over . The age of onset of cataract seems to be earlier in Asians . After adjustment for age , there were no statistically significant ethnic differences in the prevalences of open-angle glaucoma , macular degeneration or diabetic retinopathy AIMS A population based cross sectional survey was conducted to determine the magnitude of cataract blindness and the barriers to uptake of cataract services in a rural community of northern Nigeria . METHODS 1461 people out of 1924 registered eligible people were examined . The study population was chosen by two stage cluster r and om sampling . In the first sampling stage 15 villages were r and omly chosen while in the final stage 170 people who were 40 years and over were selected in each village . Each selected person had visual acuity recorded for both eyes . Those with vision of less than 3/60 in the better eye were assessed for cataract . People with cataract were asked why they had not sought medical attention . RESULTS A blindness prevalence of 8.2 % ( 95 % CI 5.8%–10.5 % ) was found among the sample d population . Cataract was responsible for 44.2 % of the blindness . Thus , a cataract blindness prevalence of 3.6 % was found . The cataract surgical coverage ( people ) was 4.0 % and the couching coverage ( people ) was 18 % . The main barrier to seeking cataract surgery was cost of the service ( 61 % ) . CONCLUSION Some regions of the world still have high burden of cataract blindness that needs attention . Such areas need an effective free cataract outreach programme OBJECTIVE To estimate the prevalence of cataract , the rate of cataract surgical coverage rate , and the rate of cataract-blindness social burden among older adults aged 50 years or above in Qidong City of Jiangsu Province , China , in 2006 . METHODS Cluster sampling was used in r and omly selected 5662 individuals aged 50 years or above in 16 clusters in Qidong City . 5141 individuals received visual acuity and eye examination from September to December 2006 . Lens and cataract operation status were evaluated by slit lamp . Multiple logistic regression analysis was employed to analyzed the prevalence of cataract , cataract surgical coverage rate , cataract blindness social burden rate and outcomes of surgery among different ages , sex and educational background . RESULTS In 5141 individuals , 1098 cases of cataract were found , the prevalence of cataract was 21.35 % among adults aged 50 or above . The prevalence of cataract was higher in the aged , female , illiterate persons ( P < 0.01 ) . In 89 eyes with cataract surgery , 25.84 % and 42.70 % of eyes were performed by the modern extra-capsular surgery and Phacoemulsification respectively . The rate of intraocular lens implantation was 69 . 66 % . Post-operative presenting and best corrected visual acuity more than 0.7 was 24.70 % and 48.31 % of operated eyes respectively . The main causes of the post-operated eyes with worse visual acuity were retinal disorders post-capsular opacity and glaucoma . The cataract surgical coverage rate was 37.96 % , and the cataract blindness social burden rate was 2.10 % . The cataract blindness social burden rate was higher in the aged persons ( P < 0.01 ) . CONCLUSIONS Cataract is the most common and important eye disease that may lead into blindness and severe visual impairment among older adults aged 50 years or above . The cataract surgical coverage rate is not so high in Qidong City , and even lower in the aged persons . The first important task in blindness prevention still is the elimination of cataract blindness . The visual outcomes of the cataract surgery should be further improved in the future Purpose To describe the prevalence of cataract in older people in 2 areas of north and south India . Design Population -based , cross-sectional study . Participants R and omly sample d villages were enumerated to identify people aged ≥60 years . Of 7518 enumerated people , 78 % participated in a hospital-based ophthalmic examination . Methods The examination included visual acuity measurement , dilatation , and anterior and posterior segment examination . Digital images of the lens were taken and grade d by type and severity of opacity using the Lens Opacity Classification System III ( LOCS III ) . Main Outcome Measures Age- and gender-st and ardized prevalence of cataract and 95 % confidence intervals ( CIs ) . We defined type of cataract based on the LOCS III grade in the worse eye of : ≥4 for nuclear cataract , ≥3 for cortical cataract , and ≥2 for posterior subcapsular cataract ( PSC ) . Any unoperated cataract was based on these criteria or ungradable dense opacities . Any cataract was defined as any unoperated or operated cataract . Results The prevalence of unoperated cataract in people aged ≥60 was 58 % in north India ( 95 % CI , 56–60 ) and 53 % ( 95 % CI , 51–55 ) in south India ( P = 0.01 ) . Nuclear cataract was the most common type : 48 % ( 95 % CI , 46–50 ) in north India and 38 % ( 95 % CI , 37–40 ) in south India ( P<0.0001 ) ; corresponding figures for PSC were 21 % ( 95 % CI , 20–23 ) and 17 % ( 95 % CI , 16–19 ; P = 0.003 ) , respectively , and for cortical cataract 7.6 % ( 95 % CI , 7–9 ) and 10.2 % ( 95 % CI , 9–11 ; P<0.004 ) . Bilateral aphakia/pseudophakia was slightly higher in the south ( 15.5 % ) than in the north ( 13.2 % ; P<0.03 ) . The prevalence of any cataracts was similar in north ( 73.8 % ) and south India ( 71.8 % ) . The prevalence of unoperated cataract increased with age and was higher in women than men ( odds ratio [ OR ] , 1.8 ) . Aphakia/pseudophakia was also more common in women , either unilateral ( OR , 1.2 ; P<0.02 ) or bilateral ( OR , 1.3 ; P<0.002 ) . Conclusions We found high rates of unoperated cataract in older people in north and south India . Posterior subcapsular cataract was more common than in western studies . Women had higher rates of cataract , which was not explained by differential access to surgery . Financial Disclosure(s ) The authors have no proprietary or commercial interest in any of the material s discussed in this article Purpose To investigate the prevalence and visual acuity ( VA ) outcomes of cataract surgery in adults of the Bai Nationality population s in rural China . Methods We conducted a population -based cross-sectional survey ( from r and omly selected block groups ) of Chinese Bai Nationality aged ≥50 years in southwestern China . Presenting visual acuity ( PVA ) , best corrected visual acuity ( BCVA ) were recorded and a detailed eye examination was carried out . For all aphakic and pseudophakic subjects identified , information on the date , setting , type , and complications of cataract surgery were recorded . In eyes with VA < 20/63 , the principal cause of visual impairment was identified . Results Of 2133 ( 77.8 % of 2742 ) subjects , 99 people ( 129 eyes ) had undergone cataract surgery . The prevalence of cataract surgery was 4.6 % . Surgical coverage among those with PVA < 20/200 in both eyes because of cataract was 52.8 % . Unoperated cataract was associated with older age . The main barrier to cataract surgery was lack of awareness and knowledge , cost , and fear . Among the 129 cataract-operated eyes , 22.5 % had PVA of ≥20/32 , 25.6 % had PVA of 20/40 to 20/63 , 23.3 % had PVA < 20/63 to 20/200 , and 28.7 % had PVA<20/200 . With BCVA , the percentages were 42.6 % , 23.3 % , 10.9 % , and 23.3 % , respectively . Aphakia ( odds ratio [ OR ] , 8.49 ; P<0.001 ) and no education ( OR , 10.18 ; P = 0.001 ) or less education ( OR , 6.49 ; P = 0.014 ) were significantly associated with postoperative visual impairment defined by PVA , while aphakia ( OR , 8.49 ; P<0.001 ) and female gender ( OR , 4.19 ; P = 0.004 ) were significantly associated with postoperative visual impairment by BCVA . The main causes of postoperative visual impairment were refractive error , retinal disorders and glaucoma . Conclusions Half of those with bilateral visual impairment or blindness because of cataract remain in need of cataract surgery in Bai population . Surgical uptake and visual outcomes should be further improved in the future Aim : To determine utilisation of eye care services in a rural population of southern India aged 40 years or older . Methods : 5150 subjects aged 40 years and older selected through a r and om cluster sampling technique from three districts in southern India underwent detailed ocular examinations for vision impairment , blindness , and ocular morbidity . Information regarding previous use of eye care services was collected from this population through a question naire administered by trained social workers before ocular examinations . Results : 3476 ( 72.7 % ) of 5150 subjects examined required eye care examinations . 1827 ( 35.5 % ) people gave a history of previous eye examinations , primarily from a general hospital ( n = 1073 , 58.7 % ) . Increasing age and education were associated with increased utilisation of eye care services . Among the 3323 people who had never sought eye care , 912 ( 27.4 % ) had felt the need to have an eye examination but did not do so . Only one third of individuals with vision impairment , cataracts , refractive errors , and glaucoma had previously utilised services . Conclusions : A large proportion of people in a rural population of southern India who require eye care are currently not utilising existing eye care services . Improved strategies to improve uptake of services is required to reduce the huge burden of vision impairment in India PURPOSE To describe the relationship of visual acuity impairment and eye disease on vision-related quality of life , as measured by the 25-item National Eye Institute Visual Function Question naire ( NEI-VFQ-25 ) , in a cross-sectional , population -based study of older Hispanic persons living in Arizona . METHODS A r and om sample of block groups with Hispanic residents in Nogales and Tucson , Arizona , were selected for study . Participants were interviewed at home with a question naire that included the NEI-VFQ-25 , an instrument measuring vision-related quality of life . Acuity was obtained with Early Treatment Diabetic Retinopathy Study ( ETDRS ) charts and st and ard protocol . Cataract was determined by clinical examination , diabetic retinopathy was diagnosed on stereo fundus photographs , and glaucoma was diagnosed on the basis of clinical examination and visual field results . Analyses were done to determine the degree of association between subscale scores and acuity in the better-seeing eye , monocular visual impairment , and specific eye diseases , with adjustment for acuity . RESULTS Of the 4774 participants in the study , 99.7 % had completed question naires that were not completed by proxy . Participants with visual impairment had associated decrements in scores on all subscales , with a decrease in presenting acuity associated with a worse score ( P < 0.05 ) , after adjustment for demographic variables . Monocular impairment was also associated with lower scores in several subscales . In those with cataract , low acuity explained most of the low scores , but those with glaucoma or diabetic retinopathy had low scores independent of acuity . CONCLUSIONS In this study of Mexican-American persons aged 40 or more , monocular impairment and better-eye acuity was associated with a decrease in most domains representing quality of life . Subjects with uncorrected refractive error , cataract , diabetic retinopathy , and glaucoma had associated decrements in quality of life , many not explained by loss of acuity . Further work on the specific measures of vision associated with reported decreases in quality of life , such as visual field or contrast sensitivity , is warranted PURPOSE The purpose of this study was to perform a reference case , cost-utility analysis of initial cataract surgery using the current literature on cataract outcomes and complications . DESIGN Computer-based econometric modeling . METHODS Visual acuity data of patients treated and observed over a 4-month postoperative period was obtained from the US National Cataract Patient Outcomes Research Team ( PORT ) . The results from this prospect i ve study were combined with other studies that investigated the complication rates of cataract surgery to complete the cohort of patients and outcomes . These synthesized data were incorporated with time-tradeoff utility values , decision analysis , and econometric modeling to account for the time value of money . MAIN OUTCOME MEASURES The number of quality -adjusted life-years ( QALYs ) gained was calculated for the study group undergoing cataract extraction in the first eye when the vision was the same in both eyes . This was divided into the cost of the procedure to find the year 2000 nominal US dollars spent per quality -adjusted life-year ( $ /QALY ) gained . RESULTS Initial cataract surgery , compared with observation , result ed in a mean gain of 1.776 QALYs per patient treated . A 3 % annual discount rate was used to account for the benefit over time , yielding 1.25 QALYs gained . The mean cost of treatment ( also discounted at a 3 % annual rate ) of each patient totaled 2525 US dollars . The cost divided by the discounted benefit result ed in $ 2020/QALY gained for this procedure . CONCLUSIONS Initial cataract surgery seems to be highly cost-effective compared with procedures across multiple medical specialties . This information , incorporating patient preferences into evidence d-based medicine , will play an increasingly important role in the evaluation of health care in the future Background / aim : Himalaya Eye Hospital ( HEH ) , established in 1993 , is rendering eye care services in the G and aki and Dhaulagiri zones . The hospital has extensive community outreach activities along with services for out patients , emergencies , and subspecialties such as vitreoretinal , paediatric , and low vision . The operation theatre is well equipped to match the surgical needs including phaco surgery for cataract . The hospital has performed more than 14 000 cataract surgeries and 250 000 treatment services during this period . The aim of this study was to estimate the prevalence of blindness , visual impairment , and cataract surgical coverage among the older adult population of three districts of G and aki Zone , where 80 % of the hospital ’s service recipients reside . Methods : People aged 45 years and older were enrolled in the study using a stratified cluster design . Subjects in 25 r and omly selected clusters from the listed 806 were recruited through door to door visits . Each recruited subject had visual acuity ( VA ) and clinical examination conducted by an ophthalmologist . The survey was preceded by pre-pilot and pilot studies to refine the operational method . To assess quality assurance the interobserver variation in VA measurement was also carried out in five different clusters . Results : Out of 5863 selected subjects 85.3 % were examined . Blindness defined as presenting VA < 6/60 in both eyes was found in 2.6 % ( 95 % confidence interval ( CI ) : 2.2 to 3.9 ) , whereas 16.8 % individuals examined had vision < 6/19 in one or both eyes . Cataract was the principal cause of blindness in 60.5 % , and refractive error was the dominant cause of vision impairment ( < 6/19 ) 83.3 % . Cataract surgical coverage was 59.5 % among the cataract blind and associated with younger age , literacy , and male sex . Conclusion : The finding suggests a positive impact of the HEH programme on the prevalence of blindness and cataract surgical services in the survey area . Strategies to further improve access and utilisation of facilities and increase cataract surgical coverage need to be developed PURPOSE To describe the prevalence and risk factors for cataract in an Australian population aged 40 years and older . METHODS Participants were recruited by a household census and stratified , r and om cluster sampling to represent residents of Victoria , Australia , aged 40 years and older . The following information was collected : initial visual acuity and best-corrected visual acuity , demographic details , health history , dietary intake of antioxidants , lifetime ocular ultraviolet B exposure , and clinical eye examination , including lens photography . Cortical opacities were measured in sixteenths . Cortical cataract was defined as opacity greater than or equal to 4/16 of pupil circumference . Nuclear opacities were grade d according to the Wilmer cataract grading scheme , and cataract was defined as greater than or equal to nuclear st and ard 2.0 of four st and ards . The height and width of any posterior subcapsular opacity was measured and recorded . Posterior subcapsular cataract was defined as posterior subcapsular opacity greater than or equal to 1 mm2 . The worse eye was selected for analysis . Backward stepwise logistic regression was used to quantify independent risk factors for cataract . RESULTS A total of 3,271 ( 83 % of eligible ) of the urban residents , 403 ( 90 % of eligible ) nursing home residents , and 1,473 ( 92 % of eligible ) rural residents participated . The urban residents ranged in age from 40 to 98 years ( mean , 59 years ) , and 1,511 ( 46 % ) were men . The nursing home residents ranged in age from 46 to 101 years ( mean , 82 years ) , and 85 ( 21 % ) were men . The rural residents ranged in age from 40 to 103 years ( mean , 60 years ) , and 701 ( 47.5 % ) were men . The overall weighted rate of cortical cataract was 11.3 % ( 95 % confidence limits , 9.68 % , 13.0 % ) excluding cataract surgery and 12.1 % ( 95 % confidence limits , 10.5 % , 13.8 % ) including cataract surgery . The risk factors for cortical cataract that remained in the multivariate logistic regression model were age , female gender , diabetes duration greater than 5 years , gout duration greater than 10 years , arthritis diagnosis , myopia , use of oral beta-blockers , and increased average annual ocular ultraviolet B exposure . Overall , 12.6 % ( 95 % confidence limits , 9.61 % , 15.7 % ) of Victorians aged 40 years and older had nuclear cataract including previous cataract surgery , and 11.6 % ( 95 % confidence limits , 8.61 % , 14.7 % ) had nuclear cataract excluding previous cataract surgery . In the urban and rural cohorts , age , female gender , rural residence , brown irides , diabetes diagnosed 5 or more years earlier , myopia , age-related maculopathy , having smoked for greater than 30 years , and an interaction between ocular ultraviolet B exposure and vitamin E were all risk factors for nuclear cataract . The rate of posterior subcapsular cataract excluding previous cataract surgery was 4.08 % ( 95 % confidence limits , 3.01 % , 5.14 % ) , whereas the overall rate of posterior subcapsular cataract including previous cataract surgery was 4.93 % ( 95 % confidence limits , 3.68 % , 6.17 % ) . The independent risk factors for posterior subcapsular cataract in the urban and rural cohorts that remained were age in years , rural location , use of thiazide diuretics , vitamin E intake , and myopia . CONCLUSIONS The expected increase in the prevalence of cataract with the aging of the population highlights the need to plan appropriate medical services and public health interventions for primary and secondary prevention . Many of the identified risk factors for cataract in the population have the potential for being modified through public health interventions Aims : To assess the prevalence of vision impairment , blindness , and cataract surgery and to evaluate visual acuity outcomes after cataract surgery in a south Indian population . Methods : Cluster sampling was used to r and omly select a cross sectional sample of people ≥50 years of age living in the Tirunelveli district of south India . Eligible subjects in 28 clusters were enumerated through a door to door household survey . Visual acuity measurements and ocular examinations were performed at a selected site within each of the clusters in early 2000 . The principal cause of visual impairment was identified for eyes with presenting visual acuity < 6/18 . Independent replicate testing for quality assurance monitoring was performed in subjects with reduced vision and in a sample of those with normal vision for six of the study clusters . Results : A total of 5795 people in 3986 households were enumerated and 5411 ( 93.37 % ) were examined . The prevalence of presenting and best corrected visual acuity ≥6/18 in both eyes was 59.4 % and 75.7 % , respectively . Presenting vision < 6/60 in both eyes ( the definition of blindness in India ) was found in 11.0 % , and in 4.6 % with best correction . Presenting blindness was associated with older age , female sex , and illiteracy . Cataract was the principal cause of blindness in at least one eye in 70.6 % of blind people . The prevalence of cataract surgery was 11.8%—with an estimated 56.5 % of the cataract blind already operated on . Surgical coverage was inversely associated with illiteracy and with female sex in rural areas . Within the cataract operated sample , 31.7 % had presenting visual acuity ≥6/18 in both eyes and 11.8 % were < 6/60 ; 40 % were bilaterally operated on , with 63 % pseudophakic . Presenting vision was < 6/60 in 40.7 % of aphakic eyes and in 5.1 % of pseudophakic eyes ; with best correction the percentages were 17.6 % and 3.7 % , respectively . Refractive error , including uncorrected aphakia , was the main cause of visual impairment in cataract operated eyes . Vision < 6/18 was associated with cataract surgery in government , as opposed to that in non-governmental/private facilities . Age , sex , literacy , and area of residence were not predictors of visual outcomes . Conclusion : Treatable blindness , particularly that associated with cataract and refractive error , remains a significant problem among older adults in south Indian population s , especially in females , the illiterate , and those living in rural areas . Further study is needed to better underst and why a significant proportion of the cataract blind are not taking advantage of free of charge eye care services offered by the Aravind Eye Hospital and others in the district . While continuing to increase cataract surgical volume to reduce blindness , emphasis must also be placed on improving postoperative visual acuity outcomes PURPOSE To describe the system for grading cataracts from photographs in the Age-Related Eye Disease Study ( AREDS ) . METHODS The system for grading cataracts in AREDS uses photographs taken in a st and ardized fashion with specially modified cameras at 11 clinical centers . The photographs are evaluated by grade rs for quality and cataract severity at a central reading center . The area of lens involvement is used to assess the severity of cortical and posterior subcapsular opacities . Optical density of nuclear opacity is grade d against a series of seven st and ard photographs . Contemporaneous variability in grading is evaluated periodically by having a second examiner re grade a subset of the photographs . Temporal variability is assessed by annually regrading a subset of photographs . RESULTS Photographs of 925 eyes , most with no or early lens opacities , were re grade d to assess inter grade r reliability . For cortical opacities , there was an absolute difference of 10 % or greater of area involved in 1.9 % of the replicate gradings . For posterior subcapsular opacities an absolute difference of 5 % of area involved was noted in 2.8 % of the re grade d photographs . For nuclear opacities , absolute differences of 1.5 or more steps were observed in 0.6 % of eyes . There was little evidence of temporal drift in grading any of the three types of opacity during four annual re grade s. CONCLUSIONS We have demonstrated a high degree of reliability in grading the severity of lens opacities in a large study cohort with mostly early lens changes , the type of cohort most likely to be entered in clinical trials involving cataract prevention . The Age-Related Eye Disease Study System for Classifying Cataracts From Photographs could be useful in studies where there is a need to st and ardize data collection over time and across different data collection sites . Limitations of the system include the cost of implementation and , currently , the limited amount of data on grading reproducibility for more advanced lens opacities OBJECTIVE To investigate possible risk factors for age-related nuclear and cortical cataracts in participants in the Age-Related Eye Disease Study ( AREDS ) . DESIGN Case-control study . PARTICIPANTS Of the 4757 persons enrolled in AREDS , 4477 age 60 to 80 years are included in the study . MAIN OUTCOME MEASURES Slit-lamp lens photographs were used to classify participants into one of three nuclear opacity groups ( moderate nuclear , mild nuclear , and controls ) , ignoring cortical opacities . Retroillumination lens photographs were used to classify participants into one of three cortical opacity groups ( moderate cortical , mild cortical , and controls ) , ignoring nuclear opacities . RESULTS Persons with moderate nuclear opacities were more likely to be female , nonwhite , and smokers and to have large drusen . Moderate nuclear opacities were less common in persons with higher educational status , a history of diabetes , and among those taking nonsteroidal antiinflammatory drugs . Moderate cortical opacities were associated with dark iris color , large drusen , weight change , and , at a borderline level of significance , higher levels of sunlight exposure and use of thyroid hormones . Moderate cortical opacities were less common in persons with higher educational status . CONCLUSION Consistent findings have now been reported across many studies for gender , educational status , sunlight exposure , and smoking . Our findings that use of nonsteroidal antiinflammatory drugs is inversely associated with nuclear cataract and that dark iris color and use of thyroid hormones may increase cortical cataract risk are less well substantiated and require further investigation |
12,534 | 30,410,758 | Across tasks , differences between individuals with AN and healthy peers have been identified , with the most consistent findings in the area of reward processing .
Measuring task performance alongside actual eating behaviour , and using experimental manipulations to probe causality , may advance underst and ing of the mechanisms of illness in AN | A salient feature of anorexia nervosa ( AN ) is the persistent and severe restriction of food , such that dietary intake is inadequate to maintain a healthy body weight .
Experimental tasks and paradigms have used illness-relevant stimuli , namely food images , to study the eating-specific neurocognitive mechanisms that promote food avoidance . | The majority of adults in the UK and US are overweight or obese due to multiple factors including excess energy intake . Training people to inhibit simple motor responses ( key presses ) to high-energy density food pictures reduces intake in laboratory studies . We examined whether online response inhibition training reduced real-world food consumption and weight in a community sample of adults who were predominantly overweight or obese ( N = 83 ) . Participants were allocated in a r and omised , double-blind design to receive four 10-min sessions of either active or control go/no-go training in which either high-energy density snack foods ( active ) or non-food stimuli ( control ) were associated with no-go signals . Participants ' weight , energy intake ( calculated from 24-h food diaries ) , daily snacking frequency and subjective food evaluations were measured for one week pre- and post-intervention . Participants also provided self-reported weight and monthly snacking frequency at pre-intervention screening , and one month and six months after completing the study . Participants in the active relative to control condition showed significant weight loss , reductions in daily energy intake and a reduction in rated liking of high-energy density ( no-go ) foods from the pre-to post-intervention week . There were no changes in self-reported daily snacking frequency . At longer-term follow-up , the active group showed significant reductions in self-reported weight at six months , whilst both groups reported significantly less snacking at one- and six-months . Excellent rates of adherence ( 97 % ) and positive feedback about the training suggest that this intervention is acceptable and has the potential to improve public health by reducing energy intake and overweight We know strikingly little about the core affective processes that drive the development and maintenance of , and recovery from anorexia nervosa ( AN ) . To partially address this knowledge gap , we measured implicit and explicit affect toward pleasant , neutral , unpleasant , food-relevant , and weight-relevant images in three groups : in patients with acute AN , individuals recovered from AN , and healthy controls with no history of AN . Compared with the other two groups , acutely ill AN participants displayed significantly greater implicit positive affect toward pleasant images and significantly greater implicit negative affect toward unpleasant , high-calorie food , and overweight body type images . Recovered participants did not differ significantly from controls on any implicit affect measure . Explicit affective patterns were similar to implicit , but explicit measures yielded much smaller effect sizes and failed to detect certain group differences . Overall , negative implicit affect toward high-calorie foods and overweight body types may represent core affective processes that are operative during acute AN OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Attentional difficulties reported in individuals with anorexia nervosa ( AN ) may be due to preferential processing of disease-salient stimuli at a pre-attentive or at a conscious level or to a general problem in attention . Attentional difficulties may be associated with duration of illness . METHOD Female participants with AN ( restricting subtype ; n=24 ) and healthy comparison women ( n=24 ) were r and omly allocated to subliminal or supraliminal exposure to visual stimuli ( food , neutral and aversive images ) while performing the 1-back and 2-back working-memory tasks . RESULTS Participants with AN made fewer errors than the healthy comparison group in the subliminal condition but significantly more errors in the supraliminal condition [ condition x group interaction , F(1 , 44)=6.82 , p<0.01 ] : this was irrespective of stimulus type ( food , neutral and aversive ) and task ( 1-back or 2-back ) . The total number of errors made correlated positively with the duration of the AN for both the 1-back task ( rs=0.46 , p<0.05 ) and for the 2-back task ( rs=0.53 , p<0.01 ) . CONCLUSIONS Decreased ability to concentrate in the presence of explicit distracters is a feature of AN and is associated with longer duration of illness . This phenomenon could be addressed in psychological interventions |
12,535 | 21,678,334 | Compared with no treatment , use of long-term , low-dose antibiotics did not significantly reduce the number of repeat symptomatic and febrile UTIs in children with VUR .
The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear . | BACKGROUND Vesicoureteric reflux ( VUR ) results in urine passing retro grade up the ureter .
Urinary tract infections ( UTI ) associated with VUR have been considered a cause of permanent renal parenchymal damage in children with VUR .
Management of these children has been directed at preventing UTI by antibiotic prophylaxis and /or surgical correction of VUR .
The optimum strategy is not clear .
OBJECTIVES To evaluate the benefits and harms of different treatment options for primary VUR . | PURPOSE We compared the development of new renal damage in small children with dilating vesicoureteral reflux r and omly allocated to antibiotic prophylaxis , endoscopic treatment or surveillance as the control group . MATERIAL S AND METHODS Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux . Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before r and omization and after 2 years . Febrile urinary tract infections were recorded during followup . Data analysis was done by the intent to treat principle . RESULTS New renal damage in a previously unscarred area was seen in 13 girls and 2 boys . Eight of the 13 girls were on surveillance , 5 received endoscopic therapy and none were on prophylaxis ( p = 0.0155 ) . New damage was more common in children with than without febrile recurrence ( 11 of 49 or 22 % vs 4 of 152 or 3 % , p < 0.0001 ) . CONCLUSIONS In boys the rate of new renal damage was low . It was significantly higher in girls and most common in the control surveillance group . There was also a strong association between recurrent febrile UTIs and new renal damage in girls PURPOSE We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux r and omly allocated to 3 management alternatives , including antibiotic prophylaxis , endoscopic treatment or surveillance only as the control . MATERIAL S AND METHODS At 23 centers a total of 203 children were included in the study , including 128 girls and 75 boys 1 to younger than 2 years . Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection ( 194 ) after prenatal screening ( 9 ) . Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before r and omization and after 2 years . The febrile urinary tract infection rate was analyzed by the intent to treat principle . RESULTS We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys ( p = 0.0001 ) . There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 ( 19 % ) on prophylaxis , 10 of 43 ( 23 % ) with endoscopic therapy and 24 of 42 ( 57 % ) on surveillance ( p = 0.0002 ) . In girls the recurrence rate was associated with persistent reflux after 2 years ( p = 0.0095 ) . However , reflux severity ( grade III or IV ) at study entry did not predict recurrence . CONCLUSIONS In this r and omized , controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys . Antibiotic prophylaxis and endoscopic treatment decreased the infection rate OBJECTIVES To compare , in a prospect i ve study , the efficacy of a single injection of polydimethylsiloxane ( Macroplastique ) or dextranomer/hyaluronic acid copolymer ( Deflux ) , a new biodegradable substance , and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents . Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux . Macroplastique has been one of the most popular bulking agents during the past years . Nevertheless , considering the synthetic property , new biodegradable substances have become more relevant . METHODS From January 2000 to June 2001 , 16 boys and 56 girls ( total of 114 ureters ) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux . A single subureteral Macroplastique or Deflux injection was performed in 34 children ( 58 ureters ) and 38 children ( 56 ureters ) , respectively . Both groups were comparable in terms of baseline parameters . Vesicoureteral reflux was grade II in 52 , grade III in 57 , and grade IV in 5 ureterorenal units . The procedure was performed on an outpatient basis , with the children under general anesthesia . In addition to the routine parameters , the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively . RESULTS Endoscopic treatment was performed without any complications in all cases . At the 3-month follow-up visit , reflux was corrected in 50 ( 86.2 % ) of 58 refluxing ureters in the Macroplastique group and in 40 ( 71.4 % ) of 56 refluxing ureters in the Deflux group . At 1 year of follow-up , reflux correction was maintained in 80.9 % of ureters in the Macroplastique group and in 67.6 % of ureters in the Deflux group . No postoperative complications were observed in either group . CONCLUSIONS A single subureteral injection of either polydimethylsiloxane ( Macroplastique ) or dextranomer/hyaluronic acid copolymer ( Deflux ) is an effective treatment modality for children with vesicoureteral reflux . The procedure was well tolerated , safe , and associated with low morbidity . Deflux , a new biocompatible , biodegradable substance , seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children , with acceptable short-term and 1-year results Approximately 35 % of children with urinary infection have vesico-ureteric reflux ( McGovern , Marshall , and Paquin , 1960 ; Ericsson , 1960 ) . It is not known whether infection causes the reflux by damaging the uretero-vesical valvular mechanism , or whether a congenital abnormality permits reflux which predisposes to infection . Yet whatever the aetiology , it seems logical to assume that when infection occurs in the presence of reflux there will be renal involvement , for it has been shown that there is a close correlation between ureteric reflux and radiological evidence ofkidney scarring ( Hodson and Edwards , 1960 ) . Despite this , it is not clear whether , besides treating the infection by giving prolonged carefully controlled courses of antibiotics , the child will gain additional benefit if a surgical operation is undertaken to eliminate the reflux . The purpose of this paper is to report the results of a controlled trial in which a group of children with surgically treated reflux was compared with an unoperated group . The trial was a prospect i ve one and the children were allotted at r and om to either the operated or control groups according to whether their birthdays fell on even or odd days . In view of the considerable divergence of opinion about the value of the surgical treatment of reflux ( Spence et al. , 1961 ) and the uncomplicated nature of this type of surgery , it was felt that it was ethically justifiable to conduct a trial in this manner . 58 children were studied , 33 having operations for their reflux and 25 acting as controls . Cases in which reflux was associated either with mechanical obstruction in the urethra , such as posterior urethral valves , or with neurogenic bladder , were excluded from the trial , as it was felt that in these the treatment of the reflux could not be considered in isolation but only as a part of the management of the associated condition OBJECTIVES . The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment , given parenterally if necessary . In support of this recommendation , data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited . Because the risk was not well defined , we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children . METHODS . The research findings are derived from 2 multicenter , prospect i ve , r and omized , controlled studies , Italian Renal Infection Study 1 and 2 , whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis , respectively . From the 2 studies , we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later . The children were 1 month to < 7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy . RESULTS . Progressive delay in antibiotic treatment of acute pyelonephritis from < 1 to ≥5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later . The risk of scarring remained relatively constant at 30.7 ± 7 % . Clinical and laboratory indices of inflammation were comparable in all groups , as was the incidence of vesicoureteric reflux . CONCLUSIONS . Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring . Furthermore , there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with older children Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis . Design Multicentre , r and omised controlled , open labelled , parallel group , non-inferiority trial . Setting 28 paediatric units in north east Italy . Participants 502 children aged 1 month to < 7 years with clinical pyelonephritis . Intervention Oral co-amoxiclav ( 50 mg/kg/day in three doses for 10 days ) or parenteral ceftriaxone ( 50 mg/kg/day in a single parenteral dose ) for three days , followed by oral co-amoxiclav ( 50 mg/kg/day in three divided doses for seven days ) . Main outcomes measures Primary outcome was the rate of renal scarring . Secondary measures of efficacy were time to defervescence ( < 37 � C ) , reduction in inflammatory indices , and percentage with sterile urine after 72 hours . An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid ( DMSA ) scintigraphy within 10 days after study entry . Results Intention to treat analysis showed no significant differences between oral ( n=244 ) and parenteral ( n=258 ) treatment , both in the primary outcome ( scarring scintigraphy at 12 months 27/197 ( 13.7 % ) v 36/203 ( 17.7 % ) , difference in risk −4 % , 95 % confidence interval −11.1 % to 3.1 % ) and secondary outcomes ( time to defervescence 36.9 hours ( SD 19.7 ) v 34.3 hours ( SD 20 ) , mean difference 2.6 ( −0.9 to 6.0 ) ; white cell count 9.8 � 109/l ( SD 3.5 ) v 9.5 � 109/l ( SD 3.1 ) , mean difference 0.3 ( −0.3 to 0.9 ) ; percentage with sterile urine 185/186 v 203/204 , risk difference −0.05 % ( −1.5 % to 1.4 % ) ) . Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry . Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children . Trial registration Clinical Trials NCT00161330 A total of 132 infants and children with grade s III and IV primary vesicoureteral reflux was entered into a prospect i ve trial comparing medical to surgical management . Inclusion criteria were an age not exceeding 10 years and a glomerular filtration rate of at least 70 ml . per minute per 1.73 m.2 . Children with significant urinary tract malformations and clinical signs/symptoms of dysfunctional voiding were not accepted into the trial . Medical therapy consisted of continuous low dose antibiotic prophylaxis until vesicoureteral reflux resolved . The type of surgical procedure used for the correction of reflux was left to the discretion of the surgeon . Outcome variables included the appearance or progression of renal lesions , rate of renal growth , recurrence rate of urinary tract infection or pyelonephritis , changes in total kidney glomerular filtration rate , development of hypertension and resolution rate of vesicoureteral reflux . Followup at 6 , 18 , 36 and 54 months after entry included , in addition to history and physical examination , voiding cystourethrography , excretory urography and a urine culture . Of the patients 68 were allocated to the medical group and 64 to the surgical group . They were stratified for age , sex and preexisting renal scarring . Of the patients 10 % were boys , 47 % were between 2 and 6 years old at entry , 93 % had a history of pyelonephritis , 67 % had either scarring or thinning of the parenchyma at entry , 87 % had grade IV vesicoureteral reflux in at least 1 unit and 56 % had bilateral reflux . There were no significant differences in the frequency distribution of entry characteristics between the patients allocated to either group . New renal scarring developed in 22 % of medical and 31 % of surgical patients ( p < 0.4 ) . Growth of kidneys with grade IV vesicoureteral reflux was slightly less than normal in the medical ( -0.67 + /- 0.15 st and ard deviation ) and surgical ( -0.42 + /- 0.11 st and ard deviation ) groups ( p < 0.7 ) . Pyelonephritis occurred in 15 medical patients versus 5 surgical patients ( p < 0.05 ) . There was no significant change in glomerular filtration rate within each treatment group and no difference in glomerular filtration rate between groups . No patient had hypertension during the followup period . The disappearance rate of vesicoureteral reflux in patients with grade IV reflux was approximately 8 % per year . Of the medical patients 75 % still had vesicoureteral reflux after 3 years of observation . ( ABSTRACT TRUNCATED AT 400 WORDS BACKGROUND Antibiotics are widely administered to children with the intention of preventing urinary tract infection , but adequately powered , placebo-controlled trials regarding efficacy are lacking . This study from four Australian centers examined whether low-dose , continuous oral antibiotic therapy prevents urinary tract infection in predisposed children . METHODS We r and omly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension ( as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight ) or placebo for 12 months . The primary outcome was microbiologically confirmed symptomatic urinary tract infection . Intention-to-treat analyses were performed with the use of time-to-event data . RESULTS From December 1998 to March 2007 , a total of 576 children ( of 780 planned ) underwent r and omization . The median age at entry was 14 months ; 64 % of the patients were girls , 42 % had known vesicoureteral reflux ( at least grade III in 53 % of these patients ) , and 71 % were enrolled after the first diagnosis of urinary tract infection . During the study , urinary tract infection developed in 36 of 288 patients ( 13 % ) in the group receiving trimethoprim-sulfamethoxazole ( antibiotic group ) and in 55 of 288 patients ( 19 % ) in the placebo group ( hazard ratio in the antibiotic group , 0.61 ; 95 % confidence interval , 0.40 to 0.93 ; P = 0.02 by the log-rank test ) . In the antibiotic group , the reduction in the absolute risk of urinary tract infection ( 6 percentage points ) appeared to be consistent across all subgroups of patients ( P > or = 0.20 for all interactions ) . CONCLUSIONS Long-term , low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children . The treatment effect appeared to be consistent but modest across subgroups . ( Australian New Zeal and Clinical Trials Registry number , ACTRN12608000470392 . Objective Our goal is to determine if antimicrobial prophylaxis with trimethoprim/sulfamethoxazole prevents recurrent urinary tract infections and renal scarring in children who are found to have vesicoureteral reflux after a first or second urinary tract infection . Design , Participants , and Methods The R and omized Intervention for Children With Vesi-coureteral Reflux ( RIVUR ) study is a double-blind , r and omized , placebo-controlled trial . Six hundred children aged 2 to 72 months will be recruited from both primary and subspecialty care setting s at clinical trial centers throughout North America . Children who are found to have grade s I to IV vesicoureteral reflux after the index febrile or symptomatic urinary tract infection will be r and omly assigned to receive daily doses of either trimethoprim/sulfamethoxazole or placebo for 2 years . Scheduled follow-up contacts include in-person study visits every 6 months and telephone interviews every 2 months . Biospecimens ( urine and blood ) and genetic specimens ( blood ) will be collected for future studies of the genetic and biochemical determinants of vesicoureteral reflux , recurrent urinary tract infection , renal insufficiency , and renal scarring . Results The primary outcome is recurrence of urinary tract infection . Secondary outcomes include time to recurrent urinary tract infection , renal scarring ( assessed by dimercaptosuccinic acid scan ) , treatment failure , renal function , re source utilization , and development of antimicrobial resistance in stool flora . Conclusions The RIVUR study will provide useful information to clinicians about the risks and benefits of prophylactic antibiotics for children who are diagnosed with vesicoureteral reflux after a first or second urinary tract infection . The data and specimens collected over the course of the study will allow research ers to better underst and the pathophysiology of recurrent urinary tract infection and its sequelae . Pediatrics 2008;122:240 - Abstract . To ascertain the outcome of childhood vesico-ureteric reflux ( VUR ) , 226 adults ( 37 males ) , mean age 27 years , were studied after 10–35 years , extended to 41 years by postal question naire in 161 . At presentation ( mean age 5 years ) all had VUR ( grade III – V in 68 ) and urinary tract infection ( UTI ) ; there was renal scarring in 85 ( acquired before referral in 11 and during follow-up in 1 ) , hypertension in 6 and impaired renal function in 5 . They were managed and followed prospect ively by one paediatrician ; 63 % of these children remained free from UTI ; VUR persisted in 63 and had resolved in 69 % of 193 children managed medically . At follow-up , 61 % of adults had remained free from infection ; 17 adults had hypertension and /or raised plasma creatinine , 16 with scarred kidneys . Their deterioration was predictable because of scar type , blood pressure or plasma creatinine levels in childhood . No new scars developed after puberty . Renal growth rates were unaffected by initial severity or persistence of VUR . On the later question naire , 9 further adults , mean age 38 years , had moderate hypertension . The adults with complications were those with extensive renal scarring and /or at least borderline hypertension in childhood . Those with VUR , but no scarring , and managed carefully in childhood , did not suffer serious consequences as adults . There is a need for early recognition and treatment of children with VUR and UTI to limit scar development PURPOSE Two reference radiologists independently review voiding cystourethrograms for the National Institutes of Health sponsored RIVUR ( R and omized Intervention for Children with Vesicoureteral Reflux ) trial for children with vesicoureteral reflux . A pilot study was required from all clinical centers before enrolling patients . MATERIAL S AND METHODS Digital images were review ed . Responses were compared and discrepancies adjudicated by teleconference to a final assessment . RESULTS A total of 75 studies from 19 sites were review ed . Discrepancies in vesicoureteral reflux grade level were noted on the left and right side in 11 ( 15 % , kappa 0.85 ) and 12 ( 16 % , kappa 0.83 ) ureters , respectively . Other areas of disagreement were the presence of paraureteral diverticulum ( left 11 % , kappa 0.31 ; right 9 % , kappa 0.34 ) , urethral anatomy ( 15 % , kappa 0.33 ) , whether the child voided ( 8 % , kappa 0.21 ) , the presence of ureteral duplication ( left 7 % , kappa 0.64 ; right 3 % , kappa 0.78 ) and the presence of bladder trabeculation ( 5 % , kappa 0.32 ) . Of 83 ureters in which reflux was seen there was grade disagreement about 23 ( 28 % ) . Of 61 ureters initially assessed as grade II or III reflux by both readers , there was disagreement on 9 ( 15 % ) . Of these 9 discrepancies 7 ( 78 % ) were adjudicated to the higher grade ( grade III ) . CONCLUSIONS Discrepancies in the assessment of intermediate grade vesicoureteral reflux were noteworthy . Recommendations for patients with grade II or III reflux advanced by studies which rely on a single reading , which categorize only grade III or higher reflux as significant , may not be valid OBJECTIVES . To evaluate the role of primary vesicoureteral reflux ( VUR ) in increasing the frequency and severity of urinary tract infections ( UTIs ) and renal parenchymal damage among patients with acute pyelonephritis and to determine whether urinary antibiotic prophylaxis reduces the frequency and /or severity of UTIs and /or prevents renal parenchymal damage among patients with mild/moderate VUR . METHODS . Patients 3 months to 18 years of age with acute pyelonephritis , with or without VUR , were assigned r and omly to receive urinary antibiotic prophylaxis or not . Patients were monitored every 3 months for 1 year . Dimercaptosuccinic acid renal scans were repeated at 6 months or if there was a recurrence of febrile UTI . Urinalysis and urine culture were performed at each clinic visit . Renal ultrasound scans and voiding cystourethrograms were repeated at the end of 1 year of follow-up monitoring . RESULTS . Of the 236 patients enrolled in the study , 218 completed the 1-year follow-up monitoring . Groups were similar with respect to age , gender , and reflux grade distribution for those with VUR . No statistically significant differences were found among the groups with respect to rate of recurrent UTI , type of recurrence , rate of subsequent pyelonephritis , and development of renal parenchymal scars . CONCLUSIONS . After 1 year of follow-up monitoring , mild/moderate VUR does not increase the incidence of UTI , pyelonephritis , or renal scarring after acute pyelonephritis . Moreover , a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study OBJECTIVE . We examined the diagnostic accuracy of routine imaging studies ( ultrasonography and micturating cystography ) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection . METHODS . This study addressed the secondary objective of a prospect i ve trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis . Data for 300 children ≤2 years of age , with normal prenatal ultrasound results , who completed the diagnostic follow-up evaluation ( ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days , cystography within 2 months , and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring ) were analyzed . Outcome measures were sensitivity , specificity , and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans . RESULTS . The kidneys and urinary tracts were mostly normal . The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54 % of cases . Renal scarring developed in 15 % of cases . The ultrasonographic and cystographic findings were poor predictors of long-term damage , showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring . CONCLUSIONS . The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal . Our findings support ( 1 ) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension , proteinuria , and renal function impairment ( although the degree of scarring was generally minor and did not impair renal function ) and ( 2 ) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation PURPOSE We review ed our experience with (99m)technetium dimercapto-succinic acid scintigraphy obtained during an imaging pilot study for a multicenter investigation ( R and omized Intervention for Children With Vesicoureteral Reflux ) of the effectiveness of daily antimicrobial prophylaxis for preventing recurrent urinary tract infection and renal scarring . We analyzed imaging methodology and its relation to diagnostic image quality . MATERIAL S AND METHODS (99m)Technetium dimercapto-succinic acid imaging guidelines were provided to participating sites . High-resolution planar imaging with parallel hole or pinhole collimation was required . Two core review ers evaluated all su bmi tted images . Analysis included appropriate views , presence or lack of patient motion , adequate magnification , sufficient counts and diagnostic image quality . Inter-reader agreement was evaluated . RESULTS We evaluated 70 , (99m)technetium dimercapto-succinic acid studies from 14 institutions . Variability was noted in methodology and image quality . Correlation ( r value ) between dose administered and patient age was 0.780 . For parallel hole collimator imaging good correlation was noted between activity administered and counts ( r = 0.800 ) . For pinhole imaging the correlation was poor ( r = 0.110 ) . A total of 10 studies ( 17 % ) were rejected for quality issues of motion , kidney overlap , inadequate magnification , inadequate counts and poor quality images . The su bmi tting institution was informed and provided with recommendations for improving quality , and resu bmi ssion of another study was required . Only 4 studies ( 6 % ) were judged differently by the 2 review ers , and the differences were minor . CONCLUSIONS Methodology and image quality for (99m)technetium dimercapto-succinic acid scintigraphy varied more than expected between institutions . The most common reason for poor image quality was inadequate count acquisition with insufficient attention to the tradeoff between administered dose , length of image acquisition , start time of imaging and result ing image quality . Inter-observer core reader agreement was high . The pilot study ensured good diagnostic quality st and ardized images for the R and omized Intervention for Children With Vesicoureteral Reflux investigation Thirty children with urinary tract infection and nonobstructive vesicoureteral reflux have been followed prospect ively for a mean of 17 months . After classification according to age and grade of reflux , 10 patients were assigned at r and om to treatment with antimicrobial prophylaxis alone or antimicrobial prophylaxis plus corrective surgery . Twenty other patients were also treated with antimicrobial prophylaxis alone . All were assigned at r and om to treatment with a single daily dose of trimethoprim-sulfamethoxazole or nitrofurantoin . Cultures of urine , complete blood cell counts , and determination of levels of aspartate aminotransferase in serum were performed regularly during follow-up . Both drugs proved effective in prevention of recurrent infection , and no significant hematologic or hepatic abnormalities were noted . Current results suggest that either prophylaxis or surgery may effectively prevent chronic pyelonephritis or reflux nephropathy , but only continuing evaluation of this group of patients will confirm these results A total of 401 children with severe vesicoureteral reflux ( 97 with grade III and 304 with grade IV ) was entered into the European branch of the International Reflux Study in Children . Of these patients 37 with grade III and 43 with grade IV reflux were allocated to medical treatment as a sideline group because the reflux grade III or IV had improved to grade II or I , or it had disappeared during the preceding 2 to 6 months ( median 4 ) . Of the remaining 321 patients with persistent grade III or IV reflux 158 were r and omly allocated to medical treatment of whom 3 switched to surgery . We report on 235 children treated medically ( 155 r and om medical and 80 sideline ) , of whom 88 % had a complete 5-year followup with x-ray and /or isotope voiding cystourethrography at 6 , 18 , 30 and 54 months . Seven children dropped out of the study after a followup of 6 months or less , including 6 with persistent vesicoureteral reflux . Cessation of vesicoureteral reflux was observed significantly more often in children with unilateral ( 40 of 74 , 54 % ) than with bilateral ( 18 of 154 , 12 % ) reflux ( p < 0.001 ) . No significant difference between grade s III and IV was noted . Vesicoureteral reflux ceased in 25 of 153 children ( 16 % ) from the r and om medical group and in 32 of 75 children ( 43 % ) in the sideline group . Of 194 children with vesicoureteral reflux detected for the first time at entry reflux resolved in 55 ( 28 % ) . In only 2 of 34 children ( 6 % ) in whom vesicoureteral reflux was detected more than 1 year before entry did reflux resolve after 5 years . Among the children in whom vesicoureteral reflux either disappeared , diminished or remained unchanged the proportion with urinary tract infection recurrences was almost the same This was a r and omised , multicentre study performed in France . Children under 15 years of age were included , with parental consent . They had various grade s of reflux , in one or both sides , in simple or duplex ureter , with or without renal damage ( as assessed radiologically ) . Patients had no simultaneous infection , immune deficiency or drug allergy . Surgery was characterised by unilateral or bilateral ureteral reimplantation only , no urinary infection on the day of operation and no requirement for postoperative transanastomosis ureteral probe Probiotics , beneficial living microorganisms , have been proven to be effective in preventing gastrointestinal infections , but their effect in preventing urinary tract infection ( UTI ) is inconclusive . A prospect i ve r and omized controlled study was done to compare the preventive effect of probiotics with conventional antibiotics in children with persistent primary vesicoureteral reflux ( VUR ) . One hundred twenty children who had had persistent primary VUR after antibiotic prophylaxis for 1 year were r and omly allocated into a probiotics ( Lactobacillus acidophilus 108 CFU/g 1 g b.i.d . , n = 60 ) or an antibiotics ( trimethoprim/sulfamethoxazole 2/10 mg/kg h.s . , n = 60 ) prophylaxis group during the second year of follow-up . The incidence of recurrent UTI was 18.3 % ( 11/60 ) in the probiotics group , which was not different from 21.6%(13/60 ) in the antibiotic group ( P = 0.926 ) . The causative organisms of recurrent UTI were not significantly different between the two groups ( P = 0.938 ) . Even after stratification by VUR grade , age , gender , phimosis , voiding dysfunction and renal scar , the incidence of recurrent UTI did not differ significantly between the two groups ( P > 0.05 ) . The development of new renal scar was not significantly different between the two groups ( P > 0.05 ) . In conclusion , probiotics prophylaxis was as effective as antibiotic prophylaxis in children with persistent primary VUR Schoolgirls shown to have covert bacteriuria ( CB ) by a screening programme and followed up for 5 years to assess whether chemotherapy had any beneficial effect , underwent a further assessment of renal function at the age of 18 years and during subsequent pregnancies . At age 18 , glomerular filtration rate ( GFR ) and urine concentrating ability were the same as in controls , but fractional reabsorption of glucose was significantly reduced in those who had previously been prescribed chemotherapy because of renal scarring or who had been r and omly allocated not to receive prophylactic chemotherapy . Those who had had CB as schoolgirls had a higher frequency of CB in pregnancy than did controls , whether or not prophylactic chemotherapy had been given to the subjects when they were schoolgirls . Furthermore , compared with girls who had had such treatment , untreated patients had smaller increments in GFR , reduced fractional reabsorption of glucose , and more than usual degree of glycosuria during pregnancy . This suggests that sub clinical renal damage may be prevented by prophylactic chemotherapy but this advantage is unmasked only by the physiological dem and s of pregnancy In children with vesicoureteral reflux ( VUR ) and urinary tract infection , retardation of growth and weight gain at the time of diagnosis and catch‐up growth during follow‐up , mostly after operating for VUR , have been reported . A controlled trial comparing the effect on growth of surgical treatment and long‐term prophylactic antibiotic treatment has not been reported previously . Between 1980 and 1985 , 306 children younger than 11 y with non‐obstructive grade III or IV VUR , with a history of symptomatic urinary tract infection , were r and omly allocated to surgical or medical treatment . Of these , 236 were followed for 10 y , 118 r and omized to surgical treatment ( mean age at entry 3.5 ± 2.3 y ) and 118 to medical treatment ( mean age at entry 3.8 ± 2.5 y ) . All children had renal function and blood pressure in the normal range . Body height , measured at start and after 1 , 5 and 10 y , was transformed to st and ard deviation score of height for chronological age ( SDSH‐CA ) and body weight to percentage of ideal body weight for height ( % IBW ) . The evolution of SDSH‐CA and % IBW was similar in both treatment groups ( SDSH‐CA : surgical : start , 0.23 ± 1.4 ; 10 y , 0.40 ± 1.0 ; medical : start , 0.14 ± 1.2 ; 10 y , 0.44 ± 1.2 ; % IBW : surgical : start , 99 ± 9 % ; 10 y , 107 ± 14 % ; medical : start , 98 ± 10 % ; 10 y , 105 ± 16 % ) . While children starting the study below the age of 3 y ( SDSH‐CA 0.55 ± 1.34 ) started significantly taller than those older than 3 y ( SDSH‐CA −0.1 ± 1.39 ) , the young ones demonstrated a significant drop in SDSH‐CA during the 1st year ( SDSH‐CA 0.19 ± 1.23 ) , which was regained up to the 10th year ( SDSH‐CA 0.6 ± 1.13 ) , and the older ones steadily gained height up to an SDSH‐CA of 0.28 ± 1.05 at 10 y. During all of the study period , treatment protocol , grade of VUR , renal parenchymal scars at entrance and urinary tract infections did not influence growth and weight gain . Age at entry and gender were the only significant correlates with growth and weight gain A total of 532 children , 401 from Europe and 131 from the United States , was recruited into an international multicenter study comparing the results of medical and surgical treatment of children with international grade III or IV vesicoureteral reflux and urinary tract infection . Patient age was less than 11 years , glomerular filtration rate was greater than 70 ml . per minute per 1.73 m.2 and there was no obstruction , renal malformation , previous urinary tract surgery or neuropathic bladder . A total of 80 children had less than grade III vesicoureteral reflux on a second pre-entry cystourethrogram required by the European protocol , and they were followed separately as a sideline group . At entry the age distribution , history of urinary tract infection and proportion of children with grade IV vesicoureteral reflux were similar in Europe and the United States . Of the European and United States children 48 % and 54 % had renal scarring , and 17 % and 14 % had parenchymal thinning , respectively . In each group renal length and planimetric area were normal in two-thirds and 5 % had small kidneys ( < 2 st and ard deviations from normal ) . Differences included sex distribution ( 24 % boys in Europe and 11 % in the United States group ) , the proportion of children in whom vesicoureteral reflux was previously known ( 18 % Europe and 69 % United States ) and the proportion of children with bilateral reflux ( 77 % Europe and 57 % United States ) . R and omization and stratification for treatment were successful For the comparison of long-term outcome of the management of medical or surgical treatment of children with severe vesicoureteral reflux ( VUR ) , children aged < 11 years with non-obstructive grade III/IV reflux , previous urinary tract infection ( UTI ) and glomerular filtration rate ( GFR ) ≥70 ml/min per 1.73 m2 body surface area were recruited , and 306 were r and omly allocated to receive antimicrobial prophylaxis or ureteral reimplantation . Primary endpoints were new renal scars and renal growth . Follow up , originally planned for 5 years , was extended to 10 years for 252 children , 223 of whom had follow-up imaging . Up to 5 years , 40 new urographic scars ( medical 19 , surgical 21 ) were seen . Between 5 years and 10 years , only two further scars were observed . Renal growth and UTI recurrence rate were similar , except that medically treated patients had more febrile infections . There was no difference in somatic growth , radionuclide imaging or renal function . A GFR < 70 ml/min per 1.73 m2 was found in only one patient . Three patients developed hypertension requiring treatment . We conclude that , with close supervision and prompt treatment of recurrences , children entering the study with GFR ≥70 ml/min per 1.73 m2 progressed remarkably well under either medical or surgical management , emphasizing the importance of continued supervision and the entry level of renal function The renal findings on intravenous urography ( IVU ) are reported in 306 children ( 73 boys , 233 girls ) from eight European centres entered into an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux followed for 5 years . One hundred and fifty-five children were r and omly allocated to medical and 151 to surgical treatment . Protocol and investigative techniques were st and ardised and r and omisation , data collection and analysis were performed central ly in Essen , Germany . At entry 149 ( 49 % ) has established renal scarring ( 79 medical , 70 surgical ) . Children with normal kidneys ( 105 ) , areas of thinned parenchyma ( 52 ) and grade of reflux were also evenly distributed . IVU was repeated at 6 , 18 and 54 months and serial urine culture,99mtechnetium-dimercaptosuccinic acid scans and plasma creatinine estimations were performed . Two hundred and seventy-two children ( 89 % ) completed this follow-up . In 174 children ( 57 % ) , ( 90 medical , 84 surgical ) there was renal growth without morphological change . New renal scars developed in 19 children treated medically and 20 surgically ; 12 ( 5 medical , 7 surgical ) developed in previously normal kidneys . Six followed post-operative obstruction . No significant difference in outcome was found between medical or surgical management in terms of the development of new renal lesions or the progression of established renal scars A total of 306 children with grade III to IV vesicoureteral reflux ( international classification ) and a history of documented urinary tract infection was r and omized into medical ( 155 patients ) or surgical ( 151 patients ) treatment arms in the European portion of the International Reflux Study in Children . Children treated medically were maintained on prophylactic antibacterials as long as the reflux persisted , while those treated surgically were covered prophylactically until followup studies at 6 months postoperatively demonstrated the reflux to be corrected . St and ard definitions for bacteriuria were used , and the distinction was made clinical ly among acute pyelonephritis , cystitis and asymptomatic bacteriuria , supported in many instances by additional laboratory testing . Urine was cultured after 3 months and whenever suspicious symptoms occurred . Urinary tract infections developed during the first 5-year followup period in 59 patients ( 38 % ) in the medical group and in 59 ( 39 % ) in the surgical group but the incidence of pyelonephritis was higher in the medical group ( 21 % ) than in the surgical group ( 10 % ) ( p < 0.01 ) . Pyelonephritis often followed catheterization or cystoscopy but asymptomatic bacteriuria was uncommon after these procedures in either group . Recurrent infections were related to age , sex and treatment center . They were common in boys and girls entering under 1 year of age but were less common in girls and rare in boys entering after 1 year of age . Recurrences were lowest among the Finnish children and highest in the German and Belgian children OBJECTIVES To determine when pyelonephritic renal scarring was detected in children with urinary tract infection ( UTI ) and characterize those with primary and acquired scarring , respectively . STUDY DESIGN A population -based cohort of 1221 children ( 989 girls and 232 boys ) with first recognized symptomatic UTI , aged 0 to 15 years , were diagnosed and followed up prospect ively at a single children 's hospital ; 652 had febrile UTI . Seven hundred fifty-three were evaluated by urography . Renal scarring was classified as primary or acquired , the latter without signs of scarring at the first investigation . To evaluate the frequency of recurrent UTI in those with acquired scarring , a comparison with group-matched children without scarring was performed . RESULTS A total of 74 children without obstruction had renal scarring ( acquired in 40 ) . Primary scarring was found in 18 of 21 ( 86 % ) of the boys and 16 of 53 ( 30 % ) of the girls ( P < .001 ) . The majority of boys with scarring had dilated reflux ( 67 % ) in contrast to girls ( 23 % ) . Recurrent UTI was rare in boys , whereas girls with acquired scarring had significantly more febrile recurrences than girls without scarring . CONCLUSIONS Most boys had primary , probably congenital , reflux-associated renal damage , whereas most girls had acquired scarring related to recurrences of febrile UTI In the European part of the International Reflux Study in Children ( 7 participating centers ) 151 infants and children were r and omly allocated to surgical treatment of primary grade s III and IV vesicoureteral reflux . Reimplantation was performed unilaterally in 65 patients and bilaterally in 86 , for a total of 237 ureters reimplanted . The patients were followed at regular intervals for 5 years . Reflux was absent in 231 of the reimplanted ureters ( 97.5 % ) at the end of 5 years . No patient underwent reoperation for reflux . In 10 ureters ( 4.2 % , 10 patients ) obstruction developed postoperatively and 7 needed reoperation . All reoperations were performed on the left side . Of the obstructed kidneys new scars developed in 6 during the 5-year followup . Including these cases , the number of new renal scars was equal in the surgical and medical groups ( 20 each ) . The number of pyelonephritic episodes during followup was significantly less in the surgical group ( without chemoprophylaxis ) than in the medical group ( on chemoprophylaxis ) . No kidneys were lost and no child became hypertensive . If voiding cystourethrography and excretory urography were normal 6 months postoperatively , the reflux had been permanently eradicated and postoperative obstruction could be ruled out . In this study the patients who underwent reimplantation had a 74 % ( 112 of 151 ) chance of an uncomplicated postoperative course ( no persisting reflux , obstruction , pyelonephritis or severe renal damage ) The International Reflux Study in Children was set up to compare prospect ively the outcome of medical or surgical management of children with grade III or IV vesicoureteral reflux and a history of symptomatic urinary tract infection . Development of new radiological scars was the main end point . Of the 306 children r and omized , 302 ( 153 medical , 149 surgical ) were available for radiological follow-up at 5 years . New scars had developed in 19 medically and 21 surgically treated children . Among 223 patients ( 113 medical , 110 surgical ) who continued follow-up with urography at 10 years , only 2 further new scars developed . Overall , 47 new scars were acquired in 42 patients ( 20 medical , 22 surgical ) , 25 of them in children with unscarred kidneys at entry ( 13 medical , 12 surgical ) . New scars occurred mostly in children under 5 years of age and were observed more frequently in children with grade IV than grade III reflux . We conclude that with careful management , only a small proportion of children with severe reflux developed new scars and rarely after the first 5-year follow up period , and that there was no difference between children treated medically or surgically Between 1982 and 1986 , 96 children with nonobstructive vesicoureteric reflux were treated in a prospect i ve study . There were 134 refluxing ureters . Results are reported after a follow-up period of 3 years in 94 children with 130 refluxing ureters . Initially all children with reflux grade III or less had antibiotic treatment only . Those with reflux grade IV were r and omized for antibiotic treatment alone versus surgery plus antibiotic treatment , while the primary treatment of reflux grade V was reimplantation . In 84 ureters treated by antibiotics alone , reflux disappeared in 52 cases and in 18 ureters the reflux was reduced . In 49 ureters treated by reimplantation , reflux was cured in 39 cases and no severe ureteric obstruction was seen . Conservative management of reflux grade IV was less successful than surgery . The results of conservative , nonsurgical treatment of reflux grade I to III are satisfactory , but for grade s IV and V reflux surgery should be the treatment of choice , provided that detrusor instability can be excluded OBJECTIVE To study the progress of vesicoureteric reflux ( VUR ) grade III or IV in children followed up prospect ively over 10 years . STUDY DESIGN One hundred forty-nine children ( 33 boys and 116 girls ) with VUR were recruited for the International Reflux Study in Children and were treated with a medical regimen and monitored by means of serial cystograms . VUR disappearance was based on negative findings on 2 consecutive cystograms . RESULTS At 5 years , VUR with dilatation was seen in 72 ( 48 % ) children and VUR without dilatation , in 55 ( 37 % ) ; 22 ( 15 % ) children had no reflux . At 10 years , VUR with dilatation was seen in 34 ( 23 % ) children and VUR without dilatation , in 37 ( 25 % ) ; 78 ( 52 % ) children had no reflux . Grade IV VUR persisted in 8 children . Absence of VUR was significantly associated with grade III versus grade IV VUR ( P = .007 ) , unilateral versus bilateral reflux ( P = .0002 ) , and age > or = 5 years at entry versus age < 5 years ( P = .001 ) . Neither sex nor renal scarring at entry individually affected resolution of VUR . Among 43 ( 29 % ) children with intermittent VUR , only 6 had reflux with dilatation at 10 years . CONCLUSION Continuing reduction in the severity of VUR in children receiving careful medical treatment was observed over 10 years . On the basis of negative findings on 2 consecutive cystograms , VUR was absent in half of the children BACKGROUND Nephropathy associated with vesicoureteric reflux ( VUR ) and urinary tract infection can result in end-stage renal failure , hypertension , or both . Whether long-term VUR contributes to these outcomes is unknown . We compared , in a r and omised trial , medical with surgical management of children with bilateral severe VUR and bilateral nephropathy . METHODS We stratified by age and glomerular filtration rate ( GFR ) 25 boys and 27 girls aged 1 - 12 years and r and omly assigned them to medical or surgical management . At enrolment and 4 years ' follow-up we estimated GFR from the plasma clearance of 51Cr-labelled edetic acid ( EDTA ) , and did intravenous urography . We also did a metastable 99mTc-labelled dimercaptosuccinic acid ( DMSA ) assay and contrast cystography . The change in GFR at 4 years , expressed as a percentage change between enrolment and 4 years , was available for 26 of 27 patients in the medical and 24 of 25 in the surgical group . We assessed GFR in 48 patients 10 years after enrolment . FINDINGS Mean GFR at enrolment was 72.4 mL/min per 1.73 m(2 ) ( SD 24.1 ) in the medical and 71.7 mL/min per 1.73 m(2 ) ( 22.6 ) in the surgical group . The mean percentage change in GFR at 4 years was 2.4 % ( SE 4.5 ) versus 4.7 % ( 5.0 ) in the medical and surgical groups , respectively . The difference in change in GFR at 4 years between the two groups was not significant ( 7.1 % , 95 % CI 6.4 % to 20.6 % ) . INTERPRETATION Our data do not lend support to the view that the outcome for renal function is improved by surgical correction of VUR in children with bilateral disease PURPOSE Primary bladder neck dysfunction has been under diagnosed as a treatable cause of vesicoureteral reflux . We evaluated the effect of prazosin administration on vesicoureteral reflux resolution and urodynamic parameters in children with idiopathic primary reflux and primary bladder neck dysfunction . MATERIAL S AND METHODS A total of 62 children ( mean ± SD age 7.9 ± 2.4 years ) with documented vesicoureteral reflux and urodynamics proved primary bladder neck dysfunction were r and omized to receive either 0.025 mg/kg α-blocker ( prazosin , 40 patients ) or placebo ( 22 ) nightly for 1 week with a subsequent increase to 2 divided doses . Patients were followed for 12 months with clinical evaluation and uroflowmetry performed every 2 months , and each patient underwent complete urodynamic study at 6-month intervals . RESULTS In the placebo group no uroflowmetry or urodynamic parameter changed significantly at 1-year followup . A 60 % decrease in reflux grade was observed in the treatment group compared to 17 % in the placebo group . Mean maximal detrusor pressure , post-void residual and opening time were significantly decreased in both followup sessions in the prazosin group ( p < 0.05 ) . Average flow rate improved from 4.30 to 12.80 ml per second at 6 months and to 13.10 ml per second at 12 months ( both p < 0.05 ) . CONCLUSIONS Special attention should be given to secondary causes of vesicoureteral reflux ( such as primary bladder neck dysfunction , an underdiagnosed entity in children ) , since conventional treatment will most likely fail if these conditions are not addressed promptly . In this study prazosin was effective therapy for children with vesicoureteral reflux and primary bladder neck dysfunction PURPOSE In the experimental model glutaraldehyde cross-linked collagen GAX 65 with a collagen concentration of 65 mg./ml . has proved to have more persistent implant volume and , therefore , a better antireflux effect than GAX 35 , which is injected more commonly . The aim of this study was to evaluate the potential clinical application of GAX 65 . MATERIAL S AND METHODS Ten boys and 8 girls an average of 4.6 years old presented with unilateral or bilateral primary reflux and were r and omly divided into 2 groups . All refluxing ureters received 1 endoscopic subureteral injection of an average of approximately 2.9 ml . collagen . In group 1 , 16 refluxing ureters were treated with GAX 65 and in group 2 , 12 were treated with GAX 35 . In all patients voiding cystourethrography was performed immediately after injection and 3 months postoperatively , and ultrasound was done on day 1 , and at 1 and 3 months . Implant volume was calculated at the day of injection and at 3 months . The distribution of reflux grade s was comparable in the 2 groups . RESULTS Both material s had excellent injection properties . Immediately after injection all ureters were reflux-free . Of the 16 ureters treated with GAX 65 14 ( 87.5 % ) were reflux-free at the 3-month followup . Three months postoperatively ultrasound revealed an average implant volume increase of one-third . However , of the 12 ureters treated with GAX 35 reflux had resolved in 59.3 % and the average implant volume had decreased by half 3 months after injection . CONCLUSIONS Three months after endoscopic subureteral injection of GAX 65 vesicoureteral reflux was absent in 87.5 % of patients . Therefore , GAX 65 has greater potential for treating reflux in the short term than GAX 35 . To define the final efficacy of GAX 65 for treating vesicoureteral reflux , long-term evaluation of this series is necessary . In addition , further studies are m and atory to prove the long-term advantage of this new injectable substance Between 1982 and 1986 95 children with non-obstructive vesicoureteric reflux were treated in a prospect i ve study . Preliminary results are reported on 94 children with 137 refluxing ureters and a follow-up period of at least 18 months . All children with reflux grade III or less had antibiotic treatment only . Those with reflux grade IV were r and omised for antibiotic treatment alone versus surgery plus antibiotic treatment , while the primary treatment of reflux grade V was reimplantation . In 91 ureters treated by antibiotics alone , reflux disappeared in 49 cases ; in 20 cases the grade of reflux was reduced . In 46 ureters treated by reimplantation , reflux was cured in 40 cases and no severe ureteric obstruction was seen . Conservative management of reflux grade IV seems to be less successful than surgery . The results of conservative , non-surgical treatment of reflux grade I to III are satisfactory , but for grade s IV and V reflux surgery seems to be the treatment of choice if detrusor instability can be excluded 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 A total of 321 children less than 11 years old with nonobstructive grade III or IV vesicoureteral reflux and with previous urinary tract infection was r and omly allocated to medical or surgical treatment in the European branch of the International Reflux Study in Children . ( R and omization was stratified for age , sex , grade of reflux , presence of renal scarring , interval since last urinary tract infection and treating hospital ) . The results of excretory urography are reported for 233 girls and 73 boys treated according to the r and om allocation , 89 % of whom were followed for 5 years . After 5 years in the medical group ( 155 children ) new renal scars were seen in 19 and new renal parenchymal thinning in 11 . The proportions were almost identical among 151 children allocated to surgical treatment with 20 new scars and 15 new thinnings . Progression of established scars was also similar in both groups . However , the new scars developed sooner after surgery than during medical treatment . In 6 surgically treated children postoperative obstruction was followed by the development of new scars . In addition , 12 patients showed new scars approximately 6 months after successful surgery , while in only 2 children scars developed more than 6 months after surgery . In 11 children of the medical group new scars were seen more than 6 months after allocation . More new scars developed in the children with parenchymal thinning at entry ( 23 % ) than in those with scarred or normal kidneys at entry ( 10 % each ) ( p < 0.05 ) . The younger the patients at entry , the higher the frequency of new scars ( less than 2 years 19.8 % ) 2 to 4 years 9.8 % and 5 years or more 4.6 % , p < 0.05 ) OBJECTIVES Dextranomer/hyaluronic acid ( Dx/HA ) copolymer has favorable properties for endoscopic treatment of vesico-ureteral reflux ( VUR ) . This open , r and omized study was performed to compare the efficacy and safety of Dx/HA copolymer with antibiotic prophylaxis in children with VUR . METHODS Children > 1 year of age with VUR grade II to IV ( confirmed by voiding cysto-urethrogram ) received endoscopic treatment with Dx/HA copolymer ( n = 40 ) or 12 months of antibiotic prophylaxis ( n = 21 ) . Patients in the latter group with reflux grade > or = II at month 3 received a second implantation . All patients were reassessed by voiding cysto-urethrogram at month 12 . Scintigraphy and ultrasound were performed to investigate renal status . RESULTS At month 12 , 69 % of patients in the Dx/HA copolymer group had reflux grade < or = I bilaterally , compared with 38 % in the antibiotic group ( P = .029 ) . Of patients with reflux grade < or = I at month 3 , 89 % showed a sustained response at month 12 . One serious adverse event was reported in the antibiotic prophylaxis group , but this was not attributed to study treatment . No other adverse events occurred . CONCLUSIONS Endoscopic treatment with Dx/HA copolymer was more effective than antibiotic prophylaxis in alleviating childhood VUR , and there were no safety concerns with either treatment OBJECTIVES To evaluate prophylaxis and endoscopic injection for children with dilating vesicoureteral reflux ( VUR ) compared to surveillance , regarding urinary tract infection ( UTI ) recurrence , new renal damage , VUR outcome , and impact of lower urinary tract ( LUT ) dysfunction on these outcomes . PATIENTS AND METHODS 203 children ( 128 girls and 75 boys ) , aged 1 to < 2 years , with VUR grade III or IV were r and omized to antibiotic prophylaxis ( n = 69 ) , endoscopic injection ( n = 66 ) or surveillance ( n = 68 ) . Voiding cystourethrography , dimercaptosuccinic acid scintigraphy and optional LUT function assessment were performed before r and omization and after 2 years . RESULTS There were 67 febrile UTIs in 42 girls and 8 in 7 boys ( p = 0.0001 ) . In girls , recurrence rate was 19 % on prophylaxis , 23 % with endoscopic treatment and 57 % on surveillance ( p = 0.0002 ) . In boys , there was no difference between treatment groups . New damage was seen in 13 girls : 8 on surveillance , 5 in the endoscopic group and none on prophylaxis ( p = 0.0155 ) , and in 2 boys . In 13 children with no or non-dilating VUR after 1 injection , dilating VUR reappeared at the 2-year follow up . LUT dysfunction at follow up was associated with persistence of VUR . CONCLUSION In girls , prophylaxis reduced the rate of UTI recurrence and new renal damage , and endoscopic injection the rate of UTI recurrence . Boys did not benefit from active treatment A total of 87 patients in the United States underwent surgical correction of vesicoureteral reflux as part of the International Reflux Study in Children . Of the 66 patients r and omized to surgical treatment 2 were transferred to the medical group before surgery was performed , while 23 patients originally assigned to receive medical management ultimately underwent surgery . Of the patients 17 ( 20 % ) were less than 1 year old , while the remaining children were evenly distributed by age in 2-year intervals up to age 9 years . Reimplantation was performed by the Cohen technique in 52 % and by the Politano-Leadbetter technique in 28 % of the patients . Bilateral reimplantation was done in 70 patients ( 80 % ) . The results were satisfactory , with no obstructions . In 81 % of the patients average followup was 3.9 years , although followup of less than 1 year in 19 % was satisfactory to determine obstruction . Only 3 % of the children were lost to followup . Postoperative reflux , which was noted in 5 patients , resolved in all but 1 ureter . These results reflect the experience of senior surgeons in pediatric urology PURPOSE To determine whether medical or surgical treatment better promotes renal growth in children with severe vesicoureteric reflux ( VUR ) and to examine factors influencing renal growth . MATERIAL S AND METHODS Three hundred two children younger than 11 years with urinary tract infection and grade III or IV VUR were r and omly assigned to surgical ( n = 149 ) or medical ( n = 153 ) treatment and were followed up at serial intravenous urography for up to 5 years ; 223 , for up to 10 years ( surgical , n = 110 ; medical , n = 113 ) . Renal size was measured planimetrically on serial intravenous urograms and was related to the virtual height of L1 through L3 by expressing it as an SD score . RESULTS There was no significant difference in mean renal growth between patients treated surgically or those treated medically after 5- or 10-year follow-up . Bilateral renal size of 80 surgical and 75 medical patients remained within 1 SD score . In patients entering the study at 2 years of age or younger and in those with grade IV VUR , bilateral VUR , or renal scars , there was a trend toward improved renal growth in those treated medically , but this finding was not statistically significant . When renal scarring or thin parenchyma was unilateral , the affected kidney grew less well , irrespective of treatment . Bilateral renal scarring was usually asymmetrical , with a corresponding effect on renal growth . CONCLUSION There was no significant difference in renal growth during 10 years between surgical and medical treatment in patients with severe reflux PURPOSE We compared the rates of febrile urinary tract infection , kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways , including antibiotic prophylaxis , endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection . MATERIAL S AND METHODS Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospect i ve , open , r and omized , controlled , multicenter study and followed for 2 years after r and omization . The main study end points were recurrent febrile urinary tract infection , renal status on dimercapto-succinic acid scintigraphy and reflux status . Outcomes were analyzed by the intent to treat principle . RESULTS During a 6-year period 128 girls and 75 boys entered the study . In 96 % of cases reflux was detected after urinary tract infection . The r and omization procedure was successful and result ed in 3 groups matched for relevant factors . Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good . Of the children 93 % were followed for the intended 2 years without a treatment arm change . All except 2 patients completed 2-year followup scintigraphy . CONCLUSIONS Recruitment was difficult but a substantial number of children were entered and r and omly assigned to 3 groups with similar basic characteristics . Good adherence to the protocol made it possible to address the central study questions PURPOSE We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups , including low dose antibiotic prophylaxis , endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection . MATERIAL S AND METHODS A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open , r and omized , controlled trial . Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer . The main end point was reflux status after 2 years . Data were analyzed by the intent to treat principle . RESULTS Reflux status improved in all 3 treatment arms . Of patients in the prophylaxis , endoscopic and surveillance groups 39 % , 71 % and 47 % , respectively , had reflux resolution or downgrading to grade I-II after 2 years . This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups ( p = 0.0002 and 0.0030 , respectively ) . After 1 or 2 injections 86 % of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20 % after 2 years . CONCLUSIONS Endoscopic treatment result ed in dilating reflux resolution or downgrading in most treated children . After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups . However , of concern is the common reappearance of dilating reflux after 2 years Abstract Objective . Dilating vesicoureteral reflux ( VUR ) has been linked to febrile urinary tract infection ( UTI ) and renal scarring . It is unclear , however , whether children with reflux should be treated surgically or medically , or just kept under close surveillance with prompt treatment of UTIs . This lack of evidence makes parental preferences a crucial factor in the choice of therapy . The Swedish Reflux Trial was set up to compare the three treatment alternatives prospect ively . This paper focuses on parental experience and satisfaction after completing the trial . Material and methods . A group of 203 children aged 12–24 months with reflux grade III or IV were r and omly assigned to antibiotic prophylaxis ( n = 69 ) , surveillance ( n = 68 ) or endoscopic injection treatment ( n = 66 ) and followed closely for 2 years . Afterwards , the families were interviewed by an investigator not involved in the care of the children about their experience of the study . Results . Parental satisfaction with the treatment given was high , with 53 % scoring 5 and 35 % 4 on a five- grade scale , with no difference between the three groups ( p = 0.5 ) . Recurrence of febrile UTI or new kidney scarring did not influence parental satisfaction . Even though the satisfaction was high regardless of therapy , parents of children in the prophylaxis group more often than others would have chosen another treatment if given a choice . Conclusions . As far as parental satisfaction and preferences are concerned , antibiotic prophylaxis , surveillance and injection treatment are equivalent treatment strategies in children with VUR In the past decade , subureteric endoscopic injection of Teflon or collagen has been propagated as a safe and successful treatment for vesicoureteral reflux . In our center , from 1990 through 1995 , 118 children and 5 adults with reflux and recurrent urinary tract infections were injected with cross-linked bovine collagen in an open , prospect i ve study . Efficacy and safety were assessed 6 and 12 months after injection , and long-term ( > or =3 years ) results were available in 78 cases . The overall success rate was 58 % ( 64 % of ureteral units ) free from reflux at 12 months and 54 % ( 58 % ) after 3 years . Analysis of anatomic , urodynamic , and technical features showed the grade of reflux to be the best predictor of success or failure . When only primary low- and middle- grade reflux , without concomitant anatomic disorders , is considered , the long-term success rate rose to 69 % ( 74 % of ureteral units ) . In conclusion , subureteric collagen injection can not ultimately replace the highly effective surgical reimplantation . However , the procedure offers a minimally invasive alternative in selected cases of mild reflux when conservative management is inadequate Abstract Objective : To review the histories of children with bilateral renal scarring and severe vesicoureteric reflux to determine whether an improvement in early management might reduce the risk of scarring . Design : Retrospective study of medical records and discussion with parents . Setting : Outpatient departments of two teaching hospitals . Patients : 52 children aged 1 - 12 years participating in a r and omised comparison of medical and surgical management . All had a history of symptomatic urinary tract infection . Two thirds presented with fever and two with hypertension or renal failure . In only one out of 32 children examined by antenatal ultrasonography was an abnormality suspected . Results - There was delay in diagnosis or appropriate imaging or effective treatment of urinary infection in 50 of the 52 children . In 41 there was delay in diagnosis ; there was delay in treating a confirmed infection in 45 ; no antibacterial prophylaxis was prescribed before imaging in 28 ; and investigation of the urinary tract was delayed in 33 . The severity of scarring was significantly related to delay in diagnosis ( X2 for trend 7.43 , P=0.01).Four children of mothers known to have reflux nephropathy were not investigated until they developed urinary tract infection . Conclusions : Efforts to reduce the incidence and severity of renal scarring should be directed towards rapid diagnosis and effective early management of urinary tract infection in infancy and childhood . Stolings and offspring of known patients with severe reflux nephropathy should be investigated for reflux PURPOSE We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grade s III and IV , and related improved dilating reflux , renal damage and recurrent urinary tract infection to dysfunction . MATERIAL S AND METHODS A total of 203 children between ages 1 to less than 2 years with reflux grade s III and IV were recruited into this open , r and omized , controlled , multicenter study . Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup . Lower urinary tract function was investigated by noninvasive methods , at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured question naire and post-void residual flow measurement in 161 . RESULTS At study entry 20 % of patients had lower urinary tract dysfunction , characterized by high bladder capacity and increased post-void residual urine . At 2 years there was dysfunction in 34 % of patients . Subdivision into groups characteristic of children after toilet training revealed that 9 % had isolated overactive bladder and 24 % had voiding phase dysfunction . There was a negative correlation between dysfunction at 2 years and improved dilating reflux ( p = 0.002 ) . Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years ( p = 0.001 ) . Recurrent urinary tract infections were seen in 33 % of children with and in 20 % without dysfunction ( p = 0.084 ) . CONCLUSIONS After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction , mainly voiding phase problems . Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome Between 1982 and 1986 , 96 children with non-obstructive vesicoureteric reflux were included in a prospect i ve study . Three patients withdrew from the study and results are therefore presented on 93 children with 135 refluxing ureters who were followed up for at least 5 years . Initially , all children with reflux grade III or less received antibiotic treatment only . Those with reflux grade IV were r and omised to antibiotic treatment alone versus surgery plus antibiotic treatment ; the primary treatment of reflux grade V was reimplantation . In 85 ureters treated by antibiotics only , reflux disappeared in 64 cases and was reduced in 12 . In 50 ureters treated by reimplantation , reflux was cured in 46 cases and no severe ureteric obstruction was seen . Conservative management of reflux grade IV was less successful than surgery . The results of conservative , non-surgical treatment of reflux grade s I-III were satisfactory , but for grade s IV and V surgery should be the treatment of choice if detrusor instability has been excluded PURPOSE We compared the long-term functional results following two different reflux prevention techniques in orthotopic ileal bladder substitution in a prospect i ve controlled r and omized study . METHODS The study included 60 patients for whom orthotopic bladder replacement was indicated . The treated patients were prospect ively r and omized into two groups : group I ( 30 patients ) underwent ileal W neobladder with serous lined extramural tunnel and group II ( 30 patients ) received hemi-Kock pouch with intussuscepted nipple valve . Laboratory evaluation included estimation of serum creatinine while radiological studies included IVU and voiding studies . Urodynamic evaluation was an integral part of our investigation . RESULTS Patients and tumor characteristics were comparable between both groups . No operative or postoperative mortality were observed in either . Early complications were encountered in 5 ( 16.7 % ) and 4 ( 13.3 % ) patients in the two treated groups respectively ( p=0.72 ) and most were treated conservatively . Twenty patients in group I and 19 in group II were evaluable . The mean follow up was 73.9+/-6.6 and 72.9+/-5.6 months in the treated groups respectively . Day and night time continence was comparable between both groups . Ascending studies demonstrated reflux in 3 ( 7.7 % ) of the reimplanted units in group I versus 2 ( 5.3 % ) in group II ( p=0.81 ) ; IVU showed uretero-ileal anastomotic strictures in 2 renal units with both the serous lined extramural tunnel ( 5.1 % ) and the ileal nipple valve ( 5.3 % ) techniques ( p=0.98 ) . One patient in group I had pouch stone compared with 5 in group II ( p=0.08 ) . Urodynamic characteristics were also comparable in both groups . CONCLUSION The study provided evidence that the long-term functional results following serous lined extramural tunnel are as equal as the nipple valve . Furthermore , it spares the use of extra-bowel length , does not need staples and allows retro grade endoscopic procedures OBJECTIVES . Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications . Antimicrobial prophylaxis has been used to reduce the risk for recurrence . We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection . METHODS . The study was a controlled , r and omized , open-label , 2-armed , noninferiority trial comparing no prophylaxis with prophylaxis ( co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day ) for 12 months . A total of 338 children who were aged 2 months to < 7 years and had a first episode of febrile urinary tract infection were enrolled : 309 with a confirmed pyelonephritis on a technetium 99 m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux . The primary end point was recurrence rate of febrile urinary tract infections during 12 months . Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99 m dimercaptosuccinic acid scan after 12 months . RESULTS . Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis : 12 ( 9.45 % ) of 127 vs 15 ( 7.11 % ) of 211 . In the subgroup of children with reflux , the recurrence of febrile urinary tract infections was 9 ( 19.6 % ) of 46 on no prophylaxis and 10 ( 12.1 % ) of 82 on prophylaxis . No significant difference was found in the secondary outcome : 2 ( 1.9 % ) of 108 on no prophylaxis versus 2 ( 1.1 % ) of 187 on prophylaxis . Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections . Whereas increasing age was protective , use of no prophylaxis was not a risk factor . CONCLUSIONS . For children with or without primary nonsevere reflux , prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode |
12,536 | 18,254,082 | There were no data to indicate that post operative anticoagulation , with or without the use of mechanical devices , can safely reduce the incidence of DVT after aortic surgery .
Neither study reported a significant effect of anticoagulants on the incidence of PE or related mortality .
The incidence of minor bleeding events was also slightly higher with anticoagulants .
AUTHORS ' CONCLUSIONS There is not enough evidence to make a definitive conclusion about the use of anticoagulant drugs ( with or without mechanical devices ) for DVT prophylaxis in patients undergoing abdominal aortic surgery | BACKGROUND Deep vein thrombosis ( DVT ) is one of the most common , preventable complications of surgery .
Although the relationship between surgery and DVT is well established in general surgical operations and most other subspecialties , the same can not be said about arterial surgery .
Deep vein thrombosis is believed to be less common in aortic surgery where its management is rather controversial with a reported incidence of DVT from 2 % to 18%.Intra-operative heparin is believed to provide protection during the period when DVT is most likely to develop .
However , the practice of using intra-operative heparin could increase the risk of haemorrhagic complications if further heparin is used during the recovery period .
This can significantly limit the use of such prophylactic measures especially with the low perceived risk of venous thromboembolism ( DVT or pulmonary embolism ( PE ) ) following abdominal aortic surgery .
However , vascular patients are usually older , with more co-morbidity and are subject to prolonged immobility , all of which increase the likelihood of developing venous thromboembolism .
OBJECTIVES To determine the efficacy of anticoagulant prophylaxis ( with or without mechanical devices ) in patients undergoing surgery for abdominal aortic aneurysm . | Central haemodynamics and blood gases were measured in 26 patients undergoing elective aortic surgery for atherosclerotic or aneurysmal disease . Recordings were made at seven defined time points , starting before anaesthesia and ending 30 min after declamping of the aorta . The patients were r and omly divided into two groups , one receiving heparin at an early stage and the other at a late stage of the operative procedure . A declamping shock phenomenon could be prevented by thorough blood and fluid replacement . After removal of the aortic clamp the cardiac output increased , except in a few patients who were considered preoperatively to be poor risks . A significant decrease in arterial oxygen tension and increase in pulmonary artery and pulmonary capillary wedge pressures occurred in patients receiving heparin at a later stage . The effect of heparin points to possible intravascular coagulation and pulmonary microembolism during the operation A series of 400 consecutive patients subjected to reconstructive arterial surgery were r and omly allocated into four equal groups in order to study the effect of dipyridamole and acetylsalicylic acid ( ASA ) in the prevention of deep venous thrombosis and pulmonary embolism . There were 11 drop-outs . In the dipyridamole-ASA group there were no thrombotic complications while in the control group without antithrombotic therapy five cases of deep venous thrombosis and two cases of fatal pulmonary embolism were encountered ( p < 0.05 ) . In the groups receiving either dipyridamole or ASA alone two and four cases of deep venous thrombosis , respectively , were found . It is concluded that treatment with dipyridamole and ASA combined is useful in preventing postoperative thrombotic complication after peripheral vascular reconstructive surgery Forty-four patients undergoing abdominal aortic surgery and twenty-eight patients undergoing carotid surgery were r and omly treated with different anticoagulant regimens . During surgery , an unfractionated heparin ( UFH ) intravenous bolus of 50 IU/kg was compared with a low molecular weight heparin ( LMWH ) bolus of either 120 IU/kg , 80 IU/kg , 40 IU/kg or 20 IU/kg . Six hours after surgery and for 48 hours , an UFH infusion was compared with an LMWH infusion of either 10,000 IU/day or 6,000 IU/day and then , a single LMWH subcutaneous injection of 3,075 IU was administered . Heparin activity was measured by factor Xa inhibitor and by prolongation of APTT which were studied 15 , 30 and 60 minutes after cross-clamping , at the end of surgery and six hours later , and on days 1 , 2 , 3 and 6 . After a descriptive analysis of clinical and pharmacokinetic profiles of each regimen , optimal LMWH treatment is proposed In a r and omised double-blind controlled trial 24 patients undergoing elective aortic bifurcation graft surgery received subcutaneous calcium heparin ( 2,500 u pre-operatively then 5,000 u 12-hourly for 7 days ) and 25 control patients received saline injections . All patients received a routine dose of intravenous sodium heparin intra-operatively . The trial was terminated because of excess bleeding complications in patients receiving subcutaneous heparin ( 8 vs. 1 , p less than 0.05 ) . Deep vein thrombosis occurred in 6 control patients and 2 patients on heparin ( p less than 0.05 ) . In this group of patients undergoing major vascular surgery the risk of bleeding due to heparin outweighed the potential benefit of thrombotic prophylaxis Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood . The objective of this investigation was to assess the effectiveness of three methods of heparin administration . Heparin sulfate ( 75 IU/kg ) administered to patients undergoing aortoiliac surgery was r and omised to one of three methods : Group I ( n = 9 ) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping ; Group II ( n = 9 ) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping ; and Group III ( n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping . Blood sample s were analysed for anticoagulant activity from both the upper and lower extremities at 5 , 15 , 30 , 60 , and 120 minutes after heparin administration . Anticoagulation , as measured by aPTT , antifactor Xa levels , and ACT , was achieved in all three groups by 5 minutes , but initially with lower heparin activity ( measured as antifactor Xa ) in the upper extremity ( Group II ) and lower extremity ( Group III ) , respectively . These differences were also evident in ACT and aPTT determinations . Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation ( anti-factor Xa approximately 1 U/ml ) in both upper and lower extremities after 5 minutes . With regional administration , rapid heparin redistribution occurs , but it takes longer to achieve the same level of anticoagulation distant from the site of administration . Nevertheless , from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation External pneumatic compression ( EPC ) devices prevent lower extremity deep venous thrombosis ( DVT ) by reducing stasis . There is a widely held belief that they also enhance endogenous fibrinolysis ; however , recent studies of tissue plasminogen activator ( the primary activator of fibrinolysis ) and plasminogen activator inhibitor-1 ( the primary inhibitor of fibrinolysis ) failed to confirm this . The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator ( uPA ) , a second activator of fibrinolysis . This was a prospect i ve trial in which 44 subjects who underwent major abdominal surgery were r and omized to receive unfractionated heparin injections , thigh-length sequential EPC devices , or both for DVT prophylaxis . Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge . Venous blood sample s were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels . Sample s were collected the day before surgery , after induction of anesthesia but before surgical incision , and on postoperative days 1 , 3 , and 5 . uPA levels ( ng/mL ) were measured with an enzyme-linked immunoassay . Baseline uPA levels ( 0.41 to 0.56 ng/mL ; P > .05 , analysis of variance with repeated measures ) were similar among the three groups . uPA levels did not change after surgery in systemic or regional blood sample s in any group . There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point ( P > .05 , analysis of variance with repeated measures ) . Enhancement of fibrinolysis with EPC devices remains unproven ; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis The risk of Deep Venous Thrombosis ( DVT ) in the immediate postoperative period varies from 0.8 to 96 % of cases depending on major or minor operations and on age of patients . We have employed 8,000 I.U. AXa/daily of LMW-Heparin injected subcutaneously from one day preoperatively and prolonged for 8 days after surgical procedures in 40 patients operated upon by an aorto-femoral bypass in 25 cases , a femoro-popliteal below the knee in 8 and an extra-anatomical bypass in 7 . The onset of DVP in the lower limbs was investigated by clinical examination , venous Doppler pressure evaluation , waveform analysis and echotomography and the 125I-Fibrinogen uptake test . There was no intraoperative increased bleeding and the preclotting of the prosthetic grafts was inaffected . A DVT was detected during the second postoperative day , by means of the 125I-Fibrinogen test in the calf of only one patient ( 1/40 - 2.5 % ) , su bmi tted to an aorto-bifemoral bypass , in whom the clinical pattern and ultrasound investigations were negative . The single daily subcutaneous administration has never caused side effects in the site of injection and it seems a real improvement in the heparin treatment . These results emphasize the advantage of the use of LMW-Heparins in patients su bmi tted to arterial surgical reconstructions of the lower limbs for the prevention of the DVT The incidence of postoperative deep vein thrombosis ( PDVT ) after aortic surgery and lower limb revascularisation has not been assessed by a large prospect i ve study . In a prospect i ve r and omised trial the effect of a low-molecular-weight heparin fragment , Enoxaparin ( ENX ) 4200 anti factor Xa IU once daily was compared to that of unfractionated heparin ( UFH ) 7500 IU twice daily . Two hundred and thirty-three consecutive patients were classified into three groups , aortic or aortoiliac and aneurysmectomy ( n = 75 ) , aorto-femoral bypass for atherosclerotic disease ( n = 71 ) , and femoropopliteal or femorodistal bypass ( n = 87 ) . Patients were analysed for development of deep vein thrombosis by Duplex scanning and , if positive , by venography between the seventh and tenth postoperative day . PDVT was present in 10 patients in the ENX group and in four patients in the UFH group ( 8.2 and 3.6 % respectively , NS ) . The incidence of PDVT was 8 % after aortic or aortoiliac aneurysmectomy , 7 % after aortofemoral revascularisation , and 3.4 % after femoropopliteal or femorodistal bypass . The overall incidence of PDVT after aortic surgery was 7.5 % ( 95 % CI 5.4 - 9.7 ) . There was no pulmonary embolism . Intra-operative blood loss and postoperative bleeding events did not differ significantly between the ENX and UFH groups . After 1 month follow-up , no clinical event or death could be related to PDVT or pulmonary embolism . In conclusion , in vascular surgery ENX is as safe and effective in the prevention of PDVT as is UFH OBJECTIVES The primary aim of this prospect i ve multi-centre study involving patients undergoing elective abdominal aortic aneurysm ( AAA ) surgery was to investigate the relationship between intraoperative intravenous heparinisation , blood loss during surgery and thrombotic complications . METHODS Two hundred and eighty-four patients were r and omised to receive intravenous heparin ( n = 145 ) or no heparin ( n = 139 ) . Groups were evenly matched for age , sex , weight , aneurysm size , haemoglobin concentration , platelet counts and distal occlusive disease measured by ankle/brachial systolic pressure . RESULTS There were no statistically significant differences in blood loss ( median 1400 ml vs. 1500 ml ; z = 0.02 , p = 0.98 , 95 % C.I. = -200 to 200 ) , blood transfused ( 4.0 units vs. 4.0 units ; z = 1.09 , p = 0.28 , 95 % C.I. = -1 to 0 ) or distal thrombosis between the two groups . However , analysis of the clinical outcome revealed that 5.7 % of the non-heparin group but only 1.4 % of the heparinised patients suffered a fatal perioperative myocardial infa rct ion ( MI ) ; p < 0.05 . All MI , including non fatal events , affected 8.5 % and 2 % respectively ( p = 0.02 ) . CONCLUSIONS Heparin does not increase blood loss or the need for blood transfusion during surgery . Heparin is not necessary to prevent distal thrombosis when the aorta is cross clamped . The results of the study are consistent with the known mechanisms leading to intraoperative MI and strategies for its prevention . Intravenous heparin , given before aortic cross clamping , is an important prophylaxic against perioperative MI in relation to AAA surgery Elective surgery of abdominal aortic aneurysm ( AAA ) sometimes leads to excessive bleeding and disseminated intravascular coagulation ( DIC ) , even in patients with normal preoperative coagulation parameters . Coagulation screen , performed routinely before surgery is of limited value in the assessment of compensated activation of the haemostatic system . In this study , we used a number of additional tests ( D-dimer , prothrombin fragment 1 + 2 , antithrombin , and activation of fibrinolysis in the platelet poor plasma ) for the diagnosis of compensated activation of the haemostatic system in AAA- patients . D-dimer and marker of thrombin generation ( prothrombin fragment 1 + 2 ) positively correlated with each other ( r = 0.768 , P < 0.001 ) . Out of 71 AAA patients , 15 patients had normal global coagulation times , but those with a D- dimer concentration above 3000 ng/ml were selected for preoperative low molecular weight heparin ( LMWH ) treatment . Administration of LMWH diminished coagulation abnormalities ( D-dimer and prothrombin fragment 1 + 2 decreased significantly ) and result ed in the increase of platelet number and fibrinogen concentration , indicating their previous consumption . Despite differences in aneurysm diameters between the groups of 15 LMWH treated patients ( mean 70.9 + /- 16 mm ) and the reference group of 20 untreated AAA patients ( mean 52.3 + /- 8.0 mm ) , intraoperative parameters ( operation time , blood loss and transfusion dem and s ) were similar This prospect i ve study evaluates , for the first time , the efficacy of heparinisation with low molecular weight heparin ( LMWH ) in aortic surgery and identifies the most effective route of administration for heparin . Sixteen patients undergoing abdominal aortic grafting for aneurysmal and occlusive disease were studied . They were r and omised to receive 10,000 anti Xa units of LMWH either intravenously or directly into the aorta before or after aortic cross-clamping . Serial venous blood sample s and a paired arterial sample from the superficial femoral artery were taken for the estimation of systemic and lower limb heparin activity . All three methods of administration gave therapeutic levels of heparin in the systemic and lower limb circulation . Intravenous and aortic administration before clamping result ed in significantly higher systemic levels when compared with aortic injection after clamping ( p less than 0.05 Mann-Whitney U test ) . Intra-aortic administration result ed in a significantly higher heparin activity in the lower limb when compared with the intravenous route ( p less than 0.05 ) . No patient developed distal thrombosis . This study demonstrates that the most effective way of giving heparin in aortic surgery is by direct injection into the aorta . Administration of LMWH after cross-clamping results in less systemic activity which may help to reduce any haemorrhagic side effects OBJECTIVE This study was undertaken to evaluate the effect of low molecular weight heparin ( LMWH ) compared with unfractionated heparin ( UFH ) on the rate of occlusion and bleeding during peripheral vascular surgery . METHODS The study was an open label , prospect i ve , r and omized trial , carried out by 20 Swedish surgical and vascular surgical departments that report to the Swedish Vascular Registry ( SWEDVASC ) . Study subjects included patients undergoing peripheral vascular procedures , except carotid surgery . Of the 849 patients included , 817 were followed up to 30 days . LMWH ( 40 mg of enoxaparin ) or UFH ( 5000 IU heparin ) was given intravenously immediately before clamping . The same formulation in diluted form was used for vascular rinsing . Main outcome measures included patent reconstruction at day 1 , perioperative blood loss , and the percentage of patients requiring protamin . Further , 30-day data for mortality , repeat operation , and recurrent occlusion are reported . RESULTS The mortality rate at 30 days was 2.7 % , with no difference between groups . The patency rate at 1 day was 91.2 % to 98.4 % , depending on diagnosis and type of reconstruction . No difference was recorded between study groups ( 0.6 < P < 1.0 ) . At 30 days the patency rate was 83.1 % to 100 % ( 0.2 < P < .9 ) . Median blood loss was 350 mL ( interquartile range [ IQR ] , 200 - 800 mL ) in the LMWH group and 425 mL ( IQR , 200 - 900 mL ) in the UFH group ( P = .02 ) . Protamin was given to significantly fewer patients in the LMWH group ( P = .001 ) . LMWH was comparable to UFH during peripheral vascular reconstruction in terms of 1-day and 30-day graft patency , operative blood loss , and hemorrhagic complications . Protamine was required less often after LMWH . In this r and omized trial LMWH was as effective as UFH in preventing thrombosis without excess bleeding or hemorrhagic complications INTRODUCTION External pneumatic compression devices ( EPC ) prevent deep venous thrombosis ( DVT ) by reducing lower extremity venous stasis . Early studies suggested they also enhance fibrinolytic activity ; however , in a recent study , EPC had no effect on systemic fibrinolysis in patients undergoing abdominal surgery . The hypothesis of this study was that EPCs enhance regional fibrinolysis in these subjects . METHODS Forty-five patients ( 44 male , one female ; mean age , 67 years ) undergoing major abdominal surgery ( 35 bowel procedures , 10 aortic reconstructions ) were prospect ively r and omized to one of three groups for DVT prophylaxis : subcutaneous heparin injections ( HEP ) , thigh-length sequential EPC devices ( EPC ) , or both ( HEP+EPC ) . Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or patient discharge . Venous blood sample s were collected from the common femoral vein for measurement of regional fibrinolysis after induction of anesthesia but before initiation of prophylaxis , and on postoperative days 1 , 3 , and 5 . A baseline sample was collected the day before surgery . Fibrinolysis was quantified with measurement of the activities of tissue plasminogen activator ( tPA ; the activator of fibrinolysis ) and its inhibitor plasminogen activator inhibitor-1 ( PAI-1 ) with amidolytic technique . RESULTS tPA activity in all groups was normal at baseline ; baseline PAI-1 activity was elevated . Within each prophylaxis group , no significant changes occurred in either tPA or PAI-1 activities after induction of anesthesia or after surgery compared with before surgery ( P > .05 , analysis of variance with repeated measures ) . No changes occurred between postoperative sample s and after anesthesia within each group . No significant enhancement of fibrinolysis , manifested as either increased tPA activity or decreased PAI-1 activity , occurred in either EPC group compared with the HEP group at any time point ( P > .05 , analysis of variance with repeated measures ) . No differences were noted when surgery was performed for malignant disease versus nonmalignant disease . CONCLUSION In this study , enhanced regional fibrinolysis in the lower extremities could not be detected with the use of EPCs , as measured with tPA and PAI-1 activity in common femoral venous blood sample s. EPC devices do not appear to prevent DVT with fibrinolytic enhancement ; effective and safe prophylaxis is provided only when the devices are used in a manner that reduces lower extremity venous stasis OBJECTIVES To study the incidence of postoperative deep venous thrombosis ( DVT ) in patients undergoing elective aortic reconstruction and to determine if aggressive DVT prophylaxis would reduce the incidence of DVT in these patients . DESIGN R and omized , prospect i ve trial . SETTING University hospital and Veterans Affairs hospital . PATIENTS One hundred patients undergoing aortic reconstruction for aneurysmal or occlusive disease r and omized to receive DVT prophylaxis ( treatment group ) or no prophylaxis ( control group ) . Exclusion criteria included a history of DVT , long-term anticoagulant use , or a malignant neoplasm . During the study period , 12 patients were ineligible for follow-up . Ninety-eight patients completed the trial , including 50 patients in the treatment group and 48 patients in the control group . Two patients in the control group died postoperatively of unrelated causes . INTERVENTION Patients in the treatment group received DVT prophylaxis using a combination of low-dose heparin sodium therapy ( 5000 U every 12 hours ) and calf-length intermittent mechanical compression devices . Control patients received no DVT prophylaxis . MAIN OUTCOME MEASURES The occurrence of acute lower extremity DVT diagnosed by interval venous duplex ultrasound scan surveillance performed on postoperative days 1 , 3 , and 7 . RESULTS The overall incidence of proximal DVT in this study was 2 % . One case of DVT occurred in the treatment group , and the other one occurred in the control group . There was no statistically significant difference ( P = .99 ) in the incidence of DVT between the 2 groups . One patients in the control group had a nonfatal pulmonary embolus ( 1 % of the patients overall ) . CONCLUSIONS The incidence of proximal DVT in patients undergoing elective aortic reconstruction is low compared with patients undergoing other major intraabdominal general surgical procedures . The use of aggressive DVT prophylaxis did not reduce the risk of postoperative proximal DVT in this study . The selective use of DVT prophylaxis in patients undergoing elective aortic surgery should be based on associated concomitant or evolving risk factors A prospect i ve comparison of I125 Fibrinogen uptake testing ( FUT ) and Impedance Plethysmography ( IPG ) was made in 22 patients ( 44 limbs ) following aortic reconstructive surgery to determine the incidence of postoperative deep venous thrombosis ( DVT ) . Normal FUT was obtained in 34 limbs , whereas ten limbs had abnormal uptake over the calf area consistent with venous thrombosis . Nine of the ten limbs with a positive scan underwent phlebography . All venograms and IPG readings obtained were normal . No evidence of DVT following aortic surgery was noted in this study . A high incidence of false positive FUT was evident . IPG is noninvasive , reliable and relatively inexpensive and is therefore recommended if prospect i ve evaluation for DVT in patients undergoing aortic surgery is desired One hundred patients undergoing elective aortic surgery were scanned prospect ively for development of deep venous thrombosis ( DVT ) . The incidence of DVT in this population was 13 % . Eleven patients showed only calf vein thrombosis on venography , whereas two had occlusive iliofemoral thrombus . The correlation between venous Doppler ultrasound and venography was 80 % . More importantly , Doppler examination correctly identified both patients with occlusive thrombus . Fibrinogen scanning was associated with a false-positive rate of 31 % . Only one patient suffered a nonfatal pulmonary embolus . Fibrinogen scanning has an unacceptably high false-positive rate ; however , Doppler ultrasound will identify significant occlusive thrombus without a high false-positive rate . The low incidence of pulmonary emboli does not warrant such definitive measures as prophylactic vena caval interruption A prospect i ve study to determine the incidence of postoperative DVT in patients undergoing vascular surgical operations was carried out . Twenty-eight patients who underwent vascular surgical procedures were studied . Five thous and units of intravenously given heparin was administered intraoperatively to each patient , with no other prophylaxis against DVT being used . DVT was detected by means of radioactive fibrinogen uptake studies . Two patients had DVT develop , an incidence of 7.1 per cent which is lower than the 30 to 40 per cent that might be expected in patients of the same age undergoing general surgical procedures . Both DVT developed in the late postoperative period . It is suggested that the single dosage of heparin given to these patients protects them against the development of DVT and is responsible for the low incidence of DVT observed in these patients Periprocedural and postprocedural anticoagulation during arterial reconstructive surgery ( ARS ) with intravenous heparin is st and ard of care . The general use and correct dosage of low-molecular-weight heparin , however , are still under debate . A prospect i ve , r and omized , double-blind trial was performed with a parallel group comparison of four dose regimen of a low-molecular-weight heparin , reviparin sodium , in patients undergoing major ARS . Sixty-five patients were r and omly allocated to receive twice-daily subcutaneous injections of reviparin , 3500 ( group A , n=17 ) , 4200 ( group B , n= 16 ) , 5950 ( group C , n= 16 ) , and 7000 ( group D , n= 16 ) anti-Xa IU per day . Patients were eligible for the trial if they had angiographically proven peripheral arterial obstructive disease with a planned arterial reconstruction of the infrarenal aorta , iliaca artery , or femoralis artery . Fifty-nine patients completed the trial . The goal was to determine the optimal dose of the low-molecular-weight heparin to achieve a minimum of early vascular events ( less than 12 % ) with a minimum of major bleeding events ( less than 10 % ) during a shortterm follow-up of up to 8 postoperative days . There was no reocclusion in the entire population . Patients r and omized into the two lower dose groups ( A and B ) , however , experienced a relatively high incidence of restenosis , whereas patients enrolled in group D , receiving the highest dose of reviparin , experienced an unacceptably high rate of bleeding events ( all bleeds , 43 % ; major bleeding , 14.3 % ) . Thus , the optimal dose of reviparin sodium to be administered in patients undergoing major ARS is half the therapeutic dose:5950 to 6300 anti Xa IU ( 75 - 85 anti Xa IU/kg body weight per day ) . Patients included in group C had no major bleeding event ( 95 % confidence interval , 0 % to 6.6 % ) , a significant improvement of the doppler anklebrachial systolic pressure index ( difference of 0.46 ± 0.29 , P=.017 ) , and a higher rate of responders with regard to the puls status measured at the tibialis posterior arteries ( 66.7 % ) compared to groups A and B ( 46.7 % and 54.5 % , respectively , P=.086 ) . The efficacy and safety of this dosage regimen in comparison to st and ard of care should be further substantiated in larger trials OBJECTIVE The incidence of deep vein thrombosis ( DVT ) has been well documented in general and orthopaedic surgery but there have been few reports of the incidence of DVT following vascular surgery . Our aim was to perform a prospect i ve study of the incidence of DVT in patients managed on the Vascular Unit at our institution . EXPERIMENTAL DESIGN One hundred and forty two consecutive patients presenting for repair of abdominal aortic aneurysm , reconstruction of lower extremity arterial occlusive disease or amputation were studied . Venous duplex ultrasound examination was performed preoperatively and between day seven to 10 postoperatively . All patients received st and ard DVT prophylaxis of 5,000 units of unfractionated heparin subcutaneously three times daily and intraoperative sequential compression devices . RESULTS Fourteen patients ( 9.8 % ) were found to have postoperative DVT with one patient ( 0.7 % ) having a documented pulmonary embolism . The incidence of DVT following reconstructive surgery was 9.1 % and 14.3 % following amputation . CONCLUSIONS In patients having vascular reconstructive surgery and , in particular , amputation , there is still a moderate risk of DVT despite the application of st and ard prophylactic measures . There may be a role for newer modalities of prophylaxis such as low molecular weight heparin especially in the higher risk amputation group Ninety-two patients undergoing vascular surgery took part in a controlled clinical trial to study the effectiveness of a new low molecular weight ( LMW ) heparin for prevention of post-operative deep vein thrombosis . Forty-six patients were treated daily , for 7 days after operation , with a single subcutaneous injection of 15,000 Anti X-activated Factor Units of the new LMW heparin ; the remaining 46 patients were treated , for the same period , with 2 daily subcutaneous injections of 5,000 International Units of calcium heparin . Deep vein thrombosis detection was by the radioactive fibrinogen uptake test , performed each day during therapy in all patients . A very low incidence of sub- clinical deep vein thrombosis was observed ; in 3 ( 6.5 % ) patients in the LMW heparin group and in 4 ( 8.6 % ) patients of the calcium heparin group . The results of laboratory investigation showed that the antithrombotic activity ( inhibition of Factor Xa ) of the LMW preparation was significantly greater than that of calcium heparin , while activated partial thromboplastin time was greater in the calcium heparin group . The new preparation also showed better local tolerance , with less pain on subcutaneous injections OBJECTIVE The incidence of venous thromboembolism ( VT ) after aortic abdominal aneurysm ( AAA ) surgery is imprecisely reported . On one h and , thromboprophylaxis has improved , on the other h and , AAA patients have become older and /or present worse comorbidities . Herein , we prospect ively analyzed the incidence of VT in a continuous series of patients operated on for AAA repair and looked for predictive factors . MATERIAL S AND METHODS Between January 1 , 2005 , and December , 31 , 2006 , 193 consecutive patients ( 177 men and 16 women ) , mean age 73 ( range , 47 - 93 ) underwent elective AAA repair , 137 open ( 71 % ) and 56 endovascular ( 29 % ) , in our institution . Thromboprophylaxis consisted of thigh-length compression b and ages or stockings , early mobilization , and a daily subcutaneous injection of low-molecular-weight heparin ( enoxaparin 40 mg per day ) . Patients with renal insufficiency or aged over 80 were given unfractionated heparin ( 5000 IU twice a day ) . Heparin was started between day 1 and day 5 ( median = day 1 ) after surgery , according to the prescription of the surgeon . A bilateral lower limb duplex venous compression ultrasonography scan using 3 to 7.5 MHz transducers was systematic ally done before and after surgery in each patient . Two groups were considered : group 1 with postoperative VT ( n = 17 ) and group 2 without ( n = 176 ) . The 17 patients with VT were compared with 51 patients r and omly chosen among the 176 patients without VT . Different characteristics such as venous risk factors , preoperative antithrombotic treatment , anatomical features of the AAA , and perioperative data were studied . RESULTS Seventeen patients ( 8.1 % ) were diagnosed with postoperative VT ( 15 asymptomatic deep vein thrombosis [ DVT ] and 2 symptomatic pulmonary embolisms [ PE ] ) . VTE tended to be more frequent in open ( 10.2 % ) than endovascular ( 5.3 % ) repair ( P = .28 ) . Among perioperative data , delay to thromboprophylaxis was related to bleeding complication ( P = .05 ) and blood transfusion ( P = .02 ) , and tended to be longer in VT patients ( 1.7 + /- 1.4 vs 0.9 + /- 0.9 day ; P = .09 ) . CONCLUSION Despite systematic prevention with heparin , surgery for AAA repair induces a high incidence of postoperative VT . This series m and ates for vigilance about VT , with particular attention to the patients who received transfusion with fresh frozen plasma . Even though this series is one of the largest ever published on this topic , the rarity of the events calls for confirmation with a larger prospect i ve study |
12,537 | 27,155,783 | No differences between interventions were revealed by the network meta- analysis of the pain data .
Based on the available evidence , talc poudrage is a more effective pleurodesis method in MPE than a number of other frequently used methods , including tetracycline and bleomycin .
Based on the strength of the evidence from both direct and indirect comparisons of r and omised data of sclerosants administered at the bedside , there is no evidence to suggest large differences between the other highly effective methods ( talc slurry , mepacrine , iodine and C. parvum ) . | BACKGROUND Malignant pleural effusion ( MPE ) is a common problem for people with cancer as a result of malignant infiltration of the pleura .
It is usually associated with considerable breathlessness .
A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid including administration of a pleurodesis agent ( either via a chest tube or at thoracoscopy ) or indwelling pleural catheter insertion .
OBJECTIVES To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success .
Additionally , to quantify differences in patient-reported outcomes and adverse effects between management strategies . | Treatment of patients with malignant pleural effusions is mostly palliative . Tetracycline and bleomycin are the two most commonly used agents for the treatment of pleurodesis . In this study , the authors used a combination of the two drugs for this particular purpose Summary The current prospect i ve r and omized study was design ed to compare the effects of intracavitary ( i.c . ) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion . Between 1992 and 1995 , a total of 42 patients with malignant effusion were registered , and 41 patients were eligible for statistical analysis . The primary diseases of the eligible patients included 27 gastric , four colorectal , four pancreatic , three lung , two liver and one oesophageal cancers . The patients with malignant effusion were r and omly assigned into one of three i.c . therapeutic regimens : chemotherapy alone with weekly injection of anticancer agents ( ACAs : cisplatin , mitomycin-C , adriamycin , etc . ) ( Group A , n = 13 ) ; immunotherapy alone with weekly injection of streptococcal preparation OK-432 ( Group B , n = 14 ) ; or immunochemotherapy with ACAs and OK-432 ( Group C , n = 14 ) . The response of the effusion , patient survival and the kinetics of cytokines in the effusion were compared . There were no differences in the patients ’ background s. The side-effects of the regimens included pain , anorexia , fever , leucopenia and anaemia and there were no differences in their incidence among the three groups . One patient died after cisplatin ( CDDP ) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23 % of Group A cases , 36 % of Group B cases and 36 % of Group C cases . The malignant effusion did not disappear in any of the Group A cases ; however , the effusion disappeared in 29 % of Group B cases and 43 % of Group C cases ( P = 0.03 , Group A vs Group C ) . Furthermore , the 50 % survival period was 1.6 months for Group A , 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7 % for Group A , 6 % for Group B and 34 % for Group C , and the 1-year survival rate was 0 % , 0 % and 17 % respectively ( P = 0.048 , Group A vs Group C by the log-rank test ) . The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c . immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c . chemotherapy alone or immunotherapy alone The optimal strategy to achieve palliation of malignant pleural effusions ( MPEs ) is unknown . This multi-institutional , prospect i ve , r and omized trial compares 2 established methods for controlling symptomatic unilateral MPEs . Patients with unilateral MPEs were r and omized to either daily tunneled catheter drainage ( TCD ) or bedside talc pleurodesis ( TP ) . This trial is patterned after a previous r and omized trial that showed that bedside TP was equivalent to thoracoscopic TP ( CALGB 9334 ) . The primary end point of the current study was combined success : consistent/reliable drainage/pleurodesis , lung expansion , and 30-day survival . A secondary end point , survival with effusion control , was added retrospectively . This trial r and omized 57 patients who were similar in terms of age ( 62 years ) , active chemotherapy ( 28 % ) , and histologic diagnosis ( lung , 63 % ; breast , 12 % ; other/unknown cancers , 25 % ) to either bedside TP or TCD . Combined success was higher with TCD ( 62 % ) than with TP ( 46 % ; odds ratio , 5.0 ; P = .064 ) . Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores ( 8.7 vs. 5.9 ; P = .036 ) , especially in the subgroup with impaired expansion ( 9.1 vs. 4.6 ; P = .042 ) . Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP ( 82 % vs. 52 % , respectively ; P = .024 ) . In this prospect i ve r and omized trial , TCD achieved superior palliation of unilateral MPEs than TP , particularly in patients with trapped lungs Background : Iodopovidone is an alternative agent used to promote pleurodesis in patients with malignant pleural effusion ( MPE ) . However , safety is a concern , and many authors still reject its use . Objectives : Our main objective is to describe the occurrence of common and severe adverse events after pleurodesis with two different doses of iodopovidone in patients with MPE . Our secondary objective is to evaluate dose dependency , efficacy , quality of life , and systemic inflammation . Methods : We conducted a double-blind , r and omized clinical trial including patients with recurrent MPE . Patients underwent chest tube insertion and were r and omized into two groups according to the doses of iodopovidone : group 1 received 1 % iodopovidone , and group 2 received 2 % iodopovidone . During follow-up , adverse events , inflammatory markers , quality of life , and imaging exams were systematic ally evaluated and registered . Results : Sixty patients were analyzed ( 55 females , 5 males , median age 55.9 years ) . Overall , 227 adverse events possibly related to pleurodesis were registered , including 47 serious adverse events ( in 34 patients ) . Pleuritic pain and hypertensive peaks were the most frequently observed serious adverse events ( 11 and 10 episodes , respectively ) . Grade 3/4 metabolic events such as hyponatremia and an increase in alkaline phosphatase , AST and ALT levels were also common . C-reactive protein ( CRP ) levels increased substantially and peaked 48 h after pleurodesis . No difference was observed between groups with regard to adverse events , CRP levels , efficacy , or quality of life . Conclusions : Adverse events after iodopovidone pleurodesis in patients with MPE are common and similar in the two doses studied BACKGROUND Malignant pleural mesothelioma incidence continues to rise , with few available evidence -based therapeutic options . Results of previous non-r and omised studies suggested that video-assisted thoracoscopic partial pleurectomy ( VAT-PP ) might improve symptom control and survival . We aim ed to compare efficacy in terms of overall survival , and cost , of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma . METHODS We undertook an open-label , parallel-group , r and omised , controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion , recruited from 12 hospitals in the UK . Eligible patients were r and omly assigned ( 1:1 ) to either VAT-PP or talc pleurodesis by computer-generated r and om numbers , stratified by European Organisation for Research and Treatment of Cancer risk category ( high vs low ) . The primary outcome was overall survival at 1 year , analysed by intention to treat ( all patients r and omly assigned to a treatment group with a final diagnosis of mesothelioma ) . This trial is registered with Clinical Trials.gov , number NCT00821860 . FINDINGS Between Oct 24 , 2003 , and Jan 24 , 2012 , we r and omly assigned 196 patients , of whom 175 ( 88 assigned to talc pleurodesis , 87 assigned to VAT-PP ) had confirmed mesothelioma . Overall survival at 1 year was 52 % ( 95 % CI 41 - 62 ) in the VAT-PP group and 57 % ( 46 - 66 ) in the talc pleurodesis group ( hazard ratio 1·04 [ 95 % CI 0·76 - 1·42 ] ; p=0·81 ) . Surgical complications were significantly more common after VAT-PP than after talc pleurodesis , occurring in 24 ( 31 % ) of 78 patients who completed VAT-PP versus ten ( 14 % ) of 73 patients who completed talc pleurodesis ( p=0·019 ) , as were respiratory complications ( 19 [ 24 % ] vs 11 [ 15 % ] ; p=0·22 ) and air-leak beyond 10 days ( five [ 6 % ] vs one [ 1 % ] ; p=0·21 ) , although not significantly so . Median hospital stay was longer at 7 days ( IQR 5 - 11 ) in patients who received VAT-PP compared with 3 days ( 2 - 5 ) for those who received talc pleurodesis ( p<0·0001 ) . INTERPRETATION VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma , and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment . FUNDING BUPA Foundation In a controlled r and omized trial , 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc , to determine which agent produced the more effective pleurodesis . Of the 37 evaluable patients , control of the effusion was achieved in 9/17 ( 56 % ) of those treated with mustine and 18/20 ( 90 % ) of the talc group ( P > 0.025 ) . This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer Thirty two patients with malignant pleural effusion were r and omly allocated to treatment with intrapleural Corynebacterium parvum or tetracycline hydrochloride in an attempt to prevent symptomatic recurrence of pleural fluid . Success in preventing recurrence of fluid at one month , using up to 2 doses of each drug , was 14 of 16 cases for Corynebacterium parvum , 5 of 9 for tetracycline given via an intercostal needle , and 6 of 7 for tetracycline given through an intercostal tube . These difference were not statistically significant . Corynebacterium parvum was significantly more likely to produce pyrexia equal or greater than 38 degrees C ( P less than 0.001 ) and pain requiring analgesia ( P less than 0.05 ) than tetracycline hydrochloride . Corynebacterium parvum is a useful agent for the management of malignant pleural effusion , but is associated with more side effects than tetracycline Introduction Malignant pleural effusion can complicate most cancers . It causes breathlessness and requires hospitalisation for invasive pleural drainages . Malignant effusions often herald advanced cancers and limited prognosis . Minimising time spent in hospital is of high priority to patients and their families . Various treatment strategies exist for the management of malignant effusions , though there is no consensus governing the best choice . Talc pleurodesis is the conventional management but requires hospitalisation ( and substantial healthcare re sources ) , can cause significant side effects , and has a suboptimal success rate . Indwelling pleural catheters ( IPCs ) allow ambulatory fluid drainage without hospitalisation , and are increasingly employed for management of malignant effusions . Previous studies have only investigated the length of hospital care immediately related to IPC insertion . Whether IPC management reduces time spent in hospital in the patients ’ remaining lifespan is unknown . A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital , reduce costs and save healthcare re sources . Methods and analysis The Australasian Malignant Pleural Effusion ( AMPLE ) trial is a multicentred , r and omised trial design ed to compare IPC with talc pleurodesis for the management of malignant pleural effusion . This study will r and omise 146 adults with malignant pleural effusions ( 1:1 ) to IPC management or talc slurry pleurodesis . The primary end point is the total number of days spent in hospital ( for any admissions ) from treatment procedure to death or end of study follow-up . Secondary end points include hospital days specific to pleural effusion management , adverse events , self-reported symptom and quality -of-life scores . Ethics and dissemination The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals . The trial results will be published in peer- review ed journals and presented at scientific conferences . Trial registration numbers Australia New Zeal and Clinical Trials Registry — ACTRN12611000567921 ; National Institutes of Health — NCT02045121 PURPOSE To compare bleomycin pleurodesis and immunotherapy with intrapleural interferon alfa-2b ( IFN ) in the palliation of malignant pleural effusions . PATIENTS AND METHODS One hundred sixty patients with rapidly recurrent malignant pleural effusion were r and omly assigned to intrapleural bleomycin ( 83 patients ) or IFN ( 77 patients ) . A 9-French intrapleural catheter was placed under sonographic guidance , and pleural effusion was completely drained before starting the treatment . Bleomycin 0.75 mg/kg was administered as a single dose . An additional dose was given if daily fluid output did not drop to less than 100 mL/d within 3 days . IFN 1 million units/10 kg was administered for six courses at 4-day intervals . Thirty-day and long-term responses were evaluated under the intention-to-treat principle . RESULTS Thirty-day response was 84.3 % in the bleomycin arm and 62.3 % in IFN arm ( P = .002 ) . Median time to progression was 93 days ( range , 12 to 395 days ) in bleomycin group , and 59 days ( range , 7 to 292 days ) in the IFN group ( P < .001 ) . Median survival was 96 days ( range , 15 to 395 ) and 85 days ( range , 16 to 292 ) in the bleomycin and IFN groups , respectively . Twenty-three patients received two doses of bleomycin , as their daily fluid output remained higher than 100 mL after the first dose . Thirteen of them had complete response , which lasted until death . CONCLUSION Intrapleural bleomycin is more effective than IFN and is a valid option for the palliative treatment of massive , rapidly recurrent malignant pleural effusions . The administration of a second dose of bleomycin to patients not responding to the first one can remarkably improve the overall outcome of the treatment Background Malignant pleural effusions continue to be a common problem in patients with metastatic disease , leading to a significant reduction in quality of life with progressive dyspnea , dry cough , chest pain and reduced physical activity . This study was conducted to compare the efficacy , safety , and outcome of Talc Powder Pleurodesis ( TPP ) with Povidone-iodine Pleurodesis ( PIP ) through a chest drain as a palliative preventive treatment of recurrent malignant pleural effusion . Methods A total of 39 neoplastic patients with recurrent malignant pleural effusion were enrolled in a prospect i ve r and omized trial . Twenty-one patients received Talc pleurodesis ( group A ) , and eighteen patients ( group B ) received Povidone-iodine pleurodesis . The continuous variables were expressed as mean values ± st and ard deviation ( SD ) and compared using the unpaired t-test . The discrete variables were expressed as percentage and compared using the chi-square test ( χ2 ) test . p-values of less than 0.05 were considered significant . Results Our study included 11 males and 28 females , the mean age was ( 71.0 ± 5.0 ) years for group A and ( 70.9 ± 5.1 ) years for group B ( non-significant ) . Post-procedure analgesic requirements were recorded in both groups . Four patients in each group had fever ( > 38 ° C ) within 48 hours of the procedure . Both groups achieved good symptomatic relief . There were no in-hospital deaths . The mean post-procedure hospital stay was ( 4.7 ± 1.2 ) days for group A and ( 4.2 ± 1.0 ) for group B ( non-significant ) . At follow-up recurrence of significant pleural effusion requiring intervention was noted in four and five patients in group A and group B , respectively ( non-significant difference ) . Conclusion Povidone-iodine pleurodesis can be considered as a good alternative to Talc pleurodesis for recurrent malignant pleural effusion . The drug is available , cost effective , safe and can be administered through an intercostal drain and repeated if necessary Twenty-one patients with proven recurrent malignant pleural effusions were r and omly allocated to treatment groups receiving either intrapleural Corynebacterium parvum in a dose of 7 mg or intrapleural mustine ( 20 mg ) . The design ated intrapleural therapy was repeated on one occasion if further pleural aspiration was required . Corynebacterium parvum ( nine patients ) proved superior to mustine ( 12 patients ) in suppressing the reaccumulation of pleural fluid , and was associated with only minimal side-effects of fever and nausea in two patients . Mustine caused marked nausea and vomiting in almost all patients . Three of the four patients who were deemed " failures " after mustine therapy had complete suppression of pleural fluid reaccumulation after a single dose of C parvum , the survival of the fourth being too short to assess a response adequately . There were no failures in the C parvum treated group . Corynebacterium parvum appears to be an effective , well-tolerated agent in the management of recurrent pleural effusions . The relative contribution of its potent immunological stimulant effect to its mode of action remains uncertain Malignant pleural effusions are commonly managed with tube thoracostomy drainage followed by chemical pleurodesis . Both tetracycline and bleomycin have been shown to be effective for intrapleural instillation , although neither agent has definitively proved advantages over the other . The aim of the present study was to compare these two agents in terms of response rate and toxicity profile . A prospect i ve , r and omized trial was carried out in a single centre . Between May 1993 and January 1996 , 62 evaluable patients with proved malignant pleural effusion were allocated to receive either intrapleural tetracycline ( 1.5 g ) or bleomycin ( 60 mg ) after the same drainage procedure . Demographic , clinical and fluid parameter data were comparable in both groups . Response was evaluated at 1 , 3 and 6 months after pleurodesis . Mean survival and time to relapse did not differ between the two groups . No statistically significant differences were found in terms of efficacy at each evaluation time . Overall , 16 ( 52 % ) and 20 ( 64 % ) patients had a recurrence of pleural effusion during follow-up in the tetracycline and bleomycin arms , respectively . Fever was most common in bleomycin-treated patients ( p=0.024 ) while pain was most frequent in the tetracycline arm ( nonsignificant ) . Since no study agent was superior to the other in this trial , we suggest that economic costs , drug availability and medical skill should be considered in the choice of a sclerosing agent Importance Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis . Objective To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion . Design , Setting , and Participants This open-label , r and omized clinical trial included participants recruited from 9 centers in Australia , New Zeal and , Singapore , and Hong Kong between July 2012 and October 2014 ; they were followed up for 12 months ( study end date : October 16 , 2015 ) . Patients ( n = 146 ) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included . Interventions Participants were r and omized ( 1:1 ) to indwelling pleural catheter ( n = 74 ) or talc pleurodesis ( n = 72 ) , minimized by malignancy ( mesothelioma vs others ) and trapped lung ( vs not ) , and stratified by region ( Australia vs Asia ) . Main Outcomes and Measures The primary end point was the total number of days spent in hospital from procedure to death or to 12 months . Secondary outcomes included further pleural interventions , patient-reported breathlessness , quality -of-life measures , and adverse events . Results Among the 146 patients who were r and omized ( median age , 70.5 years ; 56.2 % male ) , 2 withdrew before receiving the r and omized intervention and were excluded . The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group ( median , 10.0 [ interquartile range [ IQR ] , 3 - 17 ] vs 12.0 [ IQR , 7 - 21 ] days ; P = .03 ; Hodges-Lehmann estimate of difference , 2.92 days ; 95 % CI , 0.43 - 5.84 ) . The reduction was mainly in effusion-related hospitalization days ( median , 1.0 [ IQR , 1 - 3 ] day with the indwelling pleural catheter vs 4.0 ( IQR , 3 - 6 ) days with pleurodesis ; P < .001 ; Hodges-Lehmann estimate , 2.06 days ; 95 % CI , 1.53 - 2.58 ) . Fewer patients r and omized to indwelling pleural catheter required further ipsilateral invasive pleural drainages ( 4.1 % vs 22.5 % ; difference , 18.4 % ; 95 % CI , 7.7%-29.2 % ) . There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis . Adverse events were seen in 22 patients in the indwelling pleural catheter group ( 30 events ) and 13 patients in the pleurodesis group ( 18 events ) . Conclusions and Relevance Among patients with malignant pleural effusion , treatment with an indwelling pleural catheter vs talc pleurodesis result ed in fewer hospitalization days from treatment to death , but the magnitude of the difference is of uncertain clinical importance . These findings may help inform patient choice of management for pleural effusion . Trial Registration anzctr.org.au Identifier : Fifty-eight patients with malignant pleural effusions were entered into a prospect ively r and omized clinical trial comparing the efficacy of a local instillation of bleomycin or corynebacterium parvum ( C. parvum ) in controlling fluid reaccumulation after simple needle aspiration ( thoracentesis ) . The response was assessed at 30 days by chest X-ray and clinical examination . There were 44 evaluable patients ; 18 of 25 ( 72 % ) of those receiving bleomycin and 9/19 ( 47 % ) of those who had C. parvum gained a complete or partial response . This difference in response rate was not statistically significant ( p = 0.13 ) . The majority of patients had an effusion from a primary breast carcinoma and the response in this group was almost statistically significant ( p = 0.06 ) with 74 % of bleomycin patients and 43 % of C. parvum patients responding . Fever following instillation was more common with C. parvum ( 53 % of patients compared with 24 % after bleomycin , p = 0.02 ) , whereas nausea was more common after bleomycin ( 28 % vs. 10.5 % , p = 0.16 ) . Local chest pain after aspiration occurred in 52 % of the bleomycin group and 47 % of the C. parvum subjects . There was no significant difference between the groups in age , sex , tumour type , presenting symptoms , volume of aspirate , systemic therapy or number of previous aspirations . Both of these agents appeared to be active in the control of malignant pleural effusions although the response rate was higher with bleomycin and overall , both have acceptable levels of toxicity IMPORTANCE For treatment of malignant pleural effusion , nonsteroidal anti-inflammatory drugs ( NSAIDs ) are avoided because they may reduce pleurodesis efficacy . Smaller chest tubes may be less painful than larger tubes , but efficacy in pleurodesis has not been proven . OBJECTIVE To assess the effect of chest tube size and analgesia ( NSAIDs vs opiates ) on pain and clinical efficacy related to pleurodesis in patients with malignant pleural effusion . DESIGN , SETTING , AND PARTICIPANTS A 2 × 2 factorial phase 3 r and omized clinical trial among 320 patients requiring pleurodesis in 16 UK hospitals from 2007 to 2013 . INTERVENTIONS Patients undergoing thoracoscopy ( n = 206 ; clinical decision if biopsy was required ) received a 24F chest tube and were r and omized to receive opiates ( n = 103 ) vs NSAIDs ( n = 103 ) , and those not undergoing thoracoscopy ( n = 114 ) were r and omized to 1 of 4 groups ( 24F chest tube and opioids [ n = 28 ] ; 24F chest tube and NSAIDs [ n = 29 ] ; 12F chest tube and opioids [ n = 29 ] ; or 12F chest tube and NSAIDs [ n = 28 ] ) . MAIN OUTCOMES AND MEASURES Pain while chest tube was in place ( 0- to 100-mm visual analog scale [ VAS ] 4 times/d ; superiority comparison ) and pleurodesis efficacy at 3 months ( failure defined as need for further pleural intervention ; noninferiority comparison ; margin , 15 % ) . RESULTS Pain scores in the opiate group ( n = 150 ) vs the NSAID group ( n = 144 ) were not significantly different ( mean VAS score , 23.8 mm vs 22.1 mm ; adjusted difference , -1.5 mm ; 95 % CI , -5.0 to 2.0 mm ; P = .40 ) , but the NSAID group required more rescue analgesia ( 26.3 % vs 38.1 % ; rate ratio , 2.1 ; 95 % CI , 1.3 - 3.4 ; P = .003 ) . Pleurodesis failure occurred in 30 patients ( 20 % ) in the opiate group and 33 ( 23 % ) in the NSAID group , meeting criteria for noninferiority ( difference , -3 % ; 1-sided 95 % CI , -10 % to ∞ ; P = .004 for noninferiority ) . Pain scores were lower among patients in the 12F chest tube group ( n = 54 ) vs the 24F group ( n = 56 ) ( mean VAS score , 22.0 mm vs 26.8 mm ; adjusted difference , -6.0 mm ; 95 % CI , -11.7 to -0.2 mm ; P = .04 ) and 12F chest tubes vs 24F chest tubes were associated with higher pleurodesis failure ( 30 % vs 24 % ) , failing to meet noninferiority criteria ( difference , -6 % ; 1-sided 95 % CI , -20 % to ∞ ; P = .14 for noninferiority ) . Complications during chest tube insertion occurred more commonly with 12F tubes ( 14 % vs 24 % ; odds ratio , 1.91 ; P = .20 ) . CONCLUSIONS AND RELEVANCE Use of NSAIDs vs opiates result ed in no significant difference in pain scores but was associated with more rescue medication . NSAID use result ed in noninferior rates of pleurodesis efficacy at 3 months . Placement of 12F chest tubes vs 24F chest tubes was associated with a statistically significant but clinical ly modest reduction in pain but failed to meet noninferiority criteria for pleurodesis efficacy . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N33288337 BACKGROUND Symptomatic malignant pleural effusion ( MPE ) occurs frequently in patients with metastatic cancer . The associated prognosis is poor and the success rate of talc pleurodesis ( TP ) is low . Indwelling pleural catheters ( IPCs ) are commonly inserted when TP has been unsuccessful . METHODS We compared talc pleurodesis with the use of an indwelling pleural catheter in patients with recurrent MPE in a multicenter r and omized controlled trial ( superiority design ) . The primary endpoint was improvement from baseline in Modified Borg Score ( MBS ) 6weeks after r and omized treatment . Secondary endpoints were hospitalization days , re- interventions , and adverse events . RESULTS Dyspnea improved significantly ( p<0.01 ) after either treatment , but the magnitude of this improvement did not differ significantly between arms ( median 3 and 1 for TP : IPC respectively in rest , p=0.16 , ( TP 13:IPC 16 ) and 3 and 1 during exercise , p=0.72 ( TP 13:IPC 17 ) ) . There was no difference in dyspnea during exercise between TP and IPC at week 6 following treatment , while at rest TP patients ( n=13 ) reported less dyspnea than IPC patients ( n=18 ) ( median 0 vs 1 , p=0.002 ) . Compared to TP , patients with an IPC had significantly less hospital days during r and omized treatment ( median : 0 vs 5 , p<0.0001 ) , and total hospitalizations for all causes ( median : 1.6 vs 1.0 , p=0.0035 ) . Fewer IPC patients underwent more than one re-intervention ( 7/45 vs 15/43 , p=0.09 ) . The mean number of re- interventions was lower following IPC ( 0.21 vs 0.53 , p=0.05 ) . Equal number of adverse events occurred . CONCLUSIONS IPC was not superior in the primary endpoint , improvement of the modified Borg scale ( MBS ) . However , IPC patients had lower hospital stay , fewer admissions and fewer re- interventions . The IPC is an effective treatment modality in patients with symptomatic malignant pleural effusion Background : Silver nitrate ( SN ) is an alternative to talc pleurodesis in patients with malignant pleural effusion ( MPE ) . Nevertheless , SN complications have not been thoroughly investigated so far . Objective : To evaluate frequent adverse events ( AE ) of SN treatment at three different doses for pleurodesis in patients with MPE . The secondary objective was to evaluate systemic inflammation , efficacy and quality of life in these patients . Methods : A double-blind , r and omized , clinical trial was conducted in patients with recurrent MPE at a tertiary university hospital . The study patients underwent pleural catheter insertion and were r and omly assigned to one of the three pleurodesis groups treated with 30 ml 0.3 % , 30 ml 0.5 % or 60 ml 0.3 % SN . Patients were discharged 3 days after the procedure , and returned to follow-up visits on days 10 and 30 . During follow-up , AE , inflammatory markers , quality of life and CT scans were systematic ally assessed and documented . Results : Sixty patients ( 11 males and 49 females , median age 62.13 years ) were included . Overall , 199 AE were observed , including 23 serious AE . Grade 1/2 metabolic AE , such as increases in creatinine and liver enzymes , were the most frequent . Grade 3/4 hypoxia was observed in 13 patients . Four patients died , 3 due to disease progression and in 1 patient death was possibly related to pleurodesis . C-reactive protein levels increased in a dose-dependent manner and peaked 48 h after pleurodesis . No significant difference was observed among groups regarding quality of life or clinical /radiological recurrence . Conclusion : Hypoxia was the most significant AE following SN pleurodesis ; mild metabolic events were very common . SN instillation causes substantial dose-dependent systemic inflammatory responses To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin ( BLM ) , OK-432 ( a pulverized product of heat-killed Streptococcus pyogenes ) or cisplatin plus etoposide ( PE ) for the management of malignant pleural effusion ( MPE ) in previously untreated non-small cell lung cancer . Eligible patients were r and omized to the BLM arm : BLM 1mg/kg ( maximum 60mg/body ) , the OK-432 arm : OK-432 0.2 Klinische Einheit units (KE)/kg ( maximum 10KE/body ) , or the PE arm : cisplatin ( 80mg/m(2 ) ) and etoposide ( 80mg/m(2 ) ) . Pleural response was evaluated every 4 weeks according to the study -specific criteria . All responders received systemic chemotherapy consisting of PE every 3 - 4 weeks for two or more courses . Pleural progression-free survival ( PPFS ) was defined as the time from r and omization to the first observation of pleural progression or death due to any cause . The primary endpoint was the 4-week PPFS rate . Of 105 patients enrolled , 102 were assessed for response . The 4-week PPFS rate for the BLM arm was 68.6 % , 75.8 % for the OK-432 arm , and 70.6 % for PE arm . Median survival time ( MST ) for the BLM arm was 32.1 weeks , 48.1 weeks for the OK-432 arm , and 45.7 weeks for the PE arm . However , the outcomes did not differ significantly between groups . Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM . We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate BACKGROUND --A study was undertaken to compare the efficacy of short term tube thoracostomy drainage with st and ard tube thoracostomy drainage before instillation of tetracycline for sclerotherapy of malignant pleural effusions . METHODS --The study consisted of a r and omised clinical trial in a sequential sample of 25 patients with malignant pleural effusions documented cytopathologically . Fifteen patients were r and omly assigned to group 1 ( st and ard protocol ) and 10 to group 2 ( short term protocol ) . Patients in group 1 had tube thoracostomy suction drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained was < 150 ml/day , before tetracycline ( 1.5 g ) was instilled . The chest tube was removed when the amount of fluid drained after instillation was < 150 ml/day . Patients in group 2 also had suction drainage , but the tetracycline ( 1.5 g ) was instilled when the chest radiograph showed the lung to be re-exp and ed and the effusion drained , which was usually within 24 hours . The chest tube was removed the next day . RESULTS --The response to tetracycline sclerotherapy in the two groups was the same ( 80 % ) but the duration of chest tube drainage was significantly shorter for patients in group 2 ( median two days ) than for those in group 1 ( median seven days ) . CONCLUSIONS --The duration of chest tube drainage before sclerotherapy for malignant pleural effusions need not be influenced by the amount of fluid drained daily but by radiographic evidence of fluid evacuation and lung re-expansion . Shorter duration of drainage will reduce the length of hospital stay without sacrificing the efficacy of pleurodesis BACKGROUND Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis , although the optimal route of administration remains unclear . METHODS We design ed a prospect i ve , r and omized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion . From September 1993 to November 1995 , 57 patients were recruited and r and omized to either video-assisted thoracoscopic talc insufflation under general anesthesia ( n = 28 ) or talc slurry by the bedside ( n = 29 ) . Patients with poor general condition ( Karnofsky score less than 30 % ) , poor pulmonary function ( forced expiratory volume in 1 second less than 0.5 L ) , or trapped lungs were excluded from this study . Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry . RESULTS There was no statistically significant difference between the two groups of patients with respect to age , sex ratio , chest drainage duration , postprocedural hospital stay , parenteral narcotics requirement , complications , or procedure failure ( ie , recurrence ) . CONCLUSIONS Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study . Because the former dem and s more re sources , we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs STUDY OBJECTIVES To analyze and compare radiologic lung expansion after talc pleurodesis performed either by videothoracoscopy or chest tube and correlate it with clinical outcome . Secondary end points evaluated were as follows : clinical efficacy ; quality of life ; safety ; and survival . METHODS Prospect i ve r and omized study that included 60 patients ( 45 women , 15 men ; mean age , 55.2 years ) with recurrent malignant pleural effusion between January 2005 and January 2008 . They were r and omized into the following two groups : video-assisted thoracic surgery ( VATS ) talc poudrage ; and talc slurry ( TS ) administered through a chest tube . Lung expansion was evaluated through chest CT scans obtained 0 , 1 , 3 and 6 months after pleurodesis . Complications , drainage time , hospital stay , and quality of life ( Medical Outcomes Study 36-item short form and World Health Organization quality -of-life question naires ) were also analyzed . RESULTS There were no significant differences in preprocedure clinical and pathologic variables between groups . The immediate total ( ie , > 90 % ) lung expansion was observed in 27 patients ( 45 % ) and was more frequent in the VATS group ( 60 % vs 30 % , respectively ; p = 0.027 ) . During follow-up , 71 % of the patients showed unaltered or improved lung expansion and 9 patients ( 15 % ) needed new pleural procedures ( VATS group , 5 recurrences ; TS group , 4 recurrences ; p = 0.999 ) . No differences were found between groups regarding quality of life , complications , drainage time , hospital stay , and survival . Immediate lung expansion did not correlate with radiologic recurrence , clinical recurrence , or complications ( p = 0.60 , 0.15 , and 0.20 , respectively ) . CONCLUSION Immediate partial lung expansion was a frequent finding and was more frequent after TS . Nonetheless , no correlation between immediate lung expansion and clinical outcome was found in this study . TRIAL REGISTRATION Clinical Trials.gov Identifier : NTC00789087 The efficacy and safety of intrapleural LC9018 ( Yakult Co. Ltd. , Tokyo , Japan ) with or without doxorubicin ( Adriamycin ; Adria Laboratories , Columbus , OH ) were evaluated in a r and omized , controlled trial performed in 95 patients with malignant pleural effusions secondary to lung cancer . Seventy‐six patients were eligible for the assessment of efficacy . The response rate for treatment with intrapleural doxorubicin plus LC9018 ( 38 patients ) was 73.7 % , which was significantly higher than the response rate of 39.5 % for the control group treated with doxorubicin alone ( 38 patients ) ( P < 0.01 ) . The LC9018 group also showed a significantly greater improvement in performance status ( PS ) and symptoms ( chest pain , chest discomfort , and anorexia ) than the control group ( P < 0.05 ) . A significant prolongation of survival was noticed in the LC9018 group ( P < 0.05 ) . The main side effects of LC9018 were fever and transient hepatic dysfunction , but there were no serious adverse reactions . These results suggest that the intrapleural instillation of LC9018 can be recommended for the treatment of malignant pleural effusions BACKGROUND --The treatment of recurrent pleural effusion in advanced malignant disease should be efficient and with tolerable side effects . Since 1983 intrathoracic instillation of the anti-malaria drug mepacrine has been used to achieve pleurodesis . The cytotoxic drug bleomycin has been cl aim ed to be equally effective and with fewer side effects . The present study was design ed to compare these two agents . METHODS --Forty patients with carcinoma and pleural effusions refractory to repeated pleural aspirations over the previous 12 weeks were r and omised to receive treatment with intrathoracic instillation of mepacrine or bleomycin . Fluid volumes before and after pleurodesis , drainage time , and side effects were registered and analysed , and the response to treatment was evaluated by clinical examination and chest radiography . RESULTS --The amount of fluid produced after treatment in the patients receiving mepacrine was lower than in those receiving bleomycin , and the duration of chest drainage was shorter . After 30 days 16 of 20 in the mepacrine group responded to treatment and 10 of 20 in the bleomycin group . Most patients died during the three months observation period . Moderate side effects occurred equally in both groups . CONCLUSIONS --Chemical pleurodesis can reduce or stop pleural effusion in many patients , and in this study mepacrine appeared to be more efficient than bleomycin . A prospect i ve study with a larger number of patients is now warranted The aim of this prospect i ve , r and omized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter ( Cystofix catheter , CH10 , 65 cm ) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube ( CH24 ) placed in connection with diagnostic thoracoscopy . After drainage pleurodesis was performed with tetracycline as sclerosing agent . Of 18 evaluable consecutive patients ( mean age 67.8 years ) nine were r and omized for pleurodesis with the small and nine for the large catheter . In the former group , the majority ( seven of nine ) did not find insertion of the catheter more unpleasant than thoracentesis . In the latter group only a few ( two of nine ) found insertion comparable with thoracentesis ( P < 0.05 ) . All patients found the presence of the large catheter very or somewhat unpleasant ( two and seven patients ) , whereas this was only the case for a few ( no and two patients ) treated with the small catheter ( P < 0.05 ) . In the former group three patients required new thoracentesis , whereas this was only the case for two patients in the latter group ( P > 0.05 ) . No complications were seen . We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter ( Cystofix ) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient Previously , we have shown rapid and complete dispersion of tetracycline hydrochloride in the pleural space following chest tube instillation . To assess the clinical relevance of this observation , we r and omized patients with symptomatic pleural effusions to rotation ( R ) ( n = 19 ) and nonrotation ( NR ) ( n = 21 ) groups following administration of tetracycline hydrochloride , 20 mg/kg ( n = 30 ) ; 300 mg of minocycline hydrochloride ( n = 6 ) ; and 500 mg of doxycycline hydrochloride ( n = 4 ) through a chest tube . Patients in the R group were maneuvered through six positions for the 2 h that the chest tube remained clamped . The NR patients remained supine for 2 h. Rotation and nonrotation groups were similar in demographics , source of pleural effusion , symptoms , and serum and pleural fluid analyses ( all p = NS ) . A chest radiograph was scored based on pleural fluid recurrence throughout survival or up to 12 months . Survival , duration of chest tube instillation , and success of pleurodesis assessed by radiographic pleural fluid reaccumulation ( 73.7 vs 61.9 percent ; R vs NR ) were similar ( p = NS ) . Rotational maneuvers appear to offer no benefit to the success of pleural symphysis after intrapleural instillation of tetracycline class agents BACKGROUND AND OBJECTIVE Malignant pleural effusion is associated with morbidity and mortality . A r and omized controlled trial previously compared clinical outcomes and re source use with indwelling pleural catheter ( IPC ) and talc pleurodesis in this population . Using unpublished quality of life data , we estimate the cost-effectiveness of IPC compared with talc pleurodesis . METHODS Healthcare utilization and costs were captured during the trial . Utility weights produced by the EuroQol Group five-dimensional three-level question naire and survival were used to determine quality -adjusted life-years ( QALYs ) gained . The incremental cost-effectiveness ratio ( ICER ) was calculated over the 1-year trial period . Sensitivity analysis used patient survival data and modelled additional nursing time required per week for catheter drainage . RESULTS Utility scores , cost and QALYs gained did not differ significantly between groups . The ICER for IPC compared with talc was favorable at $ US10 870 per QALY gained . IPC was less costly with a probability exceeding 95 % of being cost-effective when survival was < 14 weeks , and was more costly when 2-h nursing time per week was assumed for catheter drainage . CONCLUSION IPC is cost-effective when compared with talc , although substantial uncertainty exists around this estimate . IPC appears most cost-effective in patients with limited survival . If significant nursing time is required for catheter drainage , IPC becomes less likely to be cost-effective . Either therapy may be considered as a first-line option in treating malignant pleural effusion in patients without history of prior pleurodesis , with consideration for patient survival , support and preferences The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions ( MPE ) In a prospect i ve r and omized study , patients with pleural effusions secondary to breast carcinoma were r and omly allocated to be treated by pleurodesis using either intracavitary talc or bleomycin . For 25 assessable treatments in 22 patients , recurrence of effusion was observed in 5 of 15 ( 33 per cent ) of the bleomycin group compared with none in the talc group . It is concluded that talc is superior to bleomycin in controlling pleural effusions secondary to breast carcinoma , but bleomycin may have a role in patients unfit for general anaesthesia or with extensive disease elsewhere 30 patients with malignant pleuritis were r and omised to be treated , either with intrapleural instillation of mepacrine chloride or with mitoxantrone . The patients were evaluated with chest X-ray and a symptom question naire during a follow-up period of 12 weeks . Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients . High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low , giving a plasma/intracavity ratio generally of less than 1:60 . The chest X-rays showed excellent results for both treatment modalities . However , the patients treated with mepacrine chloride experienced greater discomfort with fever and pain , and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks . We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion . However , mitoxantrone seems to have further advantages when it comes to improving the quality of life Pleural effusion is a frequent complication in patients with advanced stages of cancer [ 1 - 8 ] , and malignant pleural effusion that is resistant to chemotherapy carries a grave prognosis [ 1 - 7 ] . Respiratory symptoms in patients with this disorder usually require palliative management of the effusion . Drainage of the effusion using a chest tube or during thoracoscopy with the introduction of sclerosing agents into the pleural space for pleurodesis is the most cost-effective approach [ 2 - 8 ] . Pleurodesis is unsuccessful in patients with symptomatic malignant pleural effusion and trapped lung ( defined as poor approximation of the pleurae after drainage of the effusion ) ; insertion of a thoracostomy tube or performance of thoracoscopy in such patients provides little benefit [ 2 - 57 , 9 , 10 ] . Thus , the diagnosis of trapped lung before such invasive procedures is important but difficult [ 5 , 6 ] . The outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung , however , is difficult to predict . Therefore , we studied pleural elastance as a predictor of successful pleurodesis and compared its predictive ability with that of the biochemical characteristics of pleural fluid . Methods Patients Patients who were admitted to our institution because of symptomatic malignant pleural effusion and who required therapeutic thoracentesis were c and i date s for this 3-year prospect i ve study . Malignant effusion was diagnosed only if malignant cells were found in a pleural biopsy specimen or effusion fluid . Exclusion criteria were 1 ) previous effusion of chemotherapy-sensitive cell types [ for breast cancer , ovarian cancer , small-cell cancer of the lung , or lymphoma , for example ] , except when the patients had undergone a course of chemotherapy that had not eliminated the effusion ; 2 ) chemotherapy or radiotherapy previously administered or planned within 2 months ; 3 ) life expectancy of 1 month or less ; and 4 ) loculated pleural effusion . Measurements and Interventions Figure 1 is a diagram of the device that was used to measure the elastance of the pleural space . Measurements were done while patients were in a sitting position . Under ultrasonographic guidance , an appropriate intercostal space was selected . After a local anesthetic was administered , 20 mL of pleural effusion was drawn into a heparin-rinsed plastic syringe for the measurement of glucose level and pH and for cytologic examination . Then , a 16-gauge intracatheter needle was inserted into the pleural space . The needle was attached to a three-way stopcock with two extension tubes that led to a central venous pressure monitor and a 50-mL syringe . The whole system was filled with normal , heparinized saline . Using a leveling rod , we marked a zero point on the central venous pressure monitor at the level of the puncture site . The pleural pressure , defined as the mean of the pleural fluid pressures during inspiration and expiration , was measured immediately and after each 100 mL of effusion was withdrawn . Thoracentesis was terminated when the pressure was lower than 10 cm H2O , when the patient developed symptoms potentially related to reexpansion pulmonary edema , or when a total of 500 mL of effusion had been drained . The elastance of the pleural space was calculated as the change in pressure of the pleural effusion ( in cm H2O ) divided by the amount of fluid removed [ 11 ] ; the st and ard measure was expressed as being equivalent to the decline in pressure of the pleural effusion after 500 mL of fluid had been removed . In five patients who had a decrease in pressure of at least 19 cm H2O and trapped lung , thoracentesis was stopped before 500 mL of effusion had been drained ; the elastance value in these patients was adjusted by linear extrapolation on the basis of the change in pressure that would have occurred if 500 mL had actually been removed [ 11 ] . Figure 1 . Device used to measure the elastance of the pleural space . After these measurements had been done , a 9.3-mm thoracostomy tube connected to a watersealed bottle was placed in the pleural space for further drainage of the effusion by gravity . Suction was applied to the chest tube only if the patient had radiographic evidence of trapped lung . Radiography was done to ensure proper positioning of the thoracostomy tube . Drainage was discontinued when less than 150 mL of effusion was drained per day [ 3 , 7 , 12 ] for 2 consecutive days and the lung had reexp and ed , when less than 250 mL of effusion was drained per day for 4 consecutive days and the lung had reexp and ed , or when drainage had continued for 10 days . When one of the three criteria was met , radiography was done to evaluate the reexpansion of the affected lung and the approximation of the pleurae . Figure 2 shows the degrees of reexpansion of the affected lung and the approximation of the pleurae . In category 1 , the lung had completely reexp and ed and the pleurae had approximated well . In category 2 , the affected lung had reexp and ed and the pleurae had approximated in most areas , but a small amount of residual pneumothorax , pleural effusion , or some heterogeneous white patches were evident on radiographs . In category 3 , the lung did not reexp and and the visceral and parietal pleurae were separated by pneumothorax in most places . The radiographs were evaluated by at least two of the authors . If reexpansion of the lung and approximation of the pleurae were difficult to interpret , the patients were placed in category 2 . Patients in category 1 or 2 were classified as having a nontrapped lung . Figure 2 . Categories of reexpansion of the affected lung and approximation of the pleurae . The chest tube was then clamped , and we injected 60 mg of bleomycin diluted in 100 mL of normal saline ( usual-dose group ) [ 4 , 5 , 7 , 8 , 13 - 15 ] or , in the latter half of the study , 30 mg diluted in 50 mL of normal saline ( low-dose group ) [ 13 , 14 ] into the pleural space for pleurodesis in all patients except two who had trapped lung . The body position of the patient was changed if the patient was not too ill [ 16 - 18 ] . The chest tube was reopened 2 hours later and removed the next day [ 5 ] . Chest radiography was done to ensure that the chest tube had been removed properly . Patients were then followed closely in the outpatient clinic , and chest radiography was done to evaluate the outcome of pleurodesis . If the results were equivocal , we did either chest ultrasonography with or without diagnostic thoracentesis or computed tomography of the chest . The results of pleurodesis were evaluated 30 days after the chest tube was removed and then until the patient died or was lost to follow-up [ 3 , 4 , 12 - 15 , 19 ] . Successful pleurodesis was defined as no recurrence of effusion , recurrence of only a small amount of effusion , or loculated effusion and elimination of the requirement for further therapeutic thoracentesis to alleviate symptoms [ 10 , 12 - 15 , 19 ] . Unsuccessful pleurodesis was defined as recurrence of the effusion in an amount similar to that seen before treatment or the requirement for further therapeutic thoracentesis to alleviate symptoms . Statistical Analysis The two- sample t-test was used to compare the mean elastance , pH , glucose level , and duration of follow-up for patients with trapped and nontrapped lungs . The Fisher exact test was used to evaluate the association between categorized variables . Confidence intervals for means and proportions were determined when appropriate . Results Sixty-five patients ( 38 men and 27 women ) between 39 and 83 years of age ( mean age , 62.7 years ) were included in the study . Two patients had gastric cancer , 2 had breast cancer , 1 had renal cancer , 1 had rectal cancer , 45 had bronchogenic adenocarcinoma , and 14 had adenocarcinoma of uncertain origin . All patients had pleural effusion on chest radiography that reached the hilar level or higher in the sitting or st and ing position . Fourteen patients had trapped lung , and 51 did not have trapped lung . As Table 1 and Figure 3 show , 11 of 14 patients with trapped lung ( groups 1 and 4 ) had an elastance of 19 cm H2O or more , although only 3 of the 51 patients without trapped lung ( groups 2 , 3 , and 5 ) had such an elastance ( P < 0.001 ) . Mean elastance was 30.59 cm H2O in the 14 patients with trapped lung and 8.31 cm H2O in the 51 patients without trapped lung ( difference , 22.3 cm H2O [ 95 % CI , 11.1 to 33.5 ] ; P = 0.001 ) . Table 1 . Results of Chest-Tube Drainage and Pleurodesis at 1 Month Figure 3 . Relation of pleural elastance , effusion pH , effusion glucose level , trapped lung , and outcome of pleurodesis . Five patients who had trapped lung were lost to follow-up at 1 month ( Figure 3 ; group 1 ) ; pleurodesis was noted to have been unsuccessful in two of these five patients before they were lost to follow-up . Another five patients with elastance less than 19 cm H2O who did not have trapped lung ( Figure 3 ; group 2 ) were also not evaluated at 1 month because of loss to follow-up ( n = 3 ) , death ( n = 1 ) , or postoperative cardiac tamponade ( n = 1 ) . Tight pleural approximation was noted during surgery in the patient with postoperative cardiac tamponade . Fifty-five patients were evaluated 1 month after the thoracostomy tube was removed ( Figure 3 ; groups 3 , 4 , and 5 ) . Pleurodesis was unsuccessful in all 9 patients who had trapped lung ( Figure 3 ; group 4 ) and in the 3 patients who had an elastance of 19 cm H2O or more without trapped lung ( Figure 3 ; group 5 ) . In contrast , 42 of the 43 patients ( 98 % ) with an elastance less than 19 cm H2O without trapped lung had successful pleurodesis ( Figure 3 ; groups 3 and 5 ) . The 14 patients with trapped lung had a higher elastance ( 30.59 cm H2O ) than did the 51 patients without trapped lung ( 8.31 cm H2O ) ( P = 0.001 ) ; the effusion from the former group also had a lower pH ( 7.133 compared with 7.308 ; P = 0.001 ) and a lower glucose level ( 3.16 mmol/L compared with 5.27 mmol/L ; P = 0.011 ) than the effusion from the latter group . Duration of follow-up in the group with trapped lung ( 2.7 months ) was similar Background Malignant pleural effusion is a common problem in patients with solid tumours . It has a significant impact on quality of life , and , hence , there is a substantial need to investigate new agents to treat it . Patients and methods This is a prospect i ve r and omised controlled study , including patients with symptomatic recurrent malignant pleural effusion of different primaries . Patients were r and omised into two groups : the first group received five ampoules of mistletoe preparation with defined lectin content ( Viscum Fraxini-2 , ATOS Pharma ) diluted in 10 cc glucose 5 % solution . Re-instillation was repeated every week until complete dryness of the pleural fluid was achieved ( the maximum duration of the therapy was eight weeks ) . The second group received 60 units of bleomycin once intrapleurally . Aims The primary aim of this paper was to evaluate the efficacy of mistletoe preparation as a palliative treatment for malignant pleural effusions in comparison with bleomycin . The secondary aim was to evaluate the tolerability of the mistletoe preparation . Results A total of 23 patients were included and followed up during the study from December 2007 to January 2012 : 13 patients received mistletoe preparation , and ten patients received bleomycin . Overall clinical response was reported in 61.5 % of the mistletoe preparation arm versus 30 % in bleomycin arm ( p = 0.2138 ) , 95 % CI = ( –0.1203 , 0.6325 ) . The toxicity of both arms was mild and manageable ; the mistletoe preparation arm included fever , chills , headache , malaise , and , in two cases , allergic reaction , which was controlled by discontinuation of the drug and steroid injection . Conclusion Mistletoe preparation is an efficient and well tolerated sclerosant agent which needs further investigation Background The minimal important difference ( MID ) is essential for interpreting the results of r and omised controlled trials ( RCTs ) . Despite a number of RCTs in patients with malignant pleural effusions ( MPEs ) which use the visual analogue scale for dyspnea ( VASD ) as an outcome measure , the MID has not been established . Methods Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD ( 24 hours after the pleural drainage ) , and in parallel assessed their breathlessness on a 7 point Likert scale . Findings The mean decrease in VASD in patients with a MPE reporting a ‘ small but just worthwhile decrease ’ in their dyspnea ( i.e. equivalent to the MID ) was 19 mm ( 95 % CI 14 - 24 mm ) . The mean drainage volume required to produce a change in VASD of 19 mm was 760ml . Interpretation The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19 mm ( 95 % CI 14 - 24 mm ) . Thus choosing an improvement of 19 mm in the VASD would be justifiable in the design and analysis of future MPE studies Abstract Background . Growth factors are key inducers of fibrosis but can also mediate inflammatory responses result ing in increasing pleural effusion and acute respiratory distress syndrome . The primary aim of the study was to analyse growth factors release after performing chemical and mechanical pleurodesis in the first 48 hours at the patients with malignant pleural effusion . The secondary endpoints were to evaluate the effectiveness of the both pleurodeses , symptoms release and the quality of life of patients after the treatment . Patients and methods . A prospect i ve r and omized study included 36 consecutive female patients with breast carcinoma and malignant pleural effusion in an intention-to-treat analysis . We treated 18 patients by means of thoracoscopic mechanical pleurodesis and 18 patients by chemical pleurodesis with talcum applied over a chest tube . We gathered the pleural fluid and serum sample s in the following 48 hours under a dedicated protocol and tested them for growth factors levels . A quality of life and visual analogue pain score surveys were also performed . Results . Median measured serum vascular endothelial growth factor ( VEGF ) level after chemical pleurodesis was 930.68 pg/ml ( 95 % CI : 388.22–4656.65 ) and after mechanical pleurodesis 808.54 pg/ml . ( 95 % CI : 463.20 - 1235.13 ) ( p = 0.103 ) . Median pleural levels of transforming growth factor ( TGF ) β1 were higher after performing mechanical pleurodesis ( 4814.00 pg/ml [ 95 % CI : 2726.51–7292.94 ] ) when compared to those after performing chemical pleurodesis ( 1976.50 pg/ml [ 95 % CI : 1659.82–5136.26 ] ) ( p = 0.078 ) . We observed similar results for fibroblast growth factor ( FGF ) β ; the serum level was higher after mechanical pleurodesis ( 30.45 pg/ml [ 95 % CI : 20.40–59.42 ] ) , compared to those after chemical pleurodesis ( 13.39 pg/ml [ 95 % CI : 5.04 – 74.60 ] ) ( p = 0.076 ) . Mechanical pleurodesis was equally effective as chemical pleurodesis in terms of hospital stay , pleural effusion re-accumulation , requiring of additional thoracentesis , median overall survival , but , it shortened the mean thoracic drainage duration ( p = 0.030 ) and result ed in a higher symptoms release and in a better quality of life ( p = 0.047 ) . Conclusions . We recorded an increase in serum VEGF levels after chemical pleurodesis , however on the contrary , an increase in the pleural fluid level of TGFβ1 and FGFβ ] after mechanical pleurodesis with respect to compared group . Although the differences did not reach statistical significance , VEGF , TGFβ1 and FGFβ remain the most interesting parameters for future research . Considering the mechanisms of growth factors action , we conclude that in our study group mechanical pleurodesis might be more efficient in terms of growth factors release , thoracic drainage duration and result ed in a higher symptoms release and in a better quality of life than chemical pleurodesis Malignant pleural effusion ( MPE ) is a common complication of advanced non-small cell lung cancer ( NSCLC ) . Bevacizumab , a humanized monoclonal antibody against vascular endothelial growth factor ( VEGF ) , has been shown to be efficient in suppressing the accumulation of pleural fluid . However , whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown . The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin , an antineoplastic agent , in controlling MPE . A total of 72 NSCLC study subjects with MPE were r and omly assigned to one of two groups . The first group received intrapleural bevacizumab ( 300 mg ) with cisplatin ( 30 mg ) therapy and the second group received intrapleural cisplatin ( 30 mg ) therapy alone . Pleural fluid was collected from both groups prior to and following treatment . The levels of VEGF and carcinoembryonic antigen ( CEA ) in the pleural fluid were determined by ELISA . In 70 evaluable study subjects , the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group ( 83.33 vs. 50.00 % , respectively ; p<0.05 ) . Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid ( p<0.01 ) . In the bevacizumab group , the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment , which showed greater efficacy ( p<0.01 ) . In addition , combination therapy showed greater efficacy in the patients with high levels of VEGF expression ( p<0.01 ) . There was no significant difference in grade III/IV adverse events between the two groups . All procedures were well tolerated by the patients . Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE . We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy OBJECTIVE To compare the efficacy , safety , and outcome of thoracoscopic talc poudrage ( TTP ) versus povidone-iodine pleurodesis ( PIP ) through a thoracostomy tube as a palliative treatment of pleural effusion due to metastatic breast carcinoma ( MBC ) . METHODS A total of 42 MBC patients were prospect ively enrolled in a r and omized controlled trial . Twenty-two patients received TTP ( group A ) , whereas 20 patients ( group B ) underwent pleurodesis by instilling povidone-iodine through a thoracostomy tube , as a bedside procedure . RESULTS The mean age was 48.2 ± 9.9 ( range : 29 - 64 ) years and 50.2 ± 7 ( range : 32 - 62 ) years for groups A and B , respectively ( p = ns ) . At presentation , all patients had moderate to severe dyspnea , New York Heart Association (NYHA)>II and Medical Research Council ( MRC ) dyspnea scale 3 - 5 . Morbidity in both groups was low . Post-procedure analgesic requirements due to severe pleuritic chest pain were higher in group A ( 18 % vs 0 % , p=0.2 ) . Four patients in group A ( 18 % ) and one in group B ( 5 % ) were febrile ( > 38 ° C ) within 48 h of the procedure . Both groups achieved good symptom control , with improvement in MRC dyspnea scale ( 1 - 3 ) . There were no in-hospital deaths . Post-procedure hospital stay was lower in group B ( p=0.009 ) . The mean progression-free interval was 6.6 ( range 3 - 15 ) months . At follow-up ( mean : 22.6 ( range : 8 - 48 ) months ) , recurrence of significant pleural effusion requiring intervention was noted in two and three patients in group A and group B , respectively ( p = ns ) . CONCLUSION Povidone-iodine can be considered as a good alternative to TTP to ensure effective pleurodesis for patients with malignant pleural effusion due to MBC . The drug is available , cost effective and safe , can be given through a thoracostomy tube and can be repeated if necessary Objectives : Autologous blood pleurodesis ( ABP ) is used for the treatment of pneumothorax with a good efficacy . The aim of this study is to determine the efficacy and safety of ABP in the treatment of malignant pleural effusion ( MPE ) . Methods : A prospect i ve study was conducted at Songklanagarind Hospital , Thail and . Symptomatic MPE patients were r and omized to receive pleurodesis with either autologous blood or tetracycline . In the ABP group , 100 ml of autologous venous blood was instilled via chest tube followed by 50 ml of sterile normal saline ( NSS ) . In the tetracycline group , 20 ml of 1 % lidocaine diluted in 30 ml NSS was instilled followed by 1 g of tetracycline diluted in 100 ml of NSS . The chest tube was clamped for 2 hours , then reconnected to suction and removed . Pleurodesis effectiveness was evaluated according to Paladine ’s criteria and adverse events were recorded . Results : A total of 48 symptomatic MPE patients were recruited . Of these , 24 cases were r and omized to receive ABP and 24 cases received tetracycline . There was no difference between the two groups in baseline characteristics . The overall success rate of pleurodesis was the same in both the autologous blood group and the tetracycline group ( 83.4 % versus 87.5 % , p = 0.36 ) . In the ABP group , the pain score and fever were significantly lower ( 8.3 % versus 29.1 % , p = 0.003 ) and there was a small percentage of cases that needed analgesia ( 4.2 % versus 75 % , p < 0.001 ) ; no serious events occurred . Conclusions : ABP was as effective as tetracycline in the treatment of MPE . ABP produced less pain and fever , and could shorten the hospital stay STUDY OBJECTIVE To demonstrate the efficacy , safety , and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions ( MPEs ) . DESIGN A prospect i ve , r and omized trial was design ed to compare thoracoscopy with talc insufflation ( TTI ) to thoracostomy and talc slurry ( TS ) for patients with documented MPE . MEASUREMENTS The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-exp and ed > 90 % . Morbidity , mortality , and quality of life were also assessed . RESULTS Of 501 patients registered , those eligible were r and omized to TTI ( n = 242 ) or TS ( n = 240 ) . Patient demographics and primary malignancies were similar between study arms . Overall , there was no difference between study arms in the percentage of patients with successful 30-day outcomes ( TTI , 78 % ; TS , 71 % ) . However , the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS ( 82 % vs 67 % ) . Common morbidity included fever , dyspnea , and pain . Treatment-related mortality occurred in nine TTI patients and seven TS patients . Respiratory complications were more common following TTI than TS ( 14 % vs 6 % ) . Respiratory failure was observed in 4 % of TS patients and 8 % of TTI patients , accounting for five toxic deaths and six toxic deaths , respectively . Quality -of-life measurement demonstrated less fatigue with TTI than TS . Patient ratings of comfort and safety were also higher for TTI , but there were no differences on perceived value or convenience of the procedures . CONCLUSIONS Both methods of talc delivery are similar in efficacy ; TTI may be better for patients with either a lung or breast primary . The etiology and incidence of respiratory complications from talc need further exploration Radiology has assumed an evergrowing role in the treatment of pleural disease . Once thought to be the domain of the thoracic surgeon , the treatment of empyema is now commonly accompushed with imaging-guided , small-bore chest tubes . A growing body of literature also supports the use of small-bore tubes in the treatment of malignant pleural effusions [ 1 ] . Much of the success of small-bore chest tubes in the treatment ofempyemas hasbeen made possible through aggressive use of urokinase . Despite these promising results , little has been written on the role offibnnolytic agents in the treatment of malignant pleural effusions [ 2 ] . We present our results on the prospect i ve use of urokinase in the treatment of malignant pleural effusions Introduction The development of malignant pleural effusion ( MPE ) results in disabling breathlessness , pain and reduced physical capability with treatment a palliative strategy . Ambulatory management of MPE has the potential to improve quality of life ( QoL ) . The OPTIMUM trial is design ed to determine whether full outpatient management of MPE with an indwelling pleural catheter ( IPC ) and pleurodesis improves QoL compared with traditional inpatient care with a chest drain and talc pleurodesis . OPTIMUM is currently open for any centres interested in collaborating in this study . Methods and analysis OPTIMUM is a multicentre non-blinded r and omised controlled trial . Patients with a diagnosis of MPE will be identified and screened for eligibility . Consenting participants will be r and omised 1:1 either to an outpatient ambulatory pathway using IPCs and talc pleurodesis or st and ard inpatient treatment with chest drain and talc pleurodesis as per British Thoracic Society guidelines . The primary outcome measure is global health-related QoL at 30 days measured using the EORTC QLQ-C30 question naire . Secondary outcome measures include breathlessness and pain measured using a 100 mm Visual Analogue Scale and health-related QoL at 60 and 90 days . A sample size of 142 patients is needed to demonstrate a clinical ly significant difference of 8 points in global health status at 30 days , for an 80 % power and a 5 % significance level . Ethics and dissemination The study has been approved by the NRES Committee South East Coast — Brighton and Sussex ( reference 15/LO/1018 ) . The trial results will be published in peer- review ed journals and presented at scientific conferences . Trial registration numbers UKCRN19615 and IS RCT N15503522 ; Pre- results BACKGROUND Malignant pleural effusions are a common problem for patients with metastatic disease . Most patients are treated with tube thoracostomy and sclerotherapy , although there remains no st and ard approach . The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters . METHODS All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible . Using image guidance , a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction . When drainage fell below 200 mL/d , patients were r and omized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy . Response at 30 days was determined . RESULTS One hundred six patients were enrolled in the study . Fifteen men ( 29 % ) and 37 women ( 71 % ) with a mean age of 57 years received bleomycin sclerotherapy . Twenty-one of the 29 patients ( 72 % ) alive and evaluable at 30 days had successful sclerotherapy . Twenty-three men ( 43 % ) and 31 women ( 57 % ) with a mean age of 61 years received doxycycline sclerotherapy . Twenty-three of the 29 patients ( 79 % ) alive and evaluable at 30 days had successful sclerotherapy . There was no significant difference in response rates between doxycycline and bleomycin ( p=0.760 ) . CONCLUSIONS These data continue to support a role for small-bore chest drainage and sclerotherapy , although there was no significant difference in 30-day response rates between doxycycline and bleomycin Pleural effusion is a common complication in patients with malignant neoplasm . A r and omized controlled study of intrapleural instillation of Adriamycin ( control group , 30 patients ) and Adriamycin Nocardia rubra cell wall skeleton ( N-CWS group , 26 patients ) with tube thoracostomy was performed in 55 patients with malignant pleural effusion due to primary lung cancer . The response rates for control of pleural effusion were 73.4 % in the N-CWS group and 46.1 % in the N-CWS group . These results suggest that intrapleural instillation using a combination of anti-cancer agent and immunopotentiator is an effective treatment for malignant pleurisy . Cardiac tamponade secondary to cancer is a life-threatening complication requiring immediate treatment . Twenty-four patients with malignant pericardial effusion were treated by intrapericardial instillation of anti-cancer drugs , such as Carbazilquinone , Mitomycin-C or ACNU , with pericardial drainage . The range of survival time from the instillation of anti-cancer drug was 3 - 365 days ( average days ) . In only 4 patients , reaccumulation of pericardial effusion was recognized . There were no serious complications with this procedure . It was considered that local instillation of anti-cancer agents with pericardial drainage was a useful therapeutic modality for malignant pericarditis Eighteen patients with advanced metastatic malignancy who had 21 pleural effusions requiring sclerosis for control were r and omly allocated to intrapleural therapy with tetracycline or quinacrine . Tetracycline produced partial or complete control of the effusion in ten of 12 trials for a median duration of 6 months ( range 1.5 to 22 months ) . Partial or complete control was obtained in nine of ten trials with quinacrine , for a median duration of 3 months ( range 1 to 13 months ) . All complete responders who died achieved control of their effusions until their terminal admissions despite clinical evidence of overt systemic tumor progression in the intervening period . Single‐dose tetracycline therapy was accompanied by less fever ( p < 0.04 ) and less pleuritic pain ( p = 0.09 ) than quinacrine . Tetracycline is effective , well tolerated , easily administered , and should be considered as the initial therapy for malignant pleural effusions requiring pleural sclerosis OBJECTIVE To compare the therapeutic effects of pleural perfusion of NDP and cDDP in non-small cell lung cancer ( NSCLC ) patients with malignant pleural effusion , their quality of life and toxic side effects . METHODS Sixty-eight NSCLC patients with malignant pleural effusion after chest drainage were r and omly divided into two groups according to the pathological types : 34 cases in the NDP ( Group A ) and cDDP groups ( Group B ) , 34 cases each . They were treated with NDP ( 40 mg/m(2 ) ) and dexamethasone ( 10 mg ) dissolved in 40 ml normal saline , or cDDP ( 40 mg/m(2 ) ) and dexamethasone ( 10 mg ) dissolved in 40 ml of normal saline , respectively , through pleural perfusion weekly for 2 - 4 weeks . Routine and symptomatic treatment was used in all the patients . The therapeutic effects , life quality and toxic side effects were evaluated . RESULTS The response rates of groups A and B were 88.23 % and 61.7 % , respectively , ( P < 0.01 ) . The rates of toxic side effects in groups A and B were 39.6 % and 41.9 % , respectively , ( P > 0.05 ) . However , the rates of gastrointestinal side effects of the two groups were 5 % and 12.9 % , respectively , ( P < 0.05 ) . The Karnofsky scores of group A were higher than that in group B ( P < 0.05 ) . The survival time of group A was significantly longer than that of group B. CONCLUSION Pleural perfusion with NDP is a good treatment method with milder toxicity for patients with malignant pleural effusion caused by NSCLC Talc pleurodesis is commonly used in the palliative treatment of malignant pleural effusions but the shortest and most effective regime has not been determined . In particular , it is not clear when the intercostal drain should be removed following the insertion of sclerosant . We conducted a single-centre , r and omised , open trial of drain removal at 24 h versus 72 h following talc slurry pleurodesis . The primary outcome measure was success of pleurodesis ( no recurrence of effusion on chest radiograph at 1-month follow-up ) and secondary outcome measures included length of hospital stay and mortality . We found no difference between recurrence of pleural effusion in those r and omised to drain removal at 24 h and those r and omised to drain removal at 72 h ( p>0.5 ) . However , length of stay was significantly reduced when the chest drain was removed at 24 h ( 4 days versus 8 days ; p<0.01 ) . Mortality did not differ between the two groups . We conclude that this shorter pleurodesis regime is safe and effective Background To evaluate the efficacy of iodopovidone as an agent for pleurodesis in malignant pleural effusion ( MPE ) and to compare the efficacy of small-bore catheter ( Pleuracan , Braun , Melsungen , Germany ) and conventional large-bore chest tube in pleural fluid drainage and sclerotherapy . Methods Patients with MPE were prospect ively consecutively r and omized into two groups between August 2004 and February 2007 : pleurodesis via conventional ( 32F ) chest tube ( group 1 ) and small-bore catheter ( group 2 ) , both using iodopovidone . After 3 months ’ follow-up , response rates ( complete or partial ) , complication rates , and duration of procedures within whole group , group 1 , and group 2 were compared . Statistical analyses were performed by Mann-Whitney U , χ2 , and Fisher ’s exact test . Results Forty-three pleurodeses were performed in 41 patients . The response was complete in 26 ( 60.5 % ) and partial in 12 ( 27.9 % ) , and the overall success rate was 88.4 % . The response rate was not associated with the type of inserted tube ( P = .750 ) , pleural fluid pH ( P = .290 ) , or pleural fluid lactate dehydrogenase ( P = .727 ) . In group 1 ( n = 20 ) , 12 demonstrated complete and 6 demonstrated partial response , with a 90 % success rate ; success was 86.9 % in group 2 , with complete response in 14 and partial response in 6 patients . Success rates were similar in the two groups ( P = 1.000 ) . Of 43 procedures , complications were observed in 14 ( 32.5 % ) , and complication rates were 35 % and 30.4 % in groups 1 and 2 , respectively ( P = .750 ) . The most frequent complication was pain ( 16.2 % ) , followed by fever , subcutaneous emphysema , dyspnea , and hypotension . Conclusion Iodopovidone is an effective , inexpensive , safe , and easily available alternative in chemical pleurodesis in MPE . The success rates of pleurodesis were found to be similar regardless of the type of the tube inserted Both bleomycin and tetracycline have been suggested as the sclerosing agent of choice in the management of malignant pleural effusions . To determine if one drug is superior to the other in this role , patients with malignant pleural effusions were r and omly assigned to receive either bleomycin or tetracycline in the previously evacuated pleural space through a thoracostomy tube . Following instillation of the assigned agent , the tube was clamped for 8 hours and then reattached to suction . When the chest tube drainage had slowed to less than 40 ml in a 24-hour period or if 7 days had passed , the tube was removed . Pleural sclerosis was attempted 42 times in 34 patients . No statistically significant differences were found between the two treatment groups when prevention of effusion reaccumulation and time to removal of the chest tube ( efficiency ) were compared . Side effects including pleural pain and fever , occurred with both agents , but were manageable . Since one drug was not clearly superior to the other , and bleomycin is more costly , we suggest that tetracycline rather than bleomycin be used when pleural sclerosis is needed to manage malignant pleural effusions To determine the optimum dose of OK-432 for intrathoracic administration , a multicenter r and omized phase II trial was conducted in patients with malignant pleural effusion due to non-small cell lung cancer . Patients with histologically- or cytologically-proven malignant pleural effusions were r and omized to arm A ( 10 Klinische Einheit ( KE ) of OK-432 ) or arm B ( 1 KE of OK-432 ) . OK-432 was injected intrapleurally over 30 min on days 1 and 3 and the chest tube was clamped for 6 h. If control was inadequate on day 8 , 10 KE was administered on days 8 and 10 in each treatment arm . Forty patients were enrolled and 38 patients were eligible ( 19 in arm A and 19 in arm B ) . The effusion control rate on day 8 was 79 % in arm A and 53 % in arm B , while control rates on day 28 were 74 % and 84 % , respectively . The median drainage time after administration was significantly shorter in arm A ( 4.0 + /- 1.2 days ) than in arm B ( 7.0 + /- 1.7 days ) . The total drainage volume was also significantly less in arm A than in arm B. No grade 4 toxicities or treatment-related deaths were observed in either treatment arm . Intrathoracic injection of OK-432 is a feasible treatment for malignant pleural effusion . Although the malignant pleural effusion control rate was equivalent in each treatment arm , faster control and less drainage were achieved in arm A. A dose of OK-432 10 KE/body is , therefore , recommended for further trial BACKGROUND AND OBJECTIVE Talc is an effective and widely used agent for chemical pleurodesis . However , limited availability and high cost hamper the routine use of talc in re source poor countries . In this study , we compared the efficacy and safety of iodopovidone with that of cosmetic talc , for chemical pleurodesis . METHODS Patients with recurrent pleural effusions and /or spontaneous pneumothorax were prospect ively r and omized to undergo pleurodesis with cosmetic talc ( 5 g ) or iodopovidone ( 20mL of a 10 % solution ) by tube thoracostomy . The cosmetic talc was pretested for impurities ( asbestos-free ) and particle size ( 20 - 60 µm ) , using energy dispersive analysis by X-ray and scanning electron microscopy . The success rate ( complete or partial ) , time to pleurodesis and safety of these two agents was compared . RESULTS Pleurodesis was performed in 73 patients ( 39 with iodopovidone , 34 with cosmetic talc ; 56 men , 17 women ; mean age 51.7 years ; 38 pleural effusions , 35 pneumothoraces ) . A complete response was obtained in all patients with pneumothorax in both the iodopovidone and talc groups . Among patients with pleural effusions , a complete response was observed in 16/19 and 15/19 patients in the iodopovidone and talc groups , respectively . A partial response was observed in two additional patients from each group . The time to pleurodesis was similar in the two groups . Minor side-effects ( fever , chest pain ) were observed with similar frequencies in the two groups . None of the patients experienced hypotension or ARDS . CONCLUSIONS Iodopovidone and cosmetic talc are equally efficacious and safe agents for chemical pleurodesis Pleurodesis with doxycycline ( 100 mg and 600 mg ) and Corynebacterium parvum ( 1 mg and 7 mg ) were compared in 41 patients with malignant effusion . To evaluate the mechanisms , pleural fluid pH , leukocytes , granulocytes , interleukin-6 ( IL-6 ) and serum IL-6 , as well as C-reactive protein ( CRP ) were measured before and on 2 consecutive days after treatment . Corynebacterium parvum produced a greater acute-phase response measured with fever , serum CRP and IL-6 than doxycycline . However , no change in pleural fluid IL-6 was demonstrated . Among the 35 assessed patients , 26 had objective response , similar in all four treatment groups . Side-effects were more common with Corynebacterium parvum . Based on this preliminary study we conclude that doxycycline , even in low doses , is a highly effective and well tolerated agent for palliative treatment of malignant pleural effusion . As the responses were similar despite different inflammatory reactions , the two agents probably induce pleural obliteration through different mechanisms BACKGROUND AND OBJECTIVE p53 gene is one of cancer suppressor genes and its mutation and deletion induces almost all human cancers . This study was to evaluate the clinical efficacy and toxicity of recombinant human Ad-p53 injection ( rAd-p53 ) combined with cisplatin in treatment of malignant pleural effusion induced by lung cancer . METHODS A total of 35 cases of malignant pleural effusion were r and omly divided into the combined group ( n=17 ) and the single-agent group ( n=18 ) . On the basis of systemic treatment ( vinorelbine 25 mg/m2 , Days 1 - 8 , every 3 weeks ) , the combined group were given intracavitary administration of rAd-p53 ( 1x1012 VP ) and cisplatin ( 40 mg/m2 ) once a week for 4 weeks . The single-agent group were given the same intracavitary administration as the combined group but without rAd-p53 therapy . RESULTS The total effective rates in the combined group and the single-agent group were 82.35 % and 50.00 % ( P<0.05 ) , respectively . The total modification rates in the combined group and the single-agent group were 64.70 % and 33.33 % ( P<0.05 ) , respectively . The toxicities in the two groups were fever , stethalgia , nausea/vomiting and leukopenia . The toxic reaction in combined group was mainly self-limited fever ( P<0.05 ) , which disappeared automatically after 36 h. CONCLUSIONS rAd-p53 and cisplatin is safe and effective for malignant pleural effusion induced by lung cancer . It is worthy of application in clinical treatment Introduction The management of recurrent malignant pleural effusions ( MPE ) can be challenging . Various options are available , with the most efficacious and widely used being talc pleurodesis . Talc can either be applied via a chest drain in the form of slurry , or at medical thoracoscopy using poudrage . Current evidence regarding which method is most effective is conflicting and often method ologically flawed . The TAPPS trial is a suitably powered , multicentre , open-label , r and omised controlled trial design ed to compare the pleurodesis success rate of medical thoracoscopy and talc poudrage with chest drain insertion and talc slurry . Methods and analysis 330 patients with a confirmed MPE requiring intervention will be recruited from UK hospitals . Patients will be r and omised ( 1:1 ) to undergo either small bore ( < 14 Fr ) Seldinger chest drain insertion followed by instillation of sterile talc ( 4 g ) , or to undergo medical thoracoscopy and simultaneous poudrage ( 4 g ) . The allocated procedure will be performed as an inpatient within 3 days of r and omisation taking place . Following discharge , patients will be followed up at regular intervals for 6 months . The primary outcome measure is pleurodesis failure rates at 3 months . Pleurodesis failure is defined as the need for further pleural intervention for fluid management on the side of the trial intervention . Ethics and dissemination The trial has received ethical approval from the National Research Ethics Service Committee North West — Preston ( 12/NW/0467 ) . There is a trial steering committee which includes independent members and a patient and public representative . The trial results will be published in a peer- review ed journal and presented at international conferences , as well as being disseminated via local and national charities and patient groups . All participants who wish to know the study results will also be contacted directly on their publication . Trial registration number IS RCT N47845793 STUDY OBJECTIVES To compare the efficacy and the safety of talc slurry and silver nitrate ( SN ) in the treatment of symptomatic malignant pleural effusions . PATIENTS AND METHODS Sixty patients were enrolled into the study , and all received a chest tube ( 26F or 28F ) that was placed using local anesthesia . The patients were r and omized to receive either 5 g talc diluted to a total volume of 50 mL with saline solution or 20 mL 0.5 % SN through the chest tube . Patients were clinical ly evaluated before and after treatment regarding pain , and were evaluated at monthly intervals with respect to the effectiveness of pleurodesis . Eleven patients did not return for their 30-day follow-up visit and were excluded from further analysis . Pleurodesis therapy was considered to be successful if there was no recurrence of the effusion . The patients who did not have a pleurodesis at one visit were excluded from subsequent visits . RESULTS Forty-nine patients returned at 30 days for follow-up , including 24 patients who received SN and 25 who received talc . The groups were similar in age ( p = 0.23 ) , sex ( p = 0.70 ) , Karnofsky index ( p = 0.94 ) , and pathology ( p = 0.68 ) . After the induction of pleurodesis , neither the total mean ( + /- SE ) fluid drainage ( SN , 901 + /- 125 mL ; talc , 766 + /- 74 mL ; p = 0.36 ) nor the level of pain ( SN , 2.58 + /- 0.26 ; talc , 2.62 + /- 0.30 ; p = 0.91 ) differed significantly between the groups , and no patient in either group developed ARDS . The mean number of days spent in the hospital was nearly identical ( SN group , 3.7 + /- 0.15 days ; talc group , 3.6 + /- 0.13 days ; p = 0.47 ) . Both SN and talc were effective agents . Thirty days after the procedure , 23 of 24 patients ( 96 % ) who had received SN and 21 of 25 patients ( 84 % ) who had received talc showed an effective pleurodesis ( p = 0.35 ) . Similar results were observed after 60 days ( SN group , 18 of 18 patients [ 100 % ] ; talc group , 13 of 13 patients [ 100 % ] ; p = > 0.99 ) , 90 days ( SN group , 16 of 16 patients [ 100 % ] ; talc , 8 of 9 patients [ 89 % ] ; p = 0.36 ) , and 120 days ( SN group , 4 of 4 patients [ 100 % ] ; talc group , 4 of 4 patients [ 100 % ] ; p > 0.99 ) . CONCLUSIONS The present study suggests that SN is an effective agent for producing a pleurodesis . In the present study , SN showed a tendency to be more effective than talc , but the power of the test to detect a significance difference was low in this small group of patients . The side effects of 0.5 % SN appear to be minimal , but since only a small number of patients received SN and nearly 20 % of the patients were lost to follow-up , significant long-term side effects can not be excluded . Since SN appears to be as effective as talc , and since there is no evidence that it induces ARDS as has been reported with talc , it should be considered as an alternative to talc for the production of a pleurodesis In a controlled clinical trial we investigated 102 patients with malignant pleural effusion due to breast cancer , lung cancer , ovarian cancer and other tumors to compare the therapeutic effect and adverse events of pleurodesis with bleomycin ( BMC ) or mitoxantrone ( MIT ) via chest tube . Finally 96 patients had been treated according to the protocol . Age , gender , Broca index , performance score or distribution of primary tumors were not statistically different between the BMC ( n = 49 ) or MIT group ( n = 47 ) . We found no differences between intention-to-treat and according-to- protocol groups as well . 30 days after BMC pleurodesis we found remissions of the effusion in 91 % of patients ( complete remission [ CR ] 51 % , partial remission [ PR ] 40 % ) , after 90 days in 83 % ( 40 % CR , 43 % PR ) . 30 days after MIT instillation we found remission in 73 % of patients ( 35 % CR , 38 % PR ) , after 90 days in 61 % ( 29 % CR , 32 % PR ) ( 30 and 90 days : p < 0.05 ) . Adverse events were not different between BMC and MIT group . BMC is a safe and effective sclerosing agent for pleurodesis via chest tube OBJECTIVE Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies . Pleurodesis via bedside thoracostomy is the current treatment option most commonly used . To our knowledge , this is the first prospect i ve r and omized trial to examine which agent , bleomycin or talc slurry , is superior in terms of effectiveness , safety , and cost . PATIENTS AND METHODS Between July 1992 and March 1995 , 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospect ively r and omized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy . The conditions of patients were assessed and grade d before and after treatment concerning pain , dyspnea , and chest radiographs . RESULTS Twenty-nine patients who underwent 33 treatments ( 14 with bleomycin and 19 with talc ) were available for follow-up . Follow-up ranged from 2 weeks to 8 months ( mean , 1.7 months ) . Both groups demonstrated notable improvement in both pain and dyspnea following treatment , but there were no statistically significant differences between groups in the amount of improvement ( two-tailed Student 's t test ) . Permanent control of effusions , defined objective ly on chest radiograph , was achieved with 11 bleomycin treatments ( 79 % ) and 17 talc treatments ( 90 % ) ( p=0.388 ) . The procedures were well tolerated and no significant adverse effects were observed . Talc is a much less costly agent than bleomycin ( $ 12.36 cost to our medical center per treatment for talc vs $ 955.83 for bleomycin ) . CONCLUSION Given the similar efficacy and significant cost advantage , we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions In order to determine whether pleural drainage with talc instillation was better than pleural drainage alone , in the treatment of malignant effusion , the present trial was initiated . Thirty-one patients with malignant pleural effusion and progressive disease , resistant to conventional therapy , were included . All patients had pleural drainage applied . After re-expansion of the lung , half of the patients had talc instilled through the chest tube . Twenty-one of the 31 treated patients were evaluable . After pleural drainage with talc instillation , all of 9 treated patients obtained complete resolution of the effusion and subjective improvement . After pleural drainage alone , 7 of 12 patients obtained complete resolution of the malignant effusion . If it is possible to re-exp and the lung during pleural drainage in patients with a malignant pleural effusion , pleurodesis can be obtained in 60 % of the treated patients with pleural drainage alone . This study showed a statistically significant improvement in the treatment associated with instillation of talc into the pleural cavity and this was achieved without causing increased discomfort to the patient Pleural sclerosis after tube thoracostomy was performed in 40 patients with malignant pleural effusions . The patients were r and omly allocated to intrapleural therapy with tetracycline or mechlorethamine . Follow up was obtained on each patient to determine if a symptomatic effusion recurred . The response was classified as a complete or partial response and failure . ( Complete response : complete lack of reaccumulation of pleural fluid for at least 60 days . Partial response : small pleural effusion asymptomatic not requiring further treatment for at least 60 days . Failure : all other cases ) . Tetracycline produced complete or partial control of the effusion in 16 of 20 trials for a duration of 6.1 + /- 4.1 months ( range 2 - 14 months ) . Mechlorethamine produced control of the effusion in 12 of 20 trials for a duration of 4.4 + /- 1 months ( range 2 - 8 months ) . These findings indicate that intracavitary tetracycline is a more effective treatment than intracavitary mechlorethamine for the control of neoplastic pleural effusion PURPOSE To determine the prognostic value of pleural fluid pH , pleural fluid glucose , extent of pleural carcinomatosis ( EPC ) score , and Karnofsky Performance Scale ( KPS ) score in patients with recurrent symptomatic malignant pleural effusions . DESIGN Prospect i ve 53-month study . SETTING Referral center for interventional pulmonology . PATIENTS Eighty-five consecutive patients ( 42 men and 43 women ) with recurrent symptomatic malignant pleural effusions who were referred to the interventional pulmonary service for thoracoscopic pleurodesis . MEASUREMENTS Pleural fluid pH , pleural fluid glucose , EPC score , and KPS score . RESULTS The KPS score was the only statistically significant predictor variable . Patients with a KPS score > /= 70 had a median survival of 395 days , as opposed to a median survival of only 34 days for patients with a KPS score < /= 30 . No prognostic advantage was evident when patients were categorized by pleural fluid pH , pleural fluid glucose , or EPC score . CONCLUSION When assessing the prognosis of a patient with a recurrent symptomatic malignant pleural effusion , only the KPS score at the time of thoracoscopy is predictive of survival . Pleural fluid pH , pleural fluid glucose , and EPC scores are not as reliable as initially reported . For patients with a KPS score > /= 70 , it may be very reasonable to proceed with thoracoscopic talc pleurodesis for management of their malignant pleural effusions In a prospect i ve r and omized study the effect of pleurodesis using fibrin-glue was compared with pleurodesis using tetracycline in the management of malignant pleural effusions . Intrapleural therapy with fibrin-glue was significantly more effective concerning long-term results as relapse of pleural effusion and improvement of lung function just as time of draining pleural effusion and pain during the application of fibrin glue/tetracycline . Thus , intracavitary therapy with fibrin glue may be recommended in the control of malignant pleural effusions A r and omized phase III trial of bleomycin , tetracycline and talc following chest tube drainage and a meta- analysis of relative benefit of bleomycin and tetracycline as sclerosing agents were performed to determine the optimal approach to malignant pleural effusion ( MPE ) . Fifty patients were r and omized to receive bleomycin ( n=16 ) , tetracycline ( n=19 ) or talc ( n=16 ) following chest tube drainage . Treatment groups were balanced for pretreatment characteristics . The study was ended prematurely because of the removal of parenteral tetracycline from the market . Overall , 52 % of r and omized patients had successful control of effusion 30 days after sclerosis . There were no differences between any of the three treatment groups in terms of 30 day control of effusion , overall survival ( 6 months ) , resclerosis rate , pain with sclerosis , fever , or duration of hospitalization ( 6 days ) . A meta- analysis was performed using the four previously reported trials of tetracycline vs. bleomycin and revealed a 20.6 % advantage to the use of bleomycin ( 95 % C.I. 7.9%-33.3 % ) ( p=0.002 ) . This phase III failed to demonstrate a significant difference between the three agents in terms of control of MPE at 30 days , side effects or survival . However , because of small sample size , this study lacks sufficient power to observe potentially clinical ly important differences between treatment groups . Inclusion of data from four previous trials in a meta- analysis showed that bleomycin may be superior . The median duration of hospitalization and the overall success rate of all three sclerosing agents in this study argue convincingly that new approaches to palliate MPE are needed Between December 1985 and August 1988 , there were 115 patients at 13 centers who were entered on a r and omized comparison of tetracycline and bleomycin for treatment of malignant pleural effusions . Fifteen patients were not treated , primarily due to rapid progression of systemic cancer . Fifteen patients entered on a high-dose regimen of bleomycin ( 120 units ) were excluded from this analysis ( following early closure of that arm ) , leaving 85 patients r and omized to low-dose bleomycin ( 60 units ; 44 patients ) or tetracycline ( 1 g ; 41 patients ) . Patients were required to have a cytologically positive pleural effusion , good performance status ( 0 , 1 , or 2 ) , lung reexpansion following tube thoracostomy with drainage rates of 100 ml/24 or less , no prior intrapleural therapy , no prior systemic bleomycin therapy , no chest irradiation , and no recent ( four weeks ) change in systemic therapy . A total of 11 patients ( five with bleomycin and six with tetracycline ) were not evaluable due to technical problems with tube drainage ( one ) , loss to follow-up ( two ) , sudden death due to pulmonary embolus ( one ) , and rapid progression of systemic disease ( seven ) . There were no clinical ly significant differences in demographic factors , primary site , performance status , or presence of metastases other than pleural effusion . Overall survival did not differ between the two groups . Median time to recurrence or progression of the effusion was 32 days for tetracycline-treated patients and at least 46 days for bleomycin-treated patients ( p = 0.037 ) . The recurrence rate within 30 days of instillation was 36 percent ( 10/28 ) with bleomycin and 67 percent ( 18/27 ) with tetracycline ( p = 0.023 ) ( not all patients were restudied in the first 30 days ) . By 90 days the corresponding recurrence rates were 30 percent ( 11/37 ) for bleomycin and 53 percent ( 19/36 ) for tetracycline ( p = 0.047 ) . Toxicity was similar between groups OBJECTIVE Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions . A r and omized clinical trial was conducted to compare the efficacy of two commonly used agents , talc and bleomycin , for the pleurodesis of malignant pleural effusions . METHODOLOGY Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy . Exclusion criteria included trapped lung , loculated effusions , recurrent effusions and life expectancy < 1 month . Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient . Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis . RESULTS Treatment success was achieved in 16 out of 18 patients ( 89 % ) in the talc slurry group versus 14 out of 20 patients ( 70 % ) in the bleomycin group ( P=0.168 ) . Fever and pain were the only side-effects of pleurodesis in both groups . CONCLUSION These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions . Pleurodesis with talc instead of bleomycin can result in significant cost savings We report two trials describing whether talc pleurodesis with a mean particle size of less than 15 microm ( " mixed " talc ) produces more lung and systemic inflammation than tetracycline or " grade d " talc ( most particles < 10 microm were removed ) . First , 20 patients with malignant effusions received tetracycline or mixed talc . Changes in lung and systemic inflammation from lung clearance scans , oxygen saturations , and C-reactive protein from baseline to 48 hours after pleurodesis were recorded . Lung inflammation ( change in isotope clearance , talc -9.26 , SD 14.3 vs. tetracycline 4.10 , SD 13.8 minutes ; difference = -13.4 ; 95 % confidence interval [ CI ] , -26.6 to -0.2 ; p = 0.05 ) and systemic inflammation ( change in C-reactive protein , talc 198 SD 79.2 vs. tetracycline 74 SD 79.4 microg/L ; difference = 124 ; 95 % CI , 50 to 199 ; p = 0.004 ) were greater after talc . Second , 48 patients received mixed or grade d talc , and gas exchange was assessed from changes in the alveolar-arterial oxygen gradient . Mixed talc worsened gas exchange ( oxygen gradient change , mixed 2.17 SD 1.74 kPa , 16.3 13.1 mm Hg vs. grade d 0.72 SD 2.46 kPa 5.4 18.5 mm Hg , difference = 1.45 ; 95 % CI , 0.2 to 2.7 ; p = 0.03 ) and induced more systemic inflammation than grade d talc . We conclude that the routine use of grade d talc for pleurodesis would reduce the morbidity of this procedure OBJECTIVE The objective of the study was to see whether a rapid method of pleurodesis was superior to the st and ard protocol in patients with symptomatic malignant pleural effusion . METHODS Between January 2000 and February 2003 , a prospect i ve r and omised trial was carried out in a sequential sample of 27 patients with malignant pleural effusions documented cytopathologically . Twelve patients were allocated to group 1 ( st and ard protocol ) and 15 to group 2 ( new protocol ) . A small-bore catheter ( 12 Fr ) and oxytetracycline ( 35 mg/kg of body weight ) were used in both groups . In group 1 , patients had drainage until radiological evidence of lung re-expansion was obtained and the amount of fluid drained was less than 150 ml/day , before oxytetracycline was instilled . The catheter was removed when the amount of fluid drained after instillation was less than 150 ml/day . In group 2 , patients had the oxytetracycline instilled in a fractionated-dose manner following frequent aspirations at 6h intervals . The catheter was removed when the total amount of fluid drained after instillation of the oxytetracycline [ OT ] was less than 150 ml/last three aspirations . Response was evaluated at 1 , 3 and 6 months after pleurodesis . RESULTS There was no statistically significant difference in the demographic features , site of the primary tumour , disease characteristics , and response rates in any evaluation period in both groups ( P>0.05 ) . However , the number of days of drainage and hospitalisation , and the cost were significantly lower in the second group ( P<0.001 ) . CONCLUSIONS This new pleurodesis method provided shorter hospital stay result ing in superior cost-effectiveness and palliation without sacrificing the efficacy of pleurodesis Forty-one patients with malignant pleural effusions secondary to breast cancer were r and omly allocated to treatment with either intracavitary talc or intracavitary tetracycline . Of 33 evaluable patients , radiological control was achieved in 11/12 ( 92 % ) of the talc group compared with 10/21 ( 48 % ) of the tetracycline group ( P = 0.022 ) . Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer BACKGROUND Malignant pleural effusion is a common problem in advanced cancers , contributing to the poor quality of life in this group of patients . The aim of the study was to assess the efficiency of talc powder and doxycycline in pleurodesis in patients with malignant pleural effusion in comparable conditions . MATERIAL / METHODS Of 52 patients screened , 33 entered the trial . They were r and omized to the talc group ( n=18 ) and the doxycycline group ( n=15 ) . Both groups were comparable with regard to age , sex and the most important variables influencing effectiveness of the procedure , i.e. primary malignancy and stage of metastatic involvement of the pleura . Efficiency of pleurodesis was prospect ively assessed . RESULTS The analysis of short-term effectiveness of pleurodesis in the first 33 patients has shown a highly significant difference in favor of talc powder ( p=0.009 ) ; this difference was the reason for terminating the r and omization . Further observation has revealed in the doxycycline group an increasing number of patients with fluid reaccumulation , as time went by ; this was not observed in the talc group . A statistical analysis of the long-term effectiveness of both agents studied has shown a more significant difference in favor of the talc powder ( p=0.00003 ) . CONCLUSIONS Talc powder is superior to doxycycline in achieving pleurodesis in patients with malignant pleural effusion , in both short- and long-term observations Background : In this study , we aim ed to investigate the effectiveness of silver nitrate ( SN ) versus tetracycline in pleurodesis among patients with malignant pleural effusion ( MPE ) . Methods : In this prospect i ve r and omized clinical trial , patients with unilateral MPE c and i date for pleurodesis were enrolled . The patients r and omly allocated in two groups for receiving 20 mL 0.5 % SN or 2.5 g tetracycline diluted in 30 cc normal saline and 0.1 % lidocaine , through the chest tube . Patients were followed-up immediately ( during 24 h ) and 1-month after the procedure for evaluating recurrence of the pleural effusion using chest radiograph . They were clinical ly evaluated for chest pain and /or dyspnea and fever using a question naire that completed by the surgeon . The results were compared with two groups . Results : During this trial , 50 patients with MPE c and i date for pleurodesis were selected and r and omized into two interventional groups ( 25 patients in each group ) . Immediate and late recurrence of pleural effusion after pleurodesis were similar in two groups ( P > 0.05 ) . All patients in tetracycline group had fever and chest pain , but in SN group fever and chest pain were reported in 3 ( 12 % ) and 12 ( 48 % ) of patients , respectively ( P < 0.05 ) . Conclusion : SN is at least as effective as tetracycline for MPE treatment . In addition , its side effects were lower than tetracycline . Other advantages of SN are its low cost , availability , and safety . For more accurate results , it is recommended to design further trials with larger sample size and with lower doses of both SN and tetracycline BACKGROUND Chemical pleurodesis can be palliative for recurrent , symptomatic pleural effusions in patients who are not c and i date for a thoracic surgical procedure . We hypothesized that effective pleurodesis could be accomplished with a rapid method of pleurodesis as effective as the st and ard method . METHODS A prospect i ve r and omized ' non-inferiority ' trial was conducted in 96 patients with malignant pleural effusion ( MPE ) who are not potentially curable and /or not amenable to any other surgical intervention . They were r and omly allocated to group 1 ( rapid pleurodesis ) and to group 2 ( st and ard protocol ) . In group 1 , following complete fluid evacuation , talc slurry was instilled into the pleural space . This was accomplished within 2 h of thoracic catheter insertion , unless the drained fluid was more than 1,500 mL. After clamping the tube for 30 min , the pleural space was drained for 1 h , after which the thoracic catheter was removed . In group 2 , talc-slurry was administered when the daily drainage was lower than 300 mL/day . RESULTS No-complication developed due to talc-slurry in two groups . Complete or partial response was achieved in 35 ( 87.5 % ) and 33 ( 84.6 % ) patients in group 1 and group 2 respectively ( P=0.670 ) . The mean drainage time was 40.7 and 165.2 h in group 1 and group 2 respectively ( P<0.001 ) . CONCLUSIONS Rapid pleurodesis with talc slurry is safe and effective and it can be performed in an outpatient basis Talc pleurodesis is an effective technique for the management of symptomatic malignant pleural effusions . It is assumed that a good dispersion of talc suspension contributes to the final success of this treatment . For this purpose , guidelines often advise to rotate the patient after intra-pleural instillation of the sclerosant . This prospect i ve , r and omized study analyses the dispersion of talc suspension and the overall success rate in patients with malignant effusions . After instillation of 99mTc-sestamibi-labeled talc suspension ten subjects were rotated for 1 h , while the ten other patients remained in a stable supine body position . Scintigraphic imaging was done in two directions immediately after instillation and after 1 h with a clamped drain . The overall success of the treatment was assessed 1 month after the pleurodesis . The dispersion of talc was limited and unequal in 75 % of the subjects . In two patients with apparently good distribution on anterior views , the lateral views of the scintigraphy showed only limited distribution . Rotation of the patients did not influence the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful in 85 % of the patients after 1-month follow-up . St and ard rotation protocol s for patients with malignant pleural effusion do not affect the overall dispersion of talc suspension and should be abolished because of the discomfort caused to the patients Induction of pleurodesis offers benefit for patients with metastatic tumors and symptomatic malignant pleural effusions , but the best method for achieving this is still unknown . In this prospect i ve , r and omized comparison of two well-established pleurodesis procedures , 36 patients with malignant pleural effusions , exp and ed lungs after drainage , and expected survival of > 1 mo received either bleomycin instillation ( 60E ) via a small-bore thoracostomy tube or thoracoscopic talc poudrage ( 5 g ) under local anesthesia . Efficacy , safety , and cost could be evaluated for 32 treatments ( 17 bleomycin , 15 talc ) in 31 patients . Recurrence rates of effusion with bleomycin and talc poudrage after 30 d were 41 % and 13 % ( p = 0.12 ) , respectively , those after 90 d were 59 % and 13 % , respectively ( p = 0.01 ) , and those after 180 d were 65 % and 13 % ( p = 0.005 ) , respectively . Neither procedure showed any major adverse effect , and both were equally well tolerated . Cost estimation favored thoracoscopic talc poudrage , both for the initial hospitalization and with regard to recurrences . In conclusion , thoracoscopic talc pleurodesis under local anesthesia is superior to bleomycin instillation for pleurodesis in cases of malignant pleural effusion STUDY OBJECTIVES Pleurodesis is generally regarded to give the best palliation in recurrent pleural effusion . Talc is now increasingly recommended but in our department quinacrine has been used successfully for many decades with good results and only minor side effects . It was therefore decided to make a prospect i ve r and omized clinical study comparing quinacrine ( 500 mg ) with talc ( 5 g ) with regard to efficacy and safety . METHODS One hundred and ten eligible consecutive patients with recurrent and or malignant effusions , from 1 March 1996 till 31 March 1999 were r and omized to chemical pleurodesis with either talc or quinacrine through a chest drainage tube after medical thoracoscopy . Patients were evaluated with chest radiographs at 2 weeks and 2 , 4 , and 6 months after pleurodesis . RESULTS Chi-square test showed 84 % power to distinguish between the groups and 10 % to determine the primary endpoint . Primary success ( fluid production < 50ml/24h within the first 6 days ) was 96 % of 56 patients with talc and 91 % of 54 patients with quinacrine , a non-significant difference ( P = 0.46 ) . Quinacrine patients needed a repeated treatment in 31 % ( 17 patients ) and talc patients in 7 % ( 4 patients ) ( P < 0.05 ) . Side effects were minor with no significant difference between the substances . CONCLUSIONS Both substances are effective . Talc treatment had less often to be repeated . This indicates that the recommendation of talc for pleurodesis is well founded . However , quinacrine is a good alternative OBJECTIVE A prospect i ve r and omised study was conducted to compare the efficacy of treating malignant pleural effusions ( MPE ) in patients with breast carcinoma by thoracoscopic mechanical pleurodesis ( TMP ) as a new palliative treatment and talc pleurodesis ( TP ) at various pleural fluid pH levels and to determine whether at low pH values , when the success of TP is reduced , TMP is more successful . METHODS 87 female patients with breast carcinoma and a result ing MPE resistant to systemic therapy were divided into two groups : TMP and TP groups . In the TMP group 24 patients with pH levels above 7.3 and 21 patients with pH levels below 7.3 underwent thoracoscopic parietal and visceral pleural abrasion utilising general anaesthesia . In the TP group , 22 patients with pH levels above 7.3 and 20 patients with pH levels below 7.3 were administered 5 g of sterile talc , dissolved in 100 ml of physiological solution , via a chest tube , utilising local anaesthesia . Postoperative follow-up was performed to determine a possible recurrence of MPE with periodic radiographs , the duration of chest tube drainage and hospitalisation , occurrence of complications , and perioperative mortality . The following was used for statistical analysis : t-test for odd sample s , chi2 test , logistic regression , and multiple linear regression . RESULTS TMP and TP were equally successful ( 92 and 91 % ) in patients with pH levels above 7.3 . Differences occurred in patients with pH below 7.3 ( 81 and 55 % ) ( P = 0.07 ) . The lowest pH value at which TMP proved successful was 7.06 , while for TP this value was 7.25 . In TMP group the average duration of chest tube drainage amounted to 3.8 days and hospitalisation to 5.5 days , while in TP group it was 5.6 and 7.5 days , respectively . Differences were statistically significant ( P < 0.05 ) . 16 % of easily treatable complications and no case of perioperative mortality were identified in TMP group , while 26 % of complications and four cases of perioperative mortality were noted in TP group . CONCLUSIONS TMP is a safe palliative treatment for MPE in breast carcinoma , with a minimal number of complications and a short hospital stay ; it is more successful than TP in patients with pH of MPE below 7.3 In a r and omized trial , pleurodesis was attempted with Corynebacterium parvum in one group and bleomycin in another . Patients with malignant pleural effusion which required repeated drainage were treated with instillation of one of these agents after complete drainage of the pleural effusion . There were 32 patients who could be evaluated . Sixty-five per cent of the patients treated with C. parvum had no recurrence after one treatment and another 29 % after two treatments . In the bleomycin group , two patients needed only one treatment while the remainder - 13 out of 15 patients - needed further drainage treatments even after two instillations of the drug . The difference was highly significant ( p less than 0.001 ) Abstract Expansion of the lung is necessary for successful pleurodesis therapy in patients with malignant pleural effusion ( MPE ) . However , this is often impossible in multiloculated MPEs . The aim of this study was to investigate the effect of the fibrinolytic agent , streptokinase , on pleurodesis therapy used in the management of multiloculated MPE . Forty patients with multiloculated MPEs were r and omly assigned to two groups : fibrinolytic and control . In the fibrinolytic group , 250,000 IU of streptokinase in 50 ml saline was applied into the pleural space at 24–36–48–60 h after opening a tube thoracostomy . In the control group , the same procedure was carried out using only 50 ml saline solution . Both groups were compared based on the following : ( 1 ) volume of pleural drainage at 24–48 , 48–72 , and 24–72 h , ( 2 ) chest computer tomography images before and after therapy , ( 3 ) dyspnea symptoms after therapy , and ( 4 ) recurrence rate . The mean drainage volumes for the fibrinolytic and control groups were 493 and 248 cc at 24–48 h , 446 and 198 cc at 48–72 h , and 939 and 446 cc at 24–72 h ( P < 0.001 ) . Comparison of the two groups by computer tomography revealed that 17 patients ( 85 % ) in the fibrinolytic group had greater than 40 % improvement , whereas only 7 patients ( 35 % ) in the control group had the same degree of improvement ( P = 0.001 ) . The dyspnea symptoms disappeared in 90 % of the patients in the fibrinolytic group and in 55 % of the patients in the control group ( P = 0.03 ) . Recurrence rate was 11 % in fibrinolytic group and 45 % in control group ( P = 0.07 ) . Streptokinase is a reliable treatment option in obtaining effective pleural drainage and increasing lung expansion in patients with multiloculated MPE Background : Pleural fluid loculations or trapped lungs frequently render patients with symptomatic malignant pleural effusions ( MPEs ) unsuitable for pleurodesis . Thoracoscopic surgery or thoracotomy with decortication is generally not feasible for patients with a poor performance status . MPEs have augmented procoagulant and depressed fibrinolytic activity that contributes to fibrin deposition within the pleural space . The authors conducted an observational prospect i ve cohort study to investigate the use of intrapleural urokinase ( IPUK ) for such patients and made a comparison with a historical control group . Methods : Between March of 2000 and August of 2005 , 48 consecutive patients with symptomatic MPEs with an average Karnofsky performance scale score of 46.7 % were recruited . Dyspnea persisted with the presence of substantial residual loculated MPEs in 36 patients and trapped lungs in 12 patients , when the effectiveness of 8-French intrapleural catheter drainage had decreased despite regular saline flushes . Urokinase was instilled daily through the catheter at a dose of 100,000 IU diluted in 100 ml of normal saline for 3 days . Additional IPUK instillation was required upon partial improvement . The records and chest radiographs of another 52 patients with symptomatic MPEs had met these eligibility criteria between January of 1995 and February of 2000 and received saline flushes only were also review ed . Results : Immediate lung reexpansion and resolution of dyspnea was achieved in 29 of the 48 patients who underwent IPUK therapy ( 60.4 % ) . The mean dose of urokinase instillations per patient was 360,000 IU . There were no major complications . A significant association of earlier intervention with the success of IPUK therapy was noted . Responders also had a significantly increased drainage within the 24 hours after the first dose of IPUK . Minocycline pleurodesis was subsequently performed for the 29 IPUK responders . Eighteen patients were followed up until death , with a median survival of 6.5 months . The other remained alive at the time of analysis with a median follow-up of 5 months . Two patients had an immediate failure of pleurodesis at 1 month . Three relapses occurred at 3 , 4 , and 7 months from pleurodesis , respectively . Twenty-three patients ( 79.3 % ) had lifelong pleural symphysis , including 21 having loculated MPEs and two having trapped lungs , respectively . Compared with the historical control group , the IPUK study group had significantly greater improvement on chest radiography and a shorter duration of pleural drainage . Conclusion : These results suggest that IPUK is a safe and useful nonsurgical adjunct therapy for loculated MPEs or trapped lungs in medically inoperable cancer patients In comparative studies with other agents , insufflated talc has been shown to be the most effective agent in achieving chemical pleurodesis in patients with malignant pleural effusions . The objective of this study is to compare the efficacy of talc administered as slurry ( 5 g in 50 mL saline ) via tube thoracostomy with that of bleomycin ( 1 mg/kg in 50 mL saline ) ( which is the most effective agent other than talc ) . In a r and omised , prospect i ve comparative study , twenty-six consecutive patients with proven malignant pleural effusions ( recurrent after at least two pleuroscenteses ) in whom no pleurodesis attempt had yet been made , and who were symptomatic , had a Karnovski index < or = 50 , and an expected survival of one year or less , were included . Therapeutic failure was defined as recurrent pleural fluid > or = 50 % of initial volume or requiring pleurocentesis . Recurrence rates ( 25 % vs 21.4 % , NS ) , fever ( 25 % vs 35.7 % , NS ) , pain ( 0 % both groups ) and survival ( 3.75 + /- 3 vs 5.82 + /- 7.15 months , NS ) did not differ between bleomycin or talc treated patients . There were no major complications ( e.g. , empyema ) or side-effects . In conclusion , talc slurry and bleomycin are equally effective in achieving chemical pleurodesis via thoracostomy in patients with malignant pleural effusions , and the safety profile of both agents is similar . Since talc is substantially less expensive than bleomycin , talc slurry probably represents the agent of choice for chemical tube thoracostomy pleurodesis CONTEXT Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy . Palliation is achieved by fluid drainage , but the most effective first-line method has not been determined . OBJECTIVE To determine whether indwelling pleural catheters ( IPCs ) are more effective than chest tube and talc slurry pleurodesis ( talc ) at relieving dyspnea . DESIGN Unblinded r and omized controlled trial ( Second Therapeutic Intervention in Malignant Effusion Trial [ TIME2 ] ) comparing IPC and talc ( 1:1 ) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals . Patients were screened from April 2007-February 2011 and were followed up for a year . INTERVENTION Indwelling pleural catheters were inserted on an outpatient basis , followed by initial large volume drainage , education , and subsequent home drainage . The talc group were admitted for chest tube insertion and talc for slurry pleurodesis . MAIN OUTCOME MEASURE Patients completed daily 100-mm line visual analog scale ( VAS ) of dyspnea over 42 days after undergoing the intervention ( 0 mm represents no dyspnea and 100 mm represents maximum dyspnea ; 10 mm represents minimum clinical ly significant difference ) . Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables . RESULTS Dyspnea improved in both groups , with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group ( 95 % CI , 19.3 - 30.1 mm ) and 24.4 mm ( 95 % CI , 19.4 - 29.4 mm ) in the talc group , with a difference of 0.16 mm ( 95 % CI , −6.82 to 7.15 ; P = .96 ) . There was a statistically significant improvement in dyspnea in the IPC group at 6 months , with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm ( 95 % CI , −25.2 to −2.8 mm ; P = .01 ) . Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days ( interquartile range [ IQR ] , 0 - 1 day ) and 4 days ( IQR , 2 - 6 days ) for the talc group , with a difference of −3.5 days ( 95 % CI , −4.8 to −1.5 days ; P < .001 ) . There was no significant difference in quality of life . Twelve patients ( 22 % ) in the talc group required further pleural procedures compared with 3 ( 6 % ) in the IPC group ( odds ratio [ OR ] , 0.21 ; 95 % CI , 0.04 - 0.86 ; P = .03 ) . Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group ( OR , 4.70 ; 95 % CI , 1.75 - 12.60 ; P = .002 ) . CONCLUSION Among patients with malignant pleural effusion and no previous pleurodesis , there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N87514420 OBJECTIVE To evaluate the efficacy of combined intrapleural therapy with cisplatin , an antineoplastic agent , and OK432 , a sclerosing agent , in controlling malignant pleural effusions , when compared with monotherapy with either agent . METHODS A total of 49 non-small cell lung cancer patients with malignant pleural effusion were r and omly assigned to one of three groups : intrapleural cisplatin therapy ( n = 17 ) , intrapleural OK432 therapy ( n = 17 ) , or both ( n = 15 ) . They were compared in terms of success rate , duration of indwelling chest tube and adverse reactions . RESULTS Rates of pleural effusion recurrence within 180 days following cisplatin , OK432 , or combination therapy were 64.7 % , 52.9 % and 13.3 % , respectively , being significantly lower in the combination therapy group ( P = 0.01 ) . The mean duration of chest tube drainage was 8.4 days , 5.5 days and 12.9 days , respectively , being significantly longer in the combination therapy group ( P < 0.001 ) . All procedures were well tolerated . CONCLUSIONS Although chest tube drainage took longer because of the time required for multiple administration of the agents , intrapleural combination therapy with cisplatin and OK432 was more effective in controlling malignant pleural effusions due to non-small cell lung cancer than monotherapy with either agent Effective palliative treatment in malignant pleural effusion can only be carried out when the lung is fully exp and ed after drainage of effusion . We investigated the efficacy of intrapleural fibrinolytics for lysing fibrin deposits and improving lung reexpansion in patients with malignant pleural effusion . We r and omly allocated 47 patients with malignant pleural effusion into 2 groups : a fibrinolytic group of 24 were given 3 cycles of 250,000 U intrapleural streptokinase ; the control group of 23 received pleural drainage only . Pleurodesis with 5 mg of talc slurry was performed in all patients who had lung reexpansion after drainage . Patient characteristics , pleural drainage , lung expansion assessed by chest radiography , and pleurodesis outcomes were compared between the 2 groups . Patient characteristics were similar in both groups . Lung reexpansion was adequate for performing talc pleurodesis in 96 % of patients in the fibrinolytic group and 74 % in the control group . In the fibrinolytic group , the mean volume of daily pleural drainage before streptokinase administration was 425 mL , and it increased significantly to 737 mL after streptokinase infusion . Intrapleural administration of streptokinase is advisable for patients with malignant pleural effusion Effusions are common in advanced cancer . Intracavitary instillation of various agents such as bleomycin has achieved control rates varying between 20 % and 60 % . However , serious side effects have also been observed , and cases of death due , for instance , to bleomycin have been reported . Mitoxantrone has been tested recently in the treatment of effusions , and preliminary results suggest high efficacy of this drug in the treatment of peritoneal , pericardial , and pleural effusions . Nevertheless , certain results have been conflicting . In the present study , 29 patients with pleural effusions were treated either with intracavitary bleomycin or intracavitary mitoxantrone . Effusions were controlled almost equally by both agents ; 67 % with mitoxantrone and 64 % with bleomycin . We conclude that both agents can be used successfully in the treatment of pleural effusions From 11/87 until 7/90 103 patients entered a prospect i ve r and omized trial on the treatment of malignant pleural effusions ( MPE ) with intrapleural mitoxantrone versus placebo ( pleural tube alone with instillation of isotonic NaCl ) . Our data suggest no statistically significant difference between the two arms with respect to response and response duration . There is no influence on survival time . The toxicity is moderate , with only fever occurring more often in the mitoxantrone arm . We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16 - 20 char . Only in instances of failure it is necessary to add sclerosing agents such as tetracycline , etc The effect of local instillation of mepacrine hydrochloride ( quinacrine hydrochloride U.S.P. , Atabrine ) was compared with triethylenethiophosphoramide ( Thiotepa ) applied locally and with pleurocentesis alone . Twentyfive patients with disseminated malignant disease were allocated at r and om to one of these three treatments . A finding of more than 500 ml effusion within 3 months of instituting treatment was regarded as a failure , and subsequently one of the other treatments was used at r and om . Sixty-four per cent of the patients treated with mepacrine responded , compared with 27 % treated with triethylenethiophosphoramide , and 11 % treated with pleurocentesis alone Malignant pleural effusion is a common complication in certain malignancies . Pleurodesis is the best option most of the time . The purpose of this study was to compare the choice of belomycin with povidone-iodine , which is not only determined by the efficacy of the agent but also by its cost , accessibility , safety , ease of administration and the number of administrations to achieve a complete response . We performed a r and omized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion . Patients were selected and r and omly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine . Primary characteristics of patients were assessed and grade d before and after treatment concerning pain , dyspnea , and chest radiographs . A complete response was obtained in 79 % of belomycin group and 75 % of povidone-iodine group which was not statistically significant . Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up . This was significant after controlling for age , pain score and dyspnea score after drainage , using general linear model . Due to similar effect and significant cost advantage between bleomycin and povidone-iodine , we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions A prospect i ve r and omized study to compare the effectiveness of pleurodesis by two new sclerosing agents : OK‐432 and mitomycin C were conducted in S3 patients with malignant pleural effusion caused by lung cancer . None of the patients received concomitant systemic chemotherapy or radiation therapy during the study . After complete drainage of pleural fluid , the patients were allocated r and omly to receive 10 Klinische Einheit units of OK‐432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals . The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures . There were 26 patients who received pleurodesis with OK‐432 and 27 , with mitomycin C. Patient characteristics in the two treatment groups ( age , sex , histologic type , performance status , and prior treatment before pleurodesis ) were compatible . These results showed that pleurodesis with OK‐432 achieved a higher complete response rate ( 73 % ) than that of mitomycin C ( 41 % ) . The rates of objective treatment response ( complete response plus partial response ) were comparable in both groups ( 88 % for OK‐432 and 67 % for mitomycin C ) . The average number of intrapleural injections needed to achieve complete response was fewer in the OK‐432 group ( 1.9 + M 0.9 ) than in mitomycin C group ( 2.8 + M 0.9 ) . There was no significant difference in the median survival of the patients who received pleurodesis with OK‐432 ( 5.8 months ) or mitomycin C ( 5.1 months ) . However , the effusion‐free period in the OK‐432 group was significantly longer than that in the mitomycin C group ( 7.0 months versus 1.5 months ) . Patients who underwent OK‐432 pleurodesis had a higher complication rate ( 80 % ) than did those in the mitomycin C group ( 30 % ) . Transient febrile reaction was the most common reaction encountered . The immunologic study in OK‐432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio . The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio . It was concluded that pleurodesis with OK‐432 is an effective alternative treatment for malignant effusion in patients with lung cancer Intrapleural instillation of tetracycline ( TCN ) has been shown to be effective in preventing the recurrence of malignant pleural effusions . Although the precise mechanism of action is unknown , it has been postulated that the pH of the TCN solution may be an important factor . Thirty patients with malignant pleural effusions were r and omized in a double‐blind trial to receive intrapleural administration of either 500 mg of tetracycline in solution ( pH = 2.8 ) or a solution of similar pH and appearance . All patients had chest tube drainage of their effusion . There were 24/30 patients evaluable . There were 9/13 patients in the TCN group and 1/9 patients in the control group who had no reaccumulation of fluid ( P < 0.05 ) . These results would suggest that the efficacy of TCN as a sclerosing agent is not related to its acidic pH and that intrapleural TCN is more effective than chest tube drainage alone for control of malignant effusions Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity . Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients . To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant , 34 patients were prospect ively r and omised to a trial comparing the two treatment modalities , of whom 29 were evaluable for response . The total failure rate of primary pleurodesis was 13.4 % , the rate of recurrence of effusion within the first month was 24 % , and only 1 patient ( 3.4 % ) required repeat aspiration in that time period . There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups . Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group ( P = 0.03 ) , this is likely to be due to factors other than the method of treating the effusion . We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis The purpose of this study was to evaluate the efficacy , safety , and cost of bedside pleurodesis for malignant pleural effusions using talc slurry ( TS ) or bleomycin ( BL ) in a prospect i ve r and omized trial , and to determine prognosticators for procedure failure . From June 1997 to June 1999 a series of 71 patients entered this trial . They underwent 37 procedures with TS ( 4 g ) and 34 with BL ( 60 units ) via tube thoracostomy . Success was defined as no recurrence of pleural effusion or asymptomatic recurrence of a small amount of effusion . Pleural effusion-free survival curves were used to analyze the success rates and the prognosticators of failure . Follow-up ranged from 3 days to 26 months ( median 2.5 months ) . No difference in success rates was detected between TS or BL ( log-rank test : p = 0.724 ) . There were no major complications related to the procedure . The independent prognosticators of failed pleurodesis were the use of steroids ( p = 0.004 ) and the volume of pleural fluid drained during the first thoracentesis when it was more than 900 ml ( p = 0.029 ) . The average cost of intervention per patient was significantly lower for TS ( p < 0.001 ) . There was no significant difference between the success rates for TS and BL as agents of bedside pleurodesis for malignant pleural effusions . Because of its significantly lower cost , TS should be considered the agent of choice . The use of steroids and the volume drained during the first thoracentesis ( if more than 900 ml ) were independent prognosticators of pleurodesis failure . The role of this latter finding as a marker of pleurodesis failure awaits more data Background : The aim of this study was to compare the response of doxycycline and bleomycin in pleurodesis of malignant pleural effusions . Material s and Methods : The radiologic and clinical responses of doxycycline and bleomycin in pleurodesis of malignant pleural effusions were compared in this r and omized clinical trial . Forty-two patients were r and omized to receive either bleomycin 45 mg or doxycycline 600 mg as the sclerotherapy agent . Chest X-rays were taken before and after intervention , 10 days and 2 months later to compare the radiologic response . Dyspnea and other side effects , before and after intervention , 10 days and 2 months later were recorded and compared . Chi-square test was applied to analyze the data . Results : The prevalence of dyspnea and its different severities , 10 days and 2 months after intervention were significantly different ( P < 0.05 ) between the two groups . Analysis of pleural effusions revealed a significant difference ( P < 0.05 ) between Doxycycline vs. Bleomycin 2 months after the intervention . Three months after pleurodesis , only one patient in bleomycin group needed pleural fluid drainage . Conclusion : Pleural effusions did not change with use of doxycycline and bleomycin in short time but long-term results of doxycycline sclerotherapy was better than bleomycin sclerotherapy in malignant pleural effusions that was supported by this study . However , additional studies with larger sample size are necessary to confirm the results Rationale : Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy . Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis . The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined . Objectives : To determine whether an aggressive daily drainage strategy is superior to the current st and ard every other day drainage of pleural fluid in achieving autopleurodesis . Methods : Patients were r and omized to either an aggressive drainage ( daily drainage ; n = 73 ) or st and ard drainage ( every other day drainage ; n = 76 ) of pleural fluid via a tunneled pleural catheter . Measurements and Main Results : The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters . The rate of autopleurodesis , defined as complete or partial response based on symptomatic and radiographic changes , was greater in the aggressive drainage arm than the st and ard drainage arm ( 47 % vs. 24 % , respectively ; P = 0.003 ) . Median time to autopleurodesis was shorter in the aggressive arm ( 54 d ; 95 % confidence interval , 34‐83 ) as compared with the st and ard arm ( 90 d ; 95 % confidence interval , 70 to nonestimable ) . Rate of adverse events , quality of life , and patient satisfaction were not significantly different between the two arms . Conclusions : Among patients with malignant pleural effusion , daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter . Clinical trial registered with www . clinical trials.gov ( NCT 00978939 ) Rationale : Patients with malignant pleural effusion experience breathlessness , which is treated by drainage and pleurodesis . Incomplete drainage results in residual dyspnea and pleurodesis failure . Intrapleural fibrinolytics lyse septations within pleural fluid , improving drainage . Objectives : To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion . Methods : We conducted a prospect i ve , double‐blind , r and omized trial . Patients with nondraining effusion were r and omly allocated in a 1:1 ratio to intrapleural urokinase ( 100,000 IU , three doses , 12‐hourly ) or matched placebo . Measurements and Main Results : Co‐ primary outcome measures were dyspnea ( average daily 100‐mm visual analog scale scores over 28 d ) and time to pleurodesis failure to 12 months . Secondary outcomes were survival , hospital length of stay , and radiographic change . A total of 71 subjects were r and omized ( 36 received urokinase , 35 placebo ) from 12 U.K. centers . The baseline characteristics were similar between the groups . There was no difference in mean dyspnea between groups ( mean difference , 3.8 mm ; 95 % confidence interval [ CI ] , ‐12 to 4.4 mm ; P = 0.36 ) . Pleurodesis failure rates were similar ( urokinase , 13 of 35 [ 37 % ] ; placebo , 11 of 34 [ 32 % ] ; adjusted hazard ratio , 1.2 ; P = 0.65 ) . Urokinase was associated with decreased effusion size visualized by chest radiography ( adjusted relative improvement , ‐19 % ; 95 % CI , ‐28 to ‐11 % ; P < 0.001 ) , reduced hospital stay ( 1.6 d ; 95 % CI , 1.0 to 2.6 ; P = 0.049 ) , and improved survival ( 69 vs. 48 d ; P = 0.026 ) . Conclusions : Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and can not be recommended as an adjunct to pleurodesis . Other palliative treatments should be used . Improvements in hospital stay , radiographic appearance , and survival associated with urokinase require further evaluation . Clinical trial registered with IS RCT N ( 12852177 ) and EudraCT ( 2008‐000586‐26 ) |
12,538 | 21,887,777 | Surgery for morbid obesity increases health-related quality of life , and reduces the need for further treatments and total healthcare costs .
According to this analysis , non-operative care would be more costly for the Finnish healthcare system on average after 5 years following surgery | BACKGROUND The aim of this study was to evaluate the cost-utility of bariatric surgery ( gastric bypass , sleeve gastrectomy and gastric b and ing ) compared with ordinary treatment in the Finnish healthcare system . | BACKGROUND Obesity is associated with increased morbidity rates and pharmaceutical costs . To what extent various medication costs are affected by intentional weight loss is unknown . METHODS A cross-sectional comparison of the use of prescribed pharmaceuticals was conducted in 1286 obese individuals in the Swedish Obese Subjects ( SOS ) intervention study and 958 r and omly selected reference individuals . Medication changes for 6 years after bariatric surgery were evaluated in 510 surgically and 455 conventionally treated SOS patients . RESULTS Compared with the reference group , obese individuals were more often taking diabetes mellitus , cardiovascular disease , nonsteroidal anti-inflammatory and pain , and asthma medications ( risk ratios ranging from 2.3 - 9.2 ) . Average annual costs for all medications were 1400 Swedish kronor ( SEK ) ( US $ 140 ) in obese individuals and 800 SEK ( US $ 80 ) in the reference population ( P<.001 ) . Average yearly medication costs during follow-up were 1849 ( US $ 185 ) in surgically treated patients ( weight change -16 % ) and 1905 SEK ( US $ 190 ) in weight-stable conventionally treated patients ( P = .87 ) . The surgical group had lower costs for diabetes mellitus ( difference : -94 SEK/y ( -US $ 9 ] ) and cardiovascular disease medications ( difference : -186 SEK/y ( -US $ 19 ] ) but higher costs for gastrointestinal tract disorder ( difference : + 135 SEK/y [ US $ 13 ] ) and anemia and vitamin deficiency medications ( difference : + 50 SEK/y [ US $ 5 ] ) . CONCLUSIONS Use and cost of medications are markedly increased in obese vs reference population s. Surgical obesity treatment lowers diabetes mellitus and cardiovascular disease medication costs but increases other medication costs , result ing in similar total costs for surgically and conventionally treated obese individuals for 6 years BACKGROUND Obesity is associated with increased mortality . Weight loss improves cardiovascular risk factors , but no prospect i ve interventional studies have reported whether weight loss decreases overall mortality . In fact , many observational studies suggest that weight reduction is associated with increased mortality . METHODS The prospect i ve , controlled Swedish Obese Subjects study involved 4047 obese subjects . Of these subjects , 2010 underwent bariatric surgery ( surgery group ) and 2037 received conventional treatment ( matched control group ) . We report on overall mortality during an average of 10.9 years of follow-up . At the time of the analysis ( November 1 , 2005 ) , vital status was known for all but three subjects ( follow-up rate , 99.9 % ) . RESULTS The average weight change in control subjects was less than + /-2 % during the period of up to 15 years during which weights were recorded . Maximum weight losses in the surgical subgroups were observed after 1 to 2 years : gastric bypass , 32 % ; vertical-b and ed gastroplasty , 25 % ; and b and ing , 20 % . After 10 years , the weight losses from baseline were stabilized at 25 % , 16 % , and 14 % , respectively . There were 129 deaths in the control group and 101 deaths in the surgery group . The unadjusted overall hazard ratio was 0.76 in the surgery group ( P=0.04 ) , as compared with the control group , and the hazard ratio adjusted for sex , age , and risk factors was 0.71 ( P=0.01 ) . The most common causes of death were myocardial infa rct ion ( control group , 25 subjects ; surgery group , 13 subjects ) and cancer ( control group , 47 ; surgery group , 29 ) . CONCLUSIONS Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality The incidence of obstructive sleep apnea has been underestimated in morbidly obese patients who present for evaluation for weight loss surgery . This retrospective study shows that the incidence of obstructive sleep apnea in this patient population is greater than 70 per cent and increases in incidence as the body mass index increases . Obstructive sleep apnea ( OSA ) is a common comorbidity in obese patients who present for evaluation for gastric bypass surgery . The incidence of sleep apnea in obese patients has been reported to be as high as 40 per cent . A retrospective review of our prospect ively collected data base was performed . All patients being evaluated for weight loss surgery for obesity were screened preoperatively for OSA using a sleep study . The overall incidence of sleep apnea in our patients was 78 per cent ( 227 of 290 ) . All 227 were diagnosed by formal sleep study . There were 63 ( 22 % ) males and 227 ( 78 % ) females . The mean age was 43 years ( range , 17–75 years ) . The mean body mass index ( BMI ) was 52 kg/m2 ( range , 31–94 kg/m2 ) . The prevalence of OSA in the severely obese group ( BMI 35–39.9 kg/m2 ) was 71 per cent . For the morbidly obese group ( BMI 40–40.9 kg/m2 ) , the prevalence was 74 per cent and for the superobese group ( BMI 50–59.9 kg/m2 ) 77 per cent . Those with a BMI 60 kg/m2 or greater , the prevalence of OSA rose to 95 per cent . The incidence of sleep apnea in patients presenting for weight loss surgery was greater than 70 per cent in our study . Patients presenting for weight loss surgery should undergo a formal sleep study to diagnose OSA before bariatric surgery OBJECTIVE : To examine the effects of weight loss on health-related quality of life ( HRQL ) in subjects with severe obesity . DESIGN : Controlled clinical trial of the outcomes of surgical vs conventional weight reduction treatment . SUBJECTS : The first 487 surgical cases and their conventionally treated , matched controls were followed for two years in the Swedish Obese Subjects ( SOS ) intervention study . MEASUREMENTS : A battery of generic and study -specific self- assessment instruments or subscales was used to characterize HRQL in the severely obese ( BMI ) ≥34 kg/m2 for males and BMI ≥38 kg/m2 for females ) . Measures of general health perceptions ( general health rating index ; current health ) , mental well-being ( mood adjective check list ; pleasantness , activation and calmness ) , mood disorders ( hospital anxiety and depression scale ; anxiety and depression ) and social interaction ( sickness impact profile ) , were supplemented by obesity-specific modules on obesity-related psychosocial problems and eating behavior ( three-factor eating question naire ; restrained eating , disinhibition and perceived hunger ) . Assessment s were conducted prior to treatment and repeated after 6 , 12 and 24 months . RESULTS : Poor HRQL before intervention was dramatically improved after gastric restriction surgery , while only minor fluctuations in HRQL scores were observed in the conventionally treated controls . Peak values were observed in the surgical group at 6 or 12 months after intervention with a slight to moderate decrease at the two-year follow-up . The positive changes in HRQL after two years were related to the magnitude of weight loss , that is , the greater the weight reduction , the greater the HRQL improvements . Eating behavior improved accordingly . CONCLUSION : Quality of life in the severely obese is improved by substantial weight loss . Most patients benefit from weight reduction surgery , while HRQL in surgical patients with minor reduction in overweight is less positive . Further research is needed to determine outcome predictors of the surgical management of severe obesity and to ensure that HRQL improvements are maintained Background : Laparoscopic adjustable gastric b and ing ( GB ) is the most popular restrictive procedure for obesity in Europe . Isolated sleeve gastrectomy ( SG ) , is less common , but more invasive and with a higher learning curve . The aim of this prospect i ve r and omized study was to compare the results of GB and SG after 1 and 3 years of surgery . Methods : 80 patient c and i date s for laparoscopic restrictive surgery were operated consecutively and r and omly , between January and December 31 , 2002 , by GB ( 7 M , 33F ) or by SG ( 9 M , 31F ) ( NS ) . Median age was 36 ( 20 - 61 ) for GB versus 40 ( 22 - 65 ) for SG ( NS ) . Median BMI was 37 ( 30 - 47 ) for GB versus 39 ( 30 - 53 ) for SG ( NS ) . After 1 and 3 years : weight loss , feeling of hunger , sweet eating , gastroesophageal reflux disease ( GERD ) , complications and re-operations were recorded in both groups . Results : Median weight loss after 1 year was 14 kg ( −5 to + 38 ) for GB and 26 kg ( 0 to 46 ) for SG ( P<0.0001 ) ; and after 3 years was 17 kg ( 0 to 40 ) for GB and 29.5 kg ( 1 to 48 ) for SG ( P<0.0001 ) . Median decrease in BMI after 1 year was 15.5 kg/m 2 ( 5 to 39 ) after GB and 25 kg/m2 ( 0 to 45 ) after SG ( P<0.0001 ) ; and after 3 years was 18 kg/m2 ( 0 to 39 ) after GB and 27.5 kg/m 2 ( 0 to 48 ) after SG ( P=0.0004 ) . Median % EWL at 1 year was 41.4 % ( −11.8 to + 130.5 ) after GB and 57.7 % ( 0 to 125.5 ) after SG ( P=0.0004 ) ; and at 3 years was 48 % ( 0 to 124.8 ) after GB and 66 % ( −3.1 to + 152.4 ) after SG ( P=0.0025 ) . Loss of feeling of hunger after 1 year was registered in 42.5 % of patients with GB and in 75 % of patients with SG ( P=0.003 ) ; and after 3 years in 2.9 % of patients with GB and 46.7 % of patients with SG ( P<0.0001 ) . Loss of craving for sweets after 1 year was achieved in 35 % of patients with GB and 50 % of patients with SG ( NS ) ; and after 3 years in 2.9 % of patients with GB and 23 % of patients with SG ( NS ) . GERD appeared de novo after 1 year in 8.8 % of patients with GB and 21.8 % of patients with SG ( NS ) ; and after 3 years in 20.5 % of patients with GB and 3.1 % of patients with SG ( NS ) . Postoperative complications requiring re-operation were necessary for 2 patients after SG . Late complications requiring re-operation after GB included 3 pouch dilations treated by b and removal in 2 and 1 laparoscopic conversion to Roux-en-Y gastric bypass ( RYGBP ) , 1 gastric erosion treated by conversion to RYGBP , and 3 disconnections of the system treated by reconnection . Inefficacy affected 2 patients after GB , treated by conversion into RYGBP and 2 patients after SG treated by conversion to duodenal switch . Conclusion : Weight loss and loss of feeling of hunger after 1 year and 3 years are better after SG than GB . GERD is more frequent at 1 year after SG and at 3 years after GB . The number of re-operations is important in both groups , but the severity of complications appears higher in SG |
12,539 | 29,369,117 | In subgroup analysis , there was no mortality benefit for fluid-only goal -directed therapy , cardiac surgery patients or nonelective surgery .
Peri-operative modern goal -directed therapy reduces morbidity and mortality . | BACKGROUND Much uncertainty exists as to whether peri-operative goal -directed therapy is of benefit .
OBJECTIVES To discover if peri-operative goal -directed therapy decreases mortality and morbidity in adult surgical patients . | The use of adequate fluid therapy during cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) remains controversial . The aim of the study was to assess whether the use of fluid therapy protocol combined with goal -directed therapy ( GDT ) is associated with a significant change in morbidity , length of hospital stay , and mortality compared to st and ard fluid therapy . Patients American Society of Anesthesiologists ( ASA ) II – III undergoing CRS and HIPEC were r and omized into two groups . The GDT group ( N = 38 ) received fluid therapy according to a protocol guided by monitored hemodynamic parameters . The control group ( N = 42 ) received st and ard fluid therapy . We evaluated incidence of major complications , total length of hospital stay , total amount of fluids administered , and mortality rate . The incidence of major abdominal complications was 10.5 % in GDT group and 38.1 % in the control group ( P = 0.005 ) . The median duration of hospitalization was 19 days in GDT group and 29 days in the control group ( P < 0.0001 ) . The mortality rate was zero in GDT group vs 9.5 % in the control group ( P = 0.12 ) . GDT group received a significantly ( P < 0.0001 ) lower amount of fluid ( 5812 ± 1244 ml ) than the control group ( 8269 ± 1452 ml ) , with a significantly ( P < 0.0001 ) lower volume of crystalloids ( 3884 ± 1003 vs 68,528 ± 1413 ml ) . In CRS and HIPEC , the use of a GDT improves outcome in terms of incidence of major abdominal and systemic postoperative complications and length of hospital stay , compared to st and ard fluid therapy protocol BACKGROUND Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality . METHODS We performed a r and omized trial comparing goal -directed therapy guided by a pulmonary-artery catheter with st and ard care without the use of a pulmonary-artery catheter . The subjects were high-risk patients 60 years of age or older , with American Society of Anesthesiologists ( ASA ) class III or IV risk , who were scheduled for urgent or elective major surgery , followed by a stay in an intensive care unit . Outcomes were adjudicated by observers who were unaware of the treatment-group assignments . The primary outcome was in-hospital mortality from any cause . RESULTS Of 3803 eligible patients , 1994 ( 52.4 percent ) underwent r and omization . The base-line characteristics of the two treatment groups were similar . A total of 77 of 997 patients who underwent surgery without the use of a pulmonary-artery catheter ( 7.7 percent ) died in the hospital , as compared with 78 of 997 patients in whom a pulmonary-artery catheter was used ( 7.8 percent)--a difference of 0.1 percentage point ( 95 percent confidence interval , -2.3 to 2.5 ) . There was a higher rate of pulmonary embolism in the catheter group than in the st and ard-care group ( 8 events vs. 0 events , P=0.004 ) . The survival rates at 6 months among patients in the st and ard-care and catheter groups were 88.1 and 87.4 percent , respectively ( difference , -0.7 percentage point [ 95 percent confidence interval , -3.6 to 2.2 ] ; negative survival differences favor st and ard care ) ; at 12 months , the rates were 83.9 and 83.0 percent , respectively ( difference , -0.9 percentage point [ 95 percent confidence interval , -4.3 to 2.4 ] ) . The median hospital stay was 10 days in each group . CONCLUSIONS We found no benefit to therapy directed by pulmonary-artery catheter over st and ard care in elderly , high-risk surgical patients requiring intensive care Introduction Several studies have shown that goal -directed hemodynamic and fluid optimization may result in improved outcome . However , the methods used were either invasive or had other limitations . The aim of this study was to perform intraoperative goal -directed therapy with a minimally invasive , easy to use device ( FloTrac/Vigileo ) , and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a st and ard management protocol . Methods In this r and omized , controlled trial 60 high-risk patients scheduled for major abdominal surgery were included . Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol ( FloTrac/Vigileo device , GDT-group , n = 30 ) or a st and ard management group ( Control-group , n = 30 ) , based on st and ard monitoring data . Results The median duration of hospital stay was significantly reduced in the GDT-group with 15 ( 12 - 17.75 ) days versus 19 ( 14 - 23.5 ) days ( P = 0.006 ) and fewer patients developed complications than in the Control-group [ 6 patients ( 20 % ) versus 15 patients ( 50 % ) , P = 0.03 ] . The total number of complications was reduced in the GDT-group ( 17 versus 49 complications , P = 0.001 ) . Conclusions In high-risk patients undergoing major abdominal surgery , implementation of an intraoperative goal -directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a st and ard management protocol .Trial Registration Clinical trial registration information : Unique identifier : The objective was to compare the impact of an early goal -directed hemodynamic therapy based on cardiac output monitoring ( Endotracheal Cardiac Output Monitor , ECOM ) with a st and ard of care on postoperative outcome following coronary surgery . This prospect i ve , controlled , parallel-arm trial r and omized 100 elective primary coronary artery bypass grafting patients to a study group ( ECOM ; n = 50 ) or a control group ( control ; n = 50 ) . In the ECOM group , hemodynamic therapy was guided by respiratory stroke volume variation and cardiac index given by the ECOM system . A st and ard of care was used in the control . Goal -directed therapy was started immediately after induction of anesthesia and continued until arrival in the intensive care unit ( ICU ) . The primary endpoint was the time when patients fulfilled discharge criteria from hospital ( possible hospital discharge ) . Secondary endpoints were the hospital discharge , the time to reach extubation , the length of stay in ICU , the number of major adverse cardiac events , and in-hospital mortality . Patients in the ECOM group received more often fluid loading and dobutamine . The time to reach extubation was reduced in the ECOM group : 510 min [ 360–1,110 ] versus 570 min [ 320–1,520 ] , P = 0.005 . No significant differences were found between both groups for possible hospital discharge [ Hazard Ratio = 0.96 ( 95 % CI 0.64–1.45 ) ] and hospital discharge [ Hazard Ratio = 1.20 ( 95 % CI 0.79–1.81 ) ] . A mini-invasive early goal -directed hemodynamic therapy based on ECOM can reduce the time to reach extubation but fails to significantly reduce the length of stay in hospital and the rate of major cardiac morbidity Background and Aims : Advanced monitoring targeting haemodynamic and oxygenation variables can improve outcomes of surgery in high-risk patients . We aim ed to assess the impact of goal directed therapy ( GDT ) targeting cardiac index ( CI ) and oxygen extraction ratio ( O 2 ER ) on outcomes of high-risk patients undergoing abdominal surgery . Methods : In a prospect i ve r and omised trial , forty patients ( American Society of Anaesthesiologists II and III ) undergoing major abdominal surgeries were r and omised into two groups . In-Group A mean arterial pressure ≥ 65 mmHg , central venous pressure ≥ 8 - 10 mmHg , urine output ≥ 0.5 mL/kg/h and central venous oxygen saturation ≥ 70 % were targeted intra-operatively and 12 h postoperatively . In-Group-B ( enhanced GDT ) , in addition to the monitoring in-Group-A , CI ≥ 2.5 L/min/m 2 and O 2 ER ≤ 27 % were targeted . The end-points were lactate levels and base deficit during and after surgery . The secondary end points were length of Intensive Care Unit ( ICU ) and hospital stay and postoperative complications . Wilcoxon Mann Whitney and Chi-square tests were used for statistical assessment . Results : Lactate levels postoperatively at 4 and 8 h were lower in-Group-B ( P < 0.05 ) . The mean base deficit at 3 , 4 , 5 and 6 h intra-operatively and postoperatively after 4 , 8 and 12 h were lower in-Group-B ( P < 0.05 ) . There were no significant differences in ICU stay ( 2.10 ± 1.52 vs. 2.90 ± 2.51 days ) or hospital stay ( 10.85 + 4.39 vs. 13.35 + 6.77 days ) between Group A and B. Conclusions : Implementation of enhanced GDT targeting CI and OER was associated with improved tissue oxygenation Background The use of goal directed fluid protocol s in intermediate risk patients undergoing hip or knee replacement was studied in few trials using invasive monitoring . For this reason we have implemented two different fluid management protocol s , both based on a novel totally non-invasive arterial pressure monitoring device and compared them to the st and ard ( no- protocol ) treatment applied before the transition in our academic institution . Methods Three treatment groups were compared in this prospect i ve study : the observational ( CONTROL , N = 40 ) group before adoption of fluid protocol s and two r and omized groups after the transition to protocol fluid management with the use of the continuous non-invasive blood pressure monitoring ( CNAP ® ) device . In the PRESSURE group ( N = 40 ) st and ard variables were used for restrictive fluid therapy . Goal directed fluid therapy using pulse pressure variation was used in the GDFT arm ( N = 40 ) . The influence on the rate of postoperative complications , on the hospital length of stay and other parameters was assessed . Results Both protocol s were associated with decreased fluid administration and maintained hemodynamic stability . Reduced rate of postoperative infection and organ complications ( 22 ( 55 % ) vs. 33 ( 83 % ) patients ; p = 0.016 ; relative risk 0.67 ( 0.49–0.91 ) ) was observed in the GDFT group compared to CONTROL . Lower number of patients receiving transfusion ( 4 ( 10 % ) in GDFT vs. 17 ( 43 % ) in CONTROL ; p = 0.005 ) might contribute to this observation . No significant differences were observed in other end-points . Conclusion In our study , the use of the fluid protocol based on pulse pressure variation assessed using continuous non-invasive arterial pressure measurement seems to be associated with a reduction in postoperative complications and transfusion needs as compared to st and ard no- protocol treatment . Trial registration Background Major abdominal surgery is associated with significant risk of morbidity and mortality in the perioperative period . Optimising intraoperative fluid administration may result in improved outcomes . Our aim was to compare the effects of central venous pressure ( CVP ) , and central venous oxygen saturation (ScvO2)-assisted fluid therapy on postoperative complications in patients undergoing high risk surgery . Methods Patients undergoing elective major abdominal surgery were r and omised into control and ScvO2 groups . The target level of mean arterial pressure ( MAP ) was ≥ 60 mmHg in both groups . In cases of MAP < 60 mmHg patients received either a fluid or vasopressor bolus according to the CVP < 8 mmHg in the control group . In the ScvO2 group , in addition to the MAP , an ScvO2 of < 75 % or a > 3 % decrease indicated need for intervention , regardless of the actual MAP . Data are presented as mean ± st and ard deviation or median ( interquartile range ) . Results We observed a lower number of patients with complications in the ScvO2 group compared to the control group , however it did not reach statistical significance ( ScvO2 group : 10 vs. control group : 19 ; p = 0.07 ) . Patients in the ScvO2 group ( n = 38 ) received more colloids compared to the control group ( n = 41 ) [ 279(161 ) vs. 107(250 ) ml/h ; p < 0.001 ] . Both groups received similar amounts of crystalloid ( 1126 ± 471 vs. 1049 ± 431 ml/h ; p = 0.46 ) and norepinephrine [ 37(107 ) vs. 18(73 ) mcg/h ; p = 0.84 ] . Despite similar blood loss in both groups , the ScvO2 group received more blood transfusions ( 63 % vs. 37 % ; p = 0.018 ) . More patients in the control group had a postoperative PaO2/FiO2 < 200 mmHg ( 23 vs. 10 , p < 0.01 ) . Twenty eight day survival was significantly higher in the ScvO2 group ( 37/38 vs. 33/41 p = 0.018 ) . ConclusionS cvO2-assisted intraoperative haemodynamic support provided some benefits , including significantly better postoperative oxygenation and 28 day survival rate , compared to CVP-assisted therapy without a significant effect on postoperative complications during major abdominal surgery . Trial registration Clinical Trials.gov NCT02337010 Purpose We aim ed to investigate the influence of perioperative goal -directed fluid therapy ( GDFT ) on the prognosis of elderly patients with gastric cancer and hypertension . Methods Sixty elderly patients ( > 60 years old ) with primary hypertension who received gastric cancer radical surgery and who were American Society of Anesthesiologists ( ASA ) class II or III were enrolled in the current study . Selected patients were divided r and omly into two arms , comprising a conventional intraoperative fluid management arm ( arm C , n=30 ) and a GDFT arm ( arm G , n=30 ) . Patients in arm C were infused with crystalloids or colloids according to the methods of Miller ’s Anesthesia ( 6th edition ) , while those in arm G were infused with 200 mL hydroxyethyl starch over 15 minutes under the FloTrac/Vigileo monitoring system , with stroke volume variation between 8 % and 13 % . Hemodynamics and tissue perfusion laboratory indicators in patients were recorded continuously from 30 minutes before the operation to 24 hours after the operation . Results Compared with arm C , the average intraoperative intravenous infusion quantity in arm G was significantly reduced ( 2,732±488 mL versus 3,135±346 mL , P<0.05 ) , whereas average colloid fluid volume was significantly increased ( 1,235±360 mL versus 760±280 mL , P<0.05 ) . In addition , there were more patients exhibiting intraoperatively and postoperatively stable hemodynamics and less patients with low blood pressure in arm G. Postoperative complications were less frequent , and the time of postoperative hospital stay shorter , in arm G. No significant differences were observed in mortality between the two arms . Conclusion Our research showed that GDFT stabilized perioperative hemodynamics and reduced the occurrence of postoperative complications in elderly patients who underwent gastric cancer surgery BACKGROUND The purpose of this study was to determine the effect of algorithmic physiologic management on patients undergoing head and neck free tissue transfer and reconstruction . METHODS Ninety-four adult patients were r and omized to treatment and control groups . The blood pressure of the control group was managed consistent with contemporary st and ards . The treatment group was managed using an algorithm based on blood pressure and calculated physiologic values derived from arterial waveform analysis . Primary outcome was intensive care unit ( ICU ) length of stay . RESULTS ICU length of stay was decreased in the treatment group ( 33.7 vs 58.3 hours ; p = .026 ) . The complication rate was not increased in the treatment group . CONCLUSION The goal -directed hemodynamic management algorithm decreased the ICU length of stay . Judicious use of vasoactive drugs and goal -directed fluid administration has a role in improving perioperative outcomes for patients undergoing head and neck free tissue transfer . © 2016 Wiley Periodicals , Inc. Head Neck 38 : E1974-E1980 , 2016 BACKGROUND Patients with proximal femoral fracture ( PFF ) are at high risk of postoperative complications . Goal -directed haemodynamic treatment ( GDHT ) in other high-risk surgical patients reduces postoperative complications . We aim ed to compare effects of GDHT and routine fluid treatment ( RFT ) on postoperative outcomes after PFF surgery . METHODS PFF patients ( ≥70 yr ) were enrolled in this single-centre , open , r and omized , controlled , parallel-group superiority trial with concealed allocation using computer-generated r and omization . TREATMENTS ( i ) GDHT to attain oxygen delivery index > 600 ml min(-1 ) m(-2 ) using fluids and dobutamine and ( ii ) a protocol -guided RFT . After 150 enrolled patients , the trial was stopped due to slow recruitment . The short-term primary outcome measure was the relative risk ( RR ) of postoperative complications ; secondary measures were ( i ) administered fluid levels , ( ii ) vasopressor requirements , and ( iii ) haemodynamic responses . RESULTS For the GDHT group , 74 and for the RFT group 75 patients were design ated . The RR of postoperative complications ( GDHT vs RFT ) was 0.79 ( 95 % confidence interval 0.54 - 1.16 ) ; the volumes of i.v . fluids decreased ( 1078 vs 1440 ml , P=0.01 ) ; fewer patients required treatment of hypotension ( 18.5 % vs 75 % , P<0.005 ) ; there were more patients with increased oxygen delivery at the end of operation ( 28 % vs 8 % , P=0.04 ) , but the haemodynamic goal was achieved in only 27 % of patients in the GDHT group . CONCLUSIONS The magnitude of risk reduction of postoperative complications is clinical ly relevant , but the trial was underpowered and the null hypothesis can not be rejected BACKGROUND Morbidity after major surgery is associated with low oxygen delivery . Haemodynamic therapy aim ed at increasing oxygen delivery in an effort to reduce oxygen debt , tissue injury , and morbidity , is controversial . The most appropriate target for this strategy is unclear and might have several off-target effects , including loss of neural (parasympathetic)-mediated cellular protection . We hypothesised that individualised oxygen delivery targeted haemodynamic therapy ( goal -directed therapy ) in high-risk surgical patients would reduce postoperative morbidity , while secondarily addressing whether goal -directed therapy affected parasympathetic function . METHODS In this multicentre , r and omised , double-blind , controlled trial , adult patients undergoing major elective surgery were allocated by computer-generated r and omisation to a postoperative protocol ( fluid , with and without dobutamine ) targeted to achieve their individual preoperative oxygen delivery value ( goal -directed therapy ) or st and ardised care ( control ) . Patients and staff were masked to the intervention . The primary outcome was absolute risk reduction ( ARR ) in morbidity ( defined by Clavien-Dindo grade II or more ) on postoperative day 2 . We also assessed a secondary outcome focused on parasympathetic function , using time-domain heart rate variability measures . Analyses were done on an intention-to-treat basis . The trial was registered with Controlled Clinical Trials ( number IS RCT N76894700 ) . FINDINGS We enrolled 204 patients between May 20 , 2010 , and Feb 12 , 2014 . Intention-to-treat analysis of the 187 ( 92 % ) patients who completed the trial intervention period showed that early morbidity was similar between goal -directed therapy ( 44 [ 46 % ] of 95 patients ) and control groups ( 49 [ 53 % ] of 92 patients ) ( ARR -7 % , 95 % CI -22 to 7 ; p=0·30 ) . Prespecified secondary analysis showed that 123 ( 66 % ) of 187 patients achieved preoperative oxygen delivery ( irrespective of intervention ) . These patients sustained less morbidity ( ARR 19 % , 95 % CI 3 - 34 ; p=0·016 ) , including less infectious complications . Goal -directed therapy reduced parasympathetic activity postoperatively ( relative risk 1·33 , 95 % CI 1·01 - 1·74 ) . INTERPRETATION Achievement of preoperative oxygen delivery values in the postoperative phase was associated with less morbidity , but this was not affected by the use of an oxygen delivery targeted strategy . Reduced parasympathetic activity after goal -directed therapy was associated with the failure of this intervention to reduce postoperative morbidity . FUNDING Academy of Medical Sciences and Health Foundation Clinician Scientist Award There is continued controversy regarding the benefits of goal -directed fluid therapy , with earlier studies showing marked improvement in morbidity and length-of-stay that have not been replicated more recently . The aim of this study was to compare patient outcomes in elective colorectal surgery patients having goal -directed versus restrictive fluid therapy . Inclusion criteria included suitability for an Enhanced Recovery After Surgery care pathway and patients with an American Society of Anesthesiologists Physical Status score of 1 to 3 . Patients were intraoperatively r and omised to either restrictive or Doppler-guided goal -directed fluid therapy . The primary outcome was length-of-stay ; secondary outcomes included complication rate , change in haemodynamic variables and fluid volumes . One hundred patients , 50 in each group , were included in the analysis . Compared to restrictive therapy , goal -directed therapy result ed in a greater volume of intraoperative fluid , 2115 ( interquartile range 1350 to 2560 ) ml versus 1500 ( 1200 to 2000 ) ml , P=0.008 , and was associated with an increase in Doppler-derived stroke volume index from beginning to end of surgery , 43.7 ( 16.3 ) to 54.2 ( 21.1 ) ml/m2 , P < 0.001 , in the latter group . Length-of-stay was similar , P=0.421 . The number of patients with any complication ( minor or major ) was similar ; 60 % ( 30 ) versus 52 % ( 26 ) , P=0.42 , or major complications , 1 ( 2 % ) versus 4 ( 8 % ) , P=0.36 , respectively . The increased perioperative fluid volumes and increased stroke volumes at the end of surgery in patients receiving goal -directed therapy did not translate to a significant difference in length-of-stay and we did not observe a difference in the number of patients experiencing minor or major complications Background Our aim was to determine whether substitution of goal -directed fluid therapy ( GDT ) ( perioperative fluid administration ) for traditional therapy to manage elderly patients with coronary heart disease scheduled for gastrointestinal ( GI ) surgery was advantageous . We determined if it would reduce cardiac complications and shorten time to recovery and discharge . Methods Altogether , 60 of these elderly patients were r and omized into GDT ( n = 30 ) and control ( n = 30 ) groups . In the GDT group , fluid management was carried out under guidance of hemodynamic status indicators . Types and quantities of fluids administered , blood loss , intraoperative urine output , time of extubation , intensive care unit ( ICU ) stay , hospital stay , postoperative adverse cardiac events , and GI complications were recorded . Results Total fluids infused were 2,910 ± 645 ml ( GDT group ) and 3,640 ± 771 ml ( control group ) ( p < 0.05 ) . Numbers of adverse cardiac events in the two groups were not significantly different ( p = 0.121 ) . Return of GI function was significantly faster in the GDT group ( p < 0.001 ) . Median ICU stay was 32.5 h in the GDT group and 47.5 h in the control group ( p < 0.001 ) . Median hospital stay was 18 days in the GDT group and 22 days in the control group ( p < 0.001 ) . Conclusions GDT was associated with shorter ICU stay and time to discharge and faster return of GI function compared to traditional fluid therapy . The number of adverse cardiac events was similar in the two groups OBJECTIVES : This pilot study was design ed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies . METHODS : Eighty patients undergoing thoracoscopic lobectomy were r and omized into either a goal -directed therapy group or a control group . In the goal -directed therapy group , the stroke volume variation was controlled at 10%±1 % , and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2 . In the control group , the MAP was maintained at between 65 mm Hg and 90 mm Hg , heart rate was maintained at between 60 BPM and 100 BPM , and urinary output was greater than 0.5 mL/kg-1/h-1 . The hemodynamic variables , arterial blood gas analyses , total administered fluid volume and side effects were recorded . RESULTS : The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal -directed therapy group was significantly higher than that of the control group , but there were no differences between the goal -directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia . The extubation time was significantly earlier in the goal -directed therapy group , but there was no difference in the length of hospital stay . Patients in the control group had greater urine volumes , and they were given greater colloid and overall fluid volumes . Nausea and vomiting were significantly reduced in the goal -directed therapy group . CONCLUSION : The results of this study demonstrated that an optimization protocol , based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device , increased the PaO2/FiO2-ratio and reduced the overall fluid volume , intubation time and postoperative complications ( nausea and vomiting ) in thoracic surgery patients requiring one-lung ventilation BACKGROUND A prospect i ve , r and omized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy , in patients undergoing proximal femoral fracture repair under general anaesthesia . METHODS Ninety patients r and omized to three groups ; conventional intraoperative fluid management ( Gp CON , n=29 ) , and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure ( Gp CVP , n=31 ) or oesophageal Doppler ultrasonography ( Gp DOP , n=30 ) . Primary outcome measures were time to medical fitness to discharge , hospital stay and postoperative morbidity . RESULTS The fluid challenge result ed in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON ( mean 5 ( 95 % confidence interval 3 - 7 ) mm Hg ) ( P<0.0001 ) . Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms ( 19.7 - 79.1 ms ) in the corrected flow time , 13.5 ml ( 7.4 - 19.6 ml ) in stroke volume , and 0.9 ( 0.49 - 1.39 ) litre min(-1 ) in cardiac output . As a result , fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension ( Gp CON 28 % ( 8/29 ) , Gp CVP 9 % ( 3/31 ) , Gp DOP 7 % ( 2/30 ) , P=0.048 ( chi-squared , 2 degrees of freedom ( df ) . No differences were seen between the three groups when major morbidity and mortality were combined , P=0.24 ( chi-squared , 2 df ) . Postoperative recovery for survivors , as defined by time to be deemed medically fit for discharge , was significantly faster , in comparison with Gp CON , in both the Gp CVP ( 10 vs 14 ( 95 % confidence interval 8 - 12 vs 12 - 17 ) days , P=0.008 ( t-test ) ) , and Gp DOP ( 8 vs 14 ( 95 % confidence interval 6 - 12 vs 12 - 17 ) days , P=0.023 ( t-test ) . There were no significant differences between groups , for survivors , with respect to acute orthopaedic hospital and total hospital stay . CONCLUSIONS Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge This systematic review and meta- analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults . We included r and omized controlled trials of adult patients ( aged 16 years or older ) undergoing surgery . We included 31 studies of 5292 participants . There was no difference in mortality at the longest follow-up : 282/2615 ( 10.8 % ) died in the control group and 238/2677 ( 8.9 % ) in the treatment group , RR of 0.89 ( 95 % CI : 0.76 - 1.05 ; P=0.18 ) . However , the results were sensitive to analytical methods and withdrawal of studies with method ological limitations . The intervention reduced the rate of three morbidities ( renal failure , respiratory failure , and wound infections ) but not the rates of arrhythmia , myocardial infa rct ion , congestive cardiac failure , venous thrombosis , and other types of infections . The number of patients with complications was also reduced by the intervention . Hospital length of stay was reduced in the treatment group by 1.16 days . There was no difference in critical care length of stay . The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis , withdrawal of studies with method ological limitations , and was dominated by a single large study . Patients receiving this intervention stayed in hospital 1 day less with fewer complications . It is unlikely that the intervention causes harm . The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced Introduction Total hip replacement is one of the most commonly performed major orthopaedic operations . Goal -directed therapy ( GDT ) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia . GDT has never been formally assessed during regional anaesthesia . Methods Patients undergoing total hip replacement while under regional anaesthesia were r and omised to either the control group ( CTRL ) or the protocol group ( GDT ) . Patients in the GDT group , in addition to st and ard monitoring , were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system , and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2 . Results Patients r and omised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period ( means ± st and ard deviation ( SD ) : 6,032 ± 1,388 mL vs. 2,635 ± 346 mL ; P < 0.0001 ) , and more of the GDT patients received dobutamine ( 0 of 20 CTRL patients vs. 11 of 20 GDT patients ; P < 0.0003 ) . The GDT patients also received more blood transfused during the intraoperative period ( means ± SD : 595 ± 316 mL vs. 0 ± 0 mL ; P < 0.0001 ) , although the CTRL group received greater volumes of blood replacement postoperatively ( CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL ; P < 0.001 ) . Overall blood consumption ( intraoperatively and postoperatively ) was not different between the two groups . There were an increased number of complications in the CTRL group ( 20 of 20 CTRL patients ( 100 % ) vs. 16 of 20 GDT patients ( 80 % ) ; P = 0.05 ) . These outcomes were predominantly due to a difference in minor complications ( 20 of 20 CTRL patients ( 100 % ) vs. 15 of 20 GDT patients ( 75 % ) ; P = 0.047 ) . Conclusions GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications . Larger trials are required to confirm our findings .Trial registration S RCT Introduction Several single-center studies and meta-analyses have shown that perioperative goal -directed therapy may significantly improve outcomes in general surgical patients . We hypothesized that using a treatment algorithm based on pulse pressure variation , cardiac index trending by radial artery pulse contour analysis , and mean arterial pressure in a study group ( SG ) , would result in reduced complications , reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients , when compared to a control group ( CG ) . Methods 160 patients undergoing elective major abdominal surgery were r and omized to the SG ( 79 patients ) or to the CG ( 81 patients ) . In the SG hemodynamic therapy was guided by pulse pressure variation , cardiac index trending and mean arterial pressure . In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist . Outcome data were recorded up to 28 days postoperatively . Results The total number of complications was significantly lower in the SG ( 72 vs. 52 complications , p = 0.038 ) . In particular , infection complications were significantly reduced ( SG : 13 vs. CG : 26 complications , p = 0.023 ) . There were no significant differences between the two groups for return of bowel movement ( SG : 3 vs. CG : 2 days postoperatively , p = 0.316 ) , duration of post anesthesia care unit stay ( SG : 180 vs. CG : 180 minutes , p = 0.516 ) or length of hospital stay ( SG : 11 vs. CG : 10 days , p = 0.929 ) . Conclusions This multi-center study demonstrates that hemodynamic goal -directed therapy using pulse pressure variation , cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery . Trial registration Clinical Trial.gov , NCT01401283 Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery , which increases re source use and health care costs . Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients . Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves . The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit ( ICU ) stay . Four hundred three elective cardiac surgical patients were enrolled in the study and r and omly assigned to either the control or the protocol group . Goals of the protocol group were to maintain Svo2 > 70 % and lactate concentration ≤2.0 mmol/L from admission to the ICU and up to 8 h thereafter . Hemodynamics , oxygen transport data , and organ dysfunctions were recorded . The median hos-pital stay was shorter in the protocol group ( 6 vs 7 days , P < 0.05 ) , and patients were discharged faster from the hospital than those in the control group ( P < 0.05 ) . Discharge from the ICU was similar between groups ( P = 0.8 ) . Morbidity was less frequent at the time of hospital discharge in the protocol group ( 1.1 % vs 6.1 % , P < 0.01 ) . Increasing oxygen delivery to achieve normal Svo2 values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay . Implication s Health care economics has challenged clinicians to reduce costs and improve re source use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease . Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay Introduction Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and /or low dose inotropic therapy . The mechanisms underlying this benefit remain uncertain . The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery . Methods R and omised , controlled , single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery . For eight hours after surgery , intra-venous fluid therapy was guided by measurements of central venous pressure ( CVP group ) , or stroke volume ( SV group ) . In a third group stroke volume guided fluid therapy was combined with dopexamine ( 0.5 mcg/kg/min ) ( SV & DPX group ) . Results 135 patients were recruited ( n = 45 per group ) . In the SV & DPX group , increased global oxygen delivery was associated with improved sublingual ( P < 0.05 ) and cutaneous microvascular flow ( P < 0.005 ) ( sublingual microscopy and laser Doppler flowmetry ) . Microvascular flow remained constant in the SV group but deteriorated in the CVP group ( P < 0.05 ) . Cutaneous tissue oxygen partial pressure ( PtO2 ) ( Clark electrode ) improved only in the SV & DPX group ( P < 0.001 ) . There were no differences in serum inflammatory markers . There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group ( CVP group ten patients ( 22 % ) ; pooled SV and SV & DPX groups seven patients ( 8 % ) ; P = 0.03 ) ( post hoc analysis ) . Conclusions Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery , microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery . These observations may explain improved clinical outcomes associated with this treatment in previous trials . Trial registration numberIS RCT N BACKGROUND : In this study , our objective was to determine whether a perioperative hemodynamic protocol based on noninvasive cardiac output monitoring decreases the incidence of postoperative complications and hospital length of stay in major abdominal surgery patients requiring intensive care unit admission . Secondary objectives were the time to peristalsis recovery and the incidence of wound infection , anastomotic leaks , and mortality . METHODS : A r and omized clinical trial was conducted in 6 tertiary hospitals . One hundred forty-two adult patients scheduled for open colorectal surgery , gastrectomy , or small bowel resection were enrolled . A hemodynamic protocol including fluid administration and vasoactive drugs based on arterial blood pressure , cardiac index , and stroke volume response was compared with st and ard practice . Patients were followed until hospital discharge ( determined by a surgeon blinded to the study ) or death . In contrast to previous studies , we design ed a pragmatic trial ( as opposed to explanatory trials ) to mimic real practice and obtain maximal external validity for the study . RESULTS : Fluid administration was similar except for the number of colloid boluses ( 2.4 ± 1.8 [ treated ] vs 1.3 ± 1.4 [ control ] ; P < 0.001 ) and packed red blood cell units ( 0.6 ± 1.3 [ treated ] vs 0.2 ± 0.6 [ control ] ; P = 0.019 ) . Dobutamine was used in 25 % ( intraoperatively ) and 19.4 % ( postoperatively ) of the treated patients versus 1.4 % and 0 % in the control group ( P < 0.001 ) . We have observed a reduction in reoperations in the treated group ( 5.6 % vs 15.7 % ; P = 0.049 ) . However , no significant differences were observed in overall complications ( 40 % vs 41 % ; relative risk 0.99 [ 0.67–1.44 ] ; P = 0.397 ) , length of stay ( 11.5 [ 8–15 ] vs 10.5 [ 8–16 ] ; P = 0.874 ) , time to first flatus ( 62 hours [ 40–76 ] vs 72 hours [ 48–96 ] ; P = 0.180 ) , wound infection ( 7 vs 14 ; P = 0.085 ) , anastomotic leaks ( 2 vs 5 ; P = 0.23 ) , or mortality ( 4.2 % vs 5.7 % ; P = 0.67 ) . CONCLUSIONS : The results of our pragmatic study indicate that a perioperative hemodynamic protocol guided by a noninvasive cardiac output monitor was not associated with a decrease in the incidence of overall complications or length of stay in major abdominal surgery Goal -directed therapy ( GDT ) encompasses guidance of intravenous ( IV ) fluid and vasopressor/inotropic therapy by cardiac output or similar parameters to help in early recognition and management of high-risk cardiac surgical patients . With the aim of establishing the utility of perioperative GDT using robust clinical and biochemical outcomes , we conducted the present study . This multicenter r and omized controlled study included 130 patients of either sex , with European system for cardiac operative risk evaluation ≥3 undergoing coronary artery bypass grafting on cardiopulmonary bypass . The patients were r and omly divided into the control and GDT group . All the participants received st and ardized care ; arterial pressure monitored through radial artery , central venous pressure ( CVP ) through a triple lumen in the right internal jugular vein , electrocardiogram , oxygen saturation , temperature , urine output per hour , and frequent arterial blood gas ( ABG ) analysis . In addition , cardiac index ( CI ) monitoring using FloTrac ™ and continuous central venous oxygen saturation ( ScVO2 ) using PreSep ™ were used in patients in the GDT group . Our aim was to maintain the CI at 2.5–4.2 L/min/m2 , stroke volume index 30–65 ml/beat/m2 , systemic vascular resistance index 1500–2500 dynes/s/cm5/m2 , oxygen delivery index 450–600 ml/min/m2 , continuous ScVO2 > 70 % , and stroke volume variation < 10 % ; in addition to the control group parameters such as CVP 6–8 mmHg , mean arterial pressure 90–105 mmHg , normal ABG values , oxygen saturation , hematocrit value > 30 % , and urine output > 1 ml/kg/h . The aims were achieved by altering the administration of IV fluids and doses of inotropes or vasodilators . The data of sixty patients in each group were analyzed in view of ten exclusions . The average duration of ventilation ( 19.89 ± 3.96 vs. 18.05 ± 4.53 h , P = 0.025 ) , hospital stay ( 7.94 ± 1.64 vs. 7.17 ± 1.93 days , P = 0.025 ) , and Intensive Care Unit ( ICU ) stay ( 3.74 ± 0.59 vs. 3.41 ± 0.75 days , P = 0.012 ) was significantly less in the GDT group , compared to the control group . The extra volume added and the number of inotropic dose adjustments were significantly more in the GDT group . The two groups did not differ in duration of inotropic use , mortality , and other complications . The perioperative continuation of GDT affected the early decline in the lactate levels after 6 h in ICU , whereas the control group demonstrated a settling lactate only after 12 h. Similarly , the GDT group had significantly lower levels of brain natriuretic peptide , neutrophil gelatinase-associated lipocalin levels as compared to the control . The study clearly depicts the advantage of GDT for a favorable postoperative outcome in high-risk cardiac surgical patients Objective : To evaluate the influence of stroke volume variation (SVV)-based goal -directed therapy ( GDT ) on splanchnic organ functions and postoperative complications in orthopedic patients . Subjects and Methods : Eighty patients scheduled for major orthopedic surgery under general anesthesia were r and omly allocated to one of two equal groups to receive either intraoperative volume therapy guided by SVV ( GDT ) or st and ard fluid management ( control ) . In the SVV group , patients received colloid boluses of 4 ml/kg to maintain an SVV < 10 % when in the supine position or an SVV < 14 % if prone . In the control group , fluids were given to maintain a mean arterial pressure > 65 mm Hg , a heart rate < 100 bpm , a central venous pressure of 8 - 14 mm Hg , and a urine output > 0.5 ml/kg/h . Intraoperative organ perfusion , hemodynamic data , hospitalization , postoperative complications , and mortality were recorded . Results : The heart rate at the end of surgery was significantly lower ( p < 0.05 ) , there were fewer hypotensive episodes ( p < 0.05 ) , the arterial and gastric intramucosal pH were higher ( p < 0.05 for both ) , the gastric intramucosal PCO2 was lower ( p < 0.05 ) , the intraoperative infused colloids and the total infused volume were lower ( p < 0.05 for both ) , and the postoperative time to flatus was shorter ( p < 0.05 ) in the GDT group than in the control group . No differences in the length of hospital stay , complications , or mortality were found between the groups . Conclusion : SVV-based GDT during major orthopedic surgery reduced the volume of the required intraoperative infused fluids , maintained intraoperative hemodynamic stability , and improved the perioperative gastrointestinal function BACKGROUND After cardiac surgery , patients receive large amounts of fluid in the Intensive Care Unit ( ICU ) . We plan to conduct a multi-centre r and omised controlled trial , of a conservative fluid regime , in patients after cardiac surgery , and have reported results of a feasibility study that evaluated efficacy and safety of the proposed regime . METHODS After ethical approval , a single-centre , prospect ively r and omised interventional study was undertaken . Participants were r and omised to either usual care , or to a protocol ised algorithm , utilising stroke volume variation , to guide fluid administration to patients who were deemed to have inadequate cardiac output and were likely to be volume responsive . The study protocol lasted from ICU admission to de-sedation or 24 h , whichever occurred first . RESULTS We r and omised 144 subjects over 9 months . Less bolus fluid and less total overall fluid volume was administered in the intervention group ( median ( IQR ) 1620 ml ( 500 - 3410 ) and 2525 ml ( 1440 - 5250 ; P<0.001 ) , compared with the usual care group ( 2050 ml ( 910 - 4280 ) and 2980 ml ( 2070 - 6580 ; P=0.001 ) , from ICU admission to extubation . There was no significant difference in incidence of acute kidney injury or the average amount of fluid administered to the usual care group at the beginning compared with the end of the study . CONCLUSION It is both possible and safe to achieve a significant reduction in the amount of fluid administered to patients , allocated to a conservative fluid protocol . These results suggest that a planned multi-centre study is both justified and feasible . CLINICAL TRIAL REGISTRATION Australia New Zeal and Clinical Trials Registry www.anzctr.org.au ( ACTRN12612000754842 ) BACKGROUND We aim ed to investigate whether fluid therapy with a goal of near-maximal stroke volume ( SV ) guided by oesophageal Doppler ( ED ) monitoring result in a better outcome than that with a goal of maintaining bodyweight ( BW ) and zero fluid balance in patients undergoing colorectal surgery . METHODS In a double-blinded clinical multicentre trial , 150 patients undergoing elective colorectal surgery were r and omized to receive fluid therapy after either the goal of near-maximal SV guided by ED ( Doppler , D group ) or the goal of zero balance and normal BW ( Zero balance , Z group ) . Stratification for laparoscopic and open surgery was performed . The postoperative fluid therapy was similar in the two groups . The primary endpoint was postoperative complications defined and divided into subgroups by protocol . Analysis was performed by intention-to-treat . The follow-up was 30 days . The trial had 85 % power to show a difference between the groups . RESULTS The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups . No significant differences between the groups were found for overall , major , minor , cardiopulmonary , or tissue-healing complications ( P-values : 0.79 ; 0.62 ; 0.97 ; 0.48 ; and 0.48 , respectively ) . One patient died in each group . No significant difference was found for the length of hospital stay [ median ( range ) Z : 5.00 ( 1 - 61 ) vs D : 5.00 ( 2 - 41 ) ; P=0.206 ] . CONCLUSIONS Goal -directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery Background Intraoperative hypovolemia is common and is a potential cause of organ dysfunction , increased postoperative morbidity , length of hospital stay , and death . The objective of this prospect i ve , r and omized study was to assess the effect of goal -directed intraoperative fluid administration on length of postoperative hospital stay . Methods One hundred patients who were to undergo major elective surgery with an anticipated blood loss greater than 500 ml were r and omly assigned to a control group ( n = 50 ) that received st and ard intraoperative care or to a protocol group ( n = 50 ) that , in addition , received intraoperative plasma volume expansion guided by the esophageal Doppler monitor to maintain maximal stroke volume . Length of postoperative hospital stay and postoperative surgical morbidity were assessed . Results Groups were similar with respect to demographics , surgical procedures , and baseline hemodynamic variables . The protocol group had a significantly higher stroke volume and cardiac output at the end of surgery compared with the control group . Patients in the protocol group had a shorter duration of hospital stay compared with the control group : 5 ± 3 versus 7 ± 3 days ( mean ± SD ) , with a median of 6 versus 7 days , respectively ( P = 0.03 ) . These patients also tolerated oral intake of solid food earlier than the control group : 3 ± 0.5 versus 4.7 ± 0.5 days ( mean ± SD ) , with a median of 3 versus 5 days , respectively ( P = 0.01 ) . Conclusions Goal -directed intraoperative fluid administration results in earlier return to bowel function , lower incidence of postoperative nausea and vomiting , and decrease in length of postoperative hospital stay Introduction Several studies have shown that maximizing stroke volume ( or increasing it until a plateau is reached ) by volume loading during high-risk surgery may improve post-operative outcome . This goal could be achieved simply by minimizing the variation in arterial pulse pressure ( ΔPP ) induced by mechanical ventilation . We tested this hypothesis in a prospect i ve , r and omized , single-centre study . The primary endpoint was the length of postoperative stay in hospital . Methods Thirty-three patients undergoing high-risk surgery were r and omized either to a control group ( group C , n = 16 ) or to an intervention group ( group I , n = 17 ) . In group I , ΔPP was continuously monitored during surgery by a multiparameter bedside monitor and minimized to 10 % or less by volume loading . Results Both groups were comparable in terms of demographic data , American Society of Anesthesiology score , type , and duration of surgery . During surgery , group I received more fluid than group C ( 4,618 ± 1,557 versus 1,694 ± 705 ml ( mean ± SD ) , P < 0.0001 ) , and ΔPP decreased from 22 ± 75 to 9 ± 1 % ( P < 0.05 ) in group I. The median duration of postoperative stay in hospital ( 7 versus 17 days , P < 0.01 ) was lower in group I than in group C. The number of postoperative complications per patient ( 1.4 ± 2.1 versus 3.9 ± 2.8 , P < 0.05 ) , as well as the median duration of mechanical ventilation ( 1 versus 5 days , P < 0.05 ) and stay in the intensive care unit ( 3 versus 9 days , P < 0.01 ) was also lower in group I. Conclusion Monitoring and minimizing ΔPP by volume loading during high-risk surgery improves postoperative outcome and decreases the length of stay in hospital . Trial registration Introduction Stroke volume variation ( SVV ) is a good and easily obtainable predictor of fluid responsiveness , which can be used to guide fluid therapy in mechanically ventilated patients . During major abdominal surgery , inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity . The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery . Methods Patients undergoing elective intraabdominal surgery were r and omly assigned to a Control group ( n = 60 ) with routine intraoperative care and a Vigileo group ( n = 60 ) , where fluid management was guided by SVV ( Vigileo/FloTrac system ) . The aim was to maintain the SVV below 10 % using colloid boluses of 3 ml/kg . The laboratory parameters of organ hypoperfusion in perioperative period , the number of infectious and organ complications on day 30 after the operation , and the hospital and ICU length of stay and mortality were evaluated . The local ethics committee approved the study . Results The patients in the Vigileo group received more colloid ( 1425 ml [ 1000 - 1500 ] vs. 1000 ml [ 540 - 1250 ] ; P = 0.0028 ) intraoperatively and a lower number of hypotensive events were observed ( 2[1 - 2 ] Vigileo vs. 3.5[2 - 6 ] in Control ; P = 0.0001 ) . Lactate levels at the end of surgery were lower in Vigileo ( 1.78 ± 0.83 mmol/l vs. 2.25 ± 1.12 mmol/l ; P = 0.0252 ) . Fewer Vigileo patients developed complications ( 18 ( 30 % ) vs. 35 ( 58.3 % ) patients ; P = 0.0033 ) and the overall number of complications was also reduced ( 34 vs. 77 complications in Vigileo and Control respectively ; P = 0.0066 ) . A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization ( 9 [ 8 - 12 ] vs. 10 [ 8 - 19 ] days ; P = 0.0421 ) . No difference in mortality ( 1 ( 1.7 % ) vs. 2 ( 3.3 % ) ; P = 1.0 ) and ICU length of stay ( 3 [ 2 - 5 ] vs. 3 [ 0.5 - 5 ] ; P = 0.789 ) was found . Conclusions In this study , fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability , decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications . Trial registration Current Controlled Trials IS RCT N95085011 Abstract Objective To assess whether a nurse led , flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital . Design R and omised controlled trial . Setting Intensive care unit and cardiothoracic unit of a university teaching hospital . Participants 174 patients who underwent cardiac surgery between April 2000 and January 2003 . Interventions Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2 . Results 26 control patients had postoperative complications ( two deaths ) compared with 17 ( four deaths ) protocol patients ( P = 0.08 ) . Duration of hospital stay in the protocol group was significantly reduced from a median of nine ( interquartile range 7 - 12 ) days to seven ( 7 - 10 ) days ( P = 0.02 ) . The mean duration of hospital stay was reduced from 13.9 to 11.4 days , a saving in hospital bed days of 18 % ( 95 % confidence interval −12 % to 47 % ) . Usage of intensive care beds was reduced by 23 % ( −8 % to 59 % ) . Conclusion A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay PURPOSE To evaluate the routine use of pulmonary artery catheters ( PAC ) in patients who undergo aortic surgery . METHODS One hundred twenty patients were r and omized to placement of PACs for perioperative monitoring and hemodynamic optimization ( tune up ) in the intensive care unit on the night before aortic operation , or to intravenous hydration in the ward and perioperative monitoring without PACs . Before r and omization , all patients underwent routine adenosine thallium-201 scintigraphy . RESULTS To meet predetermined endpoints , 30 PAC patients ( 50 % ) received nitrates , inotropic agents , or both . PAC patients received more fluid in the preoperative period ( p < 0.001 ) and in the first 24 hours after operation ( p = 0.002 ) than control subjects . Eleven PAC patients ( 18 % ) and three control subjects ( 5 % ) had adverse intraoperative events ( p = 0.02 ) . There were 20 adverse postoperative events in 15 PAC patients ( 25 % ; nine cardiac , seven pulmonary , four acute tubular necrosis ) , which was not different compared with 11 postoperative events in 10 control subjects ( 17 % ; five cardiac , five pulmonary , one acute tubular necrosis ) . There were also no differences in duration of mechanical ventilation , intensive care unit stay , or hospital stay between groups . Postoperative cardiac complications were more common among patients who had a history of congestive heart failure ( p = 0.02 ; odds ratio , 3.75 ; confidence interval , 1.3 to 11 ) or reperfusion defects on adenosine thallium scintigraphy ( p = 0.01 ; odds ratio , 3.4 ; confidence interval , 1.2 to 9.4 ) , regardless of group . CONCLUSIONS Routine use of PACs for perioperative monitoring with the above protocol during aortic surgery is not beneficial and may be associated with a higher rate of intraoperative complications . Preoperative tune up does not prevent postoperative cardiac , renal , and other complications . Variables such as cardiac risk factors and adenosine thallium scintigraphy may be more important predictors of cardiac events in patients who undergo aortic operations OBJECTIVE : The optimal strategy for fluid management during gastrointestinal surgery remains unclear . Minimizing the variation in arterial pulse pressure , which is induced by mechanical ventilation , is a potential strategy to improve postoperative outcomes . We tested this hypothesis in a prospect i ve , r and omized study with lactated Ringer 's solution and 6 % hydroxyethyl starch solution . METHOD : A total of 60 patients who were undergoing gastrointestinal surgery were r and omized into a restrictive lactated Ringer 's group ( n = 20 ) , a goal -directed lactated Ringer 's group ( n = 20 ) and a goal -directed hydroxyethyl starch group ( n = 20 ) . The goal -directed fluid treatment was guided by pulse pressure variation , which was recorded during surgery using a simple manual method with a Date x Ohmeda S/5 Monitor and minimized to 11 % or less by volume loading with either lactated Ringer 's solution or 6 % hydroxyethyl starch solution ( 130/0.4 ) . The postoperative flatus time , the length of hospital stay and the incidence of complications were recorded as endpoints . RESULTS : The goal -directed lactated Ringer 's group received the greatest amount of total operative fluid compared with the two other groups . The flatus time and the length of hospital stay in the goal -directed hydroxyethyl starch group were shorter than those in the goal -directed lactated Ringer 's group and the restrictive lactated Ringer 's group . No significant differences were found in the postoperative complications among the three groups . CONCLUSION : Monitoring and minimizing pulse pressure variation by 6 % hydroxyethyl starch solution ( 130/0.4 ) loading during gastrointestinal surgery improves postoperative outcomes and decreases the discharge time of patients who are grade d American Society of Anesthesiologists physical status I/II Introduction Goal -directed therapy ( GDT ) has been shown in numerous studies to decrease perioperative morbidity and mortality . The mechanism of benefit of GDT , however , has not been clearly eluci date d. Targeted resuscitation of the vascular endothelium with GDT might alter the postoperative inflammatory response and be responsible for the decreased complications with this therapy . Methods This trial was registered at Clinical Trials.gov as NCT01681251 . Forty patients undergoing elective open repair of their abdominal aortic aneurysm , 18 years of age and older , were r and omized to an interventional arm with GDT targeting stroke volume variation with an arterial pulse contour cardiac output monitor , or control , where fluid therapy was administered at the discretion of the attending anesthesiologist . We measured levels of several inflammatory cytokines ( C-reactive protein , Pentraxin 3 , suppressor of tumorgenicity--2 , interleukin-1 receptor antagonist , and tumor necrosis factor receptor-III ) preoperatively and at several postoperative time points to determine if there was a difference in inflammatory response . We also assessed each group for a composite of postoperative complications . Results Twenty patients were r and omized to GDT and twenty were r and omized to control . Length of stay was not different between groups . Intervention patients received less crystalloid and more colloid . At the end of the study , intervention patients had a higher cardiac index ( 3.4 ± 0.5 vs. 2.5 ± 0.7 l/minute per m2 , p < 0.01 ) and stroke volume index ( 50.1 ± 7.4 vs. 38.1 ± 9.8 ml/m2 , p < 0.01 ) than controls . There were significantly fewer complications in the intervention than control group ( 28 vs. 12 , p = 0.02 ) . The length of hospital and ICU stay did not differ between groups . There was no difference in the levels of inflammatory cytokines between groups . Conclusions Despite being associated with fewer complications and improved hemodynamics , there was no difference in the inflammatory response of patients treated with GDT . This suggests that the clinical benefit of GDT occurs in spite of a similar inflammatory burden . Further work needs to be performed to delineate the mechanism of benefit of GDT.Trial registration Clinical Trials.gov Identifier : NCT01681251 . Registered 18 May 2011 Abstract Objectives : To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery , and to determine whether the inotropes , adrenaline and dopexamine , used to enhance oxygen delivery influence outcome . Design : R and omised controlled trial with double blinding between inotrope groups . Setting : York District Hospital , Engl and . Subjects:138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions . Interventions : Patients were r and omised into three groups . Two groups received invasive haemodynamic monitoring , fluid and either adrenaline or dopexamine to increase oxygen delivery . Inotropic support was continued during surgery and for at least12 hours afterwards . The third group ( control ) received routine perioperative care . Main outcome measures : Hospital mortality and morbidity . Results : Overall , 3/92 ( 3 % ) preoptimised patients died compared with 8/46 controls ( 17 % ) ( P=0.007 ) . There were no differences in mortality between the treatment groups , but 14/46 ( 30 % ) patients in the dopexamine group developed complications compared with 24/46 ( 52 % ) patients in the adrenaline group ( difference 22 % , 95%confidence interval 2 % to 41 % ) and 28 patients ( 61 % ) in the control group ( 31 % , 11 % to 50 % ) . The use of dopexamine was associated with a decreased length of stay in hospital . Conclusion : Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care Introduction Goal -directed therapy ( GDT ) has been shown to improve outcome when commenced before surgery . This requires pre-operative admission to the intensive care unit ( ICU ) . In cardiac surgery , GDT has proved effective when commenced after surgery . The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery . Methods This was a r and omised controlled trial with concealed allocation . High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management . Cardiac output was measured by lithium indicator dilution and pulse power analysis . Patients were followed up for 60 days . Results Sixty-two patients were r and omised to GDT and 60 patients to control treatment . The GDT group received more intravenous colloid ( 1,907 SD ± 878 ml versus 1,204 SD ± 898 ml ; p < 0.0001 ) and dopexamine ( 55 patients ( 89 % ) versus 1 patient ( 2 % ) ; p < 0.0001 ) . Fewer GDT patients developed complications ( 27 patients ( 44 % ) versus 41 patients ( 68 % ) ; p = 0.003 , relative risk 0.63 ; 95 % confidence intervals 0.46 to 0.87 ) . The number of complications per patient was also reduced ( 0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient ; p = 0.002 ) . The median duration of hospital stay in the GDT group was significantly reduced ( 11 days ( IQR 7 to 15 ) versus 14 days ( IQR 11 to 27 ) ; p = 0.001 ) . There was no significant difference in mortality ( seven patients ( 11.3 % ) versus nine patients ( 15 % ) ; p = 0.59 ) . Conclusion Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay . The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05 . The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001 . Doppler patients achieved significantly higher cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P<0.001 , overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity Background Perioperative goal -directed fluid therapy ( GDFT ) may improve outcome after high-risk surgery . Minimal invasive measurement of stroke volume variation ( SVV ) has been recommended to guide fluid therapy . We intended to study how perioperative GDFT with arterial-based continuous SVV monitoring influences postoperative complications in a high-risk surgical population . Methods From February 1st 2012 , all ASA 3 and 4 patients undergoing abdominal surgery in two university hospitals were assessed for r and omization into a control group or GDFT group . An arterial-line cardiac output monitor was used to measure SVV , and fluid was given after an algorithm in the intervention group . Restrictions of the method excluded patients undergoing laparoscopic surgery , patients with atrial fibrillation and patients with severe mitral/aortal stenosis . To detect a decrease in number of complication from 40 % in the control group to 20 % in the GDFT group , n = 164 patients were needed ( power 80 % , alpha 0.05 , two-sided test ) . To include the needed amount of patients , the study was estimated to last for 2 years . Results After 1 year , 30 patients were included and the study was halted due to slow inclusion rate . Of 732 high-risk patients scheduled for abdominal surgery , 391 were screened for r and omization . Of those , n = 249 ( 64 % ) were excluded because a laparoscopic technique was preferred and n = 95 ( 24 % ) due to atrial fibrillation . Conclusions Our study was stopped due to a slow inclusion rate . Method ological restrictions of the arterial-line cardiac output monitor excluded the majority of patients . This leaves the question if this method is appropriate to guide fluid therapy in high-risk surgical patients .Trial registration Clinical Trials.gov : NCT01473446 BACKGROUND Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome . Stroke volume variation ( SVV ) is considered a reliable clinical predictor of fluid responsiveness . Consequently , the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour ( APCO ) analysis , using the FloTrac/Vigileo system , to predict fluid responsiveness as measured by the oesophageal Doppler . METHODS Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring . Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time ( FTc ) to < 350 ms . Patients were connected to a monitoring device , obtaining SVV by APCO . Haemodynamic variables were recorded before and after fluid bolus application . Fluid responsiveness was defined as an increase in stroke volume index > 10 % . The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic ( ROC ) curve . RESULTS Twenty patients received 67 fluid boluses . Fifty-two of the 67 fluid boluses administered result ed in fluid responsiveness . SVV achieved an area under the ROC curve of 0.512 [ confidence interval ( CI ) 0.32 - 0.70 ] . A cut-off point for fluid responsiveness was found for SVV > or = 8.5 % ( sensitivity : 77 % ; specificity : 43 % ; positive predictive value : 84 % ; and negative predictive value : 33 % ) . CONCLUSIONS This prospect i ve , interventional observer-blinded study demonstrates that SVV obtained by APCO , using the FloTrac/Vigileo system , is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery BACKGROUND Dynamic variables , for example , systolic pressure variation ( SPV ) , are superior to filling pressures for assessing fluid responsiveness . We analysed the effects of SPV-guided intraoperative fluid management on organ function and perfusion when compared with routine care . METHODS Eighty patients ( 44 female and 36 male ) undergoing elective major abdominal surgery were r and omly assigned to a control group [ n=40 , mean age 66 ( sd 10 ) , range 40 - 84 yr ] or SPV group [ n=40 , age 61 ( 16 ) , range 26 - 100 yr ] in which intraoperative fluid management was guided by SPV ( trigger : SPV>10 % ) . Central venous O2 saturation ( ScvO2 ) , lactate and bilirubin , creatinine , indocyanine green plasma disappearance rate ( ICG-PDR ) , and gastric mucosal CO(2 ) tension were measured after induction of anaesthesia , after 3 , 6 , 12 , and 24 h. RESULTS Patient characteristics , duration of surgery [ 5.8 ( 2.5 ) vs 5.4 ( 2.5 ) h ] , and infusion volumes ( median 4865 vs 4330 ml ) were comparable between the groups . At 3 and 6 h , SPV ( P=0.04 , P=0.01 ) and Deltadown ( P=0.005 , P=0.01 ) were significantly higher in the control group . Oxygen transport and organ function were comparable : baseline and 24 h values for ICG-PDR : 28.5 ( 7.9 ) and 22.7 ( 7.8 ) vs 23.9 ( 6.9 ) and 26.1 (5.9)% min(-1 ) , 77.7 ( 6.6 ) and 72.6 ( 5.5 ) vs 79.3 ( 7.1 ) and 72.8 (6.7)% for ScvO2 and 1.0 ( 0.4 ) and 1.2 ( 0.6 ) vs 0.9 ( 0.2 ) and 1.3 ( 0.5 ) mmol litre(-1 ) for lactate . Length of mechanical ventilation , ICU stay , and mortality were comparable . CONCLUSIONS In comparison with routine care , intraoperative SPV-guided treatment was associated with slightly increased fluid adminstration whereas organ perfusion and function was similar BACKGROUND The impact of different approaches to fluid management during intraoperative volume resuscitation in patients undergoing major elective surgery is poorly defined . We compared volume effectiveness of crystalloid and colloid substitution aim ed to maintain the cardiac index ( CI ) between 2.6 and 3.8 l/min/m(2 ) as measured by transesophageal Doppler ( TED ) . METHODS A total of 115 urological patients were enrolled in the prospect i ve r and omized trial and then r and omized into 2 groups , one with volume therapy based on crystalloids ( n = 57 ) and the other with colloids ( n = 58 ) . A TED probe was inserted and then hemodynamic optimization ( therapy with Ringer 's solution or hydroxyethyl starch 6 % 130/0.4 and administration of vasoactive drugs ) was started according to TED variables to maintain the CI between 2.6 and 3.8 l/min/m(2 ) . RESULTS We observed high incidence of CI < 2.6 l/min/m(2 ) after induction of anesthesia ( 75 % ) in both groups . There were no significant differences in demographic characteristics , ASA classification , length of surgery , estimated blood loss and the CI during surgery . To maintain the CI within the requested interval , significantly different amounts of crystalloids were needed as compared to colloid ( median : 5000 ml vs 1500 ml ) . In the CRY group , more patients were treated by vasodilatators ( 40.4 vs 20.7 % ) . CONCLUSIONS The study confirmed that crystalloids and colloids are effective in correcting flow-related perfusion abnormalities . The significant difference between volumes of crystalloids and colloids proved their different characteristics such as unequal distribution between compartments . The expansion of therapeutic algorithm by using vasoactive drugs allows us to avoid adverse events result ing from fluid overload ( Tab . 1 , Fig. 5 , Ref . 35 ) INTRODUCTION : No consensus exists regarding the optimal fluid ( crystalloid or colloid ) or strategy ( liberal , restricted , or goal directed ) for fluid management after colectomy . Prior assessment s have used normal saline . This is the first assessment of st and ard , goal -directed perioperative fluid management with either lactated Ringer ’s or hetastarch/lactated Ringer ’s , with use of esophageal Doppler for guidance , in laparoscopic colectomy with an enhanced recovery protocol . METHODS : A double-blinded , prospect i ve , r and omized , three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the st and ard , goal -directed/lactated Ringer ’s and goal -directed/hetastarch groups . A st and ard anesthesia and basal fluid administration protocol was used in addition to the goal -directed strategies guided by esophageal Doppler . RESULTS : Sixty-four patients undergoing laparoscopic colectomy ( 22 st and ard , 21 goal -directed/lactated Ringer ’s , 21 goal -directed/hetastarch ) had similar operative times ( st and ard , 2.3 hours ; goal -directed/lactated Ringer ’s , 2.5 hours ; goal -directed/hetastarch , 2.3 hours ) . The lactated Ringer ’s group received the greatest amount of total and milliliters per kilogram per hour of operative fluid ( st and ard , 2,850/18 ; goal -directed/lactated Ringer ’s , 3,800/23 ; and goal -directed/hetastarch , 3,300/17 ; P < 0.05 ) . The hetastarch group had the longest stay ( st and ard , 64.9 hours ; goal -directed/lactated Ringer ’s , 71.8 hours ; goal -directed/hetastarch , 75.5 hours ; P < 0.05 ) . The st and ard group received the greatest amount of fluid during hospitalization ( st and ard , 2.5 ml/kg/h ; goal -directed/lactated Ringer ’s , 1.9 ml/kg/h ; goal -directed/hetastarch , 2.1 ml/kg/h ; P < 0.05 ) . There was one instance of operative mortality in the goal -directed/hetastarch group . CONCLUSIONS : Goal -directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly . However , goal -directed , individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocol s following colectomy because of reduced overall fluid administration Background and Aims : There is limited data on the impact of perioperative fluid therapy guided by dynamic preload variables like stroke volume variation ( SVV ) on outcomes after abdominal surgery . We studied the effect of SVV guided versus central venous pressure ( CVP ) guided perioperative fluid administration on outcomes after major abdominal surgery . Material and Methods : Sixty patients undergoing major abdominal surgeries were r and omized into two equal groups in this prospect i ve single blind r and omized study . In the st and ard care group , the CVP was maintained at 10 - 12 mmHg while in the intervention group a SVV of 10 % was achieved by the administration of fluids . The primary end-points were the length of Intensive Care Unit ( ICU ) and hospital stay . The secondary end points were intraoperative lactate , intravenous fluid use , requirement for inotropes , postoperative ventilation and return of bowel function . Results : The ICU stay was significantly shorter in the intervention group as compared to the control group ( 2.9 ± 1.15 vs. 5.4 ± 2.71 days ) . The length of hospital stay was also shorter in the intervention group , ( 9.9 ± 2.68 vs. 11.96 ± 5.15 days ) though not statistically significant . The use of intraoperative fluids was significantly lower in the intervention group than the control group ( 7721.5 ± 4138.9 vs. 9216.33 ± 2821.38 ml ) . Other secondary outcomes were comparable between the two groups . Conclusion : Implementation of fluid replacement guided by a dynamic preload variable ( SVV ) versus conventional static variables ( CVP ) is associated with lesser postoperative ICU stay and reduced fluid requirements in major abdominal surgery PURPOSE Cardiovascular optimization via esophageal Doppler can minimize gastrointestinal hypoperfusion , reducing the risk of multiple organ dysfunction and postoperative complications during major surgery . We assessed the effect of esophageal Doppler guided cardiovascular optimization in patients undergoing radical cystectomy . MATERIAL S AND METHODS We conducted a prospect i ve , r and omized , double-blind controlled trial at a United Kingdom teaching hospital between 2006 and 2009 . A total of 66 patients were r and omized to a control arm ( 34 ) and an intervention arm ( 32 ) . The control group received st and ard intraoperative fluids . The intervention group received ( additional ) Doppler guided fluid . Primary outcomes were markers of gastrointestinal morbidity such as ileus , flatus and bowel opening . Secondary outcomes were postoperative nausea and vomiting , wound infection and operative intravenous fluid volumes ( total and hourly ) . RESULTS There were significant reductions in the control and intervention arms in the incidence of ileus ( 18 vs 7 , p < 0.001 ) , flatus ( 5.36 vs 3.55 days , p < 0.01 ) and bowel opening ( 9.79 vs 6.53 days , p = 0.02 ) , respectively . Nausea and vomiting were significantly reduced in the study group at 24 and 48 hours postoperatively ( 11 vs 3 , p < 0.01 and 13 vs 1 , p < 0.0001 ) . Wound infection rates were significantly reduced ( 8 vs 1 superficial , p < 0.01 and 10 vs 2 combined , p < 0.01 ) . Study patients received significantly higher volumes ( ml/kg per minute ) of intravenous fluid ( 0.19 vs 0.23 , p < 0.01 ) related to a significantly higher volume ( ml/kg ) in the first hour of surgery ( 14.1 vs 21.0 , p = 0.0001 ) . CONCLUSIONS Cardiovascular optimization using esophageal Doppler significantly improved postoperative markers of gastrointestinal function Background and objective We hypothesized that , in vascular surgery patients , the application of a goal -directed strategy based on a pulse contour-derived cardiac index would be associated with a better haemodynamic status than the application of routine perioperative care and that the amount of fluid and /or inotropes required in such a goal -directed therapy depended on the general anaesthetic technique used . Methods Patients undergoing peripheral arterial bypass grafting were r and omly assigned to three groups . In group 1 , haemodynamic management was performed according to routine clinical practice . In the two other groups ( groups 2 and 3 ) a goal -directed therapy was applied aim ing to maintain the pulse contour-derived cardiac index above 2.5 l m−2 min−1 . Patients in groups 1 and 2 received sevoflurane-based anaesthesia and patients in group 3 propofol-based anaesthesia . Haemodynamic variables , amount of fluid and administration of inotropes were assessed at different time intervals . Results The amount of fluid administered was not significantly different between the groups . Two patients in group 1 , 13 patients in group 2 and 12 patients in group 3 were treated with dobutamine ( P < 0.001 ) . None of the patients anaesthetized with sevoflurane ( groups 1 and 2 ) experienced postoperative cardiovascular complications , whereas four patients in the total intravenous group ( group 3 ) experienced major postoperative cardiovascular complications ( P = 0.005 ) . Conclusion In the conditions of the present study , the application of a goal -directed therapy aim ing to maintain the cardiac index above 2.5 l min−1 m−2 did not result in a higher tissue oxygen delivery than when applying the st and ard haemodynamic strategy nor did it depend on the anaesthetic technique used A r and omized controlled trial was conducted to test the hypothesis that there is no difference in complications in patients receiving intravenous ( iv ) water and electrolyte , based on either stroke volume or clinical indicators at bowel surgery Early goal -directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients . Early recognition and therapy during this period may result in better outcome . In keeping with this aim in the cardiac surgery patients , we conducted the present study . The study included 30 patients of both sexes , with EuroSCORE > or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass . The patients were r and omly divided into two groups , namely , control and early goal -directed therapy ( EGDT ) groups . All the subjects received st and ardized care ; arterial pressure was monitored through radial artery , central venous pressure through a triple lumen in the right internal jugular vein , electrocardiogram , oxygen saturation , temperature , urine output per hour and frequent arterial blood gas analysis . In addition , cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group . Our aim was to maintain the cardiac index at 2.5 - 4.2 l/min/m2 , stroke volume index 30 - 65 ml/beat/m2 , systemic vascular resistance index 1500 - 2500 dynes/s/cm5/m2 , oxygen delivery index 450 - 600 ml/min/m2 , continuous central venous oximetry more than 70 % , stroke volume variation less than 10 % ; in addition to the control group parameters such as central venous pressure 6 - 8 mmHg , mean arterial pressure 90 - 105 mmHg , normal arterial blood gas analysis values , pulse oximetry , hematocrit value above 30 % and urine output more than 1 ml/kg/h . The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents . Three patients were excluded from the study and the data of 27 patients analyzed . The extra volume used ( 330+/-160 v/s 80+/-80 ml , P=0.043 ) number of adjustments of inotropic agents ( 3.4+/-1.5 v/s 0.4+/-0.7 , P=0.026 ) in the EGDT group were significant . The average duration of ventilation ( 13.8+/-3.2 v/s 20.7+/-7.1 h ) , days of use of inotropic agents ( 1.6+/-0.9 v/s 3.8+/-1.6 d ) , ICU stay ( 2.6+/-0.9 v/s 4.9+/-1.8 d ) and hospital stay ( 5.6+/-1.2 v/s 8.9+/-2.1 d ) were less in the EGDT group , compared to those in the control group . This study is inconclusive with regard to the beneficial aspects of the early goal -directed therapy in cardiac surgery patients , although a few benefits were observed BACKGROUND Today , most of the pre-emptive hemodynamic optimization algorithms are based on variables associated with invasive techniques like arterial cannulation . The non-invasive Nexfin ™ technology is able to estimate continuous Cardiac Index ( CI ) and pulse pressure variation ( PPV ) . However , the efficiency of an early goal directed therapy ( EGDT ) algorithm based on non-invasive variables has to be proven . The aim of our study was to investigate the feasibility of a non-invasive driven EGDT protocol and its impact on patient 's outcome . METHODS Seventy-nine patients ( ASA II-III ) undergoing elective major abdominal surgery were r and omized to either study group ( SG , N.=39 ) or control group ( CG , N.=40 ) . The SG was treated according to an algorithm based on non-invasive CI and PPV , whereas the CG received st and ard of care . Postoperative complications up to 28 days and length of hospital stay ( LOS ) in both groups were recorded . RESULTS There was no significant difference between the groups regarding demographics , hemodynamic variables , preoperative risk scores and duration of surgery . The total amount of complications was higher in the CG ( SG 94 vs. CG 132 complications , P=0.22 ) without reaching statistical significance . LOS revealed no difference between both groups ( SG , 9 [ 7 - 15 ] vs. CG , 9 [ 7 - 15.25 ] days , P=0.82 ) . We have seen no impact of the non-invasive optimization protocol with respect to postoperative mortality . CONCLUSIONS In this patient collective , we could demonstrate the feasibility of a non-invasive approach for hemodynamic optimization . However , EGDT based on non-invasive variables was not able to significantly improve outcome Perioperative hemodynamic optimisation improves postoperative outcome for patients undergoing high-risk surgery ( HRS ) . In this prospect i ve r and omized multicentre study we studied the effects of an individualized , goal -directed fluid management based on continuous stroke volume variation ( SVV ) and stroke volume ( SV ) monitoring on postoperative outcomes . 64 patients undergoing HRS were r and omized either to a control group ( CON , n = 32 ) or a goal -directed group ( GDT , n = 32 ) . In GDT , SVV and SV were continuously monitored ( FloTrac/Vigileo ) and patients were brought to and maintained on the plateau of the Frank-Starling curve ( SVV < 10 % and SV increase < 10 % in response to fluid loading ) . Organ dysfunction was assessed using the SOFA score and re source utilization using the TISS score . Patients were followed up to 28 days for postoperative complications . Main outcome measures were the number of complications ( infectious , cardiac , respiratory , renal , hematologic and abdominal post-operative complications ) , maximum SOFA score and cumulative TISS score during ICU stay , duration of mechanical ventilation , length of ICU stay , and time until fit for discharge . 12 patients had to be excluded from final analysis ( 6 in each group ) . During surgery , GDT received more colloids than CON ( 1,589 vs. 927 ml , P < 0.05 ) and SVV decreased in GDT ( from 9.0 to 8.0 % , P < 0.05 ) but not in CON . The number of postoperative wound infections was lower in GDT ( 0 vs. 7 , P < 0.01 ) . Although not statistically significant , the proportion of patients with at least one complication ( 46 vs. 62 % ) , the number of postoperative complications per patient ( 0.65 vs. 1.40 ) , the maximum sofa score ( 5.9 vs. 7.2 ) , and the cumulative TISS score ( 69 vs. 83 ) tended to be lower . This multicentre study shows that fluid management based on a SVV and SV optimisation protocol is feasible and decreases postoperative wound infections . Our findings also suggest that a goal -directed strategy might decrease postoperative organ dysfunction BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions Background : Early mobilization is important for postoperative recovery but is limited by orthostatic intolerance ( OI ) with a prevalence of 50 % 6 h after major surgery . The pathophysiology of postoperative OI is assumed to include hypovolemia besides dysregulation of vasomotor tone . Stroke volume – guided fluid therapy , so-called goal -directed therapy ( GDT ) , corrects functional hypovolemia , and the authors hypothesized that GDT reduces the prevalence of OI after major surgery and assessed this in a prospect i ve , double-blinded trial . Methods : Forty-two patients scheduled for open radical prostatectomy were r and omized into st and ard fluid therapy ( control group ) or GDT groups . Both groups received a fixed-volume crystalloid regimen supplemented with 1:1 replacement of blood loss with colloid , and in addition , the GDT group received colloid to obtain a maximal stroke volume ( esophageal Doppler ) . The primary outcome was the prevalence of OI assessed with a st and ardized mobilization protocol before and 6 h after surgery . Hemodynamic and hormonal orthostatic responses were evaluated . Results : Twelve ( 57 % ) versus 15 ( 71 % ) patients in the control and GDT groups ( P = 0.33 ) , respectively , demonstrated OI after surgery , group difference 14 % ( CI , −18 to 45 % ) . Patients in the GDT group received more colloid during surgery ( 1,758 vs. 1,057 ml ; P = 0.001 ) and reached a higher stroke volume ( 102 vs. 89 ml ; P = 0.04 ) . OI patients had an increased length of hospital stay ( 3 vs. 2 days ; P = 0.02 ) and impaired hemodynamic and norepinephrine responses on mobilization . Conclusion : GDT did not reduce the prevalence of OI , and patients with OI demonstrated impaired cardiovascular and hormonal responses to mobilization BACKGROUND Hip fracture is a condition with high mortality and morbidity in elderly frail patients . Intraoperative fluid optimization may be associated with benefit in this population . We investigated whether intraoperative fluid management using pulse-contour analysis cardiac monitoring , compared with st and ard care in patients undergoing spinal anaesthesia , would provide benefits in terms of reduced time until medically fit for discharge and postoperative complications . METHODS Patients undergoing surgical repair of fractured neck of femur , aged > 60 yr , receiving spinal anaesthesia were enrolled in this single-centre , blinded , r and omized , parallel group trial . Patients were allocated to either anaesthetist-directed fluid therapy or a pulse-contour-guided fluid optimization strategy using colloid ( Gelofusine ) boluses to optimize stroke volume . The primary outcome was time until medically fit for discharge . Secondary outcomes included postoperative complications , mobility , and mortality . We up date d a systematic review to include relevant trials to 2014 . RESULTS We recruited 130 patients . Time until medically fit for discharge was similar in both groups , mean [ 95 % confidence interval ( CI ) ] 12.2 ( 11.1 - 13.5 ) vs 13.1 ( 11.9 - 14.5 ) days ( P=0.31 ) , as was total length of stay 14.2 ( 12.9 - 15.8 ) vs 15.3 ( 13.8 - 17.2 ) days ( P=0.32 ) . There were no significant differences in complications , function , or mortality . An up date d meta- analysis ( four studies , 355 patients ) found non-significant reduction in early mortality [ relative risk 0.66 ( 0.24 - 1.79 ) ] and in-hospital complications [ relative risk 0.80 ( 0.61 - 1.05 ) ] . CONCLUSIONS Goal -directed fluid therapy during hip fracture repair under spinal anaesthesia does not result in a significant reduction in length of stay or postoperative complications . There is insufficient evidence to either support or discount its routine use . CLINICAL TRIAL REGISTRATION IS RCT N88284896 A key component of the Cochrane Collaboration 's risk of bias tool for critically evaluating r and omised trials is the consideration of whether baseline characteristics of the treatment groups being compared are systematic ally different . Considered under the domain of ' selection bias ' , this is currently evaluated by looking at the methods of r and omisation and specifically at the generation of the r and omised allocation sequence and the concealment of this sequence during the process of r and omisation . Assessment of the actual similarity of baseline variables across groups in demographic and clinical characteristics is seldom performed . Even when performed , the link with selection bias is sometimes not considered . Methods of r and omisation and allocation concealment are often poorly reported in published trials , yet baseline data tables are presented in a large majority of trial reports . In this article , we propose that assessment of trial baseline data should form a key and prominent part of selection bias judgements when using the risk of bias tool . We outline the possible benefits from using this approach , including reduced uncertainty in systematic review conclusions , reduced risk of chance findings being ascribed to treatment effects and better use of available evidence by a more considered approach to evaluating studies using imperfect r and omisation and allocation methods OBJECTIVE The authors determined whether the preoperative placement of a pulmonary artery catheter ( PAC ) with optimization of hemodynamics results in outcome improvement after elective vascular surgery . SUMMARY BACKGROUND DATA The PAC commonly is used not only in patients who are critically ill , but also perioperatively in major elective surgery . Few prospect i ve studies exist documenting its usefulness . METHODS One hundred four consecutive patients were r and omized to have a PAC placed the morning of operation ( group I ) or to have a PAC placed only if clinical ly indicated ( group II ) . Group I patients were resuscitated to preestablished endpoints before surgery and kept at these points both intraoperatively and postoperatively . Group II patients received st and ard care . RESULTS There was one death in each group . An intraoperative or postoperative complication developed in 13 patients in group I versus 7 patients in group II ( p = not significant ) . Group I patients received more fluid than did group II patients ( 5137 + /- 315 mL vs. 3789 + /- 306 mL ; p < 0.003 ) . There was no significant difference in either overall or surgical intensive care unit length of stay . Only one patient in group II required a postoperative PAC . CONCLUSIONS Routine PAC use in elective vascular surgery increases the volume of fluid given to patients without demonstrable improvement in morbidity or mortality BACKGROUND Previous investigations have suggested that preoperative invasive hemodynamic monitoring with " optimization " of cardiovascular function may favorably affect the outcome among patients undergoing peripheral vascular surgery . The purpose of this study was to evaluate the effect of preoperative optimization of hemodynamic parameters on outcome in patients undergoing aortic reconstruction ( AR ) or limb salvage procedures ( LSP ) in a r and omized , prospect i ve clinical trial . METHODS All 72 patients who consented to participate in this study were admitted to the intensive care unit at least 12 hours before operation for placement of a pulmonary artery catheter ( PAC ) . Patients who were r and omized to the treatment group ( n = 32 ) were " optimized " by adjusting their hemoglobin concentration , oxygen saturation ( SaO2 ) , cardiac output , or afterload until the mixed venous O2 saturation ( SvO2 ) was at least 65 % . The control group ( n = 40 ) underwent placement of a PAC and had oxygen transport parameters measured without any attempt to optimize SvO2 . RESULTS There were no significant differences between the treatment and control groups with respect to age , gender , type of operation , initial Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , SvO2 , pulmonary artery occlusion pressure , or cardiac index . All treatment patients achieved an SvO2 of at least 65 % before operation . Comparing the treatment and control groups , postoperative cardiovascular complications occurred in 25 % versus 27 % , intraoperative complications in 28 % versus 20 % , and death in 9 % versus 5 % , respectively . None of these differences was statistically significant as a whole or within the subgroups undergoing AR or LSP . CONCLUSIONS These data suggest that preoperative optimization of cardiovascular function by using achievement of SvO2 above 65 % as the end point does not result in any reduction of intraoperative or perioperative cardiac complications in patients undergoing PVS . Further studies with alternative assessment s and manipulation of different cardiopulmonary parameters may yield additional information BACKGROUND The benefits of stroke volume optimization during surgery are unclear , with recent data not replicating the positive effects of earlier studies . METHODS This was a r and omized controlled trial of st and ard fluid therapy with or without supplementary blinded intraoperative stroke volume optimization in 220 patients having major elective rectal resection or cystectomy with ileal conduit . All patients were treated using a contemporary enhanced recovery pathway . Interventional fluid challenges used Gelofusine ( B Braun , Germany ) , guided by stoke volume variability measured by LiDCOrapid ( LiDCO , UK ) . Participants were stratified by aerobic fitness ( characterized by preoperative cardiopulmonary exercise test ) , surgical specialty , and intended surgical approach ( open or laparoscopic ) . The primary outcome was the prevalence of moderate or severe complications on day 5 after surgery , defined using the postoperative morbidity survey ( POMS ) criteria . RESULTS Patients received ∼13 ml kg(-1 ) h(-1 ) of i.v . fluids during surgery . The intervention group received an additional mean ( sd ) 956 ( 896 ) ml Gelofusine . There were no statistically significant differences between groups in any primary or secondary end point . A positive POMS on postoperative day 5 was noted in 54 of 111 control subjects ( 48.6 % ) and 55 of 109 participants in the intervention group [ 50.5 % ; adjusted odds ratio 0.90 ( 95 % confidence interval 0.52 - 1.57 ) , P=0.717 ] . Mean ( sd ) hospital length of stay was 9.6 ( 6.8 ) days in the control group and 11.8 ( 11.5 ) days in the intervention group ( adjusted difference -2.1 ( -4.6 to 0.3 ) days , P=0.091 ) . There was no statistical interaction between stroke volume optimization and aerobic fitness in terms of rate of complications or length of stay . CONCLUSIONS Algorithm-driven stroke volume optimization is of no benefit when superimposed on a liberal baseline fluid regimen in patients having elective major abdominal surgery , when stratified to minimize differences in fitness and surgical approach between groups . CLINICAL TRIAL REGISTRATION IS RCT N21597243 BACKGROUND Postoperative organ failures commonly occur after major abdominal surgery , increasing the utilization of re sources and costs of care . Tissue hypoxia is a key trigger of organ dysfunction . A therapeutic strategy design ed to detect and reverse tissue hypoxia , as diagnosed by an increase of oxygen extraction ( O2ER ) over a predefined threshold , could decrease the incidence of organ failures . The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those r and omized to conventional vs a protocol ized strategy design ed to maintain O2ER < 27 % . METHODS A prospect i ve , r and omized , controlled trial was performed in nine hospitals in Italy . One hundred thirty-five high-risk patients scheduled for major abdominal surgery were r and omized in two groups . All patients were managed to achieve st and ard goals : mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h . The patients of the " protocol group " ( group A ) were also managed to keep O2ER < 27 % . MEASUREMENTS AND MAIN RESULTS In group A , fewer patients had at least one organ failure ( n = 8 , 11.8 % ) than in group B ( n = 20 , 29.8 % ) [ p < 0.05 ] , and the total number of organ failures was lower in group A than in group B ( 27 failures vs 9 failures , p < 0.001 ) . Length of hospital stay was significantly lower in the protocol group than in the control group ( 11.3 + /- 3.8 days vs 13.4 + /- 6.1 days , p < 0.05 ) . Hospital mortality was similar in both groups . CONCLUSIONS Early treatment directed to maintain O2ER at < 27 % reduces organ failures and hospital stay of high-risk surgical patients . Clinical trials.gov reference No. NCT00254150 BACKGROUND Intraoperative fluid therapy regimens using oesophageal Doppler monitoring ( ODM ) to optimize stroke volume ( SV ) ( goal -directed fluid therapy , GDT ) have been associated with a reduction in length of stay ( LOS ) and complication rates after major surgery . We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge ( RfD ) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients . METHODS In this double-blinded controlled trial , 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically ' fit ' ( n=123 ) or ' unfit ' ( n=56 ) on the basis of their performance during a cardiopulmonary exercise test . Within these fitness strata , patients were r and omized to receive a st and ard fluid regimen with or without ODM-guided intraoperative GDT . RESULTS GDT patients received an average of 1360 ml of additional intraoperative colloid . The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls . Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance ( median 6.8 vs 4.9 days , P=0.09 , and median 8.8 vs 6.7 days , P=0.09 , respectively ) . Fit GDT patients had an increased RfD ( median 7.0 vs 4.7 days ; P=0.01 ) and LOS ( median 8.8 vs 6.0 days ; P=0.01 ) compared with controls . CONCLUSIONS Intraoperative SV optimization conferred no additional benefit over st and ard fluid therapy . In an aerobically fit subgroup of patients , GDT was associated with detrimental effects on the primary outcome . TRIAL REGISTRY UK NIHR CRN 7285 , IS RCT N 14680495 . http://public.ukcrn.org.uk/ Search / Study Detail.aspx ? Study ID=7285 BACKGROUND The optimal perioperative fluid resuscitation strategy for liver resections remains undefined . Goal -directed therapy ( GDT ) embodies a number of physiologic strategies to achieve an ideal fluid balance and avoid the consequences of over- or under-resuscitation . STUDY DESIGN In a prospect i ve r and omized trial , patients undergoing liver resection were r and omized to GDT using stroke volume variation as an end point or to st and ard perioperative resuscitation . Primary outcomes measure was 30-day morbidity . RESULTS Between 2012 and 2014 , one hundred and thirty-five patients were r and omized ( GDT : n = 69 ; st and ard perioperative resuscitation : n = 66 ) . Median age was 57 years and 56 % were male . Metastatic disease comprised 81 % of patients . Overall ( 35 % GDT vs 36 % st and ard perioperative resuscitation ; p = 0.86 ) and grade 3 morbidity ( 28 % GDT vs 18 % st and ard perioperative resuscitation ; p = 0.22 ) were equivalent . Patients in the GDT arm received less intraoperative fluid ( mean 2.0 L GDT vs 2.9 L st and ard perioperative resuscitation ; p < 0.001 ) . Perioperative transfusions were required in 4 % ( 6 % GDT vs 2 % st and ard perioperative resuscitation ; p = 0.37 ) and boluses in the postanesthesia care unit were administered to 24 % ( 29 % GDT vs 20 % st and ard perioperative resuscitation ; p = 0.23 ) . Mortality rate was 1 % ( 2 of 135 patients ; both in GDT ) . On multivariable analysis , male sex , age , combined procedures , higher intraoperative fluid volume , and fluid boluses in the postanesthesia care unit were associated with higher 30-day morbidity . CONCLUSIONS Stroke volume variation-guided GDT is safe in patients undergoing liver resection and led to less intraoperative fluid . Although the incidence of postoperative complications was similar in both arms , lower intraoperative resuscitation volume was independently associated with decreased postoperative morbidity in the entire cohort . Future studies should target extensive resections and identify patients receiving large resuscitation volumes , as this population is more likely to benefit from this technique Background Acute kidney injury is a common complication after major surgery . In this study , we investigated whether an algorithm-guided goal -directed haemodynamic therapy ( GDT ) can improve renal outcome compared to good st and ard clinical care . Methods A total of 180 patients undergoing major abdominal surgery were prospect ively and r and omly assigned to one of two groups : in the GDT group , patients were treated with a GDT algorithm using transpulmonary thermodilution while st and ard care was applied to the control patients . Change in creatinine was studied as the primary end point , postoperative complications as well as 1-year mortality as secondary outcomes . Haemodynamics in GDT and control patients were compared calculating goal -achievement rates . Results Postoperative change in creatinine ( 18 ± 39 μmol/l ( control ) vs. 16 ± 42 μmol/l ( GDT ) ; mean difference ( 95 % confidence interval ) 1.6 μmol/l ( −10 to 13 μmol/l ) ) was comparable between the GDT and the control group . Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm . Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high ( > 80 % ) rates in the control group . Multivariate regression analysis revealed intraoperative hypotension ( MAP < 70 mmHg ) and postoperative hypovolaemia ( GEDI < 640 ml/m2 ) as risk factors for postoperative renal impairment . Conclusions In this study , GDT was not superior to st and ard clinical care in order to avoid renal failure after major abdominal surgery . The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group , which can not be improved by the GDT algorithm . Trial registration Clinical trials.gov ; NCT01035541 ; registered 17 December 2009 The hypothesis that optimizing hemodynamics using pulmonary artery ( PA ) catheter ( preoperative ' tune-up ' ) would improve outcome in patients undergoing limb-salvage arterial surgery was tested . Eighty-nine patients were r and omized to preoperative tune-up either in the surgical intensive care unit ( SICU ) ( group 1 ) or the preinduction room ( group 2 ) or to control ( group 3 ) . The tune-up consisted of fluid loading , afterload reduction , and /or inotropic support to achieve predetermined endpoints . Patients with a PA catheter had significantly fewer adverse intraoperative events ( p less than 0.05 ) , less postoperative cardiac morbidity ( p less than 0.05 ) , and less early graft thrombosis ( p less than 0.05 ) than the control group . The overall study mortality rate was 3.4 % , with a mortality rate of 9.5 % in the control group and 1.5 % in the PA catheter groups . There were no differences in ICU length of stay ( LOS ) , hospital LOS , or total hospital costs , although the percentage of cost from complications was higher in group 3 ( p greater than 0.05 ) . In this group of patients , preoperative cardiac assessment and optimization is associated with improved outcome OBJECTIVE to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair . METHODS a consecutive series of 100 eligible patients were r and omised to either haemodynamic optimisation through the use of a pulmonary artery catheter ( CI > 3.0 l/min/sqm , PWP > 10 and < 18 mmHg , SVR < 1450 dyne/sec/cm(-5 ) , DO(2 ) > 600 ml/min/sqm ) or conventional treatment . RESULTS there were no differences in terms of in-hospital mortality , cardiovascular morbidity , postoperative renal failure or duration of hospital stay between the groups . CONCLUSIONS in this study perioperative haemodynamic optimisation was not beneficial OBJECTIVE To test the hypothesis that perioperative plasma volume expansion would preserve gut mucosal perfusion during elective cardiac surgery . DESIGN Prospect i ve r and omized open study . SETTING Teaching hospital . PATIENTS Sixty American Society of Anesthesiology grade III patients with a preoperative left ventricular ejection fraction of 50 % or greater undergoing elective cardiac surgery . INTERVENTIONS Patients were allocated r and omly to a control or protocol group . The control group was treated according to st and ard practice s. After induction of general anesthesia , the protocol group received , in addition , 200-mL boluses of a 6 % hydroxyethyl starch solution to obtain a maximum stroke volume . This procedure was repeated every 15 minutes until the end of surgery , except when the patient underwent cardiopulmonary bypass . MEASUREMENTS AND RESULTS Cardiac stroke volume was estimated by an esophageal Doppler system , and gastric mucosal perfusion was measured by tonometric assessment of gastric intramucosal pH in all patients . Patients were followed up postoperatively until discharge from the hospital or death . The incidence of gut mucosal hypoperfusion ( gastric intramucosal pH < 7.32 ) at the end of surgery was reduced in the protocol group ( 7 % vs 56 % ) ( P < .001 ) , as were the number of patients in whom major complications developed ( 0 vs 6 ) ( P = .01 ) , mean number of days spent in the hospital ( 6.4 [ range , 5 to 9 ] vs 10.1 [ range , 5 to 48 ] ) ( P = .011 ) , and mean number of days spent in the intensive care unit ( 1 [ range , 1 to 1 ] vs 1.7 [ range 1 to 11 ] days ) ( P = .023 ) . CONCLUSIONS Perioperative plasma volume expansion with colloid during cardiac surgery , guided by esophageal Doppler measurement of cardiac stroke volume , reduced the incidence of gut mucosal hypoperfusion . This group of patients also had an improved outcome when compared with controls Objectives : To evaluate the effects of goal -directed therapy on outcomes in high-risk patients undergoing cardiac surgery . Design : A prospect i ve r and omized controlled trial and an up date d meta analysis of r and omized trials published from inception up to May 1 , 2015 . Setting : Surgical ICU within a tertiary referral university-affiliated teaching hospital . Patients : One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair . Interventions : Patients were r and omized to a cardiac output – guided hemodynamic therapy algorithm ( goal -directed therapy group , n = 62 ) or to usual care ( n = 64 ) . In the goal -directed therapy arm , a cardiac index of greater than 3 L/min/m2 was targeted with IV fluids , inotropes , and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU . Measurements and Main Results : The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications . Patients from the goal -directed therapy group received a greater median ( interquartile range ) volume of IV fluids than the usual care group ( 1,000 [ 625–1,500 ] vs 500 [ 500–1,000 ] mL ; p < 0.001 ] , with no differences in the administration of either inotropes or RBC transfusions . The primary outcome was reduced in the goal -directed therapy group ( 27.4 % vs 45.3 % ; p = 0.037 ) . The goal -directed therapy group had a lower occurrence rate of infection ( 12.9 % vs 29.7 % ; p = 0.002 ) and low cardiac output syndrome ( 6.5 % vs 26.6 % ; p = 0.002 ) . We also observed lower ICU cumulative dosage of dobutamine ( 12 vs 19 mg/kg ; p = 0.003 ) and a shorter ICU ( 3 [ 3–4 ] vs 5 [ 4–7 ] d ; p < 0.001 ) and hospital length of stay ( 9 [ 8–16 ] vs 12 [ 9–22 ] d ; p = 0.049 ) in the goal -directed therapy compared with the usual care group . There were no differences in 30-day mortality rates ( 4.8 % vs 9.4 % , respectively ; p = 0.492 ) . The meta analysis identified six trials and showed that , when compared with st and ard treatment , goal -directed therapy reduced the overall rate of complications ( goal -directed therapy , 47/410 [ 11 % ] vs usual care , 92/415 [ 22 % ] ; odds ratio , 0.40 [ 95 % CI , 0.26–0.63 ] ; p < 0.0001 ) and decreased the hospital length of stay ( mean difference , –5.44 d ; 95 % CI , –9.28 to –1.60 ; p = 0.006 ) with no difference in postoperative mortality : 9 of 410 ( 2.2 % ) versus 15 of 415 ( 3.6 % ) , odds ratio , 0.61 ( 95 % CI , 0.26–1.47 ) , and p = 0.27 . Conclusions : Goal -directed therapy using fluids , inotropes , and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery BACKGROUND : Dynamic variables predict fluid responsiveness and may improve fluid management during surgery . We investigated whether displaying the variability in the pulse oximeter plethysmogram ( pleth variability index ; PVI ) would guide intraoperative fluid management and improve circulation as assessed by lactate levels . METHODS : Eighty-two patients scheduled for major abdominal surgery were r and omized into 2 groups to compare intraoperative PVI-directed fluid management ( PVI group ) versus st and ard care ( control group ) . After the induction of general anesthesia , the PVI group received a 500-mL crystalloid bolus and a crystalloid infusion of 2 mL · kg−1 · h−1 . Colloids of 250 mL were administered if the PVI was > 13 % Vasoactive drug support was given to maintain the mean arterial blood pressure above 65 mm Hg . In the control group , an infusion of 500 mL of crystalloids was followed by fluid management on the basis of fluid challenges and their effects on mean arterial blood and central venous pressure . Perioperative lactate levels , hemodynamic data , and postoperative complications were recorded prospect ively . RESULTS : Intraoperative crystalloids and total volume infused were significantly lower in the goal -directed PVI group . Lactate levels were significantly lower in the PVI group during surgery and 48 hours after surgery ( P < 0.05 ) . CONCLUSIONS : PVI-based goal -directed fluid management reduced the volume of intraoperative fluid infused and reduced intraoperative and postoperative lactate levels Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI , DO2 , and VO2 than nonsurvivors . The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism . We tested this hypothesis in two series . In series 1 , prospect ively allocated by services , mortality and morbidity of the control group were significantly greater than those of the protocol group . In series 2 , patients who fulfilled previously defined high-risk criteria were preoperatively r and omized to one of three monitoring/treatment groups : CVP-control group , PA-control group and PA- protocol group . Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different , but PA- protocol group mortality was significantly reduced compared with its control group . The PA- protocol group had reduced complications , duration of hospitalization , duration in ICU , and mechanical ventilation , and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses BACKGROUND Emergency abdominal surgery carries a high risk of postoperative morbidity and mortality . Goal directed therapy has been advocated to improve outcome in high-risk surgery . The aim of the present pilot study was to examine the effect of goal directed therapy using fluid alone on postoperative renal function and organ failure score in patients undergoing emergency abdominal surgery . METHODS This prospect i ve r and omised pilot study included patients over the age of 50 undergoing emergency abdominal surgery . In the intervention group pulse pressure variation measurements were used to guide fluid boluses of 6 % Hydroxyethylstarch 130/0.4 . The control group received st and ard care . Serum urea , creatinine and cystatin C levels were measured prior to and at the end of surgery and postoperatively on day 1 , day 3 and day 5 . RESULTS Thirty patients were recruited . One patient died prior to surgery and was excluded from the analysis . The intervention group received a median of 750 ml of hydroxyethylstarch . The peak values of postoperative urea were 6.9 ( 2.7 - 31.8 ) vs. 6.4 (3.5 - 11.5)mmol/l ( p=0.425 ) , creatinine 100 ( 60 - 300 ) vs. 85 ( 65 - 150 ) micromol/l ( p=0.085 ) and cystatin C 1.09 ( 0.66 - 4.94 ) vs. 1.01 (0.33 - 2.29)mg/dl ( p=0.352 ) in the control and intervention group , respectively . CONCLUSIONS In the present pilot study replacing the identified fluid deficit was not associated with a change in renal function . These results do not preclude that goal directed therapy using fluid alone may have an effect on renal function but they would suggest that the effect size of fluid optimisation alone on renal function is small Summary Oesophageal Doppler monitoring allows non‐invasive estimation of stroke volume and cardiac output . We studied the impact of Doppler guided fluid optimisation on haemodynamic parameters , peri‐operative morbidity and hospital stay in patients undergoing major bowel surgery . Fifty‐seven patients were r and omly assigned to Doppler ( D ) or control ( C ) groups . All patients received intra‐operative fluid therapy at the discretion of the non‐investigating anaesthetist . In addition , Group D were given fluid challenges ( 3 ml.kg−1 ) guided by oesophageal Doppler . Group D received significantly more intra‐operative colloid than Group C ( mean 28 ( SD 16 ) vs. 19.4 ( SD 14.7 ) ml.kg−1 , p = 0.02 ) . Cardiac output increased significantly for Group D whilst that of controls remained unchanged . The mean difference between the groups in final cardiac output was 0.87 l.min−1 ( 95 % confidence interval 0.31–1.43 l.min−1 , p = 0.003 ) . Five control patients required postoperative critical care admission . Fluid titration using oesophageal Doppler during bowel surgery can improve haemodynamic parameters and may reduce critical care admissions postoperatively Intraoperative goal directed fluid therapy ( GDT ) guided by an arterial pressure-based cardiac output system has been reported to improve gastrointestinal ( GI ) recovery in high-risk patients . This study evaluates the impact of this approach on GI recovery in low to moderate risk patients undergoing major abdominal surgery . IRB approved r and omized controlled trial in low to moderate risk adults scheduled for major surgery . Patients were r and omized to st and ard ( n = 20 ) or GDT ( n = 18 ) groups , whose fluids were managed to maintain stroke volume variation ( SVV ) < 12 % . The primary outcome measure was GI recovery . Additional measures included quality of recovery score . Continuous , non-normally distributed by Mann – Whitney test ; ordinal and nominal by Chi square analysis . GDT patients had lower average intraoperative SVV . The GDT group had faster return of GI function ( p = 0.004 ) and higher quality of recovery scores . In low to moderate risk patients undergoing major abdominal surgery , intraoperative GDT guided by SVV optimization was associated with faster restoration of GI recovery and higher quality of recovery scores . These results suggest that outcome benefits related to the use of an intraoperative goal directed fluid protocol guided by SVV are not limited to high-risk patients OBJECTIVE To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery . DESIGN Prospect i ve , r and omized clinical trial . SETTING A teaching hospital general intensive care unit , London , Engl and . PATIENTS A total of 107 surgical patients , who were assessed as high risk from previously identified criteria , were studied during an 18-month period . INTERVENTIONS Patients were r and omly assigned to a control group ( n = 54 ) that received best st and ard perioperative care , or to a protocol group ( n = 53 ) that , in addition , had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion . OUTCOME MEASURES Mortality and complications were assessed to 28 days postoperatively . RESULTS Groups were similar with respect to demographics , admission criteria , operation type , and admission hemodynamic variables . Groups were treated similarly to maintain blood pressure , arterial saturation , hemoglobin concentration , and pulmonary artery occlusion pressure ; however , once additional treatment with dopexamine hydrochloride had been given , the protocol group had significantly higher oxygen delivery preoperatively ( median , 597 vs 399 mL/min per square meter ; P < .001 ) and postoperatively ( P < .001 ) . Results indicate a 75 % reduction in mortality ( 5.7 % vs 22.2 % ; P = .015 ) and a halving of the mean ( + /- SEM ) number of complications per patient ( 0.68 [ + /- 0.16 ] vs 1.35 [ + /- 0.20 ] ; P = .008 ) in patients r and omized to the protocol group . CONCLUSION Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients Intra‐operative oesophageal Doppler monitor‐guided fluid management has been associated with improved postoperative length of hospital stay and morbidity in gastrointestinal and orthopaedic surgery . We design ed a r and omised controlled trial to test the hypothesis that this approach to intra‐operative fluid management in major elective open gynaecological surgery would shorten the length of postoperative stay , defined as time to readiness for hospital discharge . Postoperative morbidity was evaluated as a secondary outcome . The oesophageal Doppler monitor group underwent intra‐operative fluid management using an oesophageal Doppler‐guided stroke volume optimisation algorithm . Control group ( conventional fluid therapy ) intra‐operative fluid management was based on conventional haemodynamic indices . In a single centre , 102 patients were r and omly assigned : 51 to the oesophageal Doppler monitor group ( 51 analysed ) and 51 to the control group ( 50 analysed ) . Evaluators who were blinded to patient assignment collected postoperative outcome data . There was no difference in the length of postoperative hospital stay between the groups : median ( IQR [ range ] ) number of days until ready for discharge was 6 ( 5–8 [ 4–25 ] ) days in the oesophageal Doppler monitor group compared with 7 ( 5–9 [ 4–42 ] ) days in the control group , p = 0.5 . There was no difference between the groups in postoperative morbidity survey scores on postoperative days 1 , 3 or 5 . Seven patients in the oesophageal Doppler monitor group and 11 in the control group experienced postoperative complications ( p = 0.41 ) . These findings question whether intra‐operative oesophageal Doppler‐guided fluid therapy is of benefit in patients undergoing open gynaecological surgery Abstract Objectives : To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture . Design : Prospect i ve , r and omised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period . Setting : Teaching hospital , London . Subjects : 40 patients undergoing repair of proximal femoral fracture under general anaesthesia . Interventions : Patients were r and omly assigned to receive either conventional intraoperative fluid management ( control patients ) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period ( protocol patients ) . Main outcome measures : Time declared medically fit for hospital discharge , duration of hospital stay ( in acute bed ; in acute plus long stay bed ) , mortality , perioperative haemodynamic changes . Results : Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume ( median 15 ml ( 95 % confidence interval 10 to 21 ml ) ) and cardiac output ( 1.2 l/min ( 0.1 to 2.3 l/min ) ) than in the conventionally managed group ( −5 ml ( −10 to 1 ml ) and −0.4 l/min ( −1.0 to 0.2 l/min ) ) ( P<0.001 and P<0.05 , respectively ) . One protocol patient and two control patients died in hospital . In the survivors , postoperative recovery was significantly faster in the protocol patients , with shorter times to being declared medically fit for discharge ( median 10 ( 9 to 15 ) days v 15 ( 11 to 40 ) days , P<0.05 ) and a 39 % reduction in hospital stay ( 12 ( 8 to 13 ) days v 20 ( 10 to 61 ) days , P<0.05 ) . Conclusions : Proximal femoral fracture repair constitutes surgery in a high risk population . Intraoperative intravascular volume loading to optimal stroke volume result ed in a more rapid postoperative recovery and a significantly reduced hospital stay . Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery , but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital Purpose : Our prospect i ve , r and omized clinical study aims to evaluate the utility of intraoperative transesophageal echocardiography ( TEE ) in patients undergoing radical cystectomy . Material s and Methods : Eighty patients were r and omized to a st and ard of care group or the intervention group that received continuous intraoperative TEE . Data are presented as means ± st and ard deviations , median ( 25th percentile , 75th percentile ) , or numbers and percentages . Characteristics were compared between groups using independent sample t-tests , Wilcoxon – Mann – Whitney tests or Chi-square tests , as appropriate . All tests were two-sided and P < 0.05 was considered to indicate statistical significance . Results : Both groups had similar preoperative demographic characteristics . There was a significant difference between central line insertion with all insertions in the control group ( 15 % , 6 vs. 0 % , 0 ; P < 0.003 ) . Of all the perioperative complications , 80 % occurred in the control group versus 20 % in the TEE group , with 21 % of controls experiencing a cardiac or pulmonary complication compared to 5 % in the TEE group ( 8 vs. 2 , P < 0.04 ) . The control group patients were more likely to have adverse cardiac complications than the TEE group ( 15 % , 6 vs. 3 % , 1 ; P < 0.040 ) . Postoperative cardiac arrhythmia was observed only in the control group ( 13 % , 5 vs. 0 % , 0 ; P < .007 ) . Prolonged intubation was only observed in the control group ( 10 % , 4 vs. 0 % , 0 ; P < 0.017 ) . Conclusion : TEE can be a useful monitoring tool in patients undergoing radical cystectomy , limiting the use of central line insertion and potentially translating into earlier extubation and decreased postoperative cardiac morbidities IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm . OBJECTIVE To evaluate the clinical effectiveness of a perioperative , cardiac output-guided hemodynamic therapy algorithm . DESIGN , SETTING , AND PARTICIPANTS OPTIMISE was a pragmatic , multicenter , r and omized , observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom . An up date d systematic review and meta- analysis were also conducted including r and omized trials published from 1966 to February 2014 . INTERVENTIONS Patients were r and omly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope ( dopexamine ) infusion during and 6 hours following surgery ( n=368 ) or to usual care ( n=366 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality . Secondary outcomes were morbidity on day 7 ; infection , critical care-free days , and all-cause mortality at 30 days ; all-cause mortality at 180 days ; and length of hospital stay . RESULTS Baseline patient characteristics , clinical care , and volumes of intravenous fluid were similar between groups . Care was nonadherent to the allocated treatment for less than 10 % of patients in each group . The primary outcome occurred in 36.6 % of intervention and 43.4 % of usual care participants ( relative risk [ RR ] , 0.84 [ 95 % CI , 0.71 - 1.01 ] ; absolute risk reduction , 6.8 % [ 95 % CI , -0.3 % to 13.9 % ] ; P = .07 ) . There was no significant difference between groups for any secondary outcomes . Five intervention patients ( 1.4 % ) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group . Findings of the meta- analysis of 38 trials , including data from this study , suggest that the intervention is associated with fewer complications ( intervention , 488/1548 [ 31.5 % ] vs control , 614/1476 [ 41.6 % ] ; RR , 0.77 [ 95 % CI , 0.71 - 0.83 ] ) and a nonsignificant reduction in hospital , 28-day , or 30-day mortality ( intervention , 159/3215 deaths [ 4.9 % ] vs control , 206/3160 deaths [ 6.5 % ] ; RR , 0.82 [ 95 % CI , 0.67 - 1.01 ] ) and mortality at longest follow-up ( intervention , 267/3215 deaths [ 8.3 % ] vs control , 327/3160 deaths [ 10.3 % ] ; RR , 0.86 [ 95 % CI , 0.74 - 1.00 ] ) . CONCLUSIONS AND RELEVANCE In a r and omized trial of high-risk patients undergoing major gastrointestinal surgery , use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality . However , inclusion of these data in an up date d meta- analysis indicates that the intervention was associated with a reduction in complication rates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N04386758 |
12,540 | 29,289,576 | As it emerges from this systematic review , the use of some phytochemicals and botanicals seems to be very promising in order to delay the onset and progression of neurodegenerative and other age‐related diseases . | & NA ; Beyond the well‐known effects on cognitive impairment of the Mediterranean diet , a number of studies have investigated the possible action on cognitive decline of different botanicals and phytochemicals , most of which are well‐known anti‐inflammatory or antioxidant agents with a good tolerability and safety profile .
In particular , the current literature supports the use of Ginkgo biloba , resveratrol , epigallocatechin‐3‐gallate and L‐theanine , Theobroma cacao , Bacopa monnieri , Crocus sativus and curcumin , which might have a positive impact on cognitive impairment used alone or in combination with other nutraceuticals or traditional drugs .
Then , the aim of the present study was to review and comment the available evidence on botanicals and phytochemicals with a clinical ly demonstrable effect on cognitive decline . | In healthy older adults , resveratrol supplementation has been shown to improve long-term glucose control , resting-state functional connectivity ( RSFC ) of the hippocampus , and memory function . Here , we aim ed to investigate if these beneficial effects extend to individuals at high-risk for dementia , i.e. , patients with mild cognitive impairment ( MCI ) . In a r and omized , double-blind interventional study , 40 well-characterized patients with MCI ( 21 females ; 50–80 years ) completed 26 weeks of resveratrol ( 200 mg/d ; n = 18 ) or placebo ( 1,015 mg/d olive oil ; n = 22 ) intake . Serum levels of glucose , glycated hemoglobin A1c and insulin were determined before and after intervention . Moreover , cerebral magnetic resonance imaging ( MRI ) ( 3 T ) ( n = 14 vs. 16 ) was conducted to analyze hippocampus volume , microstructure and RSFC , and neuropsychological testing was conducted to assess learning and memory ( primary endpoint ) at both time points . In comparison to the control group , resveratrol supplementation result ed in lower glycated hemoglobin A1c concentration with a moderate effect size ( ANOVARM p = 0.059 , Cohen 's d = 0.66 ) , higher RSFC between right anterior hippocampus and right angular cortex ( p < 0.001 ) , and led to a moderate preservation of left anterior hippocampus volume ( ANOVARM p = 0.061 , Cohen 's d = 0.68 ) . No significant differences in memory performance emerged between groups . This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c , preserves hippocampus volume , and improves hippocampus RSFC in at-risk patients for dementia . Larger trials with longer intervention time should now determine if these benefits can be vali date d and extended to cognitive function Introduction : The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie‐restriction mimicking effects . However , the evidence based on human interventional studies is scarce . We therefore aim ed to determine the effects of resveratrol on memory performance , and to identify potential underlying mechanisms using a broad array of blood‐based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra‐high field magnetic resonance imaging ( UHF‐MRI ) . Methods : In this double‐blind , r and omized controlled trial , 60 elderly participants ( 60–79 years ) with a wide body‐mass index ( BMI ) range of 21–37 kg/m2 were r and omized to receive either resveratrol ( 200mg/day ) or placebo for 26 weeks ( registered at Clinical Trials.gov : NCT02621554 ) . Baseline and follow‐up assessment s included the California Verbal Learning Task ( CVLT , main outcome ) , the ModBent task , anthropometry , markers of glucose and lipid metabolism , inflammation and neurotrophins derived from fasting blood , multimodal neuroimaging at 3 and 7 T , and question naires to assess confounding factors . Results : Multivariate repeated‐ measures ANOVA did not detect significant time by group effects for CVLT performance . There was a trend for preserved pattern recognition memory after resveratrol , while performance decreased in the placebo group ( n.s . , p=0.07 ) . Further exploratory analyses showed increases in both groups over time in body fat , cholesterol , fasting glucose , interleukin 6 , high sensitive C‐reactive protein , tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum , as well as decreases in physical activity , brain‐derived neurotrophic factor and insulin‐like growth factor 1at follow‐up , which were partly more pronounced after resveratrol . Discussion : This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range . A non‐significant trend emerged for positive effects on pattern recognition memory , while possible confounding effects of unfavorable changes in lifestyle behavior , neurotrophins and inflammatory markers occurred . Our findings also indicate the feasibility to detect (un)healthy aging‐related changes in measures of hippocampus microstructure after 6 months using 7 T diffusion MRI . More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol enhances memory performance in healthy older adults . HIGHLIGHTSIn this r and omized clinical trial , 6 months resveratrol supplementation showed no significant effects on verbal memory compared to placebo . Unfavorable changes in lifestyle factors at follow‐up might have introduced confounding . Secondary analyses showed a trend towards preserved pattern recognition . We used multimodal ultra high field MRI to detect subtle changes in microstructure of hippocampus subfields Rationale There has recently been increasing interest in the potential of flavanols , plant-derived compounds found in foods such as fruit and vegetables , to ameliorate age-related cognitive decline . Research suggests that cocoa flavanols improve memory and learning , possibly as a result of their anti-inflammatory and neuroprotective effects . These effects may be mediated by increased cerebral blood flow ( CBF ) , thus , stimulating neuronal function . Objectives The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa flavanols on regional CBF . Methods CBF was measured pre- and post-consumption of low ( 23 mg ) or high ( 494 mg ) 330 ml equicaloric flavanol drinks matched for caffeine , theobromine , taste and appearance according to a r and omized counterbalanced crossover double-blind design in eight males and ten females , aged 50–65 years . Changes in perfusion from pre- to post-consumption were calculated as a function of each drink . Results Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink , particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe . Conclusions Consumption of cocoa flavanol improves regional cerebral perfusion in older adults . This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables Flavanol consumption is favorably associated with cognitive function . We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment . We conducted a double-blind , parallel arm study in 90 elderly individuals with mild cognitive impairment r and omized to consume once daily for 8 weeks a drink containing ≈990 mg ( high flavanols ) , ≈520 mg ( intermediate flavanols ) , or ≈45 mg ( low flavanols ) of cocoa flavanols per day . Cognitive function was assessed by Mini Mental State Examination , Trail Making Test A and B , and verbal fluency test . At the end of the follow-up period , Mini Mental State Examination was similar in the 3 treatment groups ( P=0.13 ) . The time required to complete Trail Making Test A and Trail Making Test B was significantly ( P<0.05 ) lower in subjects assigned to high flavanols ( 38.10±10.94 and 104.10±28.73 seconds , respectively ) and intermediate flavanols ( 40.20±11.35 and 115.97±28.35 seconds , respectively ) in comparison with those assigned to low flavanols ( 52.60±17.97 and 139.23±43.02 seconds , respectively ) . Similarly , verbal fluency test score was significantly ( P<0.05 ) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols ( 27.50±6.75 versus 22.30±8.09 words per 60 seconds ) . Insulin resistance , blood pressure , and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups . Changes of insulin resistance explained ≈40 % of composite z score variability through the study period ( partial r2=0.4013 ; P<0.0001 ) . To the best of our knowledge , this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment . This effect appears mediated in part by an improvement in insulin sensitivity Previous research has shown that resveratrol can increase cerebral blood flow ( CBF ) in the absence of improved cognitive performance in healthy , young human subjects during the performance of cognitively dem and ing tasks . This lack of cognitive effects may be due to low bioavailability and , in turn , reduced bioefficacy of resveratrol in vivo . Piperine can alter polyphenol pharmacokinetics , but previous studies have not investigated whether this affects the efficacy of the target compound . Therefore , the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol with regard to cognition and CBF . The present study utilised a r and omised , double-blind , placebo-controlled , within-subjects design , where twenty-three adults were given placebo , trans-resveratrol ( 250 mg ) and trans-resveratrol with 20 mg piperine on separate days at least a week apart . After a 40 min rest/absorption period , the participants performed a selection of cognitive tasks and CBF was assessed throughout the period , in the frontal cortex , using near-IR spectroscopy . The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort ( n 6 ) . The results indicated that when co-supplemented , piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone . Cognitive function , mood and blood pressure were not affected . The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments , which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects , but not cognitive performance , and does this without altering bioavailability The dentate gyrus ( DG ) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline . Causal evidence is needed , however , to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function . We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging ( fMRI ) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site . Then , in a controlled r and omized trial , we applied these tools to study healthy 50–69-year-old subjects who consumed either a high or low cocoa flavanol – containing diet for 3 months . A high-flavanol intervention was found to enhance DG function , as measured by fMRI and by cognitive testing . Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration We tested whether chronic supplementation with resveratrol ( a phytoestrogen ) could improve cerebrovascular function , cognition and mood in post-menopausal women . Eighty post-menopausal women aged 45–85 years were r and omised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance , cerebral blood flow velocity and pulsatility index ( a measure of arterial stiffness ) in the middle cerebral artery ( using transcranial Doppler ultrasound ) , and cerebrovascular responsiveness ( CVR ) to both cognitive testing and hypercapnia were assessed . Mood question naires were also administered . Compared to placebo , resveratrol elicited 17 % increases in CVR to both hypercapnic ( p = 0.010 ) and cognitive stimuli ( p = 0.002 ) . Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory ( p = 0.041 ) and in overall cognitive performance ( p = 0.020 ) , which correlated with the increase in CVR ( r = 0.327 ; p = 0.048 ) . Mood tended to improve in multiple measures , although not significantly . These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women , potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline CONTEXT Ginkgo biloba is widely used for its potential effects on memory and cognition . To date , adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking . OBJECTIVE To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease ( AD ) in elderly individuals with normal cognition and those with mild cognitive impairment ( MCI ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years . Three thous and sixty-nine community volunteers aged 75 years or older with normal cognition ( n = 2587 ) or MCI ( n = 482 ) at study entry were assessed every 6 months for incident dementia . INTERVENTION Twice-daily dose of 120-mg extract of G. biloba ( n = 1545 ) or placebo ( n = 1524 ) . MAIN OUTCOME MEASURES Incident dementia and AD determined by expert panel consensus . RESULTS Five hundred twenty-three individuals developed dementia ( 246 receiving placebo and 277 receiving G. biloba ) with 92 % of the dementia cases classified as possible or probable AD , or AD with evidence of vascular disease of the brain . Rates of dropout and loss to follow-up were low ( 6.3 % ) , and the adverse effect profiles were similar for both groups . The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group . The hazard ratio ( HR ) for G. biloba compared with placebo for all-cause dementia was 1.12 ( 95 % confidence interval [ CI ] , 0.94 - 1.33 ; P = .21 ) and for AD , 1.16 ( 95 % CI , 0.97 - 1.39 ; P = .11 ) . G. biloba also had no effect on the rate of progression to dementia in participants with MCI ( HR , 1.13 ; 95 % CI , 0.85 - 1.50 ; P = .39 ) . CONCLUSIONS In this study , G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI . Trial Registration clinical trials.gov Identifier : NCT00010803 EGb 761 ( definition see editorial ) Ginkgo extract is produced by a vali date d production process . Its pharmacologically active constituents , flavonol glycosides and terpene lactones , are kept within a narrow range of 22 to 27 % and 5 to 7 % , respectively , by st and ardisation . The concentration of ginkgolic acids is below 5 ppm . The constant production process also maintains the concentrations of other constituents such as proanthocyanidins , carboxylic acids and non-flavone glycosides at a fairly constant level . In this article , we will summarise the data on the pharmacokinetics of flavonol glycosides and terpene lactones WHAT IS KNOWN Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response . Crocus sativus ( saffron ) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer 's disease ( AD ) . OBJECTIVE The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD . METHODS Forty-six patients with probable AD were screened for a 16-week , double-blind study of parallel groups of patients with mild to moderate AD . The psychometric measures , which included AD assessment scale-cognitive subscale ( ADAS-cog ) , and clinical dementia rating scale-sums of boxes , were performed to monitor the global cognitive and clinical profiles of the patients . Patients were r and omly assigned to receive capsule saffron 30 mg/day ( 15 mg twice per day ) ( Group A ) or capsule placebo ( two capsules per day ) for a 16-week study . RESULTS After 16 weeks , saffron produced a significantly better outcome on cognitive function than placebo ( ADAS-cog : F=4·12 , d.f.=1 , P=0·04 ; CDR : F=4·12 , d.f.=1 , P=0·04 ) . There were no significant differences in the two groups in terms of observed adverse events . WHAT IS NEW AND CONCLUSION This double-blind , placebo-controlled study suggests that at least in the short-term , saffron is both safe and effective in mild to moderate AD . Larger confirmatory r and omized controlled trials are called for OBJECTIVE To explore the effects of resveratrol on astrocyte and TNF-α in hippocampus of Alzheimer 's disease ( AD ) model rats . METHODS Sixty rats were r and omly divided into six groups : sham control group , model group , resveratrol 20 , 40 , 80 mg/kg group , and estradiol valerate group ( 0.8 mg/kg ) . The model of AD was established by ovariectomy combined injection of D-galactose ( 100 mg/kg ) . Twelve weeks later , the heart perfusion in vivo was done and then the hippocampus was fixed . Additionally , the changes of hippocampal astrocytes and TNF-α expression were detected by immunohistochemistry . RESULTS The levels of glial fibrillary acidic protein ( GFAP ) and TNF-α in the model group were significantly higher than those of the sham control group ( P < 0.01 ) . No marked difference in the production of GFAP was observed between the resveratrol 20 mg/kg group and the model group ( P > 0.05 ) . However , the resveratrol 40 , 80 mg/kg and estradiol valerate treated groups showed a decrease in the expression of GFAP compared with the model group ( P < 0.01 ) . Moreover , with the increasing of resveratrol concentration , the expression of GFAP decreased gradually . The levels of TNF-α decreased markedly in Res 20 , 40 , 80 mg/kg and estradiol valerate group compared with the model group ( P < 0.01 ) . CONCLUSION These results suggest that the activation of astrocytes and the secretion of TNF-α can be inhibited by Res in AD rats Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults . Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults |
12,541 | 17,935,614 | Users of academic detailing rated it as being more valuable than other forms of CME .
Generally , interview data confirmed question naire data with the exception that interview informants did not view having CME provided by a non-physician as a barrier .
Interview informants mentioned that the evidence -based approach adopted by academic detailing had led them to more critically evaluate information from other CME programs , pharmaceutical representatives , and journal articles , but not advice from specialists .
Conclusion Users of academic detailing highly value its educational value and tend to view information from other sources more critically because of its evidence -based approach .
Non-users are unlikely to adopt academic detailing despite its high educational value because they find using office time for CME too much of a barrier . | Background The efficacy of academic detailing in changing physicians ' knowledge and practice has been the subject of many primary research publications and systematic review s. However , there is little written about the features of academic detailing that physicians find valuable or that affect their use of it .
The goal of our project was to explore family physicians ' ( FPs ) perceptions of academic detailing and the factors that affect their use of it . | Abstract Objective : To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people . Design : R and omised controlled trial with three arms ( individual visits , group visits , and a control arm ) . Setting : Southwest Netherl and s. Participants : 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a data base covering all prescriptions to people covered by national health insurance in the area ( about 240 000 ) . Intervention : All general practitioners and pharmacists in both intervention arms were offered two educational visits . For physicians in groups r and omised to the individual visit arm , 43 of 70 general practitioners participated ; in the group visit intervention arm , five of seven groups ( 41 of 52 general practitioners ) participated . Main outcome measures : Numbers of elderly people ( 60 years ) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants . Results : An intention to treat analysis found a 26 % reduction in the rate of starting highly anticholinergic antidepressants in elderly people ( 95 % confidence interval —4 % to 48 % ) in the individual intervention arm and 45 % ( 8 % to 67 % ) in the group intervention arm . The use of less anticholinergic antidepressants increased by 40 % ( 6 % to 83 % ) in the individual intervention arm and 29 % ( —7 % to 79 % ) in the group intervention arm . Conclusions : Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people . These approaches are practical means to improve prescribing by continuing medical education BACKGROUND Underst and ing pre-test probability and baseline risks helps to interpret the results of diagnostic tests and the benefits of treatment , but how good is the underst and ing of these concepts ? OBJECTIVES Our aim was to assess the ability of GPs and consultant physicians to make accurate estimates and underst and the application of pre-test probability and baseline risk for two common clinical conditions . METHODS A two-stage question naire survey based on case scenarios of patients with angina and congestive heart failure was carried out of 202 physicians , r and omly selected from the members of the Royal College of Physicians in the NW of Engl and , 205 GPs r and omly chosen from the practice list of the NW Health Authorities and 128 MRCGP examiners attending an examiners meeting . A total of 115 , 106 and 81 members of these groups , respectively , responded to the first stage , and 44 , 46 and 64 to the second . The main outcome measures were the stated likelihood of true ischaemic heart disease ( IHD ) being present and the predicted 1-year mortality ; the impact of changing prevalence and baseline risk on these results ; and interpretation of different methods of risk presentation . RESULTS Estimates of pre-test probability of IHD being present ranged from 5 to 100 % and of baseline risk of 1-year mortality from 0 to 86 % . More GP examiners and consultant physicians understood the impact of increasing age on the test result than did the r and om sample of GPs . A majority of each group correctly said that increasing age would reduce the number needed to treat ( NNT ) . Presentation of benefit as relative risk reduction was a greater stimulus to starting treatment than the NNT or measures of population impact . CONCLUSION Clinicians should collect data to allow a better knowledge of the likelihood of disease and of baseline risk in their patient population s. Methods to increase the underst and ing of the influence of pre-test probability on diagnostic test results and of how to quantify and demonstrate the impact of the benefit of interventions should be explored BACKGROUND Different methods have previously been tested to affect GPs ' prescribing habits . Attention has been drawn to benzodiazepines and antipsychotic drugs that are associated with several adverse effects in the elderly . OBJECTIVE To evaluate if educational outreach visits to GP practice s can affect the prescribing of benzodiazepines and antipsychotic drugs to the elderly and to evaluate the opinions of the participating GPs on such education . METHODS In the county of Skåne , Sweden , 41 GP practice s were invited to participate in educational outreach visits . Fifteen GP practice s accepted the invitation . Practice s were r and omised to active ( 8 practice s , 23 physicians ) and control group ( 7 practice s , 31 physicians ) . After the educational outreach visits prescribing of benzodiazepines and antipsychotic drugs to patients 65 years or older were measured for 1 year . The control group participated in the education after the study period . The opinions of GPs on educational outreach visits were evaluated . RESULTS One year after the educational outreach visits there were significant decreases in the active group compared to control group in the prescribing of medium- and long-acting benzodiazepines and total benzodiazepines but not so for antipsychotic drugs . CONCLUSIONS Educational outreach visits can be effective in modifying GPs ' prescribing habits . We have shown this to be so for prescribing of benzodiazepines to elderly patients in primary health care . Educational outreach visits are also very well appreciated by participating GPs AIMS This was a pilot study of the use of a clinical pharmacist as a therapeutics adviser ( academic detailer ) to modify antibiotic prescribing by general practitioners . METHODS Following a visit by the adviser ( March-May ) , 112 general practitioners were recruited and r and omised to control or active groups . A panel of experts prepared a best practice chart of recommended drugs for upper and lower respiratory tract infections , otitis media and urinary tract infections . The adviser made a 10 - 15 min visit to each prescriber in the active group ( June-July ) , gave them the chart and discussed its recommendations briefly . Doctors in the control group were not visited nor given the chart . Prescription numbers for all prescribers were obtained from the Commonwealth Health Insurance Commission for the pre(March-May ) and postdetailing ( August-September ) periods using a three month lag time for data collection . Data for total numbers of prescriptions and for selected individual antibiotics used in these two periods were analysed using nonparametric statistics . RESULTS Prescribing patterns were similar for the control and active groups in the predetailing period . For both groups , there were significant ( P<0.03 ) increases ( 45 % for control and 40 % for active ) in total number of antibiotic prescriptions in the post compared with the predetailing period . This trend was anticipated on the basis of the winter seasonal increase in respiratory infections . In line with the chart recommendations for first-line treatment , doctors in the active group prescribed significantly more amoxycillin ( P<0.02 ) and doxycycline ( P<0.001 ) in the post vs predetailing periods . By contrast , doctors in the control group prescribed significantly more cefaclor ( P<0.03 ) and roxithromycin ( P<0.03 ) , drugs that were not recommended . The total cost of antibiotics prescribed by doctors in the control group increased by 48 % ( $ 37 150 ) from the preto postdetailing periods . In the same time period , the costs for the active group increased by only 35 % ( $ 21 020 ) . CONCLUSIONS We conclude that the academic detailing process was successful in modifying prescribing patterns and that it also decreased prescription numbers and costs . Application of the scheme on a nationwide basis could not only improve prescriber choice of the most appropriate antibiotic but also result in a significant saving of health care dollars Objective To investigate the feasibility and acceptability of academic detailing in general practice in the North-East-Fl and ers region of Belgium . Methods All local quality groups in the study region were r and omly allocated to either ( 1 ) two academic detailing visits to the individual members or ( 2 ) two academic detailing visits during the meetings of the local quality group . During these visits , the results of a systematic review of the literature on non-steroidal anti-inflammatory agents ( NSAIDs ) were presented . Results Of 14 local quality groups , 12 allocated to the individual intervention agreed to participate . Of the 184 physicians invited to receive an academic detailer , 142 had two visits on NSAIDs . One hundred and five physicians gave their opinion on the visits by means of a question naire . The great majority of the responders ( 90 % ) wished to receive an academic detailer on other topics in the future , with a frequency of two visits per year . Of 13 local quality groups , 12 allocated to the group intervention , with a total number of 192 physicians who agreed to participate . Ten local quality groups with 166 members received the information on NSAIDs . The actual attendance rate per intervention session was approximately two out of three physicians . All 166 physicians of the participating local quality groups were offered an evaluation form , and 79 responded . Of the responders who received the full group intervention , 88 % wished to have more academic detailing visits on other topics in their local quality group . A comparison between the evaluation forms of the individual and the group intervention revealed no major differences concerning the acceptability of the intervention . Conclusion The pilot study showed that academic detailing is feasible in the North-East-Fl and ers region of Belgium . Both the individual visits and the visits to the local quality groups were rated positively , and a majority of the general practitioners who returned the evaluation question naire wished to receive such visits in the future . The structure of the local quality groups implies limitations to the practical organisation of a visit , but requires less time investment than individual visits OBJECTIVE : To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy ( HRT ) is presented influences family physicians ’ intentions to prescribe this treatment . DESIGN : Family physicians were r and omized to receive information on treatment outcomes expressed in relative terms , or as the number needing to be treated ( NNT ) with HRT to prevent or cause an event . A control group received no information . SETTING : Primary care . PARTICIPANTS : Family physicians practicing in the Hunter Valley , New South Wales , Australia . INTERVENTION : Estimates of the impact of long-term HRT on risk of coronary events , hip fractures , and breast cancer were summarized as relative ( proportional ) decreases or increases in risk , or as NNT . MEASUREMENTS AND MAIN RESULTS : Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales . Of 389 family physicians working in the Hunter Valley , 243 completed the baseline survey and 215 participated in the r and omized trial . Baseline intention to prescribe varied across patients —it was highest in the presence of risk factors for hip fracture , but coexisting risk factors for breast cancer had a strong negative influence . Overall , a larger proportion of subjects receiving information expressed as NNT had reduced intentions , and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms , or the control group . However , the differences were small and only reached statistical significance for three hypothetical patients . Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer . CONCLUSIONS : Information framing had some effect on family physicians ’ intentions to prescribe HRT , but the effects were smaller than those previously reported , and they were modified by the presence of serious potential adverse treatment effects |
12,542 | 18,797,733 | Bisphosphonates were reported to have consistently reduced the risk of vertebral fractures .
Hormone replacement therapy showed positive outcomes , but its use has been found to increase the risk of cardiovascular disease and breast cancer .
Teriparatide and monofluorophosphate also showed efficacy against osteoporosis . | Osteoporosis , a typical disease of the elderly , has become a frequent and relevant public health problem .
Several drugs are available for treatment of osteoporosis , some of which are currently dispensed by the Brazilian Unified National Health System .
The objective of this study was to present a systematic review of drugs for treatment of osteoporosis , focusing on the adequacy of clinical protocol s based on existing evidence in the scientific literature . | BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption . In a phase 2 clinical trial , strontium ranelate , an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption , has been shown to reduce the risk of vertebral fractures and to increase bone mineral density . METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial , we r and omly assigned 1649 postmenopausal women with osteoporosis ( low bone mineral density ) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years . We gave calcium and vitamin D supplements to both groups before and during the study . Vertebral radiographs were obtained annually , and measurements of bone mineral density were performed every six months . RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group , with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period ( relative risk , 0.59 ; 95 percent confidence interval , 0.48 to 0.73 ) . Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck ( P<0.001 for both comparisons ) . There were no significant differences between the groups in the incidence of serious adverse events . CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures UNLABELLED The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis . The incidence of vertebral fractures was significantly reduced by 46 % . The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density , QUS , weight , and smoking . INTRODUCTION This study aim ed to determine if the bisphosphonate , clodronate ( Bonefos ) , reduced the incidence of vertebral fractures in osteoporotic women . MATERIAL S AND METHODS Women fulfilling the WHO criteria for osteoporosis at the lumbar spine ( T-score < /= -2.5 ) and /or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind , placebo-controlled study . A total of 593 patients were r and omized to two strata comprised of women with postmenopausal osteoporosis ( I , n = 483 ) and secondary osteoporosis ( II , n = 110 ) . They received either clodronate 800 mg daily orally ( n = 292 ) or an identical placebo ( n = 301 ) . All patients received a calcium supplement of 500 mg daily . BMD was measured at 6 , 12 , 24 , and 36 months , and lateral spine radiographs were obtained at baseline and annually thereafter for vertebral morphometry . RESULTS Treatment with clodronate was associated with a significant increase in mean spine BMD over 3 years ( percent change from baseline , 4.35 + /- 6.34 % versus 0.64 + /- 6.02 % in the placebo group , p < 0.0001 ) . At the hip , clodronate maintained total BMD , whereas a significant decrease was observed in the placebo group ( percent change from baseline 0.70 + /- 5.67 % versus -3.03 + /- 6.32 % in the placebo group , p < 0.0001 ) . The changes at the spine and hip were similar in both strata . Incident vertebral fractures at 3 years were observed in 63 women in the placebo group and 33 patients receiving clodronate ( relative risk , 0.54 ; 95 % CI , 0.37 - 0.80 ; p = 0.001 ) . Clodronate significantly reduced vertebral fracture risk in both strata and in women with or without prior vertebral fracture at baseline . Nonvertebral osteoporosis-associated fractures occurred in 21 women in the placebo group and in 14 women treated with clodronate . Treatment was well tolerated , with no significant difference in adverse event rates , including esophagitis , during clodronate treatment . CONCLUSION We conclude that clodronate 800 mg daily is a safe and effective treatment to reduce fracture risk in women with osteoporosis , regardless of causation The purpose of this study was to evaluate the efficacy of calcitonin on β-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis . The secondary purpose was to assess the pain and quality of life in these patients . There were 30 patients with a mean age of 58.2±5.4 years in the treatment group and 26 patients with a mean age of 58.8±5.2 years in the placebo group in this r and omized , placebo-controlled study . The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks . Baseline plasma β-endorphin levels were measured and repeated after 2 weeks . Patients ’ pain and quality of life ( QOL ) were evaluated by using the Visual Analogue Scale , Modified Face Scale , Beck Depression Index , and Nottingham Health Profile . Patients ’ global assessment of disease activity was also performed at baseline and at the end of the first and second week . We found that plasma β-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week ( p<0.001 ) . Although pain and QOL scores were improved at the end of the second week in both groups ( p<0.05 ) , the improvement in the treatment group was more significant when compared with the placebo group ( p<0.05 ) . Therefore , calcitonin is an analgesic agent , as it increases the plasma β-endorphin levels in patients with postmenopausal osteoporosis , which consequently improves QOL Objective : To compare the efficacy and tolerability of once-weekly ( OW ) alendronate ( ALN ) 70 mg and raloxifene ( RLX ) 60 mg daily in the treatment of postmenopausal osteoporosis . Design : This 12-month , r and omized , double-blind study enrolled 456 postmenopausal women with osteoporosis ( 223 ALN , 233 RLX ) at 52 sites in the United States . Efficacy measurements included lumbar spine ( LS ) , total hip , and trochanter bone mineral density ( BMD ) at 6 and 12 months , biochemical markers of bone turnover , and percent of women who maintained or gained BMD in response to treatment . The primary endpoint was percent change from baseline in LS BMD at 12 months . Adverse experiences were recorded to assess treatment safety and tolerability . Results : Over 12 months , OW ALN produced a significantly greater increase in LS BMD ( 4.4 % , P < 0.001 ) than RLX ( 1.9 % ) . The percentage of women with ≥ 0 % increase in LS BMD ( ALN , 94 % ; RLX , 75 % ; P < 0.001 ) and ≥ 3 % increase in LS BMD ( ALN , 66 % ; RLX , 38 % ; P < 0.001 ) were significantly greater with ALN than RLX . Total hip and trochanter BMD increases were also significantly greater ( P ≤0.001 ) with ALN . Greater ( P < 0.001 ) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months . No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen . Conclusion : ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months . A greater percentage of women maintained or gained BMD on ALN than RLX . Both medications had similar safety and tolerability profiles Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience . Ib and ronate is a highly potent nitrogen-containing bisphosphonate , proven to significantly increase vertebral and nonvertebral bone mineral density ( BMD ) when administered as a convenient intravenous injection . A recent double-blind , placebo-controlled , r and omized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ib and ronate injections , given once every 3 months , in 2862 women ( 55 - 76 years ) with postmenopausal osteoporosis [ one to four prevalent vertebral fractures and lumbar spine ( L1-L4 ) BMD T score of less than -2.0 and greater than -5.0 in > or=1 vertebra ] . All participants received daily vitamin D ( 400 IU ) and calcium ( 500 mg ) supplementation . The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years . However , although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo ( 9.2 % vs. 8.7 % vs. 10.7 % in the 1 mg , 0.5 mg and placebo groups , respectively ) , as well as in the incidence of nonvertebral and hip fractures , the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance . At the studied doses , intravenous ib and ronate injections also produced dose-dependent , but comparatively small , increases in lumbar spine BMD ( 4.0 % and 2.9 % , respectively ) and decreases in biochemical markers of bone resorption and formation , relative to placebo . Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover . In light of the clear dose-response relationship observed in this and other studies , this is likely to be achieved with higher intravenous doses of ib and ronate . The results of a recent phase II/III study ( Intermittent Regimen Intravenous Ib and ronate Study : the IRIS study ) provide support for this hypothesis This study evaluated the efficacy and tolerability of risedronate once a week ( 35 mg and 50 mg ) compared with risedronate 5 mg once daily in women with osteoporosis . We conducted a r and omized , double-blind , active-controlled , 2-year study ; the primary efficacy assessment was performed after 1 year . Subjects were women aged 50 years or older who had been postmenopausal for at least 5 years , with either a bone mineral density ( BMD ) T-score of -2.5 or lower ( lumbar spine or proximal femur ) or a T-score lower than -2 and at least one prevalent vertebral fracture . Subjects received risedronate 5 mg once daily , 35 mg once a week or 50 mg once a week . All subjects also received 1 g daily of elemental calcium supplementation and supplemental vitamin D if the baseline serum levels were low . The primary efficacy measure was percent change in lumbar spine BMD at 12 months . A total of 1,456 women were r and omized and received medication ; 1,209 ( 83 % ) women completed 12 months . The mean percent change ( SE ) in lumbar spine BMD after 12 months was 4.0 % ( 0.2 % ) in the 5 mg daily group , 3.9 % ( 0.2 % ) in the 35 mg group , and 4.2 % ( 0.2 % ) in the 50 mg group ; each once-a-week treatment was determined to be as effective as the daily treatment . Outcomes of the secondary efficacy measurements and safety assessment s were also similar in all 3 groups after 12 months . Risedronate 35 mg and 50 mg once a week provide the same efficacy and safety as the daily 5 mg regimen ; therefore , the lower dose , 35 mg once a week , is considered optimal for women with postmenopausal osteoporosis who desire a once-a-week regimen Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal . Less frequent dosing regimens are likely to improve patient adherence and thus , potentially , patient outcomes . A multicenter , r and omized , double-blind , noninferiority study was conducted in 235 women ( 53 - 80 yr old ; time since menopause > /== " BORDER="0 " > 3 yr ) with postmenopausal osteoporosis [ lumbar spine ( L1-L4 ) bone mineral density ( BMD ) T-score < /= -2 ] to demonstrate the noninferiority of an oral weekly ( 20 mg ) ib and ronate regimen compared with an oral daily ( 2.5 mg ) ib and ronate regimen . All patients received daily calcium ( 500 mg ) and vitamin D ( 400 IU ) . The primary analysis was the relative change in lumbar spine ( L1-L4 ) BMD from baseline after 48 wk in the per- protocol population . Daily and weekly ib and ronate significantly increased spinal BMD by 3.47 and 3.53 % , respectively , and provided substantial and similar decreases in biochemical markers of bone turnover . In the primary analysis , noninferiority of the weekly regimen to the daily regimen was demonstrated , with the boundary of the one-sided confidence interval , -0.96 % , within both the -1.65 % prespecified margin and a more stringent margin of -1.10 % . These results demonstrate that oral weekly ib and ronate provides the same efficacy and safety as oral daily ib and ronate in women with postmenopausal osteoporosis During the past 30 years , fluoride salts have been studied as agents for the treatment of osteoporosis in postmenopausal women with the expectation that stimulation of osteoblastic proliferation and activity and the subsequent increase in bone formation would be followed by a significant decrease in fracture rates [ 1 - 3 ] . It is widely accepted that fluoride is effective in increasing trabecular bone mass in the spine [ 4 ] . However , discrepant results have been obtained from studies evaluating the effects of fluoride salts on cortical bone mass and , more important , on the quality of the newly synthesized bone and on vertebral and nonvertebral fracture rates [ 5 - 9 ] . These differences are probably related to differences in fluoride dose , formulation , and regimen ; duration of therapy ; and treated population s. Because bone-forming agents such as fluoride are expected to work mainly by increasing bone mineral content without restoring disrupted bone tissue integrity , they may be particularly useful in patients with mild to moderate osteoporosis in whom the microarchitecture of the skeleton is not excessively damaged . To test this hypothesis , we studied the effect of low-dose fluoride ( sodium monofluorophosphate [ MFP ] ) plus calcium in a 4-year , r and omized , double-blind , controlled clinical trial in postmenopausal women with moderately low bone mineral density ( BMD ) of the spine . Methods Patients Our study included white postmenopausal women with lumbar ( L2 to L4 ) BMD of the spine below the 90th percentile of the distribution of BMD of the spine seen in Belgian women with osteoporosis [ 10 , 11 ] . This degree of bone loss corresponded to a T-score of 2.5,in accordance with the operational definition of osteoporosis recently proposed by a World Health Organization study group [ 12 ] . Patients were included in the study regardless of whether they had previously had vertebral or nonvertebral fractures ; most of the patients were thought to be free of vertebral fractures at enrollment . Previous hip fracture was an exclusion criterion . All patients were free of other causes of osteoporosis , such as diseases or medications known to interfere with bone metabolism ; none had been treated with any drug for postmenopausal osteoporosis ; and no such treatment was allowed during the study . Hormone replacement therapy was continued , for ethical reasons , in women for whom it had been prescribed before enrollment for purpose s other than bone therapy . R and omization was not stratified with respect to hormone replacement therapy . Patients with bone diseases other than osteoporosis , renal insufficiency , hypochlorhydria , or severe chronic disorders that could have interfered with the study were excluded . Study Design Patients were r and omly assigned in a blinded manner to one of two therapeutic groups . Every day for 4 years , they received either two chewable tablets that each contained 76 mg of MFP ( 10 mg of equivalent fluoride [ fluoride ion ] ) and 1250 mg of calcium carbonate ( 500 mg of equivalent calcium ) or two chewable tablets that each contained 1250 mg of calcium carbonate alone and were similar in appearance to the MFP-plus-calcium tablets . Total daily dosages , therefore , were 20 mg of equivalent fluoride plus 1000 mg of calcium in the MFP-plus-calcium group and 1000 mg of calcium in the calcium-only group . The two tablets were taken at different meals . We determined compliance at each study visit by asking each patient for the number of days on which she had not taken the tablets and by counting the unused tablets . Compliance was expressed as the percentage of tablets taken ( 100 % if the patient had taken all of the tablets ) . Patients received r and omization numbers sequentially . R and omization was computer generated in blocks of four according to a strict st and ard operating procedure by persons who had no contact with the persons in the center who assigned patients to study groups . The r and omization code was kept at the study sponsor 's facility under secure conditions that were detailed in writing . The clinical research center was given opaque , sealed envelopes , each of which contained the code for one patient . Treatment assignment and other relevant information were thus concealed and were to be revealed only in the case of a medical emergency . Blinding was achieved by using the following procedures . First , the persons who did the visual readings of the spine radiographs saw the codes only after the results were analyzed . Second , the data were analyzed under blinded conditions : that is , a first analysis was done with groups A and B ; the analysts did not know which group had received which treatment . Efficacy Evaluation Criteria The primary end point was the number of patients with new vertebral fractures during the 4-year treatment period , in accordance with recently published guidelines for the evaluation of drugs to be registered in Europe for the prevention or treatment of osteoporosis [ 13 ] . St and ardized lateral radiographs of the thoracic and lumbar spine were obtained at enrollment and at each year of follow-up , for up to 4 years , in a single radiology center . The radiographs were sent to an independent assessor . Films were digitized , and the anterior , middle , and posterior heights of each vertebral body from the fourth thoracic ( T4 ) to the fifth lumbar ( L5 ) were determined ( accuracy of the digitizer , 0.025 mm ) by a computer program . This was done by persons with no knowledge of treatment assignment or film sequence . A new vertebral fracture ( incident fracture ) was defined as a reduction of at least 20 % and an absolute decrease of at least 4 mm in any height of at least one vertebral body between enrollment and the latest follow-up film . All fractures , including borderline cases , were confirmed by visual reading . This definition was applied to vertebrae that were not fractured at enrollment , whereas fractures present at enrollment were determined on the digitized enrollment radiographs by using the Melton-Riggs 25 % unadjusted algorithm [ 14 ] . The possible progression of such baseline lesions was assessed with the Vertebral Deformity Index obtained for each vertebra ( T5 through L5 ) ; these were then summed to obtain the Spine Deformity Index , a continuous measure of vertebral deformities [ 15 ] . The Spine Deformity Index was also used as a secondary variable in patients with incident or progressing vertebral deformities , in whom it was expressed as the mean change between the last observed value and baseline . Bone mineral density was measured by using dual-energy x-ray absorptiometry on the same densitometer ( Hologic QDR 1000 , Waltham , Massachusetts ) at 6-month intervals at the lumbar spine ( L2 to L4 ) and the nondominant hip ( total hip ) after previously described and vali date d procedures were performed [ 11 , 16 ] . In our h and s , the long-term coefficients of variation of dual-energy x-ray absorptiometry are 0.8 % for BMD of the spine and 1.1 % for BMD of the total hip [ 17 ] . Biochemical determinations of bone remodeling were made at 6-month intervals . Bone formation was assessed by radioimmunoassay of serum bone-specific alkaline phosphatase ( Ostase , Hybritech , San Diego , California ) . For bone resorption , we measured the ratio of urinary hydroxyproline to creatinine on the second fasting urine spot ( 2-hour morning urine ) ( Hypronostikon kit , Organon Technika , Oss Boxtel , the Netherl and s ) . All peripheral ( nonvertebral ) fractures that occurred during the study were recorded independently of the nature and severity of the trauma that may have determined them . Statistical Analysis All analyses were done according to the intention-to-treat approach : that is , all patients who had at least one valid measurement after r and omization were considered in the analysis , whether they were still taking the study drug or not . In the case of drop-out and , thus , discontinuation of therapy with the study medication , the patient was invited to return to the clinic at annual intervals ( for 4 years , if possible ) so that the radiography necessary to record outcome could be done . An exact- significance chi-square test was done to compare the number of patients with new vertebral fractures in the two groups . We calculated 95 % CIs for vertebral fracture rates in each study group and for the difference in rates between the two groups , along with the point estimates of these rates . These rates were also expressed in terms of the number needed to treat for 4 years to prevent one fracture , including values for the lower and upper bounds of the 95 % CIs . Changes in the Spine Deformity Index in patients with incident or progressing vertebral deformities were compared by analysis of variance . Analysis of variance for repeated measurements was used to compare the absolute values for BMD of the spine over the course of the study in the two groups . Analysis of variance for repeated measurements was also done to compare BMD of the total hip and percentage changes in biochemical markers of bone remodeling throughout the study . All P values are two-tailed . All statistical analyses were done with the SPS/WIN 6.2 statistical package ( SPS , Inc. , Chicago , Illinois ) . Role of Study Sponsor The trial was approved by the Ethical Committee of Liege University ( registration no. 90/43 - 1262 of 14 May 1990 ) , and all patients gave full informed consent before inclusion . The Rotta Research Group , which markets MFP and calcium combinations in Germany , Italy , and other countries , provided the drugs and funding for the study . Scientists from the Rotta Research Group were directly involved in the design , monitoring , and data management of the study and agreed to be listed as authors . However , the Rotta Research Group as a corporate entity had no control over the decision to approve or su bmi t the manuscript for publication . Results Two hundred patients were enrolled in the study . The characteristics of the entire patient sample ( 100 patients were assigned to each group ) at enrollment are shown in Table 1 . Oral bisphosphonates are established therapeutics for postmenopausal osteoporosis . Alternative , simplified dosing regimens that improve tolerability and promote convenience may be advantageous . Ib and ronate is a highly potent , nitrogen-containing bisphosphonate that can be administered as a convenient intravenous ( i.v . ) injection ( over 15 - 30 s ) in schedules featuring extended between-dose intervals . In a recent fracture prevention study , 1 and 0.5 mg i.v . ib and ronate injections , given once every 3 months , were shown to dose-dependently increase lumbar spine and hip bone mineral density ( BMD ) and decrease biochemical markers of bone turnover in women with postmenopausal osteoporosis , but the overall magnitude of efficacy provided by both doses was suboptimal . In the present study ( Intermittent Regimen intravenous Ib and ronate Study : the IRIS study ) , the dose-response relationship with intermittent intravenous ib and ronate injections was further evaluated in 520 postmenopausal osteoporotic women ( aged 55 - 75 years , time since menopause > or= 5 years , lumbar spine [ L1-L4 ] BMD T score < -2.5 ) . At enrolment , participants were r and omized to receive either 2 mg ( n = 261 ) or 1 mg ( n = 131 ) ib and ronate or placebo ( n = 128 ) intravenous injections , given once every 3 months . After 1 year , ib and ronate therapy produced substantial and dose-dependent increases in lumbar spine and hip BMD , and decreases in biochemical markers of bone turnover , with the 2 mg dose providing significantly greater efficacy than the 1 mg dose . Most notably , lumbar spine BMD increased by 5.0 % and 2.8 % in the 2 and 1 mg groups , respectively , and decreased by 0.04 % in the placebo group . Furthermore , total hip BMD increased by 2.9 % , 2.2 % , and 0.6 % , respectively . Serum and urinary CTX , reflecting bone resorption , were decreased by 62.5 % and 61 % , respectively , with the 2 mg dose , and by 43.5 % and 42 % , respectively , with the 1 mg dose . Intravenous ib and ronate was well tolerated with a similar incidence of adverse events to placebo . Importantly , no indicators of renal toxicity were reported . In summary , the 2 mg ib and ronate regimen provides significantly greater BMD increases and significantly greater suppression of bone resorption markers than the 1 mg dose used in this study and in the previous fracture prevention study . Ongoing studies aim to further establish the efficacy and convenience of intermittent intravenous ib and ronate injections in postmenopausal osteoporosis CONTEXT Risedronate , a potent bisphosphonate , has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but , to our knowledge , it has not been evaluated in the treatment of established postmenopausal osteoporosis . OBJECTIVE To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998 . INTERVENTIONS Subjects were r and omly assigned to receive oral treatment for 3 years with risedronate ( 2.5 or 5 mg/d ) or placebo . All subjects received calcium , 1000 mg/d . Vitamin D ( cholecalciferol , up to 500 IU/d ) was provided if baseline levels of 25-hydroxyvitamin D were low . MAIN OUTCOME MEASURES Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessment s of radiographs ; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry . RESULTS The 2.5 mg/d of risedronate arm was discontinued after 1 year ; in the placebo and 5 mg/d of risedronate arms , 450 and 489 subjects , respectively , completed all 3 years of the trial . Treatment with 5 mg/d of risedronate , compared with placebo , decreased the cumulative incidence of new vertebral fractures by 41 % ( 95 % confidence interval [ CI ] , 18%-58 % ) over 3 years ( 11.3 % vs 16.3 % ; P= .003 ) . A fracture reduction of 65 % ( 95 % CI , 38%-81 % ) was observed after the first year ( 2.4 % vs 6.4 % ; P<.001 ) . The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39 % ( 95 % CI , 6%-61 % ) ( 5.2 % vs 8.4 % ; P = .02 ) . Bone mineral density increased significantly compared with placebo at the lumbar spine ( 5.4 % vs 1.1 % ) , femoral neck ( 1.6 % vs -1.2 % ) , femoral trochanter ( 3.3 % vs -0.7 % ) , and midshaft of the radius ( 0.2 % vs -1.4 % ) . Bone formed during risedronate treatment was histologically normal . The overall safety profile of risedronate , including gastrointestinal safety , was similar to that of placebo . CONCLUSIONS These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis In a recent multinational , double-blind , placebo-controlled , r and omized , phase III study ( BONE : IB and ronate Osteoporosis Vertebral Fracture trial in North America and Europe ) , oral daily ib and ronate ( 2.5 mg ) significantly and substantially reduced the risk of new vertebral fractures by 62 % relative to placebo after 3 years of treatment . The objective of the present study was to retrospectively analyze data from the BONE study to examine the efficacy of oral ib and ronate in preventing incident vertebral fractures of greater severity . This analysis was conducted on the placebo and oral daily ib and ronate ( 2.5 mg ) arms of the BONE study , comprising a total of 1964 women ( aged 55 - 80 years , > or=5 years postmenopause ) with osteoporosis . Vertebral fractures on annual lateral radiographs of the spine were grade d as mild , moderate , or severe , using criteria derived from an established semiquantitative technique . The findings demonstrate that in addition to being effective in significantly reducing the risk of new vertebral fractures of all severities , oral daily ib and ronate has a pronounced effect on the more severe , most clinical ly relevant , vertebral fractures : a significant and sustained reduction of 59 % in the relative risk of combined new moderate and severe vertebral fractures was observed at years 1 ( P = 0.0164 ) , 2 ( P = 0.0004 ) , and 3 ( P < 0.0001 ) Objectives To assess the efficacy and tolerability of risedronate , a pyridinyl bisphosphonate , in preventing loss of bone mineral density ( BMD ) of the lumbar spine and proximal femur in early postmenopausal women . Methods A total of 383 patients were r and omly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months . All patients received 1 g elemental calcium daily . BMD was measured by dual X-ray absorptiometry at baseline and at 3 , 6 , 12 , 18 , and 24 months . Results Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women . Significant results were observed as early as 3 months . In the control calcium-supplemented group , BMD decreased steadily at each site throughout the study . The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site . At 24 months , the differences were 4.5 ± 0.45 % at the lumbar spine , 3.3 ± 0.49 % at the femoral neck , and 4.3 ± 0.67 % at the femoral trochanter . Risedronate 2.5 mg maintained BMD at each site , although the effect was less pronounced than that of risedronate 5 mg . Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events . Conclusions Risedronate 5 mg prevents bone loss in early postmenopausal women , is well tolerated , and represents an effective choice to maintain bone mass and prevent osteoporosis Abstract : This paper presents the results of a two-center , double-masked , placebo-controlled , r and omized , oral-dose study of risedronate treatment in postmenopausal osteoporosis . Patients had at least one , but no more than four prevalent vertebral fractures at baseline . They received either 2.5 mg continuous risedronate , 2.5 mg cyclic risedronate , or placebo for 2 years . Both risedronate and placebo were formulated as hard gelatin capsules . All women furthermore received a daily calcium supplement of 1 g which was taken separately from the study drug . During the 1-year of follow-up , all women received only a daily calcium supplement of 1 g. A total of 132 patients were enrolled ( 44 in each treatment group ) , of which 73 % completed the 2-year treatment period and 70 % all 3 years . Generally the outcome of the study was negative . Lumbar spine bone mineral density ( BMD ) increased 1.2 % ( NS ) and 0.8 % ( NS ) and after 2 and 3 years in the group treated with continuous risedronate , 1.7 % ( NS ) and 2.3 % ( p < 0.05 ) in the group treated with cyclic risedronate , and 0.6 % ( NS ) and 1.7 % ( NS ) in the placebo group . BMD in the femoral neck increased 2.9 % ( p < 0.05 ) and 0.9 % ( NS ) after 2 and 3 years in the group treated with continuous risedronate , 1.3 % ( NS ) and 2.4 % ( p < 0.01 ) in the group treated with cyclic risedronate , and 1.3 % ( NS ) and 2.6 % ( p < 0.01 ) in the placebo group . The differences between all three groups in spinal and femoral BMD after 2 years were not statistically significant , bur reached statistical significance after 3 years ( p < 0.01 ) in the femoral neck . Only minor changes were observed in the measured markers of bone turnover . Both the incidence and rate of new vertebral fractures showed no overall differences between the groups . The distribution of adverse events was similar across treatment groups . None of the serious adverse events were considered causally related to risedronate . The lack of effect shown in the present study may be explained by insufficient dose regimen and /or impaired absorption from the intestinal tract . Further investigations ( ongoing phase III trials ) are needed to define future dose regimens in order to vali date the effect on bone mass , fracture rate and biochemical markers . In these studies another formulation of the drug and other dosing instructions are used Teriparatide ( rDNA origin ) injection [ recombinant human PTH ( 1 - 34 ) ] stimulates bone formation , increases bone mineral density ( BMD ) , and restores bone architecture and integrity . In contrast , bisphosphonates reduce bone resorption and increase BMD . We compared the effects of teriparatide and alendronate sodium on BMD , nonvertebral fracture incidence , and bone turnover in 146 postmenopausal women with osteoporosis . Women were r and omized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo ( n = 73 ) or oral alendronate 10 mg plus placebo injection ( n = 73 ) . Median duration of treatment was 14 months . At 3 months , teriparatide increased lumbar spine BMD significantly more than did alendronate ( P < 0.001 ) . Lumbar spine-BMD increased by 12.2 % in the teriparatide group and 5.6 % in the alendronate group ( P < 0.001 teriparatide vs. alendronate ) . Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate , but BMD at the one third distal radius decreased , compared with alendronate ( P < or = 0.05 ) . Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group ( P < 0.05 ) . Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment . In conclusion , teriparatide , a bone formation agent , increased BMD at most sites and decreased nonvertebral fractures more than alendronate We have recently reported that risedronate preserves normal bone formation and decreases bone remodeling in women with postmenopausal osteoporosis after 3 years of treatment . We report now the results of a 2-year extension study . The primary objective of this study was to determine the effect of 5 years of risedronate treatment ( 5 mg daily ) on bone quality and bone remodeling based on paired transiliac bone biopsies . There were additional measurements that included bone turnover markers and bone mineral density ( BMD ) . Histologic evaluation of biopsy sections ( placebo , n = 21 ; risedronate , n = 27 ) yielded no pathologic findings after 5 years in either treatment group . Histomorphometric assessment of paired biopsy specimens after 5 years ( placebo , n = 12 ; risedronate , n = 13 ) found no statistically significant differences between treatment groups in structural or resorption parameters . There was a significant reduction in osteoid ( −27 % ) and mineralizing surfaces ( −49 % ) from baseline values in the risedronate group that were also significantly different from placebo at 5 years . Similarly , activation frequency decreased significantly ( −77 % ) in the risedronate group , although it was not significantly different from placebo at 5 years ( 0.09 vs. 0.21 , respectively ) . Double tetracycline labels were identified in all biopsy specimens indicating continuous bone turnover . After 5 years of risedronate treatment , serum bone-specific alkaline phosphatase ( bone ALP ) and N-telopeptide ( NTX ) decreased significantly from baseline by 33.3 % and 47.5 % , respectively . In the placebo group , bone ALP decreased by 3.9 % ( P = NS ) , whereas NTX decreased by 27.0 % ( P < 0.005 ) . Lumbar spine BMD increased significantly in the risedronate group ( 9.2 % ) , whereas no significant change was seen in the placebo group ( −0.26 % ) . Risedronate was overall well tolerated ; during the 2-year study extension nonvertebral fractures occurred in 7 patients in placebo and 2 patients in risedronate groups . The findings from this study are consistent with the antiremodeling effect of risedronate and support long-term bone safety and antifracture efficacy of risedronate treatment ABSTRACT Objectives : BONE ( oral iB and ronate Osteoporosis vertebral fracture trial in North America and Europe ) determined whether less frequent dosing of ib and ronate ( dose-free interval > 2 months ) provided similar antifracture efficacy to daily dosing . As osteoporosis medications must be effective across different population s , an additional objective of BONE was to investigate and report the effect of oral ib and ronate in North American and European women , as described here . Patients and methods : BONE was a r and omized , double-blind , placebo-controlled , fracture-prevention study in 2946 postmenopausal women ( age 55 years−80 years ; ≥ 5 years since menopause ) with osteoporosis ( low lumbar spine bone mineral density and one to four prevalent vertebral fractures [ T4−L4 ] ) . Participants received daily calcium ( 500 mg ) and vitamin D ( 400 IU ) plus either placebo , oral daily ib and ronate ( 2.5 mg ) or oral intermittent ib and ronate ( 20 mg every other day for 12 doses every 3 months ) . The efficacy and tolerability of ib and ronate were assessed independently in both North American and European population s. Results : Consistent , significant efficacy was observed in the North American ( new vertebral fracture risk reduction : 60 % and 54 % with daily and intermittent ib and ronate , respectively ) and European patient population s ( 50 % and 48 % , respectively ) . Both ib and ronate regimens also significantly reduced the incidence of new , worsening , and acute clinical , vertebral fractures . Daily and intermittent ib and ronate significantly increased bone density at the spine in both North American ( 5.4 % and 4.4 % vs. baseline with daily and intermittent ib and ronate , respectively ) and European ( 7.1 % and 6.3 % vs. baseline , respectively ) population s. Significant increases were also observed for total hip bone density ( 2.6 % and 3.7 % vs. baseline for daily , and 2.5 % and 3.1 % for intermittent ; North American and European population s , respectively ) . Comparable , significant decreases in biochemical markers of bone turnover ( reductions in urinary excretion of C-telopeptide levels of 53.5 % and 67.1 % vs. baseline for daily , and 50.0 % and 53.8 % for intermittent ; North American and European population s , respectively ) were also observed in both population s ( p < 0.004 for all cited measurements in each ib and ronate group vs. placebo ) . Oral ib and ronate was well tolerated in both North American and European patients , with a safety profile similar to placebo . Conclusions : Oral ib and ronate , administered daily or intermittently , effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis . These results demonstrate the efficacy of ib and ronate administered with extended dose-free intervals , regardless of patients ’ geographical origin . Research investigating other less frequent ib and ronate regimens , such as once-monthly oral administration , is underway Abstract : This r and omized , double-masked , placebo-controlled trial evaluated the safety , tolerability and effects on bone mineral density ( BMD ) of alendronate in a large , multinational population of postmenopausal women with low bone mass . At 153 centers in 34 countries , 1908 otherwise healthy , postmenopausal women with lumbar spine BMD 2 st and ard deviations or more below the premenopausal adult mean were r and omly assigned to receive oral alendronate 10 mg ( n = 950 ) or placebo ( n = 958 ) once daily for 1 year . All patients received 500 mg elemental calcium daily . Baseline characteristics of patients in the two treatment groups were similar . At 12 months , mean increases in BMD were significantly ( p≤0.001 ) greater in the alendronate than the placebo group by 4.9 % ( 95 % confidence interval 4.6 % to 5.2 % ) at the lumbar spine , 2.4 % ( 2.0 % to 2.8 % ) at the femoral neck , 3.6 % ( 3.2 % to 4.1 % ) at the trochanter and 3.0 % ( 2.6 % to 3.4 % ) for the total hip . The incidence of nonvertebral fractures was significantly lower in the alendronate than the placebo group ( 19 vs 37 patients with fractures ) , representing a 47 % risk reduction for nonvertebral fracture for alendronate-treated patients ( 95 % confidence interval 10 % to 70 % ; p= 0.021 ) . Incidences of adverse events , including upper gastrointestinal adverse events , were similar in the two groups . Therefore , for postmenopausal women with low bone mass , alendronate is well tolerated and produces significant , progressive increases in BMD at the lumbar spine and hip in addition to significant reduction in the risk of nonvertebral fracture OBJECTIVE Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis , oral dosing may be unsuitable for some patients . An efficacious intravenously administered bisphosphonate could be beneficial for such patients . Ib and ronate , a potent nitrogen-containing bisphosphonate , can be administered using extended dosing intervals , either orally or by rapid intravenous injection . The aim of this study was to identify the optimal intravenous dosing regimen for ib and ronate in postmenopausal women with osteoporosis . METHODS In a r and omized , double-blind , double-dummy , phase III , noninferiority study , we compared 2 regimens of intermittent intravenous injections of ib and ronate ( 2 mg every 2 months and 3 mg every 3 months ) with a regimen of 2.5 mg of oral ib and ronate daily , the latter of which has proven antifracture efficacy . The study group comprised 1,395 women ( ages 55 - 80 years ) who were at least 5 years postmenopausal . All patients had osteoporosis ( lumbar spine [ L2-L4 ] bone mineral density [ BMD ] T score less than -2.5 ) . Participants also received daily calcium ( 500 mg ) and vitamin D ( 400 IU ) . The primary end point was change from baseline in lumbar spine BMD at 1 year . Changes in hip BMD and in the level of serum C-telopeptide of type I collagen ( CTX ) were also measured , as were safety and tolerability . RESULTS At 1 year , mean lumbar spine BMD increases were as follows : 5.1 % among 353 patients receiving 2 mg of ib and ronate every 2 months , 4.8 % among 365 patients receiving 3 mg of ib and ronate every 3 months , and 3.8 % among 377 patients receiving 2.5 mg of oral ib and ronate daily . Both of the intravenous regimens not only were noninferior , but also were superior ( P < 0.001 ) to the oral regimen . Hip BMD increases ( at all sites ) were also greater in the groups receiving medication intravenously than in the group receiving ib and ronate orally . Robust decreases in the serum CTX level were observed in all arms of the study . Both of the intravenous regimens were well tolerated and did not compromise renal function . CONCLUSION As assessed by BMD , intravenous injections of ib and ronate ( 2 mg every 2 months or 3 mg every 3 months ) are at least as effective as the regimen of 2.5 mg orally daily , which has proven antifracture efficacy , and are well tolerated PURPOSE We conducted a 5-year , double-blind , r and omized , placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis . SUBJECTS AND METHODS A total of 1,255 postmenopausal women with established osteoporosis were r and omly assigned to receive salmon calcitonin nasal spray ( 100 , 200 , or 400 IU ) or placebo daily . All participants received elemental calcium ( 1,000 mg ) and vitamin D ( 400 IU ) daily . Vertebral fractures were assessed with lateral radiographs of the spine . The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group . RESULTS During 5 years , 1,108 participants had at least one follow-up radiograph . A total of 783 women completed 3 years of treatment , and 511 completed 5 years . The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33 % compared with placebo [ 200 IU : 51 of 287 , placebo : 70 of 270 , relative risk ( RR ) = 0.67 , 95 % confidence interval ( CI ) : 0.47- to 0.97 , P = 0.03 ] . In the 817 women with one to five prevalent vertebral fractures at enrollment , the risk was reduced by 36 % ( RR = 0.64 , 95 % CI : 0.43- to 0.96 , P = 0.03 ) . The reductions in vertebral fractures in the 100-IU ( RR = 0.85 , 95 % CI : 0.60- to 1.21 ) and the 400-IU ( RR = 0.84 , 95 % CI : 0.59- to 1.18 ) groups were not significantly different from placebo . Lumbar spine bone mineral density increased significantly from baseline ( 1 % to 1 . 5 % , P<0.01 ) in all active treatment groups . Bone turnover was inhibited , as shown by suppression of serum type-I collagen cross-linked telopeptide ( C-telopeptide ) by 12 % in the 200-IU group ( P < 0.01 ) and by 14 % in the 400-IU group ( P<0.01 ) as compared with placebo . CONCLUSION Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis OBJECTIVE To evaluate the efficacy and safety of alendronate 35 mg once weekly compared with alendronate 5 mg daily in the prevention of osteoporosis . METHODS We compared the efficacy and safety of treatment with alendronate 35 mg once weekly ( n = 362 ) and alendronate 5 mg daily ( n = 361 ) in a 1-year , double-blind , multicenter study of postmenopausal women ( 6 months or greater ) , aged 40–70 years , with lumbar spine and femoral neck bone mineral density T-scores between −2.5 and 1 . The primary efficacy end point was the comparability of lumbar spine bone mineral density increases , defined by strict prespecified criteria . RESULTS Mean increases in lumbar spine bone mineral density at 12 months were equivalent ( difference between the alendronate 35-mg once-weekly group and the alendronate 5-mg daily group [ 90 % confidence interval ] at month 12 was −0.3 % [ −0.6 , 0.1 ] , well within the prespecified bounds of ±1.0 % ) . Bone mineral density increases at other skeletal sites and effects on bone turnover were also virtually identical for the two dosing regimens . Both treatment regimens were well tolerated , and the larger weekly unit dose was not associated with an increased frequency of upper gastrointestinal events . CONCLUSION Alendronate 35 mg once weekly is therapeutically equivalent to alendronate 5 mg daily and provides patients with greater dosing convenience , in addition to the proven efficacy of alendronate and good tolerability The safety and efficacy of raloxifene , a selective estrogen receptor modulator ( SERM ) , has been studied extensively in large , global clinical trials . However , the effect of raloxifene on bone mineral density ( BMD ) and on biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis has not been rigorously evaluated . This study was design ed to assess the safety and efficacy of raloxifene in Japanese postmenopausal women with osteoporosis following 1 year of therapy . Participants in this multicenter trial were r and omly assigned to receive placebo , raloxifene 60 mg/day ( RLX60 ) , or raloxifene 120 mg/day ( RLX120 ) . Lumbar spine BMD was measured at baseline , 24 , 40 , and 52 weeks , and biochemical markers of bone turnover were assessed at baseline , 12 , 24 , and 52 weeks . Serum lipids were assessed at baseline , 12 , 24 , 40 , and 52 weeks , and breast examinations and transvaginal ultrasound of the endometrium were performed at enrollment and 52 weeks . Compared with baseline , women taking RLX60 had significant increases in lumbar spine ( L2-L4 ) BMD at 24 weeks ( + 3.3 % , p<0.001 ) through 52 weeks ( + 3.5 % , p<0.001 ) of therapy , and similar results were observed in the RLX120 group . Markers of bone turnover and total cholesterol and LDL-C were significantly reduced , and no significant treatment-group difference was observed for patients reporting at least one adverse event following r and omization . In addition , there were no reported venous thromboembolic events ( VTE ) in any treatment group . The results of this study demonstrate that raloxifene is associated with early increases in lumbar spine BMD , has favorable effects on biochemical markers of bone turnover and lipid profile , and is well tolerated in postmenopausal Japanese women OBJECTIVES Alendronate and raloxifene are antiresorptive agents with different mechanisms of action , each used to treat osteoporosis in postmenopausal women . This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density . DESIGN R and omized , double-masked , double-dummy multicentre international study . SETTING Clinical trial centres in Europe , South America and Asia-Pacific . SUBJECTS A total of 487 postmenopausal women with low bone density , based on bone mineral density ( BMD ) of the lumbar spine or hip ( T-score < or = -2.0 ) . Interventions . Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months . MAIN OUTCOME MEASURES Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting . RESULTS Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months . Lumbar spine BMD increased 4.8 % with alendronate vs. 2.2 % with raloxifene ( P < 0.001 ) . The increase in total hip BMD was 2.3 % with alendronate vs. 0.8 % with raloxifene ( P < 0.001 ) . Reductions in bone turnover were significantly larger with alendronate than raloxifene . Overall tolerability was similar , however , the proportion of patients reporting vasomotor events was significantly higher with raloxifene ( 9.5 % ) than with alendronate ( 3.7 % , P = 0.010 ) . The proportion of patients reporting gastrointestinal events was similar between groups . CONCLUSION In postmenopausal women with low bone density , improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene UNLABELLED Once-monthly ( 50/50 , 100 , and 150 mg ) and daily ( 2.5 mg ; 3-year vertebral fracture risk reduction : 52 % ) oral ib and ronate regimens were compared in 1609 women with postmenopausal osteoporosis . At least equivalent efficacy and similar safety and tolerability were shown after 1 year . INTRODUCTION Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis . Although yet to be prospect ively shown in osteoporosis , evidence from r and omized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence . Ib and ronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of > 2 months . This report presents comparative data on the efficacy and safety of monthly and daily oral ib and ronate regimens . MATERIAL S AND METHODS MOBILE is a 2-year , r and omized , double-blind , phase III , noninferiority trial . A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ib and ronate regimens : 2.5 mg daily , 50 mg/50 mg monthly ( single doses , consecutive days ) , 100 mg monthly , or 150 mg monthly . RESULTS After 1 year , lumbar spine BMD increased by 3.9 % , 4.3 % , 4.1 % , and 4.9 % in the 2.5 , 50 /50 , 100 , and 150 mg arms , respectively . All monthly regimens were proven noninferior , and the 150 mg regimen superior , to the daily regimen . All monthly regimens produced similar hip BMD gains , which were larger than those with the daily regimen . All regimens similarly decreased serum levels of C-telopeptide , a biochemical marker of bone resorption . Compared with the daily regimen , a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine ( 6 % ) or total hip BMD ( 3 % ) . All regimens were similarly well tolerated . CONCLUSIONS Monthly ib and ronate is at least as effective and well tolerated as the currently approved daily ib and ronate regimen in postmenopausal osteoporosis The risk-reducing effect of alendronate on vertebral fractures has been consistently reported . In a 2-year , r and omized , double-blind , active drug-controlled ( 1 microg alfacalcidol ) double-dummy study , we also reported that alendronate ( 5.0 mg ) had a fracture-reducing effect in Japanese patients with preexisting vertebral fractures . The present report describes the risk-reducing effect of alendronate ( 5.0 mg ) for 3 years in postmenopausal osteoporotic patients . The 3-year treatment period consisted of the original 2-year double-blind study followed by a 1-year extension . A total of 170 postmenopausal female patients were involved in the third year ; 90 received alendronate and 80 received alfacalcidol . Both efficacy and safety were analyzed in these 170 patients . Vertebral fracture was determined by quantitative morphometry , and vertebral bone mineral density ( BMD ) was measured by the DXA method ( dual-energy X-ray absorptiometry ) . The primary efficacy endpoint was the incidence of vertebral fracture , excluding fracture cases that occurred in the first 6 months after treatment initiation . The cumulative incidence of vertebral fracture at 3 years was 7.8 % ( 7/90 ) in the alendronate group and 18.8 % ( 15/80 ) in the alfacalcidol group , indicating a significantly reduced risk of fractures in the alendronate group ( relative risk = 0.41 , 95 % CI = 0.18 - 0.97 ) . Lumbar spine BMD increased by 9.2 % in the alendronate group ( n = 26 ) and by 1.4 % in the alfacalcidol group ( n = 22 ) at 3 years . The safety profile of alendronate during 3 years of treatment was similar to that of alfacalcidol . The present study thus demonstrated that treatment with alendronate 5.0 mg for 3 years increased vertebral BMD and reduced the risk of vertebral fractures in Japanese , postmenopausal women with osteoporosis OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures . DESIGN Double-blind , r and omized , placebo-controlled clinical trial lasting 1 year . SETTING Referral-based outpatient clinic . PATIENTS Seventy-five postmenopausal women , 47 to 75 years of age , with one or more vertebral fractures due to osteoporosis . INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle . Another 39 women received placebo . MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry ; bone loss assessed by serial measurement of bone density ; and vertebral fracture rate . RESULTS Compared with the placebo group , the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine ( 5.3 compared with 0.2 ; P = 0.007 ) , femoral trochanter ( 7.6 compared with 2.1 ; P = 0.03 ) , and midradius ( 1.0 compared with -2.6 , P less than 0.001 ) but showed no significant difference at the femoral neck ( 2.6 compared with 1.4 ; P = 0.17 ) . Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration ( median change , -0.35 compared with 0.02 nmol/L ; P less than 0.001 ) . Histomorphometric evaluation of iliac biopsy sample s confirmed the effect of estrogen on bone formation rate per bone volume ( median change , -12.9 compared with -6.2 % per year ; P = 0.004 ) . Also , 8 new fractures occurred in 7 women in the estrogen group , whereas 20 occurred in 12 women in the placebo group , yielding a lower vertebral fracture rate in the estrogen group ( relative risk , 0.39 ; 95 % CI , 0.16 to 0.95 ) . CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis BACKGROUND Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis . Once-monthly oral ib and ronate has been developed to overcome this problem . OBJECTIVE To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis . METHODS MOBILE , a r and omised , phase III , non-inferiority study , compared the efficacy and safety of once-monthly ib and ronate with daily ib and ronate , which has previously been shown to reduce vertebral fracture risk in comparison with placebo . RESULTS 1609 postmenopausal women were r and omised . Substantial increases in lumbar spine bone mineral density ( BMD ) were seen in all treatment arms : 5.0 % , 5.3 % , 5.6 % , and 6.6 % in the daily and once-monthly groups ( 50 + 50 mg , 100 mg , and 150 mg ) , respectively . It was confirmed that all once-monthly regimens were at least as effective as daily treatment , and in addition , 150 mg was found to be better ( p<0.001 ) . Substantial increases in proximal femur ( total hip , femoral neck , trochanter ) BMD were seen ; 150 mg produced the most pronounced effect ( p<0.05 versus daily treatment ) . Independent of the regimen , most participants ( 70.5 - 93.5 % ) achieved increases above baseline in lumbar spine or total hip BMD , or both . Pronounced decreases in the biochemical marker of bone resorption , sCTX , observed in all arms after 3 months , were maintained throughout . The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens . Ib and ronate was well tolerated , with a similar incidence of adverse events across groups . CONCLUSIONS Once-monthly oral ib and ronate is at least as effective and well tolerated as daily treatment . Once-monthly administration may be more convenient for patients and improve therapeutic adherence , thereby optimising outcomes INTRODUCTION Treatment of osteoporosis with high-dose fluoride alone does not reduce fracture risk . We hypothesized that the antifracture efficacy of fluoride could be optimized by its use in low doses combined with an antiresorptive agent . EXPERIMENTAL SUBJECTS Subjects included 80 women with postmenopausal osteoporosis who had been taking estrogen for at least 1 yr . METHODS Subjects were r and omized to receive monofluorophosphate ( MFP ) ( fluoride content of 20 mg/d ) or placebo over 4 yr in a double-blind trial . RESULTS AND DISCUSSION There were progressive increases in lumbar spine bone density over the duration of the study ( MFP , 22 % ; placebo , 6 % ; P < 0.0001 ) . In the trabecular bone of L3 , these increases were even greater ( MFP , 49 % ; placebo , 2.5 % ; P < 0.0001 ) . In the proximal femur , there were smaller but significant treatment effects ( P = 0.015 ) . Total body scans and their subregions also showed significantly greater increases in the MFP group . Bone formation markers increased significantly in the MFP group at yr 1 . Hyperosteoidosis was present in biopsies from five of seven MFP subjects , with osteomalacia in two of seven . The hazards ratio for vertebral fractures was 0.20 ( 95 % confidence interval , 0.05 - 1.30 ) , and the incidence rate ratio was 0.12 ( 95 % confidence interval , 0.06 - 0.23 ; P < 0.01 ) . The hazards ratio for nonvertebral fractures was 3.3 ( 95 % confidence interval , 0.8 - 12.0 ) . CONCLUSIONS We conclude that fluoride at 20 mg/d produces substantial increases in bone mineral density but still interferes with bone mineralization . This indicates that most previous studies with this ion have used toxic doses and that much lower doses should be assessed to find a safe dose window for the use of this powerful anabolic agent BACKGROUND The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk , such as very elderly women or those with severe osteoporosis , is uncertain . PARTICIPANTS AND METHODS Using data from a double-blind , r and omized , placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density ( BMD ) and existing vertebral fractures , we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age , bone density , number of preexisting vertebral fractures , and history of postmenopausal fracture . The women were r and omized to oral administration of alendronate or placebo and followed up for an average of 2.9 years . The initial dose of alendronate sodium was 5 mg/d ; the dosage was increased from 5 to 10 mg/d at 24 months . New vertebral fractures , the primary end point of this arm of the trial , were defined by morphometry as a decrease of 20 % and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months . Incident clinical fractures , the secondary end point , included nonspine and clinical ( symptomatic ) vertebral fractures . All clinical fractures were confirmed with x-ray film reports or , in the case of clinical vertebral fractures , x-ray films . RESULTS Overall , there was a 47 % significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group . The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age ( relative risk [ RR ] , 0.49 in women < 75 years compared with 0.62 in those > or = 75 years ) , BMD ( RR , 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [ median ] compared with 0.53 in those with a BMD > or = 0.59 g/cm2 ) , and number of preexisting vertebral fractures ( RR , 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2 ) . The overall significant 28 % reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups . Compared with the number of lower-risk women , a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture . For example , 8 women aged 75 years or older compared with 9 women younger than 75 years , or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture , needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture . CONCLUSIONS Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD , including those women at highest risk because of advanced age or severe osteoporosis . Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories , more fractures were prevented by treating women at highest risk |
12,543 | 27,788,146 | Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association .
In additional search for T2D prediction , we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers .
Most biomarkers did not enhance the strength of prediction , but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia . | BACKGROUND Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes ( T2D ) and in underst and ing possible aetiological pathways to disease .
However , no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D .
We aim ed to systematic ally review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field .
Many biomarkers have been reported to be associated with the risk of developing T2D .
The evidence of their value in adding to underst and ing of causal pathways to disease is very limited so far . | Background Raised C-reactive protein ( CRP ) is a risk factor for type 2 diabetes . According to the Mendelian r and omization method , the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes . Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables . Methods and Findings We genotyped three tagging SNPs ( CRP + 2302 G > A ; CRP + 1444 T > C ; CRP + 4899 T > G ) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y ( Whitehall II Study ) . Homeostasis model assessment -insulin resistance ( HOMA-IR ) and hemoglobin A1c ( HbA1c ) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report . Common major haplotypes were strongly associated with serum CRP levels , but unrelated to obesity , blood pressure , and socioeconomic position , which may confound the association between CRP and diabetes risk . Serum CRP was associated with these potential confounding factors . After adjustment for age and sex , baseline serum CRP was associated with incident diabetes ( hazard ratio = 1.39 [ 95 % confidence interval 1.29–1.51 ] , HOMA-IR , and HbA1c , but the associations were considerably attenuated on adjustment for potential confounding factors . In contrast , CRP haplotypes were not associated with HOMA-IR or HbA1c ( p = 0.52–0.92 ) . The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis , with genetic variants as the instrument for serum CRP . Instrumental variables estimates differed from the directly observed associations ( p = 0.007–0.11 ) . Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings ( p = 0.25–0.88 ) . Analyses based on the Wellcome Trust Case Control Consortium ( 1,923 diabetes cases , 2,932 controls ) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations . Conclusions Observed associations between serum CRP and insulin resistance , glycemia , and diabetes are likely to be noncausal . Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP Background C-reactive protein ( CRP ) is associated with immune , cardiometabolic , and psychiatric traits and diseases . Yet it is inconclusive whether these associations are causal . Methods and Findings We performed Mendelian r and omization ( MR ) analyses using two genetic risk scores ( GRSs ) as instrumental variables ( IVs ) . The first GRS consisted of four single nucleotide polymorphisms ( SNPs ) in the CRP gene ( GRSCRP ) , and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study ( GWAS ) to date ( GRSGWAS ) . To optimize power , we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes , with up to 123,865 participants per outcome from population s of European ancestry . We performed heterogeneity tests to disentangle the pleiotropic effect of IVs . A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant . An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association , yet to be confirmed . The strengths ( F-statistics ) of the IVs were 31.92–3,761.29 and 82.32–9,403.21 for GRSCRP and GRSGWAS , respectively . CRP GRSGWAS showed a statistically significant protective relationship of a 10 % genetically elevated CRP level with the risk of schizophrenia ( odds ratio [ OR ] 0.86 [ 95 % CI 0.79–0.94 ] ; p < 0.001 ) . We vali date d this finding with individual-level genotype data from the schizophrenia GWAS ( OR 0.96 [ 95 % CI 0.94–0.98 ] ; p < 1.72 × 10−6 ) . Further , we found that a st and ardized CRP polygenic risk score ( CRPPRS ) at p-value thresholds of 1 × 10−4 , 0.001 , 0.01 , 0.05 , and 0.1 using individual-level data also showed a protective effect ( OR < 1.00 ) against schizophrenia ; the first CRPPRS ( built of SNPs with p < 1 × 10−4 ) showed a statistically significant ( p < 2.45 × 10−4 ) protective effect with an OR of 0.97 ( 95 % CI 0.95–0.99 ) . The CRP GRSGWAS showed that a 10 % increase in genetically determined CRP level was significantly associated with coronary artery disease ( OR 0.88 [ 95 % CI 0.84–0.94 ] ; p < 2.4 × 10−5 ) and was nominally associated with the risk of inflammatory bowel disease ( OR 0.85 [ 95 % CI 0.74–0.98 ] ; p < 0.03 ) , Crohn disease ( OR 0.81 [ 95 % CI 0.70–0.94 ] ; p < 0.005 ) , psoriatic arthritis ( OR 1.36 [ 95 % CI 1.00–1.84 ] ; p < 0.049 ) , knee osteoarthritis ( OR 1.17 [ 95 % CI 1.01–1.36 ] ; p < 0.04 ) , and bipolar disorder ( OR 1.21 [ 95 % CI 1.05–1.40 ] ; p < 0.007 ) and with an increase of 0.72 ( 95 % CI 0.11–1.34 ; p < 0.02 ) mm Hg in systolic blood pressure , 0.45 ( 95 % CI 0.06–0.84 ; p < 0.02 ) mm Hg in diastolic blood pressure , 0.01 ml/min/1.73 m2 ( 95 % CI 0.003–0.02 ; p < 0.005 ) in estimated glomerular filtration rate from serum creatinine , 0.01 g/dl ( 95 % CI 0.0004–0.02 ; p < 0.04 ) in serum albumin level , and 0.03 g/dl ( 95 % CI 0.008–0.05 ; p < 0.009 ) in serum protein level . However , after adjustment for heterogeneity , neither GRS showed a significant effect of CRP level ( at p < 0.0016 ) on any of these outcomes , including coronary artery disease , nor on the other 20 complex outcomes studied . Our study has two potential limitations : the limited variance explained by our genetic instruments modeling CRP levels in blood and the unobserved bias introduced by the use of summary statistics in our MR analyses . Conclusions Genetically elevated CRP levels showed a significant potentially protective causal relationship with risk of schizophrenia . We observed nominal evidence at an observed p < 0.05 using either GRSCRP or GRSGWAS — with persistence after correction for heterogeneity — for a causal relationship of elevated CRP levels with psoriatic osteoarthritis , rheumatoid arthritis , knee osteoarthritis , systolic blood pressure , diastolic blood pressure , serum albumin , and bipolar disorder . These associations remain yet to be confirmed . We can not verify any causal effect of CRP level on any of the other common somatic and neuropsychiatric outcomes investigated in the present study . This implies that interventions that lower CRP level are unlikely to result in decreased risk for the majority of common complex outcomes Summary Background Low circulating concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , are associated with an increased risk of type 2 diabetes , but whether this association is causal remains unclear . We aim ed to estimate the unconfounded , causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian r and omisation approach . Methods Using several data sources from population s of European descent , including type 2 diabetes cases and non-cases , we did a mendelian r and omisation analysis using single nucleotide polymorphisms ( SNPs ) within or near four genes related to 25(OH)D synthesis and metabolism : DHCR7 ( related to vitamin D synthesis ) , CYP2R1 ( hepatic 25-hydroxylation ) , DBP ( also known as GC ; transport ) , and CYP24A1 ( catabolism ) . We assessed each SNP for an association with circulating 25(OH)D concentration ( 5449 non-cases ; two studies ) , risk of type 2 diabetes ( 28 144 cases , 76 344 non-cases ; five studies ) , and glycaemic traits ( concentrations of fasting glucose , 2-h glucose , fasting insulin , and HbA1c ; 46 368 non-cases ; study consortium ) . We combined these associations in a likelihood-based mendelian r and omisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits , and compared them with that from a meta- analysis of data from observational studies ( 8492 cases , 89 698 non-cases ; 22 studies ) that assessed the association between 25(OH)D concentration and type 2 diabetes . Findings All four SNPs were associated with 25(OH)D concentrations ( p<10−6 ) . The mendelian r and omisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 ( 95 % CI 0·75–1·36 ; p=0·94 ) per 25·0 nmol/L ( 1 SD ) lower 25(OH)D concentration . The corresponding ( potentially confounded ) relative risk from the meta- analysis of data from observational studies was 1·21 ( 1·16–1·27 ; p=7·3 × 10−19 ) . The mendelian r and omisation-derived estimates for glycaemic traits were not significant ( p>0·25 ) . Interpretation The association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal . Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence . These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes . Funding UK Medical Research Council Epidemiology Unit and European Union Sixth Framework Programme OBJECTIVE The causal nature of associations between circulating triglycerides , insulin resistance , and type 2 diabetes is unclear . We aim ed to use Mendelian r and omization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance . RESEARCH DESIGN AND METHODS We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes ( reflecting glycemia and hepatic insulin resistance ) in 8,271 nondiabetic individuals from four studies . RESULTS Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels ( SD 0.59 [ 95 % CI 0.52–0.65 ] difference between the 20 % of individuals with the most alleles and the 20 % with the fewest alleles ) . There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes ( per weighted allele odds ratio [ OR ] 0.99 [ 95 % CI 0.97–1.01 ] ; P = 0.26 ) . In nondiabetic individuals , there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels ( SD 0.00 per weighted allele [ 95 % CI −0.01 to 0.02 ] ; P = 0.72 ) or increased fasting glucose levels ( 0.00 [ −0.01 to 0.01 ] ; P = 0.88 ) . Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk , fasting glucose , or fasting insulin and , for diabetes , showed a trend toward a protective association ( OR per 1-SD increase in log10 triglycerides : 0.61 [ 95 % CI 0.45–0.83 ] ; P = 0.002 ) . CONCLUSIONS Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals . One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal Increased adiponectin levels have been shown to be associated with a lower risk of type 2 diabetes . To underst and the relations between genetic variation at the adiponectin-encoding gene , ADIPOQ , and adiponectin levels , and subsequently its role in disease , we conducted a deep resequencing experiment of ADIPOQ in 14,002 subjects , including 12,514 Europeans , 594 African Americans , and 567 Indian Asians . We identified 296 single nucleotide polymorphisms ( SNPs ) , including 30 amino acid changes , and carried out association analyses in a subset of 3,665 subjects from two independent studies . We confirmed multiple genome-wide association study findings and identified a novel association between a low-frequency SNP ( rs17366653 ) and adiponectin levels ( P = 2.2E–17 ) . We show that seven SNPs exert independent effects on adiponectin levels . Together , they explained 6 % of adiponectin variation in our sample s. We subsequently assessed association between these SNPs and type 2 diabetes in the Genetics of Diabetes Audit and Research in Tayside Scotl and ( GO-DARTS ) study , comprised of 5,145 case and 6,374 control subjects . No evidence of association with type 2 diabetes was found , but we were also unable to exclude the possibility of substantial effects ( e.g. , odds ratio 95 % CI for rs7366653 [ 0.91–1.58 ] ) . Further investigation by large-scale and well-powered Mendelian r and omization studies is warranted BACKGROUND Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes . We aim ed to characterise trajectories of fasting and postload glucose , insulin sensitivity , and insulin secretion in individuals who develop type 2 diabetes . METHODS We analysed data from our prospect i ve occupational cohort study ( Whitehall II study ) of 6538 ( 71 % male and 91 % white ) British civil servants without diabetes mellitus at baseline . During a median follow-up period of 9.7 years , 505 diabetes cases were diagnosed ( 49.1 % on the basis of oral glucose tolerance test ) . We assessed retrospective trajectories of fasting and 2-h postload glucose , homoeostasis model assessment ( HOMA ) insulin sensitivity , and HOMA beta-cell function from up to 13 years before diabetes diagnosis ( diabetic group ) or at the end of follow-up ( non-diabetics ) . FINDINGS Multilevel models adjusted for age , sex , and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics ( 10,989 measurements ) , except for insulin secretion that did not change during follow-up . In the diabetic group ( 801 measurements ) , a linear increase in fasting glucose was followed by a steep quadratic increase ( from 5.79 mmol/L to 7.40 mmol/L ) starting 3 years before diagnosis of diabetes . 2-h postload glucose showed a rapid increase starting 3 years before diagnosis ( from 7.60 mmol/L to 11.90 mmol/L ) , and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis ( to 86.7 % ) . HOMA beta-cell function increased between years 4 and 3 before diagnosis ( from 85.0 % to 92.6 % ) and then decreased until diagnosis ( to 62.4 % ) . INTERPRETATION In this study , we show changes in glucose concentrations , insulin sensitivity , and insulin secretion as much as 3 - 6 years before diagnosis of diabetes . The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups . FUNDING Medical Research Council ( UK ) ; Economic and Social Research Council ( UK ) ; British Heart Foundation ( UK ) ; Health and Safety Executive ( UK ) ; Department of Health ( UK ) ; National Institute of Health ( USA ) ; Agency for Health Care Policy Research ( USA ) ; the John D and Catherine T MacArthur Foundation ( USA ) ; and Academy of Finl and ( Finl and ) Objective To identify existing prediction models for the risk of development of type 2 diabetes and to externally vali date them in a large independent cohort . Data sources Systematic search of English , German , and Dutch literature in PubMed until February 2011 to identify prediction models for diabetes . Design Performance of the models was assessed in terms of discrimination ( C statistic ) and calibration ( calibration plots and Hosmer-Lemeshow test).The validation study was a prospect i ve cohort study , with a case cohort study in a r and om subcohort . Setting Models were applied to the Dutch cohort of the European Prospect i ve Investigation into Cancer and Nutrition cohort study ( EPIC-NL ) . Participants 38 379 people aged 20 - 70 with no diabetes at baseline , 2506 of whom made up the r and om subcohort . Outcome measure Incident type 2 diabetes . Results The review identified 16 studies containing 25 prediction models . We considered 12 models as basic because they were based on variables that can be assessed non-invasively and 13 models as extended because they additionally included conventional biomarkers such as glucose concentration . During a median follow-up of 10.2 years there were 924 cases in the full EPIC-NL cohort and 79 in the r and om subcohort . The C statistic for the basic models ranged from 0.74 ( 95 % confidence interval 0.73 to 0.75 ) to 0.84 ( 0.82 to 0.85 ) for risk at 7.5 years . For prediction models including biomarkers the C statistic ranged from 0.81 ( 0.80 to 0.83 ) to 0.93 ( 0.92 to 0.94 ) . Most prediction models overestimated the observed risk of diabetes , particularly at higher observed risks . After adjustment for differences in incidence of diabetes , calibration improved considerably . Conclusions Most basic prediction models can identify people at high risk of developing diabetes in a time frame of five to 10 years . Models including biomarkers classified cases slightly better than basic ones . Most models overestimated the actual risk of diabetes . Existing prediction models therefore perform well to identify those at high risk , but can not sufficiently quantify actual risk of future diabetes OBJECTIVE Fetuin-A levels are associated with higher risk of type 2 diabetes , but it is unknown if the association is causal . We investigated common ( > 5 % ) genetic variants in the fetuin-A gene ( AHSG ) fetuin-A levels , fasting glucose , and risk of type 2 diabetes . RESEARCH DESIGN AND METHODS Genetic variation , fetuin-A levels , and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992–1993 . RESULTS Common AHSG variants ( rs4917 and rs2248690 ) were strongly associated with fetuin-A concentrations ( P < 0.0001 ) . In analyses of 259 incident cases of type 2 diabetes , the single nucleotide polymorphisms ( SNPs ) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included . As expected , higher fetuin-A levels were associated with higher fasting glucose concentrations ( 1.9 mg/dL [ 95 % CI , 1.2–2.7 ] higher per SD in Caucasians ) , but Mendelian r and omization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose ( −0.3 mg/dL [ 95 % CI , −1.9 to 1.3 ] lower per SD in Caucasians ) . The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant ( P = 0.001 ) . Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant . CONCLUSIONS Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations , but not with risk of type 2 diabetes or glucose concentrations , raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal Background Liver function tests might predict the risk of type 2 diabetes . An independent study evaluating utility of these markers compared with an existing prediction model is yet lacking . Methods and Findings We performed a case-cohort study , including r and om subcohort ( 6.5 % ) from 38,379 participants with 924 incident diabetes cases ( the Dutch contribution to the European Prospect i ve Investigation Into Cancer and Nutrition , EPIC-NL , the Netherl and s ) , and another population -based cohort study including 7,952 participants with 503 incident cases ( the Prevention of Renal and Vascular End-stage Disease , PREVEND , Groningen , the Netherl and s ) . We examined predictive value of combination of the Liver function tests ( gamma-glutamyltransferase , alanine aminotransferase , aspartate aminotransferase and albumin ) above vali date d models for 7.5-year risk of diabetes ( the Cooperative Health Research in the Region of Augsburg , the KORA study ) . Basic model includes age , sex , BMI , smoking , hypertension and parental diabetes . Clinical models additionally include glucose and uric acid ( model1 ) and HbA1c ( model2 ) . In both studies , addition of Liver function tests to the basic model improved the prediction ( C-statistic by∼0.020 ; NRI by∼9.0 % ; P<0.001 ) . In the EPIC-NL case-cohort study , addition to clinical model1 result ed in statistically significant improvement in the overall population ( C-statistic = + 0.009 ; P<0.001 ; NRI = 8.8 % ; P<0.001 ) , while addition to clinical model 2 yielded marginal improvement limited to men ( C-statistic = + 0.007 ; P = 0.06 ; NRI = 3.3 % ; P = 0.04 ) . In the PREVEND cohort study , addition to clinical model 1 result ed in significant improvement in the overall population ( C-statistic change = 0.008 ; P = 0.003 ; NRI = 3.6 % ; P = 0.03 ) , with largest improvement in men ( C-statistic change = 0.013 ; P = 0.01 ; NRI = 5.4 % ; P = 0.04 ) . In PREVEND , improvement compared to clinical model 2 could not be tested because of lack of HbA1c data . Conclusions Liver function tests modestly improve prediction for medium-term risk of incident diabetes above basic and extended clinical prediction models , only if no HbA1c is incorporated . If data on HbA1c are available , Liver function tests have little incremental predictive value , although a small benefit may be present in men Using mendelian r and omization , Roman Pfister and colleagues demonstrate a potentially causal link between low levels of B-type natriuretic peptide ( BNP ) , a hormone released by damaged hearts , and the development of type 2 diabetes Observational epidemiological studies suffer from many potential biases , from confounding and from reverse causation , and this limits their ability to robustly identify causal associations . Several high-profile situations exist in which r and omized controlled trials of precisely the same intervention that has been examined in observational studies have produced markedly different findings . In other observational sciences , the use of instrumental variable ( IV ) approaches has been one approach to strengthening causal inferences in non-experimental situations . The use of germline genetic variants that proxy for environmentally modifiable exposures as instruments for these exposures is one form of IV analysis that can be implemented within observational epidemiological studies . The method has been referred to as ' Mendelian r and omization ' , and can be considered as analogous to r and omized controlled trials . This paper outlines Mendelian r and omization , draws parallels with IV methods , provides examples of implementation of the approach and discusses limitations of the approach and some methods for dealing with these Many biomarkers are associated with type 2 diabetes ( T2D ) risk in epidemiological observations . The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D . A systematic literature search in PubMed and EMBASE ( until April 2015 ) was done to identify Mendelian r and omization studies that examined potential causal effects of biomarkers on T2D . To replicate the findings of identified studies , data from two large-scale , genome-wide association studies ( GWAS ) were used : DIAbetes Genetics Replication And Meta- analysis ( DIAGRAMv3 ) for T2D and the Meta-Analyses of Glucose and Insulin-related traits Consortium ( MAGIC ) for glycaemic traits . GWAS summary statistics were extracted for the same genetic variants ( or proxy variants ) , which were used in the original Mendelian r and omization studies . Of the 21 biomarkers ( from 28 studies ) , ten have been reported to be causally associated with T2D in Mendelian r and omization . Most biomarkers were investigated in a single cohort study or population . Of the ten biomarkers that were identified , nominally significant associations with T2D or glycaemic traits were reached for those genetic variants related to bilirubin , pro-B-type natriuretic peptide , delta-6 desaturase and dimethylglycine based on the summary data from DIAGRAMv3 or MAGIC . Several Mendelian r and omization studies investigated the nature of associations of biomarkers with T2D . However , there were only a few biomarkers that may have causal effects on T2D . Further research is needed to broadly evaluate the causal effects of multiple biomarkers on T2D and glycaemic traits using data from large-scale cohorts or GWAS including many different genetic variants CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and C-reactive protein ( CRP ) are associated with development of type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis Circulating bilirubin , a natural antioxidant , is associated with decreased risk of type 2 diabetes ( T2D ) , but the nature of the relationship remains unknown . We performed Mendelian r and omization in a prospect i ve cohort of 3,381 participants free of diabetes at baseline ( age 28–75 years ; women 52.6 % ) . We used rs6742078 located in the uridine diphosphate – glucuronosyltransferase locus as an instrumental variable ( IV ) to study a potential causal effect of serum total bilirubin level on T2D risk . T2D developed in a total of 210 participants ( 6.2 % ) during a median follow-up period of 7.8 years . In adjusted analyses , rs6742078 , which explained 19.5 % of bilirubin variation , was strongly associated with total bilirubin ( a 0.68-SD increase in bilirubin levels per T allele ; P < 1 × 10−122 ) and was also associated with T2D risk ( odds ratio [ OR ] 0.69 [ 95 % CI 0.54–0.90 ] ; P = 0.006 ) . Per 1-SD increase in log-transformed bilirubin levels , we observed a 25 % ( OR 0.75 [ 95 % CI 0.62–0.92 ] ; P = 0.004 ) lower risk of T2D . In Mendelian r and omization analysis , the causal risk reduction for T2D was estimated to be 42 % ( causal OR for IV estimation per 1-SD increase in log-transformed bilirubin 0.58 [ 95 % CI 0.39–0.84 ] ; P = 0.005 ) , which was comparable to the observational estimate ( Durbin-Wu-Hausman χ2 test , P for difference = 0.19 ) . These novel results provide evidence that an elevated bilirubin level is causally associated with the risk of T2D and support its role as a protective determinant Aims /hypothesisEpidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes . Using a Mendelian r and omisation approach , we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes . Methods We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case – control studies including 7,504 diabetes patients and 8,560 non-diabetic controls . We compared the observed effect size to that expected based on : ( 1 ) the association between the genetic score and uric acid levels in non-diabetic controls ; and ( 2 ) the meta-analysed uric acid level to diabetes association . Results The genetic score showed a linear association with uric acid levels , with a difference of 12.2 μmol/l ( 95 % CI 9.3 , 15.1 ) by score tertile . No significant associations were observed between the genetic score and potential confounders . No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 ( 95 % CI 0.94 , 1.04 ) per score tertile , significantly different ( p = 0.046 ) from that expected ( 1.04 [ 95 % CI 1.03 , 1.05 ] ) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 ( 95 % CI 1.14 , 1.29 ) per 60 μmol/l . Conclusions /interpretationOur results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes Abstract This study is to prospect ively investigate the association between serum uric acid and the incidence of type 2 diabetes in middle-aged and elderly Chinese . This study consisted of 924 non-diabetic adults aged 40 years or older at baseline . Subjects who received antidiabetic therapies and those who responded positively to the 75-g oral glucose tolerance test according to the 1999 World Health Organization criteria were diagnosed as having type 2 diabetes . Ninety-eight subjects developed type 2 diabetes during the 3.5-year follow-up . The hazard ratio ( HR ) for incident diabetes was 1.50 [ 95 % confidence interval ( CI ) 1.18–1.92 ] for the highest sex-specific quartile of serum uric acid compared with the lowest after controlling for confounders . Participants with hyperuricemia had an HR of 1.95 ( 95 % CI 1.11–3.44 ) for incident diabetes compared with those without hyperuricemia . Compared with the lowest quartile , the highest quartile had an HR for incident diabetes of 2.45 ( 95 % CI 1.39–4.33 ) in men and 1.39 ( 95 % CI 1.04–1.84 ) in women after fully adjustment . Adding serum uric acid to a model of conventional risk factors for diabetes improved the area under the curve for prediction of type 2 diabetes by 5 % . Serum uric acid was an independent predictor of incident type 2 diabetes in middle-aged and elderly Chinese It is unclear whether vitamin D lowers risk of type 2 diabetes ( T2D ) . In an observational study , we assessed the prospect i ve association between plasma 25-hydroxyvitamin D ( 25(OH)D ) and incident T2D , and evaluated whether it holds up for genetically determined elevated 25(OH)D. We used a case-cohort study nested within the German arm of the European Prospect i ve Investigation into Cancer . From a total cohort of 53,088 participants with a mean follow-up of 6.6 years , we identified a r and om subcohort of 2,121 participants ( 57 % women ) and 1,572 incident cases of T2D . 25(OH)D was measured in baseline plasma sample s retrieved from frozen storage . Mean plasma 25(OH)D in the subcohort was 47.1 ( 5th–95th percentile 19.6–80.7 ) nmol/L. After controlling for age , sex , center , season of blood draw , education , and lifestyle , the hazard of T2D decreased across increasing plasma concentrations of 25(OH)D ( P linear trend < 0.0001 ) . The association became non-linear after adjustment for BMI and waist circumference ( P non-linearity < 0.0001 ) , with the inverse association being restricted to participants with 25(OH)D concentrations below ~45 nmol/L ( hazard ratio per 5 nmol/L higher 25(OH)D 0.91 , 95 % CI 0.84–0.98 ) . A score predicting genetically determined plasma 25(OH)D by weighting four independent single-nucleotide polymorphisms by their effect on 25(OH)D , explained 3.7 % of the variance in 25(OH)D. The hazard ratio ( 95 % CI ) per 5 nmol/L higher genetically predicted 25(OH)D was 0.98 ( 0.89–1.08 ) in the entire study sample and 1.06 ( 0.93–1.21 ) in the sub- sample with 25(OH)D < 45 nmol/L. This latter finding casts doubt on a strong causal association of 25(OH)D with T2D , but further research in large-scale consortia is needed BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin BACKGROUND There is debate about the value of assessing levels of C-reactive protein ( CRP ) and other biomarkers of inflammation for the prediction of first cardiovascular events . METHODS We analyzed data from 52 prospect i ve studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk . We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implication s of initiation of statin therapy after the assessment of CRP or fibrinogen . RESULTS The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age , sex , smoking status , blood pressure , history of diabetes , and total cholesterol level increased the C-index , a measure of risk discrimination , by 0.0050 . The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027 , respectively ( P<0.001 ) , and yielded a net reclassification improvement of 1.52 % and 0.83 % , respectively , for the predicted 10-year risk categories of " low " ( < 10 % ) , " intermediate " ( 10 % to < 20 % ) , and " high " ( ≥20 % ) ( P<0.02 for both comparisons ) . We estimated that among 100,000 adults 40 years of age or older , 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk . Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines ( i.e. , for persons with a predicted risk of ≥20 % and for those with certain other risk factors , such as diabetes , irrespective of their 10-year predicted risk ) , additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years . CONCLUSIONS In a study of people without known cardiovascular disease , we estimated that under current treatment guidelines , assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened . ( Funded by the British Heart Foundation and others . ) We investigated cross-sectionally whether the type 2 diabetes ( T2DM ) risk alleles of rs1801282 ( PPARG2 ) and rs4607103 ( ADAMTS9 ) were associated with T2DM and /or insulin sensitivity ( IS ) and beta cell function ( βF ) in Italians without and with newly diagnosed T2DM . In 676 nondiabetic subjects ( 336 NGR and 340 IGR ) from the GENFIEV study and in 597 patients from the Verona Newly Diagnosed Type 2 Diabetes Study ( VNDS ) , we ( 1 ) genotyped rs1801282 and rs4607103 , ( 2 ) assessed βF by C-peptide/glucose modeling after OGTT , and ( 3 ) assessed IS by HOMA-IR in both studies and by euglycemic insulin clamp in VNDS only . Logistic , linear , and two-stage least squares regression analyses were used to test ( a ) genetic associations with T2DM and with pathophysiological phenotypes , ( b ) causal relationships of the latter ones with T2DM by a Mendelian r and omization design . Both SNPs were associated with T2DM . The rs4607103 risk allele was associated to impaired βF ( p < 0.01 ) in the GENFIEV study and in both cohorts combined . The rs1801282 genotype was associated with IS both in the GENFIEV study ( p < 0.03 ) and in the VNDS ( p < 0.03 ) , whereas rs4607103 did so in the VNDS only ( p = 0.01 ) . In a Mendelian r and omization design , both HOMA-IR ( instrumental variables : rs1801282 , rs4607103 ) and βF ( instrumental variable : rs4607103 ) were related to T2DM ( p < 0.03–0.01 and p < 0.03 , respectively ) . PPARG2 and ADAMTS9 variants are both associated with T2DM and with insulin resistance , whereas only ADAMTS9 may be related to βF. Thus , at least in Italians , they may be considered bona fide “ insulin resistance genes ” Identification of novel biomarkers for risk assessment is important for both effective disease prevention and optimal treatment recommendation . Discovery relies on the precious yet limited re source of stored biological sample s from large prospect i ve cohort studies . Case-cohort sampling design provides a cost-effective tool in the context of biomarker evaluation , especially when the clinical condition of interest is rare . Existing statistical methods focus on making efficient inference on relative hazard parameters from the Cox regression model . Drawing on recent theoretical development on the weighted likelihood for semiparametric models under two-phase studies ( Breslow and Wellner , 2007 ) , we propose statistical methods to evaluate accuracy and predictiveness of a risk prediction biomarker , with censored time-to-event outcome under stratified case-cohort sampling . We consider nonparametric methods and a semiparametric method . We derive large sample properties of proposed estimators and evaluate their finite sample performance using numerical studies . We illustrate new procedures using data from Framingham Offspring Study to evaluate the accuracy of a recently developed risk score incorporating biomarker information for predicting cardiovascular disease OBJECTIVE Plasma resistin level is a potential molecular link between obesity and diabetes . Causal role of resistin , type 2 diabetes mellitus ( T2DM ) and genetic variants have not been thoroughly investigated . Therefore , we conducted a genome-wide association study ( GWAS ) to identify quantitative trait loci associated with resistin levels and investigated whether these variants were prospect ively associated with the development of metabolic syndrome ( MetS ) and T2DM in an independent community-based cohort , the CardioVascular Disease risk FACtors Two-township Study ( CVDFACTS ) . RESEARCH DESIGN AND METHODS We genotyped 382 young-onset hypertensive ( YOH ) subjects with Illumina HumanHap550 chips and search ed for quantitative trait loci ( QTLs ) of resistin in the 1(st ) stage GWAS and confirmed the finding in another 559 YOH subjects . Logistic regression was used to examine the Mendelian r and omization effects between genotypes of confirmed QTLs and metabolic outcomes in 3400 subjects of CVDFACTS . RESULTS Two single nucleotide polymorphisms ( SNP ) ( rs3745367 and rs1423096 ) were significantly associated with resistin levels ( p = 5.52 × 10(-15 ) and p = 2.54 × 10(-20 ) ) and replicated in another 559 YOH subjects ( p = 1.29 × 10(-3 ) and p = 1.13 × 10(-7 ) ) , respectively . The SNP rs1423096 was further associated with the levels of HDL-C ( p = 0.006 ) , the risk of MetS ( OR = 2.21 , p = 0.0034 ) and T2DM ( OR = 1.62 , p = 0.0063 ) in the CVDFACTS . People with the haplotypes A-G and G-G determined by rs3745367 and rs1423096 showed a significantly increased T2DM risk ( p = 0.0068 and p = 0.0035 , respectively ) compared with those with A-A haplotype . CONCLUSION We have found that rs3745367 and rs1423096 on the RETN gene were significantly associated with resistin levels . However , rs1423096 , downstream of RETN , seems to be associated with MetS and T2DM risk more so than rs3745367 . The established genotype-disease association points to a causal association of resistin and T2DM |
12,544 | 24,499,149 | No protective association was found between consumption of solid cheese or fermented milk and colorectal cancer . | Colorectal cancer is the second most prevalent cancer worldwide .
A systematic review and meta- analysis of prospect i ve studies was conducted to examine the association between intake of different types of dairy foods during adulthood and the development of colorectal cancer , specifically comparing nonfermented milk , solid cheese , and fermented milk . | Dietary factors are thought to be closely associated with the development of human cancers and hence numerous studies in this area have already been conducted in the United States and other Western countries . Comparatively few prospect i ve studies have been published in Japan , especially for Hokkaido people . The present investigation was therefore performed to assess links between four leading cancers and some of the Japanese common dietary factors through a cohort study ( 1984 - 2002 ) in Hokkaido by analyzing 1,524 men and 1,634 women separately aged 40 and over . Adjusted Cox proportional hazard regression was used to calculate the relative risk ( RR ) for each dietary factor . For men , two dietary factors , miso soup ( RR=0.2 , 95 % confidence interval (95%CI)=0.1 - 0.8 ) and pickled vegetables ( RR=0.2 , 95%CI=0.1 - 0.8 ) were associated with lower risk for stomach and colorectal cancer respectively . For women , three factors , namely salty confectionary ( RR=3.5 , 95%CI=1.1 - 10.9 ) , black tea ( RR=3.8 , 95%CI=1.1 - 13.6 ) , and carbonated drink/juice ( RR=3.9 , 95 % CI=1.4 - 11.1 ) appeared related to an elevated risk of stomach cancer . However , further analysis simultaneously with all other adjusted factors indicated only carbonated drink/juice ( RR=3.1 , 95%CI=1.1 - 8.9 ) to present a significant risk factor for stomach cancer . One factor , namely wild edible plants ( RR=3.3 , 95%CI=1.1 - 9.8 ) , increased the risk for colorectal cancer in women . None of the dietary components were significantly associated with lung or pancreatic cancers . This study also indicated a wide variation in the impact of dietary factors by sex and cancer site , in line with earlier work , pointing to a necessity for careful interpretation . Further epidemiological investigations by sex with more study subjects and confounding factors will be useful for determining the contribution of individual dietary factors to development of human cancers in Hokkaido , Japan The relationship of meat , fish , fat , fibre or calcium consumption to the risk of colon cancer was examined in a prospect i ve study conducted by the Norwegian National Health Screening Service . Between 1977 and 1983 , 50,535 Norwegian men and women aged 20 - 54 attended the health screening and completed a semi-quantitative question naire about food frequency . During a mean follow-up of 11.4 years , 143 cases of colon cancer were identified for analyses through a link with the Norwegian Cancer Registry . The relative risk of colon cancer was 3.5 ( 95 % CI , 1.02 - 11.9 ) in women who consumed sausages as their main meal five or more times a month , compared with the risk in those who reported a consumption frequency of less than once a month . There was an increase in the relative risk with increasing frequency of consumption ( P for linear trends = 0.03 ) . Among men , the association was not statistically significant , but the trend was in the same direction as that of the women . The frequency of consuming meat meals in general , including meat stews , roasted meat , meat balls , fish or milk , was not associated with a risk of colon cancer . No trends in relative risks of colon cancer were found to be associated with intake of total energy intake or with energy-adjusted intake of total fat , saturated fat , monounsaturated fat , dietary fibre or calcium . In conclusions , this prospect i ve study provided no evidence of association between intake of meat , fish , fat , energy , fibre or calcium and risk of colon cancer , although an increased risk with frequent consumption of sausages was suggested The authors examined the association of intakes of different types of fat and fatty acids with risk of colorectal cancer using data from the Women 's Health Study , a r and omized trial of low-dose aspirin and vitamin E carried out among 39,876 healthy US women aged > /=45 years . Among the 37,547 women eligible for the present study , 202 developed colorectal cancer during an average follow-up period of 8.7 years ( 1993 - 2003 ) . Intakes of dietary fat and its food sources were assessed at baseline by food frequency question naire . Cox proportional hazards regression was used to estimate relative risks and 95 % confidence intervals . Total fat intake was not related to colorectal cancer risk , nor were intakes of the different types of fat and major fatty acids . However , the authors observed a positive association between intake of fried foods away from home and colorectal cancer risk ( highest quintile vs. lowest : relative risk = 1.86 , 95 % confidence interval : 1.09 , 3.16 ; p for trend = 0.01 ) . These prospect i ve cohort data provide little support for an association between dietary fat and colorectal cancer risk . However , intake of fried foods and /or other factors related to their intake may be associated with colorectal cancer development . This finding warrants further examination BACKGROUND High-fat dairy foods contain many potentially anticarcinogenic factors , including conjugated linoleic acid ( CLA ) . However , few epidemiologic studies have specifically evaluated high-fat dairy food consumption , and none have evaluated CLA intake , in relation to colorectal cancer risk . OBJECTIVE The aim of this study was to prospect ively examine the associations of long-term high-fat dairy food consumption and CLA intake and the incidence of colorectal cancer . DESIGN Our study population consisted of 60 708 women aged 40 - 76 y who participated in the Swedish Mammography Cohort . The women 's consumption of high-fat dairy foods was assessed at baseline , which was from 1987 to 1990 , and again in 1997 . RESULTS We ascertained 798 incident cases of colorectal cancer during an average 14.8 y of follow-up . After adjustment for age and other potential confounders , the women who consumed > or = 4 servings of high-fat dairy foods/d ( including whole milk , full-fat cultured milk , cheese , cream , sour cream , and butter ) had a multivariate rate ratio of colorectal cancer of 0.59 ( 95 % CI : 0.44 , 0.79 ; P for trend = 0.002 ) when compared with the women who consumed < 1 serving/d . Each increment of 2 servings of high-fat dairy foods/d corresponded to a 13 % reduction in the risk of colorectal cancer ( multivariate rate ratio : 0.87 ; 95 % CI : 0.78 , 0.96 ) . For CLA , the multivariate rate ratio of colorectal cancer in a comparison of the 2 extreme quartiles of intake was 0.71 ( 95 % CI : 0.55 , 0.91 ; P for trend = 0.004 ) . CONCLUSION These prospect i ve data suggest that high intakes of high-fat dairy foods and CLA may reduce the risk of colorectal cancer BACKGROUND Recent epidemiologic studies have generally reported a modest inverse association between calcium intake and the risk of colorectal cancer . However , findings pertaining to specific subsites in the colorectum have been conflicting . OBJECTIVE Our objective was to prospect ively examine the relations between intakes of calcium and dairy foods and the risk of colorectal cancer , overall and by anatomic subsite , in men from the Cohort of Swedish Men . DESIGN In 1997 , 45 306 men aged 45 - 79 y and without a history of cancer completed a food-frequency question naire . The men were followed through 31 December 2004 . RESULTS During a mean follow-up of 6.7 y , we ascertained 449 incident cases of colorectal cancer . After adjustment for age and other known or potential risk factors , the multivariate rate ratio ( RR ) of colorectal cancer for men in the highest quartile of total calcium intake compared with those in the lowest quartile was 0.68 ( 95 % CI : 0.51 , 0.91 ; P for trend = 0.01 ) . A high consumption of dairy foods was also associated with a lower risk of colorectal cancer . The multivariate RR of colorectal cancer for > or = 7 servings/d of total dairy foods compared with < 2 servings/d was 0.46 ( 0.30 , 0.71 ; P for trend = 0.01 ) . For cancer subsites , the corresponding RRs were 0.37 ( 0.16 , 0.88 ) for proximal colon , 0.43 ( 0.20 , 0.93 ) for distal colon , and 0.48 ( 0.23 , 0.99 ) for rectum . CONCLUSION Our findings provide support for inverse associations between intakes of calcium and dairy foods and the risk of colorectal cancer The relation between diet and female colorectal cancer was analyzed in a prospect i ve study of 14,727 women aged 34 - 65 years , who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991 . They were followed through the end of 1994 ( average 7.1 yrs ) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries , result ing in 100 incident cases of colorectal cancer . There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories , total or subclasses of fat , carbohydrate , or dietary fiber , whereas there was an inverse association with total protein . Among major food groups , there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish ( relative risk for 4th vs. 1st quartile = 0.49 , 95 % confidence interval = 0.27 - 0.89 ) . A similar inverse association was also observed for consumption of dairy products , and this association was explained mainly by calcium , not by other nutrients , such as fat or protein . The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer , whereas the relations with red meat or total fat remained unclear A protective effect of calcium and /or dairy products on colorectal cancer has been reported in epidemiological studies but the findings are considered inconsistent . In particular , it is unclear whether they act at a particular step of the adenoma‐carcinoma sequence . To investigate the effect of dairy product consumption and dietary calcium , vitamin D and phosphorus intake on the adenoma‐carcinoma sequence in the French E3N‐EPIC prospect i ve study . The population for the study of risk factors for adenomas was composed of 516 adenoma cases , including 175 high‐risk adenomas , and of 4,804 polyp‐free subjects confirmed by colonoscopy . The population for the colorectal cancer study was composed of 172 cases and 67,312 cancer‐free subjects . Diet was assessed using a self‐administered question naire completed at baseline . There was a trend of decreasing risk of both adenoma ( ptrend= 0.04 ) and cancer ( ptrend=0.08 ) with increasing calcium intake , with RRs for adenoma and cancer of 0.80 ( IC 95%=0.62–1.03 ) and 0.72 ( 95 % CI=0.47–1.10 ) , respectively , in the fourth quartile compared to the first . A protective effect of dairy products on adenoma ( RRQ4 vs. Q1= 0.80 , 95 % CI=0.62‐1.05 , ptrend= 0.04 ) was observed and of milk consumption on colorectal cancer ( RRQ4vs . Q1= 0.54 , 95 % CI=0.33–0.89 , ptrend= 0.09 ) , although the latter did not reach significance . Phosphorus intake also decreased the risk of adenoma ( RRQ4 vs. Q1=0.70 , 95 % CI=0.54–0.90 , ptrend= 0.005 ) . No vitamin D effect was identified . Our data support the hypothesis that calcium , dairy products and phosphorus exert a protective effect at certain steps of the adenoma‐carcinoma sequence . © 2005 Wiley‐Liss , To examine the associations between intakes of calcium , Vitamin D , and dairy foods and the risk of colon cancer , the authors analyzed data from a prospect i ve study of 47,935 US male professionals , 40 - 75 years of age and free of cancer in 1986 . Within this cohort , 203 new cases of colon cancer were documented between 1986 and 1992 . After adjusting for age and total energy intake , the authors found that the intake of calcium from foods and supplements was inversely associated with colon cancer risk ( relative risk ( RR ) = 0.58 , 95 % confidence interval ( CI ) 0.39 - 087 between high and low intakes of calcium ) . However , after adjusting for confounding variables , they found that the trend was no longer statistically significant ( p = 0.22 ) , and the relative risk for the highest quintile group of intake was attenuated : 0.75 ( 95 % CI 0.48 - 1.15 ) . Similar results were observed for total vitamin D intake ; the age- and energy-adjusted relative risk was 0.54 % ( 95 % CI 0/34 - 0/85 ) for the highest versus lowest quintile group , and this was attenuated in the multivariate model ( RR = 0.66 , 95 % CI 0.42 - 1.05 ) . The inverse association was weaker for dietary vitamin D ( RR highest vs. lowest quintile = 0.88 . 95 % CI 0.54 - 1.42 ) and strongest for vitamin D arising from vitamin supplements ( RR = 0.48 , 95 % CI 0.22 - 1.02 ) . Thus , it is possible that other components of multivitamin use rather than vitamin D accounted for the reduction in risk . Consumption of milk and fermented dairy products was not significantly associated with the risk of colon cancer ; individuals consuming two or more glasses of " whole " or skim milk per day had a relative risk of 1.09 ( 95 % CI 0.69 - 1.72 ) , compared with those who consumed " whole or skim milk less than once a month . These prospect i ve data do not support the hypothesis that calcium intake is strongly protective against colon cancer risk , although a modest association can not be excluded Abstract : The relationship between diet and colorectal cancer mortality was analyzed in a prospect i ve study of 45,181 men and 62,643 women aged 40 - 79 yr enrolled in the Japan Collaborative Cohort Study . Between 1988 and 1990 , subjects completed a self-administered question naire on their sociodemographic characteristics , diet , and other lifestyle habits . During the follow-up period ( average 9.9 yr ) , 284 colon cancer deaths ( 138 men and 146 women ) and 173 rectal cancer deaths ( 116 men and 57 women ) were confirmed . The only significant association of colorectal cancer mortality with vegetable intake was observed between male rectal cancer mortality and green leafy vegetable consumption [ hazard ratio ( HR ) using Cox proportional hazard models = 0.6 ; 95 % confidence interval ( CI ) = 0.3 - 0.9 ; P for trend = 0.02 ] . Yogurt intake was also inversely associated with male rectal cancer mortality ( HR = 0.5 ; 95 % CI = 0.2 - 1.0 ; P for trend = 0.04 ) . Egg consumption was positively associated with male colon cancer mortality ( P for trend = 0.04 ) . Women with high fruit consumption had increased colon cancer mortality ( HR = 1.6 ; 95 % CI = 1.0 - 2.6 ; P for trend = 0.04 ) . It should be noted that this study lacked statistical power due to small sample size and measurement error in the food-frequency question naire . Further investigation is therefore necessary to confirm the association between diet and colorectal cancer , especially by subsites and gender Objective : Calcium , vitamin D , and dairy product intake may reduce the risk of colorectal cancer . We therefore examined the association between these factors and risk of colorectal cancer in a large prospect i ve cohort of United States men and women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , medical history , and lifestyle in 1992–93 . After excluding participants with a history of cancer or incomplete dietary information , 60,866 men and 66,883 women remained for analysis . During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women , respectively . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results : Total calcium intake ( from diet and supplements ) was associated with marginally lower colorectal cancer risk in men and women ( RR = 0.87 , 95 % CI 0.67–1.12 , highest vs lowest quintiles , p trend = 0.02 ) . The association was strongest for calcium from supplements ( RR = 0.69 , 95 % CI 0.49–0.96 for ≥500 mg/day vs none ) . Total vitamin D intake ( from diet and multivitamins ) was also inversely associated with risk of colorectal cancer , particularly among men ( RR = 0.71 , 95 % CI 0.51–0.98 , p trend = 0.02 ) . Dairy product intake was not related to overall risk . Conclusions : Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer . Vitamin D was associated with reduced risk of colorectal cancer only in men BACKGROUND Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer , epidemiologic studies have been inconclusive . PURPOSE We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer . METHODS In a prospect i ve study , 89 448 female registered nurses who were free of cancer responded to a mailed , semiquantitative food-frequency question naire in 1980 ; dietary information was up date d in 1984 and 1986 . Through 1992 , 501 incident cases of colorectal cancer ( 396 colon and 105 rectal cancers ) were documented . As measures of exposure , we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three question naires : the average of intakes from the three question naires and consistent intakes , which were defined as high if women were in the upper tertile on all question naires and low if they were in the lower tertile on all question naires . To further characterize long-term intake , we conducted analyses excluding women who reported a change in their consumption of milk ( primary source of calcium and vitamin D ) in the 10 years prior to 1980 . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated using the lowest quintile of intake as a reference . The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake . In multivariate analyses , the trends were tested with use of the medians of the intake as a continuous variable in the logistic model . The P values for the trends were two-sided . RESULTS On the basis of the data from the 1980 question naire alone , the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 ( 95 % CI = 0.60 - 1.07 ) for dietary calcium , 0.84 ( 95 % CI = 0.63 - 1.13 ) for dietary vitamin D ( from foods only ) , and 0.88 ( 95 % CI = 0.66 - 1.16 ) for total vitamin D ( from foods and supplements ) . After the exclusion of women who reported a change in their milk intake , the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 ( 95 % CI = 0.36 - 1.50 ) for dietary calcium , 0.72 ( 95 % CI = 0.34 - 1.54 ) for dietary vitamin D , and 0.42 ( 95 % CI = 0.19 - 0.91 ) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 ( 95 % CI = 0.35 - 1.39 ) for dietary calcium , 0.59 ( 95 % CI = 0.30- 1.16 ) for dietary vitamin D , and 0.33 ( 95 % CI = 0.16 - 0.70 ) for total vitamin D. CONCLUSIONS These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer , but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested . IMPLICATION S Available evidence does not warrant an increase in calcium intake to prevent colon cancer , but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed In a 6-year prospect i ve study , the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study ( California , 1976 - 1982 ) who , at baseline , had no documented or reported history of cancer . The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates . The authors found a positive association with total meat intake ( risk ratio ( RR ) for > or = 1 time/week vs. no meat intake = 1.85 , 95 % confidence interval ( CI ) 1.19 - 2.87 ; p for trend = 0.01 ) and , among subjects who favored specific types of meat , positive associations with red meat intake ( RR for > or = 1 time/week vs. no red meat intake = 1.90 , 95 % CI 1.16 - 3.11 ; p for trend = 0.02 ) and white meat intake ( RR for > or = 1 time/week vs. no white meat intake = 3.29 , 95 % CI 1.60 - 6.75 ; p for trend = 0.006 ) . An inverse association with legume intake ( RR for > 2 times/week vs. < 1 time/week = 0.53 , 95 % CI 0.33 - 0.86 ; p for trend = 0.03 ) was observed . Among men , a positive association with body mass index was observed ( relative to the RR for tertile III ( > 25.6 kg/m2 ) vs. tertile I ( < 22.5 kg/m2 ) = 2.63 , 95 % CI 1.12 - 6.13 ; p for trend = 0.05 ) . A complex relation was identified whereby subjects exhibiting a high red meat intake , a low legume intake , and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables . This pattern of putative risk factors would likely contribute to increases in both insulin resistance ( high body mass , high red meat intake ) and glycemic load ( low legume intake ) , a synergism that , if causal , implicates hyperinsulinemic exposure in colon carcinogenesis . The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology Objective : To study the relationship between consumption of milk and milk products , calcium , lactose and vitamin D and occurrence of colorectal cancers . Design : Prospect i ve cohort study .Subjects : A total of 9959 men and women aged 15 y or older without history of cancer at baseline . During a 24 y follow-up , 72 new cancers of the large bowel ( 38 in the colon and 34 in the rectum ) were detected . Results : Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence , whereas no similar association was seen for rectal cancer . The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 ( 95 % confidence interval 0.14–1.46 , P for trend 0.09 ) for milk and 0.37 ( 95 % CI=0.12–1.39 , P for trend 0.06 ) for total milk products . Lactose intake showed a similar inverse relationship with colon cancer : the relative risk was 0.31 ( 95 % CI=0.08–1.15 , P for trend 0.03 ) . Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk , whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence ; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 ( 95 % CI=1.00–4.28 ) . Conclusions : Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer ; however , the association does not appear to be due to intake of calcium , vitamin D , or to specific effects of fermented milk . Sponsorship : This study was supported by a grant from the Swedish Cancer Foundation . European Journal of Clinical Nutrition ( 2001 ) 55 , Concerns have been raised regarding the possible adverse health effects of consumption of unpasteurized milk and risk of cancer . We examined the association of self-reported intake of unpasteurized milk with subsequent risk of cancer in a large population -based cohort study . The Iowa Women ’s Health Study is a prospect i ve cohort study of 55–69 year old women at baseline in 1986 . Of the 41,836 women in the cohort at baseline , 22,808 cancer-free women completed the fourth follow-up question naire in 1997 . Risk ratios ( RR ) and 95 % confidence intervals ( CI ) were calculated using Cox proportional hazards regression analysis . Reported intake of unpasteurized milk was high : 59.2 % consumed only as a child , 2.5 % consumed only as an adult , and 16.5 % consumed as a child and an adult . A total of 2,379 cancers were identified in the cohort at risk . Overall , the age-adjusted risk of cancer was lower among women who reported consumption of unpasteurized milk only as a child ( RR = 0.90 , 95 % CI : 0.82–0.99 ) or as a child and an adult ( RR = 0.85 ; 95 % CI : 0.75–0.97 ) . Adjustment for confounding factors attenuated these associations ( RR = 0.92 , 95 % CI : 0.83–1.02 for consumption only as a child , and RR = 0.91 ; 95 % CI : 0.79–1.04 for consumption as a child and an adult ) . These data suggest that consumption of unpasteurized milk does not increase risk of cancer In vivo and in vitro studies have suggested a protective role of calcium and vitamin D in the development of colorectal cancer . However , epidemiologic data have been inconclusive . The authors prospect ively assessed intakes of calcium and vitamin D in relation to risk of colorectal cancer in a large , prospect i ve , female cohort from the US Women 's Health Study . In 1993 , 39,876 women aged > or = 45 years and free of cardiovascular disease and cancer were enrolled in the study . During an average follow-up of 10 years , 223 of 36,976 women eligible for the present study developed colorectal cancer . Intakes of calcium and vitamin D from dietary sources and supplements were assessed with a baseline food frequency question naire . Cox proportional hazards regression was used to estimate relative risks and 95 % confidence intervals . Intakes of total calcium and vitamin D were not associated with risk of colorectal cancer ; multivariate relative risks comparing the highest with the lowest quintile were 1.20 ( 95 % confidence interval : 0.79 , 1.85 ; p for trend = 0.21 ) for total calcium and 1.34 ( 95 % confidence interval : 0.84 , 2.13 ; p for trend = 0.08 ) for total vitamin D. Intakes of both nutrients from specific types of sources , including diet and supplements , were also not significantly associated with colorectal cancer risk . Data provide little support for an association of calcium and vitamin D intake with colorectal cancer risk BACKGROUND Calcium has been hypothesized to reduce the risk of colon cancer , and in a recent r and omized trial , calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas . We examined the association between calcium intake and colon cancer risk in two prospect i ve cohorts , the Nurses ' Health Study ( NHS ) and the Health Professionals Follow-up Study ( HPFS ) . METHODS Our study population included 87 998 women in NHS and 47 344 men in HPFS who , at baseline ( 1980 for NHS and 1986 for HPFS ) , completed a food frequency question naire and provided information on medical history and lifestyle factors . Dietary information was up date d at least every 4 years . During the follow-up period ( 1980 to May 31 , 1996 for the NHS cohort ; 1986 to January 31 , 1996 for the HPFS cohort ) , 626 and 399 colon cancer cases were identified in women and men , respectively . Pooled logistic regression was used to estimate relative risks ( RRs ) , and all statistical tests were two-sided . RESULTS In women and men considered together , we found an inverse association between higher total calcium intake ( > 1250 mg/day versus < or = 500 mg/day ) and distal colon cancer ( women : multivariate RR = 0.73 , 95 % confidence interval [ CI ] = 0.41 to 1.27 ; men : RR = 0.58 , 95 % CI = 0.32 to 1.05 ; pooled RR = 0.65 , 95 % CI = 0.43 to 0.98 ) . No such association was found for proximal colon cancer ( women : RR = 1.28 , 95 % CI = 0.75 to 2.16 ; men : RR = 0.92 , 95 % CI = 0.45 to 1.87 ; pooled RR = 1.14 , 95 % CI = 0.72 to 1.81 ) . The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal . CONCLUSIONS Higher calcium intake is associated with a reduced risk of distal colon cancer . The observed risk pattern was consistent with a threshold effect , suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction . Future investigations on this association should concentrate on specific cancer subsites and on the dose-response relationship |
12,545 | 29,993,117 | The meta-analyses found the following additional results : outcomes intraoperative blood loss ( MD -6.75 mL , 95 % CI -85.49 to 71.99 ; moderate-certainty evidence ) ; and postoperative drain volume ( MD 30.18 mL , 95 % CI -36.26 to 96.62 ; moderate-certainty evidence ) .In addition , the meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with Fondaparinux for the following outcomes : any VTE ( DVT or PE , or both ; RR 2.51 , 95 % CI 0.89 to 7.03 ; RD 57 more per 1000 , 95 % CI 4 fewer to 228 more ; low-certainty evidence ) , major bleeding ( RR 0.74 , 95 % CI 0.45 to 1.23 ; RD 8 fewer per 1000 , 95 % CI 16 fewer to 7 more ; low-certainty evidence ) , minor bleeding ( RR 0.83 , 95 % CI 0.34 to 2.05 ; RD 8fewer per 1000 , 95 % CI 33 fewer to 52 more ; low-certainty evidence ) , thrombocytopenia ( RR 0.35 , 95 % CI 0.04 to 3.30 ; RD 14 fewer per 1000 , 95 % CI 20 fewer to 48 more ; low-certainty evidence ) , any PE ( RR 3.13 , 95 % CI 0.13 to 74.64 ; RD 2 more per 1000 , 95 % CI 1 fewer to 78 more ; low-certainty evidence ) and postoperative drain volume ( MD -20.00 mL , 95 % CI -114.34 to 74.34 ; low-certainty evidence ) AUTHORS ' CONCLUSIONS : We found no difference between perioperative thromboprophylaxis with LMWH versus UFH and LMWH compared with fondaparinux in their effects on mortality , thromboembolic outcomes , major bleeding , or minor bleeding in people with cancer .
There was a lower incidence of wound hematoma with LMWH compared to UFH | BACKGROUND The choice of the appropriate perioperative thromboprophylaxis for people with cancer depends on the relative benefits and harms of different anticoagulants .
OBJECTIVES To systematic ally review the evidence for the relative efficacy and safety of anticoagulants for perioperative thromboprophylaxis in people with cancer . | Venous thromboembolism is a serious complication following gynecologic surgery and is particularly common in patients with malignancy . A previous study of subcutaneous low-dose heparin given as one dose preoperatively and every 12 hours postoperatively failed to show a benefit in gynecologic oncology patients . In the present study , two more intense regimens of low-dose heparin were evaluated . Three hundred four patients were assigned r and omly to receive no prophylaxis ( controls ) , subcutaneous heparin 5000 units 2 hours before surgery and every 8 hours postoperatively ( low-dose heparin ) ( regimen I ) , or 5000 units heparin subcutaneously every 8 hours preoperatively ( between two and nine doses ) and every 8 hours postoperatively ( regimen II ) . All patients had thromboembolism surveillance with the fibrinogen uptake test and clinical evaluation . Eighty-four percent had a malignancy . Thromboemboli were diagnosed in 19 of 103 control patients , ten of 104 regimen I patients , and six of 97 regimen II patients , a statistically significant difference ( P < .008 ) . When compared with the control group , the study groups had no evidence of increased bleeding complications or alteration of laboratory coagulation indicators . ( Obstet Gynecol 75 : 684 , 1990 In a prospect i ve double-blind trial , low molecular weight ( LMW ) heparin ( KABI 2165 ) 5,000 U ( anti-Xa ) once daily was compared with conventional heparin 5,000 IU twice daily , both given subcutaneously , as regards prevention of postoperative deep venous thrombosis ( DVT ) in 52 patients undergoing major abdominal surgery . Radioactive fibrinogen uptake test ( FUT ) was used for DVT screening . DVT , diagnosed from positive FUT , developed in two patients from each group , but could be phlebographically confirmed in only one ( LMW ) case . No intergroup differences were found in peroperative blood loss or requirements for blood transfusion . Complications attributable to the prophylactic regimens were few . In the LMW-heparin group , the anti-Xa levels measured during operation showed considerable variation , the higher activities ( greater than 0.30 U/ml ) being nonsignificantly associated with increased blood loss . Studies with lower doses of LMW-heparin are recommended Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma ( MM ) but is associated with an increased risk of venous thromboembolism ( VTE ) . This prospect i ve , open-label , r and omized sub study of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin ( ASA ) or low-molecular-weight heparin ( LMWH ) in patients with newly diagnosed MM , treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation . Overall , 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA 100 mg/d ( n = 176 ) or LMWH enoxaparin 40 mg/d ( n = 166 ) . The incidence of VTE was 2.27 % in the ASA group and 1.20 % in the LMWH group . Compared with LMWH , the absolute difference in the proportion of VTE was 1.07 % ( 95 % confidence interval , -1.69 - 3.83 ; P = .452 ) in the ASA group . Pulmonary embolism was observed in 1.70 % of patients in the ASA group and none in the LMWH group . No arterial thrombosis , acute cardiovascular events , or sudden deaths were reported . No major hemorrhagic complications were reported . In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk , ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis BACKGROUND Ambulatory cancer patients at high-risk for venous thromboembolism ( VTE ) can be identified using a vali date d risk score ( Khorana score ) . We evaluated the benefit of outpatient thromboprophylaxis with dalteparin in high-risk patients in a multicenter r and omized study . METHODS Cancer patients with Khorana score≥3 starting a new systemic regimen were screened for VTE and if negative r and omized to dalteparin 5000units daily or observation for 12weeks . Subjects were screened with lower extremity ultrasounds every 4weeks on study and with chest CT at 12weeks . The primary efficacy endpoint was all VTE over 12weeks and primary safety endpoint was clinical ly relevant bleeding events over 13weeks . The study was terminated early due to low accrual . RESULTS Of 117 enrolled patients , 10 ( 8.5 % ) had VTE on baseline screening and were not r and omized . Of 98 r and omized patients , VTE occurred in 12 % ( N=6/50 ) of patients on dalteparin and 21 % ( N=10/48 ) on observation ( hazard ratio , HR 0.69 , 95 % CI 0.23 - 1.89 ) . Major bleeding was similar ( N=1 ) in each arm but clinical ly relevant bleeding was higher in dalteparin arm ( N=7 versus 1 on observation ) ( HR=7.0 , 95 % CI 1.2 - 131.6 ) . There was no difference in overall survival . CONCLUSIONS Thromboprophylaxis is associated with a non-significantly reduced risk of VTE and significantly increased risk of clinical ly relevant bleeding in this underpowered study . The Khorana score successfully identifies patients with high incidence of VTE both at baseline and during treatment . Future studies should continue to focus on risk-adapted approaches to reduce the burden of VTE in cancer . TRIAL REGISTRATION clinical trials.gov identifier : NCT00876915 PURPOSE : Routine deep venous thrombosis prophylaxis is controversial in Asian patients , because deep venous thrombosis incidence was considered negligible . Because of recent reports of significantly higher incidences , a r and omized , controlled trial was conducted to assess the effectiveness and complications of enoxaparin prophylaxis ( low molecular weight heparins ) in major colorectal surgery . METHODS : Three hundred twenty consecutive patients were r and omly assigned to control or low molecular weight heparins groups . Patients in the low molecular weight heparins group were given perioperative enoxaparin starting 12 hours before surgery . The surgeon ( blinded ) assessed for difficulties related to possible enoxaparin administration . Independent blinded observers performed daily clinical assessment s and Doppler studies ( at the 3rd and 5th postoperative day ) . Deep venous thrombosis was confirmed by duplex ultrasound , and pulmonary embolism was confirmed by lung scans or postmortem examinations . RESULTS : Deep venous thrombosis developed in 5 of 169 ( 3 percent ) controls and 0 of 134 low molecular weight heparins patients ( P=0.045 ) . Three of the deep venous thrombosis patients had pulmonary embolism , which was fatal in one patient . The surgeons were unable to perceive any increased surgical difficulties in the low molecular weight heparins group . The bleeding-related complications were significantly higher in the low molecular weight heparins patients ( controls , n=3 ( 1.8 percent ) ; low molecular weight heparins , n=9 ( 6.7 percent ) ) . However , apart from one subdural hematoma and two abdominal hemorrhages needing re-exploration , which also occurred in one of the controls , these complications were minor bruises at the wounds , drains , or injection sites . CONCLUSION : Deep venous thrombosis prophylaxis is needed in Asian patients undergoing major colorectal surgery Summary : A r and omized controlled trial was undertaken comparing the efficacy and safety of low molecular weight ( LMW ) heparin ( Fragmin ) with sodium heparin for prophylaxis against postoperative thromboembolic disease after major gynaecological surgery . Women were r and omized to receive subcutaneous injections of 5,000 U of either once daily LMW heparin or twice daily sodium heparin . A total of 566 women were recruited , of whom 552 completed the study . Most women ( 461 ) had malignant disease and 430 of these underwent radical surgery . The remainder underwent major , but not radical surgery . There were 5 thromboembolic events in the LMW heparin group and 2 in the sodium heparin group , with no significant difference between these groups . No significant difference was found in the incidence of intraoperative or postoperative transfusion in the 2 groups . The decision of which heparin to use in routine practice can not be made on clinical grounds BACKGROUND Unfractionated heparin and the low molecular weight heparin , dalteparin , are used for prophylaxis against venous thromboembolism in patients undergoing craniotomy . These drugs were compared in a r and omized , prospect i ve pilot study comparing intermittent pneumatic compression devices plus dalteparin to intermittent pneumatic compression devices plus heparin . METHODS One hundred patients undergoing craniotomy were r and omly allocated to receive perioperative prophylaxis with subcutaneous ( SC heparin , 5000 units every 12 hours , or dalteparin , 2,500 units once a day , begun at induction of anesthesia and continued for 7 days or until the patient was ambulating . Entry criteria were age over 18 years , no deep vein thrombosis ( DVT ) preoperatively as judged by lower limb duplex ultrasound and no clinical evidence of pulmonary embolism preoperatively . Patients with hypersensitivity to heparin , penetrating head injury or who refused informed consent were excluded . Patients underwent a duplex study 1 week after surgery and 1 month clinical follow-up . All patients were treated with lower limb intermittent pneumatic compression devices . RESULTS There were no differences between groups in age , gender , and risk factors for venous thromboembolism . There were no differences between groups in intraoperative blood loss , transfusion requirements or postoperative platelet counts . Two patients receiving dalteparin developed DVT ( one symptomatic and one asymptomatic ) . No patient treated with heparin developed DVT and no patient in either group developed pulmonary embolism . There were two hemorrhages that did not require repeat craniotomy in patients receiving dalteparin and one that did require surgical evacuation in a patient treated with heparin . Drug was stopped in two patients treated with dalteparin because of thrombocytopenia . None of these differences were statistically significant . CONCLUSION There was no significant difference in postoperative hemorrhage , venous thromboembolism or thrombocytopenia between heparin and dalteparin . The results suggest that , given the small sample size of this trial , both drugs appear to be safe and the incidence of venous thromboembolism by postoperative screening duplex ultrasound appears to be low when these agents are used in combination with intermittent pneumatic compression devices Background Advanced pancreatic cancer ( APC ) , beside its high mortality , causes the highest rates of venous thromboembolic events ( VTE ) . Enoxaparin , a low molecular weight heparin ( LMWH ) , is effective in prevention and treatment of VTE . Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms . We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in out patients with APC treated in 1st line . Methods The trial was a prospect i ve , open-label , single center investigation in out patients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH . The combined chemotherapy consisted of gemcitabine 1 g/m2 ( 30 min ) , 5-FU 750 mg/m2 ( 24 h ) , folinic acid 200 mg/m2 ( 30 min ) , and Cisplatin 30 mg/m2 ( 90 min ) on day 1 and 8 ; q3w for the first 12 weeks ( GFFC ) followed by gemcitabine alone in patients without cancer progression . The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily . Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19.0 . Results The investigation was stopped after recruitment of 19 patients . At this time 15 patients had completed the required 12 weeks of treatment . Based on 71 cycles of GFFC + enoxaparin ( median 4/pt [ range : 2–4 ] ) and 108 cycles of single-agent gemcitabine + enoxaparin ( median 4/pt [ range : 0–18 ] ) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10 % . One case ( 5 % ) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment . No severe bleeding event as defined in the protocol has been observed . The median overall survival was 10.05 [ 95 % CI : 8.67 - 18.14 ] months . Conclusions The addition of enoxaparin to GFFC chemotherapy is feasible , safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma . Based on these findings we have initiated the r and omized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome .Trial registration Clinical Trials NCT01945879 Background Advanced pancreatic cancer , in addition to its high mortality , is characterized by one of the highest rates of venous thromboembolic events ( VTE ) as compared to other types of cancer . Enoxaparin , a low molecular weight heparin ( LMWH ) , has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients . Results of some small studies suggest that this benefit might extend to patients with cancer , however , enoxaparin is not currently indicated for this use . This phase IIb study was design ed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy . Methods The aim of this prospect i ve multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients . Primary endpoint is the incidence of clinical ly relevant VTE ( symptomatic deep venous thrombosis ( DVT ) of the leg and /or pelvic and /or pulmonary embolism ( PE ) ) within the first 3 months . Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6 , 9 and 12 months as well as remission at 3 , 6 , 9 and 12 months , overall survival and bleeding . Trial registration : is rct n.org identifier CCT-NAPN-16752 , controlled-trials.com identifier : IS RCT N02140505 . Results An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding ( 5 pts vs. 6 pts , Chi2 : 0.763 ) . Conclusion PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer . Its results will lead to a new underst and ing of the role of heparins in the prevention of venous thromboembolism and of their effect on survival , remission rates and toxicity of chemotherapeutic regimens BACKGROUND The methodology of thromboprophylaxis post minimally invasive esophagectomy ( MIE ) is unclear . Thus , we compared the efficacy and safety of fondaparinux and nadroparin on the prophylaxis of venous thromboembolism ( VTE ) after MIE . MATERIAL S AND METHODS We conducted a r and omized , double-blind , treatment-controlled study . Consecutive patients undergoing MIE r and omly received a single dose of either nadroparin 2850 AxaIU ( Group H ) or fondaparinux 2.5 mg ( Group F ) daily . We used ultrasonography to identify deep vein thrombosis ( DVT ) on postoperative day 7 . The coagulation status was examined using thromboelastography ( TEG ) prior to and at 0 , 24 , 48 , and 72 h after the operation . Bleeding events were recorded during anticoagulation therapy and analysis was performed on an intention-to-treat basis . RESULTS We r and omly assigned the patients to Group H ( n = 57 ) or Group F ( n = 59 ) . Symptomatic or asymptomatic DVT was identified in seven patients in Group H and one patient in Group F ( 12.28 % vs. 1.69 % , p = 0.031 ) . Pulmonary embolism developed in one patient in Group H , and the VTE incidence was significantly lower in Group F than Group H ( 1.69 % vs. 14.04 % , RR : 0.121 , 95 % CI : 0.016 - 0.935 , p = 0.016 ) . TEG analysis showed a more inhibited coagulation profile of Group F compared with Group H reflected by the significantly prolonged R time at 48 h and 72 h after operation ( 6.8 ± 2.2 min vs. 8.4 ± 2.7 min , p = 0.005 ; 7.1 ± 1.6 min vs. 9.2 ± 3.7 min , p = 0.002 ) . Bleeding events were not recorded in either group . CONCLUSIONS Fondaparinux could provide similar efficacy and safety in postoperative thromboprophylaxis following MIE compared with nadroparin In a prospect i ve , r and omized multicentre trial the efficacy and safety of the low molecular weight heparin ( LMWH ) fraction Fraxiparin ® and unfractionated calcium heparin ( Calciparin ® ) were compared for the prevention of postoperative deep vein thrombosis . Of 1909 patients included in the trial 1896 underwent abdominal surgery and received either one daily subcutaneous injection of 7500 anti‐X a units Fraxiparin or 5000 units calcium heparin three times a day subcutaneously . Elastic compression stockings were worn by both groups of patients in the postoperative period . Before r and omization the patients were stratified in two subgroups with or without malignant disease . To assess the rate of deep vein thrombosis ( DVT ) , 125I‐labelled fibrinogen leg scanning was performed daily for 7 postoperative days . Positive results were confirmed by phlebography whenever possible . Venous thrombosis occurred in 27 of 960 patients ( 2.8 per cent ) given Fraxiparin and in 42 of 936 patients ( 4.5 per cent ) given calcium heparin ( P = 0.034 ) . The rates of proximal vein thrombosis were 0.4 per cent ( 4 patients ) and 1.4 per cent ( 13 patients ) respectively ( P<0.05 ) . Pulmonary embolism occurred in 2 of 960 patients ( 0.2 per cent ) treated with Fraxiparin and in 5 of 936 patients ( 0.5 per cent ) treated with calcium heparin . The two treatments were equally well tolerated . Intra‐ and postoperative blood loss , the number of wound haematomas as well as frequency and volume of transfusions were similar in both groups . The present trial demonstrates that a single daily subcutaneous injection of Fraxiparin is more effective than the established low dose subcutaneous heparin prophylaxis with 5000 units three times per day in preventing postoperative DVT after abdominal surgery in patients wearing compression stockings Abstract . A r and omized , double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin ( LMWH ) ( LU 47311 , Clivarine ) and st and ard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism . Altogether 1351 patients scheduled to undergo abdominal surgery were included . Main outcome measures included the incidence of thromboembolic events ( deep vein thrombosis , pulmonary embolism , or both ) and bleeding complications , including wound hematoma . A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily ; 677 patients received 5000 IU of unfractionated heparin ( UFH ) twice a day . Both drugs were found to be equally effective , as 4.7 % of patients in the LMWH group and 4.3 % in the UFH group developed postoperative thromboembolic complications . However , the incidence of bleeding complications was significantly reduced in the LMWH group : 55 ( 8.3 % ) patients in the LMWH group and 80 ( 11.8 % ) in the UFH group developed bleeding complications , a relative risk ( RR ) of 0.70 ( 95 % CI 0.51–0.97;p = 0.03 ) ; wound hematoma occurred in 29 ( 4.4 % ) of the LMWH group compared with 55 ( 7.7 % ) in those in the UFH group for an RR of 0.57 ( 95 % CI 0.37–0.88;p = 0.01 ) . This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis . At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma In a prospect i ve , double-blind , r and omized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery . Six hundred and seventy-three patients were r and omly allocated to the two prophylaxis groups ; 20 of these , however , did not undergo surgery and did not receive any prophylaxis . Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day . Treatment was initiated 2 h preoperatively and continued for 7 to 10 days . The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography . Venous thrombosis was diagnosed in 24 of 323 patients ( 7.4 % ) treated with low molecular weight heparin and in 26 of 330 patients ( 7.9 % ) treated with low-dose heparin . DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group . During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin . No pulmonary embolism was found in patients treated with low molecular weight heparin . Both prophylactic schemes were well tolerated . Intra- and postoperative blood loss , incidence of wound hematoma , frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Prophylactic therapies have demonstrated efficacy in reducing the incidence of deep venous thrombosis ( DVT ) in neurosurgical patients . Retrospective analysis of patients undergoing neurosurgical procedures at the University of Michigan demonstrated a high incidence ( 14 % ) of postoperative DVT among patients with intracranial neoplasms treated with sequential compression device ( SCD ) prophylaxis alone . Therefore , we investigated the efficacy and safety of the low-molecular weight heparin enoxaparin in preventing DVT in patients with brain tumors . The goal of the study was to compare SCD , enoxaparin , and combined SCD/enoxaparin prophylaxis among patients requiring surgery for treatment of intracranial neoplasms . METHODS Eligible patients were r and omized to SCD , enoxaparin , or combined therapy . Treatment was initiated before the induction of anesthesia and was continued throughout the hospital stay . Patients were screened for DVT , using duplex imaging , on four occasions in the first 1 month after surgery . The incidences of DVT and serious adverse events were compared between groups using analysis of variance and the Dunnet two-sided t test . RESULTS Sixty-eight patients completed the study . Postoperative DVT occurred in 3 of 22 ( 13.6 % ) SCD-treated patients , 1 of 23 ( 4.3 % ) enoxaparin-treated patients , and 4 of 23 ( 17.4 % ) SCD/enoxaparin-treated patients . Differences were not statistically significant . Postoperative intracranial hemorrhage did not occur in patients in the SCD-treated group , whereas 5 of 46 patients receiving low-molecular weight heparin suffered clinical ly significant intracranial hemorrhage . The study was terminated because of the increased incidence of adverse events in the enoxaparin-treated groups . CONCLUSION Enoxaparin therapy initiated at the time of anesthesia induction increases postoperative intracranial hemorrhage BACKGROUND Both cancer patients and patients undergoing surgery are thought to be at an increased risk of thrombo-embolic events . Consequently , low-molecular-weight heparin ( LMWH ) is administered to all such patients perioperatively . There is a lack of consensus in guidelines regarding the timing of administration and the dosage of thromboprophylactic agents . Studies have shown that thrombo-elastography ( TEG ) is a useful test in assessing global haemostatic function , and has been vali date d in monitoring the dosage of LMWH . In this study , we assess the coagulation status of patients undergoing thoracic surgery with TEG , and the effectiveness of administered LMWH for thromboprophylaxis . METHODS Thirty patients with primary lung cancer ( LC ) and 30 with benign lung disease ( BL ) were studied prospect ively . Patients were r and omised to receive subcutaneous LMWH 40 mg once or twice per day perioperatively . Their coagulation status was monitored with TEG preoperatively and postoperatively for 3 consecutive days . RESULTS Preoperative TEG parameters ( k time , alpha angle and maximum amplitude ( MA ) ) were within the normal range in both the LC and BL groups . Preoperative r time was prolonged in both the groups , but with no significant difference between the two groups ( p>0.05 ) . Postoperatively , r time was prolonged in some patients receiving LMWH twice daily , suggesting a possible adequate thromboprophylaxis in these patients only . CONCLUSION This study demonstrates that the majority of patients with LC are not hypercoagulable . We also showed that LMWH once or twice a day might not provide sufficient thromboprophylaxis . We advocate screening for patients demonstrating hypercoagulable states and ensuring adequate thromboprophylaxis in this group of patients with careful monitoring A prospect i ve , double-blind , r and omized , controlled clinical trial compared the efficacy and safety of fixed combinations of low-molecular weight heparin or st and ard unfractionated heparin plus dihydroergotamine mesylate in the prevention of deep vein thrombosis in high-risk patients undergoing elective major abdominal surgery . Two hundred patients , with a mean age of 66.6 years and almost half with malignancy , were allocated to receive either 5,000 IU unfractionated heparin plus 0.5 mg dihydroergotamine mesylate twice daily or 1,500 IU low-molecular weight heparin plus 0.5 mg dihydroergotamine mesylate once daily together with one placebo injection per day . Treatment was commenced 2 hours preoperatively and continued for at least 7 days . The incidence of deep vein thrombosis , determined by radiolabelled fibrinogen uptake and phlebography , was 11 percent in the unfractionated heparin plus dihydroergotamine mesylate group and 11.4 percent in the low-molecular weight heparin and dihydroergotamine mesylate group . Neither these figures nor those for major proximal thrombi proved significantly different . Of the four parameters used to assess hemorrhagic complications , only the decrease in postoperative hemoglobin levels in the low-molecular weight and dihydroergotamine mesylate group reached statistical significance . These results indicate that once-daily prophylaxis with a combination of low-molecular weight heparin and dihydroergotamine is safe , effective , and convenient in high-risk patients undergoing major abdominal surgery BACKGROUND Dabigatran , which is administered in a fixed dose and does not require laboratory monitoring , may be suitable for extended treatment of venous thromboembolism . METHODS In two double-blind , r and omized trials , we compared dabigatran at a dose of 150 mg twice daily with warfarin ( active-control study ) or with placebo ( placebo-control study ) in patients with venous thromboembolism who had completed at least 3 initial months of therapy . RESULTS In the active-control study , recurrent venous thromboembolism occurred in 26 of 1430 patients in the dabigatran group ( 1.8 % ) and 18 of 1426 patients in the warfarin group ( 1.3 % ) ( hazard ratio with dabigatran , 1.44 ; 95 % confidence interval [ CI ] , 0.78 to 2.64 ; P=0.01 for noninferiority ) . Major bleeding occurred in 13 patients in the dabigatran group ( 0.9 % ) and 25 patients in the warfarin group ( 1.8 % ) ( hazard ratio , 0.52 ; 95 % CI , 0.27 to 1.02 ) . Major or clinical ly relevant bleeding was less frequent with dabigatran ( hazard ratio , 0.54 ; 95 % CI , 0.41 to 0.71 ) . Acute coronary syndromes occurred in 13 patients in the dabigatran group ( 0.9 % ) and 3 patients in the warfarin group ( 0.2 % ) ( P=0.02 ) . In the placebo-control study , recurrent venous thromboembolism occurred in 3 of 681 patients in the dabigatran group ( 0.4 % ) and 37 of 662 patients in the placebo group ( 5.6 % ) ( hazard ratio , 0.08 ; 95 % CI , 0.02 to 0.25 ; P<0.001 ) . Major bleeding occurred in 2 patients in the dabigatran group ( 0.3 % ) and 0 patients in the placebo group . Major or clinical ly relevant bleeding occurred in 36 patients in the dabigatran group ( 5.3 % ) and 12 patients in the placebo group ( 1.8 % ) ( hazard ratio , 2.92 ; 95 % CI , 1.52 to 5.60 ) . Acute coronary syndromes occurred in 1 patient each in the dabigatran and placebo groups . CONCLUSIONS Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinical ly relevant bleeding than warfarin but a higher risk than placebo . ( Funded by Boehringer Ingelheim ; RE-MEDY and RE-SONATE Clinical Trials.gov numbers , NCT00329238 and NCT00558259 , respectively . ) PURPOSE Venous thromboembolism ( VTE ) is common in cancer patients . Evidence has suggested that low molecular weight heparin ( LMWH ) might improve survival in patients with cancer by preventing both VTE and the progression of metastases . No trial in a single cancer type has been powered to demonstrate a clinical ly significant survival difference . The aim of this trial was to investigate this question in patients with lung cancer . PATIENTS AND METHODS We conducted a multicenter , open-label , r and omized trial to evaluate the addition of a primary prophylactic dose of LMWH for 24 weeks to st and ard treatment in patients with newly diagnosed lung cancer of any stage and histology . The primary outcome was 1-year survival . Secondary outcomes included metastasis-free survival , VTE-free survival , toxicity , and quality of life . RESULTS For this trial , 2,202 patients were r and omly assigned to the two treatment arms over 4 years . The trial did not reach its intended number of events for the primary analysis ( 2,047 deaths ) , and data were analyzed after 2,013 deaths after discussion with the independent data monitoring committee . There was no evidence of a difference in overall or metastasis-free survival between the two arms ( hazard ratio [ HR ] , 1.01 ; 95 % CI , 0.93 to 1.10 ; P = .814 ; and HR , 0.99 ; 95 % CI , 0.91 to 1.08 ; P = .864 , respectively ) . There was a reduction in the risk of VTE from 9.7 % to 5.5 % ( HR , 0.57 ; 95 % CI , 0.42 to 0.79 ; P = .001 ) in the LMWH arm and no difference in major bleeding events but evidence of an increase in the composite of major and clinical ly relevant nonmajor bleeding in the LMWH arm . CONCLUSION LMWH did not improve overall survival in the patients with lung cancer in this trial . A significant reduction in VTE is associated with an increase in clinical ly relevant nonmajor bleeding . Strategies to target those at greatest risk of VTE are warranted BACKGROUND For many patients with venous thromboembolism , secondary prevention with vitamin K antagonists is not extended beyond six months , since the risk of recurrence may be outweighed by the risk of major bleeding . METHODS In a double-blind , multicenter trial , we r and omly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran ( 24 mg ) or placebo , taken twice daily , for 18 months without monitoring of coagulation . At base line , bilateral ultrasonography of the legs and perfusion lung scanning were performed . RESULTS Data from 612 patients in the ximelagatran group and 611 in the placebo group were analyzed . The occurrence of the primary end point , symptomatic recurrent venous thromboembolism , was confirmed in 12 patients assigned to ximelagatran and 71 patients assigned to placebo ( hazard ratio , 0.16 ; 95 percent confidence interval , 0.09 to 0.30 ; P<0.001 ) . Death from any cause occurred in 6 patients in the ximelagatran group and 7 patients in the placebo group , and bleeding occurred in 134 patients and 111 patients , respectively ( hazard ratio , 1.19 ; 95 percent confidence interval , 0.93 to 1.53 ; P=0.17 ) . The incidence of major hemorrhage was low ( six events in the ximelagatran group and five in the placebo group ) , and none of these hemorrhages were fatal . The cumulative risk of a transient elevation of the alanine aminotransferase level to more than three times the upper limit of normal was 6.4 percent in the ximelagatran group , as compared with 1.2 percent in the placebo group ( P<0.001 ) . CONCLUSIONS Oral ximelagatran was superior to placebo for the extended prevention of venous thromboembolism . There was no significant increase in the frequency of bleeding complications , but there was an increase in the number of patients with a transient elevation in the alanine aminotransferase level Background Venous thromboembolism ( VTE ) occurs when blood clots in the leg , pelvic or other deep vein ( deep vein thrombosis ) with or without transport of the thrombus into the pulmonary arterial circulation ( pulmonary embolus ) . VTE is common in patients with cancer and is increased by surgery , chemotherapy , radiotherapy and disease progression . Low molecular weight heparin ( LMWH ) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect , by reduction in the incidence of metastases . The FRAGMATIC trial will assess the effect of adding dalteparin ( FRAGMIN ) , a type of LMWH , to st and ard treatment for patients with lung cancer . Methods / Design The study design is a r and omised multicentre phase III trial comparing st and ard treatment and st and ard treatment plus daily LMWH for 24 weeks in patients with lung cancer . Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma ( small cell or non-small cell ) within 6 weeks of r and omisation , be 18 or older , and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks . A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after r and omisation . Patients will be r and omised to one of the two treatment groups in a 1:1 ratio , st and ard treatment or st and ard treatment plus dalteparin . The primary outcome measure of the trial is overall survival . The secondary outcome measures include venous thrombotic event ( VTE ) free survival , serious adverse events ( SAEs ) , metastasis-free survival , toxicity , quality of life ( QoL ) , levels of breathlessness , anxiety and depression , cost effectiveness and cost utility . Trial registration Current Controlled Trials IS RCT The efficacy of defibrotide and calcium heparin in the prevention of Deep Vein Thrombosis ( DVT ) in gynecological surgery were compared in a r and omized study . Seventy patients c and i date to gynecological surgery ( for benign conditions ) and 50 c and i date to surgery for malignancies were r and omly allocated either to defibrotide ( 400 mg b.i.d . IM from the day before operation to the 7th postoperative day , n = 60 ) or to calcium heparin ( 5000 IU t.i.d . SC from the operation to the 7th postoperative day , n = 70 ) . The diagnosis of DVT was made with impedance plethysmography and if necessary confirmed with phlebography . No patient developed established DVT in either groups and no adverse reactions were observed . These results indicate that defibrotide may be considered as an alternative to heparin in the DVT prophylaxis in gynecological surgery We initiated a prospect i ve , partially r and omized trial of the effects of perioperative prophylactic mini-dose heparin on the incidence of clinical ly evident pulmonary emboli , intraoperative blood loss , blood transfusions , duration of postoperative pelvic drainage , and lymphocele formation in 68 consecutive patients undergoing radical retropubic prostatectomy . We treated 32 patients with mini-dose heparin and 36 without it . We detected pulmonary emboli in 4 ( 11 % ) patients not treated with mini-dose heparin and in none treated with heparin ( p = 0.052 ) . Anesthesiologists estimated a mean intraoperative blood loss of 2,152 cc in the heparinized patients compared with 1,886 cc in controls ( p = 0.2 ) . At a time when our policy was to replace all blood loss , we transfused a mean of 3.9 units to heparinized patients and 3.2 units to controls ( p = 0.1 ) . Persistent lymphatic drainage requiring more than six days of closed suction drainage occurred in 12 of 32 ( 38 % ) heparinized patients as compared with 4 of 36 ( 11 % ) controls ( p = 0.01 ) . We discontinued the study after 68 patients because of the morbidity associated with mini-dose heparin . Because of the associated morbidity we do not recommend the routine use of mini-dose heparin in patients undergoing radical prostatectomy 8021 Background : Efficacy of prophylaxis with fixed dose of warfarin or low molecular weight heparin ( LMWH ) for upper limb deep vein thrombosis ( UL-DVT ) related to central vein catheter ( CVC ) has been cl aim ed after open studies with limited sample size . The rate of bleeding in cancer patients receiving prolonged prophylaxis with LMWH is unclear . The aim of this study was to evaluate the efficacy and safety of the LMWH enoxaparin in the prevention of UL-DVT in cancer patients with CVC . METHODS Consecutive cancer patients with CVC for chemotherapy were included in a multicenter double-blind r and omized placebo-controlled study performed in 11 Italian centers . Enoxaparin , 40 mg once a day , or placebo were given subcutaneously for 6 weeks , starting 2 hours before the CVC insertion . The primary endpoint of the study was UL-DVT , as detected by venography ( CVC limb ) performed at 6 weeks and /or clinical ly overt pulmonary embolism confirmed by objective testing . The secondary endpoints of the study were death from thromboembolic disease and death from any cause at 3-month . The safety endpoint was major bleeding . RESULTS 385 patients were included in the study . 321 patients underwent venography ( 83.4 % ) . The primary efficacy outcome was assessed in 310 patients with adequate venography . Enoxaparin reduced the incidence of UL-DVT from 18.1 % ( 28/155 ) to 14.2 % ( 22/155 ) , a relative risk reduction of 21.4 % ( 95 % CI : 0.47 to 1.31 , p=0.35 ) . Two patients in the enoxaparin group ( 1.0 % ) and 6 patients in the placebo group ( 3.1 % ) had a symptomatic venous thromboembolism . No major bleeding occurred in both treatment groups . Minor bleeding occurred in 6.3 % of the patients ( 12/191 ) in the enoxaparin group and 3.6 % of the patients ( 7/194 ) in the placebo group . CONCLUSIONS Enoxaparin , at the dose of 40 mg daily , produced a 21 % non significant reduction in the incidence of CVC-related DVT in cancer patients . This dose was safe and well tolerated : this leaves open the option of increasing the dose of enoxaparin to optimize its efficacy in this clinical setting . No significant financial relationships to disclose BACKGROUND Various studies have been performed in general surgery patients comparing low molecular weight heparin ( LMWH ) with st and ard heparin ( SH ) for the prevention of postoperative deep vein thrombosis ( DVT ) , revealing contradicting results . Therefore , we have compared the efficacy and safety of a LMWH for the prevention of DVT after major general surgery . PATIENTS AND METHODS Patients received either 20 mg LMWH ( enoxaparin ) once daily , or 5,000 IU SH TID , starting preoperatively in a prospect i ve , r and omized , double-blind international multicenter trial . DVT was diagnosed using fibrinogen I 125 leg scanning . Major and minor bleeding were assessed clinical ly . RESULTS A total of 718 patients were r and omized to LMWH , and 709 patients to SH . DVT was detected in 58 LMWH-treated patients ( 8.1 % , 95 % confidence interval [ CI ] 6.2 % to 10.3 % ) and in 45 patients allocated to SH ( 6.3 % , 95 % CI 4.7 % to 8.4 % , P > 0.05 ) . Major bleeding complications occurred in 11 LMWH-treated patients ( 1.5 % , 95 % CI 0.8 % to 2.7 % ) and in 18 patients to whom st and ard heparin was administered ( 2.5 % , 95 % CI 1.5 % to 3.9 % , P > 0.05 ) . Four LMWH-treated patients ( 0.6 % ) required reoperation for bleeding as compared to 13 patients in the SH group ( 1.8 % , P = 0.03 ) . CONCLUSION This LMWH appeared as effective and safe as SH . In view of its more convenient way of administration , this LMWH might be preferred for thromboprophylaxis Background Low-molecular-weight heparin ( LMWH ) is recommended and commonly used for extended treatment of cancer-associated thrombosis ( CAT ) , but its superiority over warfarin has been demonstrated in only one r and omised study . We report here the rationale , design and a priori analysis plans of Comparison of Acute Treatments in Cancer Haemostasis ( CATCH ; NCT01130025 ) , a multinational , Phase III , open-label , r and omised controlled trial comparing tinzaparin with warfarin for extended treatment of CAT . Methods / Design The primary objective is to assess the efficacy of tinzaparin in preventing recurrent venous thromboembolism ( VTE ) in patients with active cancer and acute , symptomatic proximal deep vein thrombosis and /or pulmonary embolism . The secondary objectives are to determine : safety of tinzaparin given over 6 months ; clinical and laboratory markers for recurrent VTE and /or major bleeding ; 6-month overall mortality ; incidence and severity of post-thrombotic syndrome ; patient-reported quality of life ; and healthcare re source utilisation . Nine hundred patients are r and omised to receive tinzaparin 175 IU/kg once daily for 6 months or initial tinzaparin 175 IU/kg once daily for 5–10 days and dose-adjusted warfarin ( target INR 2.0–3.0 ) for 6 months . The primary composite outcome is time to recurrent VTE , including incidental VTE and fatal pulmonary embolism . All patients are followed up to 6 months or death , whichever comes sooner . Blinded adjudication will be performed for all reported VTE , bleeding events and causes of death . Efficacy will be analysed using central ly adjudicated results of all patients according to intention-to-treat analysis . An independent Data Safety Monitoring Board is review ing data at regular intervals and an interim analysis is planned after 450 patients have completed the study . Discussion The results will add significantly to the knowledge of the efficacy , safety and cost effectiveness of tinzaparin in the prevention of recurrent VTE in patients with cancer and thrombosis . Prospect i ve data will emerge on the clinical significance of incidental VTE and risk stratification in patients with CAT . Results on post-thrombotic syndrome , quality of life and healthcare re source utilisation will inform decision makers on how to secure better patient care . If tinzaparin is shown to be more effective than warfarin , CATCH will provide valuable confirmatory data to support the use of the LMWH tinzaparin for extended treatment of CAT BACKGROUND Deep vein thrombosis and subsequently pulmonary embolism are the most common causes of increased post-operative morbidity and mortality in patients with pelvic or abdominal cancer . Aim of the study was to evaluate variations in coagulative parameters induced by two accepted primary prophylaxis patterns : st and ardized low doses of unfractioned heparin ( UFH ) or single doses of low molecular weight heparin ( LMWH ) in cancer patients su bmi tted to radical retropubic prostatectomy . METHODS Fifty patients ( 45 - 75 yr ) were r and omly assigned two groups . Group 1 received UFH ( 5000 units s.c . x 3 daily ) ; group 2 received calcium nadroparin ( single daily dose of 0.3 ml s.c . ) . In both groups prophylaxis began preoperatively and was maintained throughout the entire hospital-stay . Blood cell , platelet count , coagulative system exploring tests , thrombotic molecular markers , and physiological inhibitors of coagulation were determined at baseline conditions and on the first and seventh day after surgery . RESULTS Preoperative values of fibrinogen , F1 + 2 fragment , TAT and D-dimer result ed over normal range in both groups . A significant increase of these markers was observed also during the post-operative period . PT , aPTT , ATIII , PC , total and free PS showed the most substantial changes on the 1st post operative day , though their values ranged within normal levels on the three sampling times . The levels of haemostatic markers demonstrated a baseline hypercoagulability , probably related to cancer and thrombin activation caused by prostatectomy . Despite this thrombophylic state , neither of the two groups presented symptomatic bleeding or thromboembolic complications . CONCLUSIONS These results prove that a single daily dose of nadroparin has been safe and efficient as a thrice-daily dose of UFH , with a better risk/benefit relationship Elevated levels of circulating tissue factor‐bearing microparticles ( TFMP ) have been associated with an increased risk of developing venous thromboembolism ( VTE ) in cancer patients . We performed a r and omized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP r and omized to enoxaparin or observation . The cumulative incidence of VTE at 2 months in the higher TFMP group r and omized to enoxaparin ( N = 23 ) was 5·6 % while the higher TFMP group observation arm ( N = 11 ) was 27·3 % ( Gray test P = 0·06 ) . The cumulative incidence of VTE in the low TFMP was 7·2 % ( N = 32 ) . No major haemorrhages were observed in the enoxaparin arm . The median survival for patients with higher levels of TFMP followed by observation was 11·8 months compared with 17·8 months on enoxaparin ( P = 0·58 ) . In a prospect i ve r and omized trial , increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE . Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP , with an overall rate of VTE similar in magnitude to the lower TFMP group Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Abstract Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical in patients at moderate to high risk of venous thromboembolism . Design Double blind r and omised placebo controlled trial . Setting 35 centres in eight countries . Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure , acute respiratory illness in the presence of chronic lung disease , or acute infectious or inflammatory disease and expected to remain in bed for at least four days . Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days . Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15 . Secondary outcomes were bleeding and death . Patients were followed up at one month . Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis ( 10 were not treated ) . 644 patients ( 75.9 % ) were available for the primary efficacy analysis . Venous thrombembolism was detected in 5.6 % ( 18/321 ) of patients treated with fondaparinux and 10.5 % ( 34/323 ) of patients given placebo , a relative risk reduction of 46.7 % ( 95 % confidence interval 7.7 % to 69.3 % ) . Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group ( P = 0.029 ) . Major bleeding occurred in one patient ( 0.2 % ) in each group . At the end of follow-up , 14 patients in the fondaparinux group ( 3.3 % ) and 25 in the placebo group ( 6.0 % ) had died . Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients . The frequency of major bleeding was similar for both fondaparinux and placebo treated patients A prospect i ve , r and omized , controlled clinical trial was performed comparing the antithrombotic efficacy of the low molecular weight heparin LMWH 21–23 , ( Braun ) with an unfractionated heparin in elective general surgical patients over an observation period of 7 postoperative days . A total of 230 patients were admitted : 103 ( group I ) received low molecular weight heparin and 100 ( group II ) low-dose unfractionated heparin treatment given subcutaneously . In group I 41 patients ( 46 % ) were operated on for malignant disease and in group II 54 patients ( 54 % ) . Due to the large amount of great abdominal procedures the intra- and perioperative application of hydroxyethyl starch was allowed for volume substitution . None of the patients died due to fatal pulmonary embolism . In group I four patients revealed positive 125I-labeled fibrinogen uptake ( 3.9 % ) ; two patients belonged to the hydroxyethyl starch subgroup . In group II five patients displayed a positive fibrinogen uptake ( 5 % ) ; two belonged to the hydroxyethyl starch subgroup . The results of the hemostaseological investigations ( e.g. , prothrombin time , activated partial thromboplastin time , thrombin clotting time , fibrinogen , antithrombin III , protein C , plasminogen , α2-antiplasmin , tissue-type plasminogen activator , plasminogen activator inhibitor ) revealed no statistically significant differences between groups I and II or their subgroups , although a tendency to prolonged clotting times was observed . The antifactor Xa activity values , however , displayed a statistically significant difference between the two groups ( P < 0.05 ) . The antifactor Xa activity measured up to 0.16 U/ml for the low molecular weight heparin ( group I ) and 0.05 U/ml for the unfractionated heparin ( group II ) in the postoperative period . Major bleeding complications were not encountered in this study . Fundamental for the low incidence of thrombosis , the additive administration of hydroxyethyl starch appeared in almost one-third of the patients in both study groups The Medical Patients with Enoxaparin ( MEDENOX ) trial was a r and omized , placebo-controlled study that defined the risk of venous thromboembolism ( VTE ) in acutely ill , immobilized , general medical patients and the efficacy of the low-molecular-weight heparin , enoxaparin , in preventing thrombosis . We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness ( heart failure , respiratory failure , infection , rheumatic disorder and inflammatory bowel disease ) and pre-defined risk factors ( chronic heart and chronic respiratory failure , age , immobility , previous VTE and cancer ) . The primary outcome was the occurrence of documented VTE between days 1 and 14 . The relative risk reduction [ 95 % confidence intervals ( CI ) ] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were : acute heart failure , 0.29 ( 95 % CI , 0.10–0.84 ) ; acute respiratory failure , 0.25 ( 95 % CI , 0.10–0.65 ) ; acute infectious disease , 0.28 ( 95 % CI , 0.09–0.81 ) ; and acute rheumatic disorder , 0.48 ( 95 % CI , 0.11–2.16 ) . The relative risk reduction for VTE in the pre-defined risk factor subgroups were : chronic heart failure , 0.26 ( 95 % CI , 0.08–0.92 ) ; chronic respiratory failure , 0.26 ( 95 % CI , 0.10–0.68 ) ; age , 0.22 ( 95 % CI , 0.09–0.51 ) ; immobility , 0.53 ( 95 % CI , 0.14–1.72 ) ; previous VTE , 0.49 ( 95 % CI , 0.15–1.68 ) ; and cancer , 0.50 ( 95 % CI , 0.14–1.72 ) . The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients External pneumatic compression ( EPC ) devices prevent lower extremity deep venous thrombosis ( DVT ) by reducing stasis . There is a widely held belief that they also enhance endogenous fibrinolysis ; however , recent studies of tissue plasminogen activator ( the primary activator of fibrinolysis ) and plasminogen activator inhibitor-1 ( the primary inhibitor of fibrinolysis ) failed to confirm this . The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator ( uPA ) , a second activator of fibrinolysis . This was a prospect i ve trial in which 44 subjects who underwent major abdominal surgery were r and omized to receive unfractionated heparin injections , thigh-length sequential EPC devices , or both for DVT prophylaxis . Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge . Venous blood sample s were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels . Sample s were collected the day before surgery , after induction of anesthesia but before surgical incision , and on postoperative days 1 , 3 , and 5 . uPA levels ( ng/mL ) were measured with an enzyme-linked immunoassay . Baseline uPA levels ( 0.41 to 0.56 ng/mL ; P > .05 , analysis of variance with repeated measures ) were similar among the three groups . uPA levels did not change after surgery in systemic or regional blood sample s in any group . There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point ( P > .05 , analysis of variance with repeated measures ) . Enhancement of fibrinolysis with EPC devices remains unproven ; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis Postoperative thromboembolic complications do present an underestimated problem whenever their detection simply relies upon individual clinical judgement . Major abdominal operations are at increased risk of pulmonary embolism ( PE ) and deep vein thrombosis ( DVT ) , mostly in advanced age , overweight subject , and in patients with cardiac or malignant diseases , or with previous venous diseases . Such patients may benefit from a peri- and postoperative prophylaxis with chemical or mechanical procedures , as a recent meta- analysis seems to suggest . In our experience , a r and omized , multicentric clinical trial with defibrotide ( DF ) versus calcium-heparin ( CH ) was realized with the aim of evaluating their effectiveness and side effects in the prophylaxis of PE and DVT after major abdominal surgery ; 1296 patients were r and omly assigned to i.v . DF ( 400 mg . ) or subcutaneous CH ( 0.2 ml . = 5000 U.I. ) given one hour prior to operation and twice daily for seven days postoperatively . Definitive evaluation was carried out on 1212 patients ( 610 patients in DF and 602 in CH group , respectively ) who completed the prophylaxis and monitoring schedule acceptably . One PE ( 0.16 % ) and 38 DVT ( 6.2 % ) were detected in DF group while 2 PE ( 0.33 % ) and 40 DVT ( 6.6 % ) were reported in CH treated patients . Post-operative blood loss was 578 + /- 150 cc . ( median + /- S.E.M. ) in DF group and 604 + /- 123 in CH group ( p = n.s . ) . Wound hematoma was observed in 69 patients ( 5.7 % ) : 20 ( 3.2 % ) in DF and 49 ( 8.1 % ) in CH group of patients ( CHI-Square = 12.44 ; p = 0.0005 ) ; a significant post-operative decrease of RBC , WBC , Platelet count , and Fibrinogen was computed in both groups ( p less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS INTRODUCTION Venous thromboembolism ( VTE ) in cancer patients is an increasingly frequent clinical problem . The overall impact of VTE on cancer patients can be considerable . Targeted patient selection by identifying patients with clinical ly significant recurrent VTE may have wider health economic benefits whilst reducing patient risk through over-treatment . In the UK , dalteparin is one licensed anticoagulant for the extended treatment and prevention of recurrence of VTE in cancer patients . Rivaroxaban is a highly selective direct Factor Xa inhibitor with oral bioavailability . AIM To assess VTE recurrence in selected cancer patients at risk of recurrence of VTE treated with rivaroxaban or dalteparin . The secondary objectives include safety , acceptability , biomarker identification and health economics . MATERIAL S AND METHODS Select-d is a prospect i ve , r and omised , open label , multicentre pilot trial comparing dalteparin ( 200 IU/kg daily subcutaneously for 1 month and 150 IU/kg months 2 - 6 ) ; and rivaroxaban ( 15 mg orally twice daily for 3 weeks and 20 mg once daily for 6 months in total ) for cancer patients with VTE - symptomatic and incidental pulmonary embolism (P)E or symptomatic lower limb proximal deep vein thrombosis ( DVT ) - with a second placebo-controlled r and omisation ( rivaroxaban vs placebo ) comparing the duration of therapy ( 6 vs 12 months ) in all patients with PE and those with a DVT who are residual vein thrombosis ( RVT ) positive . 70 % of DVT patients are estimated to be RVT positive after initial treatment . 530 patients are being recruited toprovide reliable estimates of the primary outcome ( VTE recurrence rates ) to within the 95 % confidence interval of 8 % assuming VTE rates are 10 % at six months . RESULTS As of 1st December 2015 , 264 patients have been recruited from 61 open sites across the UK . Preliminary data indicate that the majority of patients presented with solid tumours ( 98 % ) , ranging from early or locally advanced ( 41 % ) to metastatic disease ( 57 % ) , and primarily comprising colorectal , lung , and breast malignancies . Only a small number of select-d patients presented with haematological malignancies ( 2 % ) , which included ; leukaemia , myeloma and lymphoma . Over half of the select-d patients had an incidental PE ( 54 % ) ; the remainder had symptomatic PE or DVT ( 46 % ) . The median number of hours on anticoagulation prior to starting select-d r and omised treatment was 48 hours . CONCLUSIONS select-d is the first r and omised trial for treatment of VTE , investigating the direct oral anticoagulants vs a low molecular weight heparin in patients with cancer . The results will support optimal treatment for this key patient group and are eagerly awaited PURPOSE In this multicenter , r and omized , placebo-controlled clinical trial , we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter ( CVC ) -associated thrombosis in patients with cancer . PATIENTS AND METHODS Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were r and omly assigned to receive warfarin 1 mg or placebo . RESULTS There were 11 ( 4.3 % ) symptomatic CVC-associated thromboses among 255 patients , with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily ( six of 130 patients ; 4.6 % ) and patients taking placebo ( five of 125 patients ; 4.0 % ; hazard ratio , 1.20 ; 95 % CI , 0.37 to 3.94 ) . Warfarin had no effect on CVC life span ( 84 days v 63 days in control and warfarin groups , respectively ; 95 % confidence limit , -16 to 55 days ; P = .09 ) , and it did not affect the number of premature CVC removals ( 23.2 % v 25.4 % in control and warfarin groups , respectively ; 95 % confidence limit of difference -8.34 to 12.71 ; P = .68 ) or the frequency of major bleeding episodes ( 2 % v 0 % in control and warfarin groups , respectively ; P = .5 , Fisher 's exact test ) . CONCLUSION Symptomatic CVC-associated thrombosis in patients with cancer , although significant , is less common than previously reported . In this study , the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer . However , the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively Deep vein thrombosis ( DVT ) is reported to be common among patients undergoing surgery for colorectal cancer . This r and omized controlled trial was aim ed to determine the efficacy of low molecular-weight heparin in the prophylaxis of DVT in this high-risk group and was truncated early in view of an unexpectedly low incidence of DVT . Between March 2002 and January 2004 , a total of 99 patients with colorectal cancer - selected for surgery in the lithotomy position - were r and omized before surgery to either receive dalteparin or no drug ( 51 and 48 patients , respectively ) during the perioperative period . Duplex ultrasonography was performed before and after the surgery . We also looked for distal venous thrombosis , pulmonary embolism , hemorrhage and any mortality . No episode of DVT occurred in either the drug arm or the observation arm . There was no death following surgery . The incidence of DVT in Indian patients operated for colorectal cancer in the lithotomy position was negligible The incidences of fatal pulmonary embolism and death in surgical patients receiving low-molecular-weight heparin thromboprophylaxis have not been previously determined in large , adequately design ed clinical trials and information on the relative efficacy and safety of unfractionated and low-molecular-weight heparin in preventing these clinical endpoints is not available . In a double-blind study , 23078 surgical patients r and omly received the low-molecular-weight heparin , certoparin ( 3000 anti Xa IU ) subcutaneously once-daily , or unfractionated heparin ( 5000 IU ) subcutaneously three-times daily , for a minimum of 5 days . The primary outcome measure , autopsy-proven fatal pulmonary embolism recorded up to 14 days after the end of prophylaxis , occurred in 0.152 % ( 95 % confidence interval ( CI ) 0.10 , 0.20 % ; 35 of 23078 patients ) of cases , with no significant difference between the certoparin-treated patients ( 0.147 % ( 95 % CI 0.077 , 0.217 % ; 17 of 11542 patients ) and patients treated with unfractionated heparin ( 0.156 % ( 95 % CI 0.084 , 0.228 % ; 18 of 11,536 patients , P=0.868 ) . The autopsy rate was 70.2 % . Comparing mortality , there was no significant difference between the groups ( 1 .44 % [ 166 of 11542 certoparin patients ] versus 1.27 % [ 146 of 11536 unfractionated heparin patients ] ; P=0.279 ) . The safety profiles of both treatment groups were similar . Once-daily certoparin and three-times daily unfractionated heparin are equally effective and safe in reducing fatal pulmonary embolism and death to low levels in surgical patients and mirror the findings of comparative efficacy studies using surrogate endpoints Recent studies suggest that low molecular weight heparin ( LMW heparin ) therapy in malignancy may improve cancer survival following surgical resection . We studied prospect ively whether cancer mortality during follow-up in women with previously untreated breast , and pelvic cancer is reduced in those who r and omly received LMW heparin ( Certoparin ) compared to patients given unfractionated heparin ( UF heparin ) for thrombosis prophylaxis during primary surgery . In a prospect i ve , r and omized , double-blind clinical trial , 160 patients received Certoparin and 164 UF heparin until post-operatively day 7 . Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients . Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days ( P=0 . 0066 ) but not thereafter when analysis was performed on all cancer cell types combined . In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer . However , in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days . Thus , breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery . These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH ( compared to UFH ) given for DVT prophylaxis in the post-operative period . An effect of UFH on disease outcome is not excluded . Further definitive trials of LMWH vs. placebo for cancer outcome ( rather then DVT ) using doses and schedules that may be more optimal are indicated INTRODUCTION External pneumatic compression ( EPC ) devices prevent lower extremity deep venous thrombosis by increasing venous flow and thereby reducing stasis . Early studies suggested that they also enhance systemic fibrinolytic activity and thus prevent thrombus formation ; more recent studies have been conflicting . The hypothesis of this study was that EPC devices enhance systemic fibrinolysis or reduce postoperative fibrinolytic impairment in patients undergoing abdominal surgical procedures . METHODS Each of 48 patients ( 98 % male ; mean age , 67 years ) undergoing major intra-abdominal surgical procedures ( 36 bowel procedures , 12 aortic reconstructions ) was prospect ively r and omized to one of three treatments for deep venous thrombosis prophylaxis : subcutaneous heparin injections ( HEP group ) , use of a thigh-length sequential EPC device ( EPC group ) , or both ( HEP + EPC group ) . Antecubital venous sample s were collected for measurement of systemic fibrinolytic activity on the day before surgery , after induction of anesthesia but before prophylaxis was initiated , and on postoperative days 1 , 3 , and 5 . Fibrinolysis was assessed through measurement of the activities of the rate limiting fibrinolytic activator , tissue plasminogen activator , and its inhibitor plasminogen activator inhibitor-1 with amidolytic methods . RESULTS On the day before surgery , plasminogen activator inhibitor-1 activity was elevated in all groups in comparison with that in age-matched and sex-matched controls ( 20.3 + /- 0.6 AU/mL ) . In the HEP group , plasminogen activator inhibitor-1 activity was further elevated above the value for the day before surgery on postoperative day 1 ( 28.5 + /- 4.3 AU/mL ; P = .04 ) and postoperative day 3 ( 25.1 + /- 1.9 AU/mL ; P = .07 ) . No significant decrease in plasminogen activator inhibitor-1 activity occurred in either group treated with EPC devices in comparison with the HEP group at any time . There were no changes in tissue plasminogen activator activity postoperatively in the HEP group and no significant increases in either EPC group at any point . CONCLUSIONS Reduced systemic fibrinolytic activity ( " fibrinolytic shutdown " ) occurred in these patients after abdominal surgery ; it was manifested as increased plasminogen activator inhibitor-1 activity . EPC devices did not enhance systemic fibrinolysis or prevent postoperative shutdown either by decreasing plasminogen activator inhibitor-1 activity or by increasing tissue plasminogen activator activity . These data suggest that EPC devices do not prevent deep venous thrombosis by fibrinolytic enhancement ; effective prophylaxis is achieved only when the devices are used in a manner that reduces lower extremity venous stasis Objective : To compare the efficacy and safety of antithrombotic prophylaxis given for 1 week or 4 weeks in patients undergoing laparoscopic surgery for colorectal cancer . Background : Extending antithrombotic prophylaxis beyond 1 week reduces the incidence of venous thromboembolism ( VTE ) after open abdominal surgery for cancer . Methods : In consecutive patients who underwent laparoscopic surgery for colorectal cancer , complete compression ultrasonography of the lower limbs was performed after 8 ± 2 days of antithrombotic prophylaxis . Patients with no evidence of VTE were r and omized to short ( heparin withdrawal ) or to extended ( heparin continued for 3 additional weeks ) prophylaxis . Complete compression ultrasonography was repeated at day 28 ± 2 after surgery by investigators blinded to treatment allocation . The primary outcome of the study was the composite of symptomatic and ultrasonography-detected VTE at day 28 ± 2 after surgery . Results : Overall , 301 patients were evaluated for inclusion in the study and 225 were r and omized . VTE occurred in 11 of 113 patients r and omized to short ( 9.7 % ) and in none of the 112 patients r and omized to extended heparin prophylaxis ( P = 0.001 ) . The incidence of VTE at 3 months was 9.7 % and 0.9 % in patients r and omized to short or to extended heparin prophylaxis , respectively ( relative risk reduction : 91 % , 95 % confidence interval : 30%–99 % ; P = 0.005 ) . The rate of bleeding was similar in the 2 treatment groups . Two patients died during the study period , 1 in each treatment group . Conclusions : After laparoscopic surgery for colorectal cancer , extended antithrombotic prophylaxis is safe and reduces the risk for VTE as compared with 1-week prophylaxis ( NCT01589146 ) Patients with severe renal insufficiency ( sRI ) have been suggested to be at an increased risk of bleeding with low-molecular-weight heparins ( LMWH ) . We aim ed at assessing the benefits and risks of certoparin in comparison to unfractionated heparin ( UFH ) in these patients . In this subgroup analysis of the CERTIFY trial , acutely ill , non-surgical patients ≥70 years received certoparin 3,000U aXa o.d . or UFH 5,000 IU t.i.d . One hundred eighty-nine patients had a glomerular filtration rate ( GFR ) ≤30 ml/min/1.73 m2 , 3,050 patients served as controls . Patients with sRI had a mean age of 85.9 ± 6.6 years ( controls 78.4 ± 6.0 ) and were treated for a mean of 9.3 ± 3.7 days ( 9.9 ± 4.3 ) . Thromboembolic event rates were comparable ( 4.55 vs. 4.21 % ; OR1.08 ; 95%CI 0.5 - 2.37 ) but bleeding was increased in sRI ( 9.52 vs. 3.54 % ; OR2.87 ; 95%CI 1.70 - 4.83 ) . The incidence of the combined end-point of proximal DVT , symptomatic non-fatal PE and VTE related death was 6.49 % with certoparin and 2.60 % with UFH ( OR2.60 ; 95%CI 0.49 - 13.85 ) . There was a decrease in total bleeding with certoparin ( OR0.33 ; 95%CI 0.11 - 0.97 ) , which was non-significant in patients with GFR > 30 ml/min/1.73 m2 . In two multivariable regression models certoparin and immobilisation < 10 days were associated with less bleeding while a GFR ≤30 ml/min/1.73 m2 was associated with increased bleeding . A total of 11.3 % of certoparin- and 18.5 % of UFH-treated patients experienced serious adverse events ( 14.8 in patients with a GFR ≤30 vs. 5.6 % vs. > 30 ml/min/1.73 m2 ) . In conclusion , certoparin 3,000U anti Xa o.d . was as efficacious as 5,000 IU UFH t.i.d . in patients with sRI but had a reduced risk of bleeding PURPOSE In patients with myeloma , thalidomide significantly improves outcomes but increases the risk of thromboembolic events . In this r and omized , open-label , multicenter trial , we compared aspirin ( ASA ) or fixed low-dose warfarin ( WAR ) versus low molecular weight heparin ( LMWH ) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens . PATIENTS AND METHODS A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA ( 100 mg/d ) , WAR ( 1.25 mg/d ) , or LMWH ( enoxaparin 40 mg/d ) . A composite primary end point included serious thromboembolic events , acute cardiovascular events , or sudden deaths during the first 6 months of treatment . RESULTS Of 659 analyzed patients , 43 ( 6.5 % ) had serious thromboembolic events , acute cardiovascular events , or sudden death during the first 6 months ( 6.4 % in the ASA group , 8.2 % in the WAR group , and 5.0 % in the LMWH group ) . Compared with LMWH , the absolute differences were + 1.3 % ( 95 % CI , -3.0 % to 5.7 % ; P = .544 ) in the ASA group and + 3.2 % ( 95 % CI , -1.5 % to 7.8 % ; P = .183 ) in the WAR group . The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib . Three major ( 0.5 % ) and 10 minor ( 1.5 % ) bleeding episodes were recorded . CONCLUSION In patients with myeloma treated with thalidomide-based regimens , ASA and WAR showed similar efficacy in reducing serious thromboembolic events , acute cardiovascular events , and sudden deaths compared with LMWH , except in elderly patients where WAR showed less efficacy than LMWH The efficacy and safety of a low‐molecular‐weight ( LMW ) heparin fraction in preventing postoperative venous thrombo‐embolism , was assessed in a double blind , r and omly allocated trial , and in an ‘ open ’ study . of 395 patients included in the double blind trial , 199 received unfractionated ( UF ) calcium heparin , and 196 the LMW heparin fraction . The data were analysed on an ‘ intention to treat ’ basis . The two groups were well matched for risk factors which could predispose to the development of venous thrombosis . Fifteen ( 7.5 per cent ) of one hundred and ninety‐nine patients receiving UF heparin , and five ( 2.5 per cent ) of one hundred and ninety‐six patients in the LMW heparin group developed DVT ( P<0.05 ) . There was no significant difference between the two groups in terms of excessive incisional or total blood loss during surgery , postoperative drainage or wound haematoma formation . Of 910 patients included in the ‘ open ’ study who received a single injection of LMW heparin every day , 30 ( 3.2 per cent ) died during the postoperative period ; in none of the autopsied patients were pulmonary emboli detected . Thirty‐one ( 3.4 per cent ) patients developed isotopic DVT ; twentyseven ( 2.9 per cent ) were receiving prophylaxis at the time the DVT was diagnosed . Thirty‐six ( 3.9 per cent ) patients developed wound haematoma ; twenty‐five ( 12.4 per cent ) of those were in the two hundred and one undergoing surgery for gynaecological conditions , and eleven ( 1.5 per cent ) in the seven hundred and nine patients having general abdominal surgery . This difference is statistically significant ( P<0.001 ) . The results of a double blind trial indicate that a single daily injection of 1850 APTT units ( 7500 antifactor X a units ) of a LMW heparin is more effective than 10000 APTT units of commercially available UF heparin in preventing postoperative DVT . The findings of the ‘ open ’ study suggest that this regimen also provides an effective prophylaxis against postoperative major pulmonary embolism Eighty patients undergoing pelvic or abdominal surgery for cancer were r and omized in two groups for prevention of postoperative thromboembolism : 40 patients received a 15,000 IU day-1 Calciparine prophylaxis and 40 patients a 5000 anti-Xa U/d Fragmin prophylaxis for 10 days . In the Calciparine group , two patients ( 5 % ) developed postoperative pulmonary embolism but none developed it in the Fragmin group . Two patients in the Fragmin group ( 5 % ) developed isotopic DVT , which was not confirmed by phlebography . There was no deep vein thrombosis of the lower limbs in the two groups . Important postoperative bleeding ( one patient in the Calciparine group and two patients in the Fragmin group ) was similar in both groups . Moderate and minor bleeding were significantly lower in the Fragmin group . Haemoglobin and haematocrit changes , total blood loss and transfusion requirements were not different in both groups . It is concluded that , over a 10-day period , one daily 5000 U Fragmin prophylaxis was as effective and safe as three daily 5000 IU Calciparine injections OBJECTIVE The aim of this study was to compare the efficacy of low molecular weight heparin ( LMWH ) combined with graduated compression stockings ( GCS ) with GCS alone as prophylactic measures for venous thromboembolism ( VTE ) in post-operative patients with gynecologic cancer . METHODS Patients diagnosed with gynecologic cancer undergoing primary major surgery between 2010 and 2011 in our institute were r and omized to receive LMWH+GCS or GCS as VTE prophylaxis post-operatively . RESULTS Altogether 247 patients were enrolled . The incidence of VTE in patients treated with LMWH + GCS was significantly lower than that in patients using GCS alone ( 0.8 % Vs . 8.1 % , P = 0.01 ) . There were no severe bleeding complications in the patients with prophylactic use of LMWH and the occurrence rate of wound dehiscence was comparable between the two groups ( P > 0.05 ) . Multivariable logistic regression analysis revealed that age over 60 years ( P = 0.015 ) , duration of operation over 3 hours ( P = 0.04 ) and without prophylactic use of LMWH ( P = 0.02 ) were independent risk factors for VTE . CONCLUSIONS Dual prophylaxis with LMWH and GCS should be recommended for gynecologic cancer patients undergoing major surgery for its better efficacy than GCS . Prophylactic use of LMWH is safe and convenient . Patients with older age and prolonged operation time are at highest risk of developing VTE post-operatively CONTEXT Venous thromboembolism ( VTE ) is the most frequent complication following craniotomy for brain tumors . At Brigham and Women 's Hospital , VTE after craniotomy for brain tumor is the leading cause of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) among patients hospitalized for conditions other than VTE . OBJECTIVE To minimize VTE among patients undergoing craniotomy for brain tumor . DESIGN R and omized , prospect i ve , double-blind clinical trial . SETTING Brigham and Women 's Hospital . PATIENTS One hundred fifty patients undergoing craniotomy for brain tumor r and omized to enoxaparin , 40 mg/d , vs heparin , 5,000 U bid , with all patients receiving graduated compression stockings and intermittent pneumatic compression . MAIN OUTCOME MEASURES The rate of DVT detected by venous ultrasonography prior to hospital discharge . RESULTS Symptomatic DVT or PE developed in none of the patients . The overall rate of asymptomatic VTE was 9.3 % , with no significant difference in the rates between the two prophylaxis groups . Ten of the 14 patients identified with VTE had thrombus limited to the deep veins of the calf . CONCLUSIONS Enoxaparin , 40 mg/d , or unfractionated heparin , 5,000 U bid , in combination with graduated compression stockings , intermittent pneumatic compression , and predischarge surveillance venous ultrasonography of the legs , result ed in 150 consecutive patients without symptomatic VTE . The low 9.3 % frequency of asymptomatic VTE comprised mostly isolated calf DVT . Therefore , this comprehensive , multimodality approach to VTE prophylaxis achieved excellent efficacy and safety In a double blind , r and omized trial the hemorrhagic complications of a reduced dose of low molecular weight heparin ( LMWH ) ( Fragmin , KabiPharmacia ) were compared to those of the conventional dose of unfractionated heparin ( UH ) . 2500 anti‐XaU of LMWH was given once daily and UH in a dose of 5000 anti‐XaU twice daily . During a one year period 141 patients undergoing gynecological surgery were included in this study . The patients were examined clinical ly for hematomas and for deep venous thrombosis ( DVT ) on the third and fifth day . Venography was performed when DVT was suspected . No patients developed clinical DVT . One woman in the LMWH group had pulmonary embolism 3 days after the prophylaxis was stopped . Two women in the LMWH group died , one from a stroke on day 2 , one from cancer on day 39 . There was no significant difference in serious bleeding complications between the two regimens , 20 % in the LMWH group and 14 % in the UH group . Even with the reduced dose of LMWH the mean plasma concentration of heparin in the LMWH group was higher ( mean 0.14 anti‐XaU/ml ) than in the UH group ( 0.029 anti‐XaUlml ) 3 hours after injection on the 2nd postoperative day . A reduced dose of LMWH ( 2500 anti XaU once daily ) does not cause more bleeding complications than the conventional heparin rcgimen to prevent thrombosis , as was the case in our previous study with 5000 anti Xa17 of LMWH once daily BACKGROUND Patients with venous thromboembolism and cancer have a substantial risk of recurrent venous thromboembolism and bleeding during anticoagulant therapy . Although monotherapy with low-molecular-weight heparin is recommended in these patients , in clinical practice many patients with venous thromboembolism and cancer do not receive this treatment . We aim ed to assess the efficacy and safety of a single-drug regimen with oral rivaroxaban compared with enoxaparin followed by vitamin K antagonists , in the subgroup of patients with cancer enrolled in the EINSTEIN-DVT and EINSTEIN-PE r and omised controlled trials . METHODS We did a subgroup analysis of patients with active cancer ( either at baseline or diagnosed during the study ) , a history of cancer , or no cancer who were enrolled in the EINSTEIN-DVT and EINSTEIN-PE trials . Eligible patients with deep-vein thrombosis ( EINSTEIN-DVT ) or pulmonary embolism ( EINSTEIN-PE ) were r and omly assigned in a 1:1 ratio to receive rivaroxaban ( 15 mg twice daily for 21 days , followed by 20 mg once daily ) or st and ard therapy ( enoxaparin 1·0 mg/kg twice daily and warfarin or acenocoumarol ; international normalised ratio 2·0 - 3·0 ) . R and omisation with a computerised voice-response system was stratified according to country and intended treatment duration ( 3 , 6 , or 12 months ) . The prespecified primary efficacy and safety outcomes of both the trials and this sub analysis were symptomatic recurrent venous thromboembolism and clinical ly relevant bleeding , respectively . We did efficacy and mortality analyses in the intention-to-treat population , and bleeding analyses for time spent receiving treatment plus 2 days in the safety population ( all patients who received at least one dose of study drug ) . The EINSTEIN-DVT and EINSTEIN-PE studies are registered at Clinical Trials.gov , numbers NCT00440193 and NCT00439777 . FINDINGS In patients with active cancer ( diagnosed at baseline or during treatment ) , recurrent venous thromboembolism occurred in 16 ( 5 % ) of 354 patients allocated to rivaroxaban and 20 ( 7 % ) of 301 patients allocated to enoxaparin and vitamin K antagonist ( hazard ratio [ HR ] 0·67 , 95 % CI 0·35 to 1·30 ) . Clinical ly relevant bleeding occurred in 48 ( 14 % ) of 353 patients receiving rivaroxaban and in 49 ( 16 % ) of 298 patients receiving st and ard therapy ( HR 0·80 , 95 % CI 0·54 to 1·20 ) . Major bleeding occurred in eight ( 2 % ) of 353 patients receiving rivaroxaban and in 15 ( 5 % ) of 298 patients receiving st and ard therapy ( HR 0·42 , 95 % CI 0·18 to 0·99 ) . The overall frequency of recurrent venous thromboembolism in patients with only a history of cancer ( five [ 2 % ] of 233 patients in the rivaroxaban group vs five [ 2 % ] of 236 in the st and ard therapy group ; HR 0·98 , 95 % CI 0·28 - 3·43 ) was similar to that of patients without cancer ( 65 [ 2 % ] of 3563 vs 70 [ 2 % ] of 3594 , respectively ; HR 0·93 , 95 % CI 0·66 - 1·30 ) , but the frequency was increased in patients with active cancer at baseline ( six [ 2 % ] of 258 vs eight [ 4 % ] of 204 , respectively ; HR 0·62 , 95 % CI 0·21 - 1·79 ) and most markedly increased in patients whose diagnosis of cancer was made during the study ( ten [ 10 % ] of 96 vs 12 [ 12 % ] of 97 , respectively ; HR 0·80 , 95 % CI 0·34 - 1·88 ) . The overall frequency of major bleeding in patients with only a history of cancer ( one [ < 1 % ] patient in the rivaroxaban group vs four [ 2 % ] patients in the st and ard therapy group ; HR 0·23 , 95 % CI 0·03 - 2·06 ) was similar to that of patients without cancer ( 31 [ 1 % ] vs 53 [ 1 % ] , respectively ; HR 0·58 , 95 % CI 0·37 - 0·91 ) , but was increased in patients with active cancer at baseline ( five [ 2 % ] vs eight [ 4 % ] , respectively ; HR 0·47 , 95 % CI 0·15 - 1·45 ) and was highest in those with cancer diagnosed during the study ( three [ 3 % ] vs seven [ 7 % ] , respectively ; HR 0·33 , 95 % CI 0·08 - 1·31 ) . INTERPRETATION In patients with active cancer and venous thromboembolism , rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism and reduced the number major bleeding events compared with treatment with enoxaparin and a vitamin K antagonist , although there was no difference between groups for clinical ly relevant bleeding . Based on these results , a head-to-head comparison of rivaroxaban with long-term low-molecular-weight heparin in patients with cancer is warranted . FUNDING Bayer HealthCare Pharmaceuticals and Janssen Research & Development Perioperative anticoagulant prophylaxis for postoperative venous thromboembolism ( VTE ) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding . Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence . In other clinical indications , low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively , with the advantage of no bleeding enhancement during surgery . Therefore , we performed a multicentre , r and omized , double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin ( LMWH ) , nadroparin , initiated postoperatively , to graduated compression stockings in the prevention of VTE . Deep-vein thrombosis was detected by m and atory venography . Bleeding was determined according to pre-defined objective criteria for major and minor episodes . An adequate bilateral venogram was obtained in 166 of 241 LMWH patients ( 68.9 % ) and 179 of 244 control patients ( 73.4 % ) . A total of 31 of 166 LMWH patients ( 18.7 % ) and 47 of 179 controls patients ( 26.3 ) had VTE up to Day 10 postoperatively ( p = 0.047 ) . The relative risk reduction ( RRR ) was 28.9 % . The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9 % and 11.5 % for the two groups , respectively ( RRR : 40.2 % ; p = 0.065 ) . Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group ( 13.7 % ) and 51 of 244 control patients ( 20.9 % ; RRR 34.5 % ; p = 0.018 ) . The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8 % and 10.2 % for the two groups , respectively , giving a RRR of 43.3 % ; p = 0.36 . Major bleeding complications , during the treatment period , occurred in six low molecular weight heparin treated patients ( 2.5 % ) and in two control patients ( 0.8 % ) ; p = 0.87 . A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period ( 22 versus 10 ; p = 0.026 ) . However , none of these deaths was judged by a blinded adjudication committee to be related to the study drug . In conclusion , this study demonstrates that the low molecular weight heparin , nadroparin , added to graduated compression stockings results in a clinical ly significant decrease in VTE without inducing any significant increase of major bleeding A total of 1290 patients were enrolled in a r and omized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin , Logiparin ® , in the prevention of deep vein thrombosis ( DVT ) in general surgery . Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT . Patients were r and omized to receive unfractionated heparin ( UH ) 5000 units b.d . , Logiparin 2500 units daily or Logiparin 3500 units daily . Each treatment was given subcutaneously 2h before surgery and continued for 7–10 days . Daily 125I‐labelled fibrinogen uptake tests ( FUTs ) were performed from day 2 to day 7 to detect DVT , and phleboangiography was used to confirm the diagnosis . The wound was examined on a daily basis to check for haematoma formation , and all patients were followed up for 1 month after operation . All three treatment arms were well matched for age , sex , weight , diagnosis and type of operation performed . The three major inclusion criteria in the trial were malignancy , age over 60 years and a history of varicose veins . Positive FUTs ( UH=4·2 per cent , Logiparin 2500 units daily = 7·9 per cent , Logiparin 3500 units daily = 3·7 per cent ) and positive angiograms ( UH=3·0 per cent , Logiparin 2500 units daily = 5·6 per cent , Logiparin 3500 units daily = 2·3 per cent ) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups . The rates of major complications ( severe haemorrhage , death , pulmonary embolism , reintervention ) were similar in the three groups Objective : To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery . Background : Venous thromboembolism is an important complication following major abdominal surgery . Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity . Methods : In this double-blind noninferiority trial , adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively , for 7 to 10 days . Patients underwent bilateral leg venography between 7 and 11 days postsurgery . The primary efficacy end point was the composite of any deep vein thrombosis , nonfatal pulmonary embolism , or all-cause death . The primary safety outcome was bleeding . Both were independently adjudicated . Results : In total , 4413 patients were r and omized ; 3030 ( 1499 in the enoxaparin and 1531 in the semuloparin groups ) were evaluable for the primary efficacy end point , which occurred in 97 patients ( 6.3 % ) in the semuloparin group and 82 patients ( 5.5 % ) in the enoxaparin group [ odds ratio ( OR ) = 1.16 , 95 % confidence interval ( CI ) : 0.84–1.59 ] . On the basis of a noninferiority margin of 1.25 , postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin . Major bleeding occurred in 63 of 2175 patients ( 2.9 % ) in the semuloparin group and 98 of 2177 patients ( 4.5 % ) in the enoxaparin group ( OR = 0.63 , 95 % CI : 0.46–0.87 ) . Conclusions : Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery . Study registered with clinical trials.gov : NCT00679588 Abstract Background Whereas routine prophylaxis for venous thromboembolism ( VTE ) is frequently utilized in the West , Asian physicians employ it much less often , based on its recorded rarity amongst their patients . This study was design ed to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer . Methods In this prospect i ve , r and omized trial , patients were assigned to either an intermittent pneumatic compression ( IPC ) only or an IPC plus enoxaparin . The primary end point of this study was to determine the VTE incidence rate within 30 days of surgery . A history with physical examinations for VTE and a serum d-dimer test was scheduled on postoperative days ( POD ) 0 , 1 , 4 , and 7 . Duplex ultrasonography ( DUS ) was performed as an objective test for deep vein thrombosis at POD 4 . An interim analysis was performed to determine if it was ethical to continue the study . This clinical trial was registered at www . clinical trials.gov ( NCT01448746 ) . Results Among the 220 patients , 3 ( all from the IPC group ) were diagnosed with VTE ; these cases were asymptomatic , having been detected only on DUS 4 days after surgery . Postoperative bleeding occurred in 12 cases , among which 11 patients were in the IPC plus enoxaparin group . Conclusions This interim analysis showed a higher incidence of VTE in the IPC group but a higher bleeding rate in the IPC plus enoxaparin group . We expect that this study , once completed , will provide information key to the determination of the optimal method for preventing VTE in Korean gastric cancer patients BACKGROUND The AMPLIFY trial compared apixaban with enoxaparin followed by warfarin for the treatment of acute venous thromboembolism ( VTE ) . OBJECTIVE To perform a subgroup analysis to compare the efficacy and safety of apixaban and enoxaparin followed by warfarin for the treatment of VTE in patients with cancer enrolled in AMPLIFY . PATIENTS / METHODS Patients with symptomatic VTE were r and omized to a 6-month course of apixaban or enoxaparin followed by warfarin . The primary efficacy outcome and principal safety outcome were recurrent VTE or VTE-related death and major bleeding , respectively . RESULTS Of the 5395 patients r and omized , 169 ( 3.1 % ) had active cancer at baseline , and 365 ( 6.8 % ) had a history of cancer without active cancer at baseline . Among patients with active cancer , recurrent VTE occurred in 3.7 % and 6.4 % of evaluable patients in the apixaban and enoxaparin/warfarin groups , respectively ( relative risk [ RR ] 0.56 , 95 % confidence interval [ CI ] 0.13 - 2.37 ) ; major bleeding occurred in 2.3 % and 5.0 % of evaluable patients , respectively ( RR 0.45 , 95 % CI 0.08 - 2.46 ) . Among patients with a history of cancer , recurrent VTE occurred in 1.1 % and 6.3 % of evaluable patients in the apixaban and enoxaparin/warfarin groups , respectively ( RR 0.17 , 95 % CI 0.04 - 0.78 ) ; major bleeding occurred in 0.5 % and 2.8 % of treated patients , respectively ( RR 0.20 , 95 % CI 0.02 - 1.65 ) . CONCLUSIONS The results of this subgroup analysis suggest that apixaban is a convenient option for cancer patients with VTE . However , additional studies are needed to confirm this concept and to compare apixaban with low molecular weight heparin in these patients OBJECTIVE This study aim ed to compare the haemorrhagic complications and efficacy of enoxaparin , a low molecular weight heparin ( LMWH ) , and conventional st and ard heparin ( SH ) in gynaecological oncologic surgery . MATERIAL S METHODS A double blind , r and omised trial was performed on 102 consecutive women undergoing gynaecologic cancer surgery with pelvic and paraaortic lymphadenectomy . The women were separated into those who were given 2,500 IU enoxaparin once daily and SH in a dose of 5,000 IU three times daily . The groups were analysed for intraoperative blood loss , drainage , transfusion requirements , perioperative haemoglobin decrease , wound haematoma , and clinical deep venous thrombosis . RESULTS The two groups were well matched for age , weight , and other factors , which could predispose to the development of deep venous thrombosis ( DVT ) and haemorrhage . No patient developed clinical significant DVT , wound haematoma or intra-abdominal bleeding . There was no significant difference in bleeding complications between the two regimens . The antiFXa level in the plasma was correlated strongly with patient weight . CONCLUSIONS A dose of 2,500 IU enoxaparin/day does not cause more bleeding complications than SH 5,000 IU three times daily when used to prevent thrombosis . However , the dose of enoxaparin must be adjusted to the patient 's weight BACKGROUND The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately design ed trials . METHODS In a double-blind study , we r and omly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin , 20 mg of enoxaparin , or placebo subcutaneously once daily for 6 to 14 days . Most patients were not in an intensive care unit . The primary outcome was venous thromboembolism between days 1 and 14 , defined as deep-vein thrombosis detected by bilateral venography ( or duplex ultrasonography ) between days 6 and 14 ( or earlier if clinical ly indicated ) or documented pulmonary embolism . The duration of follow-up was three months . RESULTS The primary outcome could be assessed in 866 patients . The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin ( 5.5 percent [ 16 of 291 patients ] ) than in the group that received placebo ( 14.9 percent [ 43 of 288 patients ] ) ( relative risk , 0.37 ; 97.6 percent confidence interval , 0.22 to 0.63 ; P < 0.001 ) . The benefit observed with 40 mg of enoxaparin was maintained at three months . There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin ( 43 of 287 patients [ 15.0 percent ] ) and the placebo group . The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group . By day 110 , 50 patients had died in the placebo group ( 13.9 percent ) , 51 had died in the 20-mg group ( 14.7 percent ) , and 41 had died in the 40-mg group ( 11.4 percent ) ; the differences were not significant . CONCLUSIONS Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses This double-blind , r and omised , multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis ( VT ) prophylaxis using 750 anti-factor Xa units of Orgaran ( a mixture of low molecular weight heparinoids ) given subcutaneously ( sc ) twice-daily with that of twice-daily injections of 5,000 units st and ard heparin . The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning , and the onset of clinical ly significant venous thromboembolism or bleeding . " Intent to treat " analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis ( 10.4 % ) than after heparin ( 14.9 % ) and there was no difference in bleeding complications between the two study groups . Results remained similar if only patients who completed the intended course of therapy ( " compliant patients ") were analysed . Other trials have shown that Orgaran prevents VT after hip surgery and stroke . We now show it is also safe and effective in patients having major surgery for cancer BACKGROUND There is not enough clinical evidence to make a strong recommendation on the optimal duration of thromboprophylaxis using low-molecular weight heparins ( LMWH ) in patients undergoing major cancer surgery . PATIENTS AND METHODS CANBESURE is a r and omized , double-blind study which enrolled patients admitted for abdominal or pelvic surgery for cancer . They received 3500 IU of bemiparin subcutaneously once daily for 8 days and were then r and omized to receive either bemiparin or placebo for 20 additional days . Bilateral venography was performed after 20 days and evaluated blinded . The primary efficacy outcome was the composite of deep vein thrombosis ( DVT ) , non-fatal pulmonary embolism ( PE ) and all-cause mortality at the end of double-blind period . Major venous thromboembolism ( proximal deep-vein thrombosis , non-fatal pulmonary embolism and venous thromboembolism-related deaths ) was also evaluated . The primary safety outcome was major bleeding . RESULTS Six hundred and twenty-five and 488 patients were included in the safety and main efficacy analyzes , respectively . The primary efficacy outcome occurred in 25 out of 248 patients ( 10.1 % ) in the bemiparin group and 32 out of 240 ( 13.3 % ) in the placebo group ( relative risk reduction 24.4 % ; 95 % CI : -23.7 - 53.8 % ; P = 0.26 ) . At the end of double-blind period , major venous thromboembolism occurred in 2 ( 0.8 % ) and 11 ( 4.6 % ) patients , respectively ( relative risk reduction 82.4 % ; 95 % CI : 21.5 - 96.1 % ; P = 0.010 ) . No significant difference was found in major bleedings . CONCLUSIONS Four weeks compared with 1 week of prophylaxis with bemiparin after abdominal or pelvic cancer surgery did not significantly reduce the primary efficacy outcome , but decreased major venous thromboembolism ( VTE ) without increasing hemorrhagic complications The efficacy and safety of dabigatran for treatment of venous thromboembolism ( VTE ) were demonstrated in two trials . It is unclear if the results pertain to patients with cancer and VTE . Data from two r and omised trials comparing dabigatran and warfarin for acute VTE were pooled . Primary efficacy outcome was symptomatic recurrent VTE and related death from r and omisation to the end of the treatment period . Safety outcomes were major , major and clinical ly relevant non-major , and any bleeding during the oral-only treatment period . Patients with active cancer ( = within 5 years ) at baseline or diagnosed during the study were analysed . Compared with 4,772 patients without cancer , recurrent VTE occurred more frequently in 335 patients with cancer at any time ( hazard ratio [ HR ] 3.3 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) and more often in 114 with cancer diagnosed during the study compared to 221 with cancer at baseline ( HR 2.6 ; 95 % CI , 1.1 - 6.2 ) . There was no significant difference in efficacy between dabigatran and warfarin for cancer at baseline ( HR 0.75 ; 95 % CI , 0.20 - 2.8 ) or diagnosed during the study ( HR 0.63 ; 95 % CI , 0.20 - 2.0 ) . Major bleeding ( HR 4.1 ; 95 % CI , 2.2 - 7.5 ) and any bleeding ( HR 1.5 ; 95 % CI , 1.2 - 2.0 ) were more frequent in patients with cancer than without , but with similar incidence in cancer with dabigatran or warfarin . In conclusion , in cancer patients , dabigatran provided similar clinical benefit as warfarin . VTE recurrence or bleeding were similar in patients on dabigatran or warfarin . The efficacy of dabigatran has not been assessed in comparison with low-molecular-weight heparin OBJECTIVE To eluci date those factors that contribute to the risk of major postoperative thromboembolism and perioperative bleeding tendency . DESIGN Retrospective multiple logistic regression analysis . SETTING 7 Sc and inavian hospitals ( 6 Swedish and 1 Norwegian ) . SUBJECTS 2070 patients undergoing elective major abdominal surgery . INTERVENTIONS Patients were r and omised to receive 2500 or 5000 XaI units of low molecular weight heparin daily . MAIN OUTCOME MEASURES Major thromboembolism ( proximal deep vein thrombosis confirmed by phlebography or necropsy , or pulmonary embolism confirmed by scintigraphy or necropsy , or both ) . Bleeding tendency ( bleeding complications which were not explained by local haemorrhagic lesions or by coexisting disease ) . RESULTS Previous thromboembolism , leg fracture or arthroplasty , present leg ulcer or malignant disease , operating time longer than 150 minutes , preoperative transfusion of 2 or more units , and preoperative hospital stay of 6 days or more ( but not age , body weight , or varicose veins ) were independent predictors for major postoperative thromboembolism . The risk was significantly increased with an increasing number of such risk factors . The risk of developing a diffuse bleeding complication was dependent on the dose of low molecular weight heparin , particularly in patients without risk factors . CONCLUSIONS The use of a narrow definition of thromboembolism lead to a pattern of risk factors which was partly different from that found in previous studies , which were usually based on diagnosis with the 125I-fibrinogen uptake test The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery OBJECTIVE Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy . STUDY DESIGN R and omized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed . All patients were evaluated with iodine-125 fibrinogen scanning of the legs . Clinical and laboratory variables associated with bleeding complications were recorded prospect ively . RESULTS Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression ( p = 0.54 ) . Low-dose heparin patients received more blood transfusions postoperatively ( p = 0.02 ) , had increased volume of retroperitoneal drainage ( p = 0.02 ) , and the activated partial thromboplastin time was more frequently prolonged ( p = 0.001 ) . CONCLUSIONS Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis . However , low-dose heparin is more frequently associated with postoperative bleeding complications PURPOSE The extent of venous thromboembolism ( VTE ) associated with central vein catheters ( CVC ) in cancer patients remains unclear . The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin , enoxaparin , in the prevention of VTE . PATIENTS AND METHODS In a multicenter , double-blind study , consecutive cancer patients scheduled for CVC insertion were r and omly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo . Treatment was started 2 hours before CVC insertion and continued for 6 weeks . The primary end points of the study were deep vein thrombosis ( DVT ) , confirmed by venography of the CVC limb performed 6 weeks after r and omization , or clinical ly overt pulmonary embolism , confirmed by objective testing during the study drug administration . Patients were assessed for bleeding complications . RESULTS Three hundred eighty-five patients were r and omized , of which 321 ( 83.4 % ) underwent venography . A venography was adequate for adjudication in 155 patients in each treatment group . A DVT was observed in 22 patients ( 14.1 % ) treated with enoxaparin and in 28 patients ( 18.0 % ) treated with placebo , corresponding to a relative risk of 0.78 ( 95 % CI , 0.47 to 1.31 ) . No major bleeding occurred . Five patients ( 2.6 % ) in the enoxaparin group and two patients ( 1.0 % ) in the placebo group died during the treatment period . CONCLUSION In this study , no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo . The dose of enoxaparin used in this study proved to be safe . Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication OBJECTIVE To explore the incidence of postoperative venous thromboembolism ( VTE ) in adult patients with primary bone tumor undergoing knee operation and evaluate its efficacy and safety in the prevention of VTE . METHODS For this prospect i ve , r and omized and negative-control single-center trial , a total of 100 eligible patients were selected and r and omly divided into observation and control groups . Observation group ( rivaroxaban ) : the first rivaroxaban tablet was taken in the first 24 hours after operation . Rivaroxaban was administered daily every 24 hours up to Day 14 . CONTROL GROUP no anticoagulant was taken postoperatively . RESULTS Efficacy indictors : 6 cases of DVT ( an incidence of 12 % ) occurred in the observation group versus 15 ( 30 % ) in the control group . Significant statistical difference existed between two groups ( P < 0.05 ) . Furthermore , neither pulmonary embolism nor death was found in either group . Safety indicators : a total of 3 bleeding ( 1 major and 2 non-major ) cases occurred in observation group versus a total of 2 bleeding ( no major and 2 non-major ) cases in control group . No significant statistical difference existed in bleeding events ( P > 0.05 ) . The total incidence of adverse effect was 6 % ( 3/50 ) in the observation group . The drainage volume of the observation group was a little more than that of the control group . But no significant statistical difference existed in drainage duration ( P > 0.05 ) . And there was almost no change in the coagulation system by laboratory examination after oral administration . CONCLUSION With an excellent safety profile and a low incidence of adverse effects , Rivaroxaban is effective and safe in the prevention of VTE in adult patients with primary bone tumor undergoing knee operation The Heparin Study in Internal Medicine ( HESIM ) compares the efficacy and safety of an unfractionated ( UF ) heparin with a low molecular weight ( LMW ) heparin ( CY 216 D ) for prevention of proximal deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) in medical in patients with a high risk for development of thromboembolism . Patients are r and omized and receive three times daily 5000 IU UF heparin or once daily 3100 IU LMW heparin and two placebo injections subcutaneously for 10 days . All patients are screened for the presence of proximal DVT at day 1 and 10 by real-time B-mode compression sonography and for PE by repeated clinical examinations . Perfusion scintigraphy is used for confirmation of the clinical diagnosis of PE . The study protocol includes a stratified r and omization of patients on admission to the hospital according to one of the following main diagnoses : malignant disease , cardiovascular disease , bronchopulmonary disease , neurologic disease , and other diseases . The present study may serve as a model for further clinical trials in medical in patients using the biometric approach of statistical analysis for proving equivalence of drug efficacy , and to adopt less sensitive but noninvasive methods for the detection of primary endpoints BACKGROUND Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism ( VTE ) , but the optimal duration of postoperative thromboprophylaxis is unknown . OBJECTIVES To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin ( dalteparin ) , administered for 28 days after major abdominal surgery compared to 7 days ' treatment . PATIENTS / METHODS A multicenter , prospect i ve , assessor-blinded , open-label , r and omized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery . In total , 590 patients were recruited , of whom 427 were r and omized and received at least 1 day of study medication , and 343 reached an evaluable endpoint . The primary efficacy endpoint was objective ly verified VTE occurring between 7 and 28 days after surgery . All patients underwent bilateral venography at day 28 . RESULTS The cumulative incidence of VTE was reduced from 16.3 % with short-term thromboprophylaxis ( 29/178 patients ) to 7.3 % after prolonged thromboprophylaxis ( 12/165 ) ( relative risk reduction 55 % ; 95 % confidence interval 15 - 76 ; P=0.012 ) . The number that needed to be treated to prevent one case of VTE was 12 ( 95 % confidence interval 7 - 44 ) . Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis . CONCLUSIONS Four-week administration of dalteparin , 5000 IU once daily , after major abdominal surgery significantly reduces the rate of VTE , without increasing the risk of bleeding , compared with 1 week of thromboprophylaxis The clinical and laboratory effects of low-dose heparin prophylaxis was prospect ively studied in a controlled trial of 182 patients undergoing major surgery for gynecologic malignancy . Low-dose heparin was given in 5000 U subcutaneously two hours preoperatively and every 12 hours for seven days postoperatively . Low-dose heparin-treated patients had a significantly increased daily retroperitoneal hemovac drainage . Although not statistically significant , low-dose heparin was associated with increased estimated intraoperative blood loss , transfusion requirements , and wound hematomas . Fifteen percent of patients receiving low-dose heparin were found to have an activated partial thromboplastin time greater than 1.5 times the control value . In these patients , all clinical bleeding parameters were significantly increased . Low-dose heparin-treated patients also had significantly prolonged activated partial thromboplastin time and lower final platelet counts as compared with the control patients . When using low-dose heparin for thromboembolism prophylaxis , patients should be closely observed for clinical hemorrhagic complications . Activated partial thromboplastin times and platelet counts should be monitored throughout therapy Three consecutive r and omized open studies have been carried out to determine the optimal dosage of low molecular weight heparin ( LMWH ) in the prevention of postoperative thrombosis in general surgery ( 892 patients ) . All patients undergoing abdominal , gynaecological , thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis : previous thromboembolism , obesity , varicose veins , malignancy ( 30 per cent ) , pre‐operative hospitalization over 5 days , oestrogen therapy , chronic cardiac disease or bronchitis . Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment ( LMWH , Enoxaparine ) or unfractionated heparin ( UH ) . The three studies compared 3 × 5000 units UH daily with 1 × 60 mg , 1 × 40 mg , 1 × 20 mg LMWH daily . Thromboembolic events rates were not significantly different from group to group ( UH : 3.8 per cent , 2.7 per cent , 7.6 per cent respectively compared with LMWH : 2.9 per cent , 2.8 per cent , 3.8 per cent ) . Bleeding episodes including wound haematoma formation , perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH . Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine ( as compared to UH ) . An analysis using the ‘ intention to treat ’ approach gave results consistent with those of an analysis of good compliers . An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH ( P = 0.20 ) , and pooling the results of the three studies using the Mantel‐Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH ( P = 0.54 ) . These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population Cancer patients undergoing surgery are at a high risk of venous thromboembolism , but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis . In a post hoc analysis of a r and omized study ( MC-4 ) , which compared the efficacy and safety of certoparin ( 3000 anti-Xa IU , subcutaneously , once-daily ) with unfractionated heparin ( 5000 IU , subcutaneously , three-times daily ) in 23078 patients undergoing surgery lasting more than 30 min , the incidence of autopsy-confirmed fatal pulmonary embolism , death and bleeding in the cancer patients ( n=6124 ) was compared with non-cancer patients ( n=16954 ) . Fatal pulmonary embolism was significantly more frequent in cancer patients ( 0.33 % [ 20/6124 ] ) than in non-cancer patients ( 0.09 % [ 15/16954 ] , relative risk ( RR ) , 3.7 [ 95 % confidence intervals ( CI ) , 1.80 , 7.77 ] , p=0.0001 ) at 14 days post-prophylaxis . Perioperative mortality was also significantly higher in cancer patients than in noncancer patients ( 3.14 % [ 192/6124 ] vs. 0.71 % [ 120/16954 ] , RR , 4.54 [ 95 % CI , 3.59 , 5.76 ] , p=0.0001 ) , as were blood loss ( p<0.0001 ) , and transfusion requirements ( p<0.0001 ) . Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge OBJECTIVE To study the incidence of late deep venous thrombosis ( DVT ) , and to evaluate a regimen of prolonged thromboprophylaxis after general surgery . DESIGN R and omised , controlled , open trial , with blinded evaluation . SETTING University hospital , Denmark . SUBJECTS 176 consecutive patients undergoing major elective abdominal or non-cardiac thoracic operations , of whom 118 were eligible for evaluation . INTERVENTIONS Thromboprophylaxis with a low-molecular-weight heparin , tinzaparin , given for four weeks ( n = 58 ) , compared with one week ( control group , n = 60 ) . MAIN OUTCOME MEASURES Presence of DVT established by bilateral venography four weeks after the operation . RESULTS The incidence of late DVT in the control group was 6/60 ( 10 % , 95 % confidence interval ( CI ) 4 % to 21 % ) . In the prophylaxis group it was 3/58 ( 5.2 % , 95 % CI 1 % to 14 % ) ( p = 0.49 ) . CONCLUSION Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery Ovarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis ( DVT ) as well as the spread of malignancy . To study further this coagulation-cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively , post-operatively on day 1 , 3 , 5 , 7 , 10 , before each of six cycles of Cisplatinum/ Epirubicin/Cyclophosphamide chemotherapy , during follow-up and in the post-operative period of second look surgery . In addition , blood coagulation tests results were determined prospect ively . Two patients were excluded from these calculations due to previous DVT 5 to 6 weeks before the diagnosis of ovarian cancer but all patients were eligible for surgery and r and omized to receive either daily low molecular weight heparin ( LMWH ) ( n = 28 ) or unfractionated heparin ( UFH ) ( n = 32 ) for perioperative thrombosis prophylaxis until the 7th post-operative day . According to the FIGO stage , patients were equally distributed in the 2 heparin treatment groups . The predictive value of pre-operative coagulation test results , clinical parameters , and type of heparin used were tested in univariate and multivariate analysis for development of post-operative DVT and overall patients survival . Impedance plethysmography for DVT screening was used . The presence of DVT was then confirmed by phlebography . Only D-dimer and fibrinogen levels were correlated significantly with the FIGO stage while antithrombin , protein C , and plasminogen activator inhibitor activity were not . The incidence of DVT was 6.7 % ( 4/60 ) up to the 7th and 8.3 % ( 5/60 ) between the 8th and 29th post-operative day . DVT occurred in 10.6 % ( 5/47 ) during chemotherapy . Pre-operative coagulation test results , the type of heparin used , and clinical parameters were not significant risk factors for post-operative DVT development in univariate analysis . The D-dimer and fibrinogen levels were significant risk factors for reduced overall survival in univariate analysis but only the FIGO stage was an independent predictor ( in multivariate analysis ) . After a median follow up of 26.5 months ( min . 8 months , max . 41 months ) , 21.4 % of LMWH treated and 37.5 % of UFH-treated patients died of cancer ( p = 0.26 ) . Pre-operative test results were neither predictive for DVT nor the outcome of cancer but patients showed an improved though not statistically significant overall survival after LMWH treatment AIM The aim of this study was to compare the efficacy and safety of enoxaparin and intermittent pneumatic compression ( IPC ) for venous thromboembolism ( VTE ) prevention in Japanese surgical patients with gynecologic malignancy . MATERIAL AND METHODS Patients ≥ 40 years old undergoing major surgery for gynecologic malignancy without preoperative VTE were included . Written informed consent was obtained . Enrolled patients received IPC immediately before surgery . After surgery , they were r and omly assigned to either an enoxaparin group or an IPC-alone group . The enoxaparin group received enoxaparin injection ( 20 mg , subcutaneous , every 12 h ) from postoperative day 2 to 8 . IPC was discontinued after the first injection . In the IPC-alone group , IPC was continued until full ambulation . The primary end-point was incidence of VTE , including pulmonary embolism and deep vein thrombosis , regardless of symptoms . An interim analysis was to be conducted when the first 30 patients had completed the study protocol . A Data and Safety Monitoring Board was established for making recommendation on the continuation or termination of the study based on the interim results . RESULTS At the time of the interim analysis , six cases of VTE were found : five in the IPC-alone group and one in the enoxaparin group ( Fisher 's exact test , P = 0.08 ) . Three patients in the IPC-alone group developed pulmonary embolism , but none in the enoxaparin group did so ( Fisher 's exact test , P = 0.10 ) . The study was terminated following the Data and Safety Monitoring Board 's recommendation . CONCLUSION Enoxaparin might have lowered the risk of VTE among surgical patients with gynecologic malignancy . Further studies are necessary to confirm this OBJECTIVE To categorize the challenges in determining the extent of missing participant data in r and omized trials and suggest potential solutions for systematic review authors . STUDY DESIGN AND SETTING During the process of updating a series of Cochrane systematic review s on the topic of anticoagulation in patients with cancer , we identified challenges and used an iterative approach to improve , and a consensus process to agree on the challenges identified , and to suggest potential ways of dealing with them . The five systematic review s included 58 trials and 75 meta-analyses for patient-important dichotomous outcomes with 27,037 r and omized participants . RESULTS We identified three categories of challenges : ( 1 ) Although systematic review ers require information about missing data to be reported by outcome , trialists typically report the information by participant ; ( 2 ) It is not always clear whether the trialists followed up participants in certain categories ( e.g. , noncompliers ) , that is , whether some categories of participants did or did not have missing data ; ( 3 ) It is not always clear how the trialists dealt with missing data in their analysis ( e.g. , exclusion from the denominator vs. assumptions made for the numerator ) . We discuss potential solutions for each one of these challenges and suggest further research work . CONCLUSION Current reporting of missing data is often not explicit and transparent , and although our potential solutions to problems of suboptimal reporting may be helpful , reliable and valid characterization of the extent and nature of missing data remains elusive . Reporting of missing data in trials needs further improvement Sixty-one consecutive patients were enrolled in a r and omized , controlled trial of thromboprophylaxis with a low molecular weight heparin ( Seleparina , CY 216 ) in major abdominal oncological surgery . Thirty patients received 2 x 3,825 anti-Xa international units of CY 216 subcutaneously on the day of surgery followed by a single daily 3,825 anti-Xa international units injection for 7 days ; thirty-one patients did not receive any form of prophylaxis . The occurrence of deep vein thrombosis ( DVT ) was detected by 125I-labelled fibrinogen leg scan . Postoperative DVT developed in 2 patients in the CY 216 group and in 11 patients in the control group ( 6.8 % vs 35.4 % , p < 0.01 ) . Although there was a higher postoperative transfusional requirement in the group receiving CY216 ( p < 0.05 ) , the total number of patients transfused was similar in the two groups ( 14 vs 13 ) . On day 1 after surgery , the two patients who later developed DVT in the CY216 group had plasma anti-Xa activity significantly lower ( p < 0.01 ) than the remaining patients . As a good relationship was found between plasma anti-Xa activity and body weight , adoption of a personalized dosage schedule might improve efficacy of CY 216 prophylaxis One hundred eighty-five patients undergoing operation for gynecologic malignancy participated in a r and omized controlled trial of low-dose heparin prophylaxis . Prospect i ve surveillance for deep venous thrombosis was performed with daily fibrinogen 125I counting in the legs and impedance plethysmography . Twelve of 97 ( 12.4 % ) patients in the control group and 13 of 88 ( 14.8 % ) patients in the low-dose heparin group developed a venous thromboembolic complication . There was no statistical difference in the incidence of proximal deep vein thrombosis , calf vein thrombosis , or pulmonary emboli between the control and low-dose heparin groups . Low-dose heparin does not afford any prophylactic benefit to patients undergoing major pelvic operative procedures for gynecologic malignancy BACKGROUND Abdominal surgery for cancer carries a high risk of venous thromboembolism , but the optimal duration of postoperative thromboprophylaxis is unknown . METHODS We conducted a double-blind , multicenter trial in which patients undergoing planned curative open surgery for abdominal or pelvic cancer received enoxaparin ( 40 mg subcutaneously ) daily for 6 to 10 days and were then r and omly assigned to receive either enoxaparin or placebo for another 21 days . Bilateral venography was performed between days 25 and 31 , or sooner if symptoms of venous thromboembolism occurred . The primary end point with respect to efficacy was the incidence of venous thromboembolism between days 25 and 31 . The primary safety end point was bleeding during the three-week period after r and omization . The patients were followed for three months . RESULTS The intention-to-treat analysis of efficacy included 332 patients . The rates of venous thromboembolism at the end of the double-blind phase were 12.0 percent in the placebo group and 4.8 percent in the enoxaparin group ( P=0.02 ) . This difference persisted at three months ( 13.8 percent vs. 5.5 percent , P=0.01 ) . Three patients in the enoxaparin group and six in the placebo group died within three months after surgery . There were no significant differences in the rates of bleeding or other complications during the double-blind or follow-up periods . CONCLUSIONS Enoxaparin prophylaxis for four weeks after surgery for abdominal or pelvic cancer is safe and significantly reduces the incidence of venographically demonstrated thrombosis , as compared with enoxaparin prophylaxis for one week PURPOSE Advanced pancreatic cancer ( APC ) , in addition to its high mortality , accounts for the highest rates of venous thromboembolic events ( VTEs ) . Enoxaparin , a low-molecular weight heparin , is effective in prevention and treatment of VTEs . Some small studies have indicated that this benefit might extend to patients with cancer . PATIENTS AND METHODS Patients with histologically proven APC were r and omly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival . RESULTS A total of 312 patients were recruited as one of the protocol end points was reached . Within the first 3 months , the numbers of symptomatic VTEs were as follows : 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group ( hazard ratio [ HR ] , 0.12 ; 95 % CI , 0.03 to 0.52 ; χ(2 ) P = .001 ) . The numbers of major bleeding events were as follows : five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm ( HR , 1.4 ; 95 % CI , 0.35 to 3.72 ; χ(2 ) P = 1.0 ) . Overall cumulative incidence rates of symptomatic VTEs were 15.1 % ( observation ) and 6.4 % ( enoxaparin ; HR , 0.40 ; 95 % CI , 0.19 to 0.83 ; P = .01 ) . Progression-free ( HR , 1.06 ; 95 % CI , 0.84 to 1.32 ; P = .64 ) and overall survival ( HR , 1.01 ; 95 % CI , 0.87 to 1.38 ; P = .44 ) did not differ between groups . CONCLUSION This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in out patients with APC . Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting Background —Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients , partly because clinical ly relevant end points have not been fully assessed in this population . We undertook an international , multicenter , r and omized , double-blind , placebo-controlled trial using clinical ly important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients . Methods and Results — Patients ( n=3706 ) were r and omly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days . The primary end point was venous thromboembolism , defined as the combination of symptomatic deep vein thrombosis , symptomatic pulmonary embolism , and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21 . The incidence of venous thromboembolism was reduced from 4.96 % ( 73 of 1473 patients ) in the placebo group to 2.77 % ( 42 of 1518 patients ) in the dalteparin group , an absolute risk reduction of 2.19 % or a relative risk reduction of 45 % ( relative risk , 0.55 ; 95 % CI , 0.38 to 0.80 ; P=0.0015 ) . The observed benefit was maintained at 90 days . The overall incidence of major bleeding was low but higher in the dalteparin group ( 9 patients ; 0.49 % ) compared with the placebo group ( 3 patients ; 0.16 % ) . Conclusions —Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding A prospect i ve r and omized double-blind trial was performed comparing conventional low-dose heparin with a LMWH fragment ( Kabi 2165 , Fragmin ) for thromboprophylaxis in elective general abdominal surgical patients . The first dose of the fragment was given in the evening before surgery , and thereafter every evening . There were 1002 analyzable patients , 826 having received correct prophylaxis . Sixty three percent of the patients were operated on for malignant diseases . The frequency of DVT was significantly reduced among patients with correct prophylaxis with the heparin fragment ( 9.2 to 5.0 % , p = 0.02 ) . In patients with malignancies the reduction was from 11.2 to 6.4 % ( p = 0.06 ) . The frequency of bleeding was 6.7 % among the heparin fragment patients and 2.7 % among the patients given conventional heparin ( p = 0.01 ) . The corresponding frequencies for patients with malignancies were 3.2 and 2.8 % , respectively ( p = 0.28 ) . All bleedings were minor and of no clinical significance . Local pain at the injection site was reported significantly less often among patients with the fragment . Twenty patients died , 13 with malignant disease , mortality being the same in the two groups . It is concluded that heparin fragment administered in the evening before surgery and then every evening is a practically acceptable alternative to prevent postoperative DVT in patients undergoing elective abdominal surgery , also when the histology shows malignancy . Thus , the advantages of using LMWH compared with conventional low-dose heparin are simplified administration routines , better thromboprophylactic effect , and less local pain at injection sites . A disadvantage is the slight increase in hemorrhagic side effects , all of minor clinical importance and not seen in patients undergoing surgery for malignancy BACKGROUND Enoxaparin sodium ( enoxaparin ) is used worldwide for the prevention of venous thromboembolism ( VTE ) . Registration trials of enoxaparin have been conducted primarily in Caucasian population s , and its preventive use in Japanese patients has yet to be established . To address this , we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer . METHODS This multicenter , open-label study r and omized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days , started 24 - 36 hours after surgery ( n=113 ) or intermittent pneumatic compression ( IPC ) as a reference ( n=38 ) . IPC was performed at least once in both groups between r and omization and surgery . The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat ( mITT ) population . The primary safety outcome was the incidence of any bleeding during treatment and follow-up . RESULTS Incidence of VTE was 1.2 % ( 95 % CI , 0.03 - 6.53 % ) ( 1/83 patients ) in the enoxaparin group and 19.4 % ( 95 % CI , 7.45 - 37.47 % ) ( 6/31 patients ) in the IPC group . In the safety population , 10/109 patients in the enoxaparin group ( 9.2 % ; 95 % CI , 4.49 - 16.23 % ) and 3/38 patients in the IPC group ( 7.9 % ; 95 % CI , 1.66 - 21.38 % ) experienced a bleeding event . There were no cases of fatal bleeding or bleeding into any critical organ . CONCLUSIONS These favorable efficacy and safety data support the use of enoxaparin ( 20 mg twice daily for 14 days started 24 - 36 hours after surgery ) in Japanese patients undergoing abdominal or pelvic cancer surgery BACKGROUND The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable . OBJECTIVES We performed a r and omized , double-blind study to compare the efficacy and safety of nadroparin 2850 IU ( 0.3 mL ) and enoxaparin 4000 IU ( 40 mg ) in the prevention of venous thromboembolism ( VTE ) after colorectal surgery for cancer . PATIENTS AND METHODS Patients undergoing resection of colorectal adenocarcinoma were r and omized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c . for 9 + /- 2 days . The primary efficacy outcome was the composite of deep vein thrombosis ( DVT ) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12 . The main safety outcome was major bleeding . A blinded independent committee adjudicated all outcomes . RESULTS Out of 1288 patients analyzed , efficacy was evaluable in 950 ( 73.8 % ) patients . The VTE rate was 15.9 % ( 74/464 ) in nadroparin-treated patients and 12.6 % ( 61/486 ) in enoxaparin-treated patients , a relative risk of 1.27 ( 95 % confidence interval ; CI : 0.93 - 1.74 ) that did not met the criterion for non-inferiority of nadroparin . The rate of proximal DVT was comparable in the two groups ( 3.2 % vs. 2.9 % , respectively ) , but that of symptomatic VTE was lower in nadroparin-treated patients ( 0.2 % vs. 1.4 % ) . There was significantly ( P = 0.012 ) less major bleeding in nadroparin- than in enoxaparin-treated patients ( 7.3 % vs. 11.5 % , respectively ) . CONCLUSION Compared with those receiving enoxaparin 4000 IU , patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT , but a lower incidence of symptomatic VTE . Nadroparin treatment was safer in terms of bleeding risk Background . Thromboembolism is a risk in major head and neck cancer surgery patients predisposed to thrombosis . This study was design ed to determine whether enoxaparin ( a low molecular weight heparin ) administered prior to surgery induces perioperative bleeding In a multicenter , double-blind clinical trial in 1,968 in patients 1 daily subcutaneous administration of LMW heparin plus 2 placebo injections or 3 x 5,000 IU unfractionated ( UF ) heparin was given for 10 ( 8 - 11 ) days . The primary end point was the incidence of proximal deep-vein thrombosis or pulmonary embolism . Patients were assessed during the study period for development of proximal deep-vein thrombosis by compression sonography at days 1 and 10 and for pulmonary embolism by scintigraphy in symptomatic patients . Aim of the study was to demonstrate the equivalence of both treatment regimens . A total of 1,968 patients were r and omized to receive UF or LMW heparin . Of these , 378 patients were excluded during the study period , so that 780 patients on UF and 810 on LMW heparin were included in the efficacy analysis . Four primary end points were observed with UF and 6 with LMW heparin , demonstrating the equivalence of treatments ( p = 0.012 ) . Additionally , pulmonary embolism was suspected as the cause of death in 6 patients who died during the study ( 3 per treatment group ) . A higher frequency of death ( n = 32 ) was observed in the LMW-heparin group ( p = 0.02 ) particularly documented in a part of the centers . Safety analysis showed a higher frequency of local pruritus , local erythema and subcutaneous hematoma , a higher increase in plasma levels of triglycerides , total cholesterol , alanine aminotransferase and aspartate aminotransferase , and a decrease of antithrombin III in patients receiving UF heparin . A decrease in platelet count ( values ranging between 40,000 and 80,000/microliter ) was observed in 4 patients with UF and in none with LMW heparin . No severe thrombocytopenia was observed . Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of thromboembolism in bedridden , hospitalized medical patients Background Low‐molecular‐weight heparin is the st and ard treatment for cancer‐associated venous thromboembolism . The role of treatment with direct oral anticoagulant agents is unclear . Methods In this open‐label , noninferiority trial , we r and omly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low‐molecular‐weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily ( edoxaban group ) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily ( dalteparin group ) . Treatment was given for at least 6 months and up to 12 months . The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after r and omization , regardless of treatment duration . Results Of the 1050 patients who underwent r and omization , 1046 were included in the modified intention‐to‐treat analysis . A primary ‐ outcome event occurred in 67 of the 522 patients ( 12.8 % ) in the edoxaban group as compared with 71 of the 524 patients ( 13.5 % ) in the dalteparin group ( hazard ratio , 0.97 ; 95 % confidence interval [ CI ] , 0.70 to 1.36 ; P=0.006 for noninferiority ; P=0.87 for superiority ) . Recurrent venous thromboembolism occurred in 41 patients ( 7.9 % ) in the edoxaban group and in 59 patients ( 11.3 % ) in the dalteparin group ( difference in risk , ‐3.4 percentage points ; 95 % CI , ‐7.0 to 0.2 ) . Major bleeding occurred in 36 patients ( 6.9 % ) in the edoxaban group and in 21 patients ( 4.0 % ) in the dalteparin group ( difference in risk , 2.9 percentage points ; 95 % CI , 0.1 to 5.6 ) . Conclusions Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding . The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin . ( Funded by Daiichi Sankyo ; Hokusai VTE Cancer Clinical Trials.gov number , NCT02073682 . OBJECTIVES To prospect ively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery . METHODS The present study was a prospect i ve , single-blind , non-inferiority r and omized trial . A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012 . A total of 298 of these patients ( fondaparinux group , 152 ; low molecular weight heparin group , 146 ) were evaluable for the intention-to-treat- analysis . Patients were r and omly assigned to low-dose unfractionated heparin , 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5 . The primary end-point was postoperative bleeding as by independent review , and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin . The other adverse events were evaluated . D-dimer and soluble fibrin monomer complex levels were measured perioperatively . RESULTS Bleeding occurred in 21 patients ( 12 in the fondaparinux group and 9 in low molecular weight heparin group , respectively ) . No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups . The D-dimer was elevated on postoperative day 1 in one patient ( 16.6 μg/mL ) . In another patient , the soluble fibrin monomer complex was elevated ( 109 μg/mL ) . CONCLUSIONS Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding . The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy BACKGROUND Venous thromboembolism occurs commonly in patients with cancer . Direct oral anticoagulants are non-inferior to conventional anticoagulants for the treatment of venous thromboembolism . We hypothesised that edoxaban , a direct oral inhibitor of activated clotting factor Xa , might be more suitable than conventional anticoagulants in the management of cancer-associated venous thromboembolism . The aim of this study was to assess the efficacy and safety of edoxaban compared with warfarin in a subgroup of patients with cancer enrolled in the Hokusai-VTE trial . METHODS We did a prespecified subgroup analysis in August , 2013 , and a post-hoc analysis of non-inferiority and safety in March , 2016 , of the patients with cancer enrolled in the r and omised , double-blind , double-dummy , multicentre , Hokusai-VTE trial done between Jan 28 , 2010 , and Oct 31 , 2012 . In this study , patients aged at least 18 years with acute symptomatic deep-vein thrombosis or acute symptomatic pulmonary embolism ( with or without deep-vein thrombosis ) were assigned to receive edoxaban 60 mg once per day ( or 30 mg once per day for patients with a creatinine clearance of 30 - 50 mL/min , bodyweight < 60 kg , or who were receiving concomitant treatment with the P-glycoprotein inhibitors quinidine or verapamil ) or warfarin ( dose adjusted to maintain the international normalised ratio between 2·0 and 3·0 ) or placebos for either group for at least 3 months up to 12 months . All patients received initial therapy with open-label enoxaparin or unfractionated heparin for at least 5 days . Edoxoban ( or placebo ) was started after discontinuation of initial heparin ; warfarin ( or placebo ) started concurrently with the study regimen of heparin . In our analysis we examined data for a subgroup of these patients who had a history of cancer or who had been categorised as having active cancer by the study physician at the time of enrolment . Additionally , all patients with a history of cancer were review ed post hoc and categorised according to the presence or absence of active cancer . The primary efficacy outcome was the proportion of these patients with symptomatic recurrent venous thromboembolism during the 12-month study period , analysed in the modified intention-to-treat population , with an upper limit of the CI for the hazard ratio ( HR ) of 1·5 . The principal safety outcome was the proportion of patients who had clinical ly relevant bleeding in the population of patients who received at least one dose of the study drug . This study is registered with Clinical Trials.gov , number NCT00986154 . FINDINGS Of 771 patients with cancer enrolled in the trial , 378 were assigned to edoxaban and 393 to warfarin . Recurrent venous thromboembolism occurred in 14 ( 4 % ) of 378 patients given edoxaban and in 28 ( 7 % ) of 393 patients given warfarin ( hazard ratio [ HR ] 0·53 , 95 % CI 0·28 - 1·00 ; p=0·0007 ) . The upper limit of this 95 % CI did not exceed the non-inferiority margin of 1·5 that was prespecified for the trial . Clinical ly relevant bleeding ( major or non-major ) occurred in 47 ( 12 % ) of 378 patients who received edoxaban and in 74 ( 19 % ) of 393 patients who received warfarin ; HR for clinical ly relevant bleeding 0·64 , 95 % CI 0·45 - 0·92 ; p=0·017 . Major bleeding occurred in ten ( 3 % ) of 378 patients with a history of cancer who received edoxaban and in 13 ( 3 % ) of 393 who received warfarin ( HR 0·80 , 95 % CI 0·35 - 1·83 ) . INTERPRETATION Edoxaban might be as effective as warfarin for the treatment of patients with cancer with venous thromboembolism , and with less clinical ly relevant bleeding . Additional clinical trials of edoxaban versus low-molecular-weight heparin for the treatment of venous thromboembolism in patients with cancer are warranted . FUNDING Daiichi Sankyo Deep vein thrombosis of upper limb is a common complication of CVC in patients with cancer . In these patients the risk factors for CVC-related thrombosis are not completely defined . The purpose of this study was to identify the risk factors for CVC-related thrombosis in patients included in a r and omized , double-blind , placebo-controlled study aim ed at assessing the efficacy and safety of enoxaparin for the prophylaxis of CVC-related thrombosis . CVC-related thrombosis was screened by m and atory venography after 6 weeks of study treatment . A number of patient baseline characteristics were assessed as potential risk factors for CVC-related deep vein thrombosis . Crude associations between risk factors and clinical outcomes were assessed by χ2 test or Fisher ’s exact test . Multiple logistic regression analysis was used to identify independent risk factors . A CVC-related thrombosis was found in 50 out of 310 patients ( 16.1 % ) . At multiple logistic regression analysis , CVC tip misplaced in the upper half of superior vena cava ( OR 4.05 , 95%CI 1.64–10.02 ) , left-sided CVC insertion ( OR 2.29 , 95%CI 1.01–5.51 ) and chest radiotherapy ( OR 7.01 , 95%CI 1.42–34.66 ) were independent risk factors for thrombosis . In addition to these risk factors , the presence of distant metastases ( OR 9.36 , 95%CI 1.53–57.05 ) increased the risk of thrombosis in patients who received placebo . An inadequate position of the CVC tip , left-sided CVC insertion and chest radiotherapy are independent risk factors for CVC-related thrombosis in cancer patients . Patients with distant metastases have an increased risk for thrombosis in absence of antithrombotic prophylaxis |
12,546 | 22,612,571 | Pooled estimates from r and omized and nonr and omized studies showed similar tumour-free survival at 1 year for imiquimod and PDT .
The PDT tumour-free survival was higher in studies with repeated treatments . | BACKGROUND Several noninvasive treatment modalities are available for superficial basal cell carcinoma ( sBCC ) .
OBJECTIVES This systematic review aims to determine residue , recurrence and tumour-free survival probabilities of patients with primary sBCC treated with the currently most frequently used therapies . | Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses . This ongoing phase III , open-label study conducted in Europe is evaluating the long-term ( 5 year ) clinical efficacy and safety of imiquimod 5 % cream applied once daily 5 times per week ( 5 x/week ) for 6 weeks for the treatment of superficial basal cell carcinoma ( sBCC ) . A total of 182 subjects were enrolled . The initial sBCC clearance rate was 90 % ( 12-week post treatment ) , whereas the proportion of subjects who were clinical ly clear at 2 years ( current time point ) was estimated to be 79.4 % . Local skin/application site reactions were the most frequently reported safety findings . Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC . The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod BACKGROUND Superficial basal cell carcinoma ( sBCC ) is an increasingly common tumor in fair-skinned population s throughout the world . Imiquimod , an immune response modifier that induces cytokines including interferons , has been shown in preliminary studies to have an effect when applied topically to BCC . OBJECTIVE We conducted a multicenter , r and omized , open-label dose-response trial of imiquimod 5 % cream in the treatment of primary sBCC assessing efficacy and safety of different dose regimens . METHODS Ninety-nine patients were r and omized to 6 weeks ' application of imiquimod in 1 of 4 treatment regimens : twice every day , once every day , twice daily 3 times/week , once daily 3 times/week . The treatment site was excised and examined histologically 6 weeks after cessation of imiquimod . RESULTS Intention-to-treat analysis revealed 100 % ( 3/3 ) histologic clearance in the twice-daily regimen , 87.9 % ( 29/33 ) clearance in the once every day regimen , 73.3 % ( 22/30 ) clearance in the twice-daily 3 times/week regimen , and 69.7 % ( 23/33 ) clearance in the once-daily 3 times/week regimen . Dose-related inflammatory skin reactions at the site of application were common . The majority were well tolerated and only 1 patient withdrew from the trial as a result of a medication-related skin reaction . CONCLUSION Imiquimod 5 % cream appears to have potential as a patient-administered treatment option in sBCC Between January 1991 and December 1992 a phase I trial of superficial photodynamic therapy ( PDT ) using topical application of 5-aminolaevulinic acid ( ALA ) was undertaken to treat Bowen 's disease , superficial basal cell carcinomas ( BCCs ) and metastatic skin secondaries from breast ( adenocarcinoma ) or pinna ( squamous cell carcinoma ) . Promising results were obtained with 36 areas of Bowen 's disease , with a complete response rate of 89 % at a median follow-up of 18 months . The treatment of BCCs was less successful , with 50 % complete responses in 16 lesions at a median follow-up of 17 months . Metastatic nodules responded poorly . The treatment was well tolerated and discomfort during light irradiation could be reduced by prior application of ' Emla ' cream . Lesions wept for 1 - 2 weeks following treatment and healed over a period of approximately 2 months . For large areas of Bowen 's disease , particularly in anatomically difficult areas and in elderly patients , PDT using ALA may constitute a single simple alternative outpatient treatment to existing therapies . Further work is required to improve the results with BCCs BACKGROUND High-energy pulsed carbon dioxide ( CO2 ) lasers have been used extensively to resurface wrinkled and photodamaged skin with a low risk of scarring . Results of histological studies demonstrate precise ablation depths in treated skin with minimal thermal damage to underlying tissue . Our objective was to determine if a pulsed CO2 laser could effectively ablate superficial malignant cutaneous neoplasms ( superficial multifocal basal cell carcinoma [ BCC ] and squamous cell carcinoma [ SCC ] in situ ) . OBSERVATIONS Thirty superficial neoplasms ( 17 BCCs and 13 SCCs ) and their surrounding 3-mm margins were treated with either 2 or 3 passes of a pulsed CO2 laser ( 500 mJ , 2 - 4 W ) using a 3-mm collimated h and piece . The treated areas were subsequently excised and evaluated histologically by serial sectioning at 5-micron intervals for residual tumor at the deep and lateral margins . Average patient age was greater for those with SCCs than for those with BCCs ( 76.5 vs 56.7 years ; P = .001 ) . The average tumor thickness of SCC in situ was significantly greater than that of superficial BCC ( 0.57 vs 0.34 mm ; P = .01 ) . All ( 9 of 9 patients ) BCCs were completely ablated with 3 passes , and residual tumor in the deep margins was seen in 5 of 8 patients treated with 2 passes of the pulsed CO2 laser ( P = .005 ) . Incomplete vaporization of the SCC depth was seen in 3 of 7 patients treated with 3 passes and in 2 of 6 patients treated with 2 passes . Those SCCs incompletely treated were significantly thicker than those completely ablated ( 0.65 vs 0.41 mm ; P = .01 ) . Positive lateral margins were seen in 1 BCC and 3 SCC specimens . CONCLUSIONS Pulsed CO2 laser treatment can be effective in ablating superficial BCC . Treatment of the neoplasm and a minimum of 4-mm margins with 3 passes ( 500 mJ , 2 - 4 W ) is recommended for complete vaporization using this laser system . Because 3 passes did not completely ablate all SCC in situ , use of this modality alone is not recommended for treatment of thick or keratotic lesions . No direct comparison of efficacy can be made with other destructive modalities that have not been evaluated with comparably sensitive histological techniques . Further study is needed to establish any cosmetic advantage of pulsed CO2 lasers over other destructive modalities for treatment of superficial malignant neoplasms and long-term cure rates Objective To evaluate the treatment of superficial basal cell carcinomas ( SBCC ) using photodynamic therapy with topically applied delta-aminolaevulinic acid ( ALA ) and a filtered short arc xenon lamp as a light source . Method An oil-in-water emulsion containing 20 % ALA was applied topically to the lesion sites which were then occluded for 3 h. Irradiation was performed in a single session of 10 min using 125 or 166 mW/cm2 in the wavelength range ( 620–670 nm , giving a radiation dose of 75 or 100 J/cm2 , respectively . Urine sample s obtained in connection with the treatment were examined for traces of porphobilinogen and porphyrin . The therapy outcome was determined by histological examination of punch biopsies or by clinical verification . A follow-up scheduled for 5 years was initiated . Patients A group of 37 patients with histologically verified SBCCs were included . A total of 190 SBCCs were treated . Also included were six patients with 10 nodular basal cell carcinomas and five patients with 18 Mb . Bowen . The urine sample s from three patients showed traces of porphyrins . Results Of the 157 SBCCs followed-up for 6 months , 144 were cleared giving a clearance rate of 92 % . Of the nodular basal cell carcinomas and Mb . Bowens , 2 of ten and 11 of 18 were cleared , respectively . Conclusion Photodynamic therapy is well suited to the treatment of SBCCs giving good cosmetic results regardless of lesion size . The filtered xenon lamp proved to be particularly suitable for photodynamic therapy This multicentre , r and omized study compared photodynamic therapy using topical methyl aminolaevulinate ( MAL PDT ) , a non-invasive modality , with cryotherapy for treatment of superficial basal cell carcinoma . Sixty patients with 114 lesions were treated with MAL cream ( 160 mg/g ) applied for 3 hours before illumination ( 570 - 670 nm , light dose 75 J/cm ) ( 1 session ) , and 58 with 105 lesions received cryotherapy ( 2 freeze-thaw cycles ) . Patients with an incomplete response at 3 months received 2 further MAL PDT sessions ( n = 20 ) or repeat cryotherapy ( n = 16 ) . 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years . There was no difference in 5-year recurrence rates with either treatment ( 20 % with cryotherapy vs. 22 % with MAL PDT , p = 0.86 ) . However , more patients had an excellent cosmetic outcome with MAL PDT ( 60 % vs. 16 % with cryotherapy , p = 0.00078 ) . These results provide support for the use of MAL PDT as a non-invasive , selective treatment alternative for primary superficial basal cell carcinoma Background Superficial basal cell carcinomas of the skin ( sBCC ) often respond poorly to single‐treatment aminolaevulinic acid‐based photodynamic therapy ( ALA – PDT ) , with a number of reports indicating a relapse rate of 50 % or more We conducted a prospect i ve , multicenter , phase 3 , open-label study to assess long-term sustained clearance of superficial basal cell carcinomas ( sBCCs ) treated with imiquimod cream 5 % . A biopsy-confirmed tumor ( area > or = 0.5 cm2 and diameter < or = 2.0 cm ) was treated once daily 7 times per week for 6 weeks . Participants with initial clinical clearance at 12 weeks posttreatment were followed for 60 months . Tumor recurrence , serious adverse events ( AEs ) , local skin reactions ( LSRs ) , and skin quality assessment s ( SQAs ) were measured . The initial clearance rate was 94.1 % ( 159/169 ) . Estimated sustained clearance ( proportion of participants who achieved initial clearance at the 12-week posttreatment visit and remained clinical ly clear at each time point during the long-term follow-up period ; N=157 ) was 85.4 % at 60 months ( life-table method : 95 % confidence interval [ CI ] , 79.3%-91.6 % ) . The overall estimate of treatment success was 80.4 % at 60 months ( N=169 ; 95 % CI , 74.4%-86.4 % ) . Of 20 recurrent tumors , 74 ( 70 % ) occurred within the first 24 months of follow-up . Local skin reactions and application site reactions , the AEs reported by the most participants , occurred predominantly during the treatment period and resolved posttreatment . Compared to baseline , investigator-assessed SQA scores for the target tumor site improved for skin surface abnormalities and hyperpigmentation , and worsened for hypopigmentation . For low-risk sBCCs , daily application of imiquimod for 6 weeks had high initial and 5-year sustained clearance rates Objectives : This study was design ed to compare the safety and efficacy of two cycled dosing regimens of imiquimod 5 % cream for treatment of superficial basal cell carcinoma ( sBCC ) . Methods : Patients ( n = 32 ) were r and omized to receive one of two treatment regimens : 8 weeks of treatment with once‐daily dosing for alternate weeks ( R1 ) and 5 weeks of once‐daily dosing with a 1‐week interval in the middle of the course ( R2 ) . Efficacy measures were tumour clearance at weeks 19 and 52 and measures of patients ' acceptability . Results : Data from 30 patients ( 13 females ) , 14 on R1 and 16 on R2 , were analysed . The results revealed an initial clearance rate of 64 % at week 19 for R1 and 81 % for R2 ( 95 % CI for difference : −14 % to 45 % , p = 0.21 ) . However , clearance rates at week 52 were significantly different : 43 % for R1 and 88 % for R2 ( 95 % CI for difference : 11 % to 68 % , p = 0.02 ) . There was no difference in acceptability of treatment as measured by composite median visual analogue scores at week 8 . Conclusion : Five weeks of 5 % imiquimod cream once daily with a 1‐week interval was more effective but as well tolerated as the 8‐week alternate week regimen for sBCC Summary Background Imiquimod 5 % cream has been investigated for non‐surgical treatment of superficial and nodular basal cell carcinoma ( BCC ) tumours OBJECTIVE To investigate the incidence of single and multiple basal cell carcinoma ( BCC ) lesions and associated risk factors . DESIGN A prospect i ve , population -based cohort study ( from January 1 , 1990 , through December 31 , 2007 ) . SETTING Two cohorts of 10 994 Dutch people , 55 years or older , were studied in 1990 ( first cohort ) and 1999 ( second cohort ) . PATIENTS Patients with BCC lesions were identified from the Dutch national pathology laboratories network , hospitals , and general practice s. MAIN OUTCOME MEASURES The associations between determinants and single and multiple BCC lesions were studied by estimating odds ratios ( ORs ) and hazards ratios , using multivariate logistic regression and And ersen-Gill models , respectively . RESULTS Of the eligible 10 820 cohort members , 524 ( 4.8 % ) had BCC , of whom 361 had single and 163 ( 31.1 % ) had multiple lesions . Age and red hair were significant risk factors for a first BCC lesion in a multivariate model . In the And ersen-Gill model , people who developed a first BCC lesion after 75.0 years of age were significantly less likely to develop multiple lesions ( > or = 75.0 years adjusted OR , 0.58 ; 95 % confidence interval [ CI ] , 0.47 - 0.71 ) . Red hair ( adjusted OR , 1.43 ; 95 % CI , 1.05 - 1.94 ) , high educational level ( 1.42 ; 1.12 - 1.81 ) , and a first BCC lesion located on the upper extremities ( 1.49 ; 1.02 - 2.15 ) were associated with a significantly increased risk of developing multiple lesions . CONCLUSION Patients who are relatively young at their first BCC diagnosis , those with red hair , those with higher socioeconomic status , and /or those with a BCC lesion on their upper extremities have a higher risk of developing multiple lesions and require closer follow-up over time Photodynamic therapy ( PDT ) of superficial basal cell carcinoma using topical 5-aminolaevulinic acid ( ALA ) and 75 - 100 J/cm2 light dose yields unsatisfactory long-term results . In several animal models , illumination with two light fractions approximately 2 h apart was considerably more effective than single illumination , suggesting the need for a pilot clinical study . Fifteen patients with a total of 86 primary superficial basal cell carcinomas , received topical ALA and were illuminated 4 and 6 h later , both with 45 J/cm2 laser light ( 633+/-1 nm ) . Fluorescence spectra were measured before and immediately after each illumination . At a mean follow-up of 59 months ( range 44 - 82 ) , 67 lesions could be evaluated , 56 of which showed a complete response ( 84 % ) . Cosmesis was good/excellent in 88 % of the complete response group and fair in 12 % . There was no correlation between protoporphyrin fluorescence and response , but a significant correlation between the percentage of fluorescence left after photobleaching by the first illumination and the amount of protoporphyrin re-synthesized 2 h later . In conclusion , the long-term complete remission rate of fractionated ALA-mediated PDT of superficial basal cell carcinoma as reported here is significantly better than after PDT with single illumination previously reported by others , but equal to studies using single illumination with a much higher light fluence . Further improvement may be possible by reducing the fluence of the first fraction , with constant total fluence Imiquimod 5 % cream is an immune response modifier approved for the treatment of superficial basal cell carcinoma ( sBCC ) once daily , 5 x per week for 6 weeks . This report reveals the final results of a 5-year follow-up study to evaluate the recurrence rate of sBCCs treated with imiquimod . As previously reported , 182 patients were enrolled in the study and 163 ( 89.6 % ) had no clinical evidence of their target sBCC at the 12-week post-treatment assessment ; these 163 were followed for up to 5 years . During the follow-up period , 18 clinical recurrences occurred at the target tumour site , 8 and 10 of which occurred during the first 6 and 12 months of follow-up , respectively . The 5-year Kaplan-Meier and life-table estimates for sustained clinical clearance of those patients initially cleared were 84.5 % and 86.9 % , respectively , and 90.3 % considering histology . The estimate of overall treatment success for all treated patients at the end of follow-up was 77.9 % ( 80.9 % considering histology ) . The data support clinical assessment of initial response as predictive of long-term outcome . Most of the recurrences occurred early , indicating that careful follow-up is important during the first year after treatment Background A previously reported r and omized clinical trial showed treatment of Bowen 's disease using photodynamic therapy ( PDT ) with topically applied δ‐aminolaevulinic acid ( ALA ) to be at least as effective as cryosurgery and to be associated with fewer adverse effects BACKGROUND To develop a nonsurgical treatment alternative for basal cell carcinomas ( BCCs ) , we evaluated intralesional sustained-release chemotherapy with 5-fluorouracil/epinephrine injectable gel ( 5-FU/epi gel ) . OBJECTIVE To optimize the dose and treatment schedule , we compared the safety , tolerance , and efficacy of six treatment regimens of 5-FU/epi gel in patients with BCCs . METHODS Two doses and four treatment schedules of 5-FU/epi gel were compared in an open-label , r and omized study of 122 patients with biopsy-proven BCCs . One BCC per patient was treated for up to 4 to 6 weeks , then observed for 3 months at which time the tumor site was completely excised for histologic examination . RESULTS Overall , 91 % of evaluable treated tumors ( 106 of 116 ) in all regimens had histologically confirmed complete tumor resolution . No clinical ly significant treatment-related systemic adverse events occurred . The best response rate , tolerance , and patient compliance with assigned dose were in patients receiving 0.5 ml of 5-FU/epi gel three times a week for 2 weeks . The complete response rate based on histologic assessment in this group was 100 % . CONCLUSION Results demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective , may result in histologically confirmed complete response rates comparable to surgery , and provides a nonsurgical treatment alternative in selected patients Abstract The aim of this prospect i ve r and omized study was to compare the clinical and cosmetic outcome of superficial basal cell carcinomas ( BCC ) , using either laser or broadb and halogen light , in photodynamic therapy with topical 5-aminolevulinic acid ( ALA ) . A total of 83 patients with 245 superficial BCC were included in the study . St and ard treatment involved 15 min of local pretreatment with 99 % dimethylsulfoxide ( DMSO ) before topical application of 20 % ALA with DMSO ( 2 % ) and ethylendiaminetetraacetic acid ( 2 % ) as cofactors for 3 h before light exposure with either laser or a broadb and lamp ( BL ) . A complete response was achieved in 95 lesions ( 86 % ) in the laser group and 110 lesions ( 82 % ) in the BL group 6 months after treatment . Of these , 80 lesions ( 84 % ) in the laser group and 101 lesions ( 92 % ) in the lamp group were independently evaluated to have an excellent or good cosmetic post-treatment score . No serious adverse events were reported . This study shows that there is no statistical significant difference in cure the rate ( P = 0.49 ) and the cosmetic outcome ( P = 0.075 ) with topical application of a modified ALA-cream between light exposure from a simple BL with continuous spectrum ( 570–740 nm ) or from a red-light laser ( monochromatic 630 nm ) . Cost and safety are further elements in favor of the BL in this setting BACKGROUND Imiquimod 5 % cream may provide an effective nonsurgical treatment for superficial basal cell carcinoma ( sBCC ) based on results of previous studies . OBJECTIVE The objective of this phase II dose-response study was to explore various dosing regimens using imiquimod 5 % cream for sBCC to find the most effective frequency of dosing with tolerable side effects . METHODS Patients ( n = 128 ) were dosed twice daily , once daily , 5 times a week , or 3 times a week in this 12-week , r and omized , double-blind , vehicle-controlled study . At 6 weeks after treatment , the entire tumor area was clinical ly evaluated , excised , and examined exhaustively for histologic evidence of residual sBCC . RESULTS Complete response rates were 100 % ( 10/10 ) , 87.1 % ( 27/31 ) , 80.8 % ( 21/26 ) , and 51.7 % ( 15/29 ) for patients in the twice daily , once daily , 5 times a week , and 3 times a week imiquimod groups , respectively , and 18.8 % ( 6/32 ) in the vehicle group . CONCLUSION Imiquimod 5 % cream was effective in the treatment of sBCC . Daily or 5 times a week dosing for 12 weeks demonstrated high efficacy results with acceptable safety profiles Background Imiquimod is an immune response modifier that acts through toll‐like receptor 7 to induce cytokine production and a subsequent innate and adaptive cell‐mediated immune response . Clinical studies have demonstrated clinical and histological clearance of superficial basal cell carcinoma ( sBCC ) after treatment with imiquimod 5 % cream BACKGROUND AND OBJECTIVE Basal cell carcinomas ( BCCs ) have supporting vasculature that could serve as a target for 595 nm pulsed dye laser ( PDL ) . The objective of this study was to determine the effect of repeated PDL treatments on BCCs of superficial and nodular subtypes and of varying diameters . STUDY DESIGN / MATERIAL S AND METHODS Twenty biopsy-proven BCCs received four 595 nm PDL treatments at 2-week intervals . The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters : one pass , 15 J/cm2 energy , 3 ms pulse length , no cooling , and 7 mm spot size with 10 % overlap . The treated area was excised and evaluated histologically for residual tumor . Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated , matched control tumors . RESULTS Nearly all BCCs < 1.5 cm in diameter ( n = 12 ) showed complete response to four PDL treatments ( 91.7 % ; n = 11/12 ) versus 16.7 % of controls ( n = 2/12 , P-value = 0.0003 ) . BCCs > or = 1.5 cm in diameter ( n = 8) showed a complete response rate of 25 % ( n = 2/8 ) versus 0 % of controls ( n = 0/8 , P-value = 0.2 ) . Mean clinical tumor diameter of the complete responders was 1.1 cm ( n = 13 ) versus 2.2 cm ( n = 7 ) for incomplete responders ( P-value = 0.005 ) . Tumor histologic types among the complete responders included superficial , nodular , micronodular , and keratinizing . Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment , with residual histologic tumor burden ranging from < 1 % to 29 % of the original clinical tumor diameter , compared to 13 - 68 % residual tumor burden for the corresponding controls ( P-value = 0.05 ) . CONCLUSIONS PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs < 1.5 cm in diameter BACKGROUND Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells . Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma ( BCC ) . OBJECTIVE We sought to evaluate the efficacy and safety of imiquimod 5 % cream compared with vehicle for treating superficial BCC ( sBCC ) . METHODS Two identical studies were conducted . Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 r and omized , double-blind , vehicle-controlled Phase III studies . The lesion site was clinical ly examined 12 weeks posttreatment and then excised for histological evaluation . RESULTS Data from both studies were pooled . Composite clearance rates ( combined clinical and histological assessment s ) for the 5 and 7x/week imiquimod groups were 75 % and 73 % , respectively . Histological clearance rates for the 5 and 7x/week imiquimod groups were 82 % and 79 % , respectively . Increasing severity of erythema , erosion , and scabbing/crusting was associated with higher clearance rates . CONCLUSION Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream . The difference in clearance rates between the two imiquimod dosing groups was not significant . The 5x/week regimen is recommended Objectives : To evaluate the safety of two applications of PEP005 ( ingenol mebutate ) gel in superficial basal cell carcinoma . Efficacy was a secondary end‐point Forty-one patients with 47 basal cell carcinomas ( BCCs ; 15 superficial , 26 nodular , and 6 sclerodermiform ) were treated with 5 % imiquimod cream once daily 5 times a week for 6 weeks in an open-label clinical trial . The overall response rate was 95.7 % . Local side effects occurred in 68 % of the patients as mild to moderate reactions with a clear association to the histological BCC subtype . Follow-up examinations for up to 17 months ( median 10 months ) showed scars in 14.9 % of the patients and a recurrence rate of 6.6 % . Overall , imiquimod represents a safe and effective treatment option for a selected cohort of BCC patients . Notably , by the second week of treatment 72.7 % of BCC biopsies were histologically tumor-free , which correlated with a substantial decrease of the inflammatory infiltrate by up to 58 % between weeks 3 to 6 . This early imiquimod response might have important implication s for the final definition of potentially shorter imiquimod treatment periods BACKGROUND Most clinical studies using photodynamic therapy ( PDT ) with topical application of delta-aminolaevulinic acid ( delta-ALA ) use red light because it allows greater depth of penetration . However , given the porphyrin-like spectrum of delta-ALA-induced photosensitivity , violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX , meaning that PDT with violet light uses less light energy to induce the phototoxic reaction . AIM To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions . METHODS Eight hours after 20 % delta-ALA was applied topically , photoirradiation was performed with an incoherent light source ( Philips HPM-10 , 400 W ) emitting predominantly violet light ( 400 - 450 nm ) . Lesions received 10 - 20 J/cm2 during an exposure time of 30 min . The 38 subjects treated included three with basal cell naevus syndrome with multiple ( > 30 ) superficial and nodular basal cell carcinomas ( BCCs ) , one subject had multiple lesions of Bowen 's disease , involving 50 % of the scalp , and the remaining 34 subjects presented a total of 35 superficial BCCs , 10 nodular BCCs , four large solar keratoses and five solitary lesions of Bowen 's disease . RESULTS Complete remission both clinical ly and histologically was seen after a single treatment in 82 % of the superficial BCCs ( 100 % after a second treatment ) , 50 % of the nodular BCCs , one of the four solar keratosis lesions ( partial remission in the other three ) and 90 - 100 % of the solitary lesions of Bowen 's disease . CONCLUSIONS delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions , especially when there are multiple lesions or large patches comprising a large area of skin Background : Although the effectiveness of daily dosing regimens of 5 % imiquimod cream for the treatment of superficial basal cell carcinomas ( sBCC ) has been documented by recent studies , concerns about long‐term outcome remain . The majority of efficacy data is based on clinical clearance and limited histological examination which may not identify tumour presence at the periphery . Objective : To assess the efficacy of 5 % imiquimod cream for sBCC using detailed histological assessment 1 year after completion of treatment . Methods : Nine individuals with biopsy‐proven sBCC treated with 5 % imiquimod cream 1 year previously and who remained clinical ly clear were recruited . Paraffin‐embedded excision specimens from the original tumour site were extensively examined by a dermatopathologist . Examination and analysis of frozen sections of the original tumour perimeter using Mohs ' micrographic surgery ( MMS ) were then performed . Results : Eight of nine individuals , 89 % ( 95 % CI 56 % to 97 % ) were histologically clear of sBCC at 52 weeks . One individual had a single focus of sBCC at one lateral margin . Conclusion : The results show agreement between the clinical and histological assessment of tumour clearance . However , the persistence of disease in one patient , although limited , indicates the need for cautious long‐term follow‐up studies on the use of 5 % imiquimod cream for sBCC We determined the trends in incidence of skin basal cell carcinoma ( BCC ) using a primary care population ‐based cohort study in the UK . 11,113 adults with a BCC diagnosis were identified from a total of 7.22 million person‐years of data between 1996 and 2003 from the Health Improvement Network data base . From a r and om sub sample of BCC cases identified from the data base , 93 % were confirmed by hospital letter and /or pathology report . The incidence of BCC was 153.9 per 100,000 person‐years ( 95 % CI 151.1 , 156.8 ) and was slightly higher in men as compared to women ( Incidence Rate Ratio 1.10 , 95 % CI 1.06 , 1.14 ) . There was a 3 % increase year on year across the study period ( IRR 1.03 , 95 % CI 1.01 , 1.04 ) , with the largest increase in incidence seen in the 30–39 year age groups , although this did not reach statistical significance . Our study indicates 53,000 new cases of BCC are estimated every year in the UK and figures are continuing to rise on a yearly basis . Incidence rates are highest for men and in particular in the older age categories . These findings are consistent with those reported for various other population s. We have also found an increase in incidence in ages 30–39 , which may suggest a cohort effect of increasing ultraviolet exposure in successive younger generations . This may have a huge public and service impact in future years in countries such as the UK , with predominantly fair‐skinned population , with high leisure exposure to ultraviolet light . Our findings underline the need for more elaborate preventive measures . © 2007 Wiley‐Liss , Imiquimod 5 % cream is approved in the USA , Europe and Australia to treat superficial basal cell carcinoma , using a regimen of once daily , 5 times per week for 6 weeks . Vehicle‐controlled , phase III clinical trials show that imiquimod is safe and effective for treating superficial basal cell carcinoma with dosing 5 or 7 times per week for 6 weeks . This phase III , open‐label study evaluates the long‐term ( 5 years ) clinical efficacy and safety of dosing once daily , for which this manuscript reports the 2‐year time point in the follow‐up period . For the 169 enrolled subjects , the tumour selected for treatment was assessed clinical ly to determine initial clearance at the 12‐week post‐treatment visit . If clinical ly clear of superficial basal cell carcinoma , subjects entered a 5‐year , long‐term follow‐up period . Subjects were evaluated for recurrence at the 3‐ , 6‐ , 12‐ and 24‐month follow‐up visits . The initial clearance rate at 12 weeks post treatment was 94.1 % . The proportion of subjects who were clinical ly clear at the 2‐year follow‐up visit was estimated to be 82.0 % . Imiquimod was tolerated when applied daily , with erythema reported for all subjects participating in the study . The recurrence rate observed suggests that once daily dosing and 5 × /week dosing yield similar clearance rates , but daily dosing increases local skin reactions Photodynamic therapy ( PDT ) of superficial basal cell carcinoma ( sBCC ) using topical 5-aminolevulinic acid ( ALA ) and a light fluence of 75 - 100 J cm(-2 ) yields unsatisfactory long-term results . In several animal models , illumination with two light fractions 2 hours apart was considerably more effective than single illumination . Response is further enhanced if the fluence of the first light fraction is reduced , although the cumulative fluence is maintained . We compared the response of sBCC to a single illumination and 2-fold illumination scheme in which two light fractions of 20 and 80 J cm(-2 ) are performed 4 and 6 hours after the application of a single dose of 20 % ALA . We r and omly assigned 154 patients with a total of 505 primary sBCC into two treatment groups . Two hundred and forty-three lesions were treated using a single illumination of 75 J cm(-2 ) at a fluence rate of 50 mW cm(-2 ) . Fractionated PDT , at the same fluence rate , was performed on 262 lesions . The complete response ( CR ) following a 2-fold illumination scheme is significantly greater than that following a single light fraction ( P=0.002 , log-rank test ) . Twelve months after therapy , CR rate to a 2-fold illumination is 97 % , whereas the CR to a single illumination is 89 % Background : Photodynamic therapy ( PDT ) of superficial basal cell carcinomas using endogenous protoporphyrin IX generated by topically applied 5-aminolevulinic acid ( 5-ALA ) is an innovative and clinical ly encouraging approach . Objective : This paper reports on the first results of an ongoing clinical study on photodynamic therapy of 55 basal cell carcinomas in 19 patients . Methods : Because of the chemical instability of 5-ALA , a novel nanocolloid lotion was developed . This formulation was applied to the lesions under occlusive dressing 6 h before irradiation with visible light from an unfiltered halogen lamp . Light-induced fluorescence was used to ascertain the superficial extension of the tumors . The response to the therapy was assessed by visual inspection and in 13 patients also by biopsies . Results : After a single treatment , 47 ( 85 % ) basal cell carcinomas showed a complete response at a follow-up time of at least 6 months . For the remaining 8 ( 15 % ) lesions , a partial response was observed , indicated by a marked reduction of the tumor size . The treatment modality without local anesthetics was well tolerated by all patients , with only slight discomfort during light irradiation . Conclusion : Our results indicate that 5-ALA-PDT with our novel formulation , a nanocolloid lotion , is a highly effective and convenient therapy for the treatment of superficial basal cell carcionomas . Its use in the treatment of nodular tumors needs further investigations OBJECTIVE To compare the efficacy and cosmetic outcome ( CO ) of photodynamic therapy with topical methyl aminolevulinate ( MAL-PDT ) with simple excision surgery for superficial basal cell carcinoma ( sBCC ) over a 1-year period . METHODS In this multicentre , r and omised , controlled , open study , patients were treated at baseline either with MAL-PDT ( two sessions , 7 days apart , repeated 3 months later if incomplete clinical response ) or surgery ( at baseline ) . Primary endpoints were clinical lesion response ( CR ) 3 months after last treatment and CO assessed by the investigator 12 months after last treatment . Secondary endpoints were CR at 12 months ( i.e. recurrence ) and CO assessed by the investigator at 3 and 6 months and by the patient at 3 , 6 and 12 months . RESULTS Overall , 196 patients were enrolled with 1.4 sBCC lesions on average per patient . Mean lesion count reduction at 3 months was 92.2 % with MAL-PDT vs. 99.2 % with surgery [ per protocol ( PP ) population ] confirming the non-inferiority hypothesis ( 95 % confidence interval , -12.1 , -1.9 ) . A total of 92.2 % lesions showed CR at 3 months with MAL-PDT vs. 99.2 % with surgery ( PP population ) . At 12 months , 9.3 % lesions recurred with MAL-PDT and none with surgery . CO was statistically superior for MAL-PDT at all time points . At 12 months , 94.1 % lesions treated with MAL-PDT had an excellent or good CO according to the investigator compared with 59.8 % with surgery . This difference was confirmed with the patients ' assessment . The proportion of excellent CO markedly improved with time with MAL-PDT unlike surgery . CONCLUSIONS MAL-PDT offers a similarly high efficacy and a much better CO than simple excision surgery in the treatment of sBCC Basal cell carcinoma is the most common skin tumor in humans which can be removed in a variety of ways ( depending on the type of the lesion , the affected area , and depth of the lesion ) . Laser therapy offers another option to the traditional methods of treatment ; thus , the purpose of this work is to valuate the efficacy of dye laser in a selected group of patients affected by superficial basal cell carcinoma . We suggest that the success of pulse dye laser treatment lies in the fact that as all tumors , basal cell carcinomas contain an increased number of dilated blood vessels . Twenty patients ( eight males and 12 females ) with superficial basal cell carcinoma were given five treatments with a flashlamp-pumped pulse dye laser every 20 days . The clinical follow up was 12 - 24 months after the fifth treatment . A complete response was obtained in 16 patients out of 20 . Three recurrences and one no response was observed during the study . Pulse dye laser is effective and safe in the treatment of superficial basal cell carcinoma |
12,547 | 29,405,865 | Results : Students who participated in a byst and er program , compared to those who had not , had more pro-social attitudes/beliefs about sexual violence and intervening to prevent it , and engaged in more byst and er behavior .
Program effects diminished over time , but meaningful changes persisted for at least three months following program delivery .
Longer programs had greater effects than shorter programs on attitudes/beliefs .
Conclusions : Byst and er programs can be a valuable addition to colleges ' violence prevention efforts | ABSTRACT Objectives : This systematic review and meta- analysis evaluates the effectiveness of byst and er programs that address sexual violence on college campuses .
Program effects on student attitudes/beliefs and byst and er behavior were examined . | OBJECTIVE Because of its high prevalence and serious consequences for victims , sexual violence is a significant problem on college campuses . Sexual assault prevention programs based on the byst and er intervention model have been shown to be effective ; however , current programs are limited in terms of ease of distribution . To address this issue , we developed and evaluated " Take Care , " an online byst and er intervention program . To our knowledge , this is the first empirical evaluation of an online byst and er intervention program design ed to prevent sexual violence . METHOD Ninety-three participants ( 80.6 % female , 19.4 % male ) recruited from social psychology classes at a mid-size university were r and omly assigned to view one of two online programs : Take Care or a control program on study skills . Before viewing the programs , participants completed measures of byst and er behaviors and feelings of efficacy for performing such behaviors . Measures were administered again post-intervention and at a two-month follow-up assessment . RESULTS Participants who viewed Take Care reported greater efficacy for engaging in byst and er behaviors at post-treatment and two months following treatment , compared to those who viewed the control program . In addition , participants who viewed Take Care reported performing relatively more byst and er behaviors for friends at the two-month follow-up assessment , compared to participants who viewed the control program . CONCLUSIONS These results suggest that sexual violence prevention programs may be effectively adapted to an online format Background Byst and er intervention approaches offer promise for reducing rates of sexual violence on college campuses . Most interventions are in-person small-group formats , which limit their reach and reduce their overall public health impact . Objective This study evaluated the efficacy of RealConsent , a Web-based byst and er approach to sexual violence prevention , in enhancing prosocial intervening behaviors and preventing sexual violence perpetration . Methods A r and om probability sample of 743 male undergraduate students ( aged 18 to 24 years ) attending a large , urban university located in the southeastern United States was recruited online and r and omized to either RealConsent ( n=376 ) or a Web-based general health promotion program ( n=367 ) . Participants were surveyed online at baseline , postintervention , and 6-months postintervention . RealConsent was delivered via a password-protected Web portal that contained six 30-minute media-based and interactive modules covering knowledge of informed consent , communication skills regarding sex , the role of alcohol and male socialization in sexual violence , empathy for rape victims , and byst and er education . Primary outcomes were self-reported prosocial intervening behaviors and sexual violence perpetration . Secondary outcomes were theoretical mediators ( eg , knowledge , attitudes ) . Results At 6-month follow-up RealConsent participants intervened more often ( P=.04 ) and engaged in less sexual violence perpetration ( P=.04 ) compared to controls . In addition , RealConsent participants reported greater legal knowledge of sexual assault ( P<.001 ) , greater knowledge of effective consent ( P<.001 ) , less rape myths ( P<.001 ) , greater empathy for rape victims ( P<.001 ) , less negative date rape attitudes ( P<.001 ) , less hostility toward women ( P=.01 ) , greater intentions to intervene ( P=.04 ) , less hyper-gender ideology ( P<.001 ) , less positive outcome expectancies for nonconsensual sex ( P=.03 ) , more positive outcome expectancies for intervening ( P<.001 ) , and less comfort with other men ’s inappropriate behaviors ( P<.001 ) . Conclusions Our results support the efficacy of RealConsent . Due to its Web-based format , RealConsent has potential for broad-based dissemination thereby increasing its overall public health impact on sexual violence . Trial Registration Clinical trials.gov : NCT01903876 ; http:// clinical trials.gov/show/NCT01903876 ( Archived by WebCite at http://www.webcitation.org/6S1PXxWKt ) Colleges and universities are high-risk setting s for sexual and relationship violence . To address these problems , institutions of higher education have implemented prevention programs , many of which train students as potential byst and ers who can step in to help diffuse risky situations , identify and challenge perpetrators , and assist victims . The impact of byst and er sexual and relationship violence prevention programs on long-term behavior of byst and ers has remained a key unanswered question for those who seek to offer the most effective programs as well as for policy makers . In this study , the research ers experimentally evaluated the effectiveness of the Bringing in the Byst and er ® in-person program . Participants were 948 1st-year college students of whom 47.8 % were women and 85.2 % identified as White ( 15 % also identified as Hispanic in a separate question ) between the ages of 18 and 24 at two universities ( one a rural , primarily residential campus and the other an urban , highly commuter campus ) in the northeastern United States . To date , this is the first study to have found positive behavior changes as long-lasting as 1 year following an educational workshop focusing on engaging byst and ers in preventing sexual and relationship violence . Even so , many questions remain to be answered about prevention and intervention of this type . More prospect i ve research is needed on byst and er-focused prevention of these forms of violence to help underst and and better predict the complicated relationships both between and among the attitudes and behaviors related to preventing sexual and relationship violence . In this regard , we make specific recommendations for design ing and evaluating programs based on our findings relating to the importance of moderators , especially two key understudied ones , readiness to help and opportunity to intervene Using a cross-sectional survey of a r and om sample of 7,945 college undergraduates , we report on the association between having received Green Dot active byst and er behavior training and the frequency of actual and observed self-reported active byst and er behaviors as well as violence acceptance norms . Of 2,504 students aged 18 to 26 who completed the survey , 46 % had heard a Green Dot speech on campus , and 14 % had received active byst and er training during the past 2 years . Trained students had significantly lower rape myth acceptance scores than did students with no training . Trained students also reported engaging in significantly more byst and er behaviors and observing more self-reported active byst and er behaviors when compared with nontrained students . When comparing self-reported active byst and er behavior scores of students trained with students hearing a Green Dot speech alone , the training was associated with significantly higher active byst and er behavior scores . Those receiving byst and er training appeared to report more active byst and er behaviors than those simply hearing a Green Dot speech , and both intervention groups reported more observed and active byst and er behaviors than nonexposed students The aim of the present study was to investigate two interventions based on Acceptance and Commitment Therapy ( ACT ) for depressive symptoms : A face-to-face treatment ( ACT group ) was compared to a guided self-help treatment delivered via the Internet consisting of two assessment sessions ( pre and post ) and an ACT-based Internet program ( iACT ) . Out patients experiencing at least mild depressive symptoms were r and omized to either approach . The iACT treatment group received access to an ACT-based Internet program and supportive web-based contact over a period of 6 weeks . The face-to-face group received ACT-based treatment once a week over the same period of time . In both groups , the results showed a significant effect on depression symptomatology , and general wellbeing after treatment and at the 18-month follow-up . However , the data indicated that the iACT group changed differently regarding depressive symptoms and wellbeing as compared to the face-to face ACT group . Results showed large pre-treatment to 18-month follow-up within-group effect sizes for all symptom measures in the iACT treatment group ( 1.59 - 2.08 ) , and for most outcome measures in the face-to-face ACT group ( 1.12 - 1.37 ) . This non-inferiority study provides evidence that guided Internet-delivered ACT intervention can be as effective as ACT-based face-to-face treatment for out patients reporting depressive symptoms , and it may offer some advantages over a face-to-face intervention Dating violence is a significant problem for older adolescents with implication s for the survivor 's health . Survivors disclose the violence to friends who are often ill equipped to help them manage the consequences . The purpose of this pilot study was to evaluate the effectiveness and feasibility of Friends Helping Friends , a community-level education program to teach older adolescents to recognize and intervene in dating violence . A convenience sample of 101 students aged 18 to 22 years were nonr and omly allocated to a treatment or control group and completed pre- and post-test measures . Compared with the control group , treatment group participants reported increased perceived responsibility to help , skills to act as a byst and er , and intention to help and decreased rape myth acceptance . Friends Helping Friends shows promise as an effective strategy for older adolescent females in the prevention and response to dating violence OBJECTIVE The present research reports on two r and omized controlled trials evaluating TakeCARE , a video byst and er program design ed to help prevent sexual violence on college campuses . METHOD In Study 1 , students were recruited from psychology courses at two universities . In Study 2 , first-year students were recruited from a required course at one university . In both studies , students were r and omly assigned to view one of two videos : TakeCARE or a control video on study skills . Just before viewing the videos , students completed measures of byst and er behavior toward friends and ratings of self-efficacy for performing such behaviors . The efficacy measure was administered again after the video , and both the byst and er behavior measure and the efficacy measure were administered at either one ( Study 1 ) or two ( Study 2 ) months later . RESULTS In both studies , students who viewed TakeCARE , compared to students who viewed the control video , reported engaging in more byst and er behavior toward friends and greater feelings of efficacy for performing such behavior . In Study 1 , feelings of efficacy mediated effects of TakeCARE on byst and er behavior ; this result did not emerge in Study 2 . CONCLUSIONS This research demonstrates that TakeCARE , a video byst and er program , can positively influence byst and er behavior toward friends . Given its potential to be easily distributed to an entire campus community , TakeCARE might be an effective addition to campus efforts to prevent sexual violence Abstract Rape myth acceptance , likelihood of raping , and sexually coercive behavior of 145 fraternity men r and omly assigned to a control group or a rape-prevention program were surveyed . One third of 23 fraternities on a mid-Atlantic public university campus volunteered to participate in the study . The rape-prevention intervention consisted of “ the men 's program , ” a victim empathy-based presentation titled “ How to help a sexual assault survivor : What men can do . ” Although no evidence of change in sexually coercive behavior was found , significant 7-month declines in rape myth acceptance and the likelihood of committing rape were shown among program participants . In the case of rape myth acceptance , the 7-month decrement remained lower in the participant group than in the control group . Implication s of using these initial findings from the men 's program for rape-prevention programming are discussed 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 This article reports findings from a longitudinal , experimental evaluation of a peer education theater program , Students Challenging Realities and Educating Against Myths ( SCREAM ) Theater . This study examines the impact of SCREAM Theater on a range of byst and er-related outcomes ( i.e. byst and er intentions , byst and er efficacy , perception of friend norms and byst and er behaviors ) in situations involving sexual violence and whether there was a differential impact of the program by participant sex . First-year college students completed three waves of surveys ( pretest , first post-test and second post-test ) . All participants received one dose of the intervention during summer orientation after the pretest . After the first post-test , participants were r and omly assigned to receive two additional doses , or to a control condition , in which they received no additional doses . Students in both one- and three-dose groups reported a number of positive increases . Overall , an intent-to-treat analysis ( n = 1390 ) indicated three doses of the intervention during the first semester of college result ed in better outcomes than the one-time intervention during summer orientation alone . Although both male and female students ' scores increased during the study period , female students consistently scored higher than male students on each outcome . The findings suggest that peer education theater holds promise for byst and er intervention education on college campuses |
12,548 | 20,528,379 | Existing AD medications were found to dominate st and ard treatment ( i.e. , no drugs ) , or they were found to be more costly and more effective than st and ard treatment . | This systematic review was conducted to summarize published pharmacoeconomic studies of Alzheimer 's disease ( AD ) medications . | Several clinical trials have demonstrated the efficacy and safety of the NMDA antagonist memantine in moderately severe to severe Alzheimer ’s disease ( AD ) patients . A 28-week pharmacoeconomic study conducted in the US also showed a reduction of total healthcare costs and informal care compared to placebo . Long-term implication s of memantine treatment were modelled in the UK and Finl and and revealed reductions in dependency , institutionalization and costs . However , these conclusions were not directly applicable to the Spanish setting where patients are mainly treated within the community . The objective of this study was to estimate the long-term implication s in terms of costs and health benefits of memantine therapy compared to st and ard care using a Spanish adaptation of previous models over a 2-year time horizon . As in previous adaptations , Markov health states were defined as a combination of severity ( mild-moderate , moderately severe , severe ) and dependency plus death as the absorbing state . Spain-specific data ( costs , mortality and epidemiological data ) were obtained from local and recently published cohorts of AD patients . Data on the effectiveness of memantine were derived from a r and omized double-blind placebo-controlled clinical trial of 252 moderately severe to severe AD patients . Effectiveness was measured as the time spent in a non-dependent health state . The evaluation was conducted over 2 years , while the efficacy of memantine was applied for 1 year only in order to ensure a conservative approach . The robustness of the model was tested by conducting stochastic analyses and various sensitivity analyses on the key assumptions . Patients receiving st and ard care were estimated to spend 6 months in a non-dependent state and to incur average total costs of € 24,700 over 2 years . The memantine strategy was associated with an additional 2.5 months in a non-dependent state and a € 700 cost reduction . Monte-Carlo simulations and sensitivity analyses supported these findings . Memantine appears to be cost-effective compared with st and ard care in moderately severe to severe AD patients in a Spanish setting . The prolonged independence provided by memantine treatment translated into cost reductions which offset drug costs and result ed in overall cost-savings A hybrid method based on cognitive interviewing and consensus panels was developed to pretest a question naire for caregivers of persons with Alzheimer disease ( AD ) . The objective of the question naire was to elicit caregivers ' attitudes and opinions on the use of medications to treat the disease . Thirty-one caregivers were divided into five pretest groups , within which each participant was asked to comment on question naire wording and design . The comments from participants in the first three groups were used to revise the question naire , and the revised version was given to participants in the remaining two groups . Overall , 81 % ( 118/146 ) of the participants ' comments were implemented . The number of comments made in the last two groups decreased relative to the number of comments made in the first three groups . The hybrid method enhanced the user-friendliness of the question naire and can serve as an alternative to common ad hoc pretest approaches that have little basis in theory Alzheimer 's disease is a progressive neurodegenerative disorder that results in tremendous economic and quality -of-life burdens . This paper presents estimates of the impact of tacrine use on the costs of caring for patients with Alzheimer 's disease . This study presents a cost analysis , based on a decision-analytic model constructed around the milestones in the progression of Alzheimer 's disease . Clinical data concerning the effectiveness of tacrine came from published results of an open-label follow-up study of 663 patients originally enrolled in a placebo-controlled clinical trial of tacrine . Data concerning longevity , nursing home time , and costs of community and nursing home care are taken from several reports based on prospect i ve cohorts of patients . The use of tacrine was associated with a cost savings of $ 9,250 ( 7.5 % ) over the patient 's lifetime from diagnosis to death , even when averaged over data from patients who discontinued tacrine treatment or took only low doses . Most of the savings were due to reduced time in nursing homes . Patients who continued higher doses of tacrine experienced a cost saving of more than $ 36,500 over 5 years . Model results persisted over a wide range of sensitivity analysis variations . The use of tacrine for patients with mild-to-moderate Alzheimer 's disease reduces the costs of medical and social services required for care , and it increases functioning and delays nursing home placement for up to 433 days . New treatments that can both improve clinical outcomes and save costs should be given serious consideration by clinicians and administrators BACKGROUND Alzheimer 's disease ( AD ) is estimated to affect up to 11 % of those aged > or = 65 years in the United States , and the number of patients with AD is predicted to increase over the next few decades as the population ages . The substantial social and economic burden associated with AD is well established , with the cost of management increasing as the disease progresses . OBJECTIVE The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care ( FTC ) . METHODS Calculations were made using the Assessment of Health Economics in Alzheimer 's Disease model , which applies predictive equations to estimate the need for FTC and the associated costs . The predictive equations were developed from longitudinal data on patients with AD . Inputs to the equations were derived by analyzing the data from 2 r and omized , placebo-controlled , galantamine clinical trials . Re source use ( from a payer perspective ) was estimated from US clinical trial data , and costs were estimated from several US data bases . Analyses were carried out over 10 years , and costs and benefits were discounted at 3 % . RESULTS In the base case , 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC , depending on dose . Treated patients spent 7 % to 8 % more time pre-FTC and 12 % to 14 % less time requiring FTC , result ing in savings of 2408 to 3601 US dollars . Time horizons below 3 years , very high discontinuation rates , or increased survival with galantamine reversed the savings . Conversely , limiting treatment to responders delayed FTC by 6 to 7 months , with savings of approximately 9097 to 11,578 US dollars . CONCLUSIONS These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly re sources such as formal home care and nursing homes , leading to cost savings over time Background In patients with moderately severe to severe Alzheimer ’s disease , the N-methyl-D-aspartate ( NMDA ) antagonist memantine has been shown to improve outcomes and to be associated with reductions in re source utilisation and total healthcare costs relative to no pharmacological intervention after 28 weeks in phase III clinical and pharmacoeconomic studies . However , the longer term cost implication s of treatment with memantine are not known . Objective To evaluate the effect of treatment with memantine in patients with moderately severe to severe Alzheimer ’s disease on re source use and on cost and patient outcomes in Finl and over a 5-year time horizon . Methods A Markov model was constructed to simulate a patient ’s progression through a finite series of health states with a time horizon of 5 years . The states were defined in terms of physical dependency , place of residency ( community or institution ) , and cognitive function . Each 6-month Markov cycle was repeated ten times . A 5 % rate was used to discount costs . Inputs for the model were derived from epidemiological data collected during the Kuopio 75 + Study , a Finnish population -based health survey of dementia and functional capacity among individuals aged ≥75 years . Costs were considered from a societal perspective . Probabilities used in the model , together with cost and re source use differences between treatment with memantine ( Ebixa ® , Namenda ® , Axura ® ) and no pharmacological intervention , were derived from a r and omised , double-blind , placebo-controlled clinical trial that included an economic assessment . This study enrolled 252 patients with moderately severe to severe Alzheimer ’s disease . We took a conservative approach that assumed that the effectiveness of treatment with memantine was limited to 12 months ’ duration . Monte Carlo simulations were performed to evaluate the effect of treatment with memantine on duration of independence and time to institutionalisation . Sensitivity analyses included memantine efficacy best- ( 5 years ) and worst- ( 6 months ) case scenarios , and an analysis in which 5 % discounting was not applied . Results Memantine therapy was associated with approximately 4 extra months of independence , 1 additional month of residence in the community , and a cost reduction relative to placebo of approximately € 1700 per patient over 5 years , despite the limiting of persistence of efficacy to 12 months ( year of costing , 2001 ) . Monte Carlo simulations and sensitivity analyses supported the findings . Conclusion : According to the model , over 5 years the additional drug costs of treating patients with moderately severe to severe Alzheimer ’s disease with memantine were amply offset by cost savings related chiefly to increased independence and delayed institutionalisation BACKGROUND Alzheimer 's disease ( AD ) places a significant burden on health care systems worldwide . As new treatments are developed , their cost-effectiveness is often assessed to help health care professionals make informed decisions . In addition to the more common practice of assessing direct medical costs , indirect costs , including time spent in caregiving , should be evaluated . METHODS This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine ( Exelon ) on caregivers of patients with AD . Results from two 26-week , placebo-controlled trials have demonstrated the clinical ly relevant and statistically significant efficacy of rivastigmine ( 6 - 12 mg/day ) compared to placebo , on cognition , activities of daily living , and global functioning . By delaying progression of AD , significant savings in caregiver burden are anticipated , as measured by time spent caregiving and its related costs . Data collected in a prospect i ve , observational study of AD patients and their caregivers were used to establish the relationship between disease severity ( based on Mini-Mental State Examination [ MMSE ] score ) and time spent caregiving ( according to the 5-item Caregivers Activity Survey score ) . A significant correlation was observed between the two scores ( N = 43 , r = -.56 , p < .0001 ) , demonstrating that more time for supervision from caregivers is required as the disease progresses . This finding was used to estimate the reduced caregiver burden result ing from the delay in disease progression that was demonstrated with use of rivastigmine . RESULTS Over a 2-year period , the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD ( MMSE score 21 - 30 ) , result ing in a total savings of approximately 11,253 dollars . Treatment of patients with moderately severe AD was also evaluated . The trend was similar but the impact was less , suggesting an economic benefit to early therapy . CONCLUSION Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients , caregivers , and payers , and should therefore be encouraged through initiatives design ed to identify and treat patients early in the course of disease Objective : To investigate the costs to society of Alzheimer disease ( AD ) care in a multinational , r and omized , placebo-controlled trial of donepezil in patients with moderate to severe AD . Methods : A total of 290 patients with AD ( screening st and ardized Mini-Mental State Examination score 5 to17 ) were r and omized to receive either donepezil ( n = 144 ; 5 mg/day for 28 days , followed by 10 mg/day as per clinician ’s judgment ) or placebo ( n = 146 ) for 24 weeks . The authors collected data on patient and caregiver health re source utilization prospect ively using the Canadian Utilization of Services Tracking question naire . Costs were calculated for patients and caregivers in each group based on re source utilization multiplied by the unit prices for each re source . A cost ( the average Ontario minimum wage for 1998 [ Can $ 6.85 per hour ] ) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living ( ADL ) . Results : Patient and caregiver demographics at baseline were similar across the two groups . After adjusting for baseline total cost per patient , the mean total societal cost per patient for the 24-week period was donepezil , Can $ 9,904 ( US $ 6,686 ) and placebo , Can $ 10,236 ( US $ 6,910 ) . This net cost saving of Can $ 332 ( US $ 224 ) included the average 24-week cost of donepezil treatment . Most of the cost-saving with donepezil treatment was due to less use of residential care by patients , and caregivers spending less time assisting patients with ADL . Conclusion : This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil Abstract Objectives : To explore whether Alzheimer ’s disease patients could rate their quality of life ( QOL ) using utility-based health indexes , and to provide new knowledge about the measurement properties of these instruments for patient and caregiver proxy ratings . Methods : A convenience sample of 60 mild-moderate AD patients and their caregivers were r and omized to complete the Quality of Well-Being Scale ( QWB ) , Health Utilities Index ( HUI3 ) or EQ-5D and visual analogue scale ( VAS ) on two occasions . Test – retest reliability ( intraclass correlation coefficients ) and convergent validity ( Spearman correlations ) of utility scores with global health status , activities of daily living , comorbidity , mood , cognition and other utility measures were assessed . Results : Completion time was shortest for the combined EQ-5D and VAS . For patients with mild dementia and for proxies , reliability was ≥ 0.70 for the EQ-5D , QWB and HUI3 . The EQ-5D had a ceiling effect for patient ratings . Convergent validity was demonstrated for patient and proxy ratings , with the strongest validity for EQ-5D ratings and the weakest validity for HUI3 patient ratings . Mean patient utility scores were significantly higher than mean proxy scores for all measures ( p<0.001 ) . Conclusions : For patient and proxy ratings , the EQ-5D had the best combination of measurement properties , although it had a substantial ceiling effect for patient ratings . Proxy QOL ratings did not accurately reflect patients ’ ratings Objective : To demonstrate the use of cost-effectiveness analysis to assess the economic impact of donepezil in the treatment of mild or moderate AD . Background : Cost-effectiveness analyses show the relationship between re sources used ( costs ) and health benefits achieved ( effects ) for an intervention compared with an alternative strategy . Methods : We developed a model to estimate the incremental cost-effectiveness of donepezil compared with no treatment . We determined costs per quality -adjusted life-years gained , a measurement that enhances the comparability of diverse studies . The model projects the progression of AD patients into more severe disease stages and into nursing homes . Data from a r and omized clinical trial of donepezil were used to assess the drug ’s impact on the 6-week probabilities of progression . Data on the costs and health-related quality of life associated with different disease stages and setting s were taken from published estimates and our companion cross-sectional study , respectively . Results : Donepezil costs are partially offset by a reduction in the costs of care due to enhancement in cognitive functioning and the delay to more costly disease stages and setting s. The magnitude of this cost offset and of the effect of donepezil on health-related quality of life depends on the model ’s assumptions about the duration of the drug effect , where controlled data are lacking . If the drug effect exceeds 2 years , the model predicts that for mild AD the drug would pay for itself in terms of cost offsets . Conclusions : The results of the cost-effectiveness model presented here suggest that donepezil may be cost-effective but additional controlled data on long-term drug efficacy are needed Objective : To estimate the prevalence of dementia with Lewy bodies ( DLB ) according to the consensus criteria in a general population aged 75 years or older . Methods : The “ Kuopio 75 + study ” is a population based health survey focused on the clinical epidemiology of dementia and functional capacity among elderly subjects aged 75 years or older . On 1 January 1998 , a r and om sample of 700 subjects was drawn from a total population born before 1 January 1923 , living in the city of Kuopio , northeast Finl and ( n = 4518 ) . The study subjects underwent a structured interview and clinical examination . Results : 601 elderly subjects ( 86 % of the r and om sample ) were examined . A dementia disorder was diagnosed in 137—a prevalence of 22.8 % ( 95 % confidence interval 19.4 % to 26.2 % ) . The prevalence of DLB was 5.0 % ( 3.2 % to 6.7 % ) , comprising 22 % of all demented subjects . Probable DLB was diagnosed in 20 subjects ( 3.3 % ( 1.9 % to 4.8 % ) ) , and possible DLB in 10 ( 1.7 % ( 0.6 % to 2.7 % ) ) . The prevalence of Alzheimer ’s disease was 10.6 % ( 47 % of all demented subjects ) , of vascular dementia , 5.3 % ( 23 % ) , and of other types of dementing disorders , 1.8 % ( 8 % ) . Conclusions : In a general population aged 75 years and older , the prevalence of a disorder fulfilling the diagnostic criteria of DLB is half that of Alzheimer ’s disease and the same as for vascular dementia A Canadian economic evaluation of propentofylline ( a therapy shown to be effective for patients with mild to moderate Alzheimer disease and /or vascular dementia ) versus st and ard care was conducted . Patients were categorized by functional abilities according to the Alberta Resident Classification System by translating measures that were originally captured through the Gottfries-Bråne-Steen scale . The Alberta Resident Classification System was then linked to a community data set of home care costs for a population with dementia . Cost and cost-effectiveness analyses were performed from the perspective of the Ministry of Health , the caregiver , and society using an intent-to-treat analysis for propentofylline versus placebo . Results , limited to the 48-week clinical trial duration , indicated that propentofylline improved health outcomes of persons with dementia as statistically significant treatment effects were found . However , although an incremental cost for the propentofylline intervention was incurred from the Ministry of Health perspective , home care and , to a larger extent , caregiver costs were reduced . Savings in these areas may have partially offset annual treatment medication costs because a non – statistically significant cost difference was observed from a societal perspective Background Clinical trials with memantine , an uncompetitive moderate-affinity NMDA antagonist , have shown improved clinical outcomes , increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer ’s disease . In a r and omised double-blind , placebo-controlled , 28-week study conducted in the US , reductions in re source utilisation and total healthcare costs were noted with memantine relative to placebo . While these findings suggest that , compared with placebo , memantine provides cost savings , further analyses may help to quantify potential economic gains over a longer treatment period . Objective To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer ’s disease over a 2-year period . Methods A Markov model was constructed to simulate patient progression through a series of health states related to severity , dependency ( determined by patient scores on the Alzheimer ’s Disease Cooperative Study -Activities of Daily Living [ ADCS-ADL ] inventory and residential status ( ‘ institutionalisation ’ ) with a time horizon of 2 years ( each 6-month Markov cycle was repeated four times ) . Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week , r and omised , double-blind , placebo-controlled clinical trial . Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study , while data on quality -adjusted life-years ( QALYs ) were derived from a Danish longitudinal study . To ensure conservative estimates from the model , the base case analysis assumed drug effectiveness was limited to 12 months . Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model . Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters . Finally , a subgroup analysis was performed to determine which patients were most likely to benefit from memantine . Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective . Results The base case analysis found that , compared with no treatment , memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence , years in the community and QALYs . Sensitivity analyses supported these findings . For each category of Alzheimer ’s disease patient examined , treatment with memantine was a cost-effective strategy . The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of ≥10 . Conclusion This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment . These benefits appear to result from prolonged patient independence and delayed institution-alisation for moderately severe and severe Alzheimer ’s disease patients on memantine compared with no pharmacological treatment OBJECTIVE To estimate per-patient potential cost savings using rivastigmine in the treatment of Alzheimer 's disease ( AD ) in Canada . BACKGROUND In recent years , new members of a class of pharmaceuticals known as cholinesterase inhibitors have been introduced for the treatment of patients with AD . Two recent studies conducted in the United Kingdom and the United States estimated potential cost savings from the new cholinesterase inhibitor rivastigmine . The present study combined the disease-progression model used in those 2 studies with Canadian costs to estimate per-patient potential savings result ing from the treatment of AD in Canada . METHODS Efficacy data from 2 pivotal , phase III clinical trials of rivastigmine were used in a hazard model of disease progression to estimate long-term differences in cognitive functioning between patients receiving rivastigmine and patients receiving no treatment . We used the Mini-Mental State Examination ( MMSE ) score as our measure of disease progression . We also used Canadian costs of AD care , estimated as a function of MMSE score , to estimate cost savings experienced by treated patients compared with patients receiving no treatment . All costs and cost savings are presented in 1997 Canadian dollars . We used a societal perspective in this analysis . RESULTS Rivastigmine was estimated to delay the transition to more severe stages of AD by up to 188 days for patients with mild AD after 2 years of treatment . For patients with mild-to-moderate and moderate disease , this delay was estimated to be 106 and 44 days , respectively . For patients with the mild stage of AD , estimated average daily cost savings ( excluding the cost of rivastigmine ) ranged from Can $ 0.45 per patient per day at 6 months to Can $ 6.44 per patient per day after 2 years of treatment . For all patients , these estimated average daily cost savings ranged from a low of Can $ 0.71 per patient per day after 6 months of treatment to a high of Can $ 4.93 per patient per day after 2 years . CONCLUSION On average , treatment with rivastigmine yields savings in the direct cost of caring for AD patients that exceed the cost of the drug after 2 years of treatment We developed a set of informant-based items describing performance of activities of daily living ( ADL ) by patients with Alzheimer 's disease ( AD ) to identify which ADL are useful for assessment of patients in clinical trials . Evaluation of ADL is an important outcome measure in AD clinical trials . For clinical trial measurement , ADL should have broad applicability , good test-retest reliability , scaling to cover a range of performance , and sensitive to detect change in disease progression . A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer 's Disease Cooperative Study Instrument protocol . Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months . Controls performed virtually all ADL items optimally at baseline and at 12 months . Among subjects with AD , 27 of the 45 ADL were widely applicable , i.e. , performed at baseline or premorbidly by > 90 % of subjects ; showed good test-retest reliability between baseline and 1 and 2 months ; correlated with MMSE scores of AD patients cross-sectionally ; and showed a decline in performance from baseline to 12 months in at least 20 % of AD patients . ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE . The remaining 18 ADL included several that may be useful for trials that target specific population s , e.g. , women with AD . Because change on specific items depends on baseline MMSE , ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial Abstract Background : Alzheimer ’s disease ( AD ) is a devastating illness that causes enormous emotional stress to affected families and is associated with substantial medical and nonmedical costs . Objective : To determine the effects of 28 weeks of memantine treatment for patients with AD on re source utilisation and costs . Study design and methods : Multicentre , prospect i ve , double-blind , r and omised , placebo-controlled clinical trial performed in the US . The Wilcoxon-Mann-Whitney test was used to examine the re source utilisation variables and logistic regression models were used for multivariate re source utilisation analyses . Analysis of covariance ( ANCOVA ) models ( log and non-log ) were computed to examine costs from a societal perspective . All costs were calculated in 1999 US dollars . Study population : Out patients with moderate to severe AD . Overall , 252 patients received r and omised treatment , and 166 patients ( placebo n = 76 , memantine n = 90 ) formed the treated-per- protocol ( TPP ) subset for the health economic analyses , on which the main cost analysis was based . Main outcome measure : Re source Utilisation in Dementia ( RUD ) scale , measuring patient and caregiver re source utilisation , and various sources for cost calculations . Results : Controlling for baseline differences between the groups , significantly less caregiver time was needed for patients receiving memantine than for those receiving placebo ( difference 51.5 hours per month ; 95 % CI −95.27 , −7.17 ; p = 0.02 ) . Analysis of residential status also favoured memantine : time to institutionalisation ( p = 0.052 ) and institutionalisation at week 28 ( p = 0.04 with the chi-square test ) . Total costs from a societal perspective were lower in the memantine group ( difference $ US1089.74/month [ non-overlapping 95 % CI for treatment difference −1954.90 , −224.58 ] ; p = 0.01 ) . The main differences between the groups were total caregiver costs ( $ US-823.77/month ; p = 0.03 ) and direct nonmedical costs ( $ US-430.84/month ; p = 0.07 ) favouring memantine treatment . Patient direct medical costs were higher in the memantine group ( p < 0.01 ) , mainly due to the cost of memantine . Conclusion : Re source utilisation and total health costs were lower in the memantine group than the placebo group . The results suggest that memantine treatment of patients with moderate to severe AD is cost saving from a societal perspective |
12,549 | 29,288,868 | The vast majority of fMRI‐nf findings suggest that self‐regulation of specific brain signatures seems viable ; however , replication of concomitant behavioral outcomes remains sparse .
We can certainly change brain activity with fMRI‐nf .
HighlightsWe conducted a systematic review of 99 fMRI neurofeedback ( fMRI‐nf ) experiments.fMRI‐nf successfully drives BOLD regulation and behavioral change .
BOLD regulation guarantees neither neural regulation nor clinical improvement .
Psychosocial factors may contribute to regulation of BOLD signal and behavior . | & NA ; Neurofeedback relying on functional magnetic resonance imaging ( fMRI‐nf ) heralds new prospect s for self‐regulating brain and behavior .
Here we provide the first comprehensive review of the fMRI‐nf literature and the first systematic data base of fMRI‐nf findings .
Whereas modulating specific brain activity promises to mold cognition , emotion , thought , and action , reducing complex mental health issues to circumscribed brain regions may represent a tenuous goal . | Attention Deficit Hyperactivity Disorder ( ADHD ) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex ( dACC ) . In the current study , we investigated for the first time whether real-time fMRI neurofeedback ( rt-fMRI ) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning . An exploratory r and omized controlled treatment study with blinding of the participants was conducted . Participants with ADHD ( n = 7 in the neurofeedback group , and n = 6 in the control group ) attended four weekly MRI training sessions ( 60-min training time/session ) , during which they performed a mental calculation task at varying levels of difficulty , in order to learn how to up-regulate dACC activation . Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC . Before and after the training , ADHD symptoms and relevant cognitive functioning was assessed . Results showed that both groups achieved a significant increase in dACC activation levels over sessions . While there was no significant difference between the neurofeedback and control group in clinical outcome , neurofeedback participants showed stronger improvement on cognitive functioning . The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients . Due to the study ’s small sample size , potential clinical benefits need to be further investigated in future studies . Trial Registration : IS RCT Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression . Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging ( fMRI ) . In a proof-of-concept study , eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions ( such as the ventrolateral prefrontal cortex ( VLPFC ) and insula ) during four neurofeedback sessions . Their clinical symptoms , as assessed with the 17-item Hamilton Rating Scale for Depression ( HDRS ) , improved significantly . A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinical ly . R and omised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression Background : Spider phobics show an exaggerated fear response when encountering spiders . This fear response is aggravated by negative and irrational beliefs about the feared object . Cognitive re appraisal can target these beliefs , and therefore has a fear regulating effect . The presented study investigated if neurofeedback derived from functional magnetic resonance imaging ( fMRI ) would facilitate anxiety regulation by cognitive re appraisal , using spider phobia as a model of anxiety disorders . Feedback was provided based on activation in left dorsolateral prefrontal cortex and right insula , as indicators of engagement and regulation success , respectively . Methods : Eighteen female spider phobics participated in a r and omized , controlled , single-blinded study . All participants completed a training session in the MRI scanner . Participants assigned to the neurofeedback condition were instructed to shape their regulatory strategy based on the provided feedback . Participants assigned to the control condition were asked to adapt their strategy intuitively . Results : Neurofeedback participants exhibited lower anxiety levels than the control group at the end of the training . In addition , only neurofeedback participants achieved down-regulation of insula activation levels by cognitive re appraisal . Group differences became more pronounced over time , supporting learning as a mechanism behind this effect . Importantly , within the neurofeedback group , achieved changes in insula activation levels during training predicted long-term anxiety reduction . Conclusions : The conducted study provides first evidence that fMRI neurofeedback has a facilitating effect on anxiety regulation in spider phobia If an individual can learn to directly control activation of localized regions within the brain , this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease . Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain . Here , we found that by using real-time functional MRI ( rtfMRI ) to guide training , subjects were able to learn to control activation in the rostral anterior cingulate cortex ( rACC ) , a region putatively involved in pain perception and regulation . When subjects deliberately induced increases or decreases in rACC fMRI activation , there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus . Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information , or using rtfMRI information derived from a different brain region , or sham rtfMRI information derived previously from a different subject . Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training . These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training , that voluntary control over activation in rACC leads to control over pain perception , and that these effects were powerful enough to impact severe , chronic clinical pain Abstract Attention Deficit Hyperactivity Disorder ( ADHD ) is associated with poor self‐control , underpinned by inferior fronto‐striatal deficits . Real‐time functional magnetic resonance neurofeedback ( rtfMRI‐NF ) allows participants to gain self‐control over dysregulated brain regions . Despite evidence for beneficial effects of electrophysiological‐NF on ADHD symptoms , no study has applied the spatially superior rtfMRI‐NF neurotherapy to ADHD . A r and omized controlled trial tested the efficacy of rtfMRI‐NF of right inferior prefrontal cortex ( rIFG ) , a key region that is compromised in ADHD and upregulated with psychostimulants , on improvement of ADHD symptoms , cognition , and inhibitory fMRI activation . To control for region‐specificity , an active control group received rtfMRI‐NF of the left parahippocampal gyrus ( lPHG ) . Thirty‐one ADHD boys were r and omly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI‐NF runs over 2 weeks . Feedback was provided through a video‐clip of a rocket that had to be moved up into space . A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life . Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11‐month follow‐up . Only the group targeting rIFG , however , showed a transfer effect , which correlated with ADHD symptom reductions , improved at trend level in sustained attention , and showed increased IFG activation during an inhibitory fMRI task . This proof‐of‐concept study demonstrates for the first time feasibility , safety , and shorter‐ and longer‐term efficacy of rtfMRI‐NF of rIFG in adolescents with ADHD . Hum Brain Mapp 38:3190–3209 , 2017 . © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals , BACKGROUND Cue-induced craving plays an important role in relapse , and the neural correlates of cue-induced craving have been eluci date d using fMRI . This study examined the utility of real-time fMRI ( rtfMRI ) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers . METHODS Nicotine-dependent smokers were r and omized to rtfMRI neurofeedback or to a no-feedback control group . Participants completed 3 neuroimaging visits . Within each visit , an initial run during which smoking-related cues were used to provoke craving , an individualized craving-related region of interest ( ROI ) in the prefrontal cortex or anterior cingulate cortex was identified . In the rtfMRI group , activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure . The control group had an identical experience with no feedback provided . RESULTS Forty-four nicotine-dependent smokers were recruited to participate in our study ; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis . Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group . LIMITATIONS As participants were not seeking treatment , clinical outcomes are lacking . CONCLUSION Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving , relative to a control group . Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinical ly meaningful treatment modality Significance Real-time functional MRI allows the use of well-localized , complex network activity patterns to drive neurofeedback , rather than a simple up/down regulation of a specific cortical region . We based our feedback on differential levels of activity in two high-order visual areas but misled participants to believe the feedback was r and om . Even without being given an explicit strategy , or having any awareness or intention of learning , our results show changes in resting-state connectivity , which are correlated with the ability to implicitly modulate interactions between neural networks to positively impact feedback . This opens up numerous possibilities for research , as well as for potential clinical intervention , even in states of altered consciousness . Recent advances in blood oxygen level-dependent – functional MRI (BOLD-fMRI)-based neurofeedback reveal that participants can modulate neuronal properties . However , it is unknown whether such training effects can be introduced in the absence of participants ' awareness that they are being trained . Here , we show unconscious neurofeedback training , which consequently produced changes in functional connectivity , introduced in participants who received positive and negative rewards that were covertly coupled to activity in two category-selective visual cortex regions . The results indicate that brain networks can be modified even in the complete absence of intention and awareness of the learning situation , raising intriguing possibilities for clinical interventions Concerns about the reliability and reproducibility of biomedical research have been voiced across several arenas . In this commentary , I discuss how a poor appreciation of the role of chance in statistical inference contributes to this problem . In particular , how poor scientific design , such as low statistical power , and question able research practice s , such as post hoc hypothesizing and undisclosed flexibility in analyses , yield a high proportion of false-positive results . I discuss how the current publication and funding system perpetuates this poor practice by rewarding positive , yet often unreliable , results over rigorous methods . I conclude by discussing how scientists can prevent being fooled by chance findings by adopting well established , but often ignored , method ological best- practice . There is increasing awareness of the problem of unreliable findings across biomedical sciences ( Ioannidis , 2005 ) . Many “ l and mark ” findings could not be replicated ( Scott et al. , 2008 ; Begley and Ellis , 2012 ; Steward et al. , 2012 ) and many promising pre clinical findings have failed to translate into clinical application ( Perel et al. , 2007 ; Prinz et al. , 2011 ) , leading many to question whether science is broken ( Economist,2013 ) . Central to this problem is a poor appreciation of the role of chance in the scientific process . As neuroscience has developed over the past 50 years , many of the large , easily observable effects have been found , and the field is likely pursuing smaller and more subtle effects . The corresponding growth in computational capabilities ( Moore , 1998 ) means that research ers can run numerous tests on a single data set in a matter of minutes . The human brain processes r and omness poorly , and the huge potential for undisclosed analytical flexibility in modern data -management packages leaves research ers increasingly vulnerable to being fooled by chance . Research ers can not measure an entire population of interest , so they take sample s and use statistical inference to determine the probability that the results BACKGROUND Many studies suggest that electroencephalographic ( EEG ) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder ( ADHD ) . However , numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial . The present trial examined the efficacy ( compared with sham neurofeedback ) and efficiency ( compared with meta-cognitive therapy ) of a st and ard EEG neurofeedback protocol in adults with ADHD . METHODS We did a concurrent , triple-blind , r and omised , controlled trial using authorised deception in adults with ADHD from one centre ( University of Tübingen ) in Tübingen , Germany . Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD , were aged between 18 years and 60 years , and had no or stable use of medication for at least 2 months with no intention to change . We excluded participants who had comorbid schizophrenia or schizoaffective disorder , bipolar disorder , borderline personality disorder , epilepsy , or traumatic brain injury ; substance abuse or dependence ; or current or planned other psychological treatment . Those eligible were r and omly assigned to three groups : a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks , a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks , or a meta-cognitive group therapy group which received 12 sessions over 12 weeks . Participants were assigned equally to one of the three interventions through a computerised minimisation r and omisation procedure stratified by sex , age , and baseline symptom severity of ADHD . Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback , but those receiving meta-cognitive therapy were aware of their treatment . Clinical assessors ( ie , those assessing outcomes ) and research staff who did the neurofeedback training were masked to participants ' r and omisation status only for neurofeedback and sham neurofeedback . The primary outcome was symptom score on the Conners ' adult ADHD rating scale , assessed before treatment , at midtreatment ( after 8 weeks ) , after treatment ( after 16 weeks ) , and 6 months later . All individuals with at least one observation after r and omisation were included in the analyses . This trial is registered with Clinical Trials.gov , number NCT01883765 . FINDINGS Between Feb 1 , 2013 , and Dec 1 , 2015 , 761 people were assessed for eligibility . 656 ( 86 % ) were excluded and 118 ( 15 % ) were eligible for participation in this study . Eligible participants were r and omly assigned to neurofeedback ( 38 [ 32 % ] ) , sham neurofeedback ( 39 [ 33 % ] ) , or meta-cognitive therapy ( 41 [ 35 % ] ) . 37 ( 97 % ) individuals for neurofeedback , 38 ( 97 % ) for sham neurofeedback , and 38 ( 93 % ) for meta-cognitive therapy were included in analyses . Self-reported ADHD symptoms decreased substantially for all treatment groups ( B=-2·58 [ 95 % CI -3·48 to -1·68 ] ; p<0·0001 ) between pretreatment and the end of 6 month follow-up , independent of treatment condition ( neurofeedback vs sham neurofeedback B=-0·89 [ 95 % CI -2·14 to 0·37 ] , p=0·168 ; neurofeedback vs meta-cognitive therapy -0·30 [ -1·55 to 0·95 ] , p=0·639 ) . No treatment-related or trial-related serious adverse events were reported . INTERPRETATION Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy . All three treatments were equivalently effective in reducing ADHD symptoms . This first r and omised , sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults . FUNDING German Research Foundation Real-time functional magnetic resonance imaging ( rt-fMRI ) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception . To further increase the effect of rt-fMRI neurofeedback on pain , we directly compared two different target regions of the pain network , notably the anterior insular cortex ( AIC ) and the anterior cingulate cortex ( ACC ) . Participants for this prospect i ve study were r and omly assigned to two age-matched groups of 14 participants each ( 7 females per group ) for AIC and ACC feedback . First , a functional localizer using block- design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC . Second , subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation . Data analysis included task-related and functional connectivity analysis . At the behavioral level , pain ratings significantly decreased during feedback vs. localizer runs , but there was no difference between AIC and ACC groups . Concerning neuroimaging , ACC and AIC showed consistent involvement of the cau date nucleus for subjects that learned down-regulation ( 17/28 ) in both task-related and functional connectivity analysis . The functional connectivity toward the cau date nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex . Consequently , the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the cau date nucleus , although functional connectivity indicates that the direct connection seems to be stronger with the ACC . Additionally , the cau date , an important area involved in pain perception and suppression , could be a good rt-fMRI target itself . Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain perception Objective : Real-time functional magnetic resonance imaging ( rt-fMRI ) neurofeedback ( NF ) uses feedback of the patient ’s own brain activity to self-regulate brain networks which in turn could lead to a change in behavior and clinical symptoms . The objective was to determine the effect of NF and motor training ( MOT ) alone on motor and non-motor functions in Parkinson ’s Disease ( PD ) in a 10-week small Phase I r and omized controlled trial . Methods : Thirty patients with Parkinson ’s disease ( PD ; Hoehn and Yahr I-III ) and no significant comorbidity took part in the trial with r and om allocation to two groups . Group 1 ( NF : 15 patients ) received rt-fMRI-NF with MOT . Group 2 ( MOT : 15 patients ) received MOT alone . The primary outcome measure was the Movement Disorder Society — Unified PD Rating Scale-Motor scale ( MDS-UPDRS-MS ) , administered pre- and post-intervention “ off-medication ” . The secondary outcome measures were the “ on-medication ” MDS-UPDRS , the PD Question naire-39 , and quantitative motor assessment s after 4 and 10 weeks . Results : Patients in the NF group were able to upregulate activity in the supplementary motor area ( SMA ) by using motor imagery . They improved by an average of 4.5 points on the MDS-UPDRS-MS in the “ off-medication ” state ( 95 % confidence interval : −2.5 to −6.6 ) , whereas the MOT group improved only by 1.9 points ( 95 % confidence interval + 3.2 to −6.8 ) . The improvement in the intervention group meets the minimal clinical ly important difference which is also on par with other non-invasive therapies such as repetitive Transcranial Magnetic Stimulation ( rTMS ) . However , the improvement did not differ significantly between the groups . No adverse events were reported in either group . Interpretation : This Phase I study suggests that NF combined with MOT is safe and improves motor symptoms immediately after treatment , but larger trials are needed to explore its superiority over active control conditions It is not currently known whether subjects can learn to voluntarily control activation in localized regions of their own brain using neuroimaging . Here , we show that subjects were able to learn enhanced voluntary control over task-specific activation in a chosen target region , the somatomotor cortex . During an imagined manual action task , subjects were provided with continuous direction regarding their cognitive processes . Subjects received feedback information about their current level of activation in a target region of interest ( ROI ) derived using real-time functional magnetic resonance imaging ( rtfMRI ) , and they received automatically-adjusted instructions for the level of activation to achieve . Information was provided both as continously upated graphs and using a simple virtual reality interface that provided an image analog of the level of activation . Through training , subjects achieved an enhancement in their control over brain activation that was anatomically specific to the target ROI , the somatomotor cortex . The enhancement took place when rtfMRI-based training was provided , but not in a control group that received similar training without rtfMRI information , showing that the effect was not due to conventional , practice -based neural plasticity alone . Following training , using cognitive processes alone subjects could volitionally induce fMRI activation in the somatomotor cortex that was comparable in magnitude to the activation observed during actual movement . The trained subjects increased fMRI activation without muscle tensing , and were able to continue to control brain activation even when real-time fMRI information was no longer provided . These results show that rtfMRI information can be used to direct cognitive processes , and that subjects are able to learn volitionally regulate activation in an anatomically-targeted brain region , surpassing the task-driven activation present before training With the use of real-time functional magnetic resonance imaging neurofeedback ( NF ) , amygdala activitiy can be visualized in real time . In this study , continuous amygdala NF was provided to patients with borderline personality disorder ( BPD ) with the instruction to down-regulate . During four sessions of NF training , patients viewed aversive pictures and received feedback from a thermometer display , which showed the amygdala blood oxygenation level-dependent signal . Conditions of regulation and viewing without regulation were presented . Each session started with a resting-state scan and was followed by a transfer run without NF . Amygdala regulation , task-related and resting-state functional brain connectivity were analyzed . Self-ratings of dissociation and difficulty in emotion regulation were collected . BPD patients down-regulated right amygdala activation but there were no improvements over time . Task-related amygdala-ventromedial prefrontal cortex connectivity was altered across the four sessions , with an increased connectivity when regulating vs viewing pictures . Resting-state amygdala-lateral prefrontal cortex connectivity was altered and dissociation , as well as scores for ' lack of emotional awareness ' , decreased with training . Results demonstrated that amygdala NF may improve healthy brain connectivity , as well as emotion regulation . A r and omized-controlled trial is needed to investigate whether amygdala NF is instrumental for improving neural regulation and emotion regulation in BPD patients Real-time fMRI ( rtfMRI ) neurofeedback ( NF ) facilitates volitional control over brain activity and the modulation of associated mental functions . The NF signals of traditional rtfMRI-NF studies predominantly reflect neuronal activity within ROIs . In this study , we describe a novel rtfMRI-NF approach that includes a functional connectivity ( FC ) component in the NF signal ( FC-added rtfMRI-NF ) . We estimated the efficacy of the FC-added rtfMRI-NF method by applying it to nicotine-dependent heavy smokers in an effort to reduce cigarette craving . ACC and medial pFC as well as the posterior cingulate cortex and precuneus are associated with cigarette craving and were chosen as ROIs . Fourteen heavy smokers were r and omly assigned to receive one of two types of NF : traditional activity-based rtfMRI-NF or FC-added rtfMRI-NF . Participants received rtfMRI-NF training during two separate visits after overnight smoking cessation , and cigarette craving score was assessed . The FC-added rtfMRI-NF result ed in greater neuronal activity and increased FC between the targeted ROIs than the traditional activity-based rtfMRI-NF and result ed in lower craving score . In the FC-added rtfMRI-NF condition , the average of neuronal activity and FC was tightly associated with craving score ( Bonferroni-corrected p = .028 ) . However , in the activity-based rtfMRI-NF condition , no association was detected ( uncorrected p > .081 ) . Non-rtfMRI data analysis also showed enhanced neuronal activity and FC with FC-added NF than with activity-based NF . These results demonstrate that FC-added rtfMRI-NF facilitates greater volitional control over brain activity and connectivity and greater modulation of mental function than activity-based rtfMRI-NF In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies |
12,550 | 23,888,484 | There was no statistically significant improvement in survival , lung , or cardiac health .
Although oxygenation improved , mild hypercapnia was noted .
Participants fell asleep quicker and spent a reduced percentage of total sleep time in rapid eye movement sleep , but there were no demonstrable improvements in qualitative sleep parameters .
Again , oxygenation improved , but mild hypercapnia result ed .
Other exercise parameters were not altered by the use of oxygen .
There are no published data to guide the prescription of chronic oxygen supplementation to people with advanced lung disease due to CF .
Short-term oxygen therapy during sleep and exercise improves oxygenation but is associated with modest and probably clinical ly inconsequential hypercapnia .
There are improvements in exercise duration , time to fall asleep and regular attendance at school or work . | BACKGROUND The most serious complications of cystic fibrosis ( CF ) relate to respiratory insufficiency .
Oxygen supplementation therapy has long been a st and ard of care for individuals with chronic lung diseases associated with hypoxemia .
Physicians commonly prescribe oxygen therapy for people with CF when hypoxemia occurs .
However , it is unclear if empiric evidence is available to provide indications for this therapy with its financial costs and often profound impact on lifestyle .
OBJECTIVES To assess whether oxygen therapy improves the longevity or quality of life of individuals with CF . | Oxygen supplementation may improve exercise tolerance and the physiological response to exercise in cystic fibrosis ( CF ) patients . Elevated barometric pressure at low altitude is a simple means of increasing the quantity of inspired oxygen . Our objectives were to examine the effect of natural oxygen enrichment ( at the Dead Sea , 396 m below sea level ) on exercise capacity , and the physiological responses to maximal and submaximal exercise in CF patients . Patients were tested twice : at sea level ( barometric pressure , 754 + /- 6 mmHg , mean + /- SD ) , and at the Dead Sea ( barometric pressure , 791 + /- 3 mmHg ) , in a r and omized crossover design . We studied 14 CF patients ( 6 females , 8 males ) , aged 15 - 45 years , with moderate to severe lung disease ( mean forced expired volume in 1 sec = 50.0 + /- 11.2 % predicted ) . Tests at each site included resting spirometry , anthropometry , a grade d submaximal exercise test , a maximal exercise test on a treadmill , and a 6-min walk test . Tests were performed in identical order at both sites . Tests at the Dead Sea were performed 72 hr after arrival . No differences between sites were observed in lung function at rest . Peak oxygen consumption was significantly improved at the Dead Sea compared with sea level ( 1.68 + /- 0.73 vs. 1.57 + /- 0.74 l/min , respectively , P = 0.05 ) , along with an improvement in the ventilatory equivalent for oxygen ( 41.2 + /- 6.3 vs. 46.1 + /- 7.1 , respectively , P < 0.05 ) . During submaximal exercise , blood oxygen saturation improved at the Dead Sea compared with sea level at all exercise intensities ( P < 0.05 ) . In conclusion , these results suggest that even a brief stay at the Dead Sea area may have physiological benefits for CF patients with moderate to severe lung disease Patients with cystic fibrosis ( CF ) and advanced pulmonary disease have pulmonary limitation of exercise , often associated with arterial oxygen desaturation . Improving oxygenation during exercise by providing supplemental oxygen may improve exercise performance in these patients . To test this , we performed grade d exercise stress tests in 22 CF patients with severe pulmonary disease ( mean PaO2 , 64 + /- 2 mm Hg [ + /- SE ] ; PaCO2 46 + /- 2 mm Hg ; RV/TLC , 57 + /- 4 percent ; FEV1 , 38 + /- 4 percent of predicted ; FEF25 - 75 % , 13 + /- 2 percent of predicted ; median age , 26 years ) and compared them to 21 controls ( RV/TLC , 27 + /- 4 percent ; FEV1 , 112 + /- 2 percent of predicted ; FEF25 - 75 % , 80 + /- 4 percent of predicted ; median age , 29 years ) . Each subject performed grade d exercise stress tests while breathing FIO2 of 0.21 and FIO2 of 0.30 . Subjects were blinded to the composition of the inspired gas , and the order of testing was r and omized . We found that CF subjects exercised longer , had a higher maximal VO2 , higher O2 pulse , and less arterial oxygen desaturation when receiving supplemental O2 . Control subjects exercised longer when breathing supplemental O2 but had no significant change in maximal VO2 , O2 pulse , or SaO2 . Both CF and control subjects had increased end-tidal PCO2 when exercising while breathing supplemental O2 . We conclude that CF patients with advanced pulmonary disease have increased exercise tolerance and aerobic capacity when exercising while breathing supplemental O2 The effects of supplemental O2 on recovery from supramaximal exercise and subsequent performance remain unknown . If recovery from exercise could be enhanced in individuals with chronic lung disease , subsequent supramaximal exercise performance could also be improved . Recovery from supramaximal exercise and subsequent supramaximal exercise performance were assessed after 10 min of breathing 100 % O2 or room air ( RA ) in 17 cystic fibrosis ( CF ) patients [ 25 + /- 10 ( SD ) yr old , 53 % men , forced expired volume in 1 s = 62 + /- 21 % predicted ] and 17 normal subjects ( 25 + /- 8 yr old , 59 % men , forced expired volume in 1 s = 112 + /- 15 % predicted ) . Supramaximal performance was assessed as the work of sustained bicycling at a load of 130 % of the maximum load achieved during a grade d maximal exercise . Peak minute ventilation ( VE ) and heart rate ( HR ) were lower in CF patients at the end of each supramaximal bout than in controls . In CF patients , single-exponential time decay constants indicated faster recovery of HR ( tau HR = 86 + /- 8 and 73 + /- 6 s in RA and O2 , respectively , P < 0.01 ) . Similarly , fast and slow time constants of two-exponential equations providing the best fit for ventilatory recovery were improved in CF patients during O2 breathing ( tau 1VE = 132.1 + /- 10.5 vs. 82.5 + /- 10.4 s ; tau 2VE = 880.3 + /- 300.1 vs. 368.6 + /- 107.1 s , P < 0.01 ) . However , no such improvements occurred in controls . Supramaximal performance after O2 improved in CF patients ( 109 + /- 6 % of the 1st bout after O2 vs. 94 + /- 6 % in RA , P < 0.01 ) . O2 supplementation had no effect on subsequent performance in controls ( 97 + /- 3 % in O2 vs. 93 + /- 3 % in RA ) . We conclude that supplemental O2 after a short bout of supramaximal exercise accelerates recovery and preserves subsequent supramaximal performance in patients with CF We tested the hypothesis that maximal exercise performance in adults with cystic fibrosis is limited by arterial hypoxemia . In study 1 , patients completed two maximal exercise tests , a control and a test with 400 ml of added dead space . Maximal O2 consumption was significantly lower in the added dead space study vs. control ( 1.04 + /- 0.15 vs. 1.20 + /- 0.11 l/min ; P < 0.05 ) , with no difference in peak ventilation . There was significant O2 desaturation during exercise that was equal in both control and added dead space studies . The decrease in maximal O2 consumption with added dead space suggests that maximal exercise in cystic fibrosis is limited by respiratory factors . We subsequently examined whether pulmonary mechanics or arterial hypoxemia limits maximal exercise performance . In study 2 , patients completed two maximal exercise tests , a control and a test with 400 ml of added dead space while also breathing 38 % O2 . Added dead space was used to overcome the suppressive effects of hyperoxia on minute ventilation . Maximal O2 consumption was significantly higher with added dead space and 38 % O2 vs. control ( 1.62 + /- 0.16 vs. 1.43 + /- 0.14 l/min ; P < 0.05 ) . Peak ventilation and O2 saturation were significantly greater in the added dead space and 38 % O2 test vs. control . The increase in maximal O2 consumption and peak ventilation with added dead space and 38 % O2 suggests that maximal exercise in cystic fibrosis is limited by arterial hypoxemia Background : The clinical benefits of domiciliary non-invasive positive pressure ventilation ( NIV ) have not been established in cystic fibrosis ( CF ) . We studied the effects of nocturnal NIV on quality of life ( QoL ) , functional and physiological outcomes in CF subjects with awake hypercapnia ( arterial carbon dioxide pressure Paco2>45 mm Hg ) . Methods : In a r and omised , placebo controlled , crossover study , eight subjects with CF , mean ( SD ) age 37 ( 8) years , body mass index 21.1 ( 2.6 ) kg/m2 , forced expiratory volume in 1 s 35 (8)% predicted and Paco2 52 ( 4 ) mm Hg received 6 weeks of nocturnal ( 1 ) air ( placebo ) , ( 2 ) oxygen and ( 3 ) NIV . The primary outcome measures were CF specific QoL , daytime sleepiness and exertional dyspnoea . Secondary outcome measures were awake and asleep gas exchange , sleep architecture , lung function and peak exercise capacity . Results : Compared with air , NIV improved the chest symptom score in the CF QoL Question naire ( mean difference 10 ; 95 % CI 5 to 16 ; p = 0.002 ) and the transitional dyspnoea index score ( mean difference 3.1 ; 95 % CI 1.2–5.0 ; p = 0.01 ) . It reduced maximum nocturnal pressure of transcutaneous CO2 ( Ptcco2 mean difference −17 mm Hg ; 95 % CI −7 to −28 mm Hg ; p = 0.005 ) and increased exercise performance on the Modified Shuttle Test ( mean difference 83 m ; 95 % CI 21 to 144 m ; p = 0.02 ) . NIV did not improve sleep architecture , lung function or awake Paco2 . Conclusion : 6 weeks of nocturnal NIV improves chest symptoms , exertional dyspnoea , nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia . Further studies are required to determine whether or not NIV can improve survival Objective The aim of the study was to evaluate the effect of the back-up rate on respiratory effort during non-invasive mechanical ventilation . Design An in vitro study evaluated the inspiratory trigger in seven domiciliary ventilators . Then , a prospect i ve , r and omized , crossover trial compared the effect on respiratory effort of three different back-up rates during pressure support ( PS ) and assist-control/volume-targeted ( AC/VT ) ventilation . Setting A research unit and a tertiary referral pediatric center . Patients Ten patients with cystic fibrosis ( CF ) . Interventions During the in vivo study , the back-up rate was progressively increased to the maximum that patients could tolerate ( Fmax ) and respiratory effort , as judged by pressure/time product of the diaphragm ( PTPdi/min ) , was compared between the two ventilatory modes . Results Differences were observed between trigger pressure , trigger time delay , trigger pressure/time product and the slope between flow and pressure in the seven ventilators . PS and AC/VT ventilation were associated with a decrease in respiratory effort ( PTPdi/min was 518±172 , 271±119 and 291±138 cmH2O . s−1 . min-1 , for spontaneous breathing , PS and AC/VT ventilation , respectively , p=0.05 ) . During the two modes , increasing the back-up rate to Fmax result ed in a greater reduction in PTPdi/min ( p=0.001 ) , which was more pronounced during AC/VT ventilation , due to the automatic adjustment of the inspiratory/expiratory time ratio . Conclusions Increasing the back-up rate during PS and AC/VT ventilation decreases respiratory effort in young patients with CF , but this effect was more marked with AC/VT ventilation Recombinant human deoxyribonuclease I ( dornase alfa ) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis . In a r and omized , placebo-controlled , double-blind clinical study in 100 infants , we investigated whether the therapeutic use of dornase alfa can be extended to ventilated , fluid-restricted children to reduce reintubation rate , ventilation duration , pediatric intensive care unit ( PICU ) stay , and ventilation complications . While reintubation rates were similar for dornase alfa 7 % vs. placebo 9 % ( odds ratio , 0.77 ; confidence interval , 0.11 - 4.9 ) , the incidence of atelectasis ( 6 vs. 17 , respectively ; P-value 0.051 ) , median ventilation time ( 2.2 vs. 3.4 days , respectively ; P-value 0.043 ) , median length of PICU stay ( 7 vs. 8 days , respectively ; P-value 0.051 ) , and mean costs ( 4,830 vs. 6,320 , respectively ) were lower in the dornase alfa group . No adverse effects were observed , even in critically ill patients . We found that dornase alfa was beneficial and safe . Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward , particularly when longer ventilation ( > 3 days ) is expected in fluid-restricted children after cardiac surgery We measured ventilation in all sleep stages in patients with cystic fibrosis ( CF ) and moderate to severe lung disease , and compared the effects of low-flow oxygen ( LFO2 ) and bilevel ventilatory support ( BVS ) on ventilation and gas exchange during sleep . Thirteen subjects , age 26 + /- 5.9 yr ( mean + /- 1 SD ) , body mass index ( BMI ) 20 + /- 3 kg/m2 , FEV1 32 + /- 11 % predicted , underwent three sleep studies breathing , in r and om order , room air ( RA ) , LFO2 , and BVS + /- O2 with recording of oxyhemoglobin saturation ( SpO2 ) ( % ) and transcutaneous carbon dioxide ( TcCO2 ) ( mm Hg ) . During RA and LFO2 studies , patients wore a nasal mask with a baseline continuous positive airway pressure ( CPAP ) of 4 to 5 cm H2O . Minute ventilation ( V I ) was measured using a pneumotachograph in the circuit and was not different between wake and non-rapid eye movement ( NREM ) sleep on any night . However , V I was reduced on the RA and LFO2 nights from awake to rapid eye movement ( REM ) ( p < 0.01 ) and from NREM to REM ( p < 0.01 ) . On the BVS night there was no significant difference in V I between NREM and REM sleep . Both BVS and LFO2 improved nocturnal SpO2 , especially during REM sleep ( p < 0.05 ) . The rise in TcCO2 seen with REM sleep with both RA and LFO2 was attenuated with BVS ( p < 0.05 ) . We conclude that BVS leads to improvements in alveolar ventilation during sleep in this patient group BACKGROUND : To date only two controlled studies have been published on the effects of domiciliary oxygen treatment on survival in patients with chronic obstructive pulmonary disease ( COPD ) with advanced respiratory failure . The survival in such patients despite oxygen treatment remains poor . The prescription of long term oxygen therapy ( LTOT ) in less severe disease remains controversial . The aim of this study was to evaluate the rationale for prescribing oxygen to patients with COPD with moderate hypoxaemia . METHODS : One hundred and thirty five patients with COPD , with PaO2 7.4 - 8.7 kPa ( 56 - 65 mmHg ) and advanced airflow limitation ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 0.83 ( 0.28 ) 1 ) , were r and omly allocated to a control ( n = 67 ) and LTOT ( n = 68 ) group . The patients were followed every three months for at least three years or until death . RESULTS : The cumulative survival rate was 88 % at one year , 77 % at two years , and 66 % at three years . No significant differences were found in survival rates between patients treated with LTOT and controls , nor did longer oxygen use ( over 15 hours per day ) improve survival . Younger age , better spirometric values , and higher body mass index predicted better survival . CONCLUSIONS : Domiciliary oxygen treatment does not prolong survival in patients with COPD with moderate hypoxaemia . Airway limitation seems to determine survival in this group of patients Background : Chest physiotherapy is essential to the management of cystic fibrosis ( CF ) . However , respiratory muscle fatigue and oxygen desaturation during treatment have been reported . The aim of this study was to determine whether non-invasive ventilation ( NIV ) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF . Methods : Twenty six patients of mean ( SD ) age 27 ( 6 ) years and forced expiratory volume in 1 second ( FEV1 ) 34 (12)% predicted completed a r and omised crossover trial comparing st and ard treatment ( active cycle of breathing technique , ACBT ) with ACBT + NIV . Respiratory muscle strength ( PImax , PEmax ) , spirometric parameters , and dyspnoea were measured before and after treatment . Pulse oximetry ( Spo2 ) was recorded during treatment . Sputum production during treatment and 4 and 24 hours after treatment was evaluated . Results : There was a significant reduction in PImax following st and ard treatment that was correlated with baseline PImax ( r=0.73 , p<0.001 ) . PImax was maintained following NIV ( mean difference from st and ard treatment 9.04 cm H2O , 95 % confidence interval ( CI ) 4.25 to 13.83 cm H2O , p=0.006 ) . A significant increase in PEmax was observed following the NIV session ( 8.04 cm H2O , 95 % CI 0.61 to 15.46 cm H2O , p=0.02 ) . The proportion of treatment time with Spo2 ⩽90 % was correlated with FEV1 ( r=−0.65 , p<0.001 ) . NIV improved mean Spo2 ( p<0.001 ) and reduced dyspnoea ( p=0.02 ) . There were no differences in FEV1 , forced vital capacity ( FVC ) or sputum weight , but FEF25–75 increased following NIV ( p=0.006 ) . Conclusion : Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF . Addition of NIV improves inspiratory muscle function , oxygen saturation and small airway function and reduces dyspnoea BACKGROUND The periodic administration of positive airway pressure combined with directed cough could aid mucus clearance in patients with cystic fibrosis ( CF ) and severe airway obstruction . OBJECTIVE To compare the short-term effect of positive expiratory pressure ( PEP ) physiotherapy via mask ( mask PEP ) , continuous positive airway pressure ( CPAP ) , and noninvasive positive-pressure ventilation ( NPPV ) physiotherapies on amount of sputum collected . METHODS Directed cough was st and ardized for each patient and used as the control treatment . We studied 17 patients with CF ( mean + /- SD age 28 + /- 7 y ) and severe airway obstruction ( forced expiratory volume in the first second 25 + /- 6 % of predicted ) admitted for pulmonary exacerbation . Mask PEP , CPAP , NPPV , and the control treatment ( directed cough ) were administered in a r and om sequence . Each patient received each treatment twice a day ( in 70-min sessions ) for 2 consecutive days . We measured the wet and dry weight of sputum collected and the number of directed and spontaneous coughs during each session . Spirometry and pulse oximetry were conducted before and after each session . For mask PEP , CPAP , and NPPV , each patient gave a subjective score for the efficacy and tolerability of the treatment , compared to the control treatment . RESULTS There was no statistically significant difference in the dry weight of sputum collected : mask PEP 0.9 + /- 0.6 g , CPAP 0.8 + /- 0.4 g , NPPV 0.9 + /- 0.6 g , control treatment 1.0 + /- 0.8 g. There was a statistically significant difference in the wet weight of sputum collected : mask PEP 15.8 + /- 5.5 g , CPAP 13.7 + /- 5.5 g , NPPV 13.2 + /- 5.0 g , control treatment 14.0 + /- 5.0 g ( p < 0.05 ) , but that difference became nonsignificant when we took into account the number of spontaneous coughs . There were no statistically significant changes in the spirometry and pulse-oximetry values . The patients ' subjective efficacy scores were similar for mask PEP , CPAP , and NPPV . Less fatigue was reported after NPPV and CPAP than after mask PEP . CONCLUSIONS There were no differences in sputum clearance or pulmonary-function measures between mask PEP and short-term administration of either CPAP or NPPV combined with directed cough . After mask PEP these patients felt more tired than after CPAP or NPPV secretion-clearance therapy Background : Patients with advanced cystic fibrosis can benefit from non-invasive positive pressure ventilation ( NPPV ) for the treatment of acute decompensation as well as for the management of chronic respiratory failure . This study was undertaken to compare the physiological effects of non-invasive proportional assist ventilation ( PAV ) and pressure support ventilation ( PSV ) on ventilatory pattern , transcutaneous blood gas tensions , and diaphragmatic effort in stable patients with cystic fibrosis and chronic CO2 retention . Methods : In 12 patients two periods of spontaneous breathing were followed r and omly by PSV ( 12 ( 3 ) cm H2O ) and PAV ( flow assist 4.9 ( 1.3 ) cm H2O/l.s , volume assist 18.9 ( 5.1 ) cm H2O/l ) set for the patient 's comfort and administered for 40 minutes with 2 cm H2O continuous positive airway pressure . Ventilatory pattern , transcutaneous blood gas tensions , and surface diaphragmatic electromyography were measured in the last 10 minutes of each application . Results : On average , both PSV and PAV improved ventilation ( + 30 % ) , tidal volume ( + 30 % ) , and transcutaneous CO2 ( −7 % ) while reducing diaphragmatic activity ( −30 % with PSV , −20 % with PAV ) . Mean inspiratory airway pressure was lower during PAV than during PSV ( 9.7 ( 1.9 ) and 12.9 ( 2.7 ) cm H2O , respectively ; p<0.05 ) . The mean coefficient of variation of tidal volume was about 20 % ( range 11–39 % ) during spontaneous breathing and did not change with either PAV or PSV . Conclusions : These results show that short term administration of nasal PAV and PSV to patients with stable cystic fibrosis with chronic respiratory insufficiency is well tolerated , improves ventilation and blood gas tensions , and unloads the diaphragm The effect of nocturnal oxygen therapy on mortality and morbidity rates and on progression of disease was tested in a double-blind , r and omized trial of 28 subjects with advanced cystic fibrosis . Patients were selected on the basis that their awake arterial oxygen tension was less than 65 mm Hg when they were clinical ly stable . Oxygen was prescribed in 1 L/min increments to obtain an awake arterial oxygen tension of greater than or equal to 70 mm Hg . Subjects received humidified oxygen or room air from modified concentrators . They were enrolled over a 3-year period and followed for an average ( + /- SD ) of 26 + /- 9 months . The average number of hours per night of concentrator use was 5.3 + /- 3.2 hours in the air group and 7.0 + /- 1.9 hours in the oxygen group . Over the follow-up period there were four deaths in each group , and oxygen therapy had no significant effect on the frequency of hospitalizations . Progression of disease was ascertained from nutritional status , pulmonary function , blood gas values , exercise ability , and right ventricular ejection fraction response to exercise ( as measured by equilibrium-gated radionuclide angiocardiography ) , and psychologic status was measured by st and ardized tests of mood , self-esteem , and cognitive function ; group comparisons for the first year revealed no significant differences ; however , school or work attendance was maintained in the oxygen group but deteriorated in the air group . Clinical signs of cor pulmonale were documented during follow-up in 10 patients in toto , and all lived at least 9 months from the onset of these signs . The lack of association between the onset of these signs and imminent death , or the usefulness of measurements of the maximal oxygen uptake during progressive exercise and the right ventricular ejection fraction response to exercise as prognostic indicators , suggest that death may not be the result of cor pulmonale . We conclude that nocturnal oxygen treatment in patients with cystic fibrosis did not appear to affect mortality rates , the frequency of hospitalizations , or the progression of disease ; oxygen use should be instituted only after the development of symptoms related to hypoxemia Fourteen female and 22 male patients with cystic fibrosis ( CF ) , 8 to 29 yr of age , performed two progressive exercise tests to exhaustion on a cycle ergometer , breathing normoxic air ( 21 % O2 ) for one test , and hyperoxic air ( 30 % O2 ) for the other test . The order of gas administration was r and omized . Minute ventilation ( VE ) , oxygen uptake ( VO2 ) , end-tidal CO2 tension ( PETCO2 ) , work rate , oxyhemoglobin saturation ( SAO2 ) , and heart rate ( HR ) were measured throughout the tests . The SaO2 of 11 patients at peak exercise was 90 % or less ( " Low Sat " group ) . The SaO2 of 23 patients remained above 90 % throughout the exercise ( " High Sat " group ) . Hyperoxic air minimized desaturation during exercise in the Low Sat group to 2 + /- 2 % compared to a decrease of 10 + /- 5 % with normoxic air . The decrease in saturation was not significant for the High Sat group ( 1 + /- 1 % for both 21 % and 30 % O2 ) . Peak work rate and VO2 did not differ significantly between normoxic and hyperoxic conditions . However , VE and HR at peak exercise tended to be lower , and PETCO2 was higher during peak exercise with 30 % O2 than 21 % O2 for both groups . During submaximal exercise , O2 desaturation was diminished and HR was significantly lower with supplemental O2 , specifically in the Low Sat group . VE was significantly lower for both groups during submaximal exercise with hyperoxic air . The results suggest that O2 supplementation minimizes O2 desaturation and enables patients with CF to exercise with reduced ventilatory and cardiovascular work Objective Home noninvasive mechanical ventilation ( NIMV ) is used with increasing frequency for the treatment of patients with respiratory failure caused by cystic fibrosis , yet the optimal mode of ventilation in such children is unknown . We compared the physiologic short-term effects of two ventilators with different modes ( one pressure support and the other assist control/volume-targeted [ AC/VT ] ) commonly used for domiciliary ventilation . Design Prospect i ve , r and omized , crossover comparison of two ventilators with different modes . Setting Tertiary pediatric university hospital . Patients Eight children with cystic fibrosis ( age , 11–17 yrs ) and chronic respiratory failure ( pH 7.4 ± 0.0 ; Pao2 , 57.5 ± 7.5 torr ; Paco2 , 46.1 ± 2.5 torr ) , naive to NIMV . Interventions Two 20-min runs of pressure support and AC/VT ventilation were performed in r and om order , each run being preceded and followed by 20 mins of spontaneous breathing . Measurements Flow and airway pressure and esophageal and gastric pressures were measured to calculate esophageal ( PTPes ) and diaphragmatic pressure-time product ( PTPdi ) and the work of breathing . Results The two NIMV sessions significantly improved blood gas variables and increased tidal volume with no change in respiratory rate . Indexes of respiratory effort decreased significantly during the two modes of NIMV compared with spontaneous breathing , with PTPdi/min decreasing from 497.8 ± 115.4 cm H2O·sec·min−1 during spontaneous breathing to 127.8 ± 98.3 cm H2O·sec·min−1 and 184.3 ± 79.8 cm H2O·sec·min−1 , during AC/VT and pressure support , respectively ( p < .0001 ) , and the work of breathing decreasing from 1.83 ± 0.12 J·L−1 during spontaneous breathing to 0.48 ± 0.32 J·L−1 and 0.75 ± 0.30 J·L−1 , during AC/VT and pressure support , respectively ( p < .0001 ) . In addition , the effect of AC/VT ventilation was significantly superior to pressure support judged by PTPes and the work of breathing , but this result was explained by three patients who adapted extremely well to the AC/VT ventilation , with the disappearance of ventilator triggering , in effect adopting a controlled mode . There was a correlation between the improvement in PTPdi/min or the work of breathing and patient ’s subjective impression of comfort during the AC/VT ventilation . Conclusions In awake , stable children with cystic fibrosis , both AC/VT and pressure support unloaded the respiratory muscles . The disappearance of ventilator triggering occurred in a subgroup of patients during AC/VT ventilation , and this explained the good tolerance and the superiority of this mode in the present study Nebulized aerosols are commonly used to deliver drugs into the lungs of patients with cystic fibrosis ( CF ) . The aim of this study was to assess the effectiveness of pressure-support ( PS ) ventilation in increasing aerosol deposition within the lungs of children with CF . An in vitro study demonstrated the feasibility of coupling a breath-actuated nebulizer to a PS device . An in vivo study was done with 18 children ( ages 6 to 21 yr ) with clinical ly stable CF , each of whom underwent both a st and ard and a PS-driven ventilation scan ( control session and PS session , respectively ) . In addition , a perfusion scan was used to determine lung outlines and to construct a geometric model for quantifying aerosol deposition by radioactivity counting in MBq . Homogeneity of nebulization was evaluated from the four first-order moments of aerosol distribution in the peripheral and central lung regions . The time-activity nebulization curve was linear in all patients , with higher slopes during the PS than during the control session ( 0.43 + /- 0.07 [ mean + /- SD ] MBq/min and 0.32 + /- 0.23 MBq/min , respectively ; p < 0.018 ) . Quantitatively , aerosol deposition was about 30 % greater after the PS session ( 4.4 + /- 2.7 MBq ) than after the control session ( 3.4 + /- 2.1 MBq ; p < 0.05 ) . Similarly , deposition efficacy ( as a percentage of nebulizer output ) was significantly better during the PS session than during the control session ( 15.3 + /- 8.3 % versus 11.5 + /- 5.7 % , p < 0.05 ) . No differences in the regional deposition pattern or in homogeneity of uptake were observed . In conclusion , our data show that driving the delivery of a nebulized aerosol by noninvasive PS ventilation enhances total lung aerosol deposition without increasing particle impaction in the proximal airways OBJECTIVE Chest physiotherapy ( CPT ) is an integral part of the treatment of patients with cystic fibrosis ( CF ) . CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue . Inspiratory pressure support ventilation ( PSV ) is a new mode of ventilatory assistance design ed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient 's inspiratory work . The aim of our study was 1 ) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2 ) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT . METHODS Sixteen CF patients in stable condition with a mean age of 13 + /- 4 years participated to the study . For CPT , we used the forced expiratory technique ( FET ) , which consisted of one or more slow active expirations starting near the total lung capacity ( TLC ) and ending near the residual volume . After each expiration , the child was asked to perform a slow , nonmaximal , diaphragmatic inspiration . After one to four forced breathing cycles , the child was asked to cough and to expectorate . A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each . During the study , each patient received two CPT sessions in r and om order on two different days , at the same time of day , with the same physiotherapist . During one of these two sessions , PSV was provided throughout the session ( PSV session ) via a nasal mask using the pressure support generator ARM25 design ed for acute patients ( TAEMA , Antony , France ) . The control session was performed with no nasal mask or PSV . Both CPT sessions were performed without supplemental oxygen . Lung function and maximal inspiratory pressures ( PImax ) and expiratory pressures ( PEmax ) were recorded before and after each CPT session . RESULTS Mean lung function parameters were comparable before the PSV and the control sessions . Baseline pulse oximetry ( SpO2 ) was significantly correlated with the baseline vital capacity ( % predicted ) and forced expiratory volume in 1 second ( FEV1 ) ( % predicted ) . PSV was associated with an increase in tidal volume ( Vt ) from 0.42 + /- 0.01 liters to 1.0 + /- 0.02 liters . Respiratory rate was significantly lower during PSV . SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session . SpO2 decreases after FET were significantly larger during the control session ( nadir : 91.8 + /- 0 . 7 % ) than during the PSV session ( 93.8 + /- 0.6 % ) . Maximal pressures decreased during the control session ( from 71.9 + /- 6.1 to 60.9 + /- 5.3 cmH2O , and from 85.3 + /- 7.9 to 77.5 + /- 4.8 cmH2O , for PImax and PEmax , respectively ) and increased during the PSV session ( from 71.6 + /- 8.6 to 83.9 + /- 8.7 cmH2O , and from 80.4 + /- 7.8 to 88.0 + /- 7.4 cmH2O , for PImax and PEmax , respectively ) . The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 ( % predicted ) . Forced expiratory flows did not change after either CPT session . The amount of sputum expectorated was similar for the two CPT sessions ( 5.3 + /- 5.3 g vs 4.6 + /- 4.8 g after the control and PSV session , respectively ; NS ) . Fifteen patients felt less tired after the PSV session . Ten patients reported that expectoration was easier with PSV , whereas 4 did not note any difference ; 2 patients did not expectorate . Nine patients expressed a marked and 5 a small preference for PSV , and 2 patients had no preference . The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients . DISCUSSION Our study in CF children shows that respiratory muscle performance , as evaluated based on various parameters , decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle . These unwanted effects of CPT |
12,551 | 26,427,905 | The findings showed increasing interest in research into the delivery of pharmacy services and public health initiatives .
Overall , the review found that provision of some health services in pharmacies was common ; however , most public health initiatives appeared to be poorly implemented , had limited evidence and were not demonstrated to be sustainable across the sector .
This indicates that the practice of community pharmacy in the region has not significantly changed over the past 14 years with respect to the scope and quality of pharmacy services provided , and fundamental policy changes are necessary to improve this situation | The development of health and healthcare systems in South-East Asia has influenced the practice of community pharmacy .
Over the years , community pharmacy in the region has striven to exp and services beyond dispensing to encompass more involvement in public health issues . | OBJECTIVE : To investigate the knowledge and practice among private pharmacy staff in Hanoi regarding case management of mild acute respiratory infection ( ARI ) in children . METHODS : Sixty private pharmacies in Hanoi were r and omly selected . Knowledge was assessed through interviews with pharmacy staff using a question naire ; practice was assessed through the Simulated Client Method . RESULTS : In the question naire , 20 % of the pharmacy staff stated that they would dispense antibiotics . In practice , 83 % of the pharmacies dispensed antibiotics . Only 36 % of the cases were h and led according to guidelines . In the question naire , 81 % of interviewees stated that antibiotics are not effective in short therapeutic courses . In practice , 48 % of the antibiotics were dispensed in courses less than five days . Traditional herbal medicines were dispensed in 41 % of the encounters . In the question naire , 53 % of the pharmacy staff stated that they would ask the patient about difficulty of breathing . In practice , questions related to difficulty of breathing were asked in less than 10 % of the encounters . CONCLUSIONS : Dispensing of antibiotics for mild ARI was common practice among private pharmacies , and there was a significant difference between knowledge and practice . Interventions are needed to improve pharmacy practice in Hanoi SETTING Ho Chi Minh City ( HCMC ) , Vietnam . OBJECTIVES To assess knowledge about tuberculosis , to describe self-reported dispensing practice s and to estimate the magnitude of anti-tuberculosis drug dispensing in private pharmacies . DESIGN Survey of a r and om sample of 147 private pharmacies out of a total of 1814 registered pharmacies . Interviews were carried out based on a structured question naire . RESULTS Eighteen per cent of interviewees identified TB as a possible diagnosis for a fictitious case with fever and cough for 4 weeks . Fifty-eight per cent reported selling anti-tuberculosis drugs often or sometimes . Interviewees estimated that 1.3 persons on average ( 95%CI 0.6 - 1.9 ) had bought anti-tuberculosis drugs during the last 4-week period , and that 24 % of them had bought anti-tuberculosis drugs without a prescription . CONCLUSION We have estimated that between 1100 and 3400 persons buy anti-tuberculosis drugs each month in the 1814 registered private pharmacies in HCMC , that about a quarter of them do so without a prescription , and that at least 40 % of all anti-tuberculosis drug dispensing in HCMC occurs in the private sector . Regulations need to be put in place urgently and collaboration strengthened between the strong National Tuberculosis Programme and the unorganised private sector in HCMC SETTING S Private pharmacies in Hanoi , Viet Nam . OBJECTIVES To explore the response of health care providers ( HCPs ) in private pharmacies to suspected tuberculosis ( TB ) patients . METHODS A simulated patient method combined with an interview in 128 r and omly selected private pharmacies and 10 private pharmacies near TB hospitals . RESULTS In the simulated patient method and interview , respectively 59 ( 46 % ) and 70 ( 55 % ) of HCPs referred the TB suspect to general health care . Only 11 ( 9 % ) referred the simulated patient to a TB care facility . Fifty-two ( 42 % ) of the HCPs identified suspected TB from a fictitious case described on paper ; 34 ( 27 % ) were aware that free treatment was provided under the National Tuberculosis Programme ( NTP ) . Knowledge about free NTP treatment predicted a higher rate of direct referrals to TB facilities ( OR 5.80 , 95%CI 1.88 - 19.62 ) and greater ability to identify suspected TB from a fictitious case on paper ( OR 5.14 , 95%CI 2.36 - 11.73 ) . Pharmacies with Good Pharmacy Practice ( GPP ) certification were less likely to refer simulated patients to TB facilities than non-GPP pharmacies ( OR 0.10 , 95%CI ≤0.01 - 0.79 ) . CONCLUSIONS Nearly half of HCPs in private pharmacies do not refer TB suspects , possibly contributing to delays in diagnosis and treatment . Knowledge about free NTP treatment predicted better performance of HCPs OBJECTIVES The study was conducted to assess how the general public in the Klang Valley , Malaysia , utilised community pharmacists . METHODS This was a prospect i ve observational study which documented interactions between community pharmacists and their customers . A research er was stationed in 10 participating community pharmacies around the Klang Valley to observe and record all the interactions , using a structured data - collection form . KEYS FINDINGS : Interactions between 1914 customers and the pharmacists of the 10 community pharmacies were recorded . A total of 2199 requests were made by these customers . The main types of request were for medications by br and name ( 32.2 % ) , advice on minor health problems ( 25.9 % ) and for health supplements ( 11.7 % ) . Only 65 prescriptions were received by the community pharmacies ; that is , fewer than two prescriptions per pharmacy per day . The pharmacists provided counselling for only 54.4 % of the requests where a medication or health supplement was dispensed . Counselling by pharmacist was significantly associated with the type of request ( P < 0.001 ) . CONCLUSIONS The main reason for the general public to visit a community pharmacy in Malaysia was to purchase a particular medication . Few prescriptions were filled at community pharmacies in Malaysia , indicating the under-utilisation of community pharmacists as a safety net for prescribed medications in primary care PURPOSE The purpose of this study was to evaluate the generic substitution ( GS ) practice s undertaken by community pharmacists in the State of Penang , Malaysia with a focus on the extent of communication between pharmacists and prescribers on issues related to GS , consumer 's acceptance on the GS and estimation of cost saving achieved for patients opted for GS . METHOD A cross-sectional descriptive study for a period of 2 months using a specific question naire as a data collection tool was undertaken with a r and om sample of 40 community pharmacies located in the State of Penang . RESULTS By the end of the study period , 34 out of 40 pharmacies contacted participated in the study . Forty-seven per cent of pharmacists consulted prescribers while promoting GS to their consumers . Majority of the prescribers ( 84.4 % ) when contacted by the pharmacists accepted the suggestion for substitution . From consumers ' perspective , 88 % ( n = 156 ) of the consumers involved in this study accepted pharmacist 's recommendation to generically substitute their prescribed medications . Through acceptance of GS , it has been estimated that the overall consumers ' expenses on drugs can be reduced to a total of RM6137 ( US$ 1615 ; US$ 1 = RM3.80 ) and this corresponds to a cost saving of 61.1 % . CONCLUSIONS The outcome of the present study showed that through GS recommendation by community pharmacist , consumers can save the expenditure of their prescribed medications Background The community pharmacist has significant potential to assist in providing health advice aim ed at the improvement outcomes pertaining to weight management , however , up to now , evidence regarding its effectiveness has been inconclusive . In Thail and , community pharmacy involvement in weight management is a novel idea and therefore needs an evaluation of its effectiveness . Objective To examine essential outcomes , comparing the pharmacist ’s interventions with a routine weight management service provided at a primary care unit ( PCU ) . Setting Maha Sarakham province , Thail and . Methods A r and omized controlled trial was design ed involving sixty-six obese patients r and omly assigned to either the control group or the experimental group . Participants in the control group received group counselling from the PCU staff as usual , while those participants in the experimental group received one-on-one advice from a community pharmacist along with the weight loss h and book for self- study . Both groups were followed up and clinical outcomes were monitored four times at weeks 0 , 4 , 8 , and 16 . Eating behaviours and knowledge about overweight and obesity were measured twice , at weeks 0 and 16 . Main outcome measure Clinical outcomes included weight , waist circumference , body mass index , measured by st and ard medical devices . Eating behaviours were measured by the theory of planned behaviour ( TPB ) question naire . Knowledge was measured by a question naire focusing on the subjects ’ level of underst and ing regarding overweight and obesity issues . Results Neither group showed improvement in clinical outcomes . The TPB average sum score significantly increased from baseline in the experimental group in terms of intention to perform healthy dieting behaviour , subjective norm , behavioural beliefs , normative beliefs , and control beliefs . ( P < 0.05 ) In the control group , scores increased significantly from the baseline only for behavioural beliefs . ( P < 0.05 ) Moreover , the knowledge score in experimental group increased significantly from 6.42 ± 1.94 to 8.75 ± 0.68 ( P < 0.05 ) . Conclusion Thai community pharmacists can help to improve both eating behaviour and knowledge about weight and obesity among obese patients . However , since the effect on clinical outcomes is unclear , a long-term study is still needed Private pharmacies are the first line of health care in many communities , commonly selling antibiotics in small doses and prescription-only drugs such as steroids without medical supervision . The aim was to study the effectiveness of a multi-faceted intervention on the dispensing practice s of drug sellers in Hanoi and Bangkok . The study was a r and omized , controlled trial with 68 Hanoi and 78 Bangkok pharmacies , r and omly selected and assigned for intervention and control . Behaviour was assessed by five simulated client visits per pharmacy per dispensing practice , at baseline and a month or more after each intervention . Three three-month interventions were implemented sequentially with four months in between : enforcement of regulations with local inspectors visiting to emphasize the importance of prescription-only medicine legislation ; education , performed face-to-face in Hanoi and by a large group in Bangkok ; and peer review , voluntary in Bangkok and compulsory in Hanoi . The intervention result ed in significant improvements in Hanoi , reducing the dispensing of illegal steroids ( 29 % vs. 62 % ) and low dose antibiotics ( 69 % vs. 90 % ) , sustained by means of the peer review ( 17 % vs. 57 % steroids and 71 % vs. 95 % antibiotics ) , and in fewer dispensers asking no questions and giving no advice ( 11 % vs. 30 % steroids and 51 % vs. 81 % antibiotics ) . The only significant improvement in Bangkok was the reduction in illegally dispensing steroids ( 25 % vs. 44 % ) after the regulatory intervention . In Bangkok , fewer of those in the group who volunteered for the peer review asked no questions and gave no advice for low-dose antibiotics requests after the peer review ( 58 % vs. 81 % ) . A multi-component intervention can have a profound effect in changing dispensers ' behaviour , but the effect is dependant on the context and the method of implementation . Possible reasons for differences are discussed OBJECTIVES To describe practice behavior and underst and ing among pharmacy personnel , both pharmacists and non-pharmacist staff , in the management of mild and moderate migraines . BACKGROUND Migraine is recognized as a prevalent and chronic neurological disorder . In developing countries , such as Thail and , community pharmacies are a widely used source of health care for various illnesses including migraine . However , the quality of migraine management and knowledge among pharmacy personnel is unclear . METHODS Cross-sectional study . The sample comprised 142 r and omly selected community pharmacies in a city in the south of Thail and . Simulated clients visited the pharmacies twice , at least 1 month apart , to ask for the treatment of mild and moderate migraines . After the encounters , question asking , drug dispensing , and advice giving by pharmacy staff were recorded . Subsequently , the providers in 135 pharmacies participated in the interview to evaluate their knowledge in migraine management . RESULTS The majority of pharmacy personnel were less likely to ask questions in cases of mild migraine when compared with moderate attack ( mean score [ full score = 12 ] 1.8 ± 1.6 vs 2.6 ± 1.5 , respectively , P < 0.001 ) . Mean difference of question asking between mild and moderate migraines was -0.8 ( 95 % confidence interval -1.1 to -0.5 , P < 0.001 ) . Approximately 33 % and 54 % of the providers appropriately dispensed non-steroidal anti-inflammatory drugs for mild attack and ergotamine for moderate migraine , respectively , P < 0.001 . Prophylactic medications ( eg , atenolol , propranolol , flunarizine ) were inappropriately recommended , particularly in moderate attack ( 28.2 % vs 17.6 % in mild migraine , P = 0.018 ) . Less than 30 % of providers advised the patients on the maximum limit of dose or discontinuity of medications when recovered . Compared with non-pharmacists , pharmacists tended to ask more questions , give more advice , and dispense less appropriately ; however , there were no significant differences . The results from the interview showed that most pharmacy personnel had inadequate knowledge on migraine management . Pharmacists had better knowledge on question asking ( mild migraine 5.1 ± 2.1 vs 3.1 ± 1.3 , respectively , P < .001 ; moderate disorder 6.5 ± 3.1 vs 3.9 ± 2.1 , respectively , P < .001 ) and tended to have more knowledge on advice giving but poorer drug dispensing in moderate migraine according to the guidelines , relative to non-pharmacists ( 20.5 % vs 40.3 % , P = .014 ) . CONCLUSIONS A large number of community pharmacists and non-pharmacist staff had inappropriate practice behavior and underst and ing . Continuing education and interventions are important to improve the practice and knowledge of pharmacy personnel , particularly the pharmacists The objective of this study was to assess the effects of a multicomponent intervention on private pharmacy practice . From 641 private pharmacies in Hanoi , 68 pharmacies were r and omly selected and matched into 34 pairs . Each pair consisted of a control and an intervention pharmacy . Three interventions were applied sequentially : Regulatory enforcement , Education , and Peer influence . Four tracer conditions were selected : uncomplicated acute respiratory infection ( ARI ) , sexually transmitted disease ( STD ) , requesting the prescription-only drugs prednisolone , and a short course of cefalexin . Practice was assessed through the Simulated Client Method ( SCM ) . The intervention pharmacies improved significantly compared to the control pharmacies ( P < .05 ) in all tracer conditions . For ARI , antibiotic dispensing decreased ( P < .02 ) and questions regarding breathing increased ( P < .01 ) . For STD , advice to go to the doctor and dispensing the correct syndromic treatment increased ( P < .01 ) . Dispensing of prednisolone and cefalexin decreased ( P < .01 ) and prescription requests increased ( P < .01 ) . Our conclusion is that it is possible to improve private pharmacy practice with a multicomponent intervention |
12,552 | 12,058,234 | Results of the analysis showed that allocation to BMT reduced risk of relapse and improved disease-free and overall survival .
In conclusion , BMT from a histocompatible family donor improves patient outcome .
Data are insufficient to determine whether this is true for all subgroups of AML , and whether ABMT is superior to non-myeloablative chemotherapy . | For children with AML in CR1 , the major consolidation therapies are BMT , ABMT and intensive chemotherapy .
The relative effectiveness of these strategies is still debated .
We conducted a systematic review and meta- analysis of trials to determine the effectiveness of BMT and ABMT in CR1 in paediatric AML . | PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation ( BMT ) and autologous bone marrow transplantation ( ABMT ) with sequential postremission chemotherapy ( SPC ) in children with acute myelogenous leukemia ( AML ) in first remission . PATIENTS AND METHODS From March 1987 to March 1990 , 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and st and ard-dose cytarabine . After initial consolidation with a course of daunorubicin , cytarabine , and thioguanine ( DAT ) , patients in complete remission ( CR ) were r and omized to receive either ABMT or SPC , except for those with an HLA-matched sibling who were assigned to undergo BMT . SPC consisted of three additional courses of DAT , followed by three pairs of drugs administered sequentially for a total of six cycles . RESULTS Overall , 127 of 161 patients attained CR ( 79 % ) . The estimated probabilities of survival and event-free survival ( EFS ) at 5 years for all patients were 42 % and 25 % , respectively ( median follow-up , 28 months ) . For the 127 complete responders , the 5-year probability of disease-free survival ( DFS ) was 31 % , with a cumulative risk of relapse of 64 % . For the purpose of this study , all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle , regardless of whether they actually received the intended therapy . The 5-year DFS was 51 % for the BMT group ( n = 24 ) , significantly higher ( P = .03 ) than that observed for the other cohorts : 21 % for ABMT ( n = 35 ) , 27 % for SPC ( n = 37 ) , and 34 % for a group of 31 nonr and omized ( NR ) patients . Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups , including the BMT cohort , in which no deaths attributable to the toxicity of the procedure were recorded . CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE ( cytosine arabinoside , daunorubicin , etoposide ) induction treatment in the second study . Due to this intensification , the relapse rate , but not the rate of induction failures , was reduced . The probability of a 6-year event-free survival increased from 38 % , SD 4 % , in study AML-BFM-78 to 49 % , SD 4 % , in study AML-BFM-83 , P = .08 . The improvement of the 6-year event-free interval ( EFI ) was significant in the second study ( 61 % , SD 4 % , versus 47 % , SD 5 % , P less than .05 ) ; it was restricted to the FAB types M1 through M4 ( EFI : 67 % , SD 5 % , versus 45 % , SD 5 % , P less than .01 ) . The difference in EFI seen in FAB M5 was not statistically significant ( EFI : 40 % , SD 10 % , versus 63 % , SD 11 % , NS ) . According to the results of the second study , two different risk groups ( low and high ) could be identified by combinations of predominantly pretherapeutic parameters . The low risk group , comprising 37 % of the patients who achieved complete remission , included the FAB types with granulocytic differentiation and specific additional features : FAB M1 with Auer rods , FAB M2 with white blood cell count of less than 20,000/microL , FAB M3 all patients , and FAB M4 with eosinophilia . The 6-year Kaplan-Meier estimation of EFI is 91 % , SD 4 % , compared with 42 % , SD 6 % in the high risk group . In future studies based on the AML-BFM-83 treatment , bone marrow transplantation in first remission should be m and atory only for children of the high risk group BACKGROUND Three strategies are used to prevent relapse in patients with acute myeloid leukaemia in first remission . Most of those with suitable donors are offered allogeneic haemopoietic-stem-cell transplant . Other patients may receive intensive chemotherapy or autologous transplantation ; we undertook this r and omised prospect i ve trial to assess which is the better option . METHODS After three courses of intensive chemotherapy , bone marrow was harvested from patients ( < 56 years of age ) in remission who lacked an HLA-matched sibling donor . These patients were then r and omised to receive , after one more course of chemotherapy , no further treatment ( n=191 ) or an autologous bone-marrow transplant ( BMT ) after preparation with cyclophosphamide and total-body irradiation ( n=190 ) . Outcome comparisons were by intention to treat with adjustment for the most important risk factors for relapse . FINDINGS 381 patients were r and omised ( 38 % of those eligible ) . Of the 190 patients allocated autologous BMT , 126 received it . On intention-to-treat analysis the number of relapses was substantially lower in the autologous BMT group than in the group assigned no further treatment ( 64/190 [ 37 % ] vs 101/191 [ 58 % ] , p=0.0007 ) , result ing in superior disease-free survival at 7 years ( 53 vs 40 % ; p=0.04 ) . These benefits were observed in all risk groups and age-groups . There were more deaths in remission in the autologous BMT group than in the no further treatment group ( 22 [ 12 % ] vs 7 [ 4 % ] , p=0008 ) . In children ( < 15 years ) and patients with good-risk disease , survival from relapse in the no further treatment group was 35 % and 38 % at 2 years . There was an overall survival advantage in the autologous BMT group at 7 years ( 57 vs 45 % , p=0.2 ) . INTERPRETATION The addition of autologous BMT to four courses of intensive chemotherapy substantially reduces the risk of relapse in all risk groups , leading to improvement in long-term survival . The good chance of salvage for children or patients with good-risk disease who relapse from chemotherapy , and the mortality , morbidity , late effects , and expense of autologous BMT , suggest that delay of autograft until second remission in these two groups may be appropriate 359 eligible children with acute myeloid leukaemia ( AML ) entered the MRC AML 10 trial between May 1988 and March 1995 . Patients received four courses of intensive induction and consolidation chemotherapy , with or without subsequent autologous ( A-BMT ) or allogeneic ( allo-BMT ) bone marrow transplant . There were r and omized comparisons of thioguanine versus etoposide in induction and of A-BMT versus not . Allo-BMT was recommended for patients with a HLA-matched sibling and was evaluated by donor versus no donor comparison . The complete remission rate was 92 % . In first remission there were 20 deaths during consolidation chemotherapy and 11 after BMT ( 8/61 allo-BMTs . 1/60 A-BMTs and 2/4 matched unrelated donor transplants ) . The relapse rate was low , decreasing from 26 % in the first year to 2 % in the fourth . Long-term outcome was excellent with survival at 7 years from entry of 56 % and event-free survival of 48 % . There were no significant differences between thioguanine and etoposide , whereas both A-BMT and allo-BMT reduced relapse risk but did not produce a significant survival benefit . It appears that over half the children entered into AML 10 are cured , a result which compares favourably with other reported series . We conclude that four courses of intensive chemotherapy are an effective approach to the treatment of paediatric AML , which avoids the acute toxicity and long-term side-effects of BMT and also avoids the need for prolonged maintenance therapy or cranial irradiation PURPOSE The objectives of this study were to determine if the addition of etoposide , thioguanine , and dexamethasone to daunorubicin and cytarabine ( five-drug regimen ) during induction would improve remission induction rates and survival of children with acute myeloid leukemia ( AML ) when compared with the st and ard regimen of cytarabine and daunorubicin ( 7 + 3 ) and whether allogeneic bone marrow transplantation ( BMT ) or intensive chemotherapy consolidation with or without maintenance would give a superior outcome . PATIENTS AND METHODS A total of 591 assessable children with AML entered Childrens Cancer Group ( CCG ) trial 213 between January 1986 and February 1989 . The status of patients as of September 1 , 1992 forms the basis of this report . The results were compared with previous AML studies . RESULTS The projected survival rate of all patients at 5 years is 39 % ( event-free survival [ EFS ] rate , 31 % ) , which is superior to that of the prior CCG study ( P = .01 ) . The induction rate was 79 % for 7 + 3 and 76 % for the five-drug regimen ( not significant ) . Comparisons of BMT to chemotherapy favored BMT , but these differences do not always reach statistical significance ( eg , 5-year disease-free survival [ DFS ] rate , 46 % v 38 % [ P = .06 ] with donor available and 54 % v 37 % [ P = .002 ] if treated according to protocol intent ) . No benefit for maintenance therapy was found and , in some comparisons , it was inferior to discontinuation of therapy ( 5-year survival rate , 46 % v 68 % , P < .01 ) . CONCLUSION The 5-year EFS rate of patients with AML is 31 % and has improved . The five-drug induction regimen is no better than st and ard induction , BMT appears superior to chemotherapy , and maintenance therapy was not beneficial Timed sequencing of cycles of induction chemotherapy in acute myeloid leukemia ( AML ) has been proposed as a way to achieve maximal leukemic cell kill through recruitment and synchronization of residual neoplastic cells . Furthermore , whether intensive induction therapy should be continued in the presence of profound myelosuppression is an important question . The Children 's Cancer Group ( CCG ) conducted a prospect i ve r and omized trial in which 589 patients with AML were r and omized at diagnosis to one of two induction approaches involving a 4-day cycle of five active chemotherapeutic agents , with the second cycle administered either 10 days after the first cycle , despite low or dropping blood counts ( intensive timing ) , or 14 days or later from the beginning of the first cycle , depending on bone marrow status ( st and ard timing ) . All patients achieving remission received a total of four cycles of induction therapy . They were then allocated to allogeneic bone marrow transplantation ( BMT ) if a compatible family donor was present or r and omized to aggressive nonmyeloablative therapy or to myeloablative therapy with purged autologous BMT rescue . The three postremission arms remain coded . Induction success and median days to complete induction were similar for the 295 patients r and omized to the intensive timing arm ( 75 % , 99 days ) compared with the 294 patients r and omized to the st and ard timing arm ( 70 % , 105 days ; P = .18 for remission ) . However , a marked improvement in outcome was demonstrated in patients r and omized to the intensive timing arm , with an actuarial event-free survival at 3 years of 42 % + /- 7 % ( 95 % confidence interval [ CI ] ) versus 27 % + /- 6 % for patients on the st and ard timing arm ( P = .0005 ) . Disease-free survival results at 3 years from the end of induction were superior for patients receiving intensively timed induction therapy ( N = 211 ) , 55 % + /- 9 % versus 37 % + /- 9 % for st and ard timing patients ( N = 195 , P = .0002 ) , with a median follow-up from achieving remission of 28 months . Superior results were documented for patients receiving intensive timing irrespective of the postremission therapy to which they were allocated . Intensively timed induction therapy for patients with AML markedly improves event-free survival , even for patients undergoing myeloablative therapy with BMT rescue . Without controlling for the type of induction therapy received , results of various BMT studies in AML comparing different preparative regimens will be difficult to interpret The objective of this study was to compare allogeneic bone marrow transplantation ( BMT ) with high-dose cytarabine containing chemotherapy in children with acute myeloid leukemia ( AML ) in first complete remission ( CR ) . One hundred and seventy-one children were enrolled on the LAME89/91 protocol . Induction chemotherapy was a combination of cytarabine and mitoxantrone . After achieving CR , patients who had an HLA-identical sibling donor underwent allogeneic BMT . Children not eligible for BMT received post remission chemotherapy which included two consolidation courses , the second consolidation consisting of high-dose cytarabine with amsacrine and asparaginase . CR was achieved in 149 children ( 87 % ) . Thirty-two had an HLA-identical sibling donor and were eligible for BMT . These 32 patients , as well as an additional child who had a one antigen HLA-mismatched father , received BMT during first CR . Consequently , 33 patients were analyzed in the BMT group and 116 in the chemotherapy group . The 4-year probability of relapse was 26 + /- 15 % in the BMT group and 47 + /- 10 % in the chemotherapy group ( P = 0.04 ) . The risk of therapy-related death was 3 % for BMT and 7.7 % for chemotherapy . Disease-free survival ( DFS ) was 72 + /- 15 % in the BMT group and 48 + /- 10 % in the chemotherapy group ( p = 0.02 ) . We conclude that allogeneic BMT from a matched sibling donor is the treatment of choice for reducing the relapse risk and for increasing DFS in children with AML in first CR Between May 1988 and March 1995 , 359 children with acute myeloid leukaemia ( AML ) were treated in the MRC AML 10 trial . Three risk groups were identified based on cytogenetics and response to treatment . One hundred and twenty-five children relapsed – 103 in the bone marrow only , 12 in the bone marrow combined with other sites , and six had isolated extramedullary relapses ( site was not known in four cases ) . Eighty-seven children received further combination chemotherapy , one all-trans retinoic acid for acute promyelocytic leukaemia , and one a matched unrelated donor allograft in relapse , and 61 achieved a second remission . One patient with no details on reinduction therapy also achieved second remission . Treatment in second remission varied – 44 children received a BMT ( 22 autografts , 12 matched unrelated donor allografts , 10 family donor allografts ) , and 17 were treated with chemotherapy alone . The overall survival rate for all children ( treated and untreated ) was 24 % at 3 years , with a disease-free survival of 44 % for those achieving a second remission . Length of first remission was the most important factor affecting response rates – children with a first remission of less than 1 year fared poorly ( second remission rate 36 % , 3 year survival 11 % ) , whereas those with longer first remissions had a higher response rate ( second remission rate 75 % , 3 year survival 49 % , P < 0.0001 ) Summary . The optimal post‐remission therapy for patients with acute myeloblastic leukaemia remains controversial . Allogeneic bone marrow transplantation , autologous bone marrow transplantation , and consolidation chemotherapy are the major options . In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospect i ve registration study . Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA‐typing and intention to treat in case of presence or absence of an HLA‐identical donor was recorded . 27/79 ( 34 % ) patients HLA‐typed at diagnosis had an identical donor identified . The estimated survivals at 3 years from HLA‐typing were 44 % and 21 % among patients with or without HLA‐identical donor , respectively ( P= 0·02 ) . 22/26 ( 85 % ) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 ( 32 % ) patients for whom autologous bone marrow transplantation was intended were indeed transplanted ( P < 0·001 ) . The survival was 50 % . 29 % and 17 % ( P= 0·004 ) for patients treated with allogeneic bone marrow transplantation , autologous bone marrow transplantation , or chemotherapy , respectively . 40/68 patients HLA‐typed in first complete remission had an HLA‐identical donor . The estimated 3‐year survival among patients typed in first remission with and without HLA‐identical donors was 42 % and 35 % ( n.s . ) , respectively . This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to r and omized trials when comparing bone marrow transplantation and other treatment options Treatment results were evaluated in 45 children with acute myeloblastic leukemia ( AML ) treated on the ANLL-9205 protocol of the Children 's Cancer Leukemia Study Group ( CCLSG , Japan ) . In this protocol , terarubicin ( THP-ADR ) , vincristine and continuous infusion of cytosine arabinoside ( Ara C ) were applied for remission induction therapy ( AVC ) , and VP16 + high dose Ara C were used sequentially for 32 or 48 weeks . Eleven patients received stem cell transplantation . Thirty-eight out of the 43 eligible patients ( 88.4 % ) achieved complete remission , and the overall 3-year event-free survival ( EFS ) was 55.6 % ( S.E.,10 % ) . This favorable response was attributed mainly to the high induction rate of patients with the M5 , M7 FAB subtypes and higher WBC counts ( > or = 10 x 10(9)/L ) . There was no difference in the 3-year EFS of these patients who discontinued treatment between 32 weeks and 48 weeks . Serious toxicities were not observed in this study . These findings suggest that the ANLL-9205 protocol is an effective and safe treatment regimen for childhood AML . When comparing the treatment period of 32 or 48 weeks , the difference was not statistically significant PURPOSE To report the impact of bone marrow transplantation ( BMT ) with busulfan/cyclophosphamide ( BuCy ) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia ( AML ) . PATIENTS AND METHODS Between May 1987 and November 1992 , 43 patients were diagnosed with AML . Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy . Conditioning for BMT was with BuCy , followed by allogeneic or unpurged autologous marrow infusion . RESULTS Of 37 patients who received chemotherapy , 35 achieved remission ( 95 % ) after one to six courses of treatment and 34 ( 92 % ) were transplanted . Five relapsed before BMT , four were subsequently transplanted in second complete remission ( CR2 ) ( n = 3 ) or untreated first relapse ( n = 1 ) , and one failed to respond to further therapy . All other patients proceeded to BMT in first complete remission ( CR1 ) . Eleven patients received allografts : one relapsed and one died of graft-versus-host disease ( GvHD ) , for a leukemia-free survival rate of 90 % at a median of 41 months after BMT ( range , 3 to 60 ) . For 23 autografts , there were two toxic deaths and eight relapses , with a leukemia-free survival rate of 61 % at a median of 11 months after BMT ( range , 0 to 66 ) . The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu . CONCLUSION With modern supportive therapy , most newly diagnosed children with AML will enter remission and are eligible for intensification therapy . BuCy is well tolerated in children , which allowed us to escalate the dose of Bu in recent patients . Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT Fifty seven patients entered the cooperative study AML II/87 of the working group " Pediatric Hematology and Oncology " of East Germany . Two patients with initial hyperleukocytosis died prior therapy . 13 patients died within the first 4 weeks of therapy , 3 patients did not respond to therapy , and one patient is not yet in remission . 38 patients ( 70 % ) attained a complete remission . 15 patients get a bone marrow transplantation in first CR ( 10 autologous BMT without purging , 5 allogenous BMT ) . 12 of them are living and well 3 to 34 months after BMT . 9 of the 23 patients under chemotherapy relapsed , one patient is lost to follow up . 13 patients are living in continuous complete remission . The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival ( DFS ) and 0.60 for event free interval ( EFI ) . The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI |
12,553 | 22,002,328 | Neither heterogeneity nor publication bias was detected .
The use of antimicrobial photodynamic therapy adjunctive to conventional treatment provides short-term benefits , but microbiological outcomes are contradictory .
There is no evidence of effectiveness for the use of antimicrobial photodynamic therapy as alternative to scaling root planing . | This meta- analysis was conducted to investigate the efficacy and safety of antimicrobial photodynamic therapy used alone or adjunctive to scaling root planing in patients with chronic periodontitis . | The aim of this study was to compare the short-term performance of a session of single photodynamic therapy ( PDT ) and of a conventional ultrasonic debridement ( UST ) in persistent pockets of maintenance patients . In a prospect i ve , r and omized , controlled , single-blind clinical study , patients with chronic periodontitis with at least two persistent pockets ( > 4 mm ) were enrolled . They were treated either with UST ( n = 29 ) or PDT ( n = 25 ) . Clinical and microbiological examinations were performed at baseline and after 3 month . For UST , the mean probing depth was reduced from 5.3 to 4.5 mm ( p = < 0.001 ) and for PDT from 5.3 to 4.7 mm ( p < 0.001 ) with no difference between the two treatment modalities . Microbial counts were significantly reduced about 30 % to 40 % immediately after debridement but returned to baseline values at month 3 irrespective of treatment . PDT is not superior to conventional mechanical treatment of persistent pockets , but it may be a meaningful therapeutic alternative ; the clinical effects were too minor to draw a definitive conclusion BACKGROUND Single photodynamic therapy ( PDT ) has been effective in initial periodontal therapy , but only improved bleeding on probing ( BoP ) in maintenance patients after a single use . Repeated PDT has not been addressed . OBJECTIVES To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance . MATERIAL AND METHODS Ten maintenance patients with 70 residual pockets [ probing pocket depth (PPD)>or=5 mm ] were r and omly assigned for treatment five times in 2 weeks ( Days 0 , 1 , 2 , 7 , 14 ) with PDT ( test ) or non-activated laser ( control ) following debridement . The primary outcome variable was PPD , and the secondary variables were clinical attachment level ( CAL ) and BoP. These were assessed at 3 , 6 and 12 months following the interventions . RESULTS Greater PPD reductions were observed in the test ( -0.67 + /- 0.34 ; p=0.01 ) compared with the control patients ( -0.04 + /- 0.33 ; NS ) after 6 months . Significant CAL gain ( + 0.52 + /- 0.31 ; p=0.01 ) was noted for the test , but not in the control ( -0.27 + /- 0.52 ; NS ) patients after 6 months . BoP percentages decreased significantly in test ( 97 - 64 % , 67 % , 77 % ) , but not control patients after 3 , 6 and 12 months . CONCLUSIONS Repeated ( five times ) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients . The effects were best documented after 6 months AIM A r and omized-controlled clinical pilot trial was design ed to evaluate photodynamic therapy ( PDT ) for its bactericidal potential and clinical effect in the treatment of periodontitis . MATERIAL AND METHODS Fifty-eight subjects with chronic periodontitis were included . Each subject exhibited at least three active periodontal pockets 5 mm or deeper , bleeding on probing and the presence of Porphyromonas gingivalis . Subjects were r and omly assigned to a control group treated by subgingival ultrasound only or to a study group additionally treated by PDT . Baseline clinical values of gingival index , bleeding on probing , probing pocket depths and clinical attachment levels were recorded and re-evaluated 90 days later . Pathogen screening for P. gingivalis , Tannerella forsythia and Treponema denticola was conducted at baseline as well as 10 , 42 and 90 days after treatment . RESULTS P. gingivalis was significantly reduced in both groups ( laser group : p=0.020 ; control group : p=0.042 ) . No significant reductions of T. forsythia and T. denticola were observed in either group . For the microbial parameters , no significant difference was found between the laser and the control group . All clinical parameters were significantly reduced in both groups after treatment . The mean probing pocket depths decreased from 5.79 to 4.55 mm in the laser group and from 5.54 to 4.51 in the control group . The intergroup difference was not significant ( p=0.82 ) . Bleeding on probing was reduced from 100 % evaluated at baseline to 47 % in the laser group and 59 % in the control group . The intergroup difference was not significant ( p=0.28 ) . No significant differences were observed in any other parameters . CONCLUSION Application of a single cycle of PDT was not effective as an adjunct to ultrasonic periodontal treatment . There were no extra reductions in pocket depths and bleeding on probing . With regard to eradicating bacteria , however , there are no additional effects as compared with conventional treatment alone In recent years , the combination of laser light and photosensitizer known as photodynamic therapy ( PDT ) has been used in periodontal therapy . However , there are not enough clinical studies to fully evaluate the effects of PDT on the periodontal tissues . This microbiological study examined the effects of PDT on the periodontal bacteria in combination with scaling and root planing ( SRP ) in the same group of patients by r and omly selecting PDT or SRP for use in different quadrants of the mouth . For the present study , PDT was compared with a diode laser ( 980 nm ) and an Nd : YA G laser ( 1,064 nm ) . Microbiological sample s were examined and evaluated over a period of three months . Significant bacterial reduction has been observed in all cases . The diode laser with SRP presented long-term positive results , while PDT showed a significant bacteria reduction during the entire observation period Recent pre clinical and clinical data have suggested the potential benefit of photodynamic therapy ( PDT ) in the treatment of periodontitis . However , currently , there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis . The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy . Twenty-four patients receiving regularly supportive periodontal therapy were r and omly treated with either subgingival scaling and root planing followed by a single episode of PDT ( test ) or subgingival scaling and root planing alone ( control ) . The following parameters were evaluated at baseline and at 3 months and 6 months after therapy : full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , bleeding on probing ( BOP ) at experimental sites , probing pocket depth ( PPD ) , gingival recession ( REC ) , and clinical attachment level ( CAL ) . Primary outcome variables were changes in PPD and CAL . Microbiological evaluation of Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , Prevotella intermedia ( P.i . ) , Tannerella forsythensis ( T.f . ) , Treponema denticola ( T.d . ) , Peptostreptococcus micros ( P.m . ) , Fusobacterium nucleatum ( F.n . ) , Campylobacter rectus ( C.r . ) , Eubacterium nodatum ( E.n . ) , Eikenella corrodens ( E.c . ) , and Capnocytophaga species ( C.s . ) was also performed at baseline and at 3 months and 6 months after therapy , using a commercially available polymerase chain reaction test . No differences in any of the investigated parameters were observed at baseline between the two groups . At 3 months and 6 months after treatment , there were no statistically significant differences between the groups in terms of PPD , CAL and FMPS . At 3 months and 6 months , a statistically significantly higher improvement of BOP was found in the test group . At 3 months after therapy , the microbiological analysis showed a statistically significant reduction of F.n . and E.n . in the test group . At 6 months , statistically significantly higher numbers of E.c . and C.s . were detected in the test group . The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PPD reduction and CAL gain , but it result ed in significantly higher reduction of bleeding scores than following scaling and root planing alone OBJECTIVE The aim of the present study was to compare the effectiveness of a photodisinfection process to that of scaling and root planing ( SRP ) for non-surgical periodontal treatment . METHODOLOGY Thirty-three subjects with moderate to advanced periodontal disease were r and omly treated in one of three study arms with either photodisinfection ( PD ) alone ( Group 1 ) using a diode laser and photosensitizer combination , with SRP alone ( Group 2 ) , or with SRP and PD combined ( Group 3 ) . Clinical assessment s of bleeding on probing ( BOP ) , probing pocket depth ( PPD ) , and clinical attachment level ( CAL ) were made at baseline , three weeks , six weeks , and 12 weeks following therapy . RESULTS No difference in any of the investigated parameters was observed at baseline between the three groups . The mean value of BOP decreased in the PD group ( Group 1 ) from baseline by 71 % at six weeks and 73 % at 12 weeks , and in the SRP alone group ( Group 2 ) from baseline by 43 % at six weeks and 56 % at 12 weeks . The BOP in the combined SRP + PD group ( Group 3 ) decreased from baseline by 65 % at six and 59 % at 12 weeks . The sites treated with PD alone demonstrated mean CAL gains of 0.09 + /- 0.38 mm and 0.14 + /- 0.65 mm at six and 12 weeks , respectively . Those sites treated with SRP alone demonstrated mean CAL gains of 0.37 + /- 0.34 mm and of 0.36 + /- 0.35 mm at six and 12 weeks , respectively . The final group of SRP + PD demonstrated mean CAL gains of 0.92 + /- 0.62 mm and 0.86 + /- 0.61 mm at six and 12 weeks , respectively ( p < 0.01 for six weeks and p < 0.02 for 12 weeks when compared to SRP alone ) . The sites treated with PD alone demonstrated mean PPD reductions of 0.69 + /- 0.33 mm and of 0.67 + /- 0.44 mm at six and 12 weeks , respectively . Those sites treated with SRP alone demonstrated mean PPD reductions of 0.78 + /- 0.47 mm and 0.74 + /- 0.43 mm at six and 12 weeks , respectively . The final group of SRP + PD demonstrated mean PPD reductions of 1.16 + /- 0.39 mm and 1.11 + /- 0.53 at six and 12 weeks , respectively ( p < 0.06 for six weeks and p < 0.05 for 12 weeks when compared to SRP alone ) . CONCLUSION Within the limits of the present study , it can be concluded that SRP combined with photodisinfection leads to significant improvements of the investigated parameters over the use of SRP alone The aim of this trial was to investigate changes occurring in the subgingival microbiological composition of subjects with aggressive periodontitis , treated with antimicrobial photodynamic therapy ( aPDT ) , in a single episode , or scaling and root planing ( SRP ) , in a split-mouth design on −7 , 0 , and + 90 days . Ten patients were r and omly assigned to either aPDT using a laser source in conjunction with a photosensitizer or SRP with h and instruments . Subgingival plaque sample s were collected and the counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization . The data were analyzed using the method of generalized estimating equations ( GEE ) to test the associations between treatments , evaluated parameters , and experimental times ( α = .05 ) . The results indicated that aPDT and SRP affects different bacterial species , with aPDT being effective in reducing numbers of A. actinomycetemcomitans than SRP . On the other h and , SRP was more efficient than aPDT in reducing the presence of periodontal pathogens of the Red Complex . Additionally , a recolonization in the sites treated by aPDT was observed , especially for T. forsythia and P. gingivalis . Under our experimental conditions , this trial demonstrates that aPDT and SRP affected different groups of bacteria , suggesting that their association may be beneficial for the non-surgical treatment of aggressive periodontitis The aim of this study was to evaluate the effects of the photodynamic therapy ( PDT ) on the inflammatory infiltrate and on the collagen network organization in human advanced chronic periodontitis . Two different drug delivery systems ( DDS ) were tested ( liposomes and nanoemulsions ) to determine if the effects of PDT could differ according to the DDS used . Sixteen patients presenting two teeth with chronic advanced periodontitis and important tooth mobility with clinical indication of extraction were included in the group liposomes ( group L , n=8 ) or in the group nanoemulsions ( group N , n=8 ) in order to compare the effects of each DDS . Seven days before extraction s one tooth of each patient was treated with PDT using phthalocyanine derivatives as photosensitizers and the contralateral tooth was taken as control . In group L the density of gingival collagen fibers ( 66±19 % ) was significantly increased ( p<0.02 ) when compared to controls ( 35±21 % ) . Concerning the antigen-presenting cells , PDT had differential effects depending on the drug delivery system ; the number of macrophages was significantly decreased ( p<0.05 ) in group L while the number of Langerhans cells was significantly decreased in group N ( p<0.02 ) . These findings demonstrate that PDT presents an impact on gingival inflammatory phenomenon during chronic periodontitis and leads to a specific decrease of antigen-presenting cells population s according to the drug delivery system used BACKGROUND Periodontitis is a major cause of tooth loss among adults . Several studies have shown a possible systemic impact of periodontal infection , including poor glycemic control in patients with diabetes . Recently , photodynamic therapy ( PDT ) was used to successfully treat periodontal infection . PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects . The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis . METHODS Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and r and omly assigned to one of the following three treatment modalities ( 15 subjects each ) : scaling and root planing ( SRP ) only , SRP plus systemic doxycycline , and SRP plus PDT . The plaque and bleeding scores , probing depth , clinical attachment level , and glycosylated hemoglobin ( HbA1c ) level were recorded at baseline and 3 months after periodontal treatment . Descriptive statistics , the paired t test , and analysis of variance ( ANOVA ) were used for data analysis . RESULTS Statistically significant differences in the mean probing depth , clinical attachment level , plaque deposit , and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups . No significant differences in periodontal parameters and glucose levels were detected among the three groups . Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group . CONCLUSION The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes AIM The purpose of the present investigation was to determine the percentage and identity of antibiotic-resistant species in subgingival plaque and saliva sample s from chronic periodontitis patients treated by scaling and root planing followed by orally administered amoxicillin or metronidazole . METHOD In all , 20 chronic periodontitis patients were selected for study . After clinical and microbiological monitoring , subjects were r and omly assigned to receive either orally administered amoxicillin at the dosage of 500 mg , 3 times daily for 14 days or orally administered metronidazole at the dosage of 250 mg , 3 times daily for 14 days . For the antibiotic resistance determinations , subgingival plaque sample s were taken from six posterior teeth at baseline , and 90 days ; and from two r and omly selected teeth at 3 , 7 and 14 days during and after antibiotic administration . Sample s were plated on enriched blood agar plates with or without either 2 micro g/mL metronidazole or 2 micro g/mL amoxicillin . Colonies were counted at 7 days . Significant differences in percentage of resistant organisms over time were determined by the Quade test . Microbial growth was washed from antibiotic-containing media and the identity of species determined using checkerboard DNA-DNA hybridization . Data were compared with those obtained in a previous study from subjects receiving SRP only or SRP followed by 14 days of orally administered doxycycline . The level of doxycycline used to determine antibiotic resistance in that study was 4 micro g/mL. RESULTS The mean percentage of resistant isolates increased during antibiotic administration and returned to baseline levels by 90 days post therapy . The mean percentages ( + /- SEM ) of isolates resistant to 2 micro g/mL metronidazole were 53 + /- 9 , 65 + /- 9 , 79 + /- 4 and 69 + /- 7 at baseline , 3 , 7 and 14 days during antibiotic administration , and 57 + /- 4 , 64 + /- 5 , 62 + /- 7 and 47 + /- 6 at 3 , 7 , 14 and 90 days after antibiotic administration . At the same time points , the percentage of resistant isolates to amoxicillin was 0.5 + /- 0.2 , 22 + /- 12 , 14 + /- 5 and 37 + /- 11 during , and 31 + /- 11 , 8 + /- 3 , 3 + /- 2 and 3 + /- 0.6 after , administration . Antibiotic-resistant isolates of resistant species detected during or after therapy were also detected prior to therapy . The most prevalent resistant species in the metronidazole-treated group were : A. naeslundii 1 , S. constellatus , A. naeslundii 2 , S. mitis , S. oralis , A. odontolyticus , S. sanguis , and in the amoxicillin-treated group : S. constellatus , P. nigrescens , E. saburreum , A. naeslundii 1 , S. oralis , P. melaninogenica and P. intermedia . CONCLUSIONS Systemic antibiotic administration transiently increased the percentage of resistant subgingival species , but a major component of subgingival plaque remained sensitive to the agents during their administration . Antibiotic-resistant isolates of resistant species could be detected in sample s both prior to and after therapy . However , % antibiotic-resistant isolates returned to baseline levels 90 days after antibiotic administration 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 Aggressive periodontitis is a specific form of periodontal disease that is characterized by rapid attachment loss and bone destruction . Cytokine profiles are of considerable value when study ing disease course during treatment . The aim of this trial was to investigate cytokine levels in the gingival crevicular fluid ( GCF ) of patients with aggressive periodontitis , after treatment with photodynamic therapy ( PDT ) or scaling and root planing ( SRP ) , in a split-mouth design on -7 , 0 , + 1 , + 7 , + 30 , and + 90 days . METHODS Ten patients were r and omly treated with PDT using a laser source associated with a photosensitizer or SRP with h and instruments . GCF sample s were collected , and the concentrations of tumor necrosis factor-alpha ( TNF-alpha ) and receptor activator of nuclear factor-kappa B lig and ( RANKL ) were determined by enzyme-linked immunosorbent assays . The data were analyzed using generalized estimating equations to test the associations among treatments , evaluated parameters , and experimental times ( alpha = 0.05 ) . RESULTS Non-surgical periodontal treatment with PDT or SRP led to statistically significant reductions in TNF-alpha level 30 days following treatment . There were similar levels of TNF-alpha and RANKL at the different time points in both groups , with no statistically significant differences . CONCLUSION SRP and PDT had similar effects on crevicular TNF-alpha and RANKL levels in patients with aggressive periodontitis 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 Practitioners are not successful in implemented treatments due to the great difficulty in completely removing bacterial deposits and their endotoxins . This study aim ed to evaluate the capacity of photodynamic therapy to reduce the numbers of viable bacteria in periodontal pockets . Microbiological sample s were collected before and after scaling and after photodynamic therapy . Photodynamic therapy was performed through the insertion of the photosensitizer toluidine blue and Endo PTC into the pocket for 3 min , followed by photosensitization with low-intensity diode of 4 J/cm2 . The results ( log10 ) were su bmi tted to a descriptive analysis and a t-test . A reduction of 81.24 % in the numbers of bacteria after scaling was observed , as well as 95.90 % after photodynamic therapy ( P < 0.01 ) . Photodynamic therapy is indicated as an adjuvant treatment to reduce the numbers of viable bacteria in periodontal diseases OBJECTIVE The purpose of this study was to evaluate the clinical effects of photodynamic therapy ( PDT ) for scaling and root planing ( SRP ) in the treatment of chronic periodontitis . BACKGROUND DATA PDT has become a potential treatment of infectious diseases with the development of laser medicine . However , there are very limited data from clinical trials to evaluate the effect of PDT in the treatment of periodontitis . MATERIAL S AND METHODS Fifty-eight patients with chronic periodontitis were included and divided into three groups . They were treated with SRP alone , SRP followed by one PDT , or SRP followed by two PDT treatments . PDT was performed at sites with a probing depth ( PD ) ≥5 mm by using Periowave(TM ) therapy . Periodontal values of bleeding on probing ( BOP ) , PD , and clinic attachment loss ( CAL ) were examined at baseline , 6 wk after treatment , and 12 wk after treatment . RESULTS Compared with the baseline , sites with baseline PD ≥5 mm in all three groups showed significant reductions of PD , CAL , and BOP at 6 and 12 wk after treatment . Although there were no differences between the three groups for PD and CAL in all three examinations , the presence of BOP sites at 12 wk , but not 6 wk , after SRP treatment significantly decreased in groups with PDT in comparison with SRP alone . CONCLUSION PDT may serve as an adjunctive therapy to SRP treatment in periodontal pockets with PD ≥5 mm to reduce the presence of bleeding in these lesions BACKGROUND The purpose of this study is to clinical ly and microbiologically evaluate the effect of photodynamic therapy ( PDT ) as a full-mouth procedure in Fusobacterium nucleatum-infected patients with periodontitis . METHODS In the present study , PDT is administered adjuvantly after scaling and root planing ( SRP ) to patients with localized chronic periodontitis ( LCP ) . Twenty-four patients , in whom only F. nucleatum was detected by baseline polymerase chain reaction ( PCR ) after SRP , were r and omly assigned to PDT and control groups . PDT was carried out once as a full-mouth disinfection in the test group . The control group was treated with the photosensitizer solution , but without laser irradiation . In all subjects , the clinical parameters plaque index , reddening , bleeding on probing ( BOP ) , probing depth ( PD ) , gingival recession , and clinical attachment level ( CAL ) were determined at the baseline examination and at 1 , 4 , and 12 weeks after PDT . Quantitative analysis of the F. nucleatum DNA concentration was performed by competitive PCR . All clinical indices were calculated for each test and control subject as were the median and interquartile range of each group . RESULTS In patients with LCP who received PDT treatment , significant reductions in reddening , BOP , and mean PD and CAL were observed during the observation period and with respect to controls . Four and 12 weeks after PDT , the mean PD and CAL showed significant differences from baseline values and from those of the control group . In the PDT group , 12 weeks after treatment , the F. nucleatum DNA concentration was found to be significantly reduced compared to the baseline level . CONCLUSION The results of this study show that the adjuvant application of the described PDT method is appropriate to reduce periodontal inflammatory symptoms and to successfully treat infection with F. nucleatum |
12,554 | 27,165,648 | CONCLUSIONS Hospital-initiated CM can be successful in reducing unplanned hospital readmissions for HF and length of hospital stay for people with HF .
9 trials described cost data ; no clear difference emerged between CM and usual care .
There was limited evidence for community-initiated CM which suggested it does not reduce admission | OBJECTIVES The aim of this systematic review of r and omised controlled trials ( RCTs ) and controlled trials ( non- RCTs , N RCTs ) is to investigate the effectiveness and related costs of case management ( CM ) for patients with heart failure ( HF ) predominantly based in the community in reducing unplanned readmissions and length of stay ( LOS ) . | BACKGROUND Case management is believed to promote continuity of care and decrease hospitalization rates , although few controlled trials have tested this approach . OBJECTIVE To assess the effectiveness of a st and ardized telephonic case-management intervention in decreasing re source use in patients with chronic heart failure . METHODS A r and omized controlled clinical trial was used to assess the effect of telephonic case management on re source use . Patients were identified at hospitalization and assigned to receive 6 months of intervention ( n = 130 ) or usual care ( n = 228 ) based on the group to which their physician was r and omized . Hospitalization rates , readmission rates , hospital days , days to first rehospitalization , multiple readmissions , emergency department visits , inpatient costs , outpatient re source use , and patient satisfaction were measured at 3 and 6 months . RESULTS The heart failure hospitalization rate was 45.7 % lower in the intervention group at 3 months ( P = .03 ) and 47.8 % lower at 6 months ( P = .01 ) . Heart failure hospital days ( P = .03 ) and multiple readmissions ( P = .03 ) were significantly lower in the intervention group at 6 months . Inpatient heart failure costs were 45.5 % lower at 6 months ( P = .04 ) . A cost saving was realized even after intervention costs were deducted . There was no evidence of cost shifting to the outpatient setting . Patient satisfaction with care was higher in the intervention group . CONCLUSIONS The reduction in hospitalizations , costs , and other re source use achieved using st and ardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches Background Many older people in long-term care do not receive evidence -based diagnosis or management for heart failure ; it is not known whether this can be achieved for this population . We initiated an onsite heart failure service , compared with ‘ usual care ’ with the aim of establishing the feasibility of accurate diagnosis and appropriate management . Methods A pilot r and omised controlled trial which r and omised residents from 33 care facilities in North-East Engl and with left ventricular systolic dysfunction ( LVSD ) to usual care or an onsite heart failure service . The primary outcome was the optimum prescription of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists at 6 months . Results Of 399 echocardiographically-screened residents aged 65–100 years , 30 subjects with LVSD were eligible ; 28 ( 93 % ) consented and were r and omised ( HF service : 16 ; routine care : 12 ) . Groups were similar at baseline ; six month follow-up was completed for 25 patients ( 89 % ) ; 3 ( 11 % ) patients died . Results for the primary outcome were not statistically significant but there was a consistent pattern of increased drug use and titration to optimum dose in the intervention group ( 21 % compared to 0 % receiving routine care , p=0.250 ) . Hospitalisation rates , quality of life and mortality at 6 months were similar between groups . Conclusions This study demonstrated the feasibility of an on-site heart failure service for older long-term care population s. Optimisation of medication appeared possible without adversely affecting quality of life ; this questions clinicians ’ concerns about adverse effects in this group . This has international implication s for managing such patients . These methods should be replicated in a large-scale study to quantify the scale of benefit . Trial registration IS RCT N19781227 http://www.controlled-trials.com/IS RCT Background — The long-term impact of chronic heart failure management programs over the typical life span of affected individuals is unknown . Methods and Results — The effects of a nurse-led , multidisciplinary , home-based intervention ( HBI ) in a typically elderly cohort of patients with chronic heart failure initially r and omized to either HBI ( n=149 ) or usual postdischarge care ( UC ) ( n=148 ) after a short-term hospitalization were studied for up to 10 years of follow-up ( minimum 7.5 years of follow-up ) . Study end points were all-cause mortality , event-free survival ( event was defined as death or unplanned hospitalization ) , recurrent hospital stay , and cost per life-year gained . Median survival in the HBI cohort was almost twice that of UC ( 40 versus 22 months ; P<0.001 ) , with fewer deaths overall ( HBI , 77 % versus 89 % ; adjusted relative risk , 0.74 ; 95 % CI , 0.53 to 0.80 ; P<0.001 ) . HBI was associated with prolonged event-free survival ( median , 7 versus 4 months ; P<0.01 ) . HBI patients had more unplanned readmissions ( 560 versus 550 ) but took 7 years to overtake UC ; the rates of readmission ( 2.04±3.23 versus 3.66±7.62 admissions ; P<0.05 ) and related hospital stay ( 14.8±23.0 versus 28.4±53.4 days per patient per year ; P<0.05 ) were significantly lower in the HBI group . HBI was associated with 120 more life-years per 100 patients treated compared with UC ( 405 versus 285 years ) at a cost of $ 1729 per additional life-year gained when we accounted for healthcare costs including the HBI . Conclusions — In altering the natural history of chronic heart failure relative to UC ( via prolonged survival and reduced frequency of recurrent hospitalization ) , HBI is a remarkably cost- and time-effective strategy over the longer term Background —It is not known to what extent initially observed benefits of postdischarge programs of care for patients with chronic congestive heart failure ( CHF ) in respect to event-free survival , readmissions , and healthcare costs persist in the long term . Methods and Results —We prospect ively studied the long-term effects of a multidisciplinary home-based intervention ( HBI ) in a cohort of CHF patients r and omly allocated to either to HBI ( n=149 ) or usual care ( n=148 ) . During a median of 4.2 years of follow-up , there were significantly fewer primary end points ( unplanned readmission or death ) in the HBI versus usual care group : a mean of 0.21 versus 0.37 primary events per patient per month ( P < 0.01 ) . Median event-free survival was more prolonged in the HBI than usual care group ( 7 versus 3 months;P < 0.01 ) . Fewer HBI patients died ( 56 % versus 65%;P = 0.06 ) and had more prolonged survival ( a median of 40 versus 22 months;P < 0.05 ) compared with usual care . Assignment to HBI was both an independent predictor of event-free survival ( RR 0.70;P < 0.01 ) and survival alone ( RR 0.72;P < 0.05 ) . Overall , HBI patients had 78 fewer unplanned readmissions compared with usual care ( 0.17 versus 0.29 readmissions per patient per month;P < 0.05 ) . The median cost of these readmissions was $ A325 versus $ A660/month per HBI and usual care patient ( P < 0.01 ) . Conclusions —The beneficial effects of HBI in reducing frequency of unplanned readmissions in CHF patients persist in the long term and are associated with prolongation of survival OBJECTIVES The goal of this study was to make a head-to-head comparison of 2 common forms of multidisciplinary chronic heart failure ( CHF ) management . BACKGROUND Although direct patient contact appears to be best in delivering CHF management overall , the precise form to optimize health outcomes is less clear . METHODS This prospect i ve , multicenter r and omized controlled trial with blinded endpoint adjudication comprised 280 hospitalized CHF patients ( 73 % male , age 71 ± 14 years , and 73 % with left ventricular ejection fraction ≤45 % ) r and omized to home-based intervention ( HBI ) or specialized CHF clinic-based intervention ( CBI ) . The primary endpoint was all-cause , unplanned hospitalization or death during 12- to 18-month follow-up . Secondary endpoints included type/ duration of hospitalization and healthcare costs . RESULTS The primary endpoint occurred in 102 of 143 ( 71 % ) HBI versus 104 of 137 ( 76 % ) CBI patients ( adjusted hazard ratio [ HR ] : 0.97 [ 95 % confidence interval ( CI ) : 0.73 to 1.30 ] , p = 0.861 ) : 96 ( 67.1 % ) HBI versus 95 ( 69.3 % ) CBI patients had an unplanned hospitalization ( p = 0.887 ) , and 31 ( 21.7 % ) versus 38 ( 27.7 % ) died ( p = 0.252 ) . The median duration of each unplanned hospitalization was significantly less in the HBI group ( 4.0 [ interquartile range ( IQR ) : 2.0 to 7.0 ] days vs. 6.0 [ IQR : 3.5 to 13 ] days ; p = 0.004 ) . Overall , 75 % of all hospitalization was attributable to 64 ( 22.9 % ) patients , of whom 43 ( 67 % ) were CBI patients ( adjusted odds ratio : 2.55 [ 95 % CI : 1.37 to 4.73 ] , p = 0.003 ) . HBI was associated with significantly fewer days of all-cause hospitalization ( -35 % ; p = 0.003 ) and from cardiovascular causes ( -37 % ; p = 0.025 ) but not for CHF ( -24 % ; p = 0.218 ) . Consequently , healthcare costs ( $ AU3.93 vs. $ AU5.53 million ) were significantly less for the HBI group ( median : $ AU34 [ IQR : 13 to 81 ] per day vs. $ AU52 [ 17 to 140 ] per day ; p = 0.030 ) . CONCLUSIONS HBI was not superior to CBI in reducing all-cause death or hospitalization . However , HBI was associated with significantly lower healthcare costs , attributable to fewer days of hospitalization . ( Which Heart failure Intervention is most Cost-effective & consumer friendly in reducing Hospital care [ WHICH ? ] ; ACTRN12607000069459 ) Abstract Objectives : To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure . Design : R and omised controlled trial . Setting : Acute medical admissions unit in a teaching hospital . Participants : 165 patients admitted with heart failure due to left ventricular systolic dysfunction . The intervention started before discharge and continued thereafter with home visits for up to 1 year . Main outcome measures : Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure . Results : 31 patients ( 37 % ) in the intervention group died or were readmitted with heart failure compared with 45 ( 53 % ) in the usual care group ( hazard ratio=0.61 , 95 % confidence interval 0.33 to 0.96).Compared with usual care , patients in the intervention group had fewer readmissions for any reason ( 86 v 114 , P=0.018 ) , fewer admissions for heart failure ( 19 v 45 , P<0.001 ) and spent fewer days in hospital for heart failure ( mean 3.43 v 7.46 days , P=0.0051 ) . Conclusions : Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure . What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this Background Chronic ( systolic ) heart failure ( CHF ) is a common and disabling condition . Adherence to evidence -based guidelines in primary care has been shown to improve health outcomes . The aim was to explore the impact of a multidisciplinary educational intervention for general practitioners ( GPs ) ( Train the trainer = TTT ) on patient and performance outcomes . Methods This paper presents the key findings from the trial and discusses the lessons learned during the implementation of the TTT trial . Primary care practice s were r and omly assigned to the TTT intervention or to the control group . 37 GPs ( 18 TTT , 19 control ) were r and omised and 168 patients diagnosed with ascertained CHF ( 91 TTT , 77 control ) were enrolled . GPs in the intervention group attended four meetings addressing clinical practice guidelines and pharmacotherapy feedback . The primary outcome was patient self-reported quality of life at seven months , using the SF-36 Physical Functioning scale . Secondary outcomes included other SF-36 scales , the Kansas City Cardiomyopathy Question naire ( KCCQ ) , total mortality , heart failure hospital admissions , prescribing , depressive disorders ( PHQ-9 ) , behavioural change ( European Heart Failure Self-Care Behaviour Scale ) , patient-perceived quality of care ( EUROPEP ) and improvement of heart failure using NT-proBNP-levels . Because recruitment targets were not achieved an exploratory analysis was conducted . Results There was high baseline achievement in both groups for many outcomes . At seven months , there were no significant mean difference between groups for the primary outcome measure ( -3.3 , 95%CI -9.7 to 3.1 , p = 0.30 ) . The only difference in secondary outcomes related to the prescribing of aldosterone antagonists by GPs in the intervention group , with significant between group differences at follow-up ( 42 vs. 24 % , adjusted OR = 4.0 , 95%CI 1.2–13 ; p = 0.02 ) . Conclusion The intervention did not change the primary outcome or most secondary outcomes . Recruitment targets were not achieved and the under-recruitment of practice s and patients alongside a selection bias of participating GPs , prohibit definite conclusions , but the CI indicates a non-effectiveness of the intervention in this sample . We describe the lessons learned from conducting the trial for the future planning and conduct of confirmatory trials in primary care . Trial registration IS RCT N08601529 While disease management appears to be effective in selected , small groups of CHF patients from r and omized controlled trials , its effectiveness in a broader CHF patient population is not known . This prospect i ve , quasi-experimental study compared patient outcomes under a nurse practitioner-led disease management model ( intervention group ) with outcomes under usual care ( control group ) in both primary and tertiary medical centers . The study included 969 veterans ( 458 intervention , 511 control ) treated for CHF at six VA medical centers . Intervention patients had significantly fewer ( p<0.05 ) CHF and all-cause admissions at one-year follow-up , and lower mortality at both one- and two-year follow-up . These data provide support for the potential effectiveness of the intervention , and suggest that the evidence from RCTs of disease management models for CHF can be translated into clinical practice , even without the benefits of a selected patient population and dedicated re sources often found in RCTs OBJECTIVE To determine the effect of a home-based intervention ( HBI ) on the frequency of unplanned readmission and out-of-hospital death among patients discharged home from acute hospital care . DESIGN A r and omized controlled trial comparing HBI with usual care ( UC ) . SETTING A tertiary referral hospital servicing the northwestern region of Adelaide , South Australia . PARTICIPANTS Medical and surgical patients ( n = 762 ) discharged home after hospitalization . INTERVENTION Home-based intervention ( n = 381 ) consisted of counseling of all patients before discharge followed by a single home visit ( by a nurse and pharmacist ) to those patients considered to be at high risk of readmission ( n = 314 ) in order to optimize compliance with and knowledge of the treatment regimen , identify early clinical deterioration , and intensify follow-up of such patients where appropriate . MEASUREMENTS The primary endpoint was the number of unplanned readmissions plus out-of-hospital deaths over a 6-month follow-up period . RESULTS During the study follow-up , the major endpoint occurred most commonly in the UC group ( 217 vs 155 episodes : P < .001 ) . Overall , the HBI group demonstrated fewer unplanned readmissions ( 154 vs 197 : P = .022 ) , out-of-hospital deaths ( 1 vs. 20 : P < .001 ) , total deaths ( 12 vs. 29 : P = .006 ) , emergency department attendances ( 236 vs 314 : P < .001 ) , and total days of hospitalization ( 1452 vs 1766 : P < .001 ) . There was a disproportionate reduction in multiple events among HBI patients ( P = .035 ) . Hospital-based costs of health care during study follow-up tended to be lower in the HBI group ( $ A2190 vs $ A2680 per patient : P = .102 ) . Mean cost of HBI was $ A190 per patient visited , whereas other community-based health care costs were similar for both groups . CONCLUSIONS Among high-risk patients discharged from acute hospital care , HBI is beneficial in limiting unplanned readmissions and reducing risk of out-of-hospital death . It may be particularly cost-effective if applied selectively to patients with a history of frequent unplanned hospital admission OBJECTIVE To assess the impact of supplementing nurse case management with Internet-connected telemonitoring on clinical outcomes in an elderly heart failure ( HF ) population . STUDY DESIGN R and omized clinical trial allocating high-risk HF subjects to the telehealth system with case management ( THCM ) versus case management ( CM ) alone . METHODS Medicare Advantage members with HF and recent hospitalization were r and omized to THCM or CM . Consenting participants received THCM for 6 months or the health plan 's usual Medicare specialized CM as long as deemed necessary . The primary outcome measure was a composite of all-cause hospitalization , ED visit , or death . Because only a subset of those who were r and omized consented and participated , the strategies were evaluated as-treated rather than by intention-to-treat , with multivariate adjustment in logistic regression models for confounding introduced by postr and omization exclusions . RESULTS The treated sample size was 164 subjects in THCM and 152 in CM . Treatment arms did not differ significantly for the primary composite outcome ( 45 % for THCM vs 40 % for CM , relative risk 1.18 ; P = .22 ) . Telehealth alerts prompted frequent telephonic contact , increasing THCM case managers ' workload . The participant population overall had 42 % fewer inpatient days during the intervention period compared with the previous year . CONCLUSIONS Despite effective implementation of an Internet-based telehealth intervention in an elderly HF population , there was no discernible impact on overall morbidity or mortality . Notably , limited postr and omization participation decreased power to detect a difference . The reduction in days hospitalized for trial participants overall underscores the benefit of CM for such HF patients BACKGROUND R and omized controlled trials have demonstrated the efficacy of nurse-led transitional care programs to reduce readmission rates for patients with heart failure ; the effectiveness of these programs in real-world health care systems is less well understood . METHODS We performed a prospect i ve study with concurrent controls to test an advanced practice nurse-led transitional care program for patients with heart failure who were 65 years or older and were discharged from Baylor Medical Center Garl and ( BMC G ) from August 24 , 2009 , through April 30 , 2010 . We compared the effect of the program on 30-day ( from discharge ) all-cause readmission rate , length of stay , and 60-day ( from admission ) direct cost for BMC G with that of other hospitals within the Baylor Health Care System . We also performed a budget impact analysis using costs and reimbursement experience from the intervention . RESULTS The intervention significantly reduced adjusted 30-day readmission rates to BMC G by 48 % during the postintervention period , which was better than the secular reductions seen at all other facilities in the system . The intervention had little effect on length of stay or total 60-day direct costs for BMC G. Under the current payment system , the intervention reduced the hospital financial contribution margin on average $ 227 for each Medicare patient with heart failure . CONCLUSIONS Preliminary results suggest that transitional care programs reduce 30-day readmission rates for patients with heart failure . This underscores the potential of the intervention to be effective in a real-world setting , but payment reform may be required for the intervention to be financially sustainable by hospitals The aim of this study was to investigate whether , in a r and omized controlled trial ( RCT ) of vulnerable elders with heart failure ( HF ) , advanced practice nurses ( APNs ) who were coordinating care in the transition from hospital to home could improve outcomes , prevent rehospitalizations , and reduce costs when compared with usual care . The APN strategies focused on improving patient and family or caregiver effectiveness in managing their illnesses , strengthening the patient-provider relationship , and managing comorbid conditions while improving overall health . The results were positive . By capitalizing on the patient 's desire to achieve their identified goals , APNs successfully educated patients about the meaning of their symptoms and appropriate self-management strategies ; improved patient-provider communication patterns ; and marshaled caregiver and community re sources to maximize patient adherence to the treatment plan and overall quality of life . While HF was the primary reason for enrollment in the study , optimal health outcomes dem and ed a strong focus on integrating management of comorbid conditions and other long-st and ing health problems . Specific strategies used by the APN to achieve these positive outcomes are addressed in this report . These strategies are compared with nursing interventions used in other RCTs of HF home management . Directions for future research are explored INTRODUCTION AND OBJECTIVES The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure . METHODS A r and omized clinical trial was carried out between January 2004 and October 2006 . In total , 283 patients admitted to hospital with a diagnosis of heart failure were r and omly allocated to a home-based intervention ( intervention group ) or usual care ( control group ) . The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up . RESULTS The primary end-point was observed in 41.7 % of patients in the intervention group and in 54.3 % in the control group . The hazard ratio was 0.70 ( 95 % confidence interval [ CI ] 0.55 - 0.99 ) . Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 ( 95 % CI 0.50 - 0.87 ) . At the end of the study , the quality of life of patients in the intervention group was better than in the control group ( 18.57 vs. 31.11 ; P < .001 ) . CONCLUSIONS A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life Background Chronic ( systolic ) heart failure ( CHF ) represents a clinical syndrome with high individual and societal burden of disease . Multifaceted interventions like case management are seen as promising ways of improving patient outcomes , but lack a robust evidence base , especially for primary care . The aim of the study was to explore the effectiveness of a new model of CHF case management conducted by doctors ' assistants ( DAs , equivalent to a nursing role ) and supported by general practitioners ( GPs ) . Methods This patient-r and omised controlled trial ( phase II ) included 31 DAs and employing GPs from 29 small office-based practice s in Germany . Patients with CHF received either case management ( n = 99 ) consisting of telephone monitoring and home visits or usual care ( n = 100 ) for 12 months . We obtained clinical data , health care utilisation data , and patient-reported data on generic and disease-specific quality of life ( QoL , SF-36 and KCCQ ) , CHF self-care ( EHFScBS ) and on quality of care ( PACIC-5A ) . To compare between groups at follow-up , we performed analyses of covariance and logistic regression models . Results Baseline measurement showed high guideline adherence to evidence -based pharmacotherapy and good patient self-care : Patients received angiotensin converting enzyme inhibitors ( or angiotensin-2 receptor antagonists ) in 93.8 % and 95 % , and betablockers in 72.2 % and 84 % , and received both in combination in 68 % and 80 % of cases respectively . EHFScBS scores ( SD ) were 25.4 ( 8.4 ) and 25.0 ( 7.1 ) . KCCQ overall summary scores ( SD ) were 65.4 ( 22.6 ) and 64.7 ( 22.7 ) . We found low hospital admission and mortality rates . EHFScBS scores ( -3.6 [ -5.7;-1.6 ] ) and PACIC and 5A scores ( both 0.5 , [ 0.3;0.7/0.8 ] ) improved in favour of CM but QoL scores showed no significant group differences ( Physical/Mental SF-36 summary scores/KCCQ-os [ 95%CI ] : -0.3 [-3.0;2.5]/-0.1 [-3.4;3.1]/1.7 [ -3.0;6.4 ] ) . Conclusions In this sample , with little room for improvement regarding evidence -based pharmacotherapy and CHF self-care , case management showed no improved health outcomes or health care utilisation . However , case management significantly improved performance and key intermediate outcomes . Our study provides evidence for the feasibility of the case management model . Trial registration numberIS RCT Background Chronic congestive heart failure ( CHF ) is a complex disease with rising prevalence , compromised quality of life ( QoL ) , unplanned hospital admissions , high mortality and therefore high burden of illness . The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients ' health outcomes , although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations . It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner ( GP ) can improve patients ' QoL. Methods / Design HICMan is a r and omised controlled trial with patients as the unit of r and omisation . Aim is to evaluate a structured , st and ardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial . Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse , who gives feedback to the GP upon urgency . Monitoring and screening address aspects of disease-specific self-management , (non)pharmacological adherence and psychosomatic and geriatric comorbidity . GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis ( data of baseline documentation ) . Patients from control group receive usual care by their GPs , who were introduced to guideline -oriented management and a tailored health counselling concept . Main outcome measurement for patients ' QoL is the scale physical functioning of the SF-36 health question naire in a 12-month follow-up . Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy question naire ( KCCQ ) , depression and anxiety disorders ( PHQ-9 , GAD-7 ) , adherence ( EHFScBS and SANA ) , quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care question naire ( PACIC ) and NT-proBNP . In addition , comprehensive clinical data are collected about health status , comorbidity , medication and health care utilisation . Discussion As the targeted patient group is mostly cared for and treated by GPs , a comprehensive primary care-based guideline implementation including somatic , psychosomatic and organisational aspects of the delivery of care ( HICMAn ) is a promising intervention applying proven strategies for optimal care . Trial registration Current Controlled Trials IS RCT N30822978 BACKGROUND Few studies have examined the potential benefits of specialist nurse-led programs of care involving home and clinic-based follow-up to optimise the post-discharge management of chronic heart failure ( CHF ) . OBJECTIVE To determine the effectiveness of a hybrid program of clinic plus home-based intervention ( C+HBI ) in reducing recurrent hospitalisation in CHF patients . METHODS CHF patients with evidence of left ventricular systolic dysfunction admitted to two hospitals in Northern Engl and were assigned to a C+HBI lasting 6 months post-discharge ( n=58 ) or to usual , post-discharge care ( UC : n=48 ) via a cluster r and omization protocol . The co- primary endpoints were death or unplanned readmission ( event-free survival ) and rate of recurrent , all-cause readmission within 6 months of hospital discharge . RESULTS During study follow-up , more UC patients had an unplanned readmission for any cause ( 44 % vs. 22 % : P=0.019 , OR 1.95 95 % CI 1.10 - 3.48 ) whilst 7 ( 15 % ) versus 5 ( 9 % ) UC and C+HBI patients , respectively , died ( P = NS ) . Overall , 15 ( 26 % ) C+HBI versus 21 ( 44 % ) UC patients experienced a primary endpoint . C+HBI was associated with a non-significant , 45 % reduction in the risk of death or readmission when adjusting for potential confounders ( RR 0.55 , 95 % CI 0.28 - 1.08 : P=0.08 ) . Overall , C+HBI patients accumulated significantly fewer unplanned readmissions ( 15 vs. 45 : P<0.01 ) and days of recurrent hospital stay ( 108 vs. 459 days : P<0.01 ) . C+HBI was also associated with greater uptake of beta-blocker therapy ( 56 % vs. 18 % : P<0.001 ) and adherence to Na restrictions ( P<0.05 ) during 6-month follow-up . CONCLUSION This is the first r and omised study to specifically examine the impact of a hybrid , C+HBI program of care on hospital utilisation in patients with CHF . Its beneficial effects on recurrent readmission and event-free survival are consistent with those applying either a home or clinic-based approach BACKGROUND Hospital admissions among patients with congestive heart failure ( CHF ) are a major contributor to health-care costs . Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and result ant readmission . METHODS Chronic CHF patients discharged home after acute hospital admission were r and omly assigned usual care ( n=100 ) or a multidisciplinary , home-based intervention ( n=100 ) , consisting of a home visit by a cardiac nurse 7 - 14 days after discharge . The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months . FINDINGS During 6 months ' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group ( p=0.02 ) . More intervention-group than usual-care patients remained event-free ( 38 vs 51 ; p=0.04 ) . Overall , there were fewer unplanned readmissions ( 68 vs 118 ; p=0.03 ) and associated days in hospital ( 460 vs 1173 ; p=0.02 ) among intervention-group patients . Hospital-based costs were Australian $ 490,300 for the intervention group and A$ 922,600 for the usual-care group ( p=0.16 ) ; the mean cost of the intervention was A$ 350 per patient , and other community-based costs were similar for both groups . INTERPRETATION A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs , prolong event-free and total survival , and improve quality of life among patients with chronic CHF BACKGROUND Disease management is effective in the general population , but it has not been tested prospect ively in a sample of solely Hispanics with heart failure ( HF ) . We tested the effectiveness of telephone case management in decreasing hospitalizations and improving health-related quality of life ( HRQL ) and depression in Hispanics of Mexican origin with HF . METHODS AND RESULTS Hospitalized Hispanics with chronic HF ( n = 134 ) were enrolled and r and omized to intervention ( n = 69 ) or usual care ( n = 65 ) . The sample was elderly ( 72 + /- 11 years ) , New York Heart Association class III/IV ( 81.3 % ) , and poorly educated ( 78.4 % less than high school education ) . Most ( 55 % ) were unacculturated into US society . Bilingual/bicultural Mexican-American registered nurses provided 6 months of st and ardized telephone case management . Data on hospitalizations were collected from automated systems at 1 , 3 , and 6 months after the index hospital discharge . Health-related quality of life and depression were measured by self-report at enrollment , 3 , and 6 months . Intention to treat analysis was used . No significant group differences were found in HF hospitalizations , the primary outcome variable ( usual care : 0.49 + /- 0.81 [ CI 0.25 - 0.73 ] ; intervention : 0.55 + /- 1.1 [ CI 0.32 - 0.78 ] at 6 months ) . No significant group differences were found in HF readmission rate , HF days in the hospital , HF cost of care , all-cause hospitalizations or cost , mortality , HRQL , or depression . CONCLUSION These results have important implication s because of the current widespread enthusiasm for disease management . Although disease management is effective in the mainstream HF patient population , in Hispanics this ill , elderly , and poorly educated , a different approach may be needed Objective : To determine the feasibility and potential impact of a non-pharmacologic multidisciplinary intervention for reducing hospital readmissions in elderly patients with congestive heart failure . Design : Prospect i ve , r and omized clinical trial , with 2:1 assignment to the study intervention or usual care . Setting : 550-bed secondary and tertiary care university teaching hospital . Patients and participants : 98 patients ≥70 years of age ( mean 79±6 years ) admitted with documented congestive heart failure . Interventions : Comprehensive multidisciplinary treatment strategy consisting of intensive teaching by a geriatric cardiac nurse , a detailed review of medications by a geriatric cardiologist with specific recommendations design ed to improve medication compliance and reduce side effects , early consultation with social services to facilitate discharge planning , dietary teaching by a hospital dietician , and close follow-up after discharge by home care and the study team . Measurements and main results : All patients were followed for 90 days after initial hospital discharge . The primary study endpoints were rehospitalization within the 90-day interval and the cumulative number of days hospitalized during follow-up . The 90-day readmission rate was 33.3 % ( 21.7%–44.9 % ) for the patients receiving the study intervention ( n=63 ) compared with 45.7 % ( 29.2–62.2 % ) for the control patients ( n=35 ) . The mean number of days hospitalized was 4.3±1.1 ( 2.1–6.5 ) for the treated patients vs. 5.7±2.0 ( 1.8–9.6 ) for the usual-care patients . In a prospect ively defined subgroup of patients at intermediate risk for readmission ( n=61 ) , readmissions were reduced by 42.2 % ( from 47.6 % to 27.5 % ; p=0.10 ) , and the average number of hospital days during follow-up decreased from 6.7±32 days to 3.2±1.2 days ( p = NS ) . Conclusions : These pilot data suggest that a comprehensive , multidisciplinary approach to reducing repetitive hospitalizations in elderly patients with congestive heart failure may lead to a reduction in readmissions and hospital days , particularly in patients at moderate risk for early rehospitalization . Further evaluation of this treatment strategy , including an assessment of the cost-effectiveness , is warranted BACKGROUND Both r and omized and nonr and omized controlled studies have linked congestive heart failure ( CHF ) case management ( CM ) to decreased readmissions and improved outcomes in mostly homogeneous setting s. The objective of this r and omized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting . METHODS A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF , left ventricular dysfunction of less than 40 % , or radiologic evidence of pulmonary edema for which they underwent diuresis were r and omized . The intervention consisted of 4 major components : early discharge planning , patient and family CHF education , 12 weeks of telephone follow-up , and promotion of optimal CHF medications . RESULTS The 90-day readmission rates were equal for the CM and usual care groups ( 37 % ) . Total inpatient and outpatient median costs and readmission median cost were reduced 14 % and 26 % , respectively , for the intervention group . Patients in the CM group were more likely to be taking CHF medication at target doses , but dosages did not increase significantly throughout 12 weeks . Although both groups took their medications as prescribed equally well , the rest of the adherence to treatment plan was significantly better in the CM group . Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group ( P = .03 ) . CONCLUSIONS These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting . One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended , nonnetworked physician setting limits the effectiveness of the CM OBJECTIVES To examine the effectiveness of a transitional care intervention delivered by advanced practice nurses ( APNs ) to elders hospitalized with heart failure . DESIGN R and omized , controlled trial with follow-up through 52 weeks postindex hospital discharge . SETTING Six Philadelphia academic and community hospitals . PARTICIPANTS Two hundred thirty-nine eligible patients were aged 65 and older and hospitalized with heart failure . INTERVENTION A 3-month APN-directed discharge planning and home follow-up protocol . MEASUREMENTS Time to first rehospitalization or death , number of rehospitalizations , quality of life , functional status , costs , and satisfaction with care . RESULTS Mean age of patients ( control n=121 ; intervention n=118 ) enrolled was 76 ; 43 % were male , and 36 % were African American . Time to first readmission or death was longer in intervention patients ( log rank chi(2)=5.0 , P=.026 ; Cox regression incidence density ratio=1.65 , 95 % confidence interval=1.13 - 2.40 ) . At 52 weeks , intervention group patients had fewer readmissions ( 104 vs 162 , P=.047 ) and lower mean total costs ( $ 7,636 vs $ 12,481 , P=.002 ) . For intervention patients , only short-term improvements were demonstrated in overall quality of life ( 12 weeks , P<.05 ) , physical dimension of quality of life ( 2 weeks , P<.01 ; 12 weeks , P<.05 ) and patient satisfaction ( assessed at 2 and 6 weeks , P<.001 ) . CONCLUSION A comprehensive transitional care intervention for elders hospitalized with heart failure increased the length of time between hospital discharge and readmission or death , reduced total number of rehospitalizations , and decreased healthcare costs , thus demonstrating great promise for improving clinical and economic outcomes BACKGROUND Congestive heart failure is the most common indication for admission to the hospital among older adults . Behavioral factors , such as poor compliance with treatment , frequently contribute to exacerbations of heart failure , a fact suggesting that many admissions could be prevented . METHODS We conducted a prospect i ve , r and omized trial of the effect of a nurse-directed , multidisciplinary intervention on rates of readmission within 90 days of hospital discharge , quality of life , and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure . The intervention consisted of comprehensive education of the patient and family , a prescribed diet , social-service consultation and planning for an early discharge , a review of medications , and intensive follow-up . RESULTS Survival for 90 days without readmission , the primary outcome measure , was achieved in 91 of the 142 patients in the treatment group , as compared with 75 of the 140 patients in the control group , who received conventional care ( P = 0.09 ) . There were 94 readmissions in the control group and 53 in the treatment group ( risk ratio , 0.56 ; P = 0.02 ) . The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group ( 54 vs. 24 , P = 0.04 ) , whereas the number of readmissions for other causes was reduced by 28.5 percent ( 40 vs. 29 , P not significant ) . In the control group , 23 patients ( 16.4 percent ) had more than one readmission , as compared with 9 patients ( 6.3 percent ) in the treatment group ( risk ratio , 0.39 ; P = 0.01 ) . In a subgroup of 126 patients , quality -of-life scores at 90 days improved more from base line for patients in the treatment group ( P = 0.001 ) . Because of the reduction in hospital admissions , the overall cost of care was $ 460 less per patient in the treatment group . CONCLUSIONS A nurse-directed , multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure BACKGROUND Heart failure ( HF ) disease management programs are widely implemented , but data about their effect on outcome have been inconsistent . METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure ( COACH ) was a multicenter , r and omized , controlled trial in which 1023 patients were enrolled after hospitalization because of HF . Patients were assigned to 1 of 3 groups : a control group ( follow-up by a cardiologist ) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF . Patients were studied for 18 months . Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization . RESULTS Mean patient age was 71 years ; 38 % were women ; and 50 % of patients had mild HF and 50 % had moderate to severe HF . During the study , 411 patients ( 40 % ) were readmitted because of HF or died from any cause : 42 % in the control group , and 41 % and 38 % in the basic and intensive support groups , respectively ( hazard ratio , 0.96 and 0.93 , respectively ; P = .73 and P = .52 , respectively ) . The number of days lost to death or hospitalization was 39 960 in the control group , 33 731 days for the basic intervention group ( P = .81 ) , and 34 268 for the intensive support group ( P = .49 ) . All-cause mortality occurred in 29 % of patients in the control group , and there was a trend toward lower mortality in the intervention groups combined ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.08 ; P = .18 ) . There were slightly more hospitalizations in the 2 intervention groups ( basic intervention group , P = .89 ; and intensive support group , P = .60 ) . CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with st and ard follow-up . There was a nonsignificant , potentially relevant reduction in mortality , accompanied by a slight increase in the number of short hospitalizations in both intervention groups . Clinical Trial Registry http://trialregister.nl Identifier : NCT 98675639 BACKGROUND Multidisciplinary disease management approaches have been shown to decrease re source use in selected sample s of patients with heart failure . We remain uncertain regarding the effectiveness of this approach in a general heart failure population and who can be expected to benefit most . The purpose of this study was to test the effectiveness of a multidisciplinary disease management intervention in an unselected population of patients with heart failure and to determine if subgroups could be identified in which the intervention is most effective . METHODS AND RESULTS Two hundred forty patients with heart failure who were matched on preadmission functional status , comorbidity , and age participated in a quasi-experimental clinical trial . Half ( n = 120 ) were given a multidisciplinary disease management intervention , whereas the other half ( n = 120 ) received usual care . Data on acute care re source use were collected 3 and 6 months after enrollment . No intervention effect was seen in the primary analysis . When the data were analyzed by preadmission functional status ( I to IV ) , acute care re source use was lower in the class II intervention patients . Class I intervention patients had a 288 % increase in total costs and a 14-fold increase in heart failure costs . A model of predictor variables explained 17.2 % of the variance in heart failure readmission at 3 months . CONCLUSIONS An intervention of this type and intensity is recommended primarily for functional class II heart failure patients . Increases in cost in class I patients may have result ed from improved access to care PURPOSE The objectives of this investigation were to prospect ively assess medication compliance rates in elderly patients with congestive heart failure , to identify factors associated with reduced compliance , and to evaluate the effect of a multidisciplinary treatment approach on medication adherence . PATIENTS AND METHODS A total of 156 patients > or = 70 years of age ( mean , 79.4 + /- 6.0 ; 67 % female , 65 % nonwhite ) hospitalized with congestive heart failure were evaluated prospect ively . Prior to discharge , patients were r and omized to the study intervention ( n = 80 ) or conventional care ( n = 76 ) . The intervention consisted of comprehensive patient education , dietary and social service consultations , medication review , and intensive postdischarge follow-up . Detailed data were collected on all prescribed medications at the time of discharge , and compliance was assessed by pill counts 30 + /- 2 days later . RESULTS The overall compliance rate during the first 30 days after discharge was 84.6 + /- 15.1 % ( range , 23.1 - 100 % ) . Compliance was 87.9 + /- 12.0 % in patients r and omized to the study intervention , compared with 81.1 + /- 17.2 % in the control group ( P = 0.003 ) . A compliance rate of > or = 80 % was achieved by 85.0 % of the treatment group versus 69.7 % of the control group ( P = 0.036 ) . By multivariate analysis , assignment to the treatment group was the strongest independent predictor of compliance ( P = 0.008 ) . Other variables included in the model were Caucasian race ( P = 0.044 ) and not living alone ( P = 0.09 ) . CONCLUSIONS A multidisciplinary treatment strategy is associated with improved medication compliance during the first 30 days following hospital discharge in elderly patients with congestive heart failure . Improved compliance may contribute to improved outcomes in these patients OBJECTIVES We compared the longer-term impact of the two most commonly applied forms of post-discharge management design ed to minimize recurrent hospitalization and prolong survival in typically older patients with chronic heart failure ( CHF ) . METHODS We followed a multi-center r and omized controlled trial cohort of Australian patients hospitalized with CHF and initially allocated to home-based or specialized CHF clinic-based intervention for 1368 ± 216 days . Blinded endpoints included event-free survival from all-cause emergency hospitalization or death , all-cause mortality and rate of all-cause hospitalization and stay . RESULTS 280 patients ( 73 % male , aged 71 ± 14 years and 73 % left ventricular systolic dysfunction ) were initially r and omized to home-based ( n=143 ) or clinic-based ( n=137 ) intervention . During extended follow-up ( complete for 274 patients ) , 1139 all-cause hospitalizations ( 7477 days of hospital stay ) and 121 ( 43.2 % ) deaths occurred . There was no difference in the primary endpoint ; 20 ( 14.0 % ) home-based versus 13 ( 7.4 % ) clinic-based patients remained event-free ( adjusted HR 0.89 , 95 % CI 0.70 to 1.15 ; p=0.378 ) . Significantly fewer home-based ( 51/143 , 35.7 % ) than clinic-based intervention ( 71/137 , 51.8 % ) patients died ( adjusted HR 0.62 , 95 % CI 0.42 to 0.90 : p=0.012 ) . Home-based versus clinic-based intervention patients accumulated 592 and 547 all-cause hospitalizations ( p=0.087 ) associated with 3067 ( median 4.0 , IQR 2.0 to 6.8 ) versus 4410 ( 6.0 , IQR 3.0 to 12.0 ) days of hospital stay ( p<0.01 for rate and duration of hospital stay ) . CONCLUSIONS Relative to clinic-based intervention , home-based intervention was not associated with prolonged event-free survival . Home-based intervention was , however , associated with significantly fewer all-cause deaths and significantly fewer days of hospital stay in the longer-term . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry number 12607000069459 ( http://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=81803 ) |
12,555 | 25,522,248 | For the treatment of patients with aggressive periodontitis , systemic antibiotics combined with non-surgical periodontal therapy result ed in a significant additional effect compared to non-surgical therapy alone .
There is a visible trend that showed metronidazole + amoxicillin is the most potent antibiotic combination | OBJECTIVE The purpose of this meta- analysis is to evaluate the effectiveness of different systemic antibiotics in combination with scaling and root planing ( SRP ) compared to SRP alone in patients with untreated aggressive periodontitis .
BACKGROUND In patients with aggressive periodontitis , SRP is often combined with the use of systemic antibiotics .
However , the effectiveness of these antibiotics over time and differences in effectiveness between different antibiotics are hardly known . | BACKGROUND / AIM Tobacco use reduces the effect of non-surgical periodontal therapy . Host-modulation with low-dose doxycycline ( LDD ) might favour repair and promote an improved treatment response . The aim of this study was to investigate the effect of LDD in smokers on non-surgical periodontal therapy . MATERIAL AND METHODS This was a parallel arm , r and omized , identical placebo-controlled trial with masking of examiner , care-giver , participant and statistician and 6 months of follow-up . Patients received non-surgical therapy and 3 months of test or control drug . Statistical analysis used both conventional methods and multilevel modelling . RESULTS Eighteen control and 16 test patients completed the study . The velocity of change was statistically greater for the test group for clinical attachment level -0.19 mm/month ( 95 % CI=-0.34 , 0.04 ; p=0.012 ) and probing depth 0.30 mm/month ( 95 % CI=-0.42 , -0.17 ; p<0.001 ) . However , no differences were observed for absolute change in clinical or biochemical markers at 6 months . CONCLUSIONS This study does not provide evidence of a benefit of using LDD as an adjunct to non-surgical periodontal therapy in smokers AIM The aim of this study was to evaluate the clinical and microbiological effects of scaling and root planing ( SRP ) alone or combined with metronidazole ( MTZ ) or with MTZ and amoxicillin ( AMX ) in the treatment of smokers with chronic periodontitis . METHODS A double-blind , placebo-controlled , r and omized clinical trial was conducted in 43 subjects who received SRP alone ( n=15 ) or combined with MTZ ( 400 mg 3 x per day , n=14 ) or with MTZ+AMX ( 500 mg 3 x per day , n=14 ) for 14 days . Clinical and microbiological examinations were performed at baseline and 3 months post-therapy . Subgingival sample s were analysed by checkerboard DNA-DNA hybridization . RESULTS Subjects receiving MTZ+AMX showed the greatest improvements in mean probing depth and clinical attachment level . Both antibiotic therapies led to additional clinical benefits over SRP alone in initially shallow , intermediate , and deep sites . The SRP+MTZ+AMX therapy led to the most beneficial changes in the subgingival microbial profile . These subjects showed significant reductions in the mean counts and proportions of periodontal pathogens such as Tannerella forsythia , Porphyromonas gingivalis and Treponema denticola , and the greatest increase in proportions of host-compatible species . CONCLUSION Significant advantages are observed when systemic antibiotics are combined with SRP in the treatment of smokers with chronic periodontitis . The greatest benefits in clinical and microbiological parameters are achieved with the use of SRP+MTZ+AMX Periodontitis , a common cause of tooth loss in adult population s , is an inflammatory response to the overgrowth of anaerobic organisms such as spirochetes and bacteroides and , in some cases , micro-aerophilic organisms in the subgingival plaque . In the present investigation , using a double-blind clinical design , we sought to determine whether 1 week of metronidazole treatment plus debridement of the tooth surfaces was superior to 1 week of placebo treatment plus debridement ( positive control ) in reducing the subsequent amount of periodontal surgery given to the patients . Thirty-nine patients were r and omly assigned to either the metronidazole or placebo ( positive control ) groups . All patients were given the necessary scaling and root planing and were unsupervised in their usage of the medication . After the completion of this treatment , they were reexamined and it was found that the metronidazole regimen caused a significant reduction in surgical needs of about 5 teeth per patient compared to the positive control ( difference before and after treatment 8.3 + /- 6.8 teeth metronidazole versus 2.9 + /- 4.8 positive control , P = 0.007 ) . The difference between groups was maintained during the 2 to 3 years ' recall period . Metronidazole had a significant effect on the site specific reduction of spirochetes : 90 % of the sites in the metronidazole group versus 64 % in the positive-control group had a decrease in the percentage of spirochetes ( P less than 0.05 ) . We conclude that systemic metronidazole given 250 mg tid for 7 days in conjunction with debridement of the tooth surfaces can significantly reduce the need for periodontal surgery compared to the st and ard regimen which included only debridement AIM To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers . METHOD A single-blind , r and omised clinical trial of 28 smokers and 56 non-smokers , stratified for periodontitis disease severity and r and omly allocated to 3 treatment groups : ( 1 ) Scaling and root planing using an ultrasonic scaler with local anaesthesia ( SRP ) , ( 2 ) SRP+ metronidazole tabs 200 mg tds for 7 days , ( 3 ) SRP + 2 subgingival applications of 25 % metronidazole gel . Probing depths ( PD ) and attachment levels ( AL ) were recorded with a Florida probe at baseline , 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . RESULTS Reductions in probing depth at 6 months were significantly less ( p < 0.001 ) in the smokers ( mean 1.23 mm , 95 % confidence intervals = 1.05 to 1.40 mm ) than in the non-smokers ( 1.92 , 1.75 to 2.09 mm ) . Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers . There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers . A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers ( p = 0.034 ) . Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor ( p < 0.001 ) for poor treatment outcome , whilst the presence or absence of adjunctive metronidazole was not ( p = 0.620 ) . CONCLUSION This study confirms that smokers have a poorer treatment response to SRP , regardless of the application of either systemic or locally applied adjunctive metronidazole BACKGROUND The purpose of this clinical trial is to evaluate the adjunctive clinical effects of the systemic administration of ornidazole ( ORN ) in the full-mouth scaling and root planing ( SRP ) of individuals with moderate-to-advanced chronic periodontitis . METHODS Fifty-eight individuals presenting ≥12 teeth with probing depth ( PD ) ≥4 mm were selected . All participants were instructed on strict oral hygiene measures and were advised to use 0.2 % chlorhexidine mouthwash for 1 week before being allocated to two groups . Thirty participants were r and omly assigned to full-mouth SRP + placebo ( control group ) , and 28 participants were assigned to full-mouth SRP + ORN ( test group ) . The clinical outcomes evaluated were plaque index , gingival index , clinical attachment level ( CAL ) , and PD . RESULTS Fifty participants could be evaluated by ≤6 months . At 6 months , the test group had greater mean reduction ( 2.84 mm ) in PD compared to the control group ( 0.84 mm ) ( P < 0.05 ) , and there was also a greater mean CAL reduction ( 2.92 mm ) in the test group compared to the control group ( 0.92 mm ) ( P < 0.05 ) . CONCLUSION The systemic use of ORN , when used in conjunction with initial periodontal treatment consisting of SRP in adults with periodontitis , achieves significantly better clinical results than initial periodontal treatment alone The present investigation was performed to study the effect of long-term , low dosage tetracycline therapy on advanced periodontal disease in humans . 14 volunteers participated in the trial . Each of the participants had at least 4 pairs of diseased sites around contralateral premolars and incisors with deep pockets and advanced bone loss . The trial extended over a 50-week period and was design ed as a double-blind split-mouth study . A Baseline examination included assessment s of oral hygiene , gingival conditions , probing depth , attachment level and analysis of the composition of the subgingival microbiota in sample s obtained from 8 selected diseased sites . All participants received oral hygiene instruction . In each patient 2 quadrants of the mouth , chosen at r and om , were treated by scaling and root planing . The 2 remaining quadrants were left unscaled . Following the Baseline examination the patients were r and omly distributed into 2 groups of 7 members each . In one of the groups the patients received tetracycline on a daily basis during a 50-week period . The participants of the control group received placebo . Reexaminations were performed 2 , 10 , 20 , 30 and 50 weeks after the Baseline examination . The findings demonstrated that in patients with advanced periodontal disease long-term tetracycline therapy in the absence of scaling result ed in the establishment of a subgingival microbiota almost devoid of motile bacteria and in markedly reduced signs of gingivitis , probing depth and attachment loss . In fact , the alterations observed as a result of tetracycline administration to patients with excellent self-performed plaque control were similar to those obtained by conventional scaling and root planing in the control group AIMS The objective of this study was to investigate the effect of the systemic administration of metronidazole and amoxicillin as an adjunct to initial periodontal therapy in patients with moderate to severe chronic periodontitis . METHODS AND MATERIAL S This r and omized , double blind , placebo controlled parallel study involved 50 adult patients with untreated periodontitis who were r and omly assigned to receive either a full-mouth scaling and root planing along with systemic metronidazole and amoxicillin ( T group ) or scaling and root planing with a placebo ( P group ) . Clinical measurements including probing depth ( PD ) , clinical attachment levels ( CAL ) , Plaque Index ( PI ) , and Bleeding Index ( BI ) were recorded at baseline and six to eight weeks after therapy . The deepest pocket was selected and sample s for microbiological testing were taken . Patients received coded study medications of either 500 mg amoxicillin in combination with 250 mg metronidazole or an identical placebo every eight hours for seven days following scaling and root planing . RESULTS There was a significant change in PD ( P=0.0001 ) , CAL ( P=0.00001 ) , PI ( P<0.05 ) , and BI ( P<0.05 ) in the T group compared to the placebo group after therapy . Parallel to the clinical changes , treatment significantly reduced the number of Actinobacillus actinomycetemcomitans ( Aa ) , Porphyromonas gingivalis ( Pg ) , and P. intermedia ( Pi ) compared with baseline in the T group ( P=0.003 , 0.021 and 0.0001 , respectively ) . However , in the P group only the Pi colony count was reduced significantly ( P=0.0001 ) . After therapy , there was a significant difference between the T and P groups in the number of patients negative for Aa , Pg , and Pi ( Pv = 0.033 ) . CONCLUSIONS The significant differences between treatment and placebo groups are in line with other studies and support the considerable adjunctive benefits of the combination of amoxicillin and metronidazole in the treatment of chronic periodontitis BACKGROUND The present r and omized , double-masked , placebo-controlled , parallel-arm study examines the impact of adjunctive subantimicrobial-dose doxycycline ( SDD ) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid ( GCF ) sample s from patients with chronic periodontitis . METHODS Forty-six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD . GCF sample s were collected and clinical parameters including probing depth , clinical attachment level , gingival index , and plaque index were recorded every 3 months for 12 months . GCF tumor necrosis factor-α , interleukin (IL)-6 , IL-4 , IL-10 , IL-13 , IL-17 , macrophage inhibitory protein 1α , macrophage inhibitory protein 1β , monocyte chemoattractant protein 1 , and regulated on activated normal T-cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay . RESULTS Significant improvements were observed in all clinical parameters in both groups over 12 months ( P < 0.0125 ) , whereas the SDD group showed significantly better reduction in gingival index , probing depth , and gain in clinical attachment compared to the placebo group ( P < 0.05 ) . Decrease in IL-6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets ( P < 0.05 ) , whereas tumor necrosis factor-α was significantly reduced in moderately deep pockets ( P < 0.05 ) . SDD result ed in a stable IL-4 and IL-10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months ( P < 0.05 ) . CONCLUSIONS These results show that SDD , as an adjunct to non-surgical periodontal therapy , stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti-inflammatory cytokines . The chemokine activity would account for the regulation of the inflammatory response to SDD therapy BACKGROUND This study evaluated the efficacy and safety of a subantimicrobial dose of doxycycline ( SDD ) in conjunction with scaling and root planing ( SRP ) . METHODS The study was a 9-month , double masked , r and omized , placebo-controlled , parallel-group trial . A total of 41 patients with moderate chronic periodontitis who received SRP were r and omly allocated to receive either a doxycycline hyclate or a placebo 2 weeks after SRP . Clinical attachment level ( CAL ) , the probing depth ( PD ) , gingival crevicular fluid ( GCF ) levels , and matrix metalloproteinase (MMP)-8 and -13 levels were measured throughout the study . The effect of SDD in conjunction with SRP on the dynamics of the periodontal microflora was also assessed using dark-field microscopic and culture analysis . Information on adverse events was collected throughout the study . RESULTS During the treatment period , per-patient reductions in PD and CAL were demonstrated for both treatment groups , with a significantly greater reduction for the SDD group . The mean value of per-patient change in the GCF was much greater for the SDD group . Microbial analysis showed there were a general tendency for cocci , non-motile rods , and aerobes to increase with increasing treatment duration and a general decreasing tendency for spirochetes , motile rods , and anaerobes and black pigmented bacteria in both treatment groups , but no significant difference between the groups . The MMP-8 and -13 levels of the SDD group gradually reduced with time , and the mean perpatient average was significantly higher than in the placebo group . The adverse events in the SDD group were similar to those in the placebo group . CONCLUSION This study suggests that a su bmi crobial dose of doxycycline as an adjunct therapy with SRP might be safe and effective in the long-term management of chronic periodontitis Azithromycin is an azalide antibiotic with excellent in vitro activity against a wide variety of oral bacteria . It has a long half-life , good tissue penetration and is preferentially taken up by phagocytes . We investigated the microbiological efficacy of azithromycin as an adjunct to the non-surgical treatment of adult chronic periodontitis ; its clinical efficacy is dealt with in a separate paper . 46 patients were treated in a double-blind placebo controlled trial . Microbiological assessment of the same periodontal pocket ( initially > 6 mm ) was made at weeks 0 , 2 , 3 , 6 , 10 and 22 . Either azithromycin 500 mg 1 x daily for 3 days or placebo was given at week 2 . Particular attention was paid to the numbers of black pigmented anaerobes and spirochaetes present since these are the most commonly implicated pathogens in periodontal disease . Pigmented anaerobes were significantly reduced at weeks 3 and 6 in patients who received azithromycin compared to placebo and remained lower , although not significantly so , throughout the study . Counts of spirochaetes were significantly reduced throughout the study in patients who received azithromycin compared to placebo . Our microbiological study suggests that azithromycin may be useful as an adjunct in the treatment of periodontal disease Abstract The present investigation was performed to test the hypothesis that the persistence of inflammatory periodontal disease in human subjects is incompatible with the elimination of the anaerobic segments of the subgingival microbiota . 16 human subjects participated in the trial . They were selected on the basis of advanced periodontal disease which had produced at least 4 pairs of contra lateral teeth with advanced disease . At the Baseline examination the diseased sites were characterized by assessment of plaque , gingivitis , probing depth and attachment level . In addition , the composition of the subgingival microbiota was determined . One pair of sites was subjected to biopsy . In the tissue sample s the size of the inflammatory cell infiltrate was assessed . Following the Baseline examination the patients were r and omly distributed into 2 treatment groups , test and control . The patients of the test group received metronidazole for 3 periods of 2 weeks each , separated by intervals of 8 weeks . In addition , all patients received detailed oral hygiene instruction and a series of subgingival scalings involving 2 quadrants of the dentition , either the right or the left jaw quadrants , Reexaminations were performed 2 , 10 , 20 , 30 and 50 weeks after the Baseline examination . Biopsies from the predetermined sites were obtained at the reexaminations performed 2,20 and 50 weeks after the initiation of the therapy . The results demonstrated that the elimination of metronidazole sensitive bacteria from the subgingival microbiota result ed in the disappearance of clinical and histopathological signs of periodontal disease . Metronidazole has a unique bactericidal range against anaerobic bacteria . The present findings , therefore , emphasize the central role played by the anaerobic segments of the subgingival plaque for the maintenance of the inflammatory component of periodontal disease BACKGROUND AND AIM Several studies have reported adjunctive benefits to scaling and root planing ( SRP ) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases . To date no comparisons have been made of these antimicrobials alone or in combination . The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined . METHODS 66 subjects < 46 years of age with advanced chronic periodontal disease participated in this r and omised , double blind , 4 parallel treatment group design ed study . All subjects received quadrant SRP and then were prescribed amoxycillin capsules ( 250 mg ) and metronidazole tablets ( 200 mg ) ( AM ) or lactate capsules and metronidazole ( PM ) or amoxycillin and calcium lactate tablets ( AP ) or lactate and calcium lactate ( PP ) . All medication was 3 of each per day for 7 days . Subgingival plaque sample s were obtained and probing depth ( PD ) , loss of attachment ( LOA ) , bleeding on probing ( BOP ) , suppuration ( SUPP ) and plaque ( DEP ) were recorded pre-treatment , 1 , 3 and 6 months post-treatment . RESULTS Final group sizes were : AM=15 , PM=16 , AP=16 and PP=15 . PD improved in all groups . Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups . Benefits of PM and AP over PP were also noted . LOA improved in all groups and showed the same highly significant treatment differences , again favouring AM . BOP improved in all groups , particularly in AM compared to the other groups . SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant . DEP changed little in any group and there were no significant differences among groups . Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month . P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months . CONCLUSION The significant differences among treatment groups and the overall trend in the data , in line with other studies , support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease OBJECTIVE To evaluate the clinical and microbiological effects of systemic azithromycin as an adjunct to scaling and root planing ( SRP ) in the treatment of Porphyromonas gingivalis-associated chronic periodontitis . METHODS Twenty-nine patients harbouring P. gingivalis were r and omized into test and placebo groups . Test patients received SRP plus 500 mg of azithromycin per day ( 3 days ) , and control patients received SRP plus placebo . Clinical [ plaque and bleeding indexes , probing pocket depth ( PPD ) , clinical attachment level ( CAL ) ] and microbiological data ( four-sites pooled sample s , processed by culture ) were collected at baseline , and 1 , 3 and 6 months , post-therapy . Clinical variables were compared by anova , and microbiological variables by chi-square , signed-rank and Wilcoxon tests . RESULTS Fifteen test and 11 placebo patients completed the study . Mean PPD decreased 0.34 mm [ 95 % confidence interval ( CI ) 0.19 - 0.49 ] in the placebo and 0.80 mm ( CI 0.57 - 1.04 ) in the test group after 6 months . For mean CAL gain , the correspondent figures were 0.29 ( CI 0.08 - 0.49 ) and 0.76 ( CI 0.46 - 1.05 ) , respectively . The frequency of detection of P. gingivalis decreased significantly ( p0.01 ) in the test group after 1 , 3 and 6 months . CONCLUSIONS Within the limitations of this study , the adjunctive use of systemic azithromycin in the treatment of P. gingivalis periodontitis demonstrated significant clinical and microbiological benefits when compared with SRP plus placebo AIM To evaluate the effects of systemic azithromycin ( AZM ) as an adjunct to scaling and root planing ( SRP ) in the treatment of generalized chronic periodontitis ( ChP ) . METHODS Forty subjects were r and omly assigned to receive SRP alone or combined with AZM ( 500 mg/day ) for 5 days ( n=20/group ) . Clinical and microbiological examinations were performed at baseline , 6 months and 1-year post-SRP . Nine plaque sample s per subject were analysed by checkerboard DNA-DNA hybridization for 40 bacterial species . Differences between groups were assessed using the Mann-Whitney test and over time using Friedman and Dunn 's tests . RESULTS No statistically significant differences were observed between groups for any parameters evaluated at 1-year post-treatments . Both therapies equally reduced the mean probing depth ( PD ) ( SRP : 3.83 ± 1.92 , AZM : 3.45 ± 1.74 ) and improved the mean clinical attachment ( SRP : 2.35 ± 1.70 , AZM : 2.68 ± 1.76 ) in sites with initial PD7 mm ( primary outcome variable ) between baseline and 1 year . The mean counts and proportions of several periodontal pathogens were reduced , and those of host-beneficial species were increased after treatments . Nonetheless , an important recolonization with red complex species was observed in both groups over the course of the study . CONCLUSION The data of the present study suggest no adjunctive benefit of AZM in the treatment of generalized AIM Diabetic patients have more severe periodontal destruction , but periodontal therapy can improve metabolic control . Recently , interest has focused on the use of subantimicrobial dose doxycycline ( SDD ) as a treatment paradigm . Therefore , this study was undertaken to evaluate clinical efficacy of SDD with scaling and root planning ( SRP ) in chronic periodontitis patients with diabetes . METHODS AND MATERIAL S Twenty chronic periodontitis patients with diabetes mellitus were r and omly allocated to either a test and a control group . Clinical measurements were recorded at baseline and at six months for probing pocket depth ( PPD ) , clinical attachment level ( CAL ) , and gingival recession ( GR ) . After SRP , patients in the test group were instructed to take SDD 20-mg capsules twice a day while patients in the control group took a placebo twice a day . Both groups were on this regimen for a six-month period . RESULTS A greater reduction in mean PPD was demonstrated in patients in the test group compared to the control group . The mean CAL increase observed in the test group was significantly greater ( 0.67 mm ) than that in the control group . CONCLUSION It can be concluded that SRP , in conjunction with the SDD therapy described , is more effective then SRP alone in terms of CAL gain and PPD reduction in diabetic patients with severe periodontal disease . CLINICAL SIGNIFICANCE Given the widespread prevalence of both chronic periodontitis and diabetes , the proposed treatment approach will prove to be of great value and contribute significantly to the overall health of the patients OBJECTIVE To assess the clinical benefit of either metronidazole and amoxicillin or doxycycline administered immediately after completion of full-mouth scaling and root planing ( FRP ) for treatment of generalized aggressive periodontitis . METHODS Patients , 18 to 40 years of age , referred to the Karadeniz Technical University department of periodontology between January 2009 and September 2009 were r and omly chosen for inclusion in the study if radiographic examination showed they had ≥ 20 teeth , clinical attachment loss and a probing pocket depth ( PPD ) ≥ 6 mm at 2 sites in ≥ 12 teeth , ≥ 3 of which were not first molars or incisors . Patients were divided into 3 groups and received FRP alone , FRP combined with metronidazole and amoxicillin , or FRP combined with doxycycline . PPD , clinical attachment level , gingival index , gingival bleeding index and plaque index values were measured at baseline and 2 months after treatment . RESULTS Thirty-eight patients with untreated generalized aggressive periodontitis participated in the study . In all 3 groups , the periodontal index values 2 months after treatment were significantly lower than baseline values ( p < 0.05 ) . Values for PPD and clinical attachment level were more improved in the antibiotic groups than in the FRP group , and more improved in the metronidazole and amoxicillin group than in the doxycycline group ( p < 0.05 ) . However , no statistically significant intergroup difference was observed in the other clinical parameters ( p > 0.05 ) . Systemic use of metronidazole and amoxicillin or doxycycline was clinical ly superior to FRP for reducing PPDs ≥ 7 mm ( p < 0.05 ) . CONCLUSION Treatment of generalized aggressive periodontitis with FRP alone or FRP combined with systemic antibiotics provided significant clinical benefits that reduced the need for periodontal surgery . Both antibiotic treatments had additional clinical benefits over those of FRP alone BACKGROUND Laminin-5 ( Ln-5 ) is involved in the apical migration of epithelial cells during the development of periodontal pockets . Low-dose doxycycline ( LDD ) can therapeutically modulate the host response with its non-antimicrobial properties . In the present r and omized , double-blind , placebo-controlled , parallel arm study , the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid ( GCF ) Ln-5 gamma2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period . METHODS GCF sample s were collected and clinical parameters including probing depth ( PD ) , clinical attachment level , gingival index ( GI ) , and plaque index were recorded . Thirty chronic periodontitis patients were r and omized either to low-dose doxcycline or placebo groups . LDD group received doxycycline ( 20 mg , b.i.d . ) for 3 months plus scaling and root planing ( SRP ) , while placebo group was given placebo capsules b.i.d . for 3 months plus SRP . The patients were evaluated every 3 months during the 12-month study period . All clinical parameters and GCF sampling were repeated at each visit . GCF Ln-5 gamma2 chain fragment levels were determined by Western immunoblotting using specific antibody and quantitated by computerized image analysis . Friedman test was used for intragroup comparisons followed by Wilcoxon signed rank test to analyze significance of changes over time . The Mann-Whitney test was used to determine differences between both LDD and placebo groups . RESULTS Both groups revealed significant improvements in all clinical parameters over the 12-month period ( P < 0.0125 ) . LDD group showed a significantly greater reduction in the mean PD scores at 9 and 12 months and in the mean GI scores at all time points than the placebo group ( P < 0.05 ) . In the LDD group , GCF Ln-5 gamma2 chain fragment levels were significantly reduced at 3 months ( P < 0.0125 ) and then slightly increased during the rest of the study period . In the placebo group , GCF 45 and 70 kDa Ln-5 gamma2 chain fragments tended to decrease at 3 months compared to baseline , but did not reach significance ; these levels continued to increase throughout the remainder of the study period . GCF Ln-5 gamma2 chain fragment levels in LDD group were significantly lower than those of the placebo group during the study period ( P < 0.05 ) . CONCLUSIONS The present data indicate that LDD therapy in combination with SRP therapy can reduce GCF Ln-5 gamma2 chain fragment levels and improve clinical periodontal parameters in patients with chronic periodontitis . Since matrix metalloproteinases (MMP)-mediated fragmentation of laminin-5 can contribute to pocket formation by stimulating epithelial cell migration , the reduction of Ln-5 gamma2 chain fragment levels could provide a new mechanism by which LDD , adjunctive to SRP , inhibits periodontal disease more effectively than SRP alone . Thus , these results provide extended and additional information about the effectiveness of the LDD therapy as an adjunct to non-surgical periodontal therapy in the long-term management of periodontal disease BACKGROUND This study assessed the long-term effects of adjunctive antimicrobial therapy on periodontal disease progression and oral colonization . METHODS Patients with previously untreated chronic periodontitis and subgingival Actinobacillus actinomycetemcomitans and /or Porphyromonas gingivalis were r and omly assigned to subgingival scaling without ( control group ) or with systemic amoxicillin plus metronidazole and CHX irrigation ( test group ) . Relative attachment levels were determined and subgingival and mucosal plaque sample s were taken at baseline , at 10 days ( plaque only ) and at 3 , 6 , 9 , 12 , 18 , and 24 months following initial therapy . During maintenance therapy , patients received supragingival debridement only . RESULTS After 24 months , the 18 test group patients showed at sites with initial probing depths ( PD ) > or = 7 mm a significantly ( P < 0.05 ) higher frequency of 2 mm or more attachment gain ( 37.3 % + /- 4.6 % ) and lower frequency of attachment loss ( 7.2 % + /- 3.1 % ) compared to the 17 controls ( 8.2 % + /- 3.9 % and 19.1 % + /- 13.1 % , respectively ) . Compared to controls , the intraoral prevalence of A. actinomycetemcomitans ( up to 18 months ) and P. gingivalis ( up to 3 months ) decreased and that of Eikenella corrodens ( at 10 days ) increased in test patients ( P < 0.05 ) . In both treatment groups , the detection frequency of Tannerella forsythensis decreased transiently , while an overall increase was recorded for Treponema ssp . CONCLUSIONS Over the 24-month period , a single course of the administered adjunctive antimicrobial therapy led to a relative risk reduction of 62 % for attachment loss at deep sites . However , with the exception of A. actinomycetemcomitans , it failed to induce long-term changes in the prevalence profiles of oral colonization BACKGROUND One-stage full-mouth scaling and root planing ( FM-SRP ) in combination with systemically administered azithromycin was shown to be clinical ly and bacteriologically effective in the treatment of chronic periodontitis . However , FM-SRP requires 2 hours for completion . Azithromycin has a long half-life . Therefore , if SRP of the full mouth is performed within 7 days while an effective concentration of azithromycin remains in the gingiva , the effects may be the same as FM-SRP . The aim of this study was to compare the clinical and bacteriologic effects of FM-SRP and partial-mouth scaling and root planing ( PM-SRP ) in patients with chronic periodontitis , which was performed in three sessions within 7 days , during the effective half-life of systemically administrated azithromycin . METHODS Thirty adult subjects with chronic periodontitis were r and omly divided into three groups ( FM-SRP , PM-SRP , and control ) . A clinical examination was conducted to record the probing depth , clinical attachment level gain , bleeding on probing , gingival index , and volume of gingival crevicular fluid ; bacterial sample s were obtained before treatment and 1 , 3 , 6 , 9 , and 12 months thereafter . Quantitative and qualitative analyses were performed using the polymerase chain reaction-Invader method . RESULTS All clinical parameters showed better improvement in FM-SRP and PM-SRP groups compared to the control group , with no significant differences between the two test groups . Periodontal bacteria were well controlled in the two test groups , but they tended to increase gradually 3 months after treatment in the control group . CONCLUSION PM- and FM-SRP demonstrated comparable clinical and bacteriologic results AIM To examine changes in levels of gingival crevicular fluid ( GCF ) cytokines , after periodontal therapy of generalized aggressive periodontitis ( GAgP ) . MATERIAL S AND METHODS Twenty-five periodontally healthy and 24 GAgP subjects had periodontal clinical parameters measured and gingival crevicular fluid ( GCF ) sample s collected from up to 14 sites/subject . GCF sample s were analysed using multiplex bead immunoassay for : GM-CSF , IFN-γ , IL-10 , IL-1β , IL-2 , IL-6 and TNF-α . Aggressive periodontitis subjects were r and omly assigned to either scaling and root planing ( SRP ) alone or SRP plus systemic amoxicillin ( 500 mg ) and metronidazole ( 400 mg ) 3 times a day for 14 days . Clinical parameters and GCF cytokines were re-measured 6 months after treatment . Differences over time were analysed using the Wilcoxon test and between groups using the Mann-Whitney test . RESULTS Significant reductions in GCF GM-CSF , IL-1β and the ratio IL-1β/IL-10 and increases in GCF IL-6 were detected after therapy . The mean change in GCF cytokines did not differ significantly between groups . CONCLUSIONS Periodontal therapy improved GCF cytokine profiles by lowering IL-1β and increasing IL-10 levels . The reduction in GCF GM-CSF after therapy implicates this cytokine in the pathogenesis of GAgP. There was no difference between therapies in changes of GCF cytokines BACKGROUND The purpose of this study was to evaluate the adjunctive clinical , microbiologic , and immunologic effects of the systemic administration of amoxicillin and metronidazole in the full-mouth ultrasonic debridement of patients with severe chronic periodontitis . METHODS Twenty-five patients presenting at least eight teeth with probing depth ( PD ) > or = 5 mm and bleeding on probing ( BOP ) were selected and r and omly assigned to full-mouth ultrasonic debridement + placebo ( control group ) or full-mouth ultrasonic debridement + amoxicillin and metronidazole ( test group ) . The clinical outcomes evaluated were visible plaque index , BOP , position of the gingival margin , relative attachment level ( RAL ) , and PD . Real-time polymerase chain reaction ( PCR ) was used for quantitative analysis of Aggregatibacter actinomycetemcomitans ( previously Actinobacillus actinomycetemcomitans ) , Porphyromonas gingivalis , and Tannerella forsythia ( previously T. forsythensis ) . The enzyme-linked immunosorbent assay ( ELISA ) technique permitted the detection of prostagl and in E(2 , ) interleukin-1beta , and interferon-gamma levels in gingival crevicular fluid . All parameters were evaluated at baseline and at 3 and 6 months post-treatment . RESULTS At 6 months , the test treatment result ed in lower BOP and an additional reduction ( 0.83 mm ) in PD ( P < 0.05 ) . Data also showed RAL gain > or = 2 mm at 43.52 % of sites in control patients compared to 58.03 % of sites in test patients ( P < 0.05 ) . However , both groups had similar mean RAL gain ( 1.68 and 1.88 mm for the control and test groups , respectively ) . Real-time PCR and ELISA failed to identify significant differences between the groups . CONCLUSIONS Both treatments result ed in significant clinical improvements ; however , there was a slight , but significantly greater , improvement in BOP and the percentage of sites with PD > or = 5 mm exhibiting RAL gain > or = 2 mm in the test group . Nevertheless , no improvement in the microbiologic or immunologic outcome was observed with the adjunctive use of systemic amoxicillin and metronidazole The present study describes selected clinical and microbiological results obtained by treatment with local ( Elyzol ) and systemic ( Flagyl ) use of metronidazole alone and /or mechanical subgingival debridement in early onset periodontitis ( EOP ) . Twelve patients , with lesions not distributed as in classical localized juvenile periodontitis , were included . They were r and omly divided into local and systemic treatment groups each comprising 6 individuals , in each of whom 4 sites ( one site/quadrant ) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities . The overall treatment design provided 6 different test groups . Groups of quadrants received 1 ) scaling and root planing 2 ) local metronidazole treatment 3 ) systemic metronidazole treatment 4 ) local metronidazole combined with scaling and root planing 5 ) systemic metronidazole combined with scaling and root planing 6 ) No treatment . The microbiological and clinical effects of treatment modalities were monitored over 42 days . The results demonstrated reductions in mean counts of obligate anaerobic and capnophilic microorganisms coupled with significant improvements in mean clinical measurements ( gingivitis , probing depth , attachment level ) in all groups , except the untreated . Scaling and root planing provided an initial clinical improvement with a selective reduction of periodontopathogens ( 92.6 % obligate anaerobes , 42.9 % capnophilic microorganisms ) , whereas the combination of local or systemic metronidazole with scaling and root planing were found superior in reducing capnophilic bacteria ( 93.7 % and 93.4 % , respectively ) . It is of critical importance to have a treatment rationale for EOP , since bacterial differences exist in the etiological subforms of periodontitis . Microbial testing may be justified before prescribing the adjunctive antibiotic and selecting the mode of delivery for the successful clinical management of EOP AIM The aim of this study was to evaluate the clinical and microbiological effects of scaling and root planing ( SRP ) alone or combined with metronidazole ( MTZ ) and amoxicillin ( AMX ) in the treatment of subjects with generalized aggressive periodontitis ( GAgP ) . MATERIAL S AND METHODS A double-blind , placebo-controlled , r and omized clinical trial was conducted in 30 subjects receiving SRP alone or combined with MTZ ( 400 mg 3 x per day ) and AMX ( 500 mg 3 x per day ) for 14 days . Clinical and microbiological examinations were performed at baseline and 3 months post-SRP . Nine subgingival plaque sample s per subject were analysed using checkerboard DNA-DNA hybridization . RESULTS Subjects receiving MTZ and AMX showed the greatest improvements in the mean full-mouth probing depth and clinical attachment level and at initially intermediate and deep sites . The most beneficial changes in the microbial profile were also observed in the MTZ+AMX group , which showed the lowest proportions of the red complex as well as a significant decrease in the proportions of the orange complex after treatment . The antibiotic therapy also reduced the levels of Aggregatibacter actinomycetemcomitans at initially deep sites . CONCLUSION Subjects with GAgP significantly benefit from the adjunctive use of MTZ and AMX . The short-term advantages are observed in the clinical and microbiological parameters In this study , the clinical efficacies of systemic doxycycline ( SD ) and local doxycycline ( LD ) in the treatment of chronic periodontitis were compared . Forty-five patients were studied in 3 main groups with 5 treatments : SD alone , SD+scaling-root planing ( SD+SRP ) , LD alone , LD+SRP and SRP alone . Antibiotic-treated patients were given doxycycline treatment alone in 1 quadrant of their upper jaws , and doxycycline+SRP was given in the contralateral quadrant . The areas included at least 4 teeth with > or = 5 mm pockets . Probing depth ( PD ) , clinical attachment level , gingival index , sulcular bleeding index and plaque index values were recorded at baseline and the 7th week . The results were statistically analyzed . All of the clinical parameters were significantly reduced by all treatments ( P < or = 0.05 ) . The SD and LD treatments alone provided significant clinical healings . The significant differences among the groups were only in PD at the 7th week . The LD treatment provided significantly higher PD reduction than the SD treatment ( P < or = 0.05 ) . No significant difference was found between the SD+SRP and the LD+SRP treatments . There was no significant difference between SD+SRP and SRP alone treatment ( P > 0.05 ) . The SD group showed lower PD reduction than SRP group ( P < or = 0.05 ) , while no significant difference was found between LD and SRP treatments . The LD alone treatment seemed more effective than SD alone treatment on PD reduction , but no significant difference was found between them when combined with the SRP . LD may be more preferable than SD as an adjunct to mechanical treatment since LD seems more effective than SD on PD reduction and does not have the side effects of SD Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists BACKGROUND The objective of this study was to assess the adjunctive clinical effect of the administration of systemic amoxicillin and metronidazole in the non-surgical treatment of generalized aggressive periodontitis ( GAP ) . METHODS Forty-one systemically healthy subjects with GAP were included in this 6-month double-blind , placebo-controlled , r and omized clinical trial . Patients received a course of full-mouth non-surgical periodontal treatment delivered over a 24 h period using machine-driven and h and instruments . Test subjects received an adjunctive course of systemic antibiotic consisting of 500 mg amoxicillin and 500 mg metronidazole three times a day for 7 days . Clinical parameters were collected at baseline , and at 2 and 6 months post-treatment . RESULTS In both the test and the placebo groups , all clinical parameters improved at 2 and 6 months . In deep pockets ( > or = 7 mm ) , the test treatment result ed in an additional 1.4 mm ( 95 % confidence interval 0.8 , 2.0 mm ) in full-mouth probing pocket depth ( PPD ) reduction and 1 mm ( 0.7 , 1.3 mm ) of life cumulative attachment loss ( LCAL ) gain at 6 months . In moderate pockets ( 4 - 6 mm ) , the adjunctive benefit was smaller in magnitude : PPD reduction was 0.4 mm ( 0.1 , 0.7 mm ) and LCAL gain was 0.5 mm ( 0.2 , 0.8 mm ) . In addition , the 6-month data showed LCAL gains > or = 2 mm at 25 % of sites in test patients compared with 16 % in placebo ( p=0.028 ) . Similarly , PPD reductions of 2 mm or more were observed in 30 % of sites in test and 21 % of sites in placebo patients . Seventy-four percent of pockets with PPD > or = 5 mm at baseline were 4 mm or shallower at 6 months in the test group . This compared with 54 % in the placebo group ( p=0.008 ) . Disease progression at 6 months was observed at 1.5 % of test and 3.3 % of sites in test and placebo , respectively ( p=0.072 ) . CONCLUSIONS These data indicate that a 7-day adjunctive course of systemic metronidazole and amoxicillin significantly improved the short-term clinical outcomes of full-mouth non-surgical periodontal debridement in subjects with GAP OBJECTIVE The current investigation evaluated the clinical effects of scaling and root planing ( SRP ) alone or in combination with systemic metronidazole and /or repeated professional removal of supragingival plaque in subjects with chronic periodontitis . METHODS Fourty-four adult subjects ( mean age : 45+/-6 years ) with periodontitis were r and omly assigned to four treatment groups ; a control ( C , n=10 ) that received SRP and placebo and three test groups treated as follows : Test 1 ( T1 ) ( n=12 ) received SRP and metronidazole ( 400 mg t.i.d . , M ) for 10 days ; Test 2 ( T2 ) ( n=12 ) received SRP , weekly professional supragingival plaque removal for three months ( professional cleaning ( PC ) ) and placebo ; and Test 3 ( T3 ) ( n=10 ) received SRP , M and PC . Pocket depth ( PD ) , attachment level ( AL ) , bleeding on probing ( BOP ) and presence of visible plaque and suppuration were measured at six sites per tooth at baseline and at 90 days post-therapy . Significance of differences over time was determined using the Wilcoxon test , and among groups using ancova . RESULTS A reduction in full-mouth mean clinical parameters was observed at 90 days after all therapies . Sites with baseline PD<4 mm showed an increase in mean PD in the control group and in mean AL in all treatment groups . Sites with baseline PD of 4 - 6 mm in subjects who received PC as part of therapy ( T2 , T3 ) showed a marked reduction in PD , AL and in the % of sites with BOP . Subjects who received metronidazole ( T1 and T3 ) showed the best clinical response at sites with an initial PD of > 6 mm . The major clinical benefit occurred when the combination of SRP , M and PC was used . Group T3 showed the least attachment loss in initially shallow pockets . This group also exhibited the greatest reduction in the % of sites with BOP and suppuration as well as in mean PD and AL at sites with baseline PD>4 mm . CONCLUSION The data suggest a significant clinical benefit in combining SRP , systemic metronidazole and weekly professional supragingival plaque removal for the treatment of chronic periodontitis Systemic metronidazole and tetracycline were compared as adjunctive agents in the treatment of localized juvenile periodontitis ( LJP ) . 27 patients with Actinobacillus actinomycetemcomitans-positive ( Aa ) LJP were treated with scaling and rootplaning , control of oral hygiene and periodontal surgery if indicated . The patients were r and omly divided into 3 equal groups : the 1st group had metronidazole 200 mg x 3 x 10 days , the 2nd tetracycline 250 mg x 4 x 12 days , the 3rd group received no medication and served as a control . 6 patients had periodontal surgery . 4 sites with the most advanced bone loss as determined on radiographs were selected in each subject for test sites . Gingival index , gingival bleeding after probing ( GB ) , probing depth ( PD ) , suppuration , and radiographic bone loss were registered , and subgingival Aa was selectively cultured . GB and PD > or = 4 mm were registered in the whole dentition as well . All parameters were monitored at baseline and at 6 and 18 months after treatment . By the end of the study , Aa was suppressed to below detection level at all test sites only in the metronidazole group , at 17/26 sites ( 4 patients ) in the tetracycline group and at 19/26 sites ( 6 patients ) in the control group . Clinical ly , all groups showed improvement . In conclusion , metronidazole was more effective than tetracycline in the suppression of Aa and the suppression of Aa appeared to produce better clinical results BACKGROUND Antibiotic therapy can be used in very specific periodontal treatment situations such as in refractory cases of periodontal disease found to be more prevalent in smokers . This study was design ed to determine the efficacy of azithromycin ( AZM ) when combined with scaling and root planing ( SRP ) for the treatment of moderate to severe chronic periodontitis in smokers . METHODS Thirty-one subjects were enrolled into a 6-month r and omized , single-masked trial to evaluate clinical , microbial ( using benzoyl- DL-arginine naphthylamine [ BANA ] assay ) , and gingival crevicular fluid ( GCF ) pyridinoline cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) levels in response to SRP alone or SRP + AZM . At baseline , patients who smoked > or = 1 pack per day of cigarettes who presented with at least five sites with probing depths ( PD ) of > or = 5 mm with bleeding on probing ( BOP ) were r and omized into the test or control groups . At baseline and 3 and 6 months , clinical measurements ( probing depth [ PD ] , clinical attachment loss [ CAL ] , and bleeding on probing [ BOP ] ) were performed . GCF bone marker assessment ( Ctelopeptide [ ICTP ] as well as BANA test analyses ) were performed at baseline , 14 days , and 3 and 6 months . RESULTS The results demonstrated that both groups displayed clinical improvements in PD and CAL that were sustained for 6 months . Using a subject-based analysis , patients treated with SRP + AZM showed enhanced reductions in PD and gains in CAL at moderate ( 4 to 6 mm ) and deep sites ( > 6 mm ) ( P < 0.05 ) . Furthermore , SRP + AZM result ed in greater reductions in BANA levels compared to SRP alone ( P < 0.05 ) while rebounds in BANA levels were noted in control group at the 6-month evaluation . No statistically significant differences between groups on mean BOP and ICTP levels during the course of the study were noted . CONCLUSIONS The utilization of AZM in combination with SRP improves the efficacy of non-surgical periodontal therapy in reducing probing depth and improving attachment levels in smokers with moderate to advanced attachment loss BACKGROUND The purpose of this study is to compare the additional benefit of systemic antimicrobials versus placebos to a repeated mechanical instrumentation combined with comprehensive local chemical plaque control for the periodontal treatment of generalized aggressive periodontitis ( GAgP ) . METHODS This was a 6-month r and omized , double-masked , placebo-controlled clinical trial . All GAgP patients received full-mouth disinfection followed by staged scaling and root planing without ( placebo group ; n = 17 ) or with ( test group ; n = 18 ) systemic antimicrobials ( 500 mg amoxicillin [ AMX ] + 250 mg metronidazole [ MET ] ; three times a day for 10 days ) . Clinical parameters were measured at baseline and 3 and 6 months post-therapy . Significant differences between groups at baseline were sought by using the Mann-Whitney U test , whereas comparisons over time were examined by using a general linear model repeated measures procedure . RESULTS Both groups demonstrated similar improvements in most parameters over time . The test group presented a greater mean probing depth ( PD ) reduction and clinical attachment level ( CAL ) gain at sites with initially moderate PD at 6 months ( P < 0.03 ) . No differences were seen between groups regarding mean reductions and mean gains , respectively , for PD and CAL initially ≥7 mm . The test group presented a higher percentage of sites that improved ≥2 mm and ended up with PD ≤4 mm or a lower percentage of sites that worsened ≥2 mm and remained with PD > 4 mm at 3 months ( P < 0.01 ) . No differences were noticed between groups for these parameters at 6 months . CONCLUSION AMX + MET brought additional clinical effects to the repeated mechanical and antiseptic treatment of GAgP in a very short time ( 3 months ) , which tended to fade away over time ( 6 months ) The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease . 16 individuals , 10 female and 6 male , aged 35 - 58 years , with advanced periodontal disease were recruited . A baseline examination included assessment of clinical , radiographical , microbiological and histopathological characteristics of periodontal disease . The 16 patients were r and omly distributed into 2 different sample s of 8 subjects each . One sample of subjects received during the first 2 weeks of active periodontal therapy , antibiotics administered via the systemic route ( metronidazole and amoxicillin ) . During the corresponding period , the 2nd sample of subjects received a placebo drug ( placebo sample ) . In each of the 16 patients , 2 quadrants ( 1 in the maxilla and 1 in the m and ible ) were exposed to non-surgical subgingival scaling and root planing . The contralateral quadrants were left without subgingival instrumentation . Thus , 4 different treatment groups were formed ; group 1 : antibiotic therapy but no scaling , group 2 : antibiotic therapy plus scaling , group 3 : placebo therapy but no scaling , group 4 : placebo therapy plus scaling . Re-examinations regarding the clinical parameters were performed , sample s of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy . The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy , and subsequently exited from the study . Groups 2 and 4 were also re-examined 24 months after baseline . The findings demonstrated that in patients with advanced periodontal disease , systemic administration of metronidazole plus amoxicillin result ed in ( i ) an improvement of the periodontal conditions , ( ii ) elimination/suppression of putative periodontal pathogens such as A. actinomycetemcomitans , P. gingivalis , P. intermedia and ( iii ) reduction of the size of the inflammatory lesion . The antibiotic regimen alone , however , was less effective than mechanical therapy with respect to reduction of BoP - positive sites , probing pocket depth reduction , probing attachment gain . The combined mechanical and systemic antibiotic therapy ( group 2 ) was more effective than mechanical therapy alone in terms of improvement of clinical and microbiological features of periodontal disease OBJECTIVE The use of antibiotics as an adjunctive therapy in the management of periodontal diseases has always been of interest for dental practitioners . Although studies have demonstrated the importance of different antibiotics as adjunct in the treatment of periodontitis , few studies have reported comparative results of antibiotics in localized aggressive periodontitis ( LAP ) . The aim of the present study was to evaluate the comparative effects of systemic tetracycline derivative doxycycline versus a combination of metronidazole and amoxicillin in the elimination/suppression of Actinobacillus actinomycetemcomitans and their clinical effects during 90 days of follow-up in patients with LAP . METHOD AND MATERIAL S Thirty patients with untreated LAP participated in the study . Patients were r and omly divided into 2 groups and given doxycycline or metronidazole plus amoxicillin , and periodontal clinical parameters were achieved at baseline and 10 , 30 , 60 , and 90 days after microbiologic sampling . Patients were also given mechanical debridement after measurement at baseline . RESULTS Both groups of patients demonstrated improvement in clinical parameters , and microbiologic sample s did not show any A actinomycetemcomitans at days 30 , 60 , and 90 . CONCLUSION Systemic use of doxycycline or metronidazole plus amoxicillin as an adjunct to conventional therapy may be used for the treatment of patients with LAP The purpose of the present investigation was to assess the effects of periodontal surgery and 4 systemically administered agents , Augmentin , tetracycline , ibuprofen or a placebo on clinical and microbiological parameters of periodontal disease . 98 subjects were monitored at 2-month intervals at 6 sites per tooth for clinical parameters . Subgingival plaque sample s were taken from the mesial surface of each tooth at each visit and evaluated for their content of 14 subgingival species using DNA probes and a colony lift method . 40 subjects who exhibited loss of attachment > 2.5 mm at 1 or more sites during longitudinal monitoring were treated using modified Widman flap surgery at sites with probing pocket depth > 4 mm , subgingival scaling at all other sites and were r and omly assigned 1 of the 4 agents . Treatment was completed within 30 days during which time the subject took the assigned agent . Overall , subjects exhibited a mean attachment level " gain " of 0.34 + /- 0.10 mm ( SEM ) and a mean pocket depth reduction of 0.62 + /- 0.09 mm 10 + /- 4 months post-therapy . However , certain subjects in each treatment group showed a poor response . Subjects receiving antibiotics exhibited significantly more attachment level " gain " ( 0.57 + /- 0.15 mm , SEM ) than subjects receiving either ibuprofen or a placebo ( 0.02 + /- 0.10 ) . The differences between Augmentin and tetracycline groups were not significant , nor were the differences between ibuprofen and placebo . 10 months post-therapy , there was a reduction in the number of sites colonized in any subject group by detectable levels ( 10(3 ) ) of P. gingivalis . Species showing similar reductions were B. forsythus , P. intermedia and P. micros . Subjects receiving systemically administered antibiotics had a significant increase in the proportion of sites colonized by C. ochracea coupled with a greater decrease in the number of sites colonized by P. gingivalis , B. forsythus , P. intermedia and P. micros post-therapy than subjects not receiving antibiotics . The results of this investigation indicate that adjunctive systemic antibiotics increase periodontal attachment " gain " and decrease the levels of some suspected periodontal pathogens in subjects with evidence of current disease progression Several studies have indicated that the combination of metronidazole and spiramycin is synergistic against anaerobic bacteria and may be effective against oral infections . The present study sought to determine the efficacy and safety of a commercial preparation of these two antibiotics ( Rodogyl ) when used adjunctively in the treatment of advanced periodontal disease . In a double-blind parallel r and omized trial , 56 patients ( mean age = 44 years ) with advanced periodontitis ( 50 of whom completed the study ) were assigned to either the Rodogyl or placebo group . Both groups were thoroughly scaled and root planned for approximately 6 hours , with one group receiving Rodogyl for 2 weeks and the other a placebo . No other therapy was received during the study period . Two sites in each patient with probing depths of at least 7 mm were selected for study . Plaque level ( P1I ) , gingival inflammation ( GI ) , probing depth ( PD ) , and attachment level ( AL ) were measured at baseline , 14 days , 1 month , and then at monthly intervals up to 6 months . Subgingival bacteria were monitored with dark-field microscopy . The development of resistant bacteria , as well as side effects to the medications , was also monitored . The Rodogyl group exhibited a greater gain in AL ( 0.67 mm ) from the 2-month interval until the end of the study . Although this difference was statistically significant ( P less than 0.05 ) , it was not necessarily of biologic significance . There was a significantly greater decline in the proportion of spirochetes in the Rodogyl group at the 14-day interval , and this difference remained significant ( P less than 0.05 ) at all study intervals . No difference in the proportion of motile organisms was observed . ( ABSTRACT TRUNCATED AT 250 WORDS In a previous study , a double-blind between subject comparison of the effects of metronidazole and placebo tablets was completed over 22 weeks in 45 subjects with chronic periodontal disease ranging in severity from moderate ( PI = 2.0 - 3.9 ) to high ( PI = 4.0 - 6.0 ) . The results showed a significantly greater reduction in the mean probing depth of pockets with the use of metronidazole , but this reduction was apparent only in subjects with severe periodontal disease ( PI = 4.0 - 6.0 ) . 3 years later , 28 subjects attended . All groups still showed statistically significant improvements in all parameters when compared with those at the first visit . However , when compared with those at the end of the trial , there were statistically significant increases in gingival bleeding and calculus scores . An increase in plaque levels was also observed but this was not statistically significant . When subjects with moderate and severe periodontal disease were grouped together , there were no significant differences in any of the parameters between test and control groups . Moreover , the significantly greater reductions in mean probing depth of pockets , achieved with the use of metronidazole in the severe group at the end of the trial , had disappeared after 3 years . However , in subjects with mild disease , statistically significant reductions in pocket probing depth , not originally apparent , were observed 3 years later It has long been question ed whether antibiotics , used as a supplement to traditional therapy , provide any lasting benefit in the treatment of chronic periodontitis . This study was design ed to evaluate Spiramycin as an adjunct to scaling and root planing in the treatment of advanced chronic periodontitis . In total , 193 patients with advanced periodontitis were recruited in seven centres using selection criteria previously described . After undergoing thorough scaling and root planing , all patients r and omly received either Spiramycin , 1,500,000 international units , twice per day ( IU , bid ) for 14 days ( 96 patients ) , or a visually-identical placebo capsule ( 97 patients ) . The clinical parameters measured were plaque index , crevicular fluid level , probing depths , bleeding on probing and attachment level changes . Data was recorded at baseline , two- , eight- , 12- and 24-weeks visits . A total of 189 patients completed the study ( 96 placebo , 93 Spiramycin ) . Statistically significant differences in probing depth , favoring Spiramycin , were seen at two weeks ( p < 0.0125 ) , eight weeks ( p < 0.0020 ) , 12 weeks ( p < 0.0032 ) and 24 weeks ( p < 0.0075 ) . Spiramycin also produced a significant improvement in attachment level at 12 weeks ( p < 0.0146 ) . All other clinical parameters showed no difference between drug and placebo . This study shows that Spiramycin , as an adjunct to thorough scaling and root planing , provides a statistically significant improvement in probing depths for up to 24 weeks when compared with scaling and root planing alone . Both longer studies and microbiologic evaluations are necessary to determine whether a more lasting benefit is possible AIM To compare the effects of systemic amoxicillin ( AMX ) plus metronidazole ( MET ) or placebos combined with anti-infective mechanical debridement on the sub-gingival microbiota of generalized aggressive periodontitis ( GAP ) . MATERIAL AND METHODS The study was a 6-month r and omized , double-blinded , placebo-controlled clinical trial . Thirty-one subjects received full-mouth ultrasonic debridement followed by scaling and root planing with chlorhexidine rinsing , brushing and irrigation . During mechanical therapy , subjects received systemic AMX (500mg)+MET ( 250 mg ) or placebo , t.i.d . for 10 days . Sub-gingival sample s were obtained from each patient and analysed for their composition by checkerboard at baseline , 3 and 6 months post-therapy . Significant differences between groups over time were examined by General Linear Model of Repeated Measures . RESULTS High levels of periodontal pathogens , as well as some " non-periodontal " species were observed . Most of the periodontal pathogens decreased significantly over time ( p<0.05 ) , whereas " non-periodontal " bacteria tended to increase in both groups . Sites that showed attachment loss and probing depth increase harboured higher levels of Dialister pneumosintes , Campylobacter rectus , Fusobacterium necrophorum , Prevotella tannerea and Peptostreptococcus anaerobius than sites that improved after both therapies ( p<0.05 ) . CONCLUSIONS Systemic AMX+MET or placebos adjunctive to anti-infective mechanical debridement were comparable in lowering periodontal pathogens up to 6 months after treatment . Species not commonly associated with GAP were less affected by both therapies OBJECTIVES To compare the subgingival microbiological outcomes of azithromycin or placebo as adjuncts to scaling and root planing ( SRP ) in the treatment of aggressive periodontitis ( AgP ) , and to secondarily evaluate the microbiological effect of supragingival scaling in AgP patients . METHODS Twenty-four AgP subjects 13 - 26 years of age received a 15-day programme of supragingival scaling ( SC ) and were then r and omly assigned to SRP with systemic azithromycin or placebo . Subgingival sample s were taken with sterile paper points at baseline , 15 days after SC , and at 3 , 6 and 12 months following SRP . Microbiological analysis was performed by the checkerboard DNA-DNA hybridization . RESULTS Changes in bacterial levels from baseline to 15 days after SC were similar in the 2 groups . When subjects were analysed as a single group , significant reductions after SC were observed for Actinomyces gerencseriae , Capnocytophaga ochracea , and Treponema denticola . During the 12-month follow-up , levels of most of the bacteria decreased in both groups in a similar pattern . For instance , Actinomyces israelli , Veillonella parvula , Streptococcus gordonii , C. ochracea , Eikenella corrodens , Eubacterium nodatum , Fusobacterium periodonticum and Fusobacterium nucleatum ssp . polymorphum decreased significantly within the groups . CONCLUSIONS Azithromycin was ineffective in lowering the subgingival levels of important putative periodontal pathogens in young AgP subjects compared to placebo . CLINICAL SIGNIFICANCE Scaling and root planing with adjunctive systemic azithromycin provides little additional benefit compared to placebo in reductions of major subgingival periodontal pathogens The present study was undertaken to compare the efficacy of two antibiotics , spiramycin and tetracycline , with a placebo when used adjunctively with scaling and root planing in the treatment of advanced adult chronic periodontitis . This was a double-blind , parallel , r and omized trial with one factor ( drug ) at three levels . Ninety-six patients ( mean age 46 + /- 1 ) were r and omly assigned into one of three groups . All groups were scaled and root planed with each respective group receiving either spiramycin , tetracycline , or a placebo for 2 weeks . Two sites with probing depth of at least 7 mm were evaluated and the following clinical parameters were measured at baseline , 2 , 8 , 12 , and 24 weeks : plaque index , bleeding on probing , crevicular fluid , probing depth , and change in the attachment level . The changes in the subgingival bacteria were monitored also using a differential staining technique . Seventy-nine patients completed the study . At the end of 24 weeks , although all three groups had shown clinical improvement when compared to the baseline data , there were no significant intergroup differences in any of the clinical parameters measured . While the proportion of spirochetes were significantly decreased ( P less than 0.05 ) at 2- and 8-week intervals in both tetracycline and spiramycin groups ( 26 % to 0.04 % and 28 % to 0.04 % , respectively ) , compared to the placebo group ( 30 % to 7 % ) , only in the spiramycin group was the proportion of spirochetes significantly lower than the placebo group at the 24-week interval ( 3 % and 11 % , respectively ) . At week 24 , the proportion of spirochetes in the tetracycline group had rebounded to 7 % , which was not significantly different from the placebo group . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract . Objective and design : The present study examined effectiveness of low-dose doxycycline ( LDD ) in combination with nonsurgical therapy on gingival crevicular fluid ( GCF ) tissue plasminogen activator ( t-PA ) levels and clinical parameters in chronic periodontitis ( CP ) a over 12-month period . Methods : GCF sample s were collected , probing depth ( PD ) , clinical attachment level ( CAL ) , gingival index ( GI ) and plaque index were recorded at baseline , 3 , 6 , 9 and 12 months . CP patients ( n = 65 ) were r and omized to LDD or placebo groups . LDD group received LDD ( 20 mg ) b.i.d for 3-months plus and root planing ( SRP ) , while placebo group was given placebo capsules b.i.d for 3-months plus SRP . GCF t-PA levels were determined by ELISA . Friedman , Wilcoxon and Mann-Whitney test was used for statistical analysis . Results : Significant improvement was observed in all clinical parameters in both groups over 12-month period ( p < 0.01 ) . LDD group had lower PD , CAL and GI scores than placebo group at 6 , 9 and 12-months ( p < 0.05 ) . GCF t-PA levels reduced in both groups over 12-month period ( p < 0.01 ) . LDD group had lower GCF t-PA levels than placebo group at 6 and 9-months ( p < 0.05 ) . Conclusions : These results provide additional information about usefulness of LDD therapy as an adjunct to nonsurgical therapy in long-term management of periodontitis The aim of the present parallel , double-blind investigation was to evaluate the effect of using systemic metronidazole alone or associated to scaling and root planing on adult chronic periodontal disease , monitored at baseline , 30 , 60 and 90 days . Twelve subjects were divided into three groups : the first group ( Group I - 22 sites ) was su bmi tted to scaling and root planing ( SRP ) alone ; the second group ( Group II - 30 sites ) received SRP and 250 mg of metronidazole ( 3 times a day for 10 days ) , and the third group ( Group III - 31 sites ) was treated with metronidazole alone . The clinical parameters evaluated were probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PlI ) , gingival index ( GI ) and bleeding upon probing ( BP ) . Microbiological ( BANA test ) and enzymatic ( Pocket Watch ) tests were also performed . All three proposed treatments produced significant improvements in clinical conditions of subjects , from baseline , 30 , 60 and 90-day period , except for clinical attachment level . The results obtained by microbiological and enzymatic tests did not show statistical differences among the groups for the 90-day period ( r = 0.7924 and r = 0.7757 , respectively ) . In relation to clinical parameters , statistical differences among groups were observed only for the gingival index ( p = 0.0261 ) between Groups I and II , and probing depth ( p = 0.0124 ) between Group I and the others . We conclude that the use of systemic metronidazole did not produce additional effects on the microbiological conditions of these patients with chronic periodontal disease AIM To evaluate and compare the effects of adjunctive metronidazole plus amoxicillin , doxycycline and metronidazole on clinical and microbiological parameters in patients with generalized aggressive periodontitis . MATERIAL AND METHODS Forty-three patients participated in this r and omized clinical trial divided into four groups . Six weeks after scaling and root planning ( SRP ) , groups 1 - 3 received adjunctive metronidazole , plus amoxicillin , doxycycline and metronidazole respectively , and group 4 acted as controls . Clinical recordings concerning probing depth , probing attachment level and bleeding on probing were performed at baseline , 6 weeks after SRP and 6 months from baseline . Subgingival sample s were analysed using the ' checkerboard ' DNA-DNA hybridization for Porphyromonas gingivalis , Actinobacillus actinomycetemcomitans , Tannerella forsythia and Treponema denticola . RESULTS All treatments result ed in improvement of clinical parameters ( ANOVA p > 0.05 ) . Systemic administration of metronidazole plus amoxicillin or metronidazole result ed in statistically significant greater reduction of the proportion of sites > 6 mm than SRP ( z-test , p < 0.05 ) . These antimicrobials yielded a significant effect on levels of important periodontal pathogens for 6 months . CONCLUSION Adjunctive metronidazole plus amoxicillin or metronidazole alone ( when A.actinomycetemcomitans is not involved ) is effective in deep pockets of aggressive periodontitis patients OBJECTIVE Along with conventional non-surgical periodontal therapy ( NSPT ) systemic antimicrobials may provide more effective treatment for chronic periodontitis by targeting tissue-invasive bacteria . The aim of this r and omized , placebo-controlled , double-masked clinical trial was to evaluate the adjunctive effects of oral clarithromycin ( CLM ) to non-surgical periodontal therapy for chronic periodontitis . METHODS 40 patients were categorized into two groups : test group - scaling and root planing ( SRP ) plus CLM ( 500 mg b.i.d . for 3 days ) and control group - SRP plus placebo . Clinical parameters were recorded at baseline and at 1 , 3 , 6 , and 9 months . They included gingival index ( GI ) , probing depth ( PD ) , and clinical attachment level ( CAL ) . Also microbial analysis of dental plaque was done at baseline , 3 and 9 months to estimate the levels of periodontopathic organisms using polymerase chain reaction . ANOVA , Chi-square and Bonferroni tests were used for statistical analysis . RESULTS Thirty-seven subjects completed the study and the results demonstrated that both groups displayed clinical improvements . Using a subject-based analysis , patients treated with SRP+CLM showed enhanced reductions in PD and gains in CAL ( p<0.001 ) over time , as compared to control group . Also significant reductions in periodontopathic organisms were noticed in the test group compared to control group . However , no statistically significant differences were noted for Tannerella forsythia levels between the groups during the course of the study . CONCLUSIONS The utilisation of CLM in combination with SRP improves the efficacy of NSPT in reducing PD , improving CAL and in lessening microbial loads . Hence , CLM may be beneficial in the non-surgical treatment regimen of chronic periodontitis BACKGROUND The aim of this study was to test the hypothesis that there are no differences in clinical parameters in generalized aggressive periodontitis patients after full-mouth scaling and root planing ( FRP ) or quadrant-wise basic periodontal therapy ( BPT ) when combined with an antibiotic regimen . METHODS Patients were allocated r and omly to BPT ( N = 15 ; mean age : 29.5 + /- 5.7 years ) or FRP ( N = 15 ; mean age : 28.4 + /- 5.7 years ) . All subjects received oral hygiene instructions including the use of a 0.12 % chlorhexidine mouthrinse solution twice a day for 2 months . Patients also received amoxicillin , 500 mg , and metronidazole , 250 mg , three times a day for 7 days . Probing depth ( PD ) , clinical attachment level , visible plaque , and bleeding on probing were recorded at baseline and at 2 , 4 , and 6 months post-therapy . Statistically significant changes within and between groups were determined using the general linear model repeated measures procedure . RESULTS Both groups showed a significant improvement in all clinical parameters post-therapy , which was particularly evident at 2 months in the sites that had been deepest at baseline . For instance , the mean PD at sites with mean PD > or = 7 mm at baseline had decreased 3.9 mm in the BPT group and 3.6 mm in the FRP group . At 6 months , the percentage of sites with PD > or = 7 mm decreased from 13.2 % + /- 3.2 % to 0 % in the BPT group and from 13.3 % + /- 3.5 % to 0.2 % + /- 0.1 % in the FRP group . No statistically significant differences were observed between groups for most clinical parameters . CONCLUSION Within the limits of the present investigation , FRP and BPT caused comparable clinical effects in aggressive periodontitis patients when an adjunctive combined antibiotic regimen was included BACKGROUND At present there is limited data concerning the efficacy of non-surgical periodontal therapy supplemented with subantimicrobial dose doxycycline ( SDD ) in the treatment of severe , generalized periodontitis . The purpose of the present study was to evaluate the effect of adjunctive SDD therapy on clinical periodontal parameters and gingival crevicular fluid ( GCF ) transforming growth factor-beta1 ( TGF-beta1 ) levels in patients with severe , generalized chronic periodontitis over a 6-month period . METHODS Thirty-five patients with severe , generalized periodontitis and 11 periodontally healthy subjects were included in the present study . Patients received full-mouth supragingival debridment at baseline and r and omized to take either SDD b.i.d . or placebo b.i.d . for 3 months . Patients received root planing and oral hygiene instruction once a week for four consecutive weeks . Clinical measurements including probing depth ( PD ) , clinical attachment level , papilla bleeding index and plaque index and GCF sampling were performed at baseline , 3 and 6 months . The GCF TGF-beta1 levels were analysed by enzyme-linked immunosorbent assay . RESULTS Thirteen patients in both study groups completed the 6-month trial . Following scaling and root planing ( SRP ) plus SDD and SRP plus placebo therapy significant improvements in clinical periodontal parameters of both groups were observed ( p<0.025 ) . In the SDD group a significantly higher percentage ( % 73.4 ) of deep pockets resolved ( PD reduction > or =3 mm from baseline ) when compared with placebo group ( % 49.7 ) at 6 months ( p<0.05 ) . At baseline there were no significant differences in GCF TGF-beta1 levels between three groups . Both total amount and concentration of GCF TGF-beta1 in SDD and placebo groups increased when compared with baseline at 3 months . However , only GCF TGF-beta1 levels of SDD group was significantly higher than baseline ( p<0.025 ) and placebo group ( p<0.017 ) at 3 months . At 6 months GCF TGF-beta1 levels of both groups were similar to baseline levels ( p<0.025 ) . CONCLUSIONS These data indicate that combination of SDD with non-surgical therapy improves clinical parameters of periodontal disease and increases GCF TGF-beta1 levels together with a decrease in prevalence of residual pockets in patients with severe , generalized chronic periodontitis . Increased GCF TGF-beta1 levels following SDD therapy might suggest a novell pleiotrophic mechanism for tetracyclines to inhibit connective tissue breakdown AIM To compare the 1-year clinical and microbiological outcomes of an enhanced anti-infective therapy with versus without systemic antimicrobials in patients with generalized aggressive periodontitis ( GAP ) . METHODS In this 12-month r and omized , double-blinded , placebo-controlled trial , 35 individuals assigned to a control ( n = 17 ) or test group ( n = 18 ) received full-mouth supra and subgingival ultrasonic debridement followed by scaling and root planing with chlorhexidine rinsing , brushing , and irrigation . Subjects received either amoxicillin ( AMX , 500 mg ) + metronidazole ( MET , 250 mg ) or placebos , TID for 10 days . Subgingival sample s were obtained and analysed for their composition by checkerboard . Data were subjected to non-parametric tests . RESULTS Both therapeutic protocol s result ed in similar significant clinical improvement for most parameters at 1 year ( p < 0.01 ) . The AMX + MET group exhibited shallower residual pockets than the placebo ( p = 0.05 ) . Most periodontal pathogens decreased , whereas beneficial bacteria increased in counts in both groups over time ( p < 0.0012 ) . High levels of some periodontal and other microbial pathogens were associated with disease persistence regardless treatment . CONCLUSIONS The enhanced anti-infective mechanical therapy is comparable with its combination with systemic AMX+MET for most clinical parameters and for maintaining low levels of periodontal pathogens for up to 1 year after treatment of GAP 48 adult patients with untreated periodontitis harboring subgingival Actinobacillus actinomycetemcomitans and /or Porphyromonas gingivalis as assessed by PCR were r and omly assigned to receive full-mouth scaling alone ( control ) or scaling with systemic metronidazole plus amoxicillin and supragingival irrigation with chlorhexidine digluconate ( test ) . In patients harboring A. actinomycetemcomitans intraorally at baseline , the adjunctive antimicrobial therapy result ed in a significantly higher incidence of probing attachment level ( PAL ) gain of 2 mm or more compared to scaling alone over 12 months ( p<0.05 ) . In addition , suppression of A. actinomycetemcomitans in subgingival plaque below detectable levels was associated with an increased incidence of PAL gain . In contrast , patients initially harboring P. gingivalis but not A. actinomycetemcomitans in the oral cavity showed a significantly higher incidence of PAL loss following adjunctive antimicrobial therapy compared to scaling alone ( p<0.05 ) . When the presence of pathogens at baseline was disregarded in the analysis , adjunctive antimicrobial therapy did not significantly enhance clinical treatment outcome . The results indicated that adults with untreated periodontitis harboring A. actinomycetemcomitans may benefit from the adjunctive antimicrobial therapy for a minimum of 12 months , whereas , the regimen may adversely affect the clinical treatment outcome of patients harboring P. gingivalis but not A. actinomycetemcomitans BACKGROUND The impact of moxifloxacin ( MOX ) was analyzed in the treatment of severe chronic periodontitis . METHODS In a r and omized , prospect i ve , clinical multicenter trial , 92 subjects with severe chronic periodontitis were treated with scaling and root planing ( SRP ) alone ( control group ; n = 21 ) , SRP plus adjunctive doxycycline ( DOX group ; n = 36 ) , or SRP plus adjunctive MOX ( MOX group ; n = 35 ) . Probing depth ( PD ) , clinical attachment level ( CAL ) , and bleeding on probing ( BOP ) were recorded at baseline and at 3 , 6 , and 12 months after non-surgical periodontal treatment . The load of periodontopathogens , the level of interleukin-8 , and the activities of granulocyte elastase and myeloperoxidase were also measured . RESULTS All three procedures led to significant reductions in PD , CAL , and BOP . PD reduction was significantly greater ( P < 0.05 ) in the MOX group ( 2.46 + /- 1.17 mm at 6 months and 2.84 + /- 1.53 mm at 12 months ) compared to the DOX group ( 1.85 + /- 1.24 mm and 2.19 + /- 1.13 mm at 6 and 12 months , respectively ) and the controls ( 1.77 + /- 0.57 mm and 1.86 + /- 0.56 mm at 6 and 12 months , respectively ) . Only in the MOX group was the load of all investigated bacteria and all inflammatory parameters reduced at each appointment compared to baseline . CONCLUSIONS The adjunctive application of antibiotics improved the treatment outcome in subjects with severe chronic periodontitis . MOX seemed to be more effective than DOX and might be an alternative drug in the treatment of periodontal diseases Abstract . Introduction The treatment of periodontal disease can consist of bacterial plaque reduction , risk factor elimination , and metalloproteinase inhibitor medication . The level of matrix metalloproteinases ( MMPs ) are regulated by endogenous tissue inhibitors of metalloproteinases ( TIMPs ) as well as therapeutic low-dose doxycycline . The aim of the study was to evaluate the effect of the initial phase of periodontal treatment and the effect of doxycycline on clinical parameters and the MMP-8 , MMP-9 , and TIMP-1 concentrations in the saliva and peripheral blood of patients with chronic periodontitis . Material s and Methods The study group consisted of 33 patients with chronic periodontitis . Conventional periodontal treatment ( scaling and root planing ) was conducted on all the patients and doxycycline ( 20 mg orally ) was administered twice daily for three months . Thirty-three controls received the conventional treatment only . Clinical scores ( PI , BI , PD , CAL ) were recorded before and three months after the treatment . MMP-8 , MMP-9 , and TIMP-1 concentrations in saliva and peripheral blood were measured by ELISA before and after the treatment of 20 patients from the study group and 13 of the controls . Results The application of doxycycline 20 mg result ed in significant improvement in clinical parameters compared with the conventional periodontal treatment . Doxycycline did not produce significant reductions in MMP-8 and MMP-9 levels in saliva observed after the conventional treatment . The study revealed increases in the TIMP-1 concentration and the MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios in saliva and blood after treatment with doxycycline . Conclusions The study confirmed the modulating effect of doxycycline on the host response in chronic periodontitis BACKGROUND Severe , generalized periodontitis is a form of chronic periodontitis that appears to be associated with an exaggerated host response . Little information is available on the benefits of using adjunctive host modulation in the management of this form of periodontal disease . METHODS Thirty subjects < or = 45 years of age with severe , generalized periodontitis received subgingival debridement and oral hygiene instructions each week for 4 weeks , plus 6 months of adjunctive subantimicrobial doxycycline ( SDD ) or placebo . Periodontal status was monitored at baseline , and at 1 , 3 , 5.25 , and 8.25 months following completion of the hygiene sessions . Maintenance therapy was performed at 3 , 5.25 , and 8.25 months for both groups . RESULTS Ten subjects in each group completed all phases of the study . Subgingival debridement plus adjunctive SDD reduced deep pockets ( > or = 7 mm at baseline ) by an average of 3.02 mm after 9 months versus 1.42 mm for the placebo group . A significant clinical response was seen in both groups as soon as 1 month , but the response was always clinical ly and statistically greater in the SDD group . In the SDD group , nearly 40 % of 237 pockets > or = 7 mm were reduced by > or = 4 mm , and 55 % were reduced by > or =3 mm . In addition , only 2 pockets deepened by > or = 4 mm in the SDD group versus 10 in the placebo group . CONCLUSIONS The supplementation of hygienist-delivered full mouth subgingival and supragingival debridement with a host-modulating agent , SDD , provides clinical ly and statistically significant benefits in the reduction of deep pockets in patients with severe , generalized periodontitis . In addition , adjunctive SDD is more effective than a placebo in preventing further increases in probing depth The objective of this study was to test the efficacy of scaling and root planing with or without adjunctive tetracycline therapy in the treatment of periodonitis in humans . The presence of plaque , gingival inflammation , probing depths and attachment levels was assessed for all teeth in 12 patients with chronic , advanced periodontitis . After an initial examination all patients were given detailed oral hygiene instructions . The teeth in one-half of each arch were then scaled and root planed . The teeth in the contralateral half were not treated . Six patients were given tetracycline ( 1 gm/day ) during the first and second weeks and the seventh and eighth weeks of the trial . The study thus included four different treatment groups : 1 ) no treatment , 2 ) scaling and root planing alone , 3 ) tetracycline administration alone , and 4 ) scaling and root planing combined with tetracycline administration . All patients were reexamined at 8 and 25 weeks subsequent to the initiation of therapy . Both PlI and GI scores decreased significantly in all groups . The GI scores were significantly lower in the scaled and root planed areas as compared to the contralateral sides at both the 8- and 25-week examinations . The PlI score was lower in the scaled and root planed areas only at the 25-week interval . The gingival probing depths were reduced in all groups . A significantly greater decrease in probing depth , however , was noted in scaled and root planed areas . There was a trend to gain of attachment in the treated areas but the magnitude of the gain was very small . The findings of the trail also revealed that the administration of tetracycline had only a minor effect on the parameters examined This study was design ed to compare both clinical and microbiological changes during the treatment of advanced periodontal disease with mechanical debridement , with or without the adjunctive use of either spiramycin or tetracycline . The study , which included 96 patients with advanced periodontitis , was performed as a controlled double-blind parallel r and omized trial . All patients received thorough scaling and root planing as well as adjunctive placebo or spiramycin or tetracycline . Probing depth measurements , attachment level changes , plaque level , gingival crevicular fluid , bleeding on probing and microbiological evaluation were carried out at baseline , 2- , 8- , 12- and 24-week visits . Seventy-nine patients ( 24 placebo , 27 tetracycline and 28 spiramycin ) completed the study . At 24 weeks there were no intergroup differences in the improvement of any of the clinical parameters . Spiramycin was the only antibiotic which produced a significantly greater decrease in the proportion of spirochaetes than the placebo group at the 24-week visit . It was concluded that mechanical debridement alone was sufficient in decreasing the subgingival bacteria to a level which would result in the return to periodontal health . The study was not long enough to determine whether or not the difference in spirochaete level was an indication that the spiramycin group would have maintained the benefits of treatment for a longer time BACKGROUND , AIMS The aim of this double-blind , parallel study was to evaluate the adjunctive effects of systemically administered amoxicillin and metronidazole in a group of adult periodontitis patients who also received supra- and subgingival debridement . METHODS 49 patients with a diagnosis of generalised severe periodontitis participated in the study . R and om assignment result ed in 26 patients in the placebo ( P ) group with a mean age of 40 years and 23 patients in the test ( T ) group which had a mean age of 45 years . Clinical measurements and microbiological assessment s were taken at baseline and 3 months after completion of initial periodontal therapy with additional placebo or antibiotic treatment . Patients received coded study medication of either 375 mg amoxicillin in combination with 250 mg metronidazole or identical placebo tablets , every 8 hours for the following 7 days . RESULTS At baseline , no statistically significant differences between groups were found for any of the clinical parameters . Except for the plaque , there was a significantly larger change in the bleeding , probing pocket depth ( PPD ) and clinical attachment level ( CAL ) in the T-group as compared to the P-group after therapy . The greatest reduction in PPD was found at sites with initial PPD of > or = 7 mm , 2.5 mm in the P-group and 3.2 mm in the T-group . The improvement in CAL was most pronounced in the PPD category > or = 7 mm and amounted to 1.5 mm and 2.0 mm in the P- and T-groups , respectively . No significant decrease was found in the number of patients positive for any of the test species in the P-group . The number of patients positive for Porphyromonas gingivalis , Bacteroides forsythus and Prevotella intermedia in the T-group showed a significant decrease . After therapy there was a significant difference between the P- and the T- group in the remaining number of patients positive for P. gingivalis , B. forsythus and Peptostreptococcus micros . 4 subgroups were created on the basis of the initial microbiological status for P. gingivalis positive ( Pg-pos ) and negative patients ( Pg-neg ) in the P- and the T-groups . The difference in reduction of PPD between Pg-pos and Pg-neg patients was particularly evident with respect to the changes in % of sites with a probing pocket depth > or = 5 mm . This % decreased from 45 % at baseline to 23 % after treatment in the Pg-pos placebo subgroup and decreased from 46 % to 11 % in the Pg-pos test subgroup ( p < or = 0.005 ) . In contrast , the changes in the proportions of sites with a probing pocket depth > or = 5 mm in the Pg-neg placebo and Pg-neg test subgroup were similar , from 43 % at baseline to 18 % after treatment versus 40 % to 12 % respectively . CONCLUSIONS This study has shown that systemic usage of metronidazole and amoxicillin , when used in conjunction with initial periodontal treatment in adult periodontitis patients , achieves significantly better clinical and microbiological results than initial periodontal treatment alone . Moreover , this research suggests that especially patients diagnosed with P. gingivalis benefit from antibiotic treatment The present study describes results on selected clinical and microbiological parameters obtained by treatment with local ( Elyzol ) and systemic ( Flagyl ) use of metronidazole alone and /or mechanical subgingival debridement in adult periodontitis . Patients were r and omly divided into local and systemic treatment groups each comprising 5 individuals in each of whom 4 sites ( one site/ quadrant ) with a probing depth of > or = 5 mm were selected and treated with separate treatment modalities . The overall treatment design provided 6 different test groups . Groups of quadrants received : ( 1 ) scaling and root planing ; ( 2 ) local metronidazole treatment ; ( 3 ) systemic metronidazole treatment ; ( 4 ) local metronidazole combined with scaling and root planing ; ( 5 ) systemic metronidazole combined with scaling and root planing ; ( 6 ) no treatment . The microbiological and clinical effects of treatment modalities were monitored over a period of 42 days . All treatments result ed in clinical improvements ( gingivitis , probing pocket depth , attachment level ) except for the untreated group . Parallel to the clinical changes , all treatments reduced the number of total bacteria and proportions of obligately anaerobic microorganisms . Although both of the combined treatment groups responded to therapy with better resolution of infection that the pure mechanical and pure metronidazole treatments , local metronidazole in combination with scaling and root planing seems to be more effective in terms of producing both clinical and microbial improvements OBJECTIVE To compare clinical changes occurring in chronic periodontitis subjects receiving SRP alone or with systemically administered azithromycin , metronidazole or a sub-antimicrobial dose of doxycycline . MATERIAL AND METHODS 92 chronic periodontitis subjects were r and omly assigned to receive SRP alone ( N=23 ) or combined with 500 mg azithromycin per day for 3 days ( N=25 ) , 250 mg metronidazole tid for 14 days ( N=24 ) or 20 mg doxycycline bid for 3 months ( N=20 ) . Gingival redness , bleeding on probing , suppuration , pocket depth and attachment level were measured at baseline and 3 , 6 and 12 months post therapy . The significance of changes in clinical parameters within groups over time was sought using the Friedman test and among groups using ANCOVA or the Kruskal Wallis test . RESULTS All groups showed clinical improvements at 12 months , with subjects receiving adjunctive agents showing a somewhat better response . Sites with initial pocket depth > 6 mm showed significantly greater pocket depth reduction and greater attachment gain in subjects receiving metronidazole or azithromycin than subjects in the other groups . Some subjects showed attachment loss at 12 months in each group ranging from 15 % to 39 % of subjects in the SDD and SRP only groups respectively . CONCLUSION This study , demonstrated that periodontal therapy provides clinical benefits and that antibiotics provide a clinical benefit over SRP alone , particularly at initially deeper periodontal pockets BACKGROUND This study examines the efficacy of azithromycin in combination with non-surgical periodontal therapy on clinical and microbiologic parameters and gingival crevicular fluid ( GCF ) matrix metalloproteinases-8 ( MMP-8 ) levels over 6 months in patients with severe generalized chronic periodontitis ( CP ) . METHODS Twenty-eight of 36 patients with severe generalized CP were included in this r and omized , double-masked , placebo-controlled , parallel-arm study . They were r and omly assigned to azithromycin or placebo groups ( 500 mg , once daily for 3 days ) . Probing depth ( PD ) , clinical attachment level , dichotomous presence or absence of supragingival plaque accumulation , and bleeding on probing were recorded . GCF sample s were obtained from one single-rooted tooth with PD ≥ 6 mm , whereas microbiologic sample s were collected from two single-rooted teeth with PD ≥ 6 mm . Microbiologic parameters were analyzed by quantitative real-time polymerase chain reaction for Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Tannerella forsythia , Fusobacterium nucleatum , Prevotella intermedia , and total bacteria . GCF MMP-8 levels were determined by immunofluorescence assay . RESULTS Azithromycin and placebo groups demonstrated similar but significant improvements in all clinical parameters ( P < 0.05 ) . A. actinomycetemcomitans , P. gingivalis , T. forsythia , P. intermedia , and total bacteria significantly decreased over the 6-month period in both groups , whereas F. nucleatum was significantly reduced in all visits in the azithromycin group , with the levels also being lower compared with those of the placebo group ( P < 0.05 ) . The azithromycin and placebo groups exhibited significant reduction in GCF MMP-8 levels at the post-treatment visit and at 2 weeks ( P < 0.05 ) . CONCLUSION On the basis of the present findings , it can be concluded that adjunctive azithromycin provides no additional benefit over non-surgical periodontal treatment on parameters investigated in patients with severe generalized CP The purpose of this study was to determine the effect of cyclic regimen of low dose doxycycline ( 20 mg ) or placebo therapy following scaling and root planing on clinical parameters and crevicular fluid alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase and elastase activities . Fifteen adults ( 13 males , 2 females ) with moderate to advanced adult periodontitis were recruited for the study . The LDD-treated group ( n = 8 subjects ) self administered low dose doxycycline b.i.d . ( 20 mg , p.o . ) from time ( treatment ) to 2 months and then no drug from 2 to 4 months and finally low-dose doxycycline b.i.d . from 4 to 6 months ( i.e. " cyclical " regimen ) . The placebo-treated group ( n = 7 subjects ) was asked to take placebo capsules ( containing inactive filler ; i.e. starchflour ) b.i.d . according to the same " cyclical " regimen . No differences were found between LDD- and placebo-treated groups regarding any of the clinical parameters and gingival crevicular fluid enzyme activities . The relative attachment gain was significantly improved in both groups . The " cyclical " regimen of low-dose doxycycline was not found to reduce alkaline phosphatase , aspartate aminotransferase , alanine aminotransferase and elastase activities in gingival crevicular fluid of the adult periodontitis patients over a 6-month time period AIM The present investigation was performed to study how type 1 diabetics responded to non-surgical periodontal treatment with and without adjunctive doxycycline . METHOD Sixty diabetic type 1 patients ( mean age 35.3+/-9 years ) with moderate-to-severe periodontal disease were selected and divided into two groups of 30 patients each . Both groups were sex and age matched and had similar amounts of periodontal destruction . Plaque index ( PI ) , bleeding on probing ( BOP ) , probing depth ( PD ) and clinical attachment levels ( CAL ) were recorded . Group 1 ( 30 patients ) was treated with oral hygiene instruction , scaling and root planing , chlorhexidine rinses twice a day and doxycycline ( 100 mg/day for 15 days ) . Group 2 ( 30 patients ) had the same treatment but without doxycycline . After 12 weeks their periodontal condition was reevaluated . RESULTS After treatment , both groups had a significant improvement in all periodontal parameters , since PI , BOP , probing pocket depth ( PPD ) and CAL were significantly reduced . However , the reduction in PD in pockets > or = 6 mm and in BOP were more evident when doxycycline was used ( group 1 ) . Differences between groups for these parameters were statistically significant ( p=0.03 ) . CONCLUSION Although both periodontal treatment regimens are effective in type 1 diabetics , the use of doxycycline as an adjunct , provided more significant results when good plaque control was achieved BACKGROUND The benefit of full-mouth disinfection ( FDIS ) over traditional scaling and root planing ( SRP ) remains equivocal , and it is not known whether the use of adjunctive antibiotics may enhance the effect of FDIS . The aim of the present study is to test the hypothesis that there is no difference in the 1-year clinical outcome of therapy among groups of patients treated with conventional SRP performed over 2 to 3 weeks , or same-day FDIS , with or without adjunctive metronidazole . METHODS A total of 184 patients with moderate-to-severe periodontitis were r and omly allocated to one of four treatment groups : 1 ) FDIS+metronidazole ; 2 ) FDIS+placebo ; 3 ) SRP+metronidazole ; or 4 ) SRP+placebo . Recordings of plaque , bleeding on probing , probing depth ( PD ) , and clinical attachment level ( CAL ) were carried out in four sites per tooth at baseline and at 3 and 12 months after treatment . RESULTS No differences were observed in the mean CAL or PD values between the four experimental groups at baseline and 3 or 12 months post-treatment . All four groups displayed significant improvements in all parameters . However , using absence of pockets ≥5 mm as the criterion for treatment success , the two groups receiving adjunctive metronidazole performed significantly better than the two placebo groups . CONCLUSION Metronidazole had a significant , adjunctive effect in patients with a metronidazole-sensitive subgingival microbiota on the clinical parameters of CAL , PD , and absence of pockets ≥5 mm The aim of this study was to assess the clinical and microbiologic effects of the combination of amoxicillin and metronidazole therapy as an adjunct to mechanical treatment in the management of localized juvenile periodontitis . Twenty-five localized juvenile periodontitis ( LJP ) patients from a Brazilian population were r and omly allocated into an experimental group receiving mechanical treatment and antibiotics , and a control group receiving mechanical treatment and placebo . Clinical and radiographic assessment s , as well as microbiologic sampling for Actinobacillus actinomycetemcomitans , were performed at baseline and one year after the end of the treatment . At the termination of the study A. actinomycetemcomitans could be isolated from the oral cavity of all patients in the control group who harbored the bacterium at baseline and in 4 out of 8 patients in the experimental group . Both treatment modalities result ed in significant benefit on an individual basis . The experimental group , however , displayed better results than did the control group regarding gingival index ( GI ) , probing depth ( PD ) , clinical attachment level ( CAL ) , and radiographic analysis of crestal alveolar bone mass , but not with respect to plaque index ( PI ) . No serious adverse effects of the antibiotic treatment were observed in the present study PURPOSE To compare the 12-month radiographic outcomes following the use of azithromycin or placebo as adjuncts to non-surgical periodontal treatment of AgP. METHODS 17 aggressive periodontitis ( AgP ) subjects 13 - 26 years old were r and omly assigned to receive scaling and root planing ( SRP ) with systemic azithromycin or placebo . St and ardized radiographs were taken at baseline and 12 months postoperatively . Recall visits consisting of oral prophylaxis and oral hygiene instructions were performed during the 12 months . Digital image subtraction analysis and linear bone measurements were conducted by a blinded and calibrated examiner . Student t-tests were used for within and between-groups comparisons . ANCOVA was applied for between-group comparisons of changes in linear bone level adjusting for baseline values . RESULTS There were significant gains in linear bone levels in the azithromycin ( 0.55 + /- 0.10 mm ) and placebo ( 0.42 + /- 0.07 mm ) groups between the baseline and 12-month postoperative visits . There were also significant gains in bone density in the two treatment groups . No significant differences were observed between the two treatments in the amount of linear bone gain or bone density during the follow-up period . The use of azithromycin as an adjunct to SRP in the treatment of AgP did not result in significant radiographic bone level changes compared to placebo Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration . The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration . 20 subjects with adult periodontitis were r and omly assigned to test ( n = 10 ) and control ( n = 10 ) groups . The subjects received full mouth clinical assessment of pocket depth , attachment level , BOP , gingival redness , suppuration and plaque accumulation at baseline and 90 days . All subjects received full mouth SRP at baseline and , additionally , the test group received 100 mg doxycycline daily for 14 days . Subgingival plaque sample s were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days . In addition , plaque sample s were taken from 2 r and omly selected teeth at 3 , 7 and 14 days during and after antibiotic administration . Control subjects were sample d at the same time points . Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection . Significance of differences between test and control groups was determined at each time point using the Mann Whitney test . Significance of changes over time within test and control groups was determined using the Quade test . A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups . A significant decrease in the % of sites with gingival redness occurred in the test group . There were no significant differences in proportions between test and control groups for 33 of the test species at any time point . Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration . After cessation of doxycycline , Actinomyces sp. increased while Streptococcus sp. returned to baseline proportions . The relationship between these 2 genera appeared to be reciprocal ; an increase in one was accompanied by a decrease in the other . Periodontal pathogens including B. forsythus , P. gingivalis , T. denticola and A. actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage The aim of the study was to evaluate the adjunctive effect of systemic tetracycline ( 250 mg qds for 14 days ) in sequential root planing and surgical phases of treatment in a r and omised , double-blind controlled trial . 38 patients who were under 26 years of age , in good general health and with localised ( 15 test/15 control ) or generalised ( 4 test/4 control ) early onset periodontitis completed the non-surgical phase . Data were analysed by ANOVA using baseline covariates and transformations where appropriate . Improvements in probing depth , probing attachment level and bleeding on probing were significantly better in the group treated with adjunctive tetracycline , at 3 months post-treatment . 26 patients ( 13 test/13 control ) subsequently completed the surgical phase ( modified Widman flap surgery with adjunctive tetracycline or placebo as before ) and were re-examined at 6 months and 12 months . In the test group , 58 % of the originally affected teeth required surgery compared to 75 % in the control group . Surgery produced further reductions in mean probing depths but no further gains in probing attachment . There were no further statistically significant differences between test and control groups for any of the clinical measures , although the tetracycline group appeared to maintain an advantage . In conclusion , systemically administered tetracycline is a useful adjunct in the management of early onset periodontitis , particularly in non-surgical treatment BACKGROUND Previous studies showed that adjunctive subantimicrobial dose doxycycline ( SDD ; 20 mg , twice daily ) provides significant clinical benefits to scaling and root planing ( SRP ) . A modified-release SDD formulation containing 40 mg doxycycline ( SDD-40 ) to be taken once daily has been developed . The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis . METHODS A 9-month , double-masked , r and omized , placebo-controlled , multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis . Subjects were treated by SRP and r and omized to receive SDD-40 or placebo for 9 months with evaluations at 3 , 6 , and 9 months . RESULTS Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points . At month 9 , at sites with baseline probing depths ( PD ) > or = 6 mm , 72 % to 76 % of sites in the SDD-40 group demonstrated clinical ly significant PD reductions and clinical attachment level ( CAL ) gains > or = 2 mm compared to 56 % to 58 % of sites in the placebo group ( P < 0.0001 ) ; 48 % to 52 % of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32 % of sites in the placebo group ( P < 0.0001 ) . In moderate sites ( baseline PD 4 to 6 mm ) , adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL ( all time points : P < 0.05 ) , PD ( 3 months : P = 0.002 ; 6 and 9 months : P = 0.001 ) , and bleeding on probing ( BOP ) ( 3 months : P < 0.01 ; 6 months : P < 0.02 ; 9 months : P < 0.05 ) . In deep sites ( baseline PD > or = 7 mm ) , SDD-40 provided significant benefits over control for mean CAL ( 3 months : P < 0.05 ; 6 and 9 months : P < 0.01 ) , PD ( all time points : P < 0.001 ) , and BOP ( 3 months : P < 0.05 ; 6 months : not statistically significant ; 9 months : P < 0.05 ) . Compliance with study medication was high ( > 92 % ) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group . CONCLUSION SDD-40 used as an adjunct to SRP result ed in significantly greater clinical benefits than SRP alone in the treatment of periodontitis OBJECTIVES To evaluate and compare the effect of nonsurgical periodontal therapy in conjunction with 2 different antibacterial agents on clinical and immunological parameters in aggressive periodontitis ( AgP ) patients . METHOD AND MATERIAL S Thirty-one AgP patients underwent clinical examination that included plaque index ( PI ) , gingival index ( GI ) , probing pocket depth ( PPD ) , and clinical attachment level ( CAL ) . GCF ( gingival crevicular fluid ) sample s were collected and assayed for PGE(2 ) , IL-1beta , and TNFalpha . Nonsurgical periodontal therapy was performed . The patients received doxycycline ( doxy group ) or metronidazole plus amoxicillin ( am-met group ) . After completion of the mechanical phase of therapy , patients were seen biweekly for oral hygiene reinforcement . After 12 weeks , clinical measurements and GCF sampling were repeated . RESULTS The combined mechanical and antimicrobial therapy result ed in overall improvement in all clinical parameters ; mean PPD reduction of 0.74 + /- 0.1 mm and mean CAL gain 0.86 + /- 0.1 mm were both statistically significant ( P = .0001 ) . Marked reduction was observed for PGE2 and IL-1beta , but not TNFalpha . There was no significant difference between the 2 groups at baseline or final examination , except for PGE(2 ) at final examination : It was significantly lower for the doxy group ( 83.61 + /- 5.8 ng ) than for the am-met group ( 124.08 + /- 15.8 ng ) , P = .0202 . CONCLUSION Both treatment protocol s result ed in significant improvements in the clinical and immunological parameters . When combined mechanical and antimicrobial protocol is desired and microbial cultures are not available , the use of both antibiotic regimens is recommended ; the treatment of choice should be based on compliance , allergies , and potential side effects BACKGROUND / AIMS The aim of the study was to investigate the clinical and microbiological effects of azithromycin as an adjunct to the non-surgical treatment of periodontitis in adults . Azithromycin is an antibiotic which is taken up by phagocytes and is released over long periods in inflamed tissue but requires a total of only three doses of 500 mg to produce its therapeutic effect . METHOD 46 patients were treated in a double-blind placebo-controlled study with assessment s at weeks 0 , 1 , 2 , 3 , 6 , 10 and 22 . Throughout the trial measurements were made of plaque , gingival bleeding , calculus , probing pocket depths and bleeding on probing . Microbiological sampling was carried out from a selected pocket > or=6 mm at each visit . The regime employed consisted of OHI , scaling and root planing at weeks 0 , 1 and 2 with reinforcement of OHI and minimal scaling at weeks 6 , 10 and 22 . Patients were r and omly assigned to receive either azithromycin , ( A ) , or placebo capsules , ( C ) , 500 mg , 1x daily for 3 days at week 2 . 44 patients completed the study . Mean pocket depths were analysed using analysis of covariance in 3 groups with initial pocket depth values of 1 - 3 mm , 4 - 5 mm and > or=6 mm . RESULTS The results of the microbiology have been reported in a separate paper . The clinical data showed that by week 22 a lower % of pockets initially > 5 mm deep remained above that level in the 23 patients taking azithromycin ( A ) , than the 21 taking the placebo ( C ) , ( A , 5.6 % ; C , 23.3 % ) . Also at week 22 , for pockets initially 4 mm or more , the test group had fewer pockets > 3 mm deep ( A , 26.1 % ; C , 44.3 % ) , fewer failing to improve in probing depth ( A , 6.6 % ; C , 21.6 % ) and fewer continuing to bleed on probing ( A , 46.9 % ; C , 55.6 % ) when compared with the control group . Pocket depths initially 4 - 5 mm or 6 - 9 mm analysed by analysis of covariance showed lower mean pocket depths in the patients on azithromycin , at weeks 6 , 10 and 22 , ( pockets initially 4 - 5 mm , p<0.001 on all occasions , pockets initially 6 - 9 mm , p<0.001 , week 6 ; p < 0.003 , week 10 ; p<0.001 , week 22 ) . CONCLUSIONS Azithromycin may be a useful adjunct in the treatment of adult periodontitis , particularly where deep pockets are present A double blind between subject comparison of the effect of metronidazole and placebo tablets was completed over 22 weeks in 45 subjects with chronic periodontal disease ranging in severity from moderate ( PI = 2.0 - 3.9 ) to high ( PI = 4.0 - 6.0 ) . All subjects used a topically applied chlorhexidine gel for the first 10 weeks . Throughout the trial plaque , bleeding and calculus were assessed on the buccal , lingual , mesial and distal surfaces of teeth 16 , 21 , 24 , 36 , 41 and 44 and their supporting tissues . The pocket depths on the same 4 aspects of all teeth present were measured . The regime employed consisted of oral hygiene instruction ( OHI ) at the initial visit followed by scaling and further OHI at visits 1 and 2 weeks later . After the third visit 16 X 200 mg metronidazole or placebo tablets were issued with instructions to take 1 that evening and 3 per day at 5-h intervals for the next 5 days . 4 weeks later , scaling and OHI were carried out and the course of test or placebo tablets was repeated . The subjects returned for further scaling and OHI 4 weeks later and the chlorhexidine gel was withdrawn . Final assessment s were made 12 weeks later . The results showed that metronidazole had no effect on plaque levels and gingival bleeding beyond the effect of OHI , scaling and chlorhexidine gel . On the other h and , significantly greater reductions in pocket depths were achieved with the use of metronidazole . A surprising and interesting finding was that these reductions were apparent only in the subjects with severe periodontal disease ( PI = 4.0 - 6.0 ) The aim of the present study was to investigate the clinical and microbiological effects of initial periodontal therapy in conjunction with systemic amoxicillin plus clavulanic acid in adult periodontitis patients using a double-blind , parallel-group , and placebo-controlled protocol . 21 patients with a clinical diagnosis of generalised adult periodontitis were recruited . Clinical measurements and microbiological assessment s were carried out at baseline , 3 , and 12 months post-treatment . Approximately 6 weeks after initial periodontal treatment ( 3 - 6 h ) , patients were r and omly assigned to receive coded study medication of 500 mg amoxicillin plus 125 mg clavulanic acid ( Augmentin ) or placebo , every 8 h for 10 days . Patients returned for follow-up visits 3 , 6 , 9 , and 12 months after completion of the medication . The mean plaque index ( PI ) at baseline was 1.1 for placebo group and 0.9 for the test group . At 3 months , the PI had dropped to 0.3 in both groups , and was maintained during the rest of the study . The changes in bleeding on probing ( BOP ) and gingival index ( GI ) in the course of the study were similar in both groups . The mean whole mouth probing pocket depth ( PPD ) in the placebo group was 3.8 mm at baseline and 3.9 mm in the test group . A mean reduction of 1.0 mm in the placebo group and 0.9 mm in the test group was observed during the first 3 months . No further reduction in PPD was noticed during the study period in either group . There was no statistically significant difference in the PPD reduction between the 2 groups . The change in clinical attachment level ( CAL ) from baseline to 3 months amounted to 0.5 mm in both groups . Between 3 and 12 months , the CAL changed in neither group . In both groups , treatment result ed in a decrease in the number of spirochetes and motile rods in positive patients , but no significant differences between either group were noted in any of the dark field microscopy observations . At baseline , 1 patient in the placebo group and 2 patients in the test group were culture positive for Actinobacillus actinomycetemcomitans ( Aa ) . After therapy , Aa was not detectable in the placebo group and 1 patient remained positive in the test group . In the placebo group , the number of patients positive for Porphyromonas gingivalis ( Pg ) decreased from 7 to 2 after therapy . In the test group , the 4 patients positive for Pg at baseline remained positive after therapy . In both groups , all subjects were positive for Prevotella intermedia ( Pi ) and Fusobacterium nucleatum ( Fn ) at baseline . At 12 months , all subjects had detectable subgingival Fn . 9 out of the 11 placebo and 8 of the 10 test patients remained positive for Pi . There were no differences in detection frequency of Peptostreptococcus micros ( Pm ) and Bacteroides forsythus ( Bf ) in both groups between baseline , 3 , and 12 months post-treatment . The findings demonstrated that , in comparison to placebo , systemic amoxicillin plus clavulanic acid provided no additional clinical and microbiological effects in the treatment of adult periodontitis patients BACKGROUND In a previous study , subantimicrobial dose doxycycline ( SDD ) significantly improved clinical parameters associated with periodontal health in patients with adult periodontitis ( AP ) when used as an adjunct to a maintenance schedule of supragingival scaling and dental prophylaxis . In this double-blind , placebo-controlled , parallel-group , multicenter study , the efficacy and safety of SDD were evaluated in conjunction with scaling and root planing ( SRP ) in patients with AP . METHODS Patients ( n = 190 ) received SRP at the baseline visit and were r and omized to receive either SDD 20 mg bid or placebo bid for 9 months . Efficacy parameters included the per-patient mean changes in clinical attachment level ( CAL ) and probing depth ( PD ) from baseline , the per-patient percentages of tooth sites with attachment loss ( AL ) > or = 2 mm and > or = 3 mm from baseline , and the per-patient percentage of tooth sites with bleeding on probing . Prior to analysis , tooth sites were stratified by the degree of disease severity evident at baseline RESULTS In tooth sites with mild to moderate disease and severe disease ( n = 183 , intent-to-treat population ) , improvements in CAL and PD were significantly greater with adjunctive SDD than with adjunctive placebo at 3 , 6 , and 9 months ( all P < 0.05 ) . In tooth sites with severe disease , the per-patient percentage of sites with AL > or = 2 mm from baseline to month 9 was significantly lower with adjunctive SDD than with adjunctive placebo ( P<0.05 ) . Improvements in clinical outcomes occurred without detrimental shifts in the normal periodontal flora or the acquisition of doxycycline resistance or multiantibiotic resistance . SDD was well tolerated , with a low incidence of discontinuations due to adverse events . CONCLUSIONS The adjunctive use of SDD with SRP is more effective than SRP alone and may represent a new approach in the long-term management of AP AIM To evaluate the clinical effects of the adjunctive use of metronidazole ( MTZ ) and amoxicillin ( AMX ) in the treatment of generalized aggressive periodontitis ( GAgP ) . METHODS Thirty subjects were r and omly assigned to receive scaling and root planing ( SRP ) alone or combined with MTZ ( 400 mg/TID ) and AMX ( 500 mg/TID ) for 14 days . Subjects were clinical ly monitored at baseline , 6 months and 1 year post-therapies . RESULTS Both therapies led to a statistically significant improvement in all clinical parameters at 1 year post-therapy ( p < 0.05 ) . Subjects receiving MTZ plus AMX exhibited the deepest reductions in mean probing depth ( PD ) and gain in clinical attachment between baseline and 1 year post-therapy in the full-mouth analysis and in initially intermediate ( PD 4 - 6 mm ) and deep ( PD ≥ 7 mm ) sites ( p < 0.01 ) . In addition , the antibiotic group presented lower mean number of residual sites with PD ≥ 5 or 6 mm as well as fewer subjects still presenting nine or more sites with PD ≥ 5 mm or three or more sites with PD ≥ 6 mm at the end of the study period . CONCLUSION The non-surgical treatment of GAgP is markedly improved by the adjunctive use of MTZ+AMX , up to 1 year post-treatment A considerable amount of circumstantial evidence indicates that most forms of periodontitis are due to the presence or dominance of a finite number of bacterial species in the subgingival plaque . Almost all of the putative pathogens are anaerobic species , indicating that most forms of periodontitis could be diagnosed as anaerobic infections . In this double-blind investigation , patients with elevated proportions or levels of spirochetes in 2 or more plaque sample s , i.e. , 60 % spirochetes , were r and omly assigned to receive either metronidazole , 250 mg 3 x a day for 1 week , or placebo ( positive-control ) after the completion of all debridement procedures . When the patients were re-examined 4 to 6 weeks later , the patients in the metronidazole group ( n = 15 ) exhibited a highly significant ( p less than 0.01 ) reduction in probing depth and apparent gain in attachment levels relative to the patients ( n = 18 ) in the positive-control group about those teeth that initially had probing depths of 4 to 6 mm . This pattern was also observed about teeth that initially had probing depths greater than or equal to 7 mm . This reduction in probing depths and apparent gain in attachment was associated with a significant reduction in the need for periodontal surgery in the metronidazole-treated patients ( difference 8.4 teeth per patient ) compared to the positive-control patients ( 2.6 teeth per patient ) . These clinical improvements in the metronidazole group were associated with significantly lower proportions of spirochetes , selenomonads , motile rods , and P. intermedius , and a significantly higher proportion of cocci in the plaques . These findings indicate that systemic metronidazole , when given after all the root surface debridement is completed , leads to additional treatment benefits , including a reduced need for surgery , beyond that which can be achieved by debridement alone BACKGROUND The aim of this study is to evaluate the effects of metronidazole-amoxicillin combination on clinical and microbiologic parameters in patients with generalized aggressive periodontitis . METHODS Twenty-eight patients were r and omly included . The test group ( n = 12 ) received amoxicillin-metronidazole combination and scaling and root planing ; the control group ( n = 16 ) received scaling and root planing alone . In addition to the clinical examinations , subgingival plaque sample s were analyzed for total cultivable bacteria and the presence of Porphyromonas gingivalis , Tannerella forsythia ( previously T. forsythensis ) , Treponema denticola , Prevotella intermedia , Prevotella nigrescens , Prevotella pallens , and Aggregatibacter actinomycetemcomitans ( previously Actinobacillus actinomycetemcomitans ) using polymerase chain reaction . RESULTS All clinical parameters improved significantly compared to baseline ( P < 0.05 ) in both groups . There was a statistically significant reduction of pockets and clinical attachment gain in the combined group compared to the control group ( P < 0.05 ) . Total counts of bacteria also decreased significantly at 3 and 6 months in both groups ( P < 0.05 ) . T. denticola and T. forsythia were the most prevalent bacteria throughout the study . T. denticola showed a continuous decrease over 6 months in the test group , whereas no change was seen in the control group beyond 3 months . P. gingivalis decreased significantly at 3 months ( P < 0.05 ) , whereas T. forsythia was the only pathogen decreased below detection limits by the combination therapy with a significant difference compared to the control group ( P < 0.05 ) . CONCLUSIONS The results from this study suggest that combined amoxicillin and metronidazole use as an adjunct to scaling and root planing leads to better clinical healing compared to mechanical treatment alone . The polypharmaceutical approach used results in a significant and substantial decrease in T. forsythia and prevents its recolonization for 6 months , suggesting that T. forsythia may determine the long-term stability of periodontal treatment outcomes OBJECTIVE To compare the clinical and microbiological effects of three protocol s for nonsurgical periodontal therapy , including full-mouth scaling and root planing plus systemic antibiotics , on the treatment of chronic periodontitis patients . METHODS Twenty-nine patients diagnosed with moderate to severe chronic periodontitis , selected according to specific criteria , were r and omly assigned to one of three treatment groups : quadrant scaling , full-mouth scaling , and full-mouth scaling supplemented by systemic antibiotics . Antibiotic selection was based on the results of individual susceptibility testing . Oral hygiene instructions and reinforcement were given during the study . All patients received a clinical periodontal and microbiological examination at baseline and at reexamination , 4 - 6 weeks after therapy . Means and st and ard deviations were calculated and differences between groups were analyzed via the Kruskal-Wallis test , p < 0.05 . RESULTS The mean age of the study sample was 49.1 + 11.6 years old , and there were 17 men and 12 women . Patients treated with antibiotics showed antimicrobial susceptibility for amoxicillin and doxycycline . All study groups showed a similar significant improvement in periodontal parameters . Plaque scores were reduced in a range of 29.0 % to 42.6 % . Bleeding on probing was reduced by 34.8 % to 55.0 % ; the reduction for the full-mouth scaling group was larger . Mean reduction in pocket depth was 1.2 to 1.3 mm in all groups . Mean bacterial counts were reduced in the groups receiving full-mouth treatment , but not in the quadrant treatment group . CONCLUSION The three protocol s for non-surgical periodontal treatment demonstrated a similar positive effect on clinical parameters ; however , only full-mouth treatment groups showed a reduction in anaerobic microbial counts at re-examination UNLABELLED Emingil G , Han B , Özdemir G , Tervahartiala T , Vural C , Atilla G , Baylas H , Sorsa T. The effect of azithromycin , as an adjunct to nonsurgical periodontal treatment , on microbiological parameters and gingival crevicular fluid biomarkers in generalized aggressive periodontitis . J Periodont Res 2012 ; 47 : 729 - 739 . © 2012 John Wiley & Sons A/S Background and Objective : To study the effectiveness of azithromycin in combination with nonsurgical periodontal therapy on clinical and microbiological parameters , and on the MMP-8 and TIMP-1 levels in gingival crevicular fluid , over a 6-mo time-period in patients with generalized aggressive periodontitis . MATERIAL AND METHODS Thirty-two patients with generalized aggressive periodontitis were included in this r and omized , double-blind , placebo-controlled , parallel-arm study . They were r and omly assigned to azithromycin or placebo groups ( 500 mg once daily for 3 d ) . Probing depth , clinical attachment levels , presence of bleeding on probing and plaque were recorded . Gingival crevicular fluid sample s were obtained from one single-rooted tooth , while microbiological sample s were obtained from two single-rooted teeth , all with a probing depth of ≥ 6 mm . Microbiological parameters were analyzed by quantitative real-time PCR for Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Tannerella forsythia , Fusobacterium nucleatum , Prevotella intermedia and total bacteria . Gingival crevicular fluid biomarkers were determined by immunofluorometric assay and ELISA . RESULTS All clinical parameters improved , and microbiological parameters and gingival crevicular fluid MMP-8 levels significantly decreased , over the 6-mo period ( p < 0.05 ) ; both groups demonstrated similar improvements . The azithromycin group presented a higher percentage of deep pockets resolved ( probing depth reduction of ≥ 3 mm from baseline ) compared with the placebo group at 1 mo ( p < 0.05 ) . CONCLUSION Adjunctive azithromycin therapy provides no additional benefit over nonsurgical periodontal treatment on clinical parameters , microbiological parameters and gingival crevicular fluid biochemical markers investigated in patients with generalized aggressive periodontitis The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Objective : To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole . Design : A single blind r and omised clinical trial of 90 subjects , stratified for periodontitis disease severity and smoking status , divided into three treatment groups : 1 . Subgingival scaling using ultrasonic scalers and local anaesthesia ; 2 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole ( 200 mg tds ) ; 3 . Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25 % metronidazole gel one week apart in all sites with probing depths more than 4 mm . Evaluations were made before treatment , and 8 weeks and 24 weeks post treatment . Main outcome measures : Probing depths , probing attachment levels and bleeding on probing were measured using a Florida probe . Bacterial morphotypes were evaluated with darkfield microscopy . Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance . Results : 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter . Mean probing depths were reduced following treatment by greater than 1.6 mm ( Group 1 = 1.68 mm , Group 2 = 1.62 mm , Group 3 = 1.74 mm at six months post treatment ) but no significant differences were detected between treatment groups at any time point . Similarly , no significant differences were detectable between treatments for changes in mean probing attachment levels , bleeding on probing , plaque scores or proportions of bacterial morphotypes . Conclusions : This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of AIM To assess the effect of systemic azithromycin as a supplement to scaling and root planing ( SRP ) in the treatment of aggressive periodontitis ( AgP ) . MATERIAL AND METHODS Twenty-four individuals ( 13 - 26 years old ) underwent a plaque control program , and then were treated with SRP . Subjects were assigned r and omly into two groups ; the test group used 500 mg azithromycin once a day for 3 days , whereas the control group used a placebo . Clinical variables were assessed at baseline , 3 , 6 , 9 , and 12 months . The periodontal status at baseline and 12 months was compared using the Wald test , and adjusting for the effect of clustering of teeth within subjects . RESULTS There were no significant differences in visible plaque , gingival bleeding , and supragingival calculus between groups throughout the study . Periodontal probing depth ( PPD ) and clinical attachment level improved significantly from baseline to 12 months in both groups , with the test group showing significantly more reduction in mean PPD compared with controls ( 2.88 mm versus 1.85 mm , respectively , p=0.025 ) . Subjects administering azithromycin showed a higher percentage of teeth with attachment gain > or=1 mm ( 81.34 versus 63.63 , p=0.037 ) , whereas the controls had higher percentage of teeth with attachment loss > or=1 mm ( 11.57 versus 2.24 , p=0.015 ) . CONCLUSIONS The adjunctive use of azithromycin has the potential to improve periodontal health of young patients with AIM To evaluate the effects of the adjunctive use of metronidazole ( MTZ ) or MTZ+amoxicillin ( AMX ) in the treatment of generalized chronic periodontitis ( ChP ) . MATERIAL S AND METHODS Fifty-one subjects ( n=17/group ) were r and omly assigned to receive scaling and root planing ( SRP ) only or combined with MTZ ( 400 mg t.i.d . ) or MTZ+AMX ( 500 mg t.i.d . ) for 14 days . Clinical and microbiological examinations were performed at baseline and 3 months post-SRP . Nine plaque sample s/subject were analysed by checkerboard DNA-DNA hybridization for 40 bacterial species . RESULTS Subjects receiving MTZ+AMX exhibited a greater mean gain of clinical attachment , reduction in probing depth ( PD ) in intermediate and deep sites and a lower percentage of sites with PD5 mm at 3 months , in comparison with those treated with SRP only ( p<0.05 ) . The major benefit from the adjunctive use of MTZ was a greater reduction in PD in deep sites . SRP+MTZ+AMX was the only treatment that significantly reduced the levels and proportions of all red complex pathogens and elicited a significantly greater beneficial change in the microbial profile in comparison with SRP only . CONCLUSION The adjunctive use of MTZ+AMX offers short-term clinical and microbiological benefits , over SRP alone , in the treatment of non-smokers subjects with generalized ChP. The added benefits of MTZ were less evident OBJECTIVE To compare the treatment outcome of scaling and root planing ( SRP ) in combination with systemic antibiotics , local antibiotic therapy and /or periodontal surgery . MATERIAL AND METHODS One hundred and eighty-seven patients were assigned to eight groups treated by SRP plus none , one , two or three adjunctive treatments and monitored for 24 months in a r and omized controlled clinical trial using a 2 × 2 × 2 factorial design . Systemic amoxicillin + metronidazole ( SMA ) , local tetracycline delivery ( LTC ) and periodontal surgery ( SURG ) were evaluated as adjuncts . Changes in clinical attachment level ( CAL ) and probing pocket depth ( PPD ) were statistically evaluated by ancova of main effects . RESULTS Effects of adjunctive therapy to SRP were minimal at 3 months . Between 3 and 6 months PPD reduction occurred particularly in patients receiving periodontal surgery . After 6 months , both CAL gain and PPD reduction reached a plateau that was maintained at 24 months in all groups . The 24-month CAL gain was improved by SMA ( 0.50 mm ) while PPD was reduced by SMA ( 0.51 mm ) and SURG ( 0.36 mm ) . Smoking reduced CAL gain and PPD reduction . CONCLUSION Patients receiving adjunctive therapies generally exhibited improved CAL gain and /or PPD reduction when compared with the outcome of SRP alone . Only additive , not synergistic effects of the various adjunctive therapies were observed BACKGROUND It has been suggested that use of systemic antibiotics should be limited to patients with specific microbiologic profiles . The main purpose of the present analysis was to study whether microbiologic testing before therapy was of value in predicting which patients would specifically benefit from adjunctive amoxicillin and metronidazole , given in the context of full-mouth scaling and root planing ( SRP ) within 48 hours . METHODS This was a 6-month , single-center , double-masked , placebo-controlled , r and omized longitudinal study . Fifty-one patients received full-mouth periodontal debridement , performed within 48 hours ; then , 25 subjects received metronidazole , 500 mg , and amoxicillin , 375 mg , three times a day for 7 days , and 26 received a placebo ( control group ) . Pooled microbiologic sample s were taken from the deepest pocket at baseline in each quadrant before and 6 months after treatment . Six periodontal pathogens were quantified by real-time polymerase chain reaction . RESULTS Forty-seven patients were followed for 6 months . After treatment , test subjects had a substantially lower mean number of persisting sites with probing depth > 4 mm and bleeding on probing than did control subjects ( 0.4 versus 3.0 ; P = 0.005 ; month 6 ) . Aggregatibacter actinomycetemcomitans ( previously Actinobacillus actinomycetemcomitans ) could not be detected in the antibiotic group after treatment . However , in the placebo group , three of six subjects positive for A. actinomycetemcomitans continued to be positive . Lower frequencies were also noted in the test group for Porphyromonas gingivalis ( P = 0.013 ) and Tannerella forsythia ( previously T. forsythensis ) ( P = 0.007 ) . However , even subjects testing negative for A. actinomycetemcomitans at baseline had a significantly better primary clinical outcome if they received the active drugs . The presence of six putative periodontal pathogens ( A. actinomycetemcomitans , Fusobacterium nucleatum spp . , P. gingivalis , Prevotella intermedia , Treponema denticola , and T. forsythia ) quantified prior to therapy was not correlated with the outcome of full-mouth SRP with or without amoxicillin and metronidazole . CONCLUSION Excellent clinical results in the antibiotics group were obtained regardless of the presence or absence of six classic periodontal periopathogens prior to treatment |
12,556 | 26,226,131 | The quality of the included studies was largely poor and , with a few exceptions , these comprised of mainly small , inadequately reported studies .When comparing treatment with a single antibiotic to a combined antibiotic regimen , those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function , but with very low quality evidence .
When limited to the four placebo-controlled studies ( n = 214 ) , no difference was observed , again with very low quality evidence .
With regard to the review 's remaining primary outcomes , there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life .
There were no effects on the secondary outcomes weight or adverse effects .
When comparing specific antibiotic combinations there were no significant differences between groups on any measure .
In the comparisons between intravenous and nebulised antibiotic or oral antibiotic ( low quality evidence ) , there were no significant differences between groups on any measure .
No specific antibiotic combination can be considered to be superior to any other , and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes . | BACKGROUND Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection , often with unusual bacteria .
Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms ( pulmonary exacerbations ) ; however , recently the assumption that exacerbations are due to increases in bacterial burden has been question ed .
OBJECTIVES To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes . | ABSTRACT The present multicenter , r and omized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis . Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime ( 200 mg/kg of body weight/day ) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion . The primary endpoint was the variation in the forced expiratory volume in 1 s ( FEV1 ) during the course of antibiotic treatment . Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment . The improvement in FEV1 at the end of therapy was not statistically different between the two treatment procedures ( + 7.6 % after continuous infusion and + 5.5 % after short infusions ) but was better after continuous ceftazidime treatment in patients harboring resistant isolates ( P < 0.05 ) . The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime ( P = 0.04 ) . The mean serum ceftazidime concentration during the continuous infusion was 56.2 ± 23.2 μg/ml ; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 μg/ml , respectively . The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens . Quality -of-life scores were similar whatever the treatment procedure , but 82 % of the patients preferred the continuous-infusion regimen . Adverse events were not significantly different between the two regimens . In conclusion , the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole , but it gave better results in patients harboring resistant isolates of P. aeruginosa The steady state pharmacokinetic properties of ciprofloxacin and ofloxacin were compared in cystic fibrosis patients . In a cross-over study eighteen adult patients with chronic Pseudomonas aeruginosa lung infection were given either oral ciprofloxacin 750 mg bid or oral ofloxacin 400 mg bid for two weeks . Three months later the alternative treatment was given . Concentrations were determined by a microbiological assay . Mean serum concentrations of ofloxacin ( peak 5.9 mg/l ) were higher than for ciprofloxacin ( peak 4.0 mg/l ) . The time to reach maximal concentrations did not differ . The apparent total body clearance was significantly greater for ciprofloxacin , but renal clearances were similar . Relative to ofloxacin ciprofloxacin had a significantly shorter serum elimination half-life ( 3.4 vs. 6.4 h ) , showed less penetration into sputum ( 18 % vs. 79 % ) and a lesser amount was recovered in urine ( 21 % vs. 71 % up to 12 h after dosing ) . No correlation was found between any pharmacokinetic parameter and change in pulmonary function BACKGROUND Intravenous tobramycin ( three-times daily ) is widely used for pulmonary exacerbations in patients with cystic fibrosis who have chronic Pseudomonas aeruginosa infection . We undertook a double-blind , r and omised controlled trial to assess the safety and efficacy of once versus three-times daily tobramycin in these patients . METHODS 244 patients from 21 cystic-fibrosis centres in the UK were r and omly assigned to once or three-times daily tobramycin ( with ceftazidime ) for 14 days . Treatment was given as 30-min infusions of tobramycin in 0.9 % saline . Primary outcome measure was change in forced expiratory volume in 1s ( FEV1 ) , over the 14 days of treatment , expressed as a percentage of the predicted normal value for age , sex , and height . We also measured the change in FEV1 expressed as a percentage of baseline . Secondary outcomes included change in serum creatinine . The study was powered for equivalence , and primary analysis was per protocol . FINDINGS 219 patients ( 107 once daily , 112 three-times daily ) completed the study per protocol . None was lost to follow-up , although 20 discontinued intervention . Of 122 patients assigned to once daily treatment , three did not receive the study regimen . The mean change in FEV1 ( % predicted ) over 14 days was similar on the two regimens ( 10.4 % [ once daily ] vs 10.0 % [ three-times daily ] ; adjusted mean difference 0.4 % [ 95 % CI -3.3 to 4.1 ] ) . Mean% change in FEV1 from baseline was also similar in both treatments ( 21.9 % vs 22.1 % ; -0.1 % [ -8.0 to 7.9 ] ) . There was no significant difference in% change in creatinine from baseline ( -1.5 % [ once daily ] vs 1.7 % [ three-times daily ] ) . However , in children , once daily treatment was significantly less nephrotoxic than was thrice daily ( mean% change in creatine -4.5 % [ once daily ] vs 3.7 % [ thrice daily ] ; adjusted mean difference -8.0 % , 95 % CI -15.7 to -0.4 ) . No patients developed hearing loss during the study , although two reported acute dizziness and were withdrawn from the study . INTERPRETATION Intravenous tobramycin has equal efficacy if given once or three-times daily ( with ceftazidime ) for pulmonary exacerbations of cystic fibrosis . The once daily regimen might be less nephrotoxic in children Purpose : We hypothesized that a single intravenous ( iv ) tobramycine infusion ( treatment B ) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa ( PA ) infection in cystic fibrosis ( CF ) as the commonly performed treatment of three doses ( treatment A ) . Toxicity and practicability may even be improved in the single-dose regimen . Methods : This was a r and omized crossover study comparing outcome after 14 and 35 days . The primary end-point was a decrease in the leukocyte count , and the secondary end-points were clinical and lung function parameters , Pseudomonas quantification in sputum , and inflammation markers ( immunoglobulin G , C-reactive protein ) in serum . 30 patients ( 20 female , mean age 11.2 years , mean age range 1.7–18.1 years ) received elective 14-day courses of treatments A or B , followed by the alternative treatment after a mean interval of 37 ( ± 21 ) weeks . Results : With the exception of PA density , there were no significant differences between both treatment strategies after 14 days of treatment . After 35 days of treatment , there were no significant changes in the leukocyte count and inflammation markers . Both treatment strategies reduced the bacterial load in the airways , as reflected by a decreased PA density in sputum . Nephrotoxicity was equal in both groups , with a transient slight elevation of urinary N-acetyl-β-glucosaminidase concentrations . St and ard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy . Mean body weight increased during the study period by 0.5 kg . Forced expiratory volume increased by approximately 5 % of the predicted volume , forced vital capacity increased by 2 % of predicted capacity , and forced mid expiratory flow rate increased by 7 % ( A ) or 4 % ( B ) of the predicted normal value , although these changes were not statistically significant . Conclusion : We conclude that tobramycin given in a daily single dose ( with the advantage of being more practical in a home environment ) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinical ly stable patients with CF Ceftazidime was administered to 41 patients with serious infections caused by Pseudomonas aeruginosa ( 24 cases ) and other bacteria ( 17 cases ) . The clinical response rate of pseudomonas infections ( 88 % ) was similar to that of other bacteria ( 94 % ) with microbiological eradication of 83 % of initial pseudomonas isolates compared to 82 % of non-pseudomonas strains . The development of resistance to ceftazidime during therapy was observed in 3 cases ( Enterobacter agglomerans , Enterobacter cloacae , and Ps . aeruginosa ) , and superinfection by a resistant Enterobacter agglomerans occurred in one case . Adverse reactions of clinical significance included two cases of leukopenia and one case each of azotaemia , diarrhoea ( Clostridium difficile toxin positive ) , and rash A r and omised controlled open comparison of azlocillin and gentamicin versus carbenicillin and gentamicin was carried out in patients with cystic fibrosis who were chronically infected with Pseudomonas aeruginosa . The clinical response was assessed by measurements of pulmonary function and of the patients ' feelings of wellbeing scored on a visual analogue scale . The sputum penetration of the antibiotics used was also studied . The two groups of 10 patients were similar in terms of age , sex , and pulmonary function at entry to the trial . Both regimens produced significant improvement in pulmonary function over 10 days . The mean FEV1 in the azlocillin group increased from 1206 to 1760 ml ( p less than 0.001 ) . In the carbenicillin group the mean FEV1 increased from 1116 to 1619 ml ( p less than 0.001 ) . Significant improvements in peak expiratory flow rate , forced vital capacity , and score on the visual analogue scale were also seen but there was no significant difference between the antibiotic regimens . Despite high serum concentrations the sputum penetration of the antibiotics was poor Background Newborn screening allows novel treatments for cystic fibrosis ( CF ) to be trialled in early childhood before irreversible lung injury occurs . As respiratory exacerbations are a potential trial outcome variable , we determined their rate , duration and clinical features in preschool children with CF ; and whether they were associated with growth , lung structure and function at age 5 years . Methods Respiratory exacerbations were recorded prospect ively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years , when all participants underwent clinical assessment , chest CT scans and spirometry . Results 168 children ( 88 boys ) experienced 2080 exacerbations , at an average rate of 3.66 exacerbations per person-year ; 80.1 % were community managed and 19.9 % required hospital admission . There was an average increase in exacerbation rate of 9 % ( 95 % CI 4 % to 14 % ; p<0.001 ) per year of age . Exacerbation rate differed by site ( p<0.001 ) and was 26 % lower ( 95 % CI 12 % to 38 % ) in children receiving 12 months of prophylactic antibiotics . The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores . Ever having a hospital-managed exacerbation was associated with bronchiectasis ( OR 2.67 , 95 % CI 1.13 to 6.31 ) in chest CT scans , and lower weight z scores at 5 years of age ( coefficient −0.39 , 95 % CI −0.74 to −0.05 ) . Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group BACKGROUND A previous retrospective study suggested that a policy of regular anti-pseudomonal antibiotic treatment improved pulmonary function and increased survival in patients with cystic fibrosis chronically infected with Pseudomonas species . The results of a prospect i ve multicentre study to compare the effects on pulmonary function and mortality of three monthly elective anti-pseudomonal antibiotic treatment with conventional symptomatic treatment are reported . METHODS Sixty patients with cystic fibrosis , chronically infected with P aeruginosa , were r and omised to the two treatment arms ( elective or symptomatic ) and followed clinical ly at yearly review s. The major end points were changes in forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) . Survival was a secondary end point . RESULTS Patients in the symptomatic group received a mean of three antibiotic treatments each year and those in the elective group received four antibiotic treatments during each year of the study . No significant differences in FEV1 and FVC were found between the two groups after three years . There was a statistically non-significant higher rate of deaths in the elective group ( n = 4 ) , three of which were associated withB cepacia infection , compared with the symptomatic group ( n = 0 ) . CONCLUSIONS This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonasspecies Piperacillin was evaluated as an antipseudomonas antibiotic in a double-blind controlled trial involving 18 pulmonary exacerbations of cystic fibrosis . St and ard antibiotic treatment ( flucloxacillin plus tobramycin ) was compared with st and ard treatment plus intravenous piperacillin administered according to two regimens . No added benefit from piperacillin was demonstrable on the basis of improvement in symptoms , physical signs , weight gain , pulmonary function tests , radiologic signs , or sputum Pseudomonas bacterial counts . Some patients experienced sensitivity reactions to piperacillin . In vitro , piperacillin was a potent antibiotic against all beta-lactamase-producing mucoid strains of Pseudomonas aeruginosa ; however , in spite of the fact that adequate serum antibiotic concentrations were achieved , sputum bacterial counts did not correlate with either the clinical status or the use of piperacillin therapy In this study , we set out to determine if home intravenous ( i.v . ) antibiotic therapy in adult patients with cystic fibrosis ( CF ) is a feasible , effective and less costly alternative to hospitalization , and to assess the impact of home therapy on quality of life . The study was a prospect i ve , r and omized , two-factor mixed design involving adults presenting with respiratory exacerbations of CF . Patients were r and omized such that they were discharged home after 2 - 4 days , or remained in hospital . Seventeen patients had 31 admissions ( 13 home and 18 hospital ) . Following 10 days of therapy , there were no significant differences between home or hospital arms with respect to body weight , 12 minute walking distance , sputum weight , pulse oximetry , or improvement in lung function ( forced expiratory volume in one second ( FEV1 ) , or forced vital capacity ( FVC ) ) . Patients who remained in hospital were less fatigued and noted a greater degree of mastery . Patients discharged early noted less disruption to their family life , personal life and sleeping pattern . The total cost for the home therapy arm was approximately half that of the hospital therapy arm . Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible , cost-effective alternative to receiving therapy in hospital . Although there was no clinical compromise associated with home therapy , there were advantages and disadvantages in terms of quality of life METHODS 14 patients with cystic fibrosis and chronic pulmonary pseudomonas infection received four courses of two-week intravenous antibiotic therapy at home and during hospitalisation over an 18-month period . Following a controlled , intra-individual cross-over design , two courses of home therapy were followed by two courses of hospital treatment or vice versa . Parameters for inflammation , lung function , and body mass index were obtained at the beginning and end of each intravenous antibiotic therapy . Health-related quality of life , i.e. physical , emotional , social and functional components as well as happiness and medical care , was assessed at the end of each course . RESULTS There was a trend towards better reduction of infection ( p = 0.20 for leukocyte reduction ) and improvement of lung function ( p = 0.20 for FEV1 improvement ) with hospital intravenous antibiotic therapy , although the differences did not attain statistical significance . Quality of life during therapy was significantly higher with home therapy regarding social ( p < 0.01 ) , functional and emotional subscales and happiness ( all p < 0.05 ) . The necessity for professional help and support from family and /or partner was emphasised . Individual answers showed that home therapy has the advantage of self-determination and continuity of daily life . Parents and partners felt impaired by day and night intravenous therapy at home . CONCLUSION From our data we conclude that home intravenous antibiotic therapy is a useful option for a selected subgroup of patients with cystic fibrosis , but professional support and family aid is important to gain an effect similar to hospital treatment The clinical efficacy and safety of ciprofloxacin and ofloxacin were compared in a prospect i ve , r and omized double blind , placebo combined cross-over study in 26 adult cystic fibrosis patients with chronic broncho-pulmonary Pseudomonas aeruginosa infection . Active treatment consisted of ciprofloxacin 750 mg orally twice daily or ofloxacin 400 mg orally twice daily ; both treatments were given for 14 days , with three months between treatment periods ; 21 patients completed both treatment periods . Treatment with both ciprofloxacin and ofloxacin was associated with a good clinical response as judged by clinical score , lung function tests and inflammatory parameters ; no difference between ciprofloxacin and ofloxacin was found . Adverse reactions were seen in nine of 24 patients who received ciprofloxacin and in six of 23 who received ofloxacin . The majority were dyspeptic reactions or photosensitivity . No serious adverse reactions occurred . Three cases of treatment failure were found , one of which was associated with development of resistant P. aeruginosa during ofloxacin treatment . The mean MIC of both drugs increased during treatment but returned to pretreatment values within three months . Ciprofloxacin and ofloxacin seem to be valuable agents for intermittent treatment of chronic P. aeruginosa lung infection in adult cystic fibrosis patients In order to evaluate the clinical efficacy and safety of oral ciprofloxacin in the treatment of acute pulmonary exacerbations of cystic fibrosis and trace the possible development of resistance over time , three trials were conducted . In an open-label , uncontrolled trial , 25 courses of ciprofloxacin were administered to 16 patients . Efficacy and safety were assessed based on changes in short-term clinical scores , white blood cell counts , Pseudomonas aeruginosa counts in sputum , pulmonary function tests , and st and ard serum chemistries and urinalysis that were performed before therapy , weekly during therapy , at the end of therapy , and at a seven-day follow-up visit after therapy . In an open-label , r and omized , controlled study , the efficacy and tolerance of oral ciprofloxacin were compared with those of intravenous tobramycin and azlocillin . In another study , the rate of susceptibility of P. aeruginosa isolated from cystic fibrosis patients during more than two years of clinical use was determined . In the uncontrolled trial , ciprofloxacin therapy was associated with clinical improvement in most cases with changes in short-term clinical score and forced expiratory volume in one second being statistically significant ( p less than 0.05 ) . Twenty-five patients were entered in the controlled trial with 12 patients in each treatment group being evaluable . The groups were comparable based on admitting demographic and disease characteristics , and no differences in therapeutic response or side effects were noted between the two treatments ( p greater than 0.5 ) . Bacterial susceptibility to ciprofloxacin has remained relatively stable over time . Based on these results as well as those from similar evaluations , ciprofloxacin appears to be efficacious in the treatment of acute pulmonary exacerbations in adults with cystic fibrosis , producing responses similar to those observed with st and ard intravenous antibiotic therapy Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were r and omized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg ( body weight ) per dose administered intravenously every 8 h for 14 days . Three patients were dropped from the study within 4 days of enrollment for reasons unrelated to drug administration . The total daily dose of ceftazidime administered was restricted by protocol design and was independent of the body weight of the patient . Thus , for datum analysis , patients were separated into three ceftazidime dosage groups ( denoted as range of milligrams per kilogram per dose ) : group 1 , 22 to 44.5 ; group 2 , 46.3 to 56.6 ; and group 3 , 66.7 to 80.6 . Ceftazidime monotherapy had no effect on sputum colony counts for any Pseudomonas cepacia isolate . In contrast , a substantial reduction in Pseudomonas aeruginosa sputum colony counts was observed , and from 19 to 31 % of isolates were suppressed greater than or equal to 10(5 ) CFU/ml after 14 days of therapy . Bacterial resistance in vitro was not observed , although a trend for increasing ceftazidime MICs was observed for group 1 patients ( P less than 0.05 ) . Overall , clinical response appeared independent of drug dose , and no relationship could be identified between the reduction in P. aeruginosa sputum colony counts and clinical outcome . Adverse effects of ceftazidime were mild and transient , necessitating drug discontinuation in one patient . These data suggest that the clinical response to ceftazidime in patients with cystic fibrosis may be maximal with 50 mg/kg per dose ( 150 mg/kg per day ) up to a total daily dose of 6 A r and omised double blind 2-week trial of monotherapy with ceftazidime and aztreonam was completed in 22 adults with cystic fibrosis . 26 courses of treatment were initiated and 22 courses were completed . Within groups , both ceftazidime and aztreonam demonstrated a significant improvement in FEV1 at 2 weeks ( ceftazidime p less than 0.05 ; aztreonam p less than 0.01 ) and a decline in sputum weight at 2 weeks ( ceftazidime p less than 0.05 ; aztreonam p less than 0.05 ) . Between groups , for spirometry and sputum weight the only change was a slower decline in FEV1 in the aztreonam group at 42 days ( p less than 0.05 ) ABSTRACT . High‐dose anti‐Pseudomonas chemotherapy is m and atory in the treatment of acute pulmonary exacerbations in patients with advanced cystic fibrosis and Pseudomonas aeruginosa isolated from their sputum . However , neither the regimen itself nor its objective evaluation have been optimized yet . In a prospect i ve controlled evaluation 42 such exacerbations were treated for two weeks with netilmicin combined by r and omisation with either azlocillin or ticarcillin . Other aspects of therapy were constant . The two therapy groups were comparable in all aspects . Both regimens produced similar improvements in clinical , radiological , laboratory , bacteriological and pulmonary function measurements . Concentrations of sputum bacteria were significantly reduced ; transient eradication was documented in 29 % and correlated with antibiotic susceptibility of the initially isolated Pseudomonas strains . The highly dosed antibiotics were well tolerated and emergence of resistance was rarely observed . It is concluded that both antibiotic combinations are beneficial and safe in cystic fibrosis . Monitoring of such intensive hospital treatment must include multiple parameters The efficacy and pharmacokinetics of piperacillin monotherapy were studied in 46 patients with cystic fibrosis . Two patients were dropped from the study within 24 hr of enrollment because of drug-associated nausea and vomiting . Initially fourteen older patients ( greater than 12 years ) receiving piperacillin 450 mg/kg/day underwent a preliminary evaluation . Based on the results , 30 younger patients ( less than or equal to 12 years ) r and omized in a double-blind fashion received either 600 or 900 mg/kg/day of piperacillin in six divided doses . Pharmacokinetic parameter estimates for t1/2 Vdss , and Cl were similar for first dose and steady-state evaluations . In 27 patients , approximately 43 % of the administered dose was recovered in the urine after 4 hr . Piperacillin CiR averaged 49 % of the total Cl . No difference in overall clinical efficacy could be identified between 600 and 900 mg/kg/day of piperacillin using two different objective scoring systems . Although a reduction in sputum Pseudomonas colony counts was greater following the 900 mg/kg/day regimen , this appeared to be independent of clinical effect . In 14 patients ( 32 % ) , a distinct adverse serum-sicknesslike reaction was observed . The incidence of this reaction appeared to increase as the dose of piperacillin increased . All signs and symptoms of this reaction resolved within 36 hr of discontinuing piperacillin administration but recurred immediately on rechallenge in four patients . All patients with the adverse reaction were subsequently treated with beta-lactam antibodies without ill effect . Overall , clinical improvement appeared to be independent of the piperacillin dose . Our data support the use of total daily piperacillin dosages not exceeding 600 mg/kg To evaluate whether the addition of an aminoglycoside might enhance the clinical efficacy of ceftazidime in cystic fibrosis patients with acute exacerbations of chronic Pseudomonas lung infections we carried out a prospect i ve , comparative , r and omized blind study with three schedules : ceftazidime vs. ceftazidime plus sisomicin ( C/S ) vs. piperacillin plus sisomicin , for a total of 60 courses of 14 days of treatment . Each treatment led to clinical and radiologic improvement with marked reduction of signs of acute infection . Statistically there was no significant difference in clinical responses among the schedules . No side effect appeared during treatments with ceftazidime or C/S. Hyperpyrexia was seen in 35 % of patients receiving piperacillin . Decrease in Pseudomonas aeruginosa count to less than 10(5 ) colony-forming units/ml of sputum was achieved in 60 % of patients treated with C/S and in 30 % of patients who received ceftazidime or piperacillin plus sisomicin ( statistically not significant ) . A transient increase in mean geometric minimal inhibitory concentrations for ceftazidime and piperacillin was observed at the end of the combined therapies . A larger percentage of persistent resistant strains of P. aeruginosa was seen after the combined therapies . We conclude that ceftazidime as monotherapy may be an effective alternative in Pseudomonas lung infections in cystic fibrosis patients . Its clinical efficacy seems not to be enhanced by the addition of an aminoglycoside , although reduction of Pseudomonas in the sputum was better achieved by the combination of Thirteen patients with cystic fibrosis ( aged 11 to 32 years ) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic ( 14 days , n = 8) or placebo ( 14 days , n = 4 ; 7 days , n = 1 ) . Tc-99 m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy , on the day before antibiotic or placebo , and on the day after completion of antibiotic or placebo therapy . Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol . Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone . Sixty-two percent showed further improvement after antibiotic or placebo was added ; this improvement was independent of whether antibiotic or placebo was administered ( P > 0.1 ) . These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations In cystic fibrosis patients with Pseudomonas aeruginosa colonization and increasing pulmonary infection , ceftazidime 150 mg/kg/day was compared with 320 mg/kg/day . Changes in clinical findings , laboratory tests , pulmonary function and chest radiographs were evaluated after 14 days of treatment in hospital . Both treatments were associated with a significant improvement , but the higher dose did not offer an additional benefit . An increase in alanine aminotransferase ( ALT ) occurred after both treatments ; with a significantly greater increase after the high-dose therapy ( mean increase + /- S.E.M. 8 % + /- 2 % vs 2 % + /- 1 % ; P < 0.01 ) . All but one of the ALT values after treatment were within normal limits Cefsulodin sodium is a narrow-spectrum cephalosporin with marked in vitro activity against clinical isolates of Pseudomonas aeruginosa . We have studied the antibiotic in a clinical trial in 10 patients admitted to the Pediatric Ward of the University of Virginia Medical Center with cystic fibrosis and recurrent acute lower respiratory tract infections with P. aeruginosa isolated from their sputa . The patients received 500 to 1,500 mg of cefsulodin every 6 hours by intravenous infusion for 10 to 22 days . Mean peak drug levels in plasma after 500 , 1,000 , and 1,500 mg were 46 , 71 , and 90 micrograms/ml , respectively , and the mean minimal inhibitory concentration of all organisms was 7.5 micrograms/ml . Detectable levels of cefsulodin in sputa were found in approximately half of the r and om sample s and ranged from 2 to 5 micrograms/ml . The clinical response was satisfactory in nine ( 90 % ) of the patients . One patient gained weight and had improved pulmonary function tests but showed no reduction in sputum production and no improvement in arterial blood gas values . In pulmonary function tests , four of five patients tested showed an average 43 % increase in forced vital capacity after initiation of therapy and five of five had an average 51 % increase in forced expired volume in 1 s. No adverse effects were observed We report the results of a clinical trial . Patients enrolled had serum IgG titres against Pseudomonas aeruginosa above the control range . Assignment to the observation or treatment group was by minimisation . Significant signs or symptoms in any patient prompted antipseudomonal treatment . In addition , the treatment group received antipseudomonal treatment at intervals of four months until the serum IgG titre returned to the control range . P aeruginosa was isolated intermittently from patients in the main trial . Nineteen patients were enrolled ( 12 observation , seven treatment ) . After one year in the trial changes in parameters studied , including forced expiratory volume in one second , IgG titre , serum IgG concentrations , and frequency of P aeruginosa isolation had improved in the treated group and worsened in the observation group CONTEXT Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality . Despite wide use of oropharyngeal cultures to identify pulmonary infection , concerns remain over their diagnostic accuracy . While bronchoalveolar lavage ( BAL ) is an alternative diagnostic tool , evidence for its clinical benefit is lacking . OBJECTIVE To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current st and ard practice relying on clinical features and oropharyngeal cultures . DESIGN , SETTING , AND PARTICIPANTS The Australasian Cystic Fibrosis Bronchoalveolar Lavage ( ACFBAL ) r and omized controlled trial , recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers . Recruitment occurred between June 1 , 1999 , and April 30 , 2005 , with the study ending on December 31 , 2009 . INTERVENTIONS BAL-directed ( n = 84 ) or st and ard ( n = 86 ) therapy until age 5 years . The BAL-directed therapy group underwent BAL before age 6 months when well , when hospitalized for pulmonary exacerbations , if Pseudomonas aeruginosa was detected in oropharyngeal specimens , and after P. aeruginosa eradication therapy . Treatment was prescribed according to BAL or oropharyngeal culture results . MAIN OUTCOME MEASURES Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography ( CF-CT ) score ( as a percentage of the maximum score ) on high-resolution chest CT scan . RESULTS Of 267 infants diagnosed with cystic fibrosis following newborn screening , 170 were enrolled and r and omized , and 157 completed the study . At age 5 years , 8 of 79 children ( 10 % ) in the BAL-directed therapy group and 9 of 76 ( 12 % ) in the st and ard therapy group had P. aeruginosa in final BAL cultures ( risk difference , -1.7 % [ 95 % confidence interval , -11.6 % to 8.1 % ] ; P = .73 ) . Mean total CF-CT scores for the BAL-directed therapy and st and ard therapy groups were 3.0 % and 2.8 % , respectively ( mean difference , 0.19 % [ 95 % confidence interval , -0.94 % to 1.33 % ] ; P = .74 ) . CONCLUSION Among infants diagnosed with cystic fibrosis , BAL-directed therapy did not result in a lower prevalence of P. aeruginosa infection or lower total CF-CT score when compared with st and ard therapy at age 5 years . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000665639 Background Despite advances in treatment of cystic fibrosis ( CF ) , pulmonary exacerbations remain common . The aim of this study was to determine if frequent pulmonary exacerbations are associated with greater declines in lung function , or an accelerated time to death or lung transplantation in adults with CF . Methods A 3-year prospect i ve cohort study was conducted on 446 adult patients with CF from Ontario , Canada who could spontaneously produce sputum . Patients enrolled from 2005 to 2008 and were stratified into groups based upon their exacerbation rates over the 3 year study : < 1 exacerbation/year ( n=140 ) , 1–2 exacerbations/year ( n=160 ) and > 2 exacerbations/year ( n=146 ) . Exacerbations were defined as acute/subacute worsening of respiratory symptoms severe enough to warrant oral or intravenous antibiotics . Patient-related factors associated with frequent exacerbations were determined , and clinical outcomes were compared among the three exacerbation groups . Results Patients with frequent exacerbations were more likely to be female , diabetic and have poorer baseline lung function . Patients with > 2 exacerbations/year had an increased risk of experiencing a 5 % decline from baseline forced expiratory volume in 1 s ( FEV1 ) ; unadjusted HR 1.47 ( 95 % CI 1.07 to 2.01 , p=0.02 ) , adjusted HR 1.55 ( 95 % CI 1.10 to 2.18 , p=0.01 ) compared with patients with < 1 exacerbation/year . Patients with > 2 exacerbations/year also had an increased risk of lung transplant or death over the 3 year study ; unadjusted HR 12.74 ( 95 % CI 3.92 to 41.36 , p<0.0001 ) , adjusted HR 4.05 ( 95 % CI 1.15 to 14.28 , p=0.03 ) . Conclusions Patients with CF with frequent exacerbations appear to experience an accelerated decline in lung function , and they have an increased 3 year risk of death or lung transplant BACKGROUND : There is evidence that administration of higher doses of aminoglycosides given less frequently improves the bactericidal effect and reduces the potential to cause side effects . To investigate this , a prospect ively r and omised open label therapeutic trial was undertaken in stratified groups of patients with cystic fibrosis to examine the efficacy and toxic potential of an aminoglycoside dosing regimen design ed to generate high peak drug concentrations at 12 hourly intervals compared with conventional dosing at eight hourly intervals . METHODS : Patients in group A received tobramycin eight hourly using a dose aim ed at generating a peak concentration of 10 mg/l with trough concentrations below 2 mg/l , and those in group B received the total daily dose required to achieve eight hourly target concentrations administered as two equal 12 hourly doses . Clinical outcomes measured and assessed included vestibular symptoms , hearing and renal function , length of hospital stay , readmission rate , and mortality . RESULTS : Twenty nine patients were recruited during a six month period , 20 to group A and nine to group B. The average peak tobramycin level was higher in group B ( 12.5 ( 2.2 ) mg/l ) than in group A ( 7.9 ( 1.9 ) mg/l ) , whilst the average trough level was higher in group A ( 0.8 ( 0.3 ) mg/l ) than in group B ( 0.5 ( 0.2 ) mg/l ) . There was a difference in the number of ototoxic events between patients in group A ( seven of 18 , 38.9 % ) and group B ( none of eight ) , but no difference was found in other outcome measures assessed . CONCLUSIONS : These results suggest that 12 hourly high peak aminoglycoside dosing may be less toxic than equivalent eight hourly dosing , without any apparent difference in efficacy The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis . Sixty adult patients with an acute respiratory exacerbation were r and omized to receive either 10 mg·kg−1 tobramycin once-daily or 3.3 mg·kg−1 tobramycin thrice-daily . Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing . Both groups showed a significant increase in respiratory function without a clinical ly significant change in renal function . For changes in forced vital capacity % predicted and serum potassium and magnesium levels , equivalence was demonstrated . For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels , there was insufficient power to demonstrate equivalence . One patient in each group showed bilateral impairment in pure tone audiogram after treatment . This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing . Equivalence between the two regimens was shown for some , but not all primary endpoints . Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results OBJECTIVES Once-daily administration of aminoglycosides in cystic fibrosis ( CF ) patients is considered equally efficacious and potentially less nephrotoxic than dosing three times a day . However , the choice of the most suitable PK/PD index ( C(max)/MIC versus AUC(24)/MIC ) to ensure optimum clinical outcome in this patient population is not clear . PATIENTS AND METHODS In a single-centre , open , r and omized , controlled , non-blinded study 33 adult CF patients ( 20 females , 19 - 37 years ) were treated with intravenous tobramycin ( 10 mg/kg/day ) for 14 days given either as single dose once a day ( Q24 ; 17 patients ) or divided into three equal doses every 8 h ( Q8 ; 16 patients ) . Tobramycin serum concentrations and MICs for Pseudomonas aeruginosa were determined on days 1 and 14 . The clinical outcome parameter , correlated to PK/PD indices , was the percentage predicted forced expiratory volume in 1 s ( FEV(1)% pred . ) . RESULTS FEV(1)% pred . improved significantly for both treatments . There was a log-linear relationship between C(max)/MIC and FEV(1)% pred . and AUC/MIC and FEV(1)% pred . for both treatments . For equal values of AUC24/MIC , however , Q24 treatment provided better improvement in lung function than Q8 dosing , whereas C(max)/MIC did not show any dosing interval dependence . A statistically significant increase was observed for MIC ( day 1 ) versus MIC ( day 14 ) for Q24 treatment , however , no such difference was observed for Q8 treatment . CONCLUSIONS The most important PK/PD parameter for clinical outcome in CF patients was C(max)/MIC . Outcome prediction of AUC(24)/MIC was dependent on the regimen . The increase of P. aeruginosa resistance after once-daily administration is linked to a long dosing interval . More and larger studies are needed to optimize the dosing regimen for maximum clinical outcome with minimum resistance development To determine the effect of antimicrobial therapy on acute pulmonary exacerbations in cystic fibrosis , a r and omized , double-blind trial of tobramycin and placebo was carried out . Clinical responses were satisfactory in all 11 children given tobramycin and in seven of 11 given placebo . Two patients in the placebo group died . No patient given placebo had improved results on pulmonary function studies , whereas improvement of 15 % or more occurred in four of the six patients given tobramycin who could cooperate with the testing . Quantitative cultures of sputum showed a decrease of 1 logarithm or greater in Pseudomonas sp concentrations in six of seven patients in the tobramycin group and in two of eight in the placebo group . No difference in staphylococcal colonization was found . Several features indicate that children with severer disease were r and omly assigned to the placebo group ; nevertheless , the trend toward improved response in patients given tobramycin suggests that empirical therapy with antibiotics is beneficial for patients with acute pulmonary exacerbations in cystic fibrosis ABSTRACT Linezolid is a treatment option for methicillin-resistant Staphylococcus aureus ( MRSA ) infections in cystic fibrosis ( CF ) patients . Little is known , however , about its pharmacokinetics in this population . Eight adults with CF were r and omized to receive intravenous ( i.v . ) and oral linezolid at 600 mg twice daily for 9 doses in a crossover design with a 9-day washout . Plasma sample s were collected after the first and ninth doses of each phase . Population pharmacokinetic analyses were performed by nonlinear mixed-effects modeling using a previously described 2-compartment model with time-dependent clearance inhibition . Monte Carlo simulation was performed to assess the activities of the linezolid dosing regimens against 42 contemporary MRSA isolates recovered from CF patients . The following pharmacokinetic parameter estimates were observed for the population : absorption rate constant , 1.91 h−1 ; clearance , 9.54 liters/h ; volume of central compartment , 26.8 liters ; volume of peripheral compartment , 17.3 liters ; and intercompartmental clearance , 104 liters/h . Linezolid demonstrated nonlinear clearance after 9 doses , which was reduced by a mean of 38.9 % ( range , 28.8 to 59.9 % ) . Mean bioavailability was 85 % ( range , 47 to 131 % ) . At steady state , 600 mg given twice daily produced 93.0 % and 87.2 % probabilities of obtaining the target pharmacodynamic exposure against the MRSA isolates for the i.v . and oral formulations , respectively . Thrice-daily dosing increased the probabilities to 97.0 % and 95.6 % , respectively . Linezolid pharmacokinetics in these adults with CF were well described by a 2-compartment model with time-dependent clearance inhibition . St and ard i.v . and oral dosing regimens should be sufficient to reliably attain pharmacodynamic targets against most MRSA isolates ; however , more frequent dosing may be required for isolates with MICs of ≥2 μg/ml The clinical efficacy of the conventional aminoglycoside plus beta-lactam treatment was compared to that of monotherapy with oral quinolones in 26 adult cystic fibrosis patients in an open prospect i ve clinical trial in which six two-week courses of antipseudomonas treatment were administered with an interval of approximately three months between treatments . In each patient two courses of conventional treatment were followed by two courses of quinolone treatment and then by another two courses of conventional treatment . The observed improvements in pulmonary function were somewhat higher when the patients received conventional treatments , and in the most seriously affected patients conventional treatment was significantly better than quinolone treatment . On the basis of these findings it is suggested that quinolone monotherapy can not replace conventional antipseudomonal chemotherapy in patients with severe pulmonary involvement Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance . Preliminary evidence from r and omized controlled trials in patients with cystic fibrosis ( CF ) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing . The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described . In this study we compare the distribution and elimination patterns of traditional dosing ( 3.3 mg/kg q8h ) versus once-daily dosing ( 10 mg/kg q24h ) of tobramycin in six adult patients with CF . The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model . No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted . The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected . The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing , to ensure completion of the distribution phase . Our data indicate that a dose of 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms ( > 20 mg/L ) and AUC(24 ) values at the upper end of the desired range ( 70 - 100 mg.h/L ) ABSTRACT We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large r and omized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis ( the TOPIC study ) . All patients were eligible to have st and ard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz . High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients . Audiometry was undertaken at the start of tobramycin treatment , at the end of a 14-day course of treatment , and at follow-up 6 to 8 weeks later . We enrolled 244 patients , of whom 219 ( 125 children and 94 adults ) completed treatment . Nineteen patients were excluded from analysis due to abnormal baseline audiometry . Complete pre- and posttreatment st and ard audiological data were obtained for 168/219 patients . We found no significant differences in hearing thresholds when they were assessed at the baseline , at the end of treatment , and at follow-up 6 to 8 weeks later were compared . In addition , no significant differences in hearing thresholds were detected between treatment regimens . Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry . We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit , no measurable effect on hearing was apparent with either once- or three-times-daily treatment . Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy , as evidence d by the patients excluded from this study due to hearing loss , also requires further characterization During a 22-month period 35 children with cystic fibrosis received 52 courses of antibiotic therapy for acute pulmonary exacerbations , including 26 cases of therapy with piperacillin and 26 courses with ticarcillin plus tobramycin . Groups were similar in age ( 5 vs. 5.4 years ) , disease severity based on Schwachman scores and presenting symptoms . Pseudomonas aeruginosa was the most common organism isolated in 90 % of sputum cultures . Mean minimal inhibitory concentrations for piperacillin , ticarcillin and tobramycin were 8 , 64 and 1 microgram/ml , respectively . Piperacillin pharmacokinetic data revealed an average half-life in serum of 36 minutes . Peak serum concentrations averaged 144 micrograms/ml , and after 4 hours serum concentrations continued to exceed the P. aeruginosa 90 % minimal inhibitory concentration in 50 % of children . The dosage requirement for tobramycin was quite variable , necessitated monitoring of aminoglycoside serum concentrations and in most cases result ed in at least one dosage adjustment . Emergence of resistant bacteria was not seen in 26 courses of piperacillin therapy . Both regimens were effective and well-tolerated . Single agent therapy has the advantage of providing reliable serum concentrations and , in contrast to the st and ard therapy , does not necessitate monitoring of serum drug concentrations Twenty-nine patients with cystic fibrosis received either cefsulodin or a reference agent ( tobramycin or ticarcillin ) in a r and omized manner for treatment of pulmonary infections associated with Pseudomonas aeruginosa . Patients ranged in age from 12 to 30 years . Their infections were classified as mild ( six ) , moderate ( 16 ) , or severe ( seven ) . Fourteen patients received cefsulodin , 14 patients were treated with tobramycin , and one patient received ticarcillin . Significant clinical improvement was noted in the majority of patients in both groups . Adverse effects and development of laboratory abnormalities were uncommon in both groups . P. aeruginosa was not permanently eradicated from the sputum of any of the patients . Resistance as measured by disk susceptibility testing may have developed during and immediately after therapy in the cefsulodin group but not in those treated with reference agents . However , this did not appear to affect the clinical outcome . Results of the nonr and omized portion of this multicenter study , in which 46 patients were treated with cefsulodin , were similar to those for the r and omized group . Thus , cefsulodin was shown to be as clinical ly effective as the reference agents in the treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis In order to determine the optimal antipseudomonal therapy in patients with cystic fibrosis aztreonam plus amikacin was compared to ceftazidime plus amikacin , and these two-week hospital regimens were followed by oral ciprofloxacin given for four weeks . Fifty-six cases of acute pulmonary exacerbation of the disease in 42 patients associated with isolation ofPseudomonas aeruginosa from the sputum were r and omly treated with either aztreonam or ceftazidime ( 300mg/kg/day i.v . ; maximum daily dose 12 g ) in combination with amikacin ( 36 mg/kg/day i.v . ; maximum daily dose 1,500 mg ) . Other aspects of the two-week treatment were constant . The two therapy groups were comparable in all respects . Both regimens were well tolerated and result ed in similar improvements in clinical , bacteriologic , radiologic and laboratory findings , and pulmonary function . Fifty patients could be reevaluated after subsequent outpatient therapy consisting of oral ciprofloxacin ( 30 mg/kg/day ; maximum daily dose 1,500 mg ) given for four weeks . During this period , the clinical and laboratory improvements persisted , and the rate of eradication ofPseudomonas aeruginosa from sputum decreased from 62 % to 34 % . Ciprofloxacin was well tolerated and there was no drug toxicity or serious adverse effect . In the 25 prepubertal patients there was neither subjective nor objective evidence of skeletal drug toxicity . In patients with cystic fibrosis , aztreonam or ceftazidime in combination with amikacin represents an effective and safe systemic anti-pseudomonal therapy . Subsequent oral ciprofloxacin therapy for four weeks prolongs the beneficial effects and is well tolerated Our objective was to compare the efficacy , safety , and microbiology of once-daily intravenous ( IV ) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa ( PA ) pulmonary exacerbations in cystic fibrosis ( CF ) . CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin ( Mono ) or conventional therapy with tobramycin/ceftazidime given 8-hourly ( Conv ) . The two longitudinal groups received therapy in a double-blind , r and omized manner over a period of 2 years . Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups . Results were assessed for both short-term changes ( efficacy and safety after 10 days of IV antibiotics during acute exacerbations ) and long-term changes ( efficacy , safety , and sputum microbiology between study entry and exit ) . Pulmonary function tests ( PFTs ) on admission were similar in both groups . After 10 days of IV antibiotics , absolute mean improvements in percent of predicted PFTs were 12.8 , 12.1 , and 13.7 for forced expiratory volume in 1 sec ( FEV(1 ) ) , forced vital capacity ( FVC ) , and forced expired flow between 25 - -75 % of FVC ( FEF(25 - -75 % ) ) in the Conv group ( n = 51 admissions ) compared to 10.6 , 9.9 , and 10.6 in the Mono group ( n = 47)(P<0.05 for all ) . Sixteen percent in the Conv group and 15 % of patients in the Mono group did not respond to therapy by day 10 . Long-term PFT patterns were similar for the Conv and Mono groups . The time between admissions did not differ . The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations ( MICs ) against PA from study entry to study exit ( P = 0.02 , n = 27 strains ) ; this failed to reach significance in the Conv group ( P = 0.08 , n = 25 ) . There was no significant increase in the number of isolates , with MIC > or = 8 mg/L in both groups . No short- or long-term changes in audiology or serum creatinine were found in either group . After 10 days of IV therapy , the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups ( P0.05 ) . This increase was greater in the Conv compared to the Mono group ( P < 0.05 ) . We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy . Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy . Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation , including the impact on susceptibility of PA to tobramycin In a prospect i ve , r and omised , cross-over study including cystic fibrosis patients with indications for HIVAT ( home intravenous antibiotic treatment ) the prospect of pharmaceutical intervention was investigated . A comparison between the use of disposable infusion devices with antibiotics from the pharmacy and when the patients prepared the drugs themselves was performed . During a first treatment course the patients received either infusion devices during 5 days or reconstituted the drugs themselves during 5 days , or vice versa . During a second treatment course the order was the reversed . Eight patients were included , out of which six completed the original design as a cross-over study , yielding a total of 550 doses of antibiotics . The patients preferred infusion devices from the pharmacy prepared according to GMP ( Good Manufacturing Practice ) as opposed to reconstituting the antibiotics themselves . Points of view presented included no anxiety over the correct dosage of drugs and less disruption of family and social life . In a practical sense , portable devices are more expensive than the preparation of the drugs by the patients themselves . However , when comparing with in-hospital treatment the direct costs for a hospital stay exceed that of the devices . Another part of the study evaluated the quality of life using a modified form of SEIQoL-DW ( Schedule for the Evaluation of Individual Quality of Life - Direct Weighting ) . Twenty patients took part in the study and the overall quality of life scores increased significantly when patients received infusion devices compared to reconstituting the drugs themselves 40 adult patients with cystic fibrosis ( CF ) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum . The patients were r and omly allocated ( 20 per group ) to receive intravenous azlocillin 5 g and gentamicin 80 mg , or oral ciprofloxacin 500 mg . Both treatments were given three times a day for 10 days . The patients were assessed on days 1 and 10 , and at 6 weeks . There was a significant improvement in lung function between days 1 and 10 in both groups ( p less than 0.001 ) . Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group . Improvement after ciprofloxacin was superior at day 10 . Sputum weight decreased in both groups ( p less than 0.001 ) . Patient-recorded symptoms also improved in both groups . There was no serious toxicity or side-effects . Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy . 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy . Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa RATIONALE Patients with cystic fibrosis periodically experience pulmonary exacerbations . Previous studies have noted that some patients ' lung function ( FEV(1 ) ) does not improve with treatment . OBJECTIVES To determine the proportion of patients treated for a pulmonary exacerbation that does not recover to spirometric baseline , and to identify factors associated with the failure to recover to spirometric baseline . METHODS Cohort study using the Cystic Fibrosis Foundation Patient Registry from 2003 - 2006 . We r and omly selected one pulmonary exacerbation treated with intravenous antibiotics per patient and compared the best FEV(1 ) in the 3 months after treatment with the best FEV(1 ) in the 6 months before treatment . Recovery to baseline was defined as any FEV(1 ) in the 3 months after treatment that was greater than or equal to 90 % of the baseline FEV(1 ) . Multivariable logistic regression was used to estimate associations with the failure to recover to baseline FEV(1 ) . MEASUREMENTS AND MAIN RESULTS Of 8,479 pulmonary exacerbations , 25 % failed to recover to baseline FEV(1 ) . A higher risk of failing to recover to baseline was associated with female sex ; pancreatic insufficiency ; being undernourished ; Medicaid insurance ; persistent infection with Pseudomonas aeruginosa , Burkholderia cepacia complex , or methicillin-resistant Staphylococcus aureus ; allergic bronchopulmonary aspergillosis ; a longer time since baseline spirometric assessment ; and a larger drop in FEV(1 ) from baseline to treatment initiation . CONCLUSIONS For a r and omly selected pulmonary exacerbation , 25 % of patients ' pulmonary function did not recover to baseline after treatment with intravenous antibiotics . We identified factors associated with the failure to recover to baseline , allowing clinicians to identify patients who may benefit from closer monitoring and more aggressive treatment Azlocillin , a new acylureidopenicillin , has been compared to carbenicillin in a controlled , double-blind study for acute exacerbations of pulmonary infections in 29 patients with cystic fibrosis . Twenty-six patients were valid for final analysis of their therapeutic results ; 12 treated with azlocillin ( group I ) at mean dosage of 252 mg/kg/day for a mean duration of 13.2 days of treatment , and 14 treated with carbenicillin ( group II ) at mean dosage of 505 mg/kg/day for a median duration of 12.6 days . Except for one patient of group I who had Staphylococcus aureus in sputum culture , the remaining patients all had Pseudomonas aeruginosa of mucoid colonial morphology with or without the same organism of rough variety in their sputum culture . Therapeutic efficacy was evaluated according to our scoring system of ten clinical factors , five radiological and five pulmonary function factors with 5 points each and 100 points total if perfect . The percentage of patients who improved by 20 % or greater in clinical scores was found in 91.7 % of patients in group I and 64.3 % of patients in group II , which was statistically significantly different . The percentage of patients who improved by 20 % or greater in total scores was found in 80 % of group I and 45.5 % of group II patients , which was less significant than the evaluation of clinical scores alone . Azlocillin was well tolerated and safe in the dosage employed . Its optimal dosage for patients with cystic fibrosis should be established A two-phase study was undertaken design ed to investigate the impact of computer-aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis . In phase one , a baseline ( historical control ) study of drug use patterns was performed . During the second phase , patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were r and omly allocated to one of two schedules . Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocol s using serum tobramycin assay data determined three times weekly . Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population -based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression . The agreed therapeutic target was a peak serum tobramycin concentration of 8 - 10 mg/L and a trough concentration of 1 - 2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges ( group A-14 % ; group B-34.7 % , chi 2 test , P less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS An aminoglycoside in association with beta-lactam antibiotic are usually the most efficient treatment for Pseudomonas aeruginosa infections in cystic fibrosis patients . Tobramycin has the lower MICs than the other aminoglycosides to Pseudomonas aeruginosa . The aim of the work was to compare pharmacokinetics of tobramycin after once daily ( 15 mg/kg/day ; 11 patients ) or thrice daily dose ( 5 mg/kg/day ; 9 patients ) in combination ceftazidime ( CAZ 200 mg/day in 3 inj . IVD ) in sputum and sera for two weeks . No statistical difference in the serum concentration obtained in each group of patients was observed between the first and the 14th day . Serum concentrations were three fold higher when tobramycin was administered in once daily dose . Low through concentrations were quickly obtained , but they were slightly higher after thrice daily doses . Bronchial concentrations were 2 to 2.5 superior and near the critical concentration of tobramycin . The clinical efficacy were comparable in the two regimens The efficacy and toxicity of a shortened tobramycin dosing interval in the treatment of exacerbations of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis patients were evaluated prospect ively . Patients ages 13 to 30 years received 34 treatment courses and were r and omized by pairs to receive tobramycin administered either every 6 or 8 hours . Peak serum concentrations were adjusted to 8 to 10 micrograms/ml ; thus a larger total daily dosage was administered to patients receiving tobramycin every 6 hours . The shorter dosing interval was associated with better pulmonary function at follow-up and significantly longer time before next hospital admission for a pulmonary exacerbation . During the study hospitalization there were no differences in pulmonary function tests , clinical score , sputum carriage of P. aeruginosa , toxicity or necessary length of hospitalization . A 6-hour tobramycin dosing interval was more efficacious than an 8-hour dosing interval in the treatment of cystic fibrosis patients 20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a r and omized cross-over study comparing ceftazidime ( 150 mg/kg body weight/24 h ) plus tobramycin ( 10 mg/kg body weight/24 h ) to ceftazidime alone ( 150 mg/kg body weight/24 h ) , both given intravenously for 2 weeks . 17 patients completed the study ; both treatment regimens improved lung function and decreased the WBC count . No difference in clinical efficacy was found between the treatments . Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments . No changes were seen in minimal inhibitory concentrations during treatment . None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated . Seventy-one percent of patients treated with ticarcillin alone responded favorably . The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone . Severity of the underlying disease was the most important determinant of response to treatment . Ticarcillin-resistant organisms were recovered during treatment in 50 % of patients who received this drug ; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clinical improvement . The ticarcillin-resistant strains persisted at follow-up , two to six months after completion of therapy , in only one of ten patients . No serious toxicity to ticarcillin was noted during the study period We studied the pharmacokinetics of ciprofloxacin in 12 adult males with and 12 adult males without cystic fibrosis ( CF ) . In a r and omized crossover sequence , the subjects received 200 mg intravenously or 750 mg orally . With intravenous dosing , subjects also received 651 mg of iothalamate , a marker of glomerular filtration , and 700 mg of antipyrine , an indicator of hepatic oxidative drug metabolism . Pharmacokinetic parameters were determined by model independent methods . In the CF subjects , the ciprofloxacin concentration in serum during the first hour after intravenous administration was higher , and the oral absorption rate was slower . Other parameters did not differ between the groups . Mean concentrations in serum 5 min postinfusion were 3.08 and 2.14 micrograms/ml , and mean peak concentrations after oral dosing were 3.24 and 3.34 micrograms/ml in subjects with and without CF , respectively . Mean values for elimination half-life in all subjects were 4.8 and 5.0 h after intravenous and oral administration , respectively . The mean renal clearances in all subjects after intravenous and oral administration were 19.4 and 14.5 liters/h and accounted for 64 and 47 % of the total clearance , respectively . These values were significantly greater than renal iothalamate clearance , indicating that tubular secretion contributed to the renal clearance of ciprofloxacin . A total of 69 and 35.4 % of the administered ciprofloxacin was recovered from the urine within 48 h after intravenous and oral administration , respectively . The mean bioavailability was 71.2 % and did not differ between the groups . We conclude that similar dosing regimens can be used to treat patients with CF and their normal counterparts Patients with cystic fibrosis hospitalized because of deterioration in their pulmonary disease were r and omly assigned to receive ten days of intravenous antibiotic therapy with either ticarcillin plus tobramycin ( previously the st and ard regimen at our hospital ) , azlocillin plus tobramycin or azlocillin plus placebo . Pulmonary function and microbiological responses were similar in the three treatment groups , although patients receiving azlocillin and placebo tended to have a smaller reduction in the concentration of bacteria in the sputum and a greater rate of acquisition of antibiotic-resistant organisms . Overall , in-hospital treatment was associated with a significant improvement in Shwachman score , pulmonary function tests , and PO2 . Improvement was noted by day 5 of therapy , continued through day 10 , and was partially maintained at follow-up clinic visit one month after discharge . There was also a statistically significant reduction in sputum bacterial concentration , but patients cultured at the conclusion of antibiotic therapy still had a mean of 10(7 ) cfu/ml in sputum . Pseudomonas aeruginosa , the principal pathogen recovered from sputum cultures in this study , was transiently suppressed to sub-detectable levels in only one patient . There was no correlation between microbiological response and change in any parameter of pulmonary function . By follow-up clinic visit , sputum bacteria had returned to pre-treatment levels , and antibiotic-resistant organisms persisted in all patients from whom they had been recovered during hospitalization A r and omized controlled trial was undertaken to compare ceftazidime vs. the combination of ticarcillin and tobramycin in the treatment of acute respiratory exacerbations of mild to moderate severity in patients with cystic fibrosis . The two antibiotic regimens were equally effective in terms of clinical improvement : 16 of 17 in the ceftazidime group and 11 of 13 in the ticarcillin/tobramycin group were judged to be improved by the patients and attending physicians and were observed to show improvement in symptom scores , vital signs , body weight and pulmonary function . Ceftazidime was more effective bacteriologically in reducing colony counts of Pseudomonas aeruginosa in the sputum . Neither regimen affected Pseudomonas cepacia . Resistance to multiple antibiotics developed in six of 12 isolates of nonmucoid P. aeruginosa in patients receiving ticarcillin/tobramycin , which was significantly more than occurred in the ceftazidime group . There was no correlation between clinical and bacteriologic outcomes in either treatment group . No clinical ly important adverse effects were observed A controlled study was design ed to clarify the indications for antibiotic therapy in children with advanced cystic fibrosis hospitalized with respiratory exacerbations . Twenty-two children with severe CF and signs of acute lower respiratory infection were r and omly assigned to receive either cloxacillin or carbenicillin plus gentamicin administered intravenously for ten days . Other aspects of therapy were constant . The groups were comparable in all respects and Pseudomonas aeruginosa was the predominant sputum pathogen in most patients . Clinical improvement , chest radiograph changes , evidence of airway obstruction , and bacteriologic flora of sputum were no different regardless of the regimen used . These results suggest that the use of anti-Pseudomonas medication in these children may not always be necessary . These observations need to be confirmed by blind-controlled studies in larger numbers of patients with mild as well as severe respiratory involvement 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 We evaluated patients with cystic fibrosis ( CF ) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement . For the first 4 days of study , all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics . During this time , the patients showed significant improvement in mean FVC , FEV1 , and maximal midexpiratory flow rate ( FEF25 - 75 ) . In 12 of 13 trials , the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days . In these 12 trials , the patients were stratified by their initial FVC and r and omized to receive either parenteral tobramycin and ticarcillin ( n = 7 ) or placebo ( n = 5 ) , in addition to continued aerosol and chest physiotherapy . In the remaining trial , the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group . During the next 14 days of therapy , the antibiotic group showed significantly ( p less than 0.01 ) greater reductions in log10 colony-forming units ( cfu ) of P. aeruginosa per gram of sputum and greater increases in FVC , FEV1 , and FEF25 - 75 than did the placebo group . The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly ( p less than 0.001 ) with the degree of improvement in FVC , FEV1 , and FEF25 - 75 . ( ABSTRACT TRUNCATED AT 250 WORDS Seventeen patients with cystic fibrosis ( CF ) and pulmonary exacerbations were r and omly assigned to two treatment groups : piperacillin 600 mg/kg/day ( P ) , and piperacillin 600 mg/kg/day plus tobramycin ( PT ) , in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections . The mean half-life of piperacillin was 0.54 hours , with a peak concentration of 232 micrograms/ml . No differences between P and PT groups were noted in clinical assessment , as judged by Shwachman scores , pulmonary function testing , or weight gain . However , during the course of treatment , quantitative sputum cultures decreased by greater than 10(2 ) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group , compared with 12 of 19 isolates from the PT group ( P less than 0.03 , Chi-square ) . Although emergence of resistance was not seen , one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml . There were no serious adverse reactions to piperacillin ; only one patient developed fever possibly related to piperacillin . Therapy with high-dose piperacillin was safe in children with CF . Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum . However , the role of antimicrobial agents in the treatment of CF remains undefined . A double-blind placebo-controlled trial is indicated BACKGROUND Tobramycin pharmacokinetics have not been evaluated previously in a large series of data collected in children and adults with CF receiving once ( OD ) or three times daily ( TD ) tobramycin . METHODS Therapeutic drug monitoring data in children and adults with CF who participated in a r and omised clinical trial evaluating efficacy and toxicity of OD versus TD tobramycin ( TOPIC study ) were analysed retrospectively . Population pharmacokinetic models stratified to treatment schedule were created , and individual pharmacokinetic parameters were calculated . RESULTS In paediatric patients , volume of distribution per kg body weight ( V1 ) was greater with OD treatment compared to TD ( 0.401+/-0.092 versus 0.354+/-0.041 , p=0.003 ) . Elimination rate was reduced in all patients receiving OD tobramycin compared to TD ( children : 0.00197+/-0.00027 versus 0.00291+/-0.00041 , p<0.001 , adults : 0.00252+/-0.00008 versus 0.00322+/-0.00050 , p<0.001 ) . Tobramycin V1 decreased with increasing age ( R(2)=0.3 , p<0.001 ) . CONCLUSIONS The reduced elimination rate in OD may either be caused by circadian pharmacokinetic behaviour of tobramycin or indicates early renal damage caused by high tobramycin doses not detected by biochemical measurements . However , results of our previous work suggest that OD tobramycin may be less nephrotoxic . The higher V1 in children implies that a relative higher tobramycin dose in these patients is needed for the same target peak serum concentration 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 Sixteen adults with cystic fibrosis and chronic bronchopulmonary infection with Pseudomonas aeruginosa , admitted to hospital for chemotherapy , were r and omized to treatment with either carbenicillin or ticarcillin . In addition all patients received gentamicin . Both antibiotic treatments produced clinical improvement and significant improvement in respiratory function , but there was no difference between them . Pseudomonas aeruginosa was not eradicated from sputum with either treatment regimen BACKGROUND Cystic fibrosis ( CF ) is characterized by chronic pulmonary infection with acute pulmonary exacerbations ( APEs ) requiring IV antibiotic treatment . We report on a blinded comparative trial of IV meropenem ( 40 mg/kg to 2 g q8h ) or ceftazidime ( 5 mg/kg to 2 g q8h ) , each of which was administered with IV tobramycin ( at a serum peak of > or = 8 microg/mL and a trough of < 2 microg/mL ) , as treatment for CF patients with APEs . METHODS Patients who were > or = 5 years of age who were infected with ceftazidime-susceptible Pseudomonas aeruginosa were stratified by lung function and r and omized to treatment with meropenem/tobramycin or ceftazidime/tobramycin . Patients infected with Burkholderia cepacia complex or ceftazidime-resistant P aeruginosa were assigned to receive open-label meropenem/tobramycin . Clinical response was assessed by spirometry to determine the change in percent predicted FEV1 and by a clinical acute change score ( ACS ) . RESULTS One hundred two patients were r and omized to meropenem/tobramycin ( n = 50 ) or ceftazidime/tobramycin ( n = 52 ) . Nineteen patients received open-label meropenem/tobramycin . FEV1 was improved at the end of treatment ( EOT ) with meropenem/tobramycin ( mean [ + /- SD ] increase , 38.8 + /- 52.3 % ) and with ceftazidime/tobramycin ( mean increase , 29.4 + /- 35.1 % ; p < 0.0001 vs baseline values ) . The proportion of patients with > or = 15 % relative increase from baseline FEV1 ( satisfactory response ) at day 7 was 62 % for the meropenem/tobramycin group and 44 % for the ceftazidime/tobramycin group ( p = 0.04 ) . The median time to FEV1 response was 4 days for meropenem/tobramycin therapy vs 6 days for ceftazidime/tobramycin therapy . Similarly , FEV1 improved in the open-label group ( mean increase , 12.5 + /- 25.7 % ; p = 0.05 ) . ACS improved in all three groups at EOT ( p < 0.0001 vs baseline values ) . CONCLUSIONS Therapy with both meropenem/tobramycin and ceftazidime/tobramycin improved pulmonary and clinical status and reduced sputum bacterial burden in CF patients with APEs . A larger proportion of patients receiving meropenem/tobramycin therapy demonstrated a satisfactory FEV1 response at day 7 . Resistant P aeruginosa emerged infrequently during treatment with both regimens A controlled prospect i ve study was undertaken to compare the efficacy and benefits of home and hospital treatment for patients with exacerbations of pulmonary disease caused by cystic fibrosis . A total of 41 home and 41 hospital treatments were analyzed . Home and hospital patients were matched according to sex , age , pulmonary function tests , and arterial blood gas values . Both home and hospital treatments result ed in statistically significant improvement in pulmonary function . A comparison of these values did not show any statistically significant difference between groups at admission or discharge . Furthermore , the mean number of treatment days for both groups , individually determined by the primary physician , was equivalent ( home 17.7 + /- 1.1 days , hospital 18.1 + /- 4.1 ) . The mean charge for a home treatment was approximately $ 10,000 , and for a hospital treatment $ 18,000 . Sixty-five percent of home care patients and 68 % of hospital patients required retreatment for pulmonary exacerbations within the study period ; the interval between pulmonary exacerbations for the two groups was not significantly different . In addition , 85 % of patients receiving treatment at home were able to maintain at least some of their school or work activities . These data indicate that home therapy for cystic fibrosis patients with pulmonary exacerbations is less costly and is as effective as in-hospital therapy The immunogenicity , allergenicity , and cross-reactivity of aztreonam were investigated in 21 patients with cystic fibrosis ( CF ) ( aged 5 to 39 years ) with well-documented histories of allergic systemic reactions ( SRs ) to penicillin and /or cephalosporin antipseudomonal beta-lactam antibiotics ( BLAs ) . Skin tests ( STs ) with penicilloyl-polylysine ( PPL ) , penicillin minor determinant mixture , and antipseudomonal BLA were positive in 19 patients ( 90 % ) . The BLA causing the most recent allergic reaction , minor determinant mixture , or PPL , was positive in 89 % , 53 % , and 32 % of ST-positive patients , respectively . Serum PPL-specific IgE antibodies were not detectable , although PPL-specific IgG antibodies were found in 64 % of patients tested . STs to aztreonam reagents were performed and were initially negative in 20 patients . One patient was ST positive to the polylysine conjugate of hydrolyzed aztreonam ( SQ 27629 ) , despite no prior exposure to aztreonam , and was not treated . Of 20 patients treated with aztreonam , four were demonstrated to be sensitized by exposure ( one had an SR during initial treatment course , two had SRs on reexposure , and one patient was asymptomatic after intravenous desensitization ) by positive aztreonam reagent skin responses on repeat testing . Aztreonyl-specific IgE and IgG serum antibodies were not detected in any patients , including patients with allergic reactions to aztreonam . Thus , aztreonam is generally well tolerated in high-risk patients with CF allergic to other BLAs and appears to have reduced immunogenicity by serologic testing . However , caution should be exercised with aztreonam in BLA-allergic patients with CF in light of 5 % preexisting ST cross-reactivity and 20 % sensitization rates found in this study BACKGROUND More data on the efficacy and safety of ciprofloxacin in pediatric cystic fibrosis patients are needed . METHODS One hundred eight pediatric cystic fibrosis patients ( ages 5 to 17 years ) with acute bronchopulmonary exacerbations entered a r and omized multicenter trial design ed to compare the safety and efficacy of antipseudomonas therapy with oral ciprofloxacin ( 15 mg/kg twice daily ; maximum dosage 750 mg twice daily ) or intravenous ceftazidime plus tobramycin ( CAZ/TM ) for 14 days . RESULTS Clinical improvement was observed in 93 % of patients treated with oral ciprofloxacin and in 96 % of those receiving parenteral therapy . Transient suppression of Pseudomonas aeruginosa was achieved in 63 % of patients at the end of the course of iv CAZ/TM therapy and in 24 % receiving ciprofloxacin . Ultrasound examination and nuclear magnetic resonance imaging scans showed no evidence of cartilage toxicity in any of the ciprofloxacin-treated patients . Musculoskeletal adverse events were reported with similar frequency in the two groups of patients ( 7 % in the group receiving ciprofloxacin therapy and 11 % in the IV CAZ/TM group ) . The only sustained musculoskeletal symptom was a case of synovitis in a patient receiving parenteral CAZ/TM . CONCLUSION Ciprofloxacin thus appears to be safe and effective for use in young patients with bronchopulmonary exacerbation of cystic fibrosis OBJECTIVE To compare once daily with thrice daily tobramycin for treatment of Pseudomonas aeruginosainfection in patients with cystic fibrosis . DESIGN 22 patients with cystic fibrosis , mean ( SD ) age 11 ( 3.4 ) years ( range 5.6–19.3 ) , with pulmonary pseudomonas exacerbations were r and omly assigned to receive a 14 day course of tobramycin ( 15 mg/kg/day ) either in three infusions ( group A ) ( n = 10 ) or a single daily infusion ( group B ) ( n = 12 ) , combined with ceftazidime ( 200 mg/kg/day as three intravenous injections ) . Efficacy was assessed by comparison of pulmonary , nutritional , and inflammatory indices on days 1 and 14 . Cochlear and renal tolerance were assessed on days 1 and 14 . Tobramycin concentration was measured in serum and sputum 1 , 2 , 3 , 4 , 8 , and 24 hours after the start of the infusion . Analysis was by non-parametric Wilcoxon test . RESULTS Variables improving ( p < 0.05 ) in both groups A and B were , respectively : weight/height ( + 4 % and + 3.1 % ) , plasma prealbumin ( + 66 and + 63 mg/l ) , forced vital capacity ( FVC ) ( + 14 % and + 11 % ) , forced expiratory volume in one second ( + 15 % and + 14 % ) , and forced expiratory flow between 25 % and 75 % of FVC ( + 13 % and + 21 % ) . Improvement was not significantly different between groups . Renal and cochlear indices remained within the normal range . Serum peak concentration of tobramycin on day 1 was 13.2 ( 7.1 ) mg/l in group A and 42.5 ( 11.2 ) mg/l in group B ( p < 0.001 ) ; serum trough was 1.1 ( 0.8 ) mg/l in group A and 0.3 ( 0.2 ) mg/l in group B ( p < 0.01 ) . Tobramycin concentrations in sputum were two to three times higher in group B than group A. CONCLUSIONS Once daily tobramycin combined with three injections of ceftazidime is safe and effective for the treatment of pseudomonas exacerbations in cystic fibrosis patients In a r and omized , double-blind study , cystic fibrosis patients 11 - 30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin , azlocillin-tobramycin , or azlocillin-placebo for 10 days . There was significant improvement in Shwachman scores and pulmonary function tests . Concentrations of sputum bacteria were significantly reduced , but after therapy patients had a mean of 10(7 ) bacteria/ml of sputum . Pseudomonas was transiently eliminated in only one patient . The three regimens had similar impacts on pulmonary function and sputum bacterial concentration . Antibiotic resistance was noted more frequently in the azlocillin-placebo group , but this trend was not statistically significant . Improvement in pulmonary function did not correlate with bacteriological response . Four weeks after discharge , 62 % of the improvement in forced expiratory volume in one second and 75 % of the improvement in vital capacity remained , but concentrations of sputum bacteria had returned to pretreatment levels , and antibiotic-resistant bacteria persisted A non-blinded , r and omized , cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis ( CF ) patients with normal renal function . On consecutive mornings the patients were given either tobramycin intravenously ( i.v . ) over 3 - 5 min ( TOB phase ) , or tobramycin i.v . over 3 - 5 min followed immediately by ticarcillin infused i.v . over 20 - 30 min ( TOB+TIC phase ) . Capillary blood sample s were taken 30 min and 330 min after administration of the tobramycin dose in each phase . Tobramycin was measured in serum by fluorescence polarization immunoassay ( TDx ) . There were decreases in serum tobramycin concentrations of 11 % at 30 min ( P < 0.001 ) and 330 min ( P = 0.012 ) when measured in the presence of ticarcillin . No difference in elimination half-life was found ( TOB phase 95 + /- 13 min , TOB+TIC phase 95 + /- 13 min , P = 0.86 ) . The volume of distribution and clearance of tobramycin increased by 14 % ( P < 0.001 ) and 13 % ( P < 0.001 ) , respectively , in the presence of ticarcillin . This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin BACKGROUND Cystic fibrosis patients have chronic bacterial infections of the respiratory tract , most commonly Pseudomonas aeruginosa . Although controversial , administration of antibiotic therapy during acute pulmonary exacerbations is st and ard practice . Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies . Because of its activity against P. aeruginosa and excellent oral bioavailability , ciprofloxacin offers a unique therapeutic alternative for this patient population . OBJECTIVE This prospect i ve , r and omized , double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection . METHODS One hundred thirty patients ( ages 5 to 17 years ) were r and omized to receive either i.v . ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v . ceftazidime 50 mg/kg every 8 h plus i.v . tobramycin 3 mg/kg every 8 h for a minimum of 10 days . Clinical , bacteriologic and safety responses were assessed throughout the study . RESULTS All 84 patients ( median age , 11 years ; range , 5 to 17 years ) valid for efficacy in both treatment groups demonstrated clinical improvement . Five patients experienced clinical relapses ( 3 ciprofloxacin , 2 ceftazidime/tobramycin ) by the 2- to 4-week follow-up . Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up . Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas . DNA profiles demonstrated that irrespective of colony morphology , usually one clonal strain was associated with each patient 's pulmonary exacerbation . Treatment-associated musculoskeletal events occurred with equal frequency ( 22 % vs. 21 % ) in both study drug groups ( n = 129 ) , and arthralgias were within the range of rates for cystic fibrosis arthropathy . None of these events required study drug discontinuation . CONCLUSION Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to st and ard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients BACKGROUND Inhaled tobramycin has been shown to improve lung function in cystic fibrosis ( CF ) patients chronically infected with Pseudomonas aeruginosa . However , to date no comparative data are available for different dose regimens used in clinical practice . OBJECTIVES To compare the clinical efficacy of the two most commonly used treatment regimens of inhaled tobramycin in patients with CF . METHODS In an open crossover study of CF patients , subjects were r and omly allocated to receive either 80 mg tobramycin twice-daily continuous treatment or 300 mg tobramycin twice daily in cycles of 28 days on and 28 days off treatment . After three months , patients were switched to the alternative treatment regimen . RESULTS A total of 32 patients with a mean ( + /- SD ) age of 18.5+/-8.6 years were included in the study . Compared with the treatment period using colistin , forced expiratory volume in 1 s decreased by -2.1+/-13.8 % in the 80 mg tobramycin group and increased by + 2.3+/-13.0 % in the 300 mg group . Similar changes were observed in forced vital capacity ( -2.5+/-12.9 % in the 80 mg tobramycin group versus + 2.5+/-9.6 % in the 300 mg tobramycin group ) . Variability in responses was large but the differences were not statistically significant . Personal preference indicated that the majority of patients preferred the high-dose cycle compared with the lower dose continuous inhalation , but this was not linked to objective data on efficacy . CONCLUSIONS The present trial fails to provide convincing evidence for superiority in efficacy of either of the two treatment regimens of inhaled tobramycin in CF patients Fourteen children with cystic fibrosis and pulmonary lung infection due to Pseudomonas aeruginosa were treated with piperacillin ( 300 mg/kg/day ) alone or piperacillin and tobramycin ( 7 mg/kg/day ) iv . The outcome with respect to clinical state , chest X-ray and lung function tests was better with combination therapy than with piperacillin alone . Bacteriological response was the same with both regimens : leucocyte content of the sputum decreased , non-mucoid Ps . aeruginosa strains were eliminated , but mucoid strains were only suppressed ( 11 children ) . Peak serum levels of piperacillin averaged 102 mg/l , the overall serum elimination was 0.75 h and the mean sputum concentrations ranged from 1.07 to 2.2 mg/l . Peak serum levels of tobramycin averaged 5.15 mg/l , the half life was 1.25 h and the mean sputum concentrations ranged from 0.57 to 0.68 mg/l . The clearance of piperacillin and tobramycin was increased significantly . Drug-resistance did not develop during therapy Twenty adult patients with cystic fibrosis who were experiencing acute pulmonary exacerbations were enrolled in a r and omized , controlled trial comparing oral ciprofloxacin with intravenous tobramycin plus azlocillin . Efficacy of the two treatments was compared based upon changes in clinical status , pulmonary function tests , white blood cell counts , and quantitative bacteriology of sputum . No statistically significant differences were detected in these parameters of response between the two treatment groups ( p greater than 0.05 ) . Ciprofloxacin appears to be therapeutically equivalent to intravenous antibiotics in the treatment of adult patients with cystic fibrosis who are experiencing pulmonary exacerbations associated with susceptible bacteria OBJECTIVE To evaluate the short term effects on nutritional status of home intravenous anti-pseudomonas antibiotic courses in cystic fibrosis ( CF ) patients chronically colonised withPseudomonas aeruginosa . DESIGN A prospect i ve study involving 38 CF patients , mean age 10.9 ( SD 4.3 ) years ( range 4.3 to 22.2 years ) , presenting with pulmonary exacerbations of P aeruginosainfection . The patients received a 14 day antibiotic course of intravenous ceftazidime ( 200 mg/kg/day ) and either amikacin ( 35 mg/kg/day ) or tobramycin ( 15 mg/kg/day ) . Nutritional evaluation on days 1 and 14 involved measurements of weight , weight/height ratio ( per cent of predicted value ) , energy intake ( per cent of recommended daily allowances ) , serum prealbumin , and body composition assessed by two methods : bioelectrical analysis ( BIA ) and skinfold anthropometry . The non-parametric Wilcoxon t test was used for statistical analysis , with a Bl and -Altman plot to assess the degree of agreement between the two methods of evaluating body composition . RESULTS Weight increased by 1.0 ( 0.8 ) kg ( p < 0.001 ) ; weight/height increased from 94.4(12.2)% to 98(12.7)% ( p < 0.001 ) , energy intake from 107(32)% to 119(41)% ( p < 0.02 ) , and prealbumin from 183 ( 63 ) to 276 ( 89 ) mg/l ( p < 0.001 ) . Fat mass increased by 0.8 ( 1.0 ) kg ( p < 0.001 ) , without any significant change in fat-free mass . The limits of agreement between BIA and anthropometry were –0.7 kg and + 1.1 kg . CONCLUSIONS Antibiotic courses allow an improvement in nutritional status in CF patients , with a gain in fat mass The combination of ticarcillin plus tobramycin ( TT ) or carbenicillin plus gentamicin ( CG ) was used to treat 82 patients with severe systemic gram-negative infection in a prospect i ve , r and omized study . Pseudomonas aeruginosa was the primary pathogen in 7 ( 93 per cent ) of these patients . Patients treated with TT responded more frequently ( 92 per cent or 37 of 40 ) than patients treated with CG ( 71 per cent or 30 of 42 ) ( p is less than 0.05 ) . This difference was primarily due to a greater response to TT in patients with pulmonary infections ( 93 per cent versus 68 per cent ) and infections due to Pseudomonas ( 92 per cent versus 70 per cent ) . Severity of underlying disease was also an important determinant of response . Except for a greater incidence of hepatotoxicity with CG ( 23 per cent versus 3 per cent ; p is less than 0.02 ) , there was no difference in toxicity , colonization with drug-resistant microorganisms or superinfection between the two treatment groups . The combination of TT appears to be superior to CG for the treatment of pulmonary infections due to Pseudomonas aeruginosa Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients . Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls . Based on these data , 30 acutely ill cystic fibrosis patients ( aged 18 to 44 years ) received 750 mg of ciprofloxacin orally every eight hours for 21 days . Multiple timed serum , urine , and sputum sample s for pharmacokinetic analysis were obtained on Days 3 , 12 , 14 , and 21 of the study . Estimates of steady-state pharmacokinetic parameters averaged ( + /- SD ) : t1/2 beta , 3.8 ( 1 ) hours ; Vd/F , 4.4 ( 2 ) liters/kg ; Cl/F , 772.9 ( 301 ) ml/minute/1.73 m2 ; Fe , 46 percent ; peak , 5.4 ( 2 ) mg/liter ; and trough , 1.8 ( 0.8 ) mg/liter . Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study . Sputum ciprofloxacin concentrations exceeded those observed in serum . Sputum cultures revealed 43 P. aeruginosa ( MIC90 = 2 micrograms/ml ) and 15 P. cepacia ( MIC90 = 16 micrograms/ml ) strains . Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold , yet only eight isolates were fully suppressed . Posttreatment sputum cultures revealed 35 P. aeruginosa ( MIC90 = 16 micrograms/ml ) and 15 P. cepacia ( MIC90 = 16 micrograms/ml ) . All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score ( median pre 49/post 60 ) . No patients experienced drug-related toxicity . Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients . The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients BACKGROUND Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased . A number of centres have adopted a policy of regular ( three monthly ) rather than on dem and intravenous antipseudomonal antibiotics . More widespread bacterial antibiotic resistance has result ed from this increased antibiotic use . Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity . A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis . METHODS Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were r and omised to receive treatment for 12 days with either colistin ( 2 MU tds intravenously ) alone or with a second anti-pseudomonal antibiotic . Comparisons of the absolute values of respiratory function tests on days 1 , 5 , and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures . Patient 's weight , clinical and chest radiographic scores , and peripheral blood markers of inflammation were also documented . The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values . Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes , creatinine clearance , and ward urine testing . Neurotoxicity was monitored by direct question ing for symptoms . RESULTS Fifty three patients , 18 of whom entered the study twice , were enrolled . The mean forced expiratory volume in one second ( FEV1 ) increased significantly in both groups , mean forced vital capacity ( FVC ) only with dual therapy . Both groups showed a non-significant increase in overnight oxygen saturation . All patients showed clinical improvement . Thirty seven adverse neurological events ( two severe ) were reported in 33 patients in the monotherapy group and 37 ( none severe ) in 36 patients in the dual therapy group . One patient withdrew because of severe weakness and dizziness . All other adverse neurological events were well tolerated and resolved during or shortly after treatment . Significant changes were seen in mean serum urea levels in both groups , but in only four patients to a level above the normal range , and in creatinine clearance in the dual therapy group . At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study . CONCLUSIONS Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis . Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity . Changes in renal function should be monitored Two open r and omized cross-over studies were undertaken comparing ceftazidime to tobramycin and ceftazidime to tobramycin plus carbenicillin in 13 and 15 cystic fibrosis ( CF ) patients , respectively , with chronic bronchopulmonary Pseudomonas aeruginosa infection . The difference in lung function improvement was statistically better in terms of FEV1 and FVC for the ceftazidime group in the study versus tobramycin plus carbenicillin . Patients receiving ceftazidime showed a tendency for a greater long-term benefit in lung function as measured at 1 and 2 months after treatment than patients receiving the other antibiotics . Development of resistance against both ceftazidime and carbenicillin was seen regularly and was not prevented by combination therapy with tobramycin . No resistance developed when tobramycin was used as monotherapy . Serum concentration curves for ceftazidime fitted a two compartment first order open model in CF patients and showed a distribution volume of 40 % of the body weight and a final serum half-life of 1.8 h. One case of Type III hypersensitivity reaction was seen during ceftazidime treatment . Ceftazidime seems to be an effective and safe antibiotic in the treatment of Ps . aeruginosa bronchopulmonary infection in CF patients , although these bacteria could not be eradicated BACKGROUND Due to limited re sources within the health service and the continuous discussion on cost containment , economic criteria should also be considered when assessing therapy concepts . Particular results in terms of economic efficiency reserves are to be expected from a transfer of care from the in-patient to the out-patient sector . METHODS In a prospect i ve , direct cost recording of all relevant uses of re sources , the direct and indirect costs of the treatment of 14 patients with cystic fibrosis ( CF ) were included in the cross-over- design . The quality of life was recorded at least once for each patient using the EuroQol . In-patient intravenous antibiotic therapy carried out during the block of out-patient care served as one of the disqualification criteria when selecting patients . RESULT Over an observation period of nine months , the average direct cost recorded were DM 35,706 for out-patient and DM 40,143 for in-patient treatment ( + 15 % ) . As far as indirect costs are concerned , the losses of production in the national economy recorded for in-patient treatment were 80 % higher . CONCLUSION The direct and indirect costs for in-patient CF-therapy are in total higher than for out-patient care . Whether these cost advantages have to be " bought " with lower medical effectiveness needs to be demonstrated by further clinical studies . In the sense of the disease management approach , the results of this study should be used to help rationally weigh up the costs of out-patient care against alternative treatment concepts Cystic fibrosis patients ( children and young adults ) with Pseudomonas spp . chest infections were treated with meropenem or ceftazidime . This study was the first to investigate the use of meropenem in cystic fibrosis . Meropenem was well tolerated with only transient elevations of serum transaminases . No patient experienced nausea and vomiting , even when meropenem was administered as a bolus injection . This allowed home therapy to be used . Meropenem appeared to be at least as active as ceftazidime even at the low doses used . Patients showed a greater improvement in respiratory function on meropenem than ceftazidime . Only one patient ( out of 60 courses ) failed to respond to meropenem ( 98 % success rate ) compared with two failures out of 21 episodes with ceftazidime ( 90 % success rate ) . There was little emergence of resistance to meropenem even though some patients were treated up to eight times over a 2 year period ABSTRACT . Seventeen cystic fibrosis patients aged 3.1 years to 19.8 years had 30 courses of intensive treatment for relapse of their pseudomonas chest infection . The combination of netilmicin and ticarcillin was compared with tobramycin and ticarcillin in an open study . A significant subjective and objective improvement occurred in all patients . Pseudomonas was cleared temporarily from the sputum in 11 out of the 30 courses of treatment ( 37 % ) . There was no significant difference between the netilmicin and tobramycin groups , nor evidence of sustained renal or ototoxicity . Intensive therapy of pseudomonas chest infection in cystic fibrosis patients is described in detail Background / aim : We hypothesized that a continuous 24-h infusion of 100 mg/kg per day ceftazidime ( treatment C ) would result in equivalent or even superior anti-infectious efficacy in chronic Pseudomonus aeruginosa ( PA ) infection in patients with cystic fibrosis ( CF ) in comparison to the usual application of 200 mg/kg per day ceftazidime in three doses ( treatment T ) . Methods : This was a r and omized crossover study comparing outcome after 14 days and 35 days . Tobramycin administered once daily ( 10 mg/kg per day ) was administered concomitantly in both groups . The primary end-point was a decrease in the leukocyte count , and the secondary endpoints were clinical and lung function parameters , Pseudomonas quantification in sputum , and inflammation markers ( immunogloblulin [ Ig ] G , C-reactive protein [ CRP ] ) in serum . All patients received antibiotics electively as 14-day courses on a regular basis , not for acute exacerbations . Results : Fifty-six patients ( 29 females , mean patient age 14.4 years , age range 5–37 ) initially received treatments C or T , followed by the alternative treatment after amean interval of 37 ( ± 21 ) weeks . After 2 weeks of antibiotic treatment , the overall study group showed significant improvements compared to baseline for body weight , leukocyte counts , CRP , forced expiratory volume in 1 s ( FEV1 ) , FVC ( forced vital capacity ) , and bacterial load in the airways , with no significant differences between treatment groups . Both regimens were well tolerated . Threeweeks after cessation of antimicrobial therapy , leukocytes and PA density had returned to pre-treatment values . Conclusion : We conclude that continuous or thrice-daily dosing of intravenous ceftazidime , both combined with once-daily tobramycin , are equally effective application regimens for elective antipseudomonal therapy in clinical ly stable patients with CF Twenty-one patients with cystic fibrosis and chronic Pseudomonas lung infection were treated at r and om with ceftazidime , 150 mg/kg/day , or with piperacillin , 300 mg/kg/day , and tobramycin , 10 and more mg/kg/day for 14 days . On admission and at discharge , body weight , erythrocyte sedimentation rate , white blood cell count , and differential were determined . Pulmonary function analysis and chest X-rays were also obtained on both occasions as was sputum bacteriology . After hospitalization , the patients were followed in the outpatient department for 14 - 26 months . Both treatments were associated with significant improvement in most of the parameters that were studied , but neither treatment was superior BACKGROUND Cystic fibrosis ( CF ) is characterized by chronic bacterial broncho-pulmonary infection . Although intravenous ( i.v . ) antibiotic therapy is regarded as st and ard treatment in CF , only few r and omised trials comparing different antibiotic compounds exist . METHODS We report on a prospect i ve multicenter interventional trial of i.v . meropenem ( 120 mg/kg/day ) or i.v . ceftazidime ( 200 - 400 mg/kg/day ) , each administered together with i.v . tobramycin ( 9 - 12 mg/kg/day ) . Outcome measures were changes in lung function , microbiological sputum burden and blood inflammatory marker . Liver and renal function values were measured to assess safety . RESULTS One hundred eighteen patients ( 59/59 ) were included into the study with the following indications : first infection of P. aeruginosa ( n=6 ) , acute pulmonary exacerbation ( n=34 ) and suppression therapy of chronic P. aeruginosa colonization ( n=78 ) . Both treatments improved lung function measures , bacterial sputum burden and CRP levels with no differences between treatment groups observed . A significant higher elevation for alkaline phosphatase ( p<0.0001 ) was observed for patients in the meropenem/tobramycin group . CONCLUSIONS i.v . antibiotic therapy in CF patients with meropenem/tobramycin is as effective as with ceftazidime/tobramycin regarding lung function , microbiological sputum burden and systemic inflammatory status . Hepato-biliary function should be monitored carefully during i.v . treatment , possibly important in CF patients with pre-existing liver disease A r and omized trial of ceftazidime versus placebo was conducted in patients with cystic fibrosis hospitalized for acute respiratory exacerbations . Patients 12 years of age or older were included if they had mild to moderately severe illness according to the following criteria : erythrocyte sedimentation rate less than or equal to 50 mm/hr and less than three other abnormalities ( leukocyte count greater than or equal to 15,000/microliter , pulse greater than or equal to 100 beats/min , respirations greater than or equal to 30/min , or temperature greater than or equal to 38.5 degrees C ) . In all 16 episodes treated with ceftazidime , the patients were rated improved in comparison with 10 of 12 patients treated with placebo . Three placebo-treated patients dropped out of the study within 3 to 5 days because they wanted antibiotic therapy . None of the 15 placebo-treated patients showed clinical deterioration . There were no significant differences in rate of improvement of symptom score , weight gain , or pulmonary function between the two treatment groups . There was no difference in the course during the 6 to 24 months after the study period . Intravenous antibiotics are not essential in the management of all acute respiratory exacerbations of mild to moderate severity in patients with cystic fibrosis We have investigated the effectiveness of seven new beta-lactam antibiotics , azlocillin , piperacillin , ceftazidime , cefsulodin , cefoperazone , latamoxef ( moxalactam ) , and cefotaxime , against acute pulmonary exacerbations caused by Pseudomonas aeruginosa in cystic fibrosis . Three hundred and fifty-five strains of Ps aeruginosa isolated from 310 sputum cultures ( 190 cystic fibrosis patients ) were tested for susceptibility to the drugs by determination of minimal inhibitory concentrations ( MIC ) . The highest activity was shown by ceftazidime ( 6 % resistant strains ) followed by cefsulodin and piperacillin ( 15 and 16 % resistant strains ) ; very low activity was found for cefotaxime and latamoxef ( moxalactam ) . Ceftazidime was the most active drug against 32 pseudomonas isolates that were resistant to both carbenicillin and aminoglycosides ( 78 % susceptible ) . A r and omized , double-blind trial of azlocillin , piperacillin , ceftazidime , cefsulodin or cefoperazone was performed in 111 cystic fibrosis patients with predominant and susceptible pseudomonas in their sputum . Results were evaluated by a clinical , radiological and bacteriological scoring system : the best results were obtained with ceftazidime , followed by cefsulodin and piperacillin . However , pseudomonas was eradicated in only 22 ( 23 % ) of the cases with the most active drugs and persisted or reappeared in all the cases 1 to 3 months later . Ceftazidime always eradicated Staph . aureus and Haemophilus influenzae associated with pseudomonas . Similar eradication occurred nearly always with cefsulodin but rarely with the other drugs . No serious drug reaction occurred but a later fever and rash with piperacillin , transient diarrhoea with cefoperazone , vomiting with cefsulodin , and very frequent eosinophilia with ceftazidime should be mentioned . These five drugs offer , in varying degree , alternatives to traditional anti pseudomonas antibiotics in cystic fibrosis pulmonary infections , but they should be used only against well-proven resistant strains . Ceftazidime is best and cefotaxime and latamoxef ( moxalactam ) least useful A double-blind controlled trail of anti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with cystic fibrosis . Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin ( treatment group ) ; nine were treated with oxacillin alone ( control group ) . The planned length of treatment was 14 days . The difference between the failure rate in the treatment group ( 3/15 ) and the control group ( 7/9 ) was statistically significant ( P less than 0.015 ) . The difference in improvement of forced expiratory volume in 1 second was also significant ( P less than 0.025 ) . At the end of the study , Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group , but was not isolated from six of the 15 patients in the treatment group . The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis Eighty-seven patients with cystic fibrosis were admitted to hospital with an acute exacerbation of pulmonary symptoms associated with isolation of Pseudomonas aeruginosa from sputum . The patients were r and omly allocated to receive intravenously administered ceftazidime ( 250 mg/kg/day ) and amikacin ( 33 mg/kg/day ) alone or with inhaled amikacin ( 100 mg twice a day ) . Other aspects of the 2-week treatment were constant . The two therapy groups were comparable in all aspects . At the completion of therapy , the addition of aerosolized amikacin produced temporary eradication of P. aeruginosa in 70 % of the patients , compared with 41 % in the intravenous therapy only group ( P less than 0.02 ) . Suppression of P. aeruginosa in sputum cultures was correlated with the amikacin sputum concentrations . However , both regimens result ed in similar improvements in clinical , radiologic , laboratory , and pulmonary function measurements , and within 4 to 6 weeks most patients were recolonized with P. aeruginosa . There was no serious toxicity or adverse effect . In patients with cystic fibrosis , the addition of aerosol aminoglycoside to systemic antipseudomonal combination therapy is not clinical ly beneficial BACKGROUND Once daily dosing of aminoglycosides is widely used but is limited by the inconvenience of the slow infusion it requires and the associated three-times daily infusion of a beta-lactam . Twice daily tobramycin can be given as a slow IV bolus and may be more convenient . This study compares twice with three-times daily dosing of both tobramycin and ceftazidime . METHODS This was a r and omised , open-label , parallel group trial . CF patients presenting with an infective exacerbation were r and omised to either twice or three-times daily ceftazidime and tobramycin . Markers of treatment efficacy and safety were measured in the two groups . The primary outcome measure was improvement in FEV1 . RESULTS 146 patients were r and omised into the study . There was no significant difference in the two groups for improvement in FEV1 % predicted ( 9.93 % and 7.98 % for twice daily and three-times daily respectively ) and similar times to next exacerbation . There were no differences in the incidence of treatment failure , nephrotoxicity and ototoxicity . DISCUSSION This study confirms that twice daily dosing of both tobramycin and ceftazidime is safe and effective and may be considered more convenient than current dosing schedules The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose . Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy . Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing , and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens . Dogs given gentamicin , tobramycin , or netilmicin once daily , with maximum serum concentrations of greater than 100 mg/liter , had less nephrotoxicity than dogs given continuous infusions . Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter . Intermittent dosing of aminoglycosides , causing infrequent large maximum serum concentrations , may be less toxic and equally efficacious as frequent dosing The efficacy of aztreonam was compared to that of st and ard therapy consisting of tobramycin and azlocillin in the treatment of acute pulmonary exacerbations of cystic fibrosis in a r and omized , open trial . Fifteen patients were r and omized to each treatment . Responses were assessed based on changes in pulmonary and clinical scores , white blood cell counts , pulmonary function tests and quantitative bacteriology of sputum which were performed before , every 5 to 7 days during and on the last day of therapy . Patients in both groups responded to therapy and there were no statistically significant differences in changes in the above indicators of response with therapy between the two groups ( P greater than 0.05 ) . The incidence of detection of Pseudomonas aeruginosa isolates resistant to all three study antibiotics increased with therapy . Side effects were limited to transient elevations of liver enzymes ( both groups ) and rash and fever in one patient treated with azlocillin . Aztreonam represents effective therapy for pulmonary exacerbations of cystic fibrosis associated with susceptible pathogens BACKGROUND We did a r and omised , double-blind , controlled clinical trial to prospect ively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria . METHODS 251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing ( MCBT ) . Patients who developed an exacerbation of pulmonary disease were r and omised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT . The primary outcome was time from r and omisation until the patient 's next pulmonary exacerbation . Analysis was by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N60187870 . FINDINGS 132 patients had a pulmonary exacerbation and were r and omised during the 4.5-year study period . The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group ( hazard ratio 0.86 in favour of the conventionally-treated group , 95 % CI 0.60 - 1.23 , p=0.40 ) . There was no difference between the groups in treatment failure rate . After 14 days of intravenous antibiotic therapy , changes in lung function , dyspnoea , and sputum bacterial density were similar in both groups . INTERPRETATION Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by st and ard culture and sensitivity techniques . The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations |
12,557 | 11,869,643 | REVIEW ER 'S CONCLUSIONS We conclude that interventions design ed to enhance partner support for smokers in cessation programs did not increase quit rates .
Limited data from several of the RCTs suggest that these interventions did not increase partner support either .
No conclusions can be made about the impact of partner support on smoking cessation . | BACKGROUND While many cessation programs are available to assist smokers in quitting , research suggests that partner involvement may encourage long-term abstinence .
OBJECTIVES The purpose of this review was to determine if an intervention to enhance partner support helps smoking cessation when added as an adjunct to a smoking cessation program . | Purpose . This study assesses buddy support in a community-based , minimal-contact smoking cessation program . Design . Telephone interviews with participants ( n=641 , response=74 % ) before and after ( end-of-program , n=1 , 023 , response=83 % ; three months n=757 , response=74 % ; six months , n=859 , response=84 % ; and 12 months , n=713 , response=70 % ) intervention provided the data to be analyzed . Setting . The Chicago metropolitan area was the setting . Subjects . Subjects were a r and om sample of registrants for the intervention program . Intervention . A self-help smoking cessation program was used , which included a manual and complementary televised segments . Engaging a buddy was optional . Measures . Background and psychosocial characteristics of participants , characteristics of buddies , program compliance , and smoking behavior were the measures used . Results . Almost one third ( 30.3 % ) engaged a buddy . Those most likely to engage a buddy were female ( 33.4 % ) , younger than 30 ( 37.2 % ) , educated beyond high school ( 33.4 % ) , highly determined to quit ( 41.8 % ) , and more likely to need help from others ( 39.8 % ) . More than half of the buddies were from outside the participant 's household ( 55.1 % ) , and more than half were nonsmokers ( 60.9 % ) . Having a buddy was associated positively with manual use ( gamma=.38 ) , viewing televised segments ( gamma=.23 ) , recalling manual segments ( gamma=.33 ) , and recalling televised segments ( gamma=.26 ) . Among those who read the manual least , having a buddy was associated with viewing televised segments ( gamma=.26 , p<.05 ) and with end-of-program quitting ( 16.8 % vs. 9.8 % , p<.05 ) . Having a buddy also was associated with higher abstinence through 12 months ( 5.8 % vs. 2.7 % , p=.013 ) . Among those with lower determination , the end-of-program quit rate was more than three times greater ( p=.013 ) for those with a buddy ( 16.1 % ) than without a buddy ( 5.2 % ) . Participants whose buddy was their spouse or partner were more likely to quit at end-of-program ( 29.1 % vs. 18.4 % , p=.031 ) . Conclusions . Buddy support should be promoted as an adjunct to minimal-contact smoking cessation programs . Impact of buddy support might be improved by guiding participants in choosing a buddy OBJECTIVE To determine the effects on cessation rates of adding a partner support group component to a large-group community-based behavioral smoking cessation program . METHODS During the past eight smoking cessation programs at the Tom Baker Cancer Centre in Calgary , Alberta , Canada , separate support group sessions were offered for support persons of prospect i ve quitters . Six hundred smokers brought 156 support people with them to the groups . Cessation rates were calculated at 3 , 6 , and 12 months postquit . RESULTS Those smokers who had support people attending at least one of the support group sessions had higher cessation rates at 3 , 6 , and 12 months ( 56 % , 46 % , and 43 % ) compared to those without a support person in attendance ( 36 % , 35 % , 32 % ) . This effect was especially strong for men , with 3- , 6- , and 12-month cessation rates for those with support of 58 % , 54 % , and 56 % , compared to 52 % , 41 % , and 36 % in the women with support . For men without a support person , the rates were 34 % , 35 % , and 33 % , compared to 38 % , 35 % , and 31 % in women without support . This indicates that although support was initially effective for women , it had no effect on sustained abstinence . CONCLUSIONS The addition of a support person group to a large-group behavioral smoking cessation program was effective in improving 3-month cessation rates in both men and women , but over 1-year of follow-up support was only associated with greater sustained abstinence in men Smokers requesting self-help material s for smoking cessation ( N = 2,021 ) were r and omized to receive ( a ) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies , ( b ) the same self-quitting guide with a support guide for the quitter 's family and friends , ( c ) self-quitting and support guides along with four brief counselor calls , or ( d ) a control guide providing motivational and quit tips and referral to locally available guides and programs . Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments . Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide , with fewer behavioral prequitting strategies and more outside treatments . Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates . Telephone counseling increased adherence to the quitting protocol and quit rates Six hundred and thirty smokers who intended to quit smoking themselves completed pre-cessation measures of self-efficacy , partner support , daily stresses and demographics . Subjects were contacted at 2 , 7 , 14 , 30 , 90 and 180 days post-cessation to determine smoking status and to re-administer the measures at 7 , 14 and 30 days post-cessation . A series of logistic regression examined which prospect i ve factors best predicted relapse between 0 - 2 days , 3 - 7 days , 8 - 14 days , 15 - 30 days , 31 - 90 days and 91 - 180 days . Relapse was predicted by different variables at different times ; however , self-efficacy was a consistent predictor of relapse over time This paper presents results from a preliminary short-term work-site intervention study aim ed at smoking cessation . The 3-month intervention included consultation for employers on the adoption of a nonsmoking policy , training for nonsmokers to provide assistance to smokers attempting to quit , and cessation classes for smokers . Eight work sites from Bloomington , Minnesota were recruited to the study and r and omly assigned to an intervention or comparison condition after a baseline survey of all employees . To assess the effect of the intervention , smokers were surveyed 1 and 6 months after the intervention was completed . At the 1-month follow-up , the overall quit rate in the intervention group was 12 % compared to 5 % in the control group ( P < .05 ) . At the 6-month follow-up , 12 % of smokers in the intervention group reported quitting , compared to 9 % in the control group ( P < .05 ) . Co-worker support for quitting was higher in the intervention group compared to the comparison group . Cessation was highest overall among smokers whose co-workers frequently asked them not to smoke and among those who worked with a high proportion of nonsmokers . These results indicate that a short-term , multifaceted smoking cessation program implemented in work sites can affect smoking cessation rates as well as the work-site norms about smoking BACKGROUND A partner 's provision of support and smoking status has been consistently associated with women 's likelihood of smoking cessation during pregnancy and relapse in postpartum . DESIGN A three-group r and omized controlled intervention trial was conducted in 1996 to 2001 , with 583 women and their partners r and omized to usual care ( UC ) , woman-only ( WO ) , or partner-assisted ( PA ) intervention . Follow-ups occurred at 28 weeks of pregnancy , and 2- , 6- , and 12-months postpartum . SETTING Womack Army Medical Center ( WAMC ) at Fort Bragg in Fayetteville , North Carolina . INTERVENTION Women in the UC condition received provider advice to quit and a self-help guide . The WO condition received UC components plus a late-pregnancy relapse prevention kit ( booklet and gift items ) and six counseling calls ( three in pregnancy and three postpartum ) initiated by a health advisor . Women in the PA condition received the WO intervention , and their partners received telephone counseling and a support guide emphasizing skills to help the woman build and maintain her confidence to quit smoking . Partners who smoked also received cessation aids and related counseling . MAIN OUTCOME MEASURE Seven-day self-reported abstinence from smoking at each follow-up . RESULTS Intent-to-treat analyses showed no significant differences by condition in women 's reports of abstinence at any follow-up . In late pregnancy , more partners were abstinent in the PA condition ( 15 % ) than in the UC condition ( 5 % ) , p = 0.02 . CONCLUSIONS Partner-assisted smoking-cessation interventions need further refinement . Influencing young couples ' support patterns may require more intensive and conjoint intervention . Partners who smoke could benefit from support for their cessation efforts BACKGROUND Although smoking cessation programs significantly reduce smoking rates in the general population , some sectors are poorly motivated by them , especially healthy men from lower socioeconomic classes . METHODS By using a significant life event ( approaching birth of a child ) we exploited a time of increased receptiveness to smoking cessation influences . A multicomponent intervention was conducted and evaluated using a stratified , r and omised control trial , with an intention to treat analysis . RESULTS Five hundred and sixty-one men were enrolled and 505 ( 90 % ) followed to the end of their partners ' pregnancy . At 6-month follow-up 16.5 % of 291 smokers of the intervention group and 9.3 % of 270 in the control group reported they had stopped smoking ( P=0.011 , OR=0.52 , 95 % CI 0.31 - 0.86 ) . The strongest predictors of smoking cessation were being in a skilled occupation , having a higher number of quit attempts in the previous year and having the first cigarette of the day relatively later . CONCLUSIONS The number of smoking men who had to be treated to achieve one stopping smoking ( NNT ) during their partner 's pregnancy was 13 to 14 . Innovative antismoking population health measures for the partners of antenatal patients are effective and perhaps should be more widely adopted OBJECTIVES This project investigated whether augmented prenatal care for high-risk African American women would improve pregnancy outcomes and patients ' knowledge of risks , satisfaction with care , and behavior . METHODS The women enrolled were African American , were eligible for Medicaid , had scored 10 or higher on a risk assessment scale , were 16 years or older , and had no major medical complications . They were r and omly assigned to augmented care ( n = 318 ) or usual care ( n = 301 ) . Augmented care included educationally oriented peer groups , additional appointments , extended time with clinicians , and other supports . RESULTS Women in augmented care rated their care as more helpful , knew more about their risk conditions , and spent more time with their nurse-providers than did women in usual care . More smokers in augmented care quit smoking . Pregnancy outcomes did not differ significantly between the groups ; however , among patients in augmented care , rates of preterm births were lower and cesarean deliveries and stays in neonatal intensive care units occurred in smaller proportions . Both groups had lower-than-predicted rates of low birthweight . CONCLUSIONS High- quality prenatal care , emphasizing education , health promotion , and social support , significantly increased women 's satisfaction , knowledge of risk conditions , and perceived mastery in their lives , but it did not reduce low birthweight To better underst and how social support operates in smoking cessation , three models of support were tested : main effect , stress-buffering , and indirect . Employees from 61 worksites received ( a ) self-help manuals ( SH ) ; ( b ) self-help manuals and incentives ( I ) ; or ( c ) self-help manuals , incentives , and social support groups ( G ) . At 24 months , results suggest that the main effect model of social support was operating in this study . That is , social support had a direct influence on smoking cessation . The group intervention significantly enhanced positive partner support across all time points , and partner support facilitated quitting smoking . Higher levels of appraisal support also significantly predicted successful quitting . The beneficial effects of social support were sustained throughout the process of quitting and long-term maintenance BACKGROUND Evaluate the feasibility , acceptability , and potential efficacy of a skills-training intervention for adults interested in helping someone to stop smoking ( i.e. , support persons ) . METHODS Sixty adult support persons ( 77 % female ) were directly recruited from the community and r and omly assigned to this intervention ( manual plus five weekly group-based sessions ) or a control condition ( one-page leaflet ) . All intervention and outcome assessment s occurred through the support persons . Assessment s occurred at weeks 0 ( baseline ) , 6 ( end of treatment ) , 12 , and 24 . The study was conducted from 1998 to 2001 ; data collection occurred from 1999 to 2000 . Outcomes were ratings of treatment acceptability , recruitment and retention rates , supportive behaviors provided to the smoker , and smoking behavior change in the smoker as reported by the support person . RESULTS Support persons were recruited in a timely manner and study retention rates were high . Support persons in skills training showed significant increases in their supportive behavior scores compared with control subjects at weeks 6 and 12 . Although not statistically significant , the skills-training intervention was associated with more quit attempts , greater improvement in stage of change , and higher 7-day point prevalence abstinence rates in the smokers than the control condition . CONCLUSIONS A skills training intervention for support persons is feasible and acceptable . Further studies are needed to test the efficacy of this approach for smoking cessation AIMS To assess the effect on abstinence rates of pairing up smokers attending a general practice smokers , clinic to provide mutual support between clinic sessions . DESIGN R and omized controlled trial comparing a " buddy " condition with a " solo condition " in which smokers received the e same treatment but were not paired up . SETTING A general practice smokers ' clinic in London . PARTICIPANTS One hundred and seventy-two smokers recruited by mailshot . INTERVENTION . Smokers attended a nurse-led smokers clinic 1 week prior to their quit date , on the quite date , 1 week later and 3 weeks after that . Smokers in the buddy condition were paired with another smoker trying to give up at the same time to provide mutual support between clinic sessions . MEASUREMENT The main outcome measure was the percentage of smokers still abstinent from cigarettes at end of treatment ( weeks from quite date ) , verified by expired air carbon monoxide concentration . FINDINGS The percentage of smokers still abstinent at the end of treatment was significantly higher in the buddy condition than the solo condition ( 27 % vs. 12 % ) . CONCLUSIONS A buddy system can provide an effective element of a smoking cessation intervention at minimal cost . Further research is needed to establish the long-term efficacy of this approach and examine the effectiveness of incorporating social support into other types of smoking cessation programmes The objective in this study was to analyse whether there is independent association between social network , social support , social influence and quitting smoking for good . The study sample ( n = 621 ) comprised a r and om half of all male Malmö residents born in 1914 , of which 500 ( 80.5 % ) participated . A new instrument based on a model with carefully defined and well differentiated concepts was used to measure different aspects of social network , social support and social influence . In logistic regression analysis , emotional support ( an important aspect of social support ) had an association to quitting smoking for good ( odds ratio 3.1 , 95 % confidence interval 1.9 - 5.4 ) , when adjustments were made for social class , marital status ( spousal support ) , alcohol consumption , physical activity , smoking of spouse and different medical conditions . Emotional support reflects the individuals ' opportunity for care , encouragement of personal value and feelings of confidence and trust . This may contribute to a deeper underst and ing of mechanisms behind smoking cessation and could be of importance in the field of health promotion , but also for improvement of the long-term results of smoking cessation programs and in our clinical work with patients who smoke Three health education interventions for urban poor hypertensive patients were introduced sequentially in a r and omized factorial design : 1 ) an exit interview to increase underst and ing of and compliance with the prescribed regimen ; 2 ) a home visit to encourage a family member to provide support for the patient 's regimen ; and 3 ) invitations to small group sessions to increase the patient 's confidence and ability to manage his/her problem . Previous evaluation of the initial two-year experience demonstrated a positive effect of the educational program on compliance with the medical treatment and blood pressure control . Data accumulated over an additional three years , including mortality analysis , are now presented . The study group consisted of the same cohort of 400 ambulatory hypertensive out patients in the eight experimental and control groups . The five-year analysis shows a continuing positive effect on appointment keeping , weight control , and blood pressure control . All-cause life table mortality rate was 57.3 per cent less for the experimental group compared to the control group ( 12.9/100 vs 30.2/100 , p less than .05 ) , while the hypertension-related mortality rate was 53.2 per cent less ( 8.9/100 vs 19.0/100 , p less than .01 ) . The results from this longitudinal study provide evidence to encourage health practitioners to utilize such educational programs in the long-term management and control of high blood pressure We evaluated the effects of adding a social support component to a worksite controlled smoking treatment program . Twenty-four participants were r and omly assigned to either a controlled smoking or a controlled smoking plus partner support condition . Within a multiple baseline across behaviors design , smokers in both conditions made efforts to achieve sequential 50 % reductions in : nicotine content of br and smoked , number of cigarettes smoked per day , and percentage of each cigarette smoked . Self-monitoring records , laboratory analyses of spent cigarette butts , and carbon monoxide determinations indicated that both conditions were effective in producing significant reductions in each of the three target behaviors and in carbon monoxide levels . All participants who quit smoking during the program maintained their abstinence at a 6-month follow-up , and those who did not quit were smoking less at follow-up than they had at pretest on all dependent variables . However , few differences were observed between controlled smoking and controlled smoking plus partner support conditions either during treatment or at the 6-month follow-up . Results are discussed with regard to previous worksite studies , future directions for research on social support , and variables that may have mediated treatment outcome BACKGROUND The aim of this study is to assess the effect of parental and partner 's education and smoking behavior on an individual 's chance of smoking cessation over the life course . METHODS Self-reported life histories of smoking behavior , education , and relationships were recorded in face-to-face interviews with a r and om general- population sample of 850 respondents and their partners ( if present ) . The data were collected in 2000 . A discrete-time event history model is applied in the analyses of cessation over the life course . RESULTS Parents ' education and smoking behavior ( during adolescence ) and partners ' education have no significant influence on cessation . Living with an ex-smoker or never-smoker increases the likelihood of quitting , compared to being single or living with a partner who smokes . Respondents whose partners were ex-smokers are almost five times more likely to quit smoking than single respondents . They are almost twice as likely to quit compared to those living with a never-smoker . CONCLUSIONS The difference between having and not having a partner seems as important for cessation as the difference between having a partner who smokes , has never smoked , or has stopped smoking . An ex-smoking partner stimulates cessation more than a partner who has never smoked . Studies into cessation should take into account partners ' smoking histories This study aim ed to assess the effect of a hospital‐based smoking cessation intervention delivered by midwives during routine antenatal and postnatal care on the smoking habits of pregnant women and their partners . At the first antenatal visit , women in the intervention group ( n=110 ) were given a demonstration of the immediate effects of smoking on foetal heart rate , brief smoking cessation advice and smoking cessation booklets for themselves and their partners ; at delivery , they were given brief advice and a booklet about postpartum cessation . Compared with an historical control group who received usual care ( n=110 ) and assuming those lost to follow‐up continued to smoke , biochemically‐verified maternal cessation sustained from at least 24 weeks gestation to late pregnancy was 6.4 % in the intervention group and 1.8 % in the comparison group . However , there was no difference between maternal quit rates at six months postpartum . Partners were more likely to try to quit in the intervention group , but quit rates did not differ . Exposure to the intervention was not associated with increased levels of psychological distress , as measured by the 12‐item General Health Question naire . We conclude that this type of intervention , when implemented by staff during routine care , is probably associated with a small improvement in maternal cessation in pregnancy , similar to that produced by minimal advice to quit smoking Smokers registering for a televised cessation program who also expressed interest in joining a support group and who had a nonsmoking buddy were r and omly assigned to 3 conditions : no-contact control , discussion , and social support . All Ss received a self-help manual and were encouraged to watch the daily TV program . Ss in the discussion and social support conditions were scheduled to attend 3 group meetings ( one with a buddy ) . Social support Ss and buddies received training in support and relapse prevention . A 4th analysis group was composed of Ss who failed to attend any of the scheduled meetings ( no shows ) . There were strong group effects at the end of treatment . Abstinence rates were highest in the social support group , followed , in order , by the discussion group , no shows , and no-contact controls . The social support group improved outcome by increasing both the level of support and program material use ( reading the manual and watching TV ) Described an examination of data collected 2 years following the onset of a media-based , worksite smoking cessation intervention . Thirty-eight companies in Chicago were r and omly assigned to one of two experimental conditions . In the inital 3-week phase , all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series design ed to accompany the manual . In addition , participants in the group ( G ) condition received six sessions emphasizing quitting techniques and social support . In the second phase , which continued for 12 months , employees in G participated in monthly peer-led support groups and received incentives , while participants in the nongroup ( NG ) condition received no further treatment . Twenty-four months after pretest , 30 % of employees in G were abstinent compared to only 19.5 % in NG . This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention In an extension and replication of previous work on social support in worksite smoking programs , 29 employees were assigned to either a basic smoking control program or to a basic treatment plus significant other support condition . Within a multiple baseline across behaviors design , all subjects received a 6 week treatment program that focused on achieving sequential reductions in nicotine content of br and smoked , number of cigarettes smoked per day , and percent of the cigarette smoked . Both treatment conditions were equally successful in producing abstinence ( verified by biochemical analyses ) and in producing reductions in smoking behavior among nonabstinent subjects at both posttest and 6-month follow-up assessment s. In contrast to previous research with this program , there was considerable relapse in both conditions by follow-up . Consistent with previous findings , supportive social interactions were not related to treatment outcome , but the level of negative ( nonsupportive ) social interactions was inversely correlated with treatment success . Implication s of these findings and directions for future research are discussed Perceptions of support for cessation of smoking during pregnancy , likelihood of quitting , and partner smoking status were explored in a sample of 688 pregnant smokers ( 372 baseline smokers and 316 baseline quitters ) . Women with nonsmoking partners were significantly more likely to be baseline quitters than women with partners who smoked . Baseline quitters reported significantly more positive support from their partners than did continuing smokers ( p = .02 ) . Neither partner smoking status nor partner support at baseline was associated with cessation or relapse later in pregnancy . Women reported greater support , both positive and negative , from nonsmoking partners than from partners who smoked ( p = .001 ) . Among partner smokers , those who were trying to quit were perceived to be particularly supportive . Cessation interventions for expectant fathers may increase pregnant women 's success at quitting OBJECTIVE The aim was to examine to what extent lifestyle , education , social support , and comorbidity predict the ability of perioperative smoking cessation , and are associated with the development of important postoperative complications . DESIGN The design was a r and omized clinical trial . SETTING University hospitals in Copenhagen , Denmark , were the setting s. PARTICIPANTS AND METHODS One hundred twenty patients scheduled for primary elective hip or knee arthroplasty were r and omized to either smoking intervention or st and ard care . Tobacco and alcohol consumption , exercise and eating habits , level of education , matrimonial status , and the presence of social support were registered . The data gathered concerned smoking cessation/reduction and severe postoperative morbidity . RESULTS Men and patients with a good social network were more likely to successfully quit smoking . Smoking intervention successfully reduced the incidence of postoperative complications , as did weekly exercise exceeding 4 h , and having a high education level . CONCLUSIONS This study emphasizes that smoking intervention programs in health care setting s are highly effective in reducing postoperative risks in hip and knee arthroplasty Smokers ( N = 99 ) were r and omly assigned to one of three conditions : nicotine gum ( NG ) , nicotine gum plus psychological treatment ( NG-PT ) , and nicotine gum plus psychological treatment and partner support ( NG-PT-PS ) . Data were collected at Weeks 0 , 4 , 12 , 26 , and 52 from study start . Contrary to expectations , NG-PT-PS and NG-PT failed to increase abstinence rates . Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions , although not significantly at Weeks 26 and 52 . Treatments without partner participation ( NG-PT and NG ) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks . The role of social support in smoking treatment is discussed Abstract This study evaluated the efficacy of a multiple treatment smoking cessation program and three maintenance strategies . Phase I of the study involved 51 subjects who participated in a 5-day smoking cessation project . The program consisted of lectures , demonstrations , practice exercises , aversive smoking , and the teaching of self-control procedures . In Phase II , all subjects were r and omly assigned to one of three maintenance conditions : a 4-week support group which offered an opportunity to discuss feelings and thoughts , a 4-week telephone contact system which enabled group members to call one another , and a no-contact control group . To evaluate efficacy , extensive follow-up data were collected at the end of treatment and at 2 , 4 , 6 , and 12 months post-treatment . The treatment program was extremely effective ; 100 % of the subjects were abstinent at the end of treatment , and at 1 year post-treatment , 63 % of the subjects reported total abstinence . As to sex differences , at the 1-year period 66 % of the women and 59 % of the men were ex-smokers . Recidivists reported a smoking rate that was 52 % of baseline at the 6-month follow-up . At 2 months post-treatment , 40 % of the abstainers reported that the quitting experience was easy , and subjects reported an average weight gain of only 4.69 lb . The authors offer suggestions for future smoking cessation research based upon the promising findings of this study Smoking cessation interventions have posed significant challenges for health professionals , particularly when directed at high risk , low income , pregnant smokers . Typical quit rates for pregnant women who receive publicly financed obstetrical care have rarely exceeded 12–16%.1 As many as 70 % of women who quit smoking during pregnancy relapse within one year of delivery.2 Two areas that have received particular attention as possible adjuncts to behaviour change are the use of reinforcements and social supports . Reinforcement in the form of incentives/rewards for positive behaviours has been controversial as an intervention strategy . Some argue that the “ overjustification effect ” of external rewards may cause subjects to lose internal motivation to modify behaviour over the long term.3 However , results of several studies , including two meta-analyses on reinforcement , provide compelling evidence that positive reinforcement provides positive behavioural changes.4 - 8 A second area of study that has been explored in the behaviour change research is the role of social support in motivating and sustaining selected behaviour change . Recent studies have empirically linked tobacco quit rates with daily interaction with a supportive “ other , ” preferably one who did not smoke.9 10 The primary objective of our intervention was to determine whether the combination of bolstered social support and financial incentives had an effect in significantly reducing smoking behaviour among low income , high risk , pregnant and postpartum women who participate in Oregon 's Women , Infants , and Children ( WIC ) program . The Significant Other Supporter ( SOS ) program was a r and omised , experimentally design ed smoking cessation study implemented in four Oregon WIC program sites . Criteria for entry into the study included the following : age 15 years or older ; self reported smoker ( “ even a puff in the last seven days ” ) ; English speaker/reader ; WIC eligible ; and 28 weeks gestation or less . Eligible subjects were r and omised into one of two groups , and were OBJECTIVES In 1986 , the state health departments of Colorado , Maryl and , and Missouri conducted a federally-funded demonstration project to increase smoking cessation among pregnant women receiving prenatal care and services from the Women , Infants , and Children ( WIC ) program in public clinics . METHODS Low-intensity interventions were design ed to be integrated into routine prenatal care . Clinics were r and omly assigned to intervention or control status ; pregnant smokers filled out question naires and gave urine specimens at enrollment , in the eighth month of pregnancy , and postpartum . Urine cotinine concentrations were determined at CDC by enzyme-linked immunosorbent assay and were used to verify self-reported smoking status . RESULTS At the eighth month of pregnancy , self-reported quitting was higher for intervention clinics than control clinics in all three states . However , the cotinine-verified quit rates were not significantly different . CONCLUSIONS Biochemical verification of self-reported quitting is essential to the evaluation of smoking cessation interventions . Achieving changes in smoking behavior in pregnant women with low-intensity interventions is difficult This article evaluates the relationship of social support to smoking cessation and continued abstinence of 3923 men and women with mild to moderate airway obstruction in the Lung Health Study . At both the end of a 12-week group program and after 1 year , men but not women who were supported in quitting were more likely to be successful . Married status facilitated quitting but was less strongly related to long-term abstinence . Participants supported by an ex-smoker who had attended the group program with them were very likely not smoking after 1 year ( men , 74.7 % ; women , 72.4 % ) . Participants supported by a smoker were less than half as likely to have achieved abstinence after 1 year but still had cessation rates greater than 30 % . The nature of these relationships has implication s for the distinction between women and men in studies of social support and for intervention strategies . Support people should be included in cessation intervention programs . Spouse involvement , however , is more evidently useful for men than for women Deux etudes longitudinales , prospect ives , examinent le role du soutien social dans le maintien de la decision de ne plus fumer : soutien d'un partenaire ; existence d'un climat social encourageant le sevrage ; participation a un reseau social . Part de chacun des facteurs dans le maintien de la decision et l'absence de rechute . Etudes & NA ; This article describes preliminary findings of an experimental , r and omized , three‐group , controlled design examining the effectiveness of a smoking cessation intervention for pregnant teens . The three groups are : Teen FreshStart with a buddy program ( TFSB ) , a Teen FreshStart program ( TFS ) without peer support , and the Usual Care ( UC ) control group . Forty‐six subjects completed the post‐intervention assessment of smoking status . The TFSB group consistently achieved greater smoking cessation across all measures when compared to the subjects in the other two groups . These results indicate that the use of peer support may be an effective adjunct in smoking cessation programs for pregnant adolescents This study involved 137 participants who were assessed on 12 relevant predictor variables and then r and omly assigned to social support or self-control treatment . Outcome across treatments was predicted by cotinine levels , treatment history , previous abstinence , happiness , self-efficacy , and perceived social support for quitting . Social support treatment was more effective than self-control treatment for participants with high baseline self-control orientation scores and participants with high self-efficacy scores . All other hypothesized Subject x Treatment interaction effects were nonsignificant . The study provided an example of a coherent approach to matching research and demonstrated the difficulty involved in providing treatments that are different enough from each other to benefit different smokers . Matching research has important theoretical value but may have limited potential for improving smoking treatment effectiveness It has repeatedly been demonstrated that increased levels of social support are positively associated with a smoker 's likelihood of achieving abstinence . It remains unclear , however , what specific support behaviors influence smoking cessation . This study explores the effects of supportive and undermining behaviors experienced by subjects ( N = 624 ) in the context of a romantic/marital relationship on a number of smoking cessation outcomes . The associations of social support behaviors with one- , two- , and three-year abstinence and recycling and making quit attempts at 6 , 12 , 24 , and 34 months were examined . Frequencies of both supportive and undermining behaviors predicted the dependent variables under study . Subjects whose spouses demonstrated fewer undermining behaviors were more likely to be successful continuous abstainers , whereas participants ' recycling and making quit attempts seemed to be best predicted by a greater frequency of supportive behaviors . Initial success at cessation might be associated with increased supportive behaviors by a spouse , whereas lower rates of undermining behaviors might be associated with long-term maintenance . Long-term tailored feedback to spouses of smokers wanting to quit might be helpful Purpose . The purpose of this study was to compare a culturally specific , multicomponent behavioral smoking cessation program for Hispanic smokers with a low-intensity , enhanced self-help control condition . Design . Participants who completed pretreatment assessment were r and omly assigned to treatment conditions . Smoking status was evaluated at posttreatment , 6-month follow-up , and 12-month follow-up intervals . Setting . The study was based in predominantly Hispanic neighborhoods in Queens , New York . Participants . Ninety-three Hispanic smokers participated : 48 men and 45 women . Intervention . The multicomponent treatment involved a clinic-based group program that incorporated a culturally specific component consisting of videotaped presentations of culturally laden smoking-related vignettes . The self-help control program was enhanced by the use of an introductory group session and follow-up supportive telephone calls . Measures . Smoking outcomes were based on cotinine-vali date d abstinence and self-reported smoking rates . Predictors of abstinence were examined , including sociodemographic variables , smoking history , nicotine dependence , acculturation , partner interactions , reasons for quitting , self-efficacy , and linguistic competence . Results . Significant group differences in cotinine-vali date d abstinence rates in favor of the multicomponent group were obtained , but only at posttreatment . With missing data included and coded for nonabstinence , vali date d abstinence rates at posttreatment were 21 % for the multicomponent group and 6 % for the self-help group . At the 6-month follow-up , the rates were 13 % for the multicomponent group and 9 % for the self-help group . By the 12-month follow-up , the rates declined to 8 % and 7 % for the multicomponent and self-help groups , respectively . A dose-response relationship between attendance at group sessions and abstinence status was shown at posttreatment and 6-month follow-up intervals . Conclusions . The results of the present study failed to show any long-term benefit from use of a clinic-based , culturally specific multicomponent smoking cessation intervention for Hispanic smokers relative to a minimal-contact , enhanced self-help control |
12,558 | 27,118,430 | The findings support that habitual regulatory processes measured via self-report are directly associated with physical activity beyond conscious processes , and that there is likely interdependency between habit strength and intentions .
A small body of evidence demonstrated a variety of priming effects on physical activity . | ABSTRACT Physical activity theories have almost exclusively focused on conscious regulatory processes such as plans , beliefs , and expected value .
The aim of this review was to aggregate the burgeoning evidence showing that physical activity is also partially determined by non-conscious processes ( e.g. , habits , automatic associations , priming effects ) . | Both habit strength and action planning have been found to moderate the intention-exercise behaviour relationship , but no research exists that has investigated how habit strength and action planning simultaneously influence this relationship . The present study was design ed to explore this issue in a prospect i ve sample of undergraduate students ( N = 415 ) : action planning , habit strength , intention , attitudes , subjective norms and perceived behavioural control were assessed at baseline and exercise behaviour was assessed 2 weeks later . Both habit strength and action planning moderated the intention-exercise relationship , with stronger relationship at higher levels of planning or habit strength . Decomposing a significant action planning × habit strength × intention interaction showed that the strength of the intention-exercise relationship progressed linearly through levels of action planning and habit strength . These novel results show that action planning strengthens the intention-habit strength interaction in the exercise domain : exercise interventions should therefore focus on simultaneously bolstering action planning and habit strength Rationale Since implicit attitudes toward alcohol play an important role in drinking behavior , a possible way to obtain a behavioral change is changing these implicit attitudes . Objectives This study examined whether a change in implicit attitudes and in drinking behavior can be achieved via evaluative conditioning . Methods Participants were r and omly assigned to an experimental condition and a control condition . In the experimental condition , participants were subjected to an evaluative conditioning procedure that consistently pairs alcohol-related cues with negative stimuli . In the control condition , alcohol-related cues were consistently paired with neutral stimuli during the evaluative conditioning phase . Implicit attitudes , explicit attitudes , and drinking behavior were measured before and after the evaluative conditioning phase . Results Following the evaluative conditioning procedure , participants in the experimental condition showed stronger negative implicit attitudes toward alcohol and consumed less alcohol compared to participants in the control condition . However , this effect was only found when the evaluative conditioning task paired alcohol-related cues with general negative pictures , but not when using pictures of frowning faces . Conclusions These results demonstrate that evaluative conditioning can effectively change implicit attitudes toward alcohol and also suggest that this procedure can be used to change drinking behavior . Hence , evaluative conditioning may be a useful new intervention tool to combat alcohol misuse An implicit association test ( IAT ) measures differential association of 2 target concepts with an attribute . The 2 concepts appear in a 2-choice task ( 2-choice task ( e.g. , flower vs. insect names ) , and the attribute in a 2nd task ( e.g. , pleasant vs. unpleasant words for an evaluation attribute ) . When instructions oblige highly associated categories ( e.g. , flower + pleasant ) to share a response key , performance is faster than when less associated categories ( e.g. , insect & pleasant ) share a key . This performance difference implicitly measures differential association of the 2 concepts with the attribute . In 3 experiments , the IAT was sensitive to ( a ) near-universal evaluative differences ( e.g. , flower vs. insect ) , ( b ) expected individual differences in evaluative associations ( Japanese + pleasant vs. Korean + pleasant for Japanese vs. Korean subjects ) , and ( c ) consciously disavowed evaluative differences ( Black + pleasant vs. White + pleasant for self-described unprejudiced White subjects ) Intention is considered the proximal determinant of behavior in many popular theories applied to underst and ing physical activity , yet intention – behavior discordance is high . Thus , an underst and ing of constructs that facilitate or inhibit the successful translation of intentions into behavior is both timely and important . The action control approach of dividing the intention – behavior relationship into quadrants of successful/unsuccessful intenders has shown utility in the past by demonstrating the magnitude of intention – behavior discordance and allowing for an outcome variable to test predictors . The purpose of this article was to evaluate automaticity and cross-behavioral regulation as predictors of exercise action control , in conjunction with other more st and ard social cognitive predictors of perceived behavioral control and affective and instrumental attitudes . Participants were a r and om sample of 263 college students who completed predictor measures at time one , followed by exercise behavior two weeks later . Participants were classified into three intention – behavior profiles : ( 1 ) nonintenders ( 14.1 % ; n = 31 ) , ( 2 ) unsuccessful intenders ( 35.5 % ; n = 78 ) , and ( 3 ) successful intenders ( 48.6 % ; n = 107 ) . Affective attitude , perceived behavioral control , automaticity , and cross-behavioral regulation were predictors of action control . The results demonstrate that automaticity and cross-behavioral regulation , constructs not typically used in intention-based theories , predict intention – behavior discordance OBJECTIVE Habit might be usefully characterized as a form of automaticity that involves the association of a cue and a response . Three studies examined habitual automaticity in regard to different aspects of the cue-response relationship characteristic of unhealthy and healthy habits . DESIGN , MAIN OUTCOME MEASURES , AND RESULTS In each study , habitual automaticity was assessed by the Self-Report Habit Index ( SRHI ) . In Study 1 SRHI scores correlated with attentional bias to smoking cues in a Stroop task . Study 2 examined the ability of a habit cue to elicit an unwanted habit response . In a prospect i ve field study , habitual automaticity in relation to smoking when drinking alcohol in a licensed public house ( pub ) predicted the likelihood of cigarette-related action slips 2 months later after smoking in pubs had become illegal . In Study 3 experimental group participants formed an implementation intention to floss in response to a specified situational cue . Habitual automaticity of dental flossing was rapidly enhanced compared to controls . CONCLUSION The studies provided three different demonstrations of the importance of cues in the automatic operation of habits . Habitual automaticity assessed by the SRHI captured aspects of a habit that go beyond mere frequency or consistency of the behavior CONTEXT Participation in regular physical activity is recognized as one of the most important health behaviors associated with the prevention of chronic disease and the promotion of health and well-being among the elderly . Although a number of cross-sectional studies have reported predictors of physical activity participation , few studies have assessed changes in intervention-related mediators associated with physical activity adherence in the elderly . OBJECTIVE The purpose of this study was to compare the relative abilities of cognitive mediating variables ( i.e. , self-efficacy beliefs and outcome expectancies/realizations ) versus a social mediating variable ( i.e. , exercise-related social support ) to examine mediators of a telephone-based , exercise-counseling intervention on exercise adherence during months 7 to 12 of an exercise intervention . METHOD Participants were 103 community-dwelling , healthy , sedentary , older adults ( 67 women and 36 men ) . Self-efficacy for exercise , outcome expectancies/realizations , and social support for exercise were assessed at baseline , 6 months , and 12 months . Participants received telephone-based exercise counseling to promote exercise adherence during the course of two 12-month exercise programs ( i.e. , aerobic/strength or flexibility exercises ) . RESULTS Changes in cognitive mediators ( i.e. , self-efficacy and fitness outcome realizations ) were associated with 7- to 12-month exercise adherence while exercise-related social support was not . CONCLUSION Attention should be given to increasing confidence in the elderly to overcome barriers to exercise and achieve relevant fitness outcomes in exercise programs This study was design ed to examine the moderating influence of habit strength on daily action planning effects on physical activity and sedentary behavior . A 2 by 2 design was used with experimental factors corresponding to action planning interventions for ( a ) engaging in physical activity and ( b ) limiting or interrupting sedentary behavior . At the end of each day for 1 week , university students ( n = 195 ) completed ( a ) a question naire about their behavior during the day and behavioral intentions for the following day and ( b ) a planning intervention(s ) corresponding to their r and omly assigned experimental condition . Action planning increased physical activity in those with weak habits but decreased physical activity in those with strong habits compared with those who did not create action plans . Action planning did not impact sedentary behavior . Action planning was a useful behavior change technique for increasing physical activity in people with weak habits , but may be iatrogenic for those with strong habits OBJECTIVES The theory of planned behavior proposes that physical activity is the result of intentions ; however little is known about whether the relation between intentions and behavior differs between vigorous , moderate physical activity , and walking . For university students , vigorous physical activity is oftentimes enacted as a goal -directed behavior ; whereas walking is oftentimes a means to achieving a goal other than physical activity ( e.g. , transportation ) . DESIGN The study was a one-week prospect i ve study . METHODS Undergraduate students ( N=164 ) reported intentions for walking , moderate physical activity , and vigorous physical activity and self-reported these behaviors one week later . RESULTS Hierarchical linear modeling revealed that intentions were more strongly related to vigorous physical activity than to moderate physical activity or walking . CONCLUSIONS Intention-enhancing interventions may effectively promote vigorous physical activity , but other motivational processes may be more appropriate to target in interventions of walking and moderate physical activity |
12,559 | 20,091,510 | This review demonstrated that no single fluid affects any outcome measure significantly more than another fluid across a range of outcomes .
There are no studies examining the effects of combination fluid therapy . | BACKGROUND Surgery on the abdominal aorta to treat aneurysms or occlusive disease is a major undertaking which requires intensive physiological support and fluid management .
Blood products are often used but the main fluid replacement is with crystalloids or colloids .
For years there has been controversy over which fluid is optimal and a number of studies have examined the subject .
This is an up date of a Cochrane review first published in 2000 and previously up date d in 2002 .
OBJECTIVES To determine the effectiveness of different non-blood replacement fluids used in abdominal aorta procedures with a view to identifying the optimal fluid for use . | OBJECTIVE To specifically compare the effect of two hydroxyethyl starches ( HES ) on the splanchnic microcirculation and systemic inflammation during abdominal aortic aneurysm ( AAA ) surgery . MATERIAL S AND METHODS A prospect i ve r and omised study was carried out on 62 patients who received HES of molecular-weight 200 kDa ( HES200/0.62 ) , 130 kDa ( HES130/0.4 ) or gelatine for 24h peri-operatively . Gastric-mucosal pHi ( GpHi ) and anti-endotoxin antibody were used as markers of splanchnic perfusion and endotoxaemia respectively . C-reactive protein ( CRP ) and lung-injury score ( LIS ) were used as markers of systemic inflammation and end-organ dysfunction respectively . Data was collected prospect ively . RESULTS The drop in GpHi was least with HES200/0.62 compared to HES130/0.4 and gelatine at reperfusion ( 7.32 vs 7.28 and 7.28 , p=0.017 and 0.009 respectively ) and compared to gelatine at 2h as well ( 7.43 vs 7.28 , p=0.001 ) . GpHi dropped less with HES130/0.4 compared to gelatine at 2h ( 7.39 vs 7.28 , p=0.002 ) . Endotoxaemia increased only with gelatine . CRP was lower with HES200/0.62 ( 178 mg/mL ) than gelatine ( 221 mg/mL ) and HES130/0.4 ( 223 mg/mL ) at 48 h ( p=0.049 and p=0.009 respectively ) . There was no difference in LIS but ventilation duration was less with HES200/0.62 compared with gelatine ( 4 vs 11h , p=0.012 ) . CONCLUSION During AAA surgery , HES200/0.62 provides the best splanchnic microcirculation protection , also reducing inflammation and duration of ventilation BACKGROUND Gastric intramucosal pH ( pHi ) , a surrogate marker of splanchnic oxygenation , falls following abdominal aortic aneurysm surgery . AIM To investigate the effects of volume expansion with hydroxyethyl starch ( eloHAES ) on splanchnic perfusion compared to another colloid such as gelofusine . PATIENTS AND METHODS Twenty-two consecutive patients undergoing AAA repair were r and omised to receive either eloHAES or gelofusine as plasma exp and ers . Tissue oxygenation was monitored ( 10 gelofusine and 12 eloHAES ) indirectly by measuring pHi using a nasogastric tonometer . RESULTS Compared to the eloHAES group , the fall in pHi was significantly greater in the gelofusine group at clamp release ( 7.29 vs 7.33 , P=0.003 ) and at 4 h following clamp release ( 7.29 vs 7.33 , P=0.03 ) . There was a good inverse correlation between the lowest pHi and the peak serum interleukin-6 ( r(s)= -0.47 , P=0.03 ) . By multivariate analysis , the only factor that influenced the pHi was the type of colloid used ( F=5.54 , P=0.005 ) . The eloHAES treated patients required significantly less colloid on the first postoperative day ( 3175 + /- 175 vs 4065 + /- 269 ml , P=0.01 ) . CONCLUSION In patients undergoing abdominal aortic aneurysm repair , plasma expansion with eloHAES improves microvascular perfusion and splanchnic oxygenation In a prospect i ve r and omized trial of 16 patients undergoing abdominal vascular reconstructive procedures , changes in plasma volume , serum oncotic pressure ( pis ) , serum albumin and total protein concentration , alveolar to arterial oxygen tension differences ( AaDO2 , FIO2 = 1.0 ) , creatinine clearance , body weight , and fluid and sodium intake were examined . By r and om assignment patients received either an albumin- or a sodium-rich intraoperative fluid regimen . Pulmonary arteriovenous admixture was significantly less in the albumin group ( n = 7 ) than in the electrolyte group ( n = 9 ) on the first postoperative day . The change in AaDO2 correlated positively with the total sodium intake in the electrolyte group . Despite the larger fluid load and significantly greater gain of body weight , patients in the electrolyte group had a postoperative plasma volume significantly lower than the preoperative value . Postoperative values of albumin concentration , circulating albumin mass and pis were significantly greater in the albumin group in comparison to the electrolyte group . Creatinine clearance values were not different between the two groups . The change in pis correlated significantly with sodium intake and circulating albumin mass . Pulmonary shunting and expansion of the extracellular fluid volume may be minimized without adverse effects on renal function by administration of fluids rich in albumin in preference to sodium AIM The present study was design ed to assess whether prophylactic use of bicarbonated Ringer 's solution ameliorates metabolic acidosis in patients undergoing aortic surgery . METHODS Twenty patients undergoing elective infrarenal aortic aneurysm repair were r and omly assigned to receive either bicarbonated Ringer 's solution or acetated Ringer 's solution . The pH , PaCO(2 ) , and base excess ( BE ) were measured before surgical incision ( T0 ) , 5 min before reperfusion ( T1 ) , 5 min after reperfusion ( T2 ) , and 30 min after reperfusion ( T3 ) . Data were compared between the two groups . RESULTS Both pH and BE initially showed a slight decrease in both groups during clamping . After unclamping of the aorta , an additional decrease in pH was observed in both groups ( T0 to T2 , and T3 ) . There were no significant differences in pH between the groups throughout the study period . CONCLUSIONS Aortic cross-clamping leads to the development of metabolic acidosis , with a decrease in pH and BE . The effect of administration of bicarbonated infusion fluid during elective abdominal aortic surgery had not significant compared with that of acetated Ringer 's solution with respect to acid-base homeostasis PURPOSE The net benefit of routine intraoperative autotransfusion ( IAT ) in patients undergoing elective infrarenal aortic surgery was studied . METHODS One hundred patients undergoing abdominal aortic aneurysm ( AAA ) repair ( n = 50 ) or aortofemoral bypass ( AFB ) for occlusive disease ( n = 50 ) were r and omized to IAT and control groups . This experience accounted for 58 % of patients undergoing aortic surgery during the 16-month study period . RESULTS IAT and control groups were balanced for preoperative demographics , disease ( 50:50 split of AFB : AAA in each group ) , and risk factors . There were no significant differences between patients r and omized to IAT and control patients in estimated blood loss ( EBL ) , allogeneic blood transfusion ( units administered intraoperatively , postoperatively , and total ) , proportion of patients not receiving allogeneic blood ( 34 % of patients r and omized to IAT and 28 % of control patients ) , postoperative hemoglobin/hematocrit levels , and complications . IAT did not reduce allogeneic blood transfusion among all patients undergoing aortic surgery nor in any subgroups that might be more likely to benefit , such as those undergoing AAA repair , those with 1000 mL or more EBL , and those receiving larger volumes of IAT-processed blood . CONCLUSION We could find no net benefit of IAT in patients undergoing elective , infrarenal aortic surgery Metabolic acidosis and changes in serum osmolarity are consequences of 0.9 % normal saline ( NS ) solution administration . We sought to determine if these physiologic changes influence patient outcome . Patients undergoing aortic reconstructive surgery were enrolled and were r and omly assigned to receive lactated Ringer ’s ( LR ) solution ( n = 33 ) or NS ( n = 33 ) in a double-blinded fashion . Anesthetic and fluid management were st and ardized . Multiple measures of outcome were monitored . The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy ( 30 ± 62 mL in the NS group versus 4 ± 16 mL in the LR group ; mean ± sd ) , which was given if the base deficit was greater than −5 mEq/L. The NS patients also received a larger volume of platelet transfusion ( 478 ± 302 mL in the NS group versus 223 ± 24 mL in the LR group ; mean ± sd ) . When all blood products were summed , the NS group received significantly more blood products ( P = 0.02 ) . There were no differences in duration of mechanical ventilation , intensive care unit stay , hospital stay , and incidence of complications . When NS was used as the primary intraoperative solution , significantly more acidosis was seen on completion of surgery . This acidosis result ed in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products . These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration Preoperative normovolemic hemodilution ( PNH ) has been proposed for patients scheduled to undergo aortic surgery . Coronary artery disease is frequent in these patients . The aim of the study was to assess the effect of PNH on hemodynamics and segmental wall motion ( SWM ) evaluated by transesophageal echocardiography in such patients . Twenty patients with coronary artery disease were allocated r and omly to either PNH or no PNH ; PNH was performed after anesthetic induction using dextran 60,000 . Patients were operated on under general anesthesia and monitored intraoperatively with electrocardiographic lead CM5 , radial and pulmonary artery catheters , and transesophageal echocardiography positioned to obtain a short-axis view . Hemodynamic and transesophageal echocardiographic data were collected after anesthetic induction and after PNH , before and 5 min after aortic clamping , after unclamping , and at the end of surgery . Aortic clamping induced a significant increase in systemic vascular resistance and arteriovenous difference in oxygen and a decrease in cardiac index ( P < 0.05 ) , but the effect of aortic clamping was inversely related to hemodilution . The SWM score ( grade d from 1 = normal to 5 = dyskinesia ) was significantly increased after aortic clamping , mainly in the anterior segment ( P < 0.05 ) . Four patients in the control ( no PNH ) group and one in the PNH group developed new SWM abnormalities indicative of myocardial ischemia during surgery ( P = NS ) . This study suggests that PNH may improve hemodynamic tolerance to aortic clamping in patients with coronary artery disease . The observed changes in SWM indicate that PNH may not worsen myocardial ischemia in patients scheduled to undergo aortic surgery Objective To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit ( ICU ) or the hospital after elective repair of infrarenal abdominal aortic aneurysms . Design Prospect i ve , r and omized study . Setting Surgical intensive care unit ( SICU ) of a University Hospital . Patients Fifty-five consecutive patients r and omized to group 1 ( pHi-guided therapy ) or to group 2 ( control ) . Interventions Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospect i ve protocol in order to increase their pHi to 7.32 or more . Measurements and results pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals . In group 2 , the treating physicians were blinded for the pHi values . Complications , APACHE II scores , duration of endotracheal intubation , fluid and vasoactive drug treatment , treatment with vasoactive drugs , length of stay in the SICU and in the hospital and hospital mortality were recorded . There were no differences between groups in terms of the incidence of complications . We found no differences in APACHE II scores on admission , the duration of intubation , SICU or hospital stay , or hospital mortality . In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable ( 41 % and 42 % in groups 1 and 2 , respectively ) . Patients with pHi lower than 7.32 had more major complications during SICU stay ( p<0.05 ) , and periods more than 10 h of persistently low pHi values ( < 7.32 ) were associated with a higher incidence of SICU complications ( p<0.01 ) . Conclusions Low pHi values ( < 7.32 ) and their persistence are predictors of major complications . Treatment to elevate low pHi values does not improve postoperative outcome . Based on these data , we can not recommend the routine use of gastric tonometers for pHi-guided therapy in these patients . Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient ’s postoperative course and outcome Intentional normovolemic hemodilution was chosen as the model to compare a 6 % low molecular weight hydroxyethyl starch ( LMW HES ) to 4 % albumin . The study ran over the plasma exchange period for 24 h. Nine patients , scheduled for abdominal aortic surgery , were included in each group . After basal measurements , blood was withdrawn and simultaneously replaced by either 4 % albumin ( Group 1 ) or 6 % LMW HES ( Group 2 ) to achieve a final hematocrit of approximately 30 % . Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution then at 30 min , 1 , 2 , 3 , and 24 h after the end of hemodilution . Basal value for total blood volume was 4377±162 ml in group 1 and 4138±315 ml in group 2 . As in both groups the decrease in blood cell volume was exactly compensated by the increase in plasma volume , no significant change in total blood volume ( respectively 4432±159 and 4305±267 ml ) was observed . Throughout the study , in both groups , no significant change in mean arterial and right atrial pressures was observed . In group 2 ( LMW HES ) , a significant increase of pulmonary capillary wedge pressure was noted 120 min after hemodilution . After hemodilution , despite a significant decrease in arterial oxygen O2 content , systemic oxygen transport did not significantly vary until 24 h in relation to the increased cardiac index . An increase in O2 extraction was observed until the 24 h. No significant chagnes either in global O2 consumption or in lactate concentration were detected . Plasma renin activity fell in both groups while atrial natriuretic factor increased with a peak value at the 2 h. These data suggest that LMW HES as well as 4 % albumin was able to maintain at least normovolemia during a 24 h period after intentional hemodilution BACKGROUND Restoring blood flow to ischaemic tissue can cause lung damage with pulmonary oedema . Hydroxyethyl starch ( HES ) solution , when used for volume replacement , may modify and reduce the degree of ischaemia-reperfusion injury . We compared the effects of HES solution with those of Gelofusine solution on pulmonary function , microvascular permeability and neutrophil activation in patients undergoing elective infrarenal abdominal aortic aneurysm surgery . METHODS Forty patients were r and omized into two groups . The anaesthetic technique was st and ardized . Lung function was assessed with the PO(2)/FI(O(2 ) ) ratio , respiratory compliance , chest x-ray and a score for lung injury . Microvascular permeability was determined by measuring microalbuminuria . Neutrophil activation was determined by measurement of plasma elastase . RESULTS Four hours after surgery , the median ( quartile values ) PO(2)/FI(O(2 ) ) ratio was 40.3 ( 37.8 , 53.1 ) kPa for the HES-treated patients compared with 33.9 ( 31.2 , 40.9 ) kPa for the Gelofusine-treated patients ( P<0.01 , Mann-Whitney test ) . The respiratory compliance was 80 ( 73.5 , 80 ) ml cm(-1 ) H(2)O in the HES-treated patients compared with 60.1 ( 50.8 , 73.3 ) ml cm(-1 ) H(2)O in the Gelofusine-treated patients ( P<0.01 , Mann-Whitney test ) . The lung injury score 4 h after surgery was less for the patients treated with HES compared with the patients treated with Gelofusine ( 0.33 vs 0.71 , P=0.01 , Wilcoxon rank sum test ) . Mean ( SD ) plasma elastase was less in the HES-treated patients on the first postoperative day ( 1.96 ( 0.17 ) vs 2.08 ( 0.24 ) , P<0.05 ) . The log mean microalbuminuria was less in the HES-treated patients ( 0.41 vs 0.91 mg mmol(-1 ) , P<0.05 ) . This difference in microvascular permeability was associated with different volumes of colloid required to maintain stable cardiovascular measurements in the two groups of patients studied ( 3000 vs 3500 ml , P<0.01 , Mann-Whitney test ) . CONCLUSION Compared with Gelofusine , the perioperative pulmonary function of patients treated with HES after abdominal aortic aneurysm surgery was better BACKGROUND The optimal type of fluid for treating hypovolaemia without evoking pulmonary oedema is still unclear , particularly in the presence of pulmonary vascular injury , as may occur after cardiac and major vascular surgery . METHODS In a single-centre , prospect i ve , single-blinded clinical trial 67 mechanically ventilated patients were r and omly assigned to receive saline , gelatin 4 % , HES 6 % or albumin 5 % , according to a 90 min fluid loading protocol with target central venous pressure of 13 and pulmonary capillary wedge pressure of 15 mm Hg , within 3 h after cardiac or major vascular surgery . Before and after the protocol , we recorded haemodynamics and ventilatory variables and took chest radiographs . The pulmonary vascular injury was evaluated using the 67Ga-transferrin pulmonary leak index ( PLI ) and extravascular lung water ( EVLW ) . Plasma colloid osmotic pressure ( COP ) was determined and the lung injury score ( LIS ) was calculated . RESULTS More saline was infused than colloid solutions ( P<0.005 ) . The COP increased in the colloid groups and decreased in patients receiving saline . Cardiac output increased more in the colloid groups . At baseline , PLI and EVLW were above normal in 60 and 30 % of the patients , with no changes after fluid loading , except for a greater PLI decrease in HES than in gelatin-loaded patients . The oxygenation ratio improved in all groups . In the colloid groups , the LIS increased , because of a decrease in total respiratory compliance , probably associated with an increase in intrathoracic plasma volume . CONCLUSIONS Provided that fluid overloading is prevented , the type of fluid used for volume loading does not affect pulmonary permeability and oedema , in patients with acute lung injury after cardiac or major vascular surgery , except for HES that may ameliorate increased permeability . During fluid loading , changes in LIS ( and respiratory compliance ) do not represent changes in pulmonary permeability or oedema OBJECTIVES To determine the effect of acute normovolaemic haemodilution ( ANH ) on the inflammatory response and clinical outcome in elective open abdominal aortic aneurysm ( AAA ) repair . DESIGN R and omised controlled clinical trial . METHODS Thirty-six patients were r and omised to undergo ANH or act as controls . Cell salvage was permitted in both groups . Heterologous blood was transfused according to pre-determined triggers . Outcome measures were markers of the systemic inflammatory response in serum and urine observed at multiple time points , and clinical recovery . RESULTS Median 890 ( range 670 - 1620 ) ml of blood was removed at ANH in 16 patients . There were no differences in peri-operative changes in neutrophil count ( P = 0.13 ) , serum C-reactive protein ( P = 0.38 ) , interleukin-6 ( P = 0.50 ) , total antioxidant capacity ( P = 0.73 ) , urinary secretion of albumin ( P = 0.97 ) or retinol binding protein ( P = 0.41 ) . There were no differences in the mortality and morbidity rates , systemic inflammatory response syndrome , ITU or hospital stay . CONCLUSIONS ANH , when used in combination with cell salvage , made no impact on systemic inflammatory response and clinical outcome when compared to cell salvage alone after AAA repair . ANH can not be recommended for routine use in patients undergoing abdominal aortic aneurysm surgery when cell salvage is available The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospect ively in 29 patients undergoing abdominal aortic surgery . Blood loss was replaced with packed red cells and extracellular volume with either Ringer 's Lactate ( RL ) or 5 % albumin in Ringer 's lactate ( ALB ) . Fluids were given to maintain the pulmonary capillary wedge pressure ( PCWP ) equal to or within 5 torr above preoperative ( PO ) levels , the cardiac output ( CO ) equal to or greater than preoperative values , and the urine output at least 50 ml/hr . Serum colloid osmotic pressure ( COP ) , CO , PCWP , the gradient between COP and PCWP ( COP-PCWP ) , and intrapulmonary shunt ( Qs/Qt ) were measured PO , intraoperatively ( IO ) , and daily for 3 days . The measured variables were similar PO in both groups . Operation time , estimated blood loss , and transfusions were similar . Total fluids received for resuscitation ( day of operation ) was 11.3 + /- 0.8 liters ( RL ) and 6.2 + /- 0.4 liters ( ALB ) . Fluid balance at the end of resuscitation was 8.4 + /- 0.8 liters ( RL ) and 3.4 + /- 0.5 liters ( ALB ) . Maximum decrease in COP was 40 % ( P less than 0.001 ) in the RL group and was insignificant in the ALB group . The COP-PCWP decreased from 11 + /- 1 to 2 + /- 1 in RL ( P less than 0.001 ) and insignificantly in ALB . Qs/Qt increased slightly in both groups following operation but was not different between groups . Fluid balance , total fluid infused , sodium balance , total sodium infused , COP , or COP-PCWP did not significantly correlate with Qs/Qt . Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs . There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group . These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation . When titrated to physiological end points , even large volumes of balanced salt solutions are tolerated well Objective : To evaluate the magnitude and cause of metabolic acidosis after infusion of 7.5 % sodium chloride 6 % dextran 70 . Design : R and omized , prospect i ve clinical study . Setting : University hospital . Patients : Two groups of 14 patients each , undergoing repair of abdominal aortic aneurysm . Interventions : Patients were r and omly assigned to receive either 250 mL of hypertonic saline dextran ( HSD ) or a conventional fluid regimen with 250 mL of hydroxyethyl starch in normal saline solution ( H-NS ) during the period of aortic clamping . Additionally , normal saline was used in both groups to reach a target pulmonary artery occlusion pressure of 15–18 mmHg . pH , Paco2 , and serum concentrations of sodium , potassium , magnesium , calcium , chloride , lactate , albumin , and phosphate were measured . Strong ion difference was calculated as ( sodium + potassium + magnesium + calcium ) − ( chloride + lactate ) . The amount of weak plasma acid was calculated . Measurements and Main Results : The infusion of HSD result ed in an immediate large increase in serum sodium ( 19 mmol/L ) and chloride ( 22 mmol/L ) , whereas the infusion of H-NS led only to mild increases in serum sodium ( 3 mmol/L ) and chloride ( 6 mmol/L ) . Both HSD and H-NS caused concomitant and equal decreases in the amount of weak plasma acid , strong ion difference , and pH ( 7.28–7.30 ) . The reduction of bicarbonate was also identical and proportional to the extent of dilution due to infusion of HSD and H-NS . This induced metabolic acidosis was corrected spontaneously in both groups 24 hrs after surgery . Conclusion : Both the intravenous administration of 7.5 % sodium chloride and the conventional fluid regimen with saline-based 6 % hydroxyethyl starch solution result ed in a metabolic acidosis of equal extent . This suggests dilution of plasma buffers or a decrease in strong ion difference to be the primary cause of metabolic acidosis PURPOSE Gastric intramucosal pH ( pHi ) , a surrogate marker of tissue oxygenation , falls following abdominal aorta aneurysm ( AAA ) repair . We tested the hypothesis that volume replacement with a hydroxyethyl starch solution would result in better preserved splanchnic oxygenation than would volume replacement with crystalloid solutions . MATERIAL S AND METHODS This was a prospect i ve , r and omized , nonblinded study set in a university-affiliated community hospital . Thirty patients undergoing elective AAA repair were studied . Patients were r and omly selected to receive intraoperative and postoperative fluid replacement with either hetastarch or crystalloid . According to the study protocol , patients could not receive in excess of 3,000 mL of hetastarch . Tissue oxygenation was assessed indirectly by measuring pHi using a nasogastric tonometer . Hemodynamic , oxygenation , and pHi data were collected preoperatively , preclamp , before unclamping , at the end of the procedure and postoperatively for 24 hours . Coagulation parameters were determined preoperatively and postoperatively for 24 hours . RESULTS Fifteen patients were r and omized to each group . There were 18 male and 12 female patients , whose mean age was 66 + /- 9 years . The intraoperative fluid balance was significantly greater in the crystalloid compared with the hetastarch group ( 4,194 + /- 1,500 mL v 2,949 + /- 1,123 mL ; P = .05 , 95 % confidence interval [ C ] 23 to 2,519 mL ) . There were no significant differences in the amount of intraoperative blood loss or postoperative transfusion requirements between the two groups . The difference between the preoperative pHi and nadir was 0.07 + /- 0.03 in the hetastarch group compared with 0.13 + /- 0.04 in the crystalloid group ( P = .001 , Cl 0.03 to 0.09 ) . By multivariate analysis the only variable that influenced the fall in pHi was the type of resuscitation fluid ( F ratio of 7.63 ; P = .01 ) . There were no significant differences in hemodynamic- and oxygenation-derived variables or coagulation parameters between the two groups of patients . The length of mechanical ventilation , intensive care unit , and hospital stay was comparable between the two groups of patients . CONCLUSION In patients undergoing major surgery , volume resuscitation with hydroxyethyl starch solutions may improve microvascular blood flow and tissue oxygenation We studied 34 patients undergoing elective repair of an abdominal aortic aneurysm under combined general anaesthesia and epidural block to evaluate the acute effects of diaspirin crosslinked haemoglobin ( DCLHb ) 50 , 100 and 200 mg kg-1 i.v . Haemodynamic variables were measured continuously using pulmonary and radial artery catheters , and oxygen delivery and consumption were calculated at regular intervals . DCLHb was shown to be vasoactive , producing an increase in mean arterial pressure of approximately 25 % with each dose , with small decreases in cardiac index and calculated oxygen delivery . These effects persisted beyond the end of infusion and provided a degree of cardiovascular stability during the operative procedure . The effects of DCLHb on oxygen consumption at these doses were minimal In two consecutive studies ( Study A and Study B ) , we evaluated the effects of increasing doses of HBOC-201 , a bovine hemoglobin-based oxygen carrier , on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery . After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer 's solution , 24 patients ( 12 in each study ) were r and omly assigned to receive , within 30 min , a predetermined volume of either HBOC-201 or 6 % hydroxyethyl starch ( Study A 6.9 mL/kg ; Study B 9.2 mL/kg ) . Monitored variables included systemic and pulmonary arterial pressures , arterial and mixed venous blood gases , and calculations of cardiac index ( CI ) , systemic ( SVRI ) and pulmonary ( PVRI ) vascular resistance indices , oxygen delivery index ( Do2 I ) , oxygen consumption index ( Vo2 I ) , and oxygen extraction ratio ( O2 ER ) . In both studies , the infusion of HBOC-201 was associated with increases in SVRI ( Study A 121 % ; Study B 71 % ) and PVRI ( Study A 70 % ; Study B 53 % ) and with a decrease in CI ( 29 % both studies ) . Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch , but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI , with a result ing net decrease in both CI and Do2 I ( Study A 30 % ; Study B 28 % ) ; Vo2 I was maintained by increased O2 ER . In terms of hemodynamics and oxygen transport , hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch . Implication s : Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients . In terms of hemodynamics and oxygen transport , hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch . ( Anesth Analg 1998;87:284 - 91 In 40 patients , whose expected hemodynamic instability during surgery necessitated invasive monitoring ( Swan-Ganz catheter ) and arterial pressure monitoring the hemodynamic and oxygen transport parameters in conditions of hypervolemic hemodilution were investigated in r and omized tests . After insertion of an arterial catheter ( arteria radialis ) as well as Swan-Ganz pulmonary arterial catheter via the vena jugularis interna , one of the two volume substitutes selected at r and om was infused in quantities of 125 ml/5 min and the hemodynamic changes were measured after infusion of 500 ml and finally after a wedge pressure of 18 mmHg was reached . Using either solution , the measurements indicated significant increases in mean arterial pressure as well as in central venous pressure ( ZVD ) and wedge pressure . The cardiac index , left ventricular stroke work index , and stroke output rose consecutively and pulmonary vascular resistance went down in both test groups . In the case of both volume substitutes , there was an improvement in oxygen availability . The hemoglobin content decreased in both groups , though to different degrees in each group . Although the hydroxyethyl starch group registered a greater improvement in the cardiac index , a bigger decrease in pulmonary vascular resistance , a higher rise in the left ventricular stroke work index and a more significant improvement in stroke output , smaller quantities of the volume substitute were required in this group than in the group in which volume substitution was carried out with human albumin 5 % . ( ABSTRACT TRUNCATED AT 250 WORDS Background and objective : Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery . This study investigated the safety profile of a recent medium‐molecular‐weight hydroxyethyl starch ( HES ) preparation with a low molar substitution ( HES 130/0.4 ) in this sensitive patient group . Methods : Sixty‐five patients were r and omly allocated to receive either 6 % hydroxyethyl starch ( Voluven ® ; n = 32 ) or 3 % gelatin ( Plasmion ® ; n = 33 ) for perioperative volume substitution . At baseline , renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min−1 . The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery . Results : Both treatment groups were compared for non‐inferiority ( pre‐defined non‐inferiority range hydroxyethyl starch < gelatin + 17.68 & mgr;mol L−1 or 0.2 mg dL−1 ) . Other renal safety parameters included minimum postoperative creatinine clearance , incidence of oliguria and adverse events of the renal system . Baseline characteristics , surgical procedures and the mean total infusion volume were comparable . Non‐inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non‐parametric one‐sided 95 % CI for the difference hydroxyethyl starch − gelatin [ −∞ , 11 & mgr;mol L−1 ] . Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group . One patient receiving gelatin required dialysis secondary to surgical complications . Two patients of each treatment group died . Conclusion : As we found no drug‐related adverse effects of hydroxyethyl starch on renal function , we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery Abstract Objective To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery . Design and setting A single-centre , single-blinded , r and omized clinical trial at the intensive care unit of a university hospital . Patients and methods Patients ( n = 67 ) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9 % or the colloids gelatin 4 % , hydroxyethyl starch 6 % or albumin 5 % . Biochemical variables and haemodynamics ( transpulmonary thermodilution ) were measured . Results An amount of 1800 ( 1300–1800 ) ml of saline or 1600 ( 750–1800 ) ml of colloid solution ( P < 0.005 ) was infused . Colloid osmotic pressure ( COP ) decreased in the saline group and increased in the colloid groups ( P < 0.001 ) . Plasma volume increased by 3.0 % ( –18 to 24 ) in the saline versus 19 % ( –11 to 50 ) in the colloid groups ( P < 0.001 ) . Cardiac index increased by median 13 % ( ns ) in the saline group and by 22 % in the colloid groups ( P < 0.005 ) . The rise in left ventricular stroke work index was greater in the colloid than in the saline groups . The different colloids were equally effective . The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume , confirming plasma volume and preload augmentation by the fluid loading . Conclusion After cardiac or major vascular surgery , the pressure- and time-guided fluid response is dependent on the type of fluid used . Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline , because of greater plasma volume expansion following an increase in plasma COP OBJECTIVE To assess the effect of human atrial natriuretic peptide ( HANP ) on the pulmonary and systemic circulations during infrarenal abdominal aortic aneurysmectomy . DESIGN A prospect i ve , r and omized study . SETTING A university hospital . PARTICIPANTS Forty-five patients undergoing infrarenal abdominal aortic aneurysmectomy . INTERVENTIONS Abdominal aortic aneurysmectomy patients were r and omly assigned to 1 of 3 groups ( n = 15 for each group ) . They were infused with normal saline solution ( SA ) , 0.02 microg/kg/min of HANP ( LH ) , or 0.05 microg/kg/min of HANP ( HH ) , starting 5 minutes after clamping . Hemodynamic variables were measured before/after clamping and unclamping . MEASUREMENTS AND MAIN RESULTS Both mean pulmonary arterial pressure ( MPAP ) and the pulmonary vascular resistance index ( PVRI ) increased ( v baseline ) in the SA group . HANP attenuated the rises in MPAP and PVRI dose dependently ( LH and HH groups v SA ) . Mean arterial pressure and systemic vascular resistance index were not significantly different among the 3 groups . CONCLUSION HANP , infused during aortic clamping and abdominal aortic aneurysmectomy , attenuates the rises in pulmonary artery pressure and vascular resistance without severe systemic hypotension . This may result from direct and /or indirect pulmonary vascular effects of HANP because no HANP-induced changes in endothelin-1 , angiotensin-II , and thromboxane B(2 ) were detected Objective To compare a solution of 3 % dextran-60 ( D60 ) in Ringer 's lactate ( RL ) with RL alone as maintenance fluids for abdominal aortic surgery . Design R and omized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery . Setting A surgical ICU in a university hospital . Patients Consecutive patients , mean age 64 yr . Five patients had abdominal aneurysm , 12 had aortic obstruction disease , and three had aortic renal bypass surgery . These patients were followed for 1 month . Interventions Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output > 30 mL/h were used to guide the intraoperative fluid infusion rates , which were 36 and 104 mL/kg of D60 and RL , respectively ( ratio 1:2.9 ) . Measurements and Main Results Body weight at 24 hr had increased more with RL ( 7.8 kg ) than with D60 ( 3.2 kg ) infusion ( p < .01 ) , despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60 , respectively . Total intravascular albumin decreased from 0.7 g/kg ( 1.4 to 0.7 g/kg ) in both groups , corresponding to a plasma volume ( PV ) loss of 13 mg/kg without fluid infusions . A total intravascular dextran of 0.5 g/kg result ed in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level , in sharp contrast to 7.0 mL/kg decrease in PV with RL . Of the intraoperative 3 % D60 and RL infused , an estimated 51 % D60 and 6 % RL remained as PV expansion at 1 hr . Conclusion A diluted colloid solution in Ringer 's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures . ( Crit Care Med 1991 ; 19:36 We conducted a pilot study to evaluate the effects of HBOC-201 , a bovine hemoglobin-based oxygen carrier , on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery . After induction of anesthesia and isovolemic hemodilution with 1 L of lactated Ringer 's solution , 13 patients were r and omly assigned to receive , within 30 min , 3 mL/kg of either HBOC-201 or 6 % hydroxyethyl starch ( HES ) . Monitored variables included invasive arterial and pulmonary artery pressures , arterial and mixed venous blood gases , and calculations of cardiac index ( CI ) , systemic and pulmonary vascular resistance indices , oxygen delivery index ( DO ( 2 ) I ) , oxygen consumption index ( VO2 I ) , and oxygen extraction ratio ( O2 ER ) . Thirty minutes after HBOC-201 infusion , mean arterial pressure , systemic vascular resistance index , and CI were 149 % ( P = 0.028 ) , 169 % ( P = 0.046 ) , and 75 % ( P = 0.046 ) of the preinfusion values , respectively . No significant changes were noticed in heart rate and pulmonary vascular resistance index . DO2 I and VO2 I , 30 min after the infusion of HBOC-201 , were 79 % ( P = 0.046 ) and 76 % ( P = 0.028 ) of the preinfusion values , respectively , whereas CaO2 and O2 ER remained unaffected . We conclude that HBOC-201 , at a dose of 3 mL/kg , impairs oxygen delivery because of adverse effects on cardiac output . ( Anesth Analg 1996;83:921 - 7 Hemodynamic , pulmonary , and renal variables were measured in 24 patients scheduled for major abdominal aortic operations . Control values were obtained before preoperative medications were given . All patients received 5 % dextrose in Lactated Ringer 's solution intraoperatively . Postoperatively , group 1 patients received 5 % dextrose in water plus albumin , group 2 received 5 % dextrose in 0.45 sodium chloride solution , and group 3 received 5 % dextrose in lactated Ringer 's solution . There were significant increases in Qs/Qt and AaDO2 , 48 hours after operation in group 3 . Oxygen consumption and cardiac output increased in all groups 24 hours after operation . Twenty-four hours later , these two variables returned to control values in group 1 but continued to rise in the other two groups . Significant diuresis occurred in group 1 , 48 hours postoperatively , whereas the other two groups continued to retain water . Use of albumin and 5 % dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables , than the other two groups The effect of optimal hydration on haemodynamics and renal function during infrarenal aortic cross clamping was studied in 26 consecutive patients operated on because of an infrarenal aortic aneurysm . The patients were r and omly divided over two groups . The patients of group B ( n = 13 ) were optimally hydrated before the operation . The Starling curve was used as st and ard . Patients of group A ( n = 13 ) served as control . The pre-operative and postoperative renal functions of both groups were compared , as were the haemodynamic parameters . The haemodynamic parameters were measured at five minutes intervals during the entire procedure . During aortic clamping the heart rate was significantly lower in patients of group B , indicating a lower myocardial oxygen consumption . Neither the haemodynamic parameters nor the renal function showed other beneficial effects on optimal hydration Fluid resuscitation with hypertonic hydroxyethyl starch solutions ( HES ) is effective in haemorrhagic shock due to the rapid mobilisation of fluids into the intravascular compartment . Declamping of the abdominal aorta with acute redistribution of blood into the vessels of the lower body half causes declamping-induced hypotension . Usually large amount of fluids or vasopressors are necessary to restore hemodynamic stability . Therefore , infusion of a hypertonic colloid solution may be an attractive option to achieve hemodynamic stability . This study was conducted to determine the amount of fluid of either hypertonic HES ( HES 6%;7.2 % NaCl ) or isotonic HES ( HES 6%;0.9 % NaCl ) needed to attain best wedge pressure ( PCWP ) cardiac index ( CI ) relation after declamping . Thirty-two high-risk patients undergoing elective abdominal aneurysm resection were enrolled in a prospect i ve , r and omised , double blinded study . The individual optimised PCWP/CI relation was determined after induction of anaesthesia . After declamping , both solutions were titrated in small boluses of 100 mL until the previously determined best wedge was reached . The amount of fluid after declamping was significantly reduced in the hypertonic HES- group 162 mL vs. 265 mL in the control group ( P < 0.05 ) . Resuscitation time was shortened , and cardiac index was slightly higher in the treatment group . The use of hypertonic HES-solution after aortic declamping led to a significant reduction of fluids necessary to attain optimised PCWP/CI relation . In this clinical trial with moderate blood loss in high-risk patients , hypertonic HES applied in a titrated fashion restored hemodynamic stability faster and without volume overload Objective To evaluate the efficacy of acute normovolemic hemodilution ( ANH ) and intraoperative cell salvage ( ICS ) in blood-conservation strategies for infrarenal aortic surgery . Summary Background Data Recent concerns over the risks of transfusion-related infection have result ed in sharp rises in the cost of blood preparations . Autologous transfusion may be a safe alternative to allogeneic transfusion , which has been associated with immune modulation and postoperative infection . Methods This multicenter prospect i ve r and omized trial compared st and ard transfusion practice with autologous transfusion combining ANH with ICS in 145 patients undergoing elective aortic surgery . The primary outcome measures were the proportion of patients requiring allogeneic blood and the volume of allogeneic transfusion . The secondary outcome measures were the frequency of complications , including postoperative infection , and postoperative hospital stay . Results The combination of ANH and ICS reduced the volume of allogeneic blood transfused from a median of two units to zero units . The proportion of patients transfused was 56 % in allogeneic and 43 % in autologous . There were no significant differences in complications or length of hospital stay . Conclusions Both ANH and ICS were safe and reduced the allogeneic blood requirement in patients undergoing elective infrarenal aortic surgery The effects of mannitol on renal impairment following infrarenal aortic aneurysm repair were studied . Patients received either mannitol 0.3 g/kg ( n = 15 ) or saline ( n = 13 ) as a rapid intravenous infusion before aortic cross‐clamping . One patient in the control group developed fatal postoperative renal failure but there was no renal failure in the mannitol group . Two patients treated with mannitol died from perioperative myocardial infa rct ion . There were no significant differences in postoperative blood urea level , serum creatinine concentration or creatinine clearance between mannitol and control groups . In patients who had mannitol there was a significant diuresis on the first day after operation ( mean urine output 2250 ml ) compared with before operation ( 1557ml ) ( P = 0.007 ) . Compared with controls , patients treated with mannitol had lower mean(s.e.m . ) postoperative levels of urinary albumin ( 160(32 ) versus 500(140 ) mg per mmol creatinine ; P = 0.036 ) and N‐acetyl glucosaminidase ( 143(34 ) versus 271(70 ) μmol per mmol creatinine ; P = 0.04 ) indicating a reduced level of sub clinical glomerular and renal tubular damage . These data demonstrate that mannitol reduces sub clinical renal injury following infrarenal aortic aneurysm repair We evaluated the safety , pharmacokinetics , and pharmacodynamics of diaspirin cross-linked hemoglobin ( DCLHb ) solution in patients after repair of abdominal aortic aneurysm . We performed a r and omized , single-blind controlled study with 10 patients in the surgical intensive care unit of a tertiary care facility . Within 24 hours after repair of an abdominal aortic aneurysm , each patient received an infusion of DCLHb ( 50 mg/kg or 35 mL for a 70-kg patient ) or an equal volume of hetastarch . Variables were measured before infusion , at 15 and 30 minutes postinfusion , and at hourly intervals up to 72 hours . Compared with controls , the experimental group had significantly greater mean pulmonary artery pressure at 30 minutes ( mean + /- SD , 26.4 + /- 3.18 vs. 22.8 + /- 2.86 mm Hg ) , greater mean arterial pressure through 30 minutes ( 100.8 + /- 8.67 vs. 81.6 + /- 13.8 mm Hg ) , and greater plasma hemoglobin through 2 hours ( 69.3 + /- 6.08 vs. 1.8 + /- 0 g/dL ) . Cardiac output was significantly less in the DCLHb group at 2 hours ( 5.34 + /- 7.92 vs. 6.18 + /- 0.54 L/minute ) , levels of serum bilirubin were significantly less at 24 and 48 hours ( 94 + /- 0.26 vs. 1.56 + /- 0.73 mg/dL ) , and platelet counts were significantly greater at 24 hours ( 128 + /- 35.8 vs. 101 + /- 55.7 mg/dL ) . The two groups did not differ in oxygen delivery or consumption . One patient treated with DCLHb had a myocardial infa rct ion 36 hours postinfusion . No patient had antibodies to DCLHb . At this dosage , DCLHb was well tolerated without severe organ dysfunction or toxicity . However , its use may lead to decreases in cardiac output because of increases in afterload , which may pose serious problems with left ventricular function OBJECTIVE To investigate the effect of HES , used as a plasma volume exp and er , on endothelial cell activation induced by ischaemia-reperfusion in humans . MATERIAL AND METHODS Forty patients undergoing elective infrarenal aneurysm repair were r and omised to receive either gelatine or hydroxyethyl starch solution as plasma exp and ers . The anaesthetic technique was st and ardised . All patients received the same crystalloid as per st and ard protocol . Urine sample s and blood sample s were collected at various times for assessment of microalbuminuria and von Willebr and factor ( vWf ) and CRP . RESULTS The peak C-reactive protein was significantly lower in the patients treated with HES than those treated with gelofusine [ 142 mg/L ( 113,196 mg/L ) vs 246 mg/L ( 189,291 mg/L ) mg/L , P < 0.01 , Mann-Whitney test ] . The peak ACR was also significantly lower in the HES treated patients ( 9.3 mg/mmol vs 23.3 mg/mmol , P < 0.05 ) . The plasma level of vWf was significantly higher in the gelofusine treated patients than those treated with HES [ 173.5 U/dl Vs 80.5 U/dl , P < 0.001 , at 4 hr ; 160 U/dl Vs 82.5 U/dl , P < 0.001 , at 8 hr ; 191 U/dl Vs 100.5 U/dl , P < 0.001 , at 12 hr ; 209 U/dl Vs 81.0 U/dl , P < 0.001 , at 24 hr ] . CONCLUSION HES may damp down the systemic inflammatory response and reduce endothelial cell dysfunction PURPOSE In an investigation of the effects of isovolemic hemodilution , 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function , renal artery blood flow , and cardiac hemodynamics . METHODS The patients were r and omly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28 % , with 20 patients receiving hemodilution and 19 being control subjects . RESULTS Twelve ( 63 % ) of the control group had renal impairment , compared with only four ( 20 % in the group receiving hemodilution ( p < 0.01 ) . Hemodilution also prevented the fall in cardiac output induced by cross-clamping ( p < 0.01 ) and significantly reduced the need for transfusion of donor blood ( p < 0.01 ) . CONCLUSIONS Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation During abdominal aortic aneurysmectomy ( AAAectomy ) and before aortic unclamping ( XU ) , we studied the effects of albumin administration on pulmonary arterial and right ventricular responses in 39 anesthetized patients using a modified thermodilution technique . Group 1 patients ( n = 18 ) were given no extra IV fluids . Group 2 patients ( n = 21 ) were given additional albumin administration ( 5 % albumin at 10 mL/kg ) before XU . After XU , mean arterial blood pressure ( MAP ) decreased significantly in each group , and MAP and stroke volume index ( SVI ) were not significantly higher in Group 2 than in Group 1 . At 5 min after XU , the patients in Group 2 had a higher mean pulmonary arterial pressure and pulmonary vascular resistance index and a lower right ventricular ejection fraction than those in Group 1 ( P < 0.05 ) , but their SVIs were well maintained . These results indicate that albumin administration before XU may not always prevent post-XU hypotension . It caused a significant increase in right ventricular afterload and a significant dilation of the right ventricular cavity ; however , right ventricular function was almost equally maintained in both groups . However , because SVI did not increase in some patients ( Group 2 ) with the increase in right ventricular end-diastolic volume index after XU , albumin administration should be performed carefully before XU during AAAectomy . Implication s : We studied the effects of albumin administration before aortic unclamping on pulmonary arterial and right ventricular responses during abdominal aortic aneurysmectomy using a modified thermodilution technique . Albumin administration before aortic unclamping may not always prevent hypotension , and it may cause a higher pulmonary arterial pressure than in patients without albumin administration . ( Anesth Analg 1998;87:1020 - 6 The effects of hetastarch and human albumin solutions on perioperative bleeding and coagulation parameters during abdominal aortic aneurysm repair were compared . In two r and omized groups of 20 patients , albumin 5 % ( group 1 ) or hetastarch 6 % ( group 2 ) 1 g/kg was given during surgery . The remaining perioperative fluids consisted of lactated ringers and packed red blood cells . Perioperative coagulation measurements included partial thromboplastin time , prothrombin time , activated clotting time , platelet count , and bleeding time . Estimated blood loss and the total amount of crystalloid and blood infused were also measured . The surgeon , blind to the colloid used , subjectively rated bleeding on a scale of 1 to 10 . There was no significant difference between groups for any measured parameter at any time . Measurements of coagulation function were within normal limits for both groups . Hetastarch does not cause clotting disorders in patients undergoing abdominal aortic aneurysm repair , at least if the quantities used in this study are not exceeded Hypertonic-hyperoncotic solutions ( HHT ) are presently being utilized to resuscitate patients in shock . However , so far , the effects of HHT on human atrial natriuretic factor ( hANF ) have not yet been investigated in a clinical trial . The effects of HHT on hANF were studied in a st and ardized preoperative and clinical setting in patients undergoing aneurysmectomy . Twenty-three conscious patients were included in two groups : 11 HHT and 12 HES ( HHT : 7.5 % NaCl/10 % HES 200 ; HES : .9 % NaCl/10 % HES 200 ) . Stepwise infusion of 50 mL was titrated preoperatively according to individual Frank-Starling relationships . Central venous pressure ( CVP ) and pulmonary capillary wedge pressure ( PCWP ) were determined before , during and after volume application . hANF , cGMP were also measured before and 1,10 , 30 , 60 , and 120 min after administration . The volumes necessary to produce the same volume status were : 213.6 ± 63.6 mL of HHT , 409.9 ± 136.2 mL of HES ( p<.001 ) . The sodium load was 273.9 ± 81.5 mmol of [ HHT ] , 63.1 ± 21.0 mmol of [ HES ] ( p<.001 ) . The data before and after volume loading were : PCWP : 7.9 ± 3.9 to 14.9 ± 4.3 mmHg of [ HHT ] , 7.9 ± 5.2 to 14.5 ± 4.3 mmHg of [ HES ] ( p<.001 ) ; CVP : 3.5 ± 2.3 to 6.9 ± 2.9 mmHg of [ HHT ] , 3.3 ± 3.1 to 7.5 ± 3.2 mmHg of [ HES ] ( p<.001 ) ; hANF : 42.5 ± 11.7 to 81.6 ± 30.8 pg/mL [ HHT ] ( p<.01 ) , 42.0 ± 11.2 to 74.1 ± 47.6 pg/mL [ HES ] ( p<.05 ) ; cGMP : 4.4 ± 1.2 to 10.5 ± 4.2 nM [ HHT ] ( p<.01 ) , 4.9 ± 1.7 to 12.6 ± 5.8 nM [ HES ] ( p<.001 ) . The changes in CVP and PCWP were identical after infusion of HHT or HES in normovolemic patients . The increased hANF levels produced by identical atrial dilation with different dosages . Furthermore , plasma-hANF excretion was due to an acute volume expansion of the right atrium . Acute sodium load had no effects on hANF excretion Previous studies suggest that supplementary exogenous albumin may adversely affect hepatic protein synthesis . To test this , 18 patients undergoing elective abdominal aortic surgery were studied . Based on r and omisation , nine patients received an average of 53.3 g albumin as part of blood replacement therapy , followed by 20 g albumin daily for the first three postoperative days . The remainder received no albumin . Sequential changes in plasma concentrations of albumin , transferrin , C-reactive protein , orosomucoid , fibrinogen and immunoglobulin G and A were monitored for the first week , as were changes in plasma volume and plasma colloid osmotic pressure . Supplementary albumin caused significant differences in plasma colloid osmotic pressure on postoperative days 1 , 2 and 4 ( p less than 0.01 ) and in albumin concentration at all postoperative measurement times ( p less than 0.01 ) . Plasma volumes did not differ between the groups . All protein fractions other than albumin showed identical curve sequences and peak concentrations . The significant decrease ( p less than 0.01 ) in concentration of all proteins except albumin of the albumin group was quantitatively explained by unreplaced plasma loss . The study rules out consequences of clinical importance of albumin supplementation on hepatic protein synthesis INTRODUCTION When blood flow is decreased , as in prolonged hypovolaemia and hypotension , or in the course of transversal clamping of the aorta during aortic reconstruction , nutritive tissue perfusion can also fall below the critical level . AIM The objective of this study was to analyse the effects of hypertonic-hyperoncotic solution on cardiovascular function during reconstruction of the abdominal aorta . METHOD This prospect i ve r and omised study included 40 patients . All patients underwent surgery of the abdominal aorta under general endotracheal anaesthesia . Based on the type of solution infused from the time of clamping to the moment of the removal of the transversal aortic clamp , the patients were divided into two groups of 20 . The study group was infused with a small volume of hypertonic-hyperoncotic solution , while the controls were administered infusions of isotonic solution . Patients with a preoperative creatinine level over 130 micromol L(-1 ) and an ejection fraction of less than 40 % were excluded from the study . RESULTS Cardiac output increased from 5.67 + /- 2.95 to 7.05 + /- 3.39 L min(-1 ) in the study group , in comparison to the controls , where it increased from 4.98 + /- 2.06 to 5.99 + /- 3.02 L min(-1 ) ( p = 0.004 ) . Central venous pressure increased from 8.75 + /- 3.67 to 9.30 + /- 2.77 mm Hg in the study group , in comparison to the controls , where the values decreased from 6.84 + /- 2.73 to 6.45 + /- 2.50 mm Hg ( p = 0.022 ) . Diastolic pulmonary artery pressure increased from 15.92 + /- 5.61 to 16.65 + /- 6.53 mm Hg in the study group , in comparison to the controls , where it decreased from 12.65 + /- 4.28 to 11.85 + /- 3.91 mm Hg ( p = 0.021 ) . The amount of given crystalloids 24 hours after the removal of the aortic clamp totalled 2562.5 + /- 485.82 mL in the study group , versus 3350 + /- 727.29 mL in the control group ( p = 0.000 ) . The amount of given human albumins 24 hours after the removal of the aortic clamp totalled 30 + /- 49.74 mL in the study group versus 100 + /- 4.34 mL in the control group ( p = 0.001 ) . CONCLUSION Haemodynamic stability of patients and adequate organ perfusion during surgery are achieved through the infusion of hypertonic-hyperoncotic solution , which maintains optimal values of : cardiac output , mixed venous oxygen saturation , and delivery of oxygen , while reducing alveolo-arterial oxygen difference . The balance of fluids , 24 hours after the removal of the aortic clamp , was maintained with the aid of hypertonic-hyperoncotic solution , while isotonic solution produced an excess of over 1000 mL of fluid in the control patients . Hypertonic-hyperoncotic solution increases cardiac output considerably more than does isotonic solution , and its application significantly reduces the accumulation of crystalloid solutions and human albumins OBJECTIVE To evaluate the impact of st and ard fluid management on the effectiveness of ANH as a blood conservation method in elective open AAA repair . DESIGN Prospect i ve r and omised controlled study . METHODS Thirty-four patients undergoing elective AAA repair were r and omised to have ANH ( 16 ) or act as controls ( 18 ) . Intra-operative cell salvage was permitted in both groups . Haemoglobin ( Hb ) concentrations were determined at variable intervals peri-operatively . Blood loss and the use of heterologous blood were recorded . RESULTS The pre- and post-operative Hb concentrations , surgical blood loss and the use of cell salvage were similar in both groups . Hb concentration ( median , range ) decreased significantly from pre-operative to aortic clamping ( with blood loss < 100 ml ) in ANH patients from 8.8 ( 7.5 - 10.2 ) to 5.7 (4.2 - 6.6)mmol/l following ANH but also in controls from 8.6 ( 7.5 - 9.7 ) to 7.0 (4.5 - 9.0)mmol/l due to fluid infusion ( P<0.01 for every comparison ) . Bank blood requirements were similar : median 2 units in ANH and 2.5 units in control patients ( P=0.68 ) . CONCLUSIONS Large volumes of fluids infused during AAA repair already conserve blood by the mechanism of hypervolaemic haemodilution . When cell salvage is used with st and ard fluid management during AAA repair , additional ANH is ineffective in saving blood To demonstrate the advantages of a 1.8 % hypertonic saline solution ( HS ) over a Ringer 's lactate solution ( RL ) during and after major intra-abdominal surgery , 28 patients were r and omly allocated to one of two groups as follows : 13 patients received RL and 15 patients received HS . All patients were studied preoperatively , peroperatively and postoperatively for 72 hours . Peroperatively RL or HS were infused at a rate sufficient to maintain a pulmonary capillary wedge pressure ( PCWP ) and central venous pressure ( CVP ) within 3 mm Hg of the initial value . The left ventricular end-diastolic volume index ( LVEDVI ) was calculated from determination of stroke index and ejection fraction with a mobile gamma camera . Biopsy specimens were taken from the rectus abdominis muscle for evaluation of edema . The two groups of patients were comparable for age , length of surgery and length of aortic cross-clamping . Preoperatively natremia , serum osmolarity , PCWP and LVEDVI were similar in both groups . A significant ( p = 0.01 ) difference was noted , during and after surgery , between the sodium levels in the two groups , but the levels remained within normal limits . Serum osmolarity remained similar for the two groups ( p = 0.49 ) . During and after surgery , PCWP ( p = 0.1 ) and CVP ( p = 0.7 ) remained within 3 mm Hg of the initial values with no significant difference between the two groups . The HS group received significantly ( p = 0.002 ) less liquid than the RL group . At the end of surgery , the LVEDVI dropped in both groups . This drop was significantly ( p = 0.04 ) more important in the RL group than in the HS group . ( ABSTRACT TRUNCATED AT 250 WORDS Fifty-eight patients who were to undergo aortic reconstruction were prospect ively r and omized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions . Blood loss was replaced with packed red blood cells , and additional fluid was given as either Ringer 's lactate solution ( RL , 130 mEq sodium/L , 274 mOsm/L ) or a hypertonic balanced salt solution ( HSL , 250 mEq sodium/L , 514 mOsm/L ) . Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output ( CO ) at or above the preoperative level . The groups were similar with respect to age , preexisting disease , duration of operation , and operative blood loss . During the operation , the RL group required 9.5 + /- 0.8 L of fluid , whereas the HSL group required 4.5 + /- 0.3 L ( P less than 0.001 ) . Pulmonary , cardiac , and renal functions were adequately maintained in both groups . There were no significant differences between the groups with regard to CO , urine output , or creatinine clearance during the operation and early postoperative period . Postoperatively , the intrapulmonary shunt was 20 + /- 1 % in the RL group and it was 16 + /- 1 % in the HSL group ( P less than 0.05 ) . The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups . Serum sodium and osmolarity were significantly greater in the HSL group ( P less than 0.001 ) , reaching a maximum of 151 + /- 1 mEq/L and 305 + /- 2 mOsm/L , respectively . Two patients in the HSL group had a persistent elevation in serum osmolarity ( greater than 320 mOsm/L ) during operation , for which they received RL for the balance of the resuscitation . There were no complications that could be attributed to the hypertonicity of the solution . HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration OBJECTIVE Because of allogenic red blood cell ( RBC ) availability and infection problems , novel alternatives , including hemoglobin-based oxygen-carrying solutions ( HBOC ) , are being explored to minimize the perioperative requirement of RBC transfusions . This study evaluated HBOC-201 , a room-temperature stable , polymerized , bovine-HBOC , as a substitute for allogenic RBC transfusion in patients undergoing elective infrarenal aortic operations . METHODS In a single blind , multicenter trial , 72 patients were prospect ively r and omized two-to-one to HBOC ( n = 48 ) or allogenic RBC ( n = 24 ) at the time of the first transfusion decision , either during or after elective infrarenal aortic reconstruction . Patients r and omized to the HBOC group received 60 g of HBOC for the initial transfusion and had the option to receive three more doses ( 30 g each ) within 96 hours . In this group , any further blood requirement was met with allogenic RBCs . Patients r and omized to the allogenic RBC group received only st and ard RBC transfusions . The efficacy analysis was a means of assessing the ability of HBOC to eliminate the requirement for any allogenic RBC transfusions from the time of r and omization through 28 days . Safety was evaluated by means of st and ard clinical trial methods . RESULTS The two treatment groups were comparable for all baseline characteristics . Although all patients in the allogenic RBC group required at least one allogenic RBC transfusion , 13 of 48 patients ( 27 % ; 95 % CI , 15 % to 42 % ) in the HBOC group did not require any allogenic RBC transfusions . The only significant changes documented were a 15 % increase in mean arterial pressure and a three-fold peak increase in serum urea nitrogen concentration after HBOC . The complications were similar in both groups , with no allergic reactions . There were two perioperative deaths ( 8 % ) in the allogenic RBC group and three perioperative deaths ( 6 % ) in the HBOC group ( P = 1.0 ) . CONCLUSION HBOC significantly eliminated the need for any allogenic RBC transfusion in 27 % of patients undergoing infrarenal aortic reconstruction , but did not reduce the median allogenic RBC requirement . HBOC transfusion was well tolerated and did not influence morbidity or mortality rates Abdominal aortic surgery patients are at risk for renal dysfunction , notably if preoperatively the renal function is impaired . This sensitive patient population was chosen to prove that the recent hydroxyethyl starch ( HES ) 130/0.4 has no adverse renal effects as asserted for less metabolisable HES preparations . After IRB approval and signed informed consent , 65 adult patients scheduled for abdominal aortic surgery were r and omly allocated to receive either 6 % HES 1300.4 ( Voluven , n = 32 ) or 3 % gelatin solution ( Plasmion , n = 33 ) for perioperative volume substitution . The daily dose limitation for HES was 50 ml/kg body weight Baseline renal function was impaired in all patients ( creatinine clearance ( CrCl ) < 80 ml/min ) . The primary renal safety parameter was the peak increase in serum creatinine through day 6 after surgery . Both groups were compared for non-inferiority of HES ( predefined non-inferiority range HES < gelatin + 17.68 mol/l or 0.2 mg/dl ) . Other renal safety parameters were minimum postoperative CrCl , incidence of oliguria ( urine output < 500 ml/day ) , and adverse events ( AEs ) related to the renal system until hospital discharge . Baseline characteristics , surgical procedures , and the mean total infused colloid volumes were similar between both groups . Postoperatively , the mean peak increase in creatinine was slightly higher in gelatin patients . Non-inferiority of HES was statistically proven by means of the appropriate nonparametric one-sided 95 % CI for the difference HES-gelatin ( -∞ , 11 μmol/l ) . The minimum postoperative CrCl was lower for gelatin ( see Table Table1,1 , mean values ± SD ) . Oliguria occurred in a few patients only ( three HES vs four gelatin patients ) . One patient of the gelatin group required dialysis treatment following a cascade of AEs related to surgical complications . Mortality in both groups was 6 % ( two deaths/ group ) . No drug-related unfavourable effects on renal function were found for volume substitution with HES 130/0.4 compared with gelatin in patients with mild to severe renal insufficiency undergoing infrarenal abdominal aortic surgery . Table |
12,560 | 26,866,804 | Based on the studies included in this review , the overall therapeutic effect of skin grafts and tissue replacements used in conjunction with st and ard care shows an increase in the healing rate of foot ulcers and slightly fewer amputations in people with diabetes compared with st and ard care alone . | BACKGROUND Foot ulceration is a major problem in people with diabetes and is the leading cause of hospitalisation and limb amputations .
Skin grafts and tissue replacements can be used to reconstruct skin defects for people with diabetic foot ulcers in addition to providing them with st and ard care .
Skin substitutes can consist of bioengineered or artificial skin , autografts ( taken from the patient ) , allografts ( taken from another person ) or xenografts ( taken from animals ) .
OBJECTIVES To determine the benefits and harms of skin grafting and tissue replacement for treating foot ulcers in people with diabetes . | OBJECTIVE Determine the cost-effectiveness of extracellular matrix ( ECM ) relative to human fibroblast-derived dermal substitute ( HFDS ) on diabetic foot ulcer ( DFU ) wound closure . METHOD Outcomes data were obtained from a 12-week , r and omised , clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU . Patients were treated with either ECM or HFDS treatment . A two-state Markov model ( healed and unhealed ) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient . Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation ( primary outcome ) . The perspective of the analysis was that of the payer , specifically the Centers for Medicare and Medicaid Services . No cost discounting was performed because of the short duration of the study . RESULTS The study consisted of 26 patients , with 13 in each group . In the ECM group , 10 wounds closed ( 77 % ) , with an average closure time of 36 days ; 11 wounds closed in the HFDS group ( 85 % ) , with an average closure time of 41 days . There was no significant difference between these results ( p=0.73 ) . Over 12 weeks , the expected cost per DFU was $ 2522 ( £ 1634 ) for ECM and $ 3889 ( £ 2524 ) for HFDS . Patients treated with HFDS incurred total treatment costs that were approximately 54 % higher than those treated with ECM . Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $ 500 ( £ 325 ) . CONCLUSION In patients with DFU , ECM yielded similar clinical outcomes to HFDS but at a lower cost . Health-care providers should consider ECM as a cost-saving alternative to HFDS . DECLARATION OF INTEREST A.M. Gilligan , and C.R. Waycaster , are employees of Smith & Nephew Inc .. This study was funded by Smith & Nephew Inc .. A.L. L and sman , reports no conflicts of interest An estimated 25 % of all people with diabetes may experience a foot ulcer in their lifetime , which may lead to serious complications including infection and amputation . A prospect i ve , multicenter , r and omized , controlled clinical trial was conducted to compare an in vitro-engineered , human fibroblast-derived dermal skin ( HFDS ) substitute and a biologically active cryopreserved human skin allograft ( HSA ) to determine the relative number of diabetic foot ulcers ( DFUs ) healed ( 100 % epithelialization without any drainage ) and the number of grafts required by week 12 . Secondary variables included the proportion of healed patients at weeks 16 and 20 , time to healing during the study , and wound size progression . The 23 eligible participants ( 11 r and omized to the HSA , 12 to the HFDS group ) were recruited from two hospital-based outpatient wound care centers . Baseline patient ( body mass index , age , gender , race , type and duration of diabetes , presence of neuropathy and /or peripheral arterial disease , tobacco use ) and wound characteristics ( size and duration ) were recorded , and follow-up visits occurred every week for up to 20 weeks . Descriptive and multivariate regression analyses were used to compare wound outcomes . At baseline , no statistically significant differences between patients and wounds were observed . At week 12 , seven ( 63.6 % ) patients in the HSA and four ( 33.3 % ) in the HFDS group were healed ( P = 0.0498 ) . At the end of the 20-week evaluation period , 90.91 % of HSA versus 66.67 % of HFDS were healed ( P = 0.4282 ) . Among the subset of wounds that healed during the first 12 weeks of treatment , an average of 4.36 ( range 2 - 7 ) HSA grafts were applied versus 8.92 ( range 6 - 12 ) in the HFDS subset ( P < 0.0001 , SE 0.77584 ) . Time to healing in the HSA group was significantly shorter ( 8.9 weeks ) than in the HFDS group ( 12.5 weeks ) ( log-rank test , P = 0.0323 ) . The results of this study are similar to previous outcomes reported using these treatment modalities and suggest that , after 12 weeks of care , DFUs managed with HSA are approximately twice as likely to heal as DFUs managed with HFDS with approximately half the number of grafts required . Research confirming these results with a larger sample size and in patients with different types of wounds is warranted OBJECTIVE To test the safety , efficacy , and immunological impact of a cultured allogeneic human skin equivalent ( HSE ) in the treatment of venous ulcers . DESIGN Prospect i ve , r and omized study . SETTING Multicenter study in the outpatient setting . INTERVENTION Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE . The patients were evaluated for HSE safety , complete ( 100 % ) ulcer healing , time to wound closure , wound recurrence , and immune response to the HSE . OUTCOME The study was completed as planned in 293 r and omized patients . RESULTS Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months ( 63 % vs 49 % ; P=.02 , Fisher exact test , 2-tailed ) and the median time to complete wound closure ( 61 days vs 181 days ; P=.003 , log-rank test ) . Treatment with HSE was superior to compression therapy in healing larger ( > 1000 mm2 ; P=.02 ) and deeper ulcers ( P=.003 ) and ulcers of more than 6 months ' duration ( P=.001 ) . Occurrence of adverse events was similar in both groups . No symptoms or signs of rejection occurred in response to treatment with HSE , and no HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts . CONCLUSIONS Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone . There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application . These data suggest that HSE represents a significant advance in the treatment of venous ulcers , particularly those that are difficult to heal A prospect i ve , multicenter , r and omized , controlled 12-week study was undertaken to evaluate the effectiveness of a human fibroblast-derived dermis for treating foot ulcers in the diabetic patient . This report summarizes the findings from one center . Following a 2-week screening period , patients were r and omized to either human fibroblast-derived dermis ( HFDD ) ( Dermagraft ) plus saline-moistened gauze or to the control group ( CT ) of saline-moistened gauze alone . Effectiveness end points were : 1 ) wound closure by week 12 , 2 ) time to wound closure , and 3 ) percent wound closure by week 12 . Safety was assessed by review of adverse events and laboratory findings . Patients r and omized to HFDD received an application at day 0 and up to seven additional treatments . All patients in each group received shoes with custom-molded inserts and were seen weekly . The study population was comprised of 28 patients ( 14 HFDD/14 CT ) with chronic ulcers ( > 6 weeks ' duration at time of screening ) . By week 12 , significantly more chronic ulcers healed in the HFDD group than in the CT group ( 71.4 % versus 14.3 % , p = .003 ) . Healed HFDD patients achieved wound closure significantly faster than CT patients ( p = .004 ) . Patients treated with HFDD showed a statistically significant higher percent of wound closure by week 12 than did CT patients ( p = .002 ) . The percent of patients who experienced an infection involving their study wound was less in the HFDD group than in the CT group . It was concluded that HFDD is a safe and effective treatment for chronic foot ulcers in diabetic patients Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts ( EpiFix ® , MiMedx , Kennesaw , GA ) versus st and ard of care . An IRB-approved , prospect i ve , r and omised , single-centre clinical trial was performed . Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion . Patients were r and omised to receive st and ard care alone or st and ard care with the addition of EpiFix . Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated . In the st and ard care group ( n = 12 ) and the EpiFix group ( n = 13 ) wounds reduced in size by a mean of 32·0 % ± 47·3 % versus 97·1 % ± 7·0 % ( P < 0·001 ) after 4 weeks , whereas at 6 weeks wounds were reduced by −1·8 % ± 70·3 % versus 98·4 % ± 5·8 % ( P < 0·001 ) , st and ard care versus EpiFix , respectively . After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77 % and 92 % , respectively , whereas st and ard care healed 0 % and 8 % of the wounds ( P < 0·001 ) , respectively . Patients treated with EpiFix achieved superior healing rates over st and ard treatment alone . These results show that using EpiFix in addition to st and ard care is efficacious for wound healing OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) . St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care OBJECTIVE To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers . RESEARCH DESIGN AND METHODS A total of 79 patients with diabetic dorsal ( n = 37 ) or plantar ( n = 42 ) ulcers were r and omized to either the control group with nonadherent paraffin gauze ( n = 36 ) or the treatment group with autologous tissue-engineered grafts ( n = 43 ) . Weekly assessment , aggressive debridement , wound infection control , and adequate pressure relief ( fiberglass off-loading cast for plantar ulcers ) were provided in both groups . Complete wound healing was assessed within 11 weeks . Safety was monitored by adverse events . RESULTS Complete ulcer healing was achieved in 65.3 % of the treatment group and 49.6 % of the control group ( P = 0.191 ) . The Kaplan-Meier mean time to closure was 57 and 77 days , respectively , for the treatment versus control groups . Plantar foot ulcer healing was 55 % and 50 % in the treatment and control groups , respectively . Dorsal foot ulcer healing was significantly different , with 67 % in the treatment group and 31 % in the control group ( P = 0.049 ) . The mean healing time in the dorsal treatment group was 63 days , and the odds ratio for dorsal ulcer healing compared with the control group was 4.44 ( P = 0.037 ) . Adverse events were equally distributed between the two groups , and none were related to the treatments . CONCLUSIONS The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current st and ard dressing . For plantar ulcers , the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment . This treatment , however , may be useful in patients for whom the total off-loading cast is not recommended and only a less effective off-loading device can be applied OBJECTIVE To compare results of skin graft healing in diabetic ulcers between the meshed skin graft method and split thickness skin graft method . Duration of complete skin graft healing in both groups was recorded . The relations between ulcer size and complete skin graft healing duration were analyzed . PATIENTS AND METHOD This research used a prospect i ve r and omized controlled study with 80 diabetic ulcer patients from January 2002-June 2003 . Thirty-eight cases were treated by the meshed skin graft method with expansion ratio 1:3 and another 42 cases were treated with the ordinary split-thickness skin . RESULTS The means of complete healing duration were 19.84 + /- 7.37 days in the meshed skin group and 20.36 + /- 7.21 days in the normal split-thickness skin graft group . There was no statistically significant difference between the groups in duration of complete graft healing and efficacy of treatment . The cosmetic result was accepted in both skin graft methods . There was no statistically significant difference between wound size and complete skin graft healing duration . CONCLUSION The meshed skin graft method is as good for diabetic ulcer coverage as the ordinary split thickness skin graft This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft — a 2-step HYAFF autograft — in the treatment of diabetic foot ulcers compared with st and ard care . In all , 180 patients with dorsal or plantar diabetic foot ulcers ( unhealed for ≥1 month ) were r and omized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks ( n = 90 ; treatment group ) or nonadherent paraffin gauze ( n = 90 ; control group ) . Efficacy and adverse events were assessed weekly for 12 weeks , at 20 weeks , and at 18 months . The primary efficacy outcome was complete ulcer healing at 12 weeks . Wound debridement , adequate pressure relief , and infection control were provided to both groups . At 12 weeks , complete ulcer healing was similar in both groups ( 24 % of treated vs 21 % controls ) . A 50 % reduction in ulcer area was achieved significantly faster in the treatment group ( mean 40 vs 50 days ; P = .018 ) . Weekly percentage ulcer reduction was consistently higher in the treatment group . At 20 weeks , ulcer healing was achieved in 50 % of the treated group as compared with 43 % of controls . Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment ( P = .047 ) . In a subgroup with hard-to-heal ulcers , there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers ( P = .035 ) . Adverse events were similar in both groups . The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers OBJECTIVE To assess the effect of a tissue-engineered human dermis ( Dermagraft ) in healing diabetic foot ulcers . RESEARCH DESIGN AND METHODS This controlled prospect i ve multicenter r and omized single-blinded pilot study evaluated healing over a 12-week period in 50 patients with diabetic foot ulcers . These patients were r and omized into four groups ( three different dosage regimens of Dermagraft and one control group ) . All patients received identical care except for the use of Dermagraft tissue . Ulcer healing was assessed by percentage of wounds achieving complete or 50 % closure , time to complete or 50 % closure , and volume and area measurements . RESULTS Ulcers treated with the highest dosage of Dermagraft , one piece applied weekly for 8 weeks ( group A ) , healed significantly more often than those treated with conventional wound closure methods ; 50 % ( 6 of 12 ) of the Dermagraft-treated and 8 % ( 1 of 13 ) of the control ulcers healed completely ( P = 0.03 ) . The percentage of wounds achieving 50 % closure was also significantly higher ( 75 vs. 23 % ; P = 0.018 ) , and the time to complete or 50 % closure was faster ( P = 0.056 ) . The group A regimen was more effective than other treatment regimens . All three were better than the control , however , and a dose-response was observed . There were no safety concerns . After a mean of 14 months of follow-up ( range 11 - 22 months ) , there were no recurrences in the Dermagraft-healed ulcers . CONCLUSIONS Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers . The recurrence data may indicate an improved quality of wound healing Diabetic ulcer complications are a leading cause of hospitalization and amputation . Of the 20 million individuals with diabetes , 10–15 % are at risk for developing diabetic ulcers . St and ard therapy involves the use of dressings to protect the wound bed from trauma and to absorb exsu date ; offloading high pressure from the wound bed , e.g. , by prescribing protective footwear ; and wound bed preparation to accelerate endogenous healing and facilitate the effectiveness of topically applied substances . But these measures are often deficient in healing all diabetic ulcers when the patient 's own intrinsic wound-healing system is insufficient . In such patients , skin replacement therapies are second-line treatment options ; however , the effectiveness of skin replacement therapies in treatment of diabetic ulcers is unclear . The objective of this study is to assess their effectiveness using evidence from r and omized trials in diabetic leg and foot ulceration . We search ed the Cochrane Controlled Trials Register ( 1970–2006 ) , MEDLINE ( 1966–2006 ) , EMBASE ( 1980–2006 ) , and CINAHL ( 1982–2006 ) using a combination of text and keywords in addition to a filter for controlled clinical trials . The last up date of search es was performed on 30 September 2007 . We included trials if the allocation of participants was described as r and omized , with participants of any age and in any care setting having diabetic leg or foot ulceration . We included studies that compared the following types of grafts with any other intervention : 1 ) autografts ( pinch , split or full-thickness skin grafts , cultured keratinocytes , or fibroblasts ) , 2 ) allografts ( cultured keratinocytes or fibroblasts ) , 3 ) xerografts , and 4 ) bioengineered skin . Two review ers independently evaluated Aims /hypothesisThe effect of a foot ulcer on health-related quality of life ( HRQoL ) of patients with diabetes mellitus and their caregivers is unclear , and was therefore evaluated prospect ively in this multicentre study . Methods HRQoL according to the 36-item health-related quality of life question naire ( SF-36 ) of 294 patients ( ulcer duration ≥4 weeks ) and 153 caregivers was analysed at baseline ( time-point zero [ T0 ] ) , once the ulcer was healed or after 20 weeks ( time-point 1 [ T1 ] ) , and 3 months later ( time-point 2 [ T2 ] ) . Patients with severe ischaemia were excluded . Results The mean age of the patients was 60 years , 72 % were male , and time since diagnosis of diabetes was 17 years . Patients reported a low HRQoL on all SF-36 subscales . At T1 , HRQoL scores in physical and social functioning were higher in patients with a healed vs a non-healed ulcer ( p<0.05 ) . At T2 , these differences were larger , with higher scores for physical and social functioning , role physical and the physical summary score ( all p<0.05 ) . Within-group analysis revealed that HRQoL improved in different subscales in patients with a healed ulcer and worsened in patients with a persistent ulcer from T0 to T2 ( all p<0.05 ) . The caregivers of patients with a persisting ulcer had more emotional difficulties at T2 . Conclusions /interpretationDiabetic patients with a healed foot ulcer had a higher HRQoL than patients with a persisting ulcer . Healing of a foot ulcer result ed in a marked improvement of several SF-36 subscales 3 months after healing ( from T0 to T2 ) . HRQoL declined progressively when the ulcer did not heal . A diabetic foot ulcer appeared to be a large emotional burden on the patients ’ caregivers , as well BACKGROUND Chronic diabetes-related foot ulcers result from predisposition , tissue injury , and inadequate reparative mechanisms . St and ard care for diabetes-related foot ulcers includes weight off-loading , pressure-relieving footwear , aggressive surgical debridement , and frequent dressing changes . Graftskin is a recently developed living skin construct . OBJECTIVE To compare Graftskin and st and ardized wound care to st and ardized wound care alone in the treatment of difficult to heal diabetes-related neuropathic foot ulcers , and to assess the h and ling and application characteristics of Graftskin . METHODS A university dermatology clinic was part of a 24-center prospect i ve , r and omized , controlled , parallel group comparative trial of Graftskin for the treatment of difficult to heal neuropathic diabetes-related foot ulcers . Patients were r and omly assigned to treatment with Graftskin with aggressive debridement and st and ardized wound care , or aggressive debridement and st and ardized wound care alone . Blinding was not feasible due to device visibility during application . RESULTS Five of nine patients ( 56 % ) treated with Graftskin therapy had complete healing . Three of eight control patients ( 37 % ) had complete healing . CONCLUSION Graftskin as an adjunct to aggressive debridement and st and ardized wound care appears to be a valuable treatment adjunct in patients with difficult to heal diabetes-related neuropathic foot ulcers . The application learning curve was steep and the ease of application exceptional OBJECTIVE To compare healing rates at 12 weeks for full-thickness diabetic foot ulcers treated with OASIS Wound Matrix , an acellular wound care product , versus Regranex Gel . DESIGN R and omized , prospect i ve , controlled multicenter trial at 9 outpatient wound care clinics . SUBJECTSA total of 73 patients with at least 1 diabetic foot ulcer were entered into the trial and completed the protocol . INTERVENTION Patients were r and omized to receive either OASIS Wound Matrix ( n = 37 ) or Regranex Gel ( n = 36 ) and a secondary dressing . Wounds were cleansed and debrided , if needed , at a weekly clinic visit . Dressings were changed as needed . The maximum treatment period for each patient was 12 weeks . PRIMARY OUTCOME MEASUREIncidence of healing in each group at 12 weeks . RESULTS After 12 weeks of treatment , 18 ( 49 % ) OASIS-treated patients had complete wound closure compared with 10 ( 28 % ) Regranex-treated patients . CONCLUSION Although the sample size was not large enough to demonstrate that the incidence of healing in the OASIS group was statistically superior ( P = .055 ) , the study results showed that treatment with OASIS is as effective as Regranex in healing full-thickness diabetic foot ulcers by 12 weeks AIM To compare the rate of healing of diabetic neuropathic ulcers using cultured autologous keratinocytes delivered on chemically defined transfer discs ( Myskin ) ( active treatment ) versus healing obtained with cell-free discs ( placebo ) . MATERIAL S AND METHODS After a 4-week lead-in period patients ( r and omly assigned ) received active or placebo treatments weekly for 6 weeks . All patients then received active treatments for a maximum of 12 treatments where required . Altogether , 16 patients with a total of 21 ulcers resistant to conventional therapy were recruited from four specialist diabetic centers in three cities . RESULTS All 21 ulcers were treated and of these ten healed and eight improved , with two failing to respond ( one ulcer was lost due to autoamputation ) . For analysis according to the study criteria , however , only the 12 patients with 12 index ulcers who completed treatment protocol s were eligible - five in the placebo group and seven in the active group . Of these , five ulcers healed completely and seven were reduced by more than 50 % . Complete healing took a median of ten active applications . CONCLUSIONS Repeated regular applications of the patient 's keratinocytes , delivered on the carrier dressing , initiated wound healing in ulcers resistant to conventional therapy , with 18 out of 21 ulcers responding . The healing observed did not appear attributable to patient recruitment or the cell-free carrier dressing but to the delivery of the cultured cells Diabetic foot ulcers often pose a difficult treatment problem . Repeated applications of cell-based products have been reported to result in acceleration of diabetic wound healing . The purpose of this clinical trial study was to report preliminary findings of the efficacy and safety of the cultured allogeneic keratinocyte sheets in the treatment of diabetic foot ulcers . Fifty-nine patients with diabetic foot ulcers were r and omized to either the keratinocyte treatment group ( n = 27 ) or the control group treated with vaseline gauze ( n = 32 ) . Except for the application of keratinocytes , treatment of study ulcers was identical for patients in both groups . Either keratinocyte sheet or vaseline gauze was applied at the beginning of the study and weekly thereafter for a maximum of 11 weeks . The maximum follow-up period for each patient was 12 weeks . Complete ulcer healing was achieved in 100 % of the treatment group and 69 % of the control group ( p < 0.05 ) . The Kaplan-Meier median times to complete closure were 35 and 57 days for the keratinocyte and control groups , respectively . No adverse events related to the treatment occurred . These results indicate that cultured allogeneic keratinocytes may offer a safe and effective treatment for diabetic foot ulcers The purpose of this study was to analyze long-term costs for foot ulcers in diabetic patients . Patients were treated and followed prospect ively by a foot care team . A retrospective economic analysis was performed of costs for 274 patients during 3 years from healing of an initial foot ulcer , with or without amputation . Costs were estimated for inpatient care , outpatient care , home care , and social service . The cost calculations include costs due to complications and disability related to the initial ulcer , costs related to recurrence of ulcer , and costs for prevention of new ulcers . Expected total present value cost per patient during 3 years of observation was $ 26,700 ( U.S. dollars ) for primary healed patients with critical ischemia and $ 16,100 for primary healed patients without critical ischemia . For patients who healed with an amputation , the corresponding costs were $ 43,100 after a minor amputation and $ 63,100 after a major amputation . When estimating the costs for diabetic foot ulcers , it is not sufficient to calculate short-term costs . Long-term costs are high , mainly due to the need for increased home care and social service , but also due to costs for recurrent ulcers and new amputations UNLABELLED Background . It was hypothesized that the rate of wound closure and the number of grafts required will be the same when treating diabetic foot ulcers with TheraSkin ® , a cryopreserved split-thickness skin allograft ( SSA ) , as compared to Apligraft ® , a bioengineered skin substitute ( BSS ) . METHODS A prospect i ve study using sequentially enrolled patients seen in a large podiatric practice encompassing multiple locations was conducted . Patients were sequentially enrolled and treated with either BSS or SSA . All other factors of treatment were st and ardized across the patient population . Data analysis included an analysis of co-factors in each group in order to determine if anything else may have influenced the outcomes . RESULTS Data from 17 wounds ( 16 patients ) treated with BSS and 12 wounds treated with SSA were analyzed . The average wound sizes were comparable , as was the average number of applications utilized . These data revealed that 41.3 % of the wounds treated with BSS closed within 12 weeks , as compared to 66.7 % of the wounds treated with SSA . At 20 weeks , 47.1 % of the wounds in the BSS group closed , while 66.7 % of the SSA wounds closed . There were a comparable number of adverse events in each group , with none that were a direct result of the biologic material being used . CONCLUSION SSA result ed in a higher percentage of wounds closing after 12 and 20 weeks , as compared to wounds treated with BSS . There were no adverse events noted that were directly related to either graft material OBJECTIVE Diabetic foot ulcers ( DFUs ) often pose a treatment problem . Bioengineered skin substitutes have been reported to result in accelerated diabetic wound healing . The purpose of this clinical trial was to evaluate the efficacy and safety of the autologous fibroblast-hyaluronic acid complex for treating DFUs . METHOD A stratified , r and omised , controlled , multicentre study was carried out . Patients with DFUs were allocated to either a treatment group with grafting of an autologous fibroblast-hyaluronic acid complex or a control group with non-adherent foam dressing . Except for application of the fibroblast complex , treatment of the study ulcers was identical for patients in both groups . The maximum follow-up period for each patient was 12 weeks . RESULTS Complete ulcer healing was achieved in 84 % ( 26/31 patients ) of the treatment group and 34 % ( 11/32 patients ) of the control group ( p<0.05 ) . The times required for complete healing were 36.4 ± 17.6 and 48.4 ± 13.1 days in the treatment and control groups , respectively ( p<0.05 ) . No adverse events related to treatment occurred . CONCLUSION These results indicate that autologous fibroblast-hyaluronic acid complex may offer a safe and effective treatment for DFUs This 12-week , prospect i ve , r and omised , controlled multi-centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix ( AM ) ( study group ) and st and ard of care ( control group ) therapies . Eighty-six patients were r and omised into study ( 47 patients ) and control ( 39 patients ) groups . No significant differences in demographics or pre-treatment ulcer data were calculated . Complete healing and mean healing time were 69.6 % and 5.7 weeks , respectively , for the study group and 46.2 % and 6.8 weeks , respectively , for the control group . The proportion of healed ulcers between the groups was statistically significant ( P = 0.0289 ) , with odds of healing in the study group 2.7 times higher than in the control group . Kaplan-Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate ( P = 0.015 ) for the control group ( 53.9 % ) compared with the study group ( 30.4 % ) . After adjusting for ulcer size at presentation , which was a statistically significant covariate ( P = 0.0194 ) , a statistically significant difference in non healing rate between groups was calculated ( P = 0.0233 ) , with odds of healing 2.0 times higher in the study versus control group . This study supports the use of single-application AM therapy as an effective treatment of diabetic , neuropathic ulcers A prospect i ve , single-centre , r and omized controlled study was performed to evaluate the effectiveness of Graftjacket , a human acellular regenerative tissue matrix as a treatment option for chronic non healing lower extremity wounds . Twenty-eight diabetic patients with full-thickness wounds that had been present for at least 6 weeks were treated with sharp debridement and r and omized to a single application of Graftjacket tissue matrix plus mineral oil-soaked fluff compression dressing or to a control treatment of wound gel with gauze dressings . All patients were seen weekly . By week 16 , 12 of 14 patients treated with Graftjacket tissue matrix demonstrated complete wound closure compared with 4 of 14 patients in the control group . Patients treated with Graftjacket tissue matrix showed a statistically significant higher percentage of wound healing with respect to wound area , and clinical ly significant differences in wound depth and wound volume . This comparison is not performed to demonstrate that the application of the Grafjacket is more effective than sharp debridement . This study is done to help assign a role to the use of Graftjacket matrix in lower extremity wound care OBJECTIVE To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers . RESEARCH DESIGN AND METHODS A r and omized , controlled , multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks . Patients were r and omized to either the Dermagraft treatment group or control ( conventional therapy ) . Except for the application of Dermagraft , treatment of study ulcers was identical for patients in both groups . All patients received pressure-reducing footwear and were allowed to be ambulatory during the study . RESULTS The results demonstrated that patients with chronic diabetic foot ulcers of > 6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone . With regard to complete wound closure by week 12 , 30.0 % ( 39 of 130 ) of Dermagraft patients healed compared with 18.3 % ( 21 of 115 ) of control patients ( P = 0.023 ) . The overall incidence of adverse events was similar for both the Dermagraft and control groups , but the Dermagraft group experienced significantly fewer ulcer-related adverse events . CONCLUSIONS The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers OBJECTIVE : Diabetic foot ulcers ( DFUs ) are frequently recalcitrant and at risk for infection , which may lead to lower-extremity amputation or bone resection . Reporting the incidence of amputations/bone resections may shed light on the relationship of ulcer healing to serious complications . This study aim ed to evaluate the incidence of amputations/bone resections in a r and omized controlled trial comparing human fibroblast-derived dermal substitute plus conventional care with conventional care alone for the treatment of DFUs . DESIGN : Ulcer-related amputation/bone resection data were extracted from data on all adverse events reported for the intent-to-treat population ( N = 314 ) , and amputations were categorized by type : below the knee , Syme , Chopart , transmetatarsal , ray , toe , or partial toe . Data were analyzed retrospectively for the incidence of amputation/bone resection by treatment . SETTING : R and omized controlled trial . PATIENTS : Patients with full-thickness DFUs greater than 6 weeks ’ duration . INTERVENTIONS : St and ard wound care plus human fibroblast-derived dermal substitute versus st and ard wound care alone . MAIN RESULTS : The incidence of amputation/bone resection in the study was 8.9 % ( 28/314 ) overall , 5.5 % ( 9/163 ) for patients receiving human fibroblast-derived dermal substitute , and 12.6 % ( 19/151 ) for patients receiving conventional care ( P = .031 ) . Of the 28 cases of amputation/bone resection , 27 were preceded by ulcer-related infection . CONCLUSION : There were significantly fewer amputations/bone resections in patients who received human fibroblast-derived dermal substitute versus conventional care , likely related to the lower incidence of infection adverse events observed in the human fibroblast-derived dermal substitute treatment group In a r and omised , controlled study , we compared the efficacy of Grafix ( ® ) , a human viable wound matrix ( hVWM ) ( N = 50 ) , to st and ard wound care ( n = 47 ) to heal diabetic foot ulcers ( DFUs ) . The primary endpoint was the proportion of patients with complete wound closure by 12 weeks . Secondary endpoints included the time to wound closure , adverse events and wound closure in the crossover phase . The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix ( 62 % ) compared with controls ( 21 % , P = 0·0001 ) . The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls ( P = 0·019 ) . There were fewer Grafix patients with adverse events ( 44 % versus 66 % , P = 0·031 ) and fewer Grafix patients with wound-related infections ( 18 % versus 36·2 % , P = 0·044 ) . Among the study subjects that healed , ulcers remained closed in 82·1 % of patients ( 23 of 28 patients ) in the Grafix group versus 70 % ( 7 of 10 patients ) in the control group ( P = 0·419 ) . Treatment with Grafix significantly improved DFU healing compared with st and ard wound therapy . Importantly , Grafix also reduced DFU-related complications . The results of this well-controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than st and ard wound therapy This study compared the efficacy and safety of Apligraf ( Organogenesis , Inc. , Canton , MA ) in combination with st and ard therapy versus st and ard therapy alone in the treatment of neuropathic diabetic foot ulcers . Efficacy was assessed by time to complete wound healing ( by 12 weeks ) and incidence of complete wound closure ( at 12 weeks ) . This was an international multi-center , r and omized , controlled study . Patients were eligible for entry into the study if the following criteria were met : type 1 or type 2 diabetes mellitus , age 18 to 80 years , adequate glycemic control , and the presence of a full-thickness neuropathic ulcer for at least 2 weeks prior to the initial screening visit . Following the 2-week screening period , the 2 treatment groups received st and ard ulcer care consistent with international treatment guidelines that comprised sharp debridement , saline-moistened dressings , and a non — weight bearing regimen . There were 106 subjects screened for enrollment , 82 r and omized to the treatment groups , and 72 treated ( 33 Apligraf subjects and 39 st and ard therapy subjects ) before the study was terminated . Kaplan — Meier curves indicated a trend for shorter time to complete wound healing in the Apligraf group compared with the st and ard therapy group ( p = .059 ; log-rank test ) . The median time to healing was 84 days in the Apligraf group , whereas no median time to healing could be determined for the st and ard therapy group because < 50 % of the st and ard therapy subjects healed . By 12 weeks , 51.5 % ( 17/33 ) Apligraf subjects had achieved complete wound closure compared with 26.3 % ( 10/38 ) of st and ard therapy subjects ( p = .049 ; Fisher 's exact test ) . Even though the study was halted prematurely , this study suggested that the use of Apligraf result ed in a higher incidence of wound closure by 12 weeks |
12,561 | 28,891,366 | No statistically significant difference in any aspect of meta- analysis was noted between ibrutinib and idelalisib | Ibrutinib and idelalisib , B-cell receptor ( BCR ) signaling pathway inhibitors , have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia ( CLL ) . | BACKGROUND Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy . Bendamustine plus rituximab is often used in the relapsed or refractory setting . We assessed the efficacy and safety of adding ibrutinib , an oral covalent inhibitor of Bruton 's tyrosine kinase ( BTK ) , to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma . METHODS The HELIOS trial was an international , double-blind , placebo-controlled , phase 3 study in adult patients ( ≥18 years of age ) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease ( > 1·5 cm ) by CT scan , and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 1 , and adequate bone marrow , liver , and kidney function . Patients with del(17p ) were excluded because of known poor response to bendamustine plus rituximab . Patients who had received previous treatment with ibrutinib or other BTK inhibitors , refractory disease or relapse within 24 months with a previous bendamustine-containing regimen , or haemopoietic stem-cell transplant were also excluded . Patients were r and omly assigned ( 1:1 ) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks ' duration ( bendamustine : 70 mg/m(2 ) intravenously on days 2 - 3 in cycle 1 , and days 1 - 2 in cycles 2 - 6 ; rituximab : 375 mg/m(2 ) on day 1 of cycle 1 , and 500 mg/m(2 ) on day 1 of cycles 2 - 6 for a maximum of six cycles ) with either ibrutinib ( 420 mg daily orally ) or placebo until disease progression or unacceptable toxicity . Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy . The primary endpoint was independent review committee (IRC)-assessed progression-free survival . Crossover to ibrutinib was permitted for patients in the placebo group with IRC-confirmed disease progression . Analysis was by intention-to-treat and is continuing for further long-term follow-up . The trial is registered with Clinical Trials.gov , number NCT01611090 . FINDINGS Between Sept 19 , 2012 , and Jan 21 , 2014 , 578 eligible patients were r and omly assigned to ibrutinib or placebo in combination with bendamustine plus rituximab ( 289 in each group ) . The primary endpoint was met at the preplanned interim analysis ( March 10 , 2015 ) . At a median follow-up of 17 months ( IQR 13·7 - 20·7 ) , progression-free survival was significantly improved in the ibrutinib group compared with the placebo group ( not reached in the ibrutinib group ( 95 % CI not evaluable ) vs 13·3 months ( 11·3 - 13·9 ) in the placebo group ( hazard ratio [ HR ] 0·203 , 95 % CI 0·150 - 0·276 ; p<0·0001 ) . IRC-assessed progression-free survival at 18 months was 79 % ( 95 % CI 73 - 83 ) in the ibrutinib group and 24 % ( 18 - 31 ) in the placebo group ( HR 0·203 , 95 % CI 0·150 - 0·276 ; p<0·0001 ) . The most frequent all- grade adverse events were neutropenia and nausea . 222 ( 77 % ) of 287 patients in the ibrutinib group and 212 ( 74 % ) of 287 patients in the placebo group reported grade 3 - 4 events ; the most common grade 3 - 4 adverse events in both groups were neutropenia ( 154 [ 54 % ] in the ibrutinib group vs 145 [ 51 % ] in the placebo group ) and thrombocytopenia ( 43 [ 15 % ] in each group ) . A safety profile similar to that previously reported with ibrutinib and bendamustine plus rituximab individually was noted . INTERPRETATION In patients eligible for bendamustine plus rituximab , the addition of ibrutinib to this regimen results in significant improvements in outcome with no new safety signals identified from the combination and a manageable safety profile . FUNDING Janssen Research & Development BACKGROUND The TP53 gene , encoding tumour suppressor protein p53 , is located on the short arm of chromosome 17 ( 17p ) . Patients with 17p deletion ( del17p ) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy . We assessed the activity and safety of ibrutinib , an oral covalent inhibitor of Bruton 's tyrosine kinase , in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma . METHODS We did a multicentre , international , open-label , single-arm study at 40 sites in the USA , Canada , Europe , Australia , and New Zeal and . Patients ( age ≥18 years ) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity . The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis . Preplanned exploratory analyses were progression-free survival , overall survival , sustained haematological improvement , and immunological improvement . Patient enrolment is complete , but follow-up is ongoing . Treatment discontinuation owing to adverse events , unacceptable toxicity , or death were collected as a single combined category . This study is registered with Clinical Trials.gov , number NCT01744691 . FINDINGS Between Jan 29 , 2013 , and June 19 , 2013 , 145 patients were enrolled . The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug , with a median age of 64 years ( IQR 57 - 72 ) and a median of two previous treatments ( IQR 1 - 3 ) . At the prespecified primary analysis after a median follow-up of 11·5 months ( IQR 11·1 - 13·8 ) , 92 ( 64 % , 95 % CI 56 - 71 ) of 144 patients had an overall response according to independent review committee assessment ; 119 patients ( 83 % , 95 % CI 76 - 88 ) had an overall response according to investigator assessment . In an extended analysis with median follow-up of 27·6 months ( IQR 14·6 - 27·7 ) , the investigator-assessed overall response was reported in 120 patients ( 83 % , 95 % CI 76 - 89 ) . 24-month progression-free survival was 63 % ( 95 % CI 54 - 70 ) and 24-month overall survival was 75 % ( 67 - 81 ) . Sustained haematological improvement was noted in 72 ( 79 % ) of 91 patients with any baseline cytopenia . No clinical ly relevant changes were noted from baseline to 6 months or 24 months in IgA ( median 0·4 g/L at baseline , 0·6 g/L at 6 months , and 0·7 g/L at 24 months ) , IgG ( 5·0 g/L , 5·3 g/L , and 4·9 g/L ) , or IgM ( 0·3 g/L at each timepoint ) concentrations . Common reasons for treatment discontinuation were progressive disease in 34 ( 24 % ) patients and adverse events , unacceptable toxicity , or death in 24 ( 17 % ) patients . Major bleeding occurred in 13 ( 9 % ) patients ( 11 [ 8 % ] grade 3 - 4 ) . Grade 3 or worse infections occurred in 43 ( 30 % ) patients , including pneumonia in 19 ( 13 % ) patients . In the extended analysis , 38 patients died , 18 as a result of adverse events ( four pneumonia , three chronic lymphocytic leukaemia , two Richter 's syndrome , two sepsis , and one each of acute myocardial infa rct ion , septic shock , encephalopathy , general deterioration in physical health , abnormal hepatic function , myocardial infa rct ion , and renal infa rct ion ) . INTERPRETATION A high proportion of patients had an overall response to ibrutinib and the risk : benefit profile was favourable , providing further evidence for use of ibrutinib in the most difficult subset of patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma . Ibrutinib represents a clinical advance in the treatment of patients with del17p chronic lymphocytic leukaemia and has been incorporated into treatment algorithms as a primary treatment for these patients . FUNDING Pharmacyclics LLC , an AbbVie Company In a phase 1 trial , idelalisib ( GS-1101 , CAL-101 ) , a selective inhibitor of the lipid kinase PI3Kδ , was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia ( CLL ) with adverse characteristics including bulky lymphadenopathy ( 80 % ) , extensive prior therapy ( median 5 [ range 2 - 14 ] prior regimens ) , treatment-refractory disease ( 70 % ) , unmutated IGHV ( 91 % ) , and del17p and /or TP53 mutations ( 24 % ) . Patients were treated at 6 dose levels of oral idelalisib ( range 50 - 350 mg once or twice daily ) and remained on continuous therapy while deriving clinical benefit . Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines . The most commonly observed grade ≥3 adverse events were pneumonia ( 20 % ) , neutropenic fever ( 11 % ) , and diarrhea ( 6 % ) . Idelalisib treatment result ed in nodal responses in 81 % of patients . The overall response rate was 72 % , with 39 % of patients meeting the criteria for partial response per IWCLL 2008 and 33 % meeting the recently up date d criteria of PR with treatment-induced lymphocytosis.(1,2 ) The median progression-free survival for all patients was 15.8 months . This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib . Our findings support the further development of idelalisib in patients with CLL . These trials were registered at clinical trials.gov as # NCT00710528 and # NCT01090414 Despite promising results with targeted drugs , chemoimmunotherapy with fludarabine , cyclophosphamide ( FC ) , and rituximab ( R ) remains the st and ard therapy for fit patients with untreated chronic lymphocytic leukemia ( CLL ) . Herein , we present the long-term follow-up of the r and omized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-naïve patients with CLL . The primary end point was progression-free survival ( PFS ) . With a median follow-up of 5.9 years , median PFS were 56.8 and 32.9 months for the FCR and FC group ( hazard ratio [ HR ] , 0.59 ; 95 % confidence interval [ CI ] , 0.50 - 0.69 , P < .001 ) . Median overall survival ( OS ) was not reached for the FCR group and was 86.0 months for the FC group ( HR , 0.68 ; 95 % CI , 0.54 - 0.89 , P = .001 ) . In patients with mutated IGHV ( IGHV MUT ) , FCR improved PFS and OS compared with FC ( PFS : HR , 0.47 ; 95 % CI , 0.33 - 0.68 , P < .001 ; OS : HR , 0.62 ; 95 % CI , 0.34 - 1.11 , P = .1 ) . This improvement remained applicable for all cytogenetic subgroups other than del(17p ) . Long-term safety analyses showed that FCR had a higher rate of prolonged neutropenia during the first year after treatment ( 16.6 % vs 8.8 % ; P = .007 ) . Secondary malignancies including Richter 's transformation occurred in 13.1 % in the FCR group and in 17.4 % in the FC group ( P = .1 ) . First-line chemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL , in particular those with IGHV MUT . This trial was registered at www . clinical trials.gov as # NCT00281918 SUMMARY : The r and omized ISAT demonstrated the superiority of endovascular treatment in patients with ruptured intracranial aneurysms considered suitable for either clipping or coiling . A later publication proposed a second look at the results , demonstrating that older patients with ruptured MCA aneurysms appeared to benefit from clipping , in disagreement with the general findings of the trial . Subgroup analyses in r and omized trials and observational studies examine whether effects of interventions differ between subgroups according to the characteristics of patients . However , many apparent subgroup effects have been shown to be spurious . Misleading subgroup effects can result in withholding efficacious treatment from patients who would benefit or can encourage ineffective or potentially harmful treatments for patients who would fare better without . Some guidelines for the prudent interpretation of subgroup findings are review ed PURPOSE Rituximab , a monoclonal antibody that targets the CD20 cell surface antigen , has clinical activity in patients with non-Hodgkin 's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy . Promising results have previously been reported in nonr and omized studies in patients with chronic lymphocytic leukemia ( CLL ) . This trial was design ed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL . PATIENTS AND METHODS This international , multicenter , r and omized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide ( R-FC ) with six cycles of fludarabine and cyclophosphamide alone ( FC ) in patients with previously treated CLL . A total of 552 patients with Binet stage A ( 1 % ) , B ( 59 % ) , or C ( 31 % ) disease entered the study and were r and omly assigned to receive R-FC ( n = 276 ) or FC ( n = 276 ) . RESULTS After a median follow-up time of 25 months , rituximab significantly improved progression-free survival in patients with previously treated CLL ( hazard ratio = 0.65 ; P < .001 ; median , 30.6 months for R-FC v 20.6 months for FC ) . Event-free survival , response rate , complete response rate , duration of response , and time to new CLL treatment or death were also significantly improved . Although the rates of adverse events , grade 3 or 4 events , and serious adverse events were slightly higher in the R-FC arm , R-FC was generally well tolerated , with no new safety findings and no detrimental effect on quality of life . CONCLUSION R-FC significantly improved the outcome of patients with previously treated CLL BACKGROUND Chronic lymphocytic leukaemia ( CLL ) is an incurable and chronic disorder , with worsening prognosis for patients as their disease progresses . We compared the efficacy and safety of the combination of fludarabine and alemtuzumab with fludarabine monotherapy in previously treated patients with relapsed or refractory CLL . METHODS Patients ( aged ≥ 18 years ) with CLL Binet stage A , B , or C or Rai stages I-IV were r and omly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment ( fludarabine 30 mg/m(2 ) per day and alemtuzumab 30 mg per day on days 1 - 3 ) or monotherapy ( fludarabine 25 mg/m(2 ) on days 1 - 5 ) by use of an interactive voice response system . Both regimens were given intravenously for a maximum of six 28-day cycles . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00086580 . FINDINGS Fludarabine plus alemtuzumab ( n=168 ) result ed in better PFS than did fludarabine monotherapy ( n=167 ; median 23·7 months [ 95 % CI 19·2 - 28·4 ] vs 16·5 months [ 12·5 - 21·2 ] ; hazard ratio 0·61 [ 95 % CI 0·47 - 0·80 ] ; p=0·0003 ) and overall survival ( median not reached vs 52·9 months [ 40·9-not reached ] ; 0·65 [ 0·45 - 0·94 ] ; p=0·021 ) compared with fludarabine alone . All-cause adverse events occurred in 161 ( 98 % ) of 164 patients in the combination treatment group and 149 ( 90 % ) of 165 in the fludarabine alone group . Patients in the fludarabine plus alemtuzumab group had more cytomegalovirus events ( 23 [ 14 % ] vs one [ < 1 % ] ) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions ( 102 [ 62 % ] vs 22 [ 13 % ] ) . Grade 3 or 4 toxicities in the combination treatment and monotherapy groups were leucopenia ( 121 [ 74 % ] of 164 vs 55 [ 34 % ] of 164 ) , lymphopenia ( 149 [ 94 % ] of 158 vs 53 [ 33 % ] of 161 ) , neutropenia ( 93 [ 59 % ] of 157 vs 110 [ 68 % ] of 161 ) , thrombocytopenia ( 18 [ 11 % ] of 164 vs 27 [ 17 % ] of 163 ) , and anaemia ( 14 [ 9 % ] of 163 vs 28 [ 17 % ] of 164 ) . The incidence of serious adverse events was higher in the combination treatment group ( 54 [ 33 % ] of 164 vs 41 [ 25 % ] of 165 ) ; deaths due to adverse events were similar between the two groups ( ten [ 6 % ] vs 12 [ 7 % ] ) . INTERPRETATION The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL . FUNDING Genzyme Bendamustine demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from st and ard alkylating agents . This study assessed its efficacy in patients with chronic lymphocytic leukemia pre-treated with an alkylator , in comparison to fludarabine . Patients with relapsed chronic lymphocytic leukemia requiring treatment after one previous systemic regimen ( usually chlorambucil-based ) were r and omized to either receive bendamustine 100 mg/m2 on days 1 and 2 of a 4-week cycle or st and ard fludarabine treatment consisting of 25 mg/m2 on days 1 to 5 every 4 weeks . The primary objective was to achieve non-inferior progression-free survival ( PFS ) with bendamustine . Out of a total of 96 patients r and omized , 92 were eligible , 49 allocated to bendamustine and 43 to fludarabine . About half of the patients received six or more cycles . Overall response rates were 76 % on bendamustine and 62 % on fludarabine , with clinical complete response rates of 27 and 9 % , respectively . Median PFS was 20.1 and 14.8 months ( hazard ratio , 0.87 ; 90 % confidence interval , 0.60–1.27 ) , median overall survival 43.8 and 41.0 months ( hazard ratio , 0.82 ) . Thrombocytopenia and gastrointestinal toxicities were marginally more frequent on bendamustine , albeit CTC grade 3/4 event incidence was similar . These data suggest at least comparable efficacy of bendamustine vs. fludarabine , pointing to an alternative treatment option in relapsing CLL patients after chlorambucil containing initial chemotherapy BACKGROUND Idelalisib , a selective inhibitor of PI3Kδ , is approved for the treatment of patients with relapsed chronic lymphocytic leukaemia ( CLL ) in combination with rituximab . We aim ed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-CD20 antibody , ofatumumab , in a similar patient population . METHODS In this global , open-label , r and omised , controlled phase 3 trial , we enrolled patients with relapsed CLL progressing less than 24 months from last therapy . Patients refractory to ofatumumab were excluded . Patients were stratified by relapsed versus refractory disease , presence or absence of del(17p ) or TP53 mutation , or both , and IGHV mutated versus unmutated . We r and omised patients in a 2:1 ratio using a web-based interactive system that generated a unique treatment code , and assigned patients to receive either idelalisib plus ofatumumab ( oral idelalisib 150 mg twice daily continuously plus ofatumumab 300 mg intravenously in week 1 , then 1000 mg intravenously weekly for 7 weeks , and every 4 weeks for 16 weeks ) or ofatumumab alone ( ofatumumab dosing as per the combination group , except 2000 mg was substituted for the 1000 mg dose ) . An independent review committee assessed response , including progressive disease , based on imaging using modified International Workshop on Chronic Lymphocytic Leukaemia 2008 criteria . The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat population . We did a primary analysis ( data cutoff Jan 15 , 2015 ) and an up date d analysis ( data cutoff Sept 1 , 2015 ) . This trial is registered with Clinical trials.gov , number NCT01659021 . FINDINGS Between Dec 17 , 2012 , and March 31 , 2014 , we enrolled 261 patients ( median age 68 years [ IQR 61 - 74 ] , median previous therapies three [ IQR 2 - 4 ] ) . At the primary analysis , median progression-free survival was 16·3 months ( 95 % CI 13·6 - 17·8 ) in the idelalisib plus ofatumumab group and 8·0 months ( 5·7 - 8·2 ) in the ofatumumab group ( adjusted hazard ratio [ HR ] 0·27 , 95 % CI 0·19 - 0·39 , p<0·0001 ) . The most frequent grade 3 or worse adverse events in the idelalisib plus ofatumumab group were neutropenia ( 59 [ 34 % ] patients vs 14 [ 16 % ] in the ofatumumab group ) , diarrhoea ( 34 [ 20 % ] vs one [ 1 % ] ) , and pneumonia ( 25 [ 14 % ] vs seven [ 8 % ] ) . The most frequent grade 3 or worse adverse events in the ofatumumab group were neutropenia ( 14 [ 16 % ] ) , pneumonia ( seven [ 8 % ] ) , and thrombocytopenia ( six [ 7 % ] vs 19 [ 11 % ] in the idelalisib plus ofatumumab group ) . Serious infections were more common in the idelalisib plus ofatumumab group and included pneumonia ( 23 [ 13 % ] patients in the idelalisib plus ofatumumab group vs nine [ 10 % ] in the ofatumumab group ) , sepsis ( 11 [ 6 % ] vs one [ 1 % ] ) , and Pneumocystis jirovecii pneumonia ( eight [ 5 % ] vs one [ 1 % ] ) . 22 treatment-related deaths occurred in the idelalisib plus ofatumumab group ( the most common being sepsis , septic shock , viral sepsis , and pneumonia ) . Six treatment-related deaths occurred in the ofatumumab group ( the most common being progressive multifocal leukoencephalopathy and pneumonia ) . INTERPRETATION The idelalisib plus ofatumumab combination result ed in better progression-free survival compared with ofatumumab alone in patients with relapsed CLL , including in those with high-risk disease , and thus might represent a new treatment alternative for this patient population . FUNDING Gilead Sciences , Purpose : Ibrutinib , a first-in-class , once-daily , oral inhibitor of Bruton tyrosine kinase , promotes apoptosis , and inhibits B-cell proliferation , adhesion , and migration . Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) who were treatment-naïve ( TN ) or had relapsed/refractory ( R/R ) CLL after ≥1 prior therapy in a phase Ib/II study ( PCYC-1102 ) . Subsequently , the ibrutinib 420 mg dose was approved in CLL . Experimental Design : We report data with 44 months of follow-up on 94 patients with TN and R/R CLL/SLL receiving ibrutinib 420 mg once-daily in PCYC-1102 and the long-term extension study PCYC-1103 . Results : Ninety-four CLL/SLL patients ( 27 TN , 67 R/R ) were treated with ibrutinib ( 420 mg/day ) . Patients with R/R disease had received a median of four prior therapies ( range , 1–12 ) . Responses were rapid and durable and median duration of response was not reached . Best overall response was 91 % [ 85 % TN ( complete response , CR 26 % ) and 94 % R/R ( 9 % CR ) ] . Median progression-free survival ( PFS ) was not reached in either group . The 30-month PFS rate was 96 % and 76 % for TN and R/R patients , respectively . Ibrutinib was well tolerated with extended follow-up ; rates of grade ≥3 cytopenias and fatigue , as well as discontinuations due to toxicities decreased over time . Conclusions : Single-agent ibrutinib at 420 mg once-daily result ed in durable responses and was well tolerated with up to 44 months follow-up in patients with TN and R/R CLL/SLL . Currently , 66 % of patients continue on ibrutinib . Clin Cancer Res ; 23(5 ) ; 1149–55 . © 2017 AACR BACKGROUND Patients with relapsed chronic lymphocytic leukemia ( CLL ) who have clinical ly significant coexisting medical conditions are less able to undergo st and ard chemotherapy . Effective therapies with acceptable side-effect profiles are needed for this patient population . METHODS In this multicenter , r and omized , double-blind , placebo-controlled , phase 3 study , we assessed the efficacy and safety of idelalisib , an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase , in combination with rituximab versus rituximab plus placebo . We r and omly assigned 220 patients with decreased renal function , previous therapy-induced myelosuppression , or major coexisting illnesses to receive rituximab and either idelalisib ( at a dose of 150 mg ) or placebo twice daily . The primary end point was progression-free survival . At the first prespecified interim analysis , the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy . RESULTS The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group ( hazard ratio for progression or death in the idelalisib group , 0.15 ; P<0.001 ) . Patients receiving idelalisib versus those receiving placebo had improved rates of overall response ( 81 % vs. 13 % ; odds ratio , 29.92 ; P<0.001 ) and overall survival at 12 months ( 92 % vs. 80 % ; hazard ratio for death , 0.28 ; P=0.02 ) . Serious adverse events occurred in 40 % of the patients receiving idelalisib and rituximab and in 35 % of those receiving placebo and rituximab . CONCLUSIONS The combination of idelalisib and rituximab , as compared with placebo and rituximab , significantly improved progression-free survival , response rate , and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy . ( Funded by Gilead ; Clinical Trials.gov number , NCT01539512 . ) BACKGROUND In patients with chronic lymphoid leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ) , a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome . We evaluated the efficacy of ibrutinib , a covalent inhibitor of Bruton 's tyrosine kinase , in patients at risk for a poor outcome . METHODS In this multicenter , open-label , phase 3 study , we r and omly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab . The primary end point was the duration of progression-free survival , with the duration of overall survival and the overall response rate as secondary end points . RESULTS At a median follow-up of 9.4 months , ibrutinib significantly improved progression-free survival ; the median duration was not reached in the ibrutinib group ( with a rate of progression-free survival of 88 % at 6 months ) , as compared with a median of 8.1 months in the ofatumumab group ( hazard ratio for progression or death in the ibrutinib group , 0.22 ; P<0.001 ) . Ibrutinib also significantly improved overall survival ( hazard ratio for death , 0.43 ; P=0.005 ) . At 12 months , the overall survival rate was 90 % in the ibrutinib group and 81 % in the ofatumumab group . The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group ( 42.6 % vs. 4.1 % , P<0.001 ) . An additional 20 % of ibrutinib-treated patients had a partial response with lymphocytosis . Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues . The most frequent nonhematologic adverse events were diarrhea , fatigue , pyrexia , and nausea in the ibrutinib group and fatigue , infusion-related reactions , and cough in the ofatumumab group . CONCLUSIONS Ibrutinib , as compared with ofatumumab , significantly improved progression-free survival , overall survival , and response rate among patients with previously treated CLL or SLL . ( Funded by Pharmacyclics and Janssen ; RESONATE Clinical Trials.gov number , NCT01578707 . ) BACKGROUND New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia ( CLL ) , but complete remissions remain uncommon . Venetoclax has a distinct mechanism of action ; it targets BCL2 , a protein central to the survival of CLL cells . METHODS We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma ( SLL ) to assess safety , pharmacokinetic profile , and efficacy . In the dose-escalation phase , 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day . In an expansion cohort , 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day . RESULTS The majority of the study patients had received multiple previous treatments , and 89 % had poor prognostic clinical or genetic features . Venetoclax was active at all dose levels . Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort , with one death . After adjustments to the dose-escalation schedule , clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort . Other toxic effects included mild diarrhea ( in 52 % of the patients ) , upper respiratory tract infection ( in 48 % ) , nausea ( in 47 % ) , and grade 3 or 4 neutropenia ( in 41 % ) . A maximum tolerated dose was not identified . Among the 116 patients who received venetoclax , 92 ( 79 % ) had a response . Response rates ranged from 71 to 79 % among patients in subgroups with an adverse prognosis , including those with resistance to fludarabine , those with chromosome 17p deletions ( deletion 17p CLL ) , and those with unmutated IGHV . Complete remissions occurred in 20 % of the patients , including 5 % who had no minimal residual disease on flow cytometry . The 15-month progression-free survival estimate for the 400-mg dose groups was 69 % . CONCLUSIONS Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL , including those with poor prognostic features . ( Funded by AbbVie and Genentech ; Clinical Trials.gov number , NCT01328626 . ) Abstract In this multicenter , open-label , phase III study , patients with relapsed chronic lymphocytic leukemia ( CLL ) were r and omized ( 1:1 ) to receive ofatumumab plus fludarabine and cyclophosphamide ( OFA + FC ) or FC alone ; the primary endpoint being progression-free survival ( PFS ) assessed by an independent review committee ( IRC ) . Between March 2009 and January 2012 , 365 patients were r and omized ( OFA + FC : n = 183 ; FC : n = 182 ) . Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC ( hazard ratio = 0.67 ; 95 % confidence interval , 0.51–0.88 ; p = .0032 ) . Grade ≥3 adverse events ( ≤60 days after last dose ) were reported in 134 ( 74 % ) OFA + FC-treated patients compared with 123 ( 69 % ) FC-treated patients . Of these , neutropenia was the most common ( 89 [ 49 % ] vs. 64 [ 36 % ] ) . OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone , thus providing an alternative treatment option for patients with relapsed CLL . Trial registration : www . clinical trials.gov ( NCT00824265 ) Idelalisib is a small-molecule inhibitor of PI3Kδ with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia ( CLL ) . To evaluate idelalisib as front-line therapy , we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab . After a median follow-up period of 14.7 months , hepatotoxicity was found to be a frequent and often severe adverse event . A total of 19 subjects ( 79 % ) experienced either grade ≥1 ALT or AST elevation during the study , and 13 subjects ( 54 % ) experienced grade ≥3 transaminitis . The median time to development of transaminitis was 28 days , occurring before ofatumumab introduction . Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity . Multiple lines of evidence suggest that this hepatotoxicity was immune mediated . A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis , and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity . All cases of transaminitis resolved either by holding the drug , initiating immunosuppressants , or both , and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated . A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy , which is consistent with an immune-mediated mechanism . These results suggest that caution should be taken as drugs within this class are developed for CLL , particularly in younger patients who have not received prior disease-specific therapy . This study was registered at www . clinical trials.gov as # NCT02135133 |
12,562 | 31,914,791 | For the best known and studied modifications , conclusions could be drawn about their effect on clot formation and structure .
Oxidation , high levels of nitration , and glycosylation inhibit the rate of polymerization , result ing in dense clots with thinner fibers , while low levels of nitration increase the rate of polymerization .
Glycation showed different results for polymerization , but fibrinolysis was found to be decreased , as a consequence of increased density and decreased permeability of clots .
Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis .
Other modifications were studied less or contrasting results were found .
Conclusions : Overall , post-translational modifications do affect clot formation and characteristics . | Objective : Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases .
In this systematic review , we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics . | Patients with CKD on hemodialysis exhibit increased cardiovascular risk . Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events , but little is known about the influence of clot density on outcome in patients on hemodialysis . We determined fibrin clot structure parameters and effect on mortality in a prospect i ve cohort of 171 patients on chronic hemodialysis ( mean±SD age = 59±11 years old ; 54 % men ) using a vali date d turbidimetric assay . Kaplan-Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all-cause and cardiovascular mortality risks ( log rank P=0.004 and P=0.003 , respectively ) . Multivariate Cox regression models ( adjusted for age , diabetes , sex , and duration of dialysis or fibrinogen , C-reactive protein , and complement C3 ) confirmed that denser clots are independently related to mortality risk . We also purified fibrinogen from healthy controls and patients on hemodialysis using the calcium-dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy . Whereas purified fibrinogen from healthy controls displayed no post-translational modifications , fibrinogen from patients on hemodialysis was glycosylated and guanidinylated . Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals ( mean±SD = 63±2 and 77±2 nm , respectively ; P<0.001 ) . In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers , suggesting that difference in fiber thickness might be at least partially due to post-translational modifications . Thus , in patients on hemodialysis , a denser clot structure may be a potent independent risk factor for mortality The effect of acetylsalicylic acid in preventing cardiovascular complications is ascribed to acetylation of the enzyme cyclo-oxygenase thereby inhibiting prostagl and in synthesis . Acetylsalicylic acid , however , also acetylates fibrinogen . In the present pilot study , we investigated the permeability , i.e. porosity , of the fibrin gel in male patients with stable angina pectoris treated with this drug before and at 1 and 2 weeks after withdrawal . Ten patients were treated with 75 mg and eight with 160 mg . The results were compared to those in seven untreated healthy controls . Bleeding times were longer during treatment and were reduced after withdrawal indicating patient compliance . Fibrin gels were more porous during treatment although there were large inter-individual variations in porosity . One week after withdrawal , the porosity was reduced by 30 41 % , i.e. the network became tighter ( 75 mg group P = 0.001 ; 160 mg group P = 0.002 ) . The tightness was more pronounced after withdrawal than in the untreated controls . In conclusion , the protective effect of acetylsalicylic acid may be ascribed to its effect not only on platelets but also on fibrinogen . The withdrawal of acetylsalicylic acid may clause a markedly reduced fibrin gel porosity that we assume is disadvantageous in patients with cardiovascular disease Despite multiple interventions to reduce the risk of cardiovascular disease , the majority of people with diabetes develop macrovascular complications , and mortality following myocardial infa rct ion remains unacceptably high [ 1 ] . Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease , although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [ 2 ] . In fact , there is little direct evidence supporting its efficacy in this group of patients . Instead , there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes . In a meta- analysis of 287 r and omised trials , antiplatelet treatment ( aspirin in most studies ) reduced the risk of ischaemic events by 22 % , but the risk reduction in the subgroup with diabetes was only 7 % , which was not statistically significant [ 3 ] . This outcome was mirrored in the Primary Prevention Project trial , which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [ 4 ] . Despite this , there are no published studies specifically design ed to evaluate the clinical efficacy of aspirin in individuals with diabetes , a surprising omission in the era of ‘ evidence based ’ medicine . These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of aspirin in patients with diabetes compared with a nondiabetic population . Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk — a possibility that has led to the hotly debated concept of aspirin resistance [ 5 , 6 ] . Unfortunately , aspirin resistance suffers from a lack of a st and ardised definition , although now generally thought of as either ( 1 ) reflecting clinical aspirin resistance ( or perhaps , more accurately , treatment failure ) , characterised by the occurrence of a thrombotic episode despite treatment with aspirin ; or ( 2 ) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin . Controversy remains as to the cause of biochemical aspirin resistance , its relevance to clinical outcomes , and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients . All of this highlights the urgent need to underst and the mechanisms that underpin the interactions between diabetes and aspirin , to establish the role of aspirin in particular , and antiplatelet therapy in general , in the amelioration of cardiovascular events in individuals with diabetes . Diabetologia ( 2008 ) 51:385–390 DOI 10.1007/s00125 - 007 - 0898 - Diabetic subjects have been shown to have altered fibrin network structures . One possible cause may be fibrinogen glycation result ing in altered structure/function properties . We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes . Blood sample s were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures . The subjects were then treated with insulin until blood glucose control was achieved before end blood sample s were taken . Twenty age- and BMI -matched non-diabetic subjects were included as a reference group . The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects ( 7.84 vs. 3.89 mol glucose / mol fibrinogen ; p < 0.001 ) . This was significantly reduced during the intervention ( 7.84 to 5.24 mol glucose / mol fibrinogen ; p < 0.0002 ) in the diabetic group . Both groups had high mean fibrinogen concentrations ( 4.25 and 4.02 g/l , diabetic and non-diabetic subjects respectively ) . There was no difference in fibrinogen concentration , porosity , compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline , nor were there any changes during the intervention despite the reduced fibrinogen glycation . Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control . Improved glycaemic control result ed in decreased fibrinogen glycation but not fibrinogen concentration . It seems as though porosity , compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model St and ard coagulation assays were performed with control and oxidized fibrinogen ( Fg ) , using prothrombin time ( PT ; 12.5 ± 0.4 vs 25 ± 0.8 seconds , P < .001 ) and activated partial thromboplastin time ( aPTT ; 33 ± 2.5 vs 63 ± 4.7 seconds , P < .001 ) . Fibrin clot ( MA ) , clot formation initiation ( r ) , and rate of clot lysis ( LY30 ) were measured , a reflection exposure of Fg to Fe3+/ ascorbate oxidative system by thrombelastograph ( TEG ) analysis ( 0 , 6 , 12 , 24 , and 48 hours , 6.2 ± 1.3 vs 5.5 ± 1.2 , 4.3 ± 1.0 [ P < .01 ] , 3.9 ± 1.6 , 3.2 ± 0.8 , [ P < .001 ] ) . Maximum amplitude level was found to be lower than control ( 69.1 ± 7.2 vs 67.9 ± 12.4 , 64.0 ± 11.4 , 60.2 ± 21.2 , 42.2 ± 15.2 , P < .001 ) . The lysis rate was changed according to oxidation time between Fg exposed to Fe3+/ascorbate and control exposed to Fe 3+/ascorbate for the same treatment time ( 1.9 ± 0.71 vs 7 ± 0.5 , 1.6 ± 0.1 , 1.2 ± 0.5 , 0.9 ± 1.3 , P < .001 ) . We revealed dysregulation of hemostatic system with contribution of oxidized Fg , which was in direct proportion to the intensity of Fg oxidation |
12,563 | 32,221,811 | The relationship between physical function and pancreatic/liver cancer resection outcome remains unclear , although anaerobic threshold appears the strongest predictor of postoperative outcomes . | Surgery is the only potentially curative treatment for pancreatic and liver cancer .
However , even in high-volume centres , surgical resection is associated with significant morbidity with result ant physical decline .
This systematic review explored physical function and its ’ implication s in the management of resectable cancer of the pancreas and liver .
Physical function across the pancreatic/liver cancer trajectory has been under investigated . | IMPORTANCE Cardiorespiratory fitness ( CRF ) as assessed by formalized incremental exercise testing is an independent predictor of numerous chronic diseases , but its association with incident cancer or survival following a diagnosis of cancer has received little attention . OBJECTIVE To assess the association between midlife CRF and incident cancer and survival following a cancer diagnosis . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , observational cohort study conducted at a preventive medicine clinic . The study included 13 949 community-dwelling men who had a baseline fitness examination . All men completed a comprehensive medical examination , a cardiovascular risk factor assessment , and incremental treadmill exercise test to evaluate CRF . We used age- and sex-specific distribution of treadmill duration from the overall Cooper Center Longitudinal Study population to define fitness groups as those with low ( lowest 20 % ) , moderate ( middle 40 % ) , and high ( upper 40 % ) CRF groups . The adjusted multivariable model included age , examination year , body mass index , smoking , total cholesterol level , systolic blood pressure , diabetes mellitus , and fasting glucose level . Cardiorespiratory fitness levels were assessed between 1971 and 2009 , and incident lung , prostate , and colorectal cancer using Medicare Parts A and B cl aims data from 1999 to 2009 ; the analysis was conducted in 2014 . MAIN OUTCOMES AND MEASURES The main outcomes were ( 1 ) incident prostate , lung , and colorectal cancer and ( 2 ) all-cause mortality and cause-specific mortality among men who developed cancer at Medicare age ( ≥65 years ) . RESULTS Compared with men with low CRF , the adjusted hazard ratios ( HRs ) for incident lung , colorectal , and prostate cancers among men with high CRF were 0.45 ( 95 % CI , 0.29 - 0.68 ) , 0.56 ( 95 % CI , 0.36 - 0.87 ) , and 1.22 ( 95 % CI , 1.02 - 1.46 ) , respectively . Among those diagnosed as having cancer at Medicare age , high CRF in midlife was associated with an adjusted 32 % ( HR , 0.68 ; 95 % CI , 0.47 - 0.98 ) risk reduction in all cancer-related deaths and a 68 % reduction in cardiovascular disease mortality following a cancer diagnosis ( HR , 0.32 ; 95 % CI , 0.16 - 0.64 ) compared with men with low CRF in midlife . CONCLUSIONS AND RELEVANCE There is an inverse association between midlife CRF and incident lung and colorectal cancer but not prostate cancer . High midlife CRF is associated with lower risk of cause-specific mortality in those diagnosed as having cancer at Medicare age Purpose Physical , nutritional and quality -of-life compromises are known sequelae of oesophageal cancer ( OC ) treatment . Inflammation and oxidative stress may be relevant to adverse consequences . Multimodal rehabilitation involving exercise and diet prescription may attenuate some of the negative consequences and optimise survivorship , and this was assessed in this feasibility study in OC patients at least 1 year post-oesophagectomy . Methods The 12-week programme included supervised and home-based exercise , dietetic counselling to ensure energy balance and multidisciplinary education . Baseline and post-intervention assessment s examined aerobic fitness , physical activity and body composition . Serum interleukin (IL)-1β , tumour necrosis factor (TNF)-α , IL-6 and IL-8 were measured via multiplex arrays . Lactate secretion , lipid peroxidation ( 4-HNE ) and oxidative stress ( 8-iso-PGF2α ) were measured by enzyme-linked immunosorbent assay ( ELISA ) . Results Twelve patients ( mean ( SD ) age 64(1.29 ) years ) participated . IL-8 reduced significantly from pre- to post-intervention ( percentage change −11.25 % ( 95 % CI −20.98 to −1.51 % ) , p = 0.03 ) , and there was a non-significant trend towards lower expression patterns of other inflammatory mediators . At baseline , inflammatory status correlated inversely with sedentary behaviour ( IL-6 rho = −0.74 , IL-8 rho = −0.59 , TNF-α rho = −0.69 ; p < 0.05 ) . While energy metabolism did not change , post-intervention lactate concentration correlated strongly and inversely with aerobic fitness ( rho = −0.68 , p = 0.02 ) . Body composition was maintained throughout the intervention . Conclusions Results suggest that multimodal rehabilitation following OC treatment reduced inflammatory status without compromising body composition . Findings will be further examined in a larger r and omised controlled trial Purpose Preoperative chemo(radio)therapy for oesophageal cancer ( OC ) may have an attritional impact on body composition and functional status , impacting postoperative outcome . Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation . This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC . Methods Measures of body composition ( axial computerised tomography ) , muscle strength ( h and grip ) , functional capacity ( walking distance ) , anthropometry ( weight , height and waist circumference ) , physical activity , quality -of-life and nutritional status were captured prospect ively . Sarcopenia status was defined as pre-sarcopenic ( low muscle mass only ) , sarcopenic ( low muscle mass and low muscle strength or function ) or severely sarcopenic ( low muscle mass and low muscle strength and low muscle function ) . Results Twenty-eight participants were studied at both time points ( mean age 62.86 ± 8.18 years , n = 23 male ) . Lean body mass reduced by 4.9 ( 95 % confidence interval 3.2 to 6.7 ) kg and mean grip strength reduced by 4.3 ( 2.5 to 6.1 ) kg from pre- to post-neoadjuvant therapy . Quality -of-life scores capturing gastrointestinal symptoms improved . Measures of anthropometry , walking distance , physical activity and nutritional status did not change . There was an increase in sarcopenic status from diagnosis ( pre-sarcopenic n = 2 ) to post-treatment ( pre-sarcopenic n = 5 , severely sarcopenic n = 1 ) . Conclusions Despite maintenance of body weight , functional capacity and activity habits , participants experience declines in muscle mass and strength . Interventions involving exercise and /or nutritional support to build muscle mass and strength during preoperative therapy , even in patients who are functioning normally , are warranted Objectives Poor cardiorespiratory fitness ( CRF ) is associated with death from cancer . If follow-up time is short , this association may be confounded by sub clinical disease already present at the time of CRF assessment . This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up , respectively . Setting , participants and main outcome measures Middle-aged , employed and cancer-free Danish men from the prospect i ve Copenhagen Male Study , enrolled in 1970–1971 , were included . CRF ( maximal oxygen consumption ( VO2max ) ) was estimated using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors , social class and self-reported physical activity . Death from cancer and all-cause mortality was assessed using Danish national registers . Follow-up was 100 % complete . Results In total , 5131 men were included , mean ( SD ) age 48.8 ( 5.4 ) years . During 44 years of follow-up , 4486 subjects died ( 87.4 % ) , 1527 ( 29.8 % ) from cancer . In multivariable models , CRF was highly significantly inversely associated with death from cancer and all-cause mortality ( ( HR ( 95 % CI ) ) 0.83 ( 0.77 to 0.90 ) and 0.89 ( 0.85 to 0.93 ) per 10 mL/kg/min increase in estimated VO2max , respectively ) . A similar association was seen across specific cancer groups , except death from prostate cancer ( 1.00 ( 0.82 to 1.2 ) ; p=0.97 ; n=231 ) . The associations between CRF and outcomes remained essentially unchanged after excluding subjects dying within 10 years ( n=377 ) and 20 years ( n=1276 ) of inclusion . Conclusions CRF is highly significantly inversely associated with death from cancer and all-cause mortality . The associations are robust for exclusion of subjects dying within 20 years of study inclusion , thereby suggesting a minimal influence of reverse causation CONTEXT Although several studies have examined peri-operative nutritional supplementation in patients undergoing pancreaticoduodenectomy all provided support at various timepoints with a variety of protocol s. OBJECTIVE This study undertakes a detailed nutritional and anthropometric assessment of patients due to undergo pancreaticoduodenectomy with particular reference to pre-operative nutritional status and peri-operative outcome . PATIENTS Twenty-six patients undergoing pancreaticoduodenectomy . SETTING A regional hepatobiliary service . MAIN OUTCOME MEASURES Nutritional , anthropometric and clinical course details . DESIGN Data were collected prospect ively . RESULTS There was no significant change in any anthropometric index from baseline to immediately prior to surgery . However , there was a significant fall in BMI comparing baseline measurements to observations at time of discharge from hospital ( P<0.001 ) . There was , in addition , a significant difference between baseline and BMI at 3 months ( P<0.001 ) . Similar trends were observed in mid-arm circumference , triceps skin fold thickness and h and -grip . There was no in-hospital or 3-month post-operative mortality in this series . CONCLUSION Nutritional and anthropometric indices remain stable from the time of index admission to operation . However , there is a drastic and sustained reduction in nutritional indices in the post-operative period with this deficiency being sustained at 3-months after operation BACKGROUND Preserving functional walking capacity and nutritional status is important for patients with esophageal cancer , but no effective intervention is available , particularly during active treatment . METHODS This pilot r and omized controlled trial tested the effects of a walk- and -eat intervention for patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy . Participants with locally advanced esophageal cancer stage IIB or higher ( n = 59 ) were r and omly assigned to receive the walk- and -eat intervention ( n = 30 ; nurse-supervised walking three times per week and weekly nutritional advice ) or usual care ( n = 29 ; control group ) during 4 - 5 weeks of chemoradiotherapy . Primary endpoints were changes in distance on the 6-minute walk test , h and -grip strength , lean muscle mass , and body weight between initiation and completion of intervention . RESULTS Participants ( mean age : 59.6 years ) were mostly male ( 92.9 % ) with squamous cell carcinoma ( 96.4 % ) . During chemoradiotherapy , participants who received the walk- and -eat intervention had 100-m less decline than controls in walk distance ( adjusted p = .012 ) , 3-kg less decrease in h and -grip strength ( adjusted p = .002 ) , and 2.7-kg less reduction in body weight ( adjusted p < .001 ) , regardless of age . The intervention group also had significantly lower rates of need for intravenous nutritional support and wheelchair use . CONCLUSION The nurse-led walk- and -eat intervention is feasible and effective to preserve functional walking capacity and nutritional status for patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy 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 OBJECTIVE Despite the potential for nutritional deficits in patients undergoing pancreaticoduodenectomy or Whipple procedure , long-term assessment of nutritional status has largely been ignored . This study assessed nutritional status of 24 Whipple patients compared with matched post-cholecystectomy controls . METHODS Clinical assessment was by subjective global assessment , body composition was assessed by bioelectric impedance analysis and functional assessment was by respiratory muscle strength and skeletal muscle function performed by electrical stimulation of the ulnar nerve of the wrist and h and -grip dynamometry . RESULTS Whipple patients studied 4.6+/-0.7 years since surgery and controls ( 4.8+/-0.7 years since surgery ) were all judged clinical ly to be in a good nutritional state . Compared with controls , Whipple patients had significantly lower body weight ( Whipple : 72.5+/-2.8 kg , control : 83.9+/-3.3 kg , p<0.05 ) however , the mean body weight of both Whipple and controls was above ideal weight ( Whipple : 113.3+/-4.3 % , control : 122.3+/-3.7 % p = NS ) . No significant differences in functional performance were observed between groups . Energy intake of Whipple and controls was also comparable . In the Whipple group , neither the extent of gastric resection or the pathological diagnosis had an effect on the nutritional parameters studied . CONCLUSIONS Long-term follow-up of patients having undergone Whipple procedure failed to reveal the presence of any nutritional or functional deficits suggesting that a full nutritional recovery is possible after this surgery BACKGROUND Neoadjuvant chemotherapy ( NAC ) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone . However NAC has adverse effects . We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery . METHODS We prospect ively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness , of whom 89 underwent cardiopulmonary exercise testing ( CPET ) before NAC and proceeded to surgery . 39 patients were tested after all cycles of NAC but prior to surgery . Physical fitness was assessed by measuring oxygen uptake ( VO₂ in ml kg(-1 ) min(-1 ) ) at the estimated lactate threshold ( θL ) and at peak exercise ( VO₂ peak in ml kg(-1 ) min(-1 ) ) . RESULTS VO₂ at θL and at peak were significantly lower after NAC compared to pre-NAC values : VO₂ at θL 14.5 ± 3.8 ( baseline ) vs. 12.3 ± 3.0 ( post-NAC ) ml kg(-1 ) min(-1 ) ; p ≤ 0.001 ; VO₂ peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1 ) min(-1 ) ; p ≤ 0.001 ; absolute VO₂ ( ml min(-1 ) ) at θL and peak were also lower post-NAC ; p ≤ 0.001 . Decreased baseline VO₂ at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery ; p = 0.014 . CONCLUSION NAC before cancer surgery significantly reduced physical fitness in the overall cohort . Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery , but not in patients who did not complete NAC . It is possible that in some patients the harms of NAC may outweigh the benefits . Trials Registry Number : NCT01335555 IMPORTANCE The prognosis for patients with pancreatic cancer is poor , even after resection with curative intent . Gemcitabine-based chemotherapy is st and ard treatment for advanced pancreatic cancer , but its effect on survival in the adjuvant setting has not been demonstrated . OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival . DESIGN , SETTING , AND PATIENTS CONKO-001 ( Charité Onkologie 001 ) , a multicenter , open-label , phase 3 r and omized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection . Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria . Follow-up ended in September 2012 . INTERVENTIONS After stratification for tumor stage , nodal status , and resection status , patients were r and omly assigned to either adjuvant gemcitabine treatment ( 1g/m2 d 1 , 8 , 15 , q 4 weeks ) for 6 months or to observation alone . MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival . Secondary end points included treatment safety and overall survival , with overall survival defined as the time from date of r and omization to death . Patients lost to follow-up were censored on the date of their last follow-up . RESULTS A total of 368 patients were r and omized , and 354 were eligible for intention-to-treat- analysis . By September 2012 , 308 patients ( 87.0 % [ 95 % CI , 83.1%-90.1 % ] ) had relapsed and 316 patients ( 89.3 % [ 95 % CI , 85.6%-92.1 % ] ) had died . The median follow-up time was 136 months . The median disease-free survival was 13.4 ( 95 % CI , 11.6 - 15.3 ) months in the treatment group compared with 6.7 ( 95 % CI , 6.0 - 7.5 ) months in the observation group ( hazard ratio , 0.55 [ 95 % CI , 0.44 - 0.69 ] ; P < .001 ) . Patients r and omized to adjuvant gemcitabine treatment had prolonged overall survival compared with those r and omized to observation alone ( hazard ratio , 0.76 [ 95 % CI , 0.61 - 0.95 ] ; P = .01 ) , with 5-year overall survival of 20.7 % ( 95 % CI , 14.7%-26.6 % ) vs 10.4 % ( 95 % CI , 5.9%-15.0 % ) , respectively , and 10-year overall survival of 12.2 % ( 95 % CI , 7.3%-17.2 % ) vs 7.7 % ( 95 % CI , 3.6%-11.8 % ) . CONCLUSIONS AND RELEVANCE Among patients with macroscopic complete removal of pancreatic cancer , the use of adjuvant gemcitabine for 6 months compared with observation alone result ed in increased overall survival as well as disease-free survival . These findings provide strong support for the use of gemcitabine in this setting . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 BACKGROUND The effect of adjuvant treatment on survival in pancreatic cancer is unclear . We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and up date the interim results . METHODS In a multicenter trial using a two-by-two factorial design , we r and omly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone ( 20 Gy over a two-week period plus fluorouracil ) , 75 patients to chemotherapy alone ( fluorouracil ) , 72 patients to both chemoradiotherapy and chemotherapy , and 69 patients to observation . RESULTS The analysis was based on 237 deaths among the 289 patients ( 82 percent ) and a median follow-up of 47 months ( interquartile range , 33 to 62 ) . The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy ( P=0.05 ) . The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy ( P=0.009 ) . The benefit of chemotherapy persisted after adjustment for major prognostic factors . CONCLUSIONS Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer , whereas adjuvant chemoradiotherapy has a deleterious effect on survival Objective Pancreaticoduodenectomy is the st and ard of care for tumors confined to the head of pancreas and can be undertaken with low operative mortality . The procedure has a high morbidity , particularly in older patient population s with preexisting comorbidities . This study evaluated the role of cardiopulmonary exercise testing to predict postoperative morbidity and outcome in high-risk patients undergoing pancreaticoduodenectomy . Methods In a prospect i ve cohort of consecutive patients undergoing pancreaticoduodenectomy , those aged over 65 years ( or younger with comorbidity ) were categorized as high risk and underwent preoperative assessment by cardiopulmonary exercise testing ( CPET ) according to a predefined protocol . Data were collected on functional status , postoperative complications , and survival . Results A total of 143 patients underwent preoperative assessment , 50 of whom were deemed to be at low risk for surgery per study protocol . Of 93 high-risk patients , 64 proceeded to surgery after preoperative CPET . Neither anaerobic threshold ( AT ) nor maximal oxygen consumption ( $ $ \dot{V } $ $ V˙o2 MAX ) predicted patient mortality or morbidity . However , ventilatory equivalent of carbon dioxide ( $ $ \dot{V } $ $ V˙e/$$ \dot{V } $ $ V˙co2 ) at AT was a predictive marker of postoperative mortality , with an area under the curve ( AUC ) of 0.84 ( 95 % confidence interval [ CI ] 0.63–1.00 , p = 0.020 ) ; a threshold of 41 was 75 % sensitive and 95 % specific ( positive predictive value 50 % , negative predictive value 98 % ) . Above this threshold , raised $ $ \dot{V } $ $ V˙e/$$ \dot{V } $ $ V˙co2 predicted poor long-term survival ( hazard ratio 2.05 , 95 % CI 1.09–3.86 , p = 0.026 ) . Conclusions CPET is a useful adjunctive test for predicting postoperative outcome in patients being assessed for pancreaticoduodenectomy . Raised CPET-derived $ $ \dot{V } $ $ V˙e/$$ \dot{V } $ $ V˙co2 predicts early postoperative death and poor long-term survival BACKGROUND The aim of this study was to examine the outcomes of exercise therapy in patients with hepatocellular carcinoma who underwent hepatectomy . METHODS Fifty-one patients with hepatocellular carcinoma were r and omized to diet therapy alone ( n = 25 ) or to exercise in addition to diet therapy ( n = 26 ) . Exercise at the anaerobic threshold of each patient was started 1 month preoperatively , resumed from 1 week postoperatively , and continued for 6 months . RESULTS Whole body mass and fat mass in the exercise group compared with the diet group were significantly decreased at 6 months postoperatively . Fasting serum insulin and the homeostasis model assessment score were also significantly decreased . At 6 months , anaerobic threshold and peak oxygen consumption were significantly increased , while serum insulin and insulin resistance were significantly improved in a high-frequency exercise subgroup compared with a low-frequency group . CONCLUSIONS Perioperative exercise therapy for patients with hepatocellular carcinoma with liver dysfunction may improve insulin resistance associated with hepatic impairment and suggests a benefit to the early resumption of daily exercise after hepatectomy Objective : To prospect ively evaluate the additional value of geriatric assessment ( GA ) for predicting surgical outcomes in a cohort of older patients undergoing a pancreaticoduodenectomy ( PD ) for pancreatic tumors . Background : Older patients are less often referred for possible PD . St and ard preoperative assessment s may underestimate the likelihood of significant adverse outcomes . The prospect i ve utility of vali date d GA has not been studied in this group . Methods : PD-eligible patients were enrolled in a prospect i ve outcome study . St and ard preoperative assessment s were recorded . Elements of vali date d GA were also measured , including components of Fried 's model of frailty , the Vulnerable Elders Survey ( VES-13 ) , and the Short Physical Performance Battery ( SPPB ) . All postoperative adverse events were recorded , systematic ally review ed , and grade d using the Clavien-Dindo system by a surgeon blinded to the GA results . Multivariate regression analyses were conducted . Results : Seventy-six older patients underwent a PD . Significant unrecognized vulnerability was identified at the baseline : Fried 's “ exhaustion ” ( 37.3 % ) , SPPB < 10 ( 28.5 % ) , and VES-13 > 3 ( 15.4 % ) . Within 30 days of PD , 46 % experienced a severe complication ( Clavien-Dindo grade ≥III ) . In regression analyses controlling for age , the body mass index , the American Society of Anesthesiologists score , and comorbidity burden , Fried 's “ exhaustion ” predicted major complications [ odds ratio ( OR ) = 4.06 ; P = 0.01 ] , longer hospital stays ( & bgr ; = 0.27 ; P = 0.02 ) , and surgical intensive care unit admissions ( OR = 4.30 ; P = 0.01 ) . Both SPPB ( OR = 0.61 ; P = 0.04 ) and older age predicted discharge to a rehabilitation facility ( OR = 1.1 ; P < 0.05 ) and age correlated with a lower likelihood of hospital readmission ( OR = 0.94 ; P = 0.02 ) . Conclusions : Controlling for st and ard preoperative assessment s , worse scores on GA prospect ively and independently predicted important adverse outcomes . Geriatric assessment may help identify older patients at high risk for complications from PD Objective : The Rehabilitation Strategies in Esophagogastric cancer ( RESTORE ) r and omized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life ( HRQOL ) of esophagogastric cancer survivors . Background : Patients following treatment for esophagogastric cancer are at risk of physical deconditioning , nutritional compromise , and sarcopenia . Accordingly , compelling rationale exists to target these impairments in recovery . Methods : Disease-free patients treated for esophagogastric cancer were r and omized to either usual care or the 12-week RESTORE program ( exercise training , dietary counseling , and multidisciplinary education ) . The primary outcome was cardiopulmonary exercise testing ( VO2peak ) . Secondary outcomes included body composition ( bioimpedance analysis ) , and HRQOL ( EORTC-QLQ-C30 ) . Outcomes were assessed at baseline ( T0 ) , postintervention ( T1 ) , and at 3-month follow-up ( T2 ) . Results : Twenty-two participants were r and omized to the control group [ mean ( st and ard deviation ) age 64.14 ( 10.46 ) yr , body mass index 25.67 ( 4.83 ) kg/m2 , time postsurgery 33.68 ( 19.56 ) mo ] , and 21 to the intervention group [ age 67.19(7.49 ) yr , body mass index 25.69(4.02 ) kg/m2 , time postsurgery 23.52(15.23 ) mo ] . Mean adherence to prescribed exercise sessions were 94(12)% ( supervised ) and 78(27)% ( unsupervised ) . Correcting for baseline VO2peak , the intervention arm had significantly higher VO2peak at both T1 , 22.20 ( 4.35 ) versus 21.41 ( 4.49 ) mL · min−1 · kg−1 , P < 0.001 , and T2 , 21.75 ( 4.27 ) versus 20.74 ( 4.65 ) mL · min−1 · kg−1 , P = 0.001 , compared with the control group . Correcting for baseline values , no changes in body composition or HRQOL were observed . Conclusions : The RESTORE program significantly improved cardiorespiratory fitness of disease-free patients after esophagogastric cancer surgery , without compromise to body composition . This r and omized controlled trial provides proof of principle for rehabilitation programs in esophagogastric cancer . Clinical Trial Registration Number : NCT03314311 Importance Preserving functional capacity is a key element in the care continuum for patients with esophagogastric cancer . Prehabilitation , a preoperative conditioning intervention aim ing to optimize physical status , has not been tested in upper gastrointestinal surgery to date . Objective To investigate whether prehabilitation is effective in improving functional status in patients undergoing esophagogastric cancer resection . Design , Setting , and Participants A r and omized clinical trial ( available-case analysis based on completed assessment s ) was conducted at McGill University Health Centre ( Montreal , Quebec , Canada ) comparing prehabilitation with a control group . Intervention consisted of preoperative exercise and nutrition optimization . Participants were adults awaiting elective esophagogastric resection for cancer . The study date s were February 13 , 2013 , to February 10 , 2017 . Main Outcomes and Measures The primary outcome was change in functional capacity , measured with absolute change in 6-minute walk distance ( 6MWD ) . Preoperative ( end of the prehabilitation period ) and postoperative ( from 4 to 8 weeks after surgery ) data were compared between groups . Results Sixty-eight patients were r and omized , and 51 were included in the primary analysis . The control group were a mean ( SD ) age , 68.0 ( 11.6 ) years and 20 ( 80 % ) men . Patients in the prehabilitation group were a mean ( SD ) age , 67.3 ( 7.4 ) years and 18 ( 69 % ) men . Compared with the control group , the prehabilitation group had improved functional capacity both before surgery ( mean [ SD ] 6MWD change , 36.9 [ 51.4 ] vs −22.8 [ 52.5 ] m ; P < .001 ) and after surgery ( mean [ SD ] 6MWD change , 15.4 [ 65.6 ] vs −81.8 [ 87.0 ] m ; P < .001 ) . Conclusions and Relevance Prehabilitation improves perioperative functional capacity in esophagogastric surgery . Keeping patients from physical and nutritional status decline could have a significant effect on the cancer care continuum . Trial Registration Clinical Trials.gov Identifier : Objectives Maintaining or improving muscle mass and muscle strength is an important treatment goal in pancreatic cancer ( PC ) patients because of high risk of cachexia . Therefore , we assessed feasibility and effectivity of a 6-month progressive resistance training ( RT ) in PC patients within a r and omized controlled trial . Methods Sixty-five PC patients were r and omly assigned to either supervised progressive RT ( RT1 ) , home-based RT ( RT2 ) , or usual care control group ( CON ) . Both exercise groups performed training 2 times per week for 6 months . Muscle strength for knee , elbow , and hip extensors and flexors and cardiorespiratory fitness and body weight were assessed before and after the intervention period . Results Of 65 patients , 43 patients were analyzed . Adherence rates were 64.1 % ( RT1 ) and 78.4 % ( RT2 ) of the prescribed training sessions . RT1 showed significant improvements in elbow flexor/extensor muscle strength and in maximal work load versus CON and RT2 ( P < 0.05 ) . Further , knee extensors were significantly improved for RT1 versus CON ( P < 0.05 ) . Body weight revealed no significant group differences over time . Conclusions Progressive RT was feasible in PC patients and improved muscle strength with significant results for some muscle groups . Supervised RT seemed to be more effective than home-based RT Background Oesophagectomy remains the only curative intervention for oesophageal cancer , with defined nutritional and health-related quality of life ( HR-QOL ) consequences . It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified . This study prospect ively examines change in physical functioning and habitual physical activity participation , from pre-surgery through 6-months post-oesophagectomy . Methods Patients scheduled for oesophagectomy with curative intent were recruited . Key domains of physical functioning including exercise tolerance ( six-minute walk test ( 6MWT ) ) and muscle strength ( h and -grip strength ) , and habitual physical activity participation , including sedentary behaviour ( accelerometry ) were measured pre-surgery ( T0 ) and repeated at 1-month ( T1 ) and 6-months ( T2 ) post-surgery . HR-QOL was measured using the EORTC-QOL C30 . Results Thirty-six participants were studied ( mean age 62.4 ( 8.8 ) years , n = 26 male , n = 26 transthoracic oesophagectomy ) . Mean 6MWT distance decreased significantly from T0 to T1 ( p = 0.006 ) and returned to T0 levels between T1 and T2 ( p < 0.001 ) . Percentage time spent sedentary increased throughout recovery ( p < 0.001 ) and remained significantly higher at T2 in comparison to T0 ( p = 0.003 ) . In contrast , percentage time spent engaged in either light or moderate-to-vigorous intensity activity , all reduced significantly ( p < 0.001 for both ) and remained significantly lower at T2 in comparison to T0 ( p = 0.009 and p = 0.01 respectively ) . Patients reported deficits in multiple domains of HR-QOL during recovery including global health status ( p = 0.04 ) , physical functioning ( p < 0.001 ) and role functioning ( p < 0.001 ) . Role functioning remained a clinical ly important 33-points lower than pre-operative values at T2 . Conclusion Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy . Physical activity is a measurable and modifiable target for physical rehabilitation , which is closely aligned with patient-reported deficits in role functioning . Rehabilitation aim ed at optimising physical health in oesophageal cancer survivorship is warranted OBJECTIVE The objective of this study was to investigate the effect of prehabilitation on survival after colorectal cancer surgery . SUMMARY OF BACKGROUND DATA Preoperative multimodal exercise and nutritional programs ( prehabilitation ) improve functional capacity and recovery following colorectal surgery . Exercise may also affect cancer outcomes by mediating the systemic inflammatory response . The effect of prehabilitation on cancer outcomes is unknown . METHODS Pooled data from 3 prehabilitation trials ( 2 r and omized controlled trials , 1 cohort ) in patients undergoing elective , biopsy-proven , primary non-metastatic colorectal cancer surgery from 2009 to 2014 within an enhanced recovery program were analyzed . Patients were grouped into + prehab or-prehab . The primary outcomes were 5-year disease-free ( DFS ) and overall survival ( OS ) . DFS and OS were analyzed using Kaplan-Meier curves and multiple Cox regression . RESULTS A total of 202 patients were included ( + prehab 104 , -prehab 98 ) . Median prehabilitation duration was 29 days ( interquartile range 20 - 40 ) . Patient and tumor characteristics were well-balanced ( 33 % stage III ) . Postoperative complications and time to adjuvant chemotherapy were similar . Mean duration of follow-up was 60.3 months ( st and ard deviation 26.2 ) . DFS was similar for the combined group of stage I-III patients ( P = 0.244 ) . For stage III patients , prehabilitation was associated with improved DFS ( 73.4 % vs 50.9 % , P = 0.044 ) . There were no differences in OS ( P = 0.226 ) . Prehabilitation independently predicted improved DFS ( hazard ratio 0.45 ; 95 % confidence interval , 0.21 - 0.93 ) , adjusting for stage and other confounders . Prehabilitation did not independently predict OS . CONCLUSION In this report , prehabilitation is associated with improved 5-year DFS in stage III colorectal cancer . This finding should be confirmed in future trials BACKGROUND Despite the rising incidence of hepatocellular carcinoma ( HCC ) , challenges and controversy persist in optimizing treatment . As recent r and omized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC , the relative morbidity of the 2 approaches is a central issue in treatment decisions . Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units , it is not clear that they can be replicated in broader practice . Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions . STUDY DESIGN Mortality and morbidity data were extracted from the 2005 - 2010 NSQIP Participant Use Data Files based on Current Procedural Terminology ( hepatectomy and ablation ) and ICD-9 ( HCC ) . Perioperative outcomes were review ed , and factors associated with morbidity and mortality were identified with multivariable logistic regression . RESULTS Eight hundred and thirty-seven ( 52 % ) underwent minor hepatectomy , 444 ( 28 % ) underwent major hepatectomy , and 323 ( 20 % ) underwent surgical ablation . Mortality rates were 3.4 % for minor hepatectomy , 3.7 % for ablation , and 8.3 % for major hepatectomy ( p < 0.01 ) . Major complication rates were 21.3 % for minor hepatectomy , 9.3 % for ablation , and 35.1 % for major hepatectomy ( p < 0.01 ) . When controlling for confounders , ablation was associated with decreased mortality ( adjusted odds ratio = 0.20 ; 95 % CI , 0.04 - 0.97 ; p = 0.046 ) and major complications ( adjusted odds ratio = 0.34 ; 95 % CI , 0.22 - 0.52 ; p < 0.001 ) . CONCLUSIONS Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment . These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible |
12,564 | 32,321,448 | There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes .
Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better underst and ing the discrete pathophysiology of delirium in the context of co-existing illness | Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer .
Underst and ing of delirium pathophysiology is largely hypothetical , with some evidence for involvement of inflammatory systems , neurotransmitter alterations and glucose metabolism .
To date , there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease , for example , cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue .
This systematic review explores biomarker overlap in delirium , specific advanced cancer-related syndromes and prediction of cancer prognosis . | Background Suitable biomarkers associated with the development of delirium are still not known . Urinary proteomics has successfully been applied to identify novel biomarkers associated with various disease states , but its value has not been investigated in delirium patients . Results In a prospect i ve explorative study hyperactive delirium patients after cardiac surgery were included for urinary proteomic analyses . Delirium patients were matched with non-delirium patients after cardiac surgery on age , gender , severity of illness score , LOS-ICU , Euro-score , C-reactive protein , renal function and aorta clamping time . Urine was collected within 24 hours after the onset of delirium . Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry ( MALDI-TOF MS ) was applied to detect differences in the urinary proteome associated with delirium in these ICU patients . We included 10 hyperactive delirium and 10 meticulously matched non-delirium post-cardiac surgery patients . No relevant differences in the urinary excretion of proteins could be observed . Conclusions We conclude that MALDI-TOF MS of urine does not reveal a clear hyperactive delirium proteome fingerprint in ICU patients .Trial Registration Clinical Trial Register number : Animal research suggests that leptin may have an important role in the regulation of energy balance . The role of leptin in the progressive involuntary weight loss associated with cancer in humans is of considerable interest . However , such studies are limited . In this study , we compared circulating leptin concentrations in gastrointestinal cancer patients and weight loss ( n = 27 ) with those of healthy subjects ( n = 27 ) . The effect of the presence of an inflammatory response on leptin concentrations was also examined . There were significantly lower leptin concentrations in male ( median , 2.4 microg/liter ; range , < 0.5 - 6.0 microg/liter ) and female ( median , 3.4 microg/liter ; range , < 0.5 - 9.8 microg/liter ) cancer patients than there were in male ( median , 6.5 microg/liter ; range , 3.1 - 10.9 microg/liter ) and female ( median , 18.7 microg/liter ; range , 8.0 - 31.5 mcirog/liter ) healthy subjects ( P < 0.001 ) . However , the leptin concentrations in both patients and normal subjects were related to the predicted percentage of body fat ( r = 0.731 ; P < 0.001 ) . Circulating leptin concentrations in the cancer patients were not altered by the presence of an inflammatory response . These results suggest that cancer anorexia/cachexia is not due to a simple dysregulation of leptin production BACKGROUND Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases . Their effects are mediated through complex regulatory networks . Human cytokine profiles could define patient subgroups and represent new potential biomarkers . The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS We conducted a prospect i ve study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects . Cytokine levels and data -mining profiles were associated with clinical , quality of life and pathological outcomes . RESULTS NSCLC patients had higher levels of interleukin (IL)-6 , IL-8 , IL-12p70 , IL-17a and interferon (IFN)-γ , and lower levels of IL-33 and IL-29 compared with controls . The pro-inflammatory cytokines IL-1b , IL-6 and IL-8 were associated with lower hemoglobin levels , worse functional performance status ( Eastern Cooperative Oncology Group , ECOG ) , fatigue and hyporexia . The anti-inflammatory cytokines IL-4 , IL-10 and IL-33 were associated with anorexia and lower body mass index . We identified three clusters of patients according to data -mining analysis with different overall survival ( OS ; 25.4 , 16.8 and 5.09 months , respectively , P = 0.0012 ) . Multivariate analysis showed that ECOG performance status and data -mining clusters were significantly associated with OS ( RR 3.59 , [ 95 % CI 1.9 - 6.7 ] , P < 0.001 and 2.2 , [ 1.2 - 3.8 ] , P = 0.005 ) . CONCLUSION Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC . These cytokines may represent potential biomarkers , particularly in the immunotherapy era in cancer research Introduction The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting . We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium . Methods We investigated 23 adult patients with sepsis , severe sepsis , or septic shock with an extracranial focus of infection and no history of intracranial pathology . Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit . Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit . Mean arterial pressure ( MAP ) , blood flow velocity ( FV ) in the middle cerebral artery using transcranial Doppler , and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour . An index of cerebrovascular autoregulation was calculated from MAP and FV data . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , S-100β , and cortisol were measured during each data acquisition . Results Data from 16 patients , of whom 12 had sepsis-associated delirium , were analysed . There were no significant correlations or associations between MAP , cerebral blood FV , or tissue oxygenation and sepsis-associated delirium . However , we found a significant association between sepsis-associated delirium and disturbed autoregulation ( P = 0.015 ) . IL-6 did not differ between patients with and without sepsis-associated delirium , but we found a significant association between elevated CRP ( P = 0.008 ) , S-100β ( P = 0.029 ) , and cortisol ( P = 0.011 ) and sepsis-associated delirium . Elevated CRP was significantly correlated with disturbed autoregulation ( Spearman rho = 0.62 , P = 0.010 ) . Conclusion In this small group of patients , cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium . However , the state of autoregulation differed between the two groups . This may be due to inflammation impeding cerebrovascular endothelial function . Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted . Trial registration Clinical Trials.gov NCT00410111 Purpose Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival . The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins , and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer . The purpose of our prospect i ve study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer ( NSCLC ) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction . A secondary aim was to compare several biochemical markers ( CRP , IL-6 , protein , and albumin ) with time to tumor progression in order to assess prognostic value or to guide a treatment . Methods Between December 2013 and April 2015 , the prospect i ve cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV , who were referred consecutively to Department for Respiratory Diseases “ Jordanovac , ” was evaluated . Anthropometric measurements and biochemical data ( CRP , albumin , protein , IL-6 , haemoglobin ) together with body composition measurements ( total muscle cross-sectional area , lumbar skeletal muscle index ) were obtained for each patient before starting with platinum-doublet therapy . Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography , and sarcopenia was defined using a previously published cutoff point . Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospect ively . Results One hundred patients with advanced lung cancer were recruited : 67 were male and median age was 64 years . The median time to disease progression was 187 days . The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 % , respectively . CRP , IL-6 , and albumin concentration in cachectic compared to non-cachectic patients demonstrated statistically significant difference ( p = 0.020 , p = 0.040 , p = 0.003 ) . Cachexia and sarcopenia were not found to be predictors of chemotoxicity nor was time to tumor progression . On the contrary , albumin concentration with established cutoff point of 37.5 g/L was clearly proved as the predictive factor of both chemotoxicity ( OR ( 95 % CI ) = 0.85 ; p < 0.001 ) and survival ( HR ( 95 % CI ) = 0.55 ) . Conclusions Albumin level has been shown to be more important predictive marker of chemotherapy toxicity and survival than cachexia and sarcopenia are . This approach in clinical setting s can be used to guide the choice of oncologic treatment Background The association between C‐reactive protein ( CRP ) level , symptoms , and activities of daily living ( ADL ) in advanced cancer patients is unclear . Methods Secondary data analysis of a multicenter prospect i ve cohort study consisted of 2426 advanced cancer patients referred to palliative care setting s was conducted to examine the cross‐sectional relationships between CRP level , symptoms , and ADL disabilities . Laboratory data , symptoms , ADL , and manual muscle testing ( MMT ) results were obtained at baseline . Participants were divided into four groups : low ( CRP < 1 mg/dl ) , moderate ( 1 = < CRP < 5 mg/dl ) , high ( 5 = < CRP < 10 mg/dl ) , and very high CRP ( 10 mg/dl = < CRP ) . The proportions of eight symptoms , five ADL disabilities , and three categories of MMT according to the CRP groups were tested by chi‐square tests . Multiple‐adjusted odd ratios ( ORs ) were calculated by using ordinal logistic regression after adjustment for age , gender , site of primary cancer , metastatic disease , performance status , chemotherapy , and setting of care . Results A total of 1702 patients were analysed . Positive rates of symptoms and ADL disabilities increased with increasing CRP level . In the very high‐CRP group , rates of positivity for anorexia , fatigue , and weight loss were 89.8 % , 81.0 % , and 79.2 % , respectively , and over 70 % of patients received assistance for bathing , dressing , going to the toilet , and transfer . The grade of MMT also deteriorated with increasing CRP level . Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate‐CRP , high‐CRP , and very high‐CRP groups [ 1.6 ( 95 % confidence interval 1.2–2.0 ) , P < 0.001 ; 2.5 ( 1.9–3.2 ) , P < 0.001 ; 3.5 ( 2.7–4.6 ) , P < 0.001 , respectively ] . Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high‐CRP groups [ 2.1 ( 1.5–2.9 ) , P < 0.001 ] . Conclusions Associations between CRP level , symptoms , and ADL were observed in advanced cancer patients receiving palliative care Purpose : Cancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma ( HNSCC ) . The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC . The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors . Experimental Design : For the primary objective , cross-sectional data were obtained from prospect ively recruited patients identified as cachexia cases and matching cachexia-free controls . For the secondary objective , a retrospective cohort design with matched controls was used . Results : Clinical characteristics associated with cancer cachexia in HNSCC were T4 status ( P = 0.01 ) , increased C-reactive protein ( P = 0.01 ) , and decreased hemoglobin ( P < 0.01 ) . Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 ( P = 0.04 ) . A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients ( P = 0.02 ) . Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients ( P < 0.01 ) . All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor . There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients ( each P > 0.05 ) . No tumors expressed the cachexia factor proteolysis-inducing factor . Conclusion : We have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC . The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state . We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia Introduction Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality . Septic patients with delirium may differ from a general critically ill population . The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and non-septic critically ill patients . Methods We performed a prospect i ve cohort study in a 20-bed mixed intensive care unit ( ICU ) including 78 ( delirium = 31 ; non-delirium = 47 ) consecutive patients admitted for more than 24 hours . At enrollment , patients were allocated to septic or non-septic groups according to internationally agreed criteria . Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit ( CAM-ICU ) during the first 72 hours of ICU admission . Blood sample s were collected within 12 hours of enrollment for determination of tumor necrosis factor (TNF)-α , soluble TNF Receptor (STNFR)-1 and -2 , interleukin (IL)-1β , IL-6 , IL-10 and adiponectin . Results Out of all analyzed biomarkers , only STNFR1 ( P = 0.003 ) , STNFR2 ( P = 0.005 ) , adiponectin ( P = 0.005 ) and IL-1β ( P < 0.001 ) levels were higher in delirium patients . Adjusting for sepsis and sedation , these biomarkers were also independently associated with delirium occurrence . However , none of them were significant influenced by sepsis . Conclusions STNFR1 , STNFR2 , adiponectin and IL-1β were associated with delirium . Sepsis did not modify the relationship between the biomarkers and delirium occurrence In this prospect i ve study the frequency of delirium after cardiac surgery with cardiopulmonary bypass ( CPB ) was determined . Furthermore , we investigated the impact of intra- and postoperative levels of albumin as a biomarker of delirium . Thirty-four patients who underwent elective CPB at the Department of Cardiac Surgery , Ludwig-Maximilians-University of Munich , Germany , were enroled in this prospect i ve study . During the intensive care unit ( ICU ) stay and shortly after discharge from the ICU , delirious state was evaluated daily using the Delirium-Rating-Scale . Albumin was assayed pre-anaesthesia , immediately after induction of anaesthesia , at the beginning of the heart-lung-apparatus period , immediately before the opening and 5min after the opening of the aortic clamp , 24h and 48h postoperatively and on the day before discharge . After CPB , a clinical significant delirious state was observed in 11 patients ( 32.4 % ) . The albumin level decreased during the surgical intervention and increased postoperatively with a maximum level at the time of discharge . CPB patients with delirious state showed a significantly lower albumin level 24h and 48h postoperatively than those without delirium . A low level of postoperative albumin seems to be a useful biomarker to identify patients with high risk of delirious state after CPB Purpose To assess the associations between a priori-selected markers of inflammation and coagulation and delirium during critical illness . Methods In this prospect i ve cohort study , we collected blood from mechanically ventilated medical intensive care unit ( ICU ) patients and measured nine plasma markers of inflammation and coagulation . We assessed patients daily for delirium using the Confusion Assessment Method for the ICU and used multivariable regression to analyze the associations between plasma markers and subsequent delirium , after adjusting for age , severity of illness , and sepsis . Results Among the 138 patients studied , with median age of 66 years and median Acute Physiology and Chronic Health Evaluation ( APACHE ) II of 27 , 107 ( 78 % ) were delirious at some point during the study . Two markers of inflammation and one of coagulation were significantly associated with delirium . After adjusting for covariates , lower plasma concentrations of matrix metalloproteinase-9 ( MMP-9 ) and protein C were associated with increased probability of delirium ( p = 0.04 and 0.01 , respectively ) , and higher concentrations of soluble tumor necrosis factor receptor-1 ( sTNFR1 ) were associated with increased probability of delirium ( p < 0.01 ) . Concentrations of C-reactive protein ( p = 0.82 ) , myeloperoxidase ( p = 0.11 ) , neutrophil gelatinase-associated lipocalin ( p = 0.70 ) , D-dimer ( p = 0.83 ) , plasminogen activator inhibitor type 1 ( p = 0.98 ) , and Von Willebr and factor antigen ( p = 0.65 ) were not associated with delirium . Conclusions In this study , MMP-9 , protein C , and sTNFR1 were independently associated with subsequent ICU delirium . These results suggest that specific aspects of inflammation and coagulation may play a role in the evolution of delirium during critical illness and that these markers should be examined in larger studies of ICU patients Chronic systemic inflammatory response is proposed as an underlying mechanism for development of cancer cachexia . We conducted a prospect i ve study to examine changes in inflammatory biomarkers during the disease course and the relationship between inflammatory biomarkers and cachexia in patients with inoperable pancreatic cancer . Twenty patients , median ( range ) age 67.5 ( 35–79 ) years , 5 females , were followed for median 5.5 ( 1–12 ) months . Cachexia was diagnosed according to the 2011 consensus-based classification system ( weight loss > 5 % past six months , BMI < 20 kg/m2 and weight loss > 2 % , or sarcopenia ) and the modified Glasgow Prognostic score ( mGPS ) that combines CRP and albumin levels . Inflammatory biomarkers were measured by enzyme immunoassays . The patients had increased levels of most inflammatory biomarkers , albeit not all statistically significant , both at study entry and close to death , indicating ongoing inflammation . According to the consensus-based classification system , eleven ( 55 % ) patients were classified as cachectic upon inclusion . They did not differ from non-cachectic patients with regard to inflammatory biomarkers or energy intake . According to the mGPS , seven ( 35 % ) were defined as cachectic and had a higher IL-6 ( p < 0.001 ) than the non-cachectic patients . They also had a slightly , but insignificantly longer survival than non-cachectic patients ( p = 0.08 ) . The mGPS should be considered as an additional framework for identification of cancer cachexia Purpose The Glasgow prognostic score ( GPS ) , which uses C-reactive protein and albumin levels , is a good predictor of prognosis in cancer patients undergoing anti-tumor therapy . The objective of this study was to investigate the correlation between GPS and survival among cancer patients in palliative setting s , as findings in such population s have not been well described . Methods This was a sub analysis of a multicenter , prospect i ve , cohort study in patients who were adults , diagnosed with advanced cancer , and first referred to palliative care service in Japan . Patients who were not receiving anti-tumor therapy and who had undergone laboratory examinations were eligible . Clinical features were analyzed to investigate prognostic factors . Results A total of 1160 patients were enrolled ( 41.6 % female ; median age , 72 years ) . The independent predictors were Eastern Cooperative Oncology Group performance status ( ECOG PS ) score of 4 ( hazard ratio ( HR ) , 1.54 ) , liver metastasis ( HR , 1.21 ) , dyspnea ( HR , 1.35 ) , edema ( HR , 1.25 ) , prognostic performance index ( HR , 1.56 ) , neutrophil-lymphocyte ratio ( HR , 1.43 ) , and GPS of 2 ( HR , 1.36 ) . The sensitivity and specificity for 3-week prognosis of a GPS of 2 were 0.879 and 0.410 . Median survival time with GPS of 0 , 1 , and 2 was 58 days ( 95 % confidence interval , 48–81 ) , 43 days ( 37–50 ) , and 21 days ( 19–24 ) , respectively ( log-rank test , p < 0.001 ) . Conclusion The GPS was a good prognostic indicator for cancer patients in palliative setting OBJECTIVES Delirium is a common complication in elderly patients after cardiac surgery and is associated with adverse outcomes including prolonged hospital stay and increased mortality . Therefore , prevention or early detection of delirium is indicated . Our objective was to identify preoperative and operative characteristics that could predict delirium after cardiac surgery in elderly patients . METHODS We conducted a prospect i ve cohort study in which we analysed 201 patients of 70 years and older who underwent cardiac surgery , for developing a delirium . Patients were assessed daily using the Confusion Assessment Method -Intensive Care Unit . RESULTS Sixty-three patients ( 31 % ) developed a delirium after cardiac surgery . The Mini-Mental State Examination ( MMSE ) score prior to surgery was lower in the delirious patients when compared with the non-delirious patients ( 27 vs. 28 , P = 0.026 ) , creatinine level was higher ( 98 vs. 88 μmol/l , P = 0.003 ) and extracorporeal circulation ( ECC ) time was longer ( 145 vs. 113 min , P < 0.001 ) . Mortality during the first 30 days after surgery in patients with delirium was significantly higher than that in the non-delirious patients ( 14 vs. 0 % , P < 0.001 ) . CONCLUSIONS Low MMSE score and high creatinine level prior to surgery as well as increased ECC time are important independent predictors of delirium . In addition , delirium is an important predictor of 30-day mortality . Patients with a substantial risk for delirium should be c and i date s for interventions to reduce postoperative delirium and to potentially improve overall surgical outcomes Objective To explore the risk factors associated with postoperative delirium ( PD ) in elderly patients following total hip arthroplasty ( THA ) for hip fracture . Methods This prospect i ve study enrolled elderly patients ( ≥ 65 years ) with hip fractures who underwent THA under general anaesthesia , and who had a complete set of postoperative observations . Detailed medical history and perioperative characteristics were recorded . During the postoperative period , patients were assessed twice daily for PD using the Confusion Assessment Method . Results A total of 572 patients were eligible for inclusion in the study . Of these , 120 patients ( 21.0 % ) were diagnosed with PD and 452 patients ( 79.0 % ) did not experience PD . Multivariate stepwise logistic regression analyses showed that older age , a history of stroke , lower albumin , higher blood glucose , higher total bilirubin , higher C-reactive protein , longer surgery duration and higher volume of red blood cell transfusions were independent risk factors for PD . Conclusions Correcting the modifiable risk factors might help prevent PD . Strategies might include nutritional support , tight blood glucose control , improvement of liver function , preoperative infection control and minimizing surgical injury or blood loss Background Delirium is common , associated with poor outcome , but its pathophysiology remains obscure . The aim of the present study was to study a possible role of monocyte chemoattractant protein-1 ( MCP-1 ) in the development of delirium . Findings A prospect i ve cohort of 19 hip fracture patients ( median age 83 years ) were screened for delirium daily by vali date d methods . MCP-1 was measured on arrival and postoperatively . The number of patients with a raise in MCP-1 was statistically significantly higher in the group with delirium in the postoperative phase compared to the no-delirium group ( 5/6 vs. 1/7 , p = .03 ) . Conclusions MCP-1 might play a role in the development of delirium The aim of this study was to examine whether serum anticholinergic activity ( SAA ) is a reliable indicator of delirium in the ICU , and whether there is a significant correlation between SAA and quantitative electroencephalographic ( EEG ) data in delirious patients . In a prospect i ve cohort study , we assessed ICU patients diagnosed with delirium ( n = 37 ) . EEG measurements and blood analysis including SAA were performed 48 h following ICU admission . The presence of delirium was evaluated using the Confusion Assessment Method for critically ill patients in ICU ( CAM‐ICU ) . The SAA level was measured using a competitive radioreceptor binding assay for muscarinergic receptors and quantitative EEG was measured using the CATEEM ® system . We found that , under comparable conditions , patients in the delirium group showed a higher relative EEG theta power and a reduced alpha power ( n = 17 ) than did the non‐delirious patients ( n = 20 ) . No difference in measured SAA levels were seen ; therefore , there was no correlation between SAA and EEG measurements in delirious patients . We conclude that , in contrast to the EEG , the SAA level can not be proposed as a tool for diagnosing delirium in ICU patients PURPOSE Few studies looking for an effective biomarker to predict delirium have been performed . This study was design ed to investigate whether a change in inflammatory status , indicated by blood natural killer ( NK ) cell activity , predicts delirium . METHODS This prospect i ve study , performed in 4 university and 1 general hospital from September , 2011 to October , 2012 , included 29 patients . Eligible patients were 65 - 89years old , newly and emergently admitted . Patients were assessed daily , up to 7days , for occurrence of DSM-IV-defined delirium . The main outcome measure was change in blood NK cell activity between the first and second mornings after admission . RESULTS The mean change in blood NK cell activity on the second morning , compared to the first morning , in patients developing delirium ( n=9 ) was significantly greater than that in patients without delirium ( n=20 ) ( 6.0 % [ SD 8.4 ] vs. -1.4 % [ 9.0 ] , respectively , t=2.10 , P=0.045 ) . Significant difference between the groups was still found after adjusting for age , the history of previous delirium , and the Clinical Dementia Rating score ( F=6.63 , P=0.017 ) . Of note is that 8 of 9 ( 89 % ) patients developing delirium had increased blood NK cell activity , as did only 8 of 20 ( 40 % ) patients without delirium , giving measurement of this parameter , for distinguishing the two groups , a sensitivity of 89 % , specificity 60 % , positive predictive value 50 % , negative predictive value 92 % , positive likelihood ratio 2.22 , and negative likelihood ratio 0.19 . When combining this predictor with another predictor , a Delirium Rating Scale-Revised-98 severity score of 5 or more at baseline , positive and negative likelihood ratios were 7.80 and 0.24 , respectively . CONCLUSION Increase in blood NK cell activity may be associated with developing delirium . Further studies including larger numbers of patients are needed to justify the preventive use of drugs for patients meeting criteria for both predictors BACKGROUND Pain is one of the most common symptoms in patients suffering from advanced cancer and receiving palliative care and is often responsible for a poor quality of life . To date , there exists no published correlation between biological , measurable biomarkers and pain intensity . OBJECTIVES The primary objective was to search and identify pain-associated cytokines ( biomarkers ) correlating with changes in numeric rating scale ( NRS ) pain scores in patients with cancer before and after pain treatment . The secondary objectives were to assess cytokine serum level differences between patients and healthy controls and to evaluate possible relationships between pain entities , pain intensity ( in NRS ) , gender , location of primary tumor , and the patients ' cytokine baseline concentrations . STUDY DESIGN Controlled , prospect i ve study . SETTING University medical center . METHODS Eligible patients with exacerbated cancer-related pain ( NRS = 5 ) and healthy controls with no pain were included . Serum level changes of 19 cytokines were analyzed before and during opioid treatment . RESULTS Of 19 analyzed biomarkers , 5 ( IL-7 , IL-18 , MCP-1 , MIP-1α , MIP-1β and OPG ) turned out to correlate significantly with pain relief . In healthy controls , all analyzed cytokines showed no significant differences . In the secondary analysis , only one significant correlation was detected between OPG and pain entities . Furthermore , IL-4 , IL-7 , IFN-γ and OPG appeared to account for the ability to predict a patient 's gender . LIMITATIONS Our findings should be considered as preliminary and need to be confirmed in further studies . CONCLUSION Our results provide preliminary evidence of a significant correlation of pain relief in patients with cancer and at least 5 cytokines . These biomarkers may serve as the basis for development of diagnostic tools for pain assessment and could serve as potential new targets for pain control Aim To investigate the level of interleukin-6 in advanced non-small cell lung cancer and to analyze the relationship with malnutrition and survival . Methods and study design Seventy-one newly diagnosed advanced non-small cell lung cancer patients were enrolled in this prospect i ve study . Malnutrition was defined by using subjective global assessment . Performance status was assessed by the Karnofsky scale . Serum levels of albumin , transferrin , C-reactive protein , lymphocytes/mm3 , lactate dehydrogenase and growth hormone were determined before treatment . The patients were followed , and the factors affecting survival were analyzed . Results The mean follow-up after diagnosis was 180 days . IL-6 levels increased in 48 ( 68 % ) of 71 patients . According to the subjective global assessment , 28 ( 39 % ) patients were well nourished and 43 ( 61 % ) were malnourished . Of the 43 malnourished patients , 29 ( 41 % ) were moderately malnourished or suspected of being malnourished and 14 ( 20 % ) were severely malnourished . The IL-6 level was related to impaired performance status ( P = 0.0001 ) , severe malnutrition ( P = 0.004 ) , increased C-reactive protein ( P = 0.013 ) , higher growth hormone ( P = 0.025 ) and transferrin ( P = 0.03 ) levels . On univariate analysis , impaired performance status , moderate and severe malnutrition , decreased serum albumin and transferrin , a raised IL-6 and lactate dehydrogenase levels were the significant prognostic factors for survival . Multivariate analysis indicated that a raised IL-6 , severe malnutrition and a low serum level of albumin were independent prognostic factors for survival in patients with advanced non-small cell lung cancer . Conclusions IL-6 secretion may play a role in the pathophysiology of malnutrition in advanced lung cancer . Results show a relation between elevated IL-6 serum levels and malnutrition , poor performance status , acute phase response and shorter survival in patients affected by advanced non-small cell lung cancer Background : In Alzheimer disease ( AD ) , systemic inflammation is known to give rise to a delirium . However , systemic inflammation also gives rise to other central ly mediated symptoms in the absence of a delirium , a concept known as sickness behavior . Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor – α ( TNFα ) and interleukin-6 ( IL-6 ) that mediate immune to brain communication and the development of sickness behavior . Objective : To determine if raised serum TNFα or IL-6 are associated with the presence of sickness behavior symptoms , independent of the development of delirium , in a prospect i ve cohort study of subjects with AD . Methods : A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers . Cognitive assessment s , including assessment s to detect the development of a delirium , and blood sample s were repeated at 2 , 4 , and 6 months . The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2 , 4 , and 6 months . Results : Raised serum TNFα and IL-6 , but not CRP , were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior . These relationships are independent of the development of delirium . Conclusions : Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior , which are common neuropsychiatric features found in AD . This association was independent of the presence of delirium Background Delirium is a profound neuropsychiatric disturbance precipitated by acute illness . Although dementia is the major risk factor this has typically been considered a binary quantity ( i.e. , cognitively impaired versus cognitively normal ) with respect to delirium risk . We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and /or cognitive impairment progressively alters delirium risk . Methods Humans in a population -based longitudinal study , Vantaa 85 + , were followed for incident delirium . Odds for reporting delirium at follow-up ( outcome ) were modeled using r and om-effects logistic regression , where prior cognitive impairment measured by Mini-Mental State Exam ( MMSE ) ( exposure ) was considered . To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change , mice at three stages of neurodegenerative disease progression ( ME7 model of neurodegeneration : controls , 12 weeks , and 16 weeks ) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide ( LPS ; 100 μg/kg ) . Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry . Results In the Vantaa cohort , 465 persons ( 88.4 ± 2.8 years ) completed MMSE at baseline . For every MMSE point lost , risk of incident delirium increased by 5 % ( p = 0.02 ) . LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls , respectively . This was associated with progressive thalamic synaptic loss and axonal pathology . Conclusion A human population -based cohort with grade d severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology Aim Pathophysiological disorders after surgery might be related to postoperative delirium ( POD ) . This study was design ed to eluci date the pathogenesis of POD in elderly oral cancer patients by determining the perioperative kinetics of inflammatory cytokines , cortisol , and amyloid β1 - 40 ( Aβ1 - 40 ) . Methods A total of 257 elderly oral cancer patients who underwent tumor resection surgery were selected . Venous blood was collected prior to surgery ( T0 ) , at the end of surgery ( T1 ) , and at 12 hours after surgery ( T2 ) . During the first three postoperative days , patients were examined using the confusion assessment method twice a day ( 8 am and 8 pm ) . Mini-Mental State Examination scores were recorded at T0 and on postoperative days 1 , 3 , and 7 . Ultimately , 56 patients suffering from POD made up the POD group , and 56 patients r and omly selected from a cohort of patients without POD were allocated to the no POD ( NPOD ) group . Subsequently , interleukin-6 , C-reactive protein , procalcitonin , cortisol , and Aβ1 - 40 in plasma from the two groups were measured . Results The two groups displayed comparable basic characteristics . There were no differences in all tested biomarkers between the two groups at T0 . However , after surgery , the biomarker levels displayed distinct patterns between the two groups . The peak levels of all biomarkers were higher in the POD group than in the NPOD group . Conversely , the Mini-Mental State Examination scores after surgery were lower in the POD group than in the no POD group . Conclusion The boost of inflammatory cytokines , cortisol , and Aβ1 - 40 after surgery might be involved in POD onset among elderly oral cancer patients . POD was accompanied by progressive cognitive deficiency CONTEXT Patients with advanced cancer often experience symptoms such as pain , anorexia , and fatigue . Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient 's symptom burden . OBJECTIVES To examine the association between serum cortisol and testosterone levels , opioid therapy , and symptom distress in patients with cancer . METHODS A retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia . We collected information regarding cortisol levels ( am or r and om ) , testosterone levels ( men only ) , morphine equivalent daily dose ( MEDD ) , and symptom severity measured by the Edmonton Symptom Assessment Scale . Nonparametric correlation analysis was performed . RESULTS The median age was 63 years ( range 24 - 79 ) , and 62 % were men ( n=48 ) . Most patients had gastrointestinal ( n=33 , 43 % ) or thoracic ( n=21 , 27 % ) malignancies and were Caucasian ( n=46 , 60 % ) . The median r and om cortisol level was 19.1 μg/dL ( Q1-Q3 , 13.4 - 23.8 [ normal , 4.3 - 22.4 ] ) , which correlated with MEDD ( Spearman coefficient , 0.25 , P=0.032 ) and symptoms including pain ( 0.50 , P<0.001 ) , fatigue ( 0.29 , P=0.012 ) , nausea ( 0.34 , P=0.003 ) , depression ( 0.24 , P=0.032 ) , and anxiety ( 0.25 , P=0.031 ) . Pain and nausea remained significant after Bonferroni correction . Median morning cortisol level ( n=28 ) was 20.6 μg/dL ( Q1-Q3 , 16.6 - 25.4 ) and significantly correlated with pain ( 0.55 , P=0.003 ) after Bonferroni correction . Patients with a MEDD < 30 mg/day had a mean r and om cortisol level of 16.6 μg/dL , whereas patients with a MEDD ≥ 30 mg/day had a mean r and om cortisol level of 20.6 μg/dL ( P=0.01 ) . In 44 male patients with cancer , MEDD was inversely correlated with the total testosterone level ( -0.52 , P=0.001 ) . CONCLUSION In patients with advanced cancer , elevated r and om cortisol levels were associated with pain and opioid use , although abnormally low levels of cortisol were found to be infrequent . Patients on higher opioid therapy ( MEDD > 30 ) had increased cortisol levels , and male patients had lower testosterone levels . Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis . Future studies are needed BACKGROUND Delirium occurs frequently in the intensive care unit ( ICU ) , but its pathophysiology is still unclear . Low levels of insulin-like growth factor 1 ( IGF-1 ) , a hormone with neuroprotective properties , have been associated with delirium in some non-ICU studies , but this relationship has not been examined in the ICU . We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness . METHODS Mechanically ventilated medical ICU patients were prospect ively enrolled , and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay . Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale , respectively . The association between IGF-1 and delirium was evaluated with logistic regression . In addition , the association between IGF-1 and duration of normal mental state , measured as days alive without delirium or coma , was assessed using multiple linear regression . RESULTS Among 110 patients , the median age was 65 years ( IQR , 52 - 75 ) and APACHE II was 27 ( IQR , 22 -32 ) . IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement ( p = 0.97 ) , at which time 65 % of the assessable patients were delirious . No significant association was found between IGF-1 levels and duration of normal mental state ( p = 0.23 ) . CONCLUSIONS This pilot study , the first to investigate IGF-1 and delirium in critically ill patients , found no association between IGF-1 and delirium . Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness Goals of workC-reactive protein ( CRP ) has been investigated as a predictor of life expectancy in terminal cancer in one previous study . However , the other variables such as patient ’s symptom or physical examination findings were not considered . The aim of this study is to prove serum CRP level as a predictor of survival time , considering patient ’s symptoms , physical examination findings , and various serological variables in terminally ill cancer patients with a prospect i ve cohort design . Patients and methods Forty-four terminally ill cancer patients were divided into two groups by serum CRP levels and followed up until death . We adjusted the influence of some clinical and laboratory variables on survival by use of Cox ’s proportional hazard model . Using the stepwise variable selection method , we found the final model . For 19 patients , CRP levels at 2 weeks and a week before death were compared by Wilcoxon signed ranks test . Main results All 44 study subjects died during the study period , and the median survival time was 17 days . Survival time of the elevated CRP group ( ≥2.2 mg/dl ) was found to be significantly shorter than the lower CRP group in univariate analysis ( hazard rate = 3.221 , P = 0.001 ) . In multivariate analysis , elevated CRP level ( ≥2.2 mg/dl ) was selected as one of the unfavorable indicators regarding survival . Dyspnea and hyperbilirubinemia were also found significant predictors of shorter life expectancy in the final model . Serum CRP levels were significantly increased between the first and the second week before death . Conclusions Our results showed that serum CRP level can be a useful indicator predictive of survival time of terminally ill cancer patients Objectives High serum level of interleukin 6 ( IL-6 ) is associated with high degree of tumor progression and systemic weakness . Anti – IL-6 therapy possibly improves the deterioration of clinical characteristics in patients with high IL-6 level . However , IL-6–related factors in patients with treatment-naive advanced pancreatic cancer ( PC ) have not been established . The goal of this study was to identify IL-6–related factors in patients with advanced PC who were scheduled to undergo first-line chemotherapy . Methods Patients with treatment-naive advanced PC were eligible for inclusion in this study . Patients who did not receive first-line chemotherapy were excluded . Serum IL-6 levels and clinical parameters were prospect ively recorded . Analyses were performed to identify risk factors for high IL-6 levels . Results Eighty patients were analyzed . IL-6–related factors were advanced age ( P < 0.01 ) , the presence of liver metastasis ( P < 0.01 ) , the large volume of liver metastasis ( P < 0.01 ) , severe fatigue ( P = 0.02 ) , high carcinoembryonic antigen levels ( P = 0.02 ) , anemia ( P < 0.01 ) , and high C-reactive protein levels ( P = 0.02 ) in multivariate analyses . Decreased skeletal muscle mass tended to be associated with high IL-6 levels . Conclusions High serum IL-6 was related to advanced age , the presence of hepatic metastasis , large tumor burden in liver , severe fatigue , high carcinoembryonic antigen , high C-reactive protein , and anemia in patients with treatment-naive advanced PC Background : Hip fracture is a frequent injury in the elderly , and is associated with a high incidence of functional impairment , complications and mortality . Objective : To determine kinetics of C-reactive protein ( CRP ) , fibrinogen and erythrocyte sedimentation rate ( ESR ) in hip-fractured patients over a 1-month post-operative period ; to examine the relationship of these parameters to cognition , operation type , post-operational complications , functional level 1 month post-operatively and 6-month mortality . Methods and Subjects : 32 aged patients operated on for hip fracture were prospect ively followed-up for 6 months . Fracture , type of operation and anesthetic risk were recorded . Cognition was evaluated by the Mini-Mental State Examination and pre-fracture functional level evaluated by the Katz Index of ADL . Follow-up included complications , mortality and functional outcome . CRP , fibrinogen and ESR were assessed during the first 10 h post-fracture ; 48–60 h , and 7 and 30 days post-operatively , respectively . Results : Only CRP kinetics were found to differ in patients with complications vs. those without , as a group ( p = 0.006 ) , and in patients suffering infections , delirium and cardiovascular complication vs. patients with no complications ( p = 0.06 , 0.03 , 0.02 , respectively ) . Mean ( ±SEM ) CRP 48–60 h post-operatively was 20.9 ± 2.1 and 13.1 ± 1.6 mg/dl in complicated and uncomplicated patients , respectively ( p = 0.002 ) . The mean CRP 48–60 h post-operatively was highly correlated with the CRP area under the curve , R = 0.88 ( p < 0.001 ) . A cut-off level of 15 mg/dl for CRP , 48– 60 h post-operatively , was calculated for patients with complications ( sensitivity 93 % , specificity 65 % , p = 0.003 ) . CRP , fibrinogen and ESR were not related to fracture or type of operation , cognition , anesthetic risk , 1-month post-operative functioning and 6-month mortality . Conclusions : CRP measurement in elderly patients operated for hip fracture may be valuable in assessing and monitoring complications Background Cancer cachexia , a catabolic state characterized by weight loss , occurs frequently in patients with terminal-stage neoplastic diseases . Gastrointestinal hormones and cytokines may be associated with anorexia and wasting in cancer cachexia . Methods This study aim ed to examine the mechanism of anorexia in cachectic patients through a prospect i ve investigation of plasma cytokines , ghrelin , and leptin in 16 cachectic patients with cancer of the digestive organs and 10 healthy volunteers . Results Tumor necrosis factor (TNF)-α , interleukin (IL)-6 , IL-1 receptor antagonist ( IL-1Ra ) , and ghrelin levels were significantly higher in cachectic cancer patients than in the healthy volunteers , whereas leptin was significantly lower in the cachectic cancer patients . Plasma leptin levels and cytokine levels ( TNF-α and IL-6 ) correlated significantly with body mass index ( BMI ) , but plasma ghrelin levels did not correlate with BMI or with the grade of symptoms . Conclusion Neither weight loss nor the grade of symptoms seemed to be directly associated with the increase in ghrelin levels . Hence , it is considered that the increase in ghrelin levels can not simply be explained by an increase in ghrelin secretion , suggesting that other mechanisms , such as the decreased inactivation of ghrelin , may also play a role . Further studies are needed to clarify the mechanisms of the increase in ghrelin levels . Additionally , the changes in plasma cytokines ( TNF-α and IL-6 ) and leptin in cachectic cancer patients suggest that these molecules may be useful markers for the evaluation of cancer cachexia Purpose The purpose of this study was to evaluate the prognostic role of interleukin-6 ( IL-6 ) and tumour necrosis factor-alpha ( TNF-α ) in the survival of patients with advanced cancer . Methods In this prospect i ve cohort study between three hospice and palliative care centres in South Korea , we followed 98 advanced cancer patients until death or the end of the study . Approximately 60 % of the patients had poor functional status ( Eastern Cooperative Oncology Group score ≥3 ) . We investigated the symptoms of cancer cachexia anorexia syndrome , possible cytokine-related confounders such as infection and medication records . Influence from clinical variables was adjusted using the Cox proportional hazard model . Results The median survival time was 27 days . On multivariate analysis , elevated IL-6 ( hazard ratio , 2.139 ; p = 0.003 ) was found to be an independent significant prognostic factor . TNF-α was not a significant factor . Poor performance status and male gender were also independently related to shortened survival . Conclusions IL-6 level can be a useful indicator of survival time of patients with advanced cancer at the very end of life . In contrast , the prognostic role of TNF-α requires further study BACKGROUND AND PURPOSE Delirium is thought to be associated with systemic inflammatory response . However , its association with the most widely used inflammatory biomarker C-reactive protein ( CRP ) has not been well established . We aim ed to examine whether CRP on intensive care unit ( ICU ) entry was associated with subsequent development of delirium . DESIGN AND SETTING This prospect i ve observational study was conducted in a mixed 24-bed ICU in a tertiary teaching hospital . METHODS All patients admitted to the ICU from February 2011 to June 2012 were screened for eligibility . Demographic data and clinical characteristics of included patients were recorded . Patients were screened for the presence of delirium by using the tool Confusion Assessment Method for the ICU ( CAM-ICU ) . C-reactive protein was obtained on ICU entry and 24 hours thereafter . Eligible patients were followed up for 28 days or until death . Univariate and multivariate analyses were performed to evaluate independent risk factors for delirium . Clinical outcome included the length of stay ( LOS ) in the ICU , 28-day mortality , and duration of mechanical ventilation . Two-tailed P < .05 was considered statistically significant . RESULTS A total of 223 patients were included during study period . In univariate analysis , patients with delirium showed significantly higher CRP values than those without ( 120.5 vs 57.5 mg/L ; P = .0001 ) . By adjusting for confounding variables ( including age , sex , Acute Physiology and Chronic Health Evaluation II , intubation , living alone , physical restraint , alcohol drinking , smoking , type of medical condition , and hospital LOS before ICU admission ) in logistic regression model , CRP remained an independent predictor of delirium ( odds ratio , 1.07 ; 95 % confidence interval , 1.01 - 1.15 ) . As compared with nondelirious patients , those with delirium showed longer LOS in ICU ( 13 vs 5 days ; P < .001 ) and duration of mechanical ventilation ( 6 vs 1 days ; P < .001 ) . An increase in CRP greater than 8.1 mg/L within 24 hours was associated with 4-fold increase in the risk of delirium ( odds ratio : 4.47 , 95 % confidence interval , 1.28 - 15.60 ) . CONCLUSION C-reactive protein measured on ICU entry and its changes within 24 hours are risk indicators of delirium . Further studies exploring the treatment of delirium according to CRP levels are warranted OBJECTIVES To examine whether delirium in individuals with hip fracture is associated with high C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and soluble IL-6 receptor ( sIL-6R ) levels in the cerebrospinal fluid ( CSF ) . DESIGN Prospect i ve cohort study . SETTING Two university hospitals in Oslo , Norway , and Edinburgh , United Kingdom . PARTICIPANTS Individuals admitted with acute hip fracture ( N = 151 ) . MEASUREMENTS Participants were assessed for delirium pre- and postoperatively using the Confusion Assessment Method . Prefracture cognitive impairment was detected using the Informant Question naire on Cognitive Decline in the Elderly ( IQCODE ) . Serum was collected preoperatively and CSF just before the onset of spinal anesthesia . Cytokine levels in serum and CSF sample s were determined using an enzyme-linked immunosorbent assay . Student t-tests or Mann-Whitney U-tests were used for between-group comparisons . Spearman rho was used for correlations . RESULTS Sixty participants had prior cognitive impairment ( IQCODE score ≥3.44 ) . Delirium was diagnosed in 46 participants ( 77 % ) with prior cognitive impairment and 25 ( 29 % ) without . In participants without prior cognitive impairment , CSF CRP levels were higher in participants with delirium ( median 0.05 μg/mL , interquartile range ( IQR ) 0.02 - 0.12 μg/mL ) than in those without delirium ( median 0.01 μg/mL , IQR 0.00 - 0.06 μg/mL ) ( P = .01 ) ; there were no differences in participants with prior cognitive impairment . In secondary analyses , in participants with prior cognitive impairment , the concentration of CSF sIL-6R was higher in those participants who developed delirium than in the other subgroups , but this difference was not statistically significant . Serum levels of CRP , IL-6 , and sIL-6R were not different according to delirium in participants with or without prefracture cognitive impairment . CONCLUSION High CSF levels of CRP and sIL-6R may be associated with delirium . Different pathophysiological mechanisms may operate in different subgroups , notably in relation to the presence of prior cognitive impairment OBJECTIVES To examine the association between plasma levels of pterins and amino acids and postoperative delirium . DESIGN Prospect i ve cohort study . SETTING Cardiothoracic service in an university hospital in Rotterdam , the Netherl and s. PARTICIPANTS One hundred twenty-five individuals aged 70 and older undergoing elective cardiac surgery . MEASUREMENTS Plasma pterins and amino acids were measured pre- and postoperatively . Using multiple logistic regression analyses , the associations between pterins and amino acid levels and postoperative delirium were examined in relation to age , sex , comorbidity , cognitive functioning ( Mini-Mental State Examination ( MMSE ) score ) , and cardiac risk factors . RESULTS Delirium incidence in the main study group was 31.3 % . The preoperative measures associated with delirium were neopterin ( odds ratio ( OR ) = 1.05 , P = .009 ) ; MMSE score less than 28 ( OR = 4.39 , P = .001 ) ; European System for Cardiac Operative Risk Evaluation score greater than 6 ( OR = 2.84 , P = .03 ) ; and combined coronary artery bypass graft ( CABG ) and aortic , mitral , or tricuspid valve surgery ( OR = 4.32 , P = .01 ) . Postoperative measures associated with delirium were neopterin ( OR = 3.84 , P = .02 ) , homovanillic acid ( HVA , OR = 1.01 , P = .04 ) , and preoperative MMSE score less than 28 ( OR = 3.32 , P = .008 ) . CONCLUSION Preoperatively high neopterin levels predicted delirium after cardiac surgery in older adults , in addition to the well-known risk factors of poor cognitive function , high cardio-surgical risk , and combined CABG and valve surgery . Postoperative neopterin and HVA levels were also found to be associated with delirium , together with preoperative cognitive functioning . Plasma neopterin may be a c and i date biomarker for delirium after cardiac surgery in these older adults OBJECTIVES To compare the time-course of cytokine levels in patients with and without delirium and investigate differences in cytokine concentrations in delirium subtypes . DESIGN Prospect i ve cohort study . SETTING Academic Medical Center , Amsterdam , 2005 through 2007 . PARTICIPANTS Patients aged 65 and older admitted for surgery after hip fracture . MEASUREMENTS Experienced geriatric physicians used the Confusion Assessment Method to assess delirium and the Delirium Symptom Interview to assess delirium subtype . Tumor necrosis factor alpha ( TNF-alpha ) and interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , and IL-12 were assayed in repeated serum sample s using a cytometric bead array immunoassay . RESULTS Of 221 admitted patients , 98 ( mean age 84 , 50 patients with delirium ) were included , result ing in a total of 324 sample s. Ninety-six percent of these sample s had TNF-alpha , IL-1beta , and IL-10 levels below the reliable detection level . Differences between patients with and without delirium were observed in IL-6 ( median 51 vs 36 pg/mL , P=.01 ) and IL-8 ( median 15 vs 9 pg/mL , P=.03 ) levels . Changes over time in IL-6 and IL-8 levels in patients with delirium differed significantly from changes in levels in patients without delirium . The highest levels of IL-6 were present during delirium , and the highest levels of IL-8 were present before the development of delirium . Patients with the hyperactive ( median 71 pg/mL ) or mixed ( median 73 pg/mL ) subtype of delirium had higher IL-6 levels than patients with hypoactive delirium ( median 16 pg/mL ) ( P=.02 ) . CONCLUSION IL-6 and IL-8 may contribute to the pathogenesis of postoperative delirium in elderly people . IL-6 may play a role in the hyperactive behavior of delirium OBJECTIVES To determine the relationship between perioperative delirium and cortisol , glucose , and insulin in older adults acutely admitted for hip fracture . DESIGN Prospect i ve cohort study . SETTING Tertiary university center . PARTICIPANTS Consecutive individuals aged 65 and older acutely admitted for hip fracture were invited to participate . MEASUREMENTS All participants were repeatedly examined to determine presence and severity of delirium . Blood sample s for cortisol , glucose , and insulin were drawn at 11:00 a.m. Differences in characteristics of participants with and without delirium were evaluated using t-tests and Mann-Whitney tests . A logistic regression analysis was performed to correct for other important risk factors for delirium . RESULTS One hundred forty-three participants , 70 ( 49 % ) with delirium and 73 ( 51 % ) without , were included . In univariate analyses , there was a trend toward higher cortisol levels ( odds ratio = 1.003 ( 95 % confidence interval = 1.001 - 1.004 , P = .004 ) , but this association was not statistically significant after multivariable analysis and may reflect an association between high cortisol and preexisting cognitive and functional impairment , and there was no association with insulin or glucose levels . Adjusting for sex and prefracture cognitive and functional impairment made the trend with cortisol and delirium statistically nonsignificant . CONCLUSION Delirium in older adults acutely admitted for hip fracture may be linked with higher cortisol concentrations , but it may be that this association reflects an association between higher cortisol and preexisting cognitive and functional impairment We aim to confirm the prognostic value of an inflammation-based prognostic score ( the Glasgow Prognostic Score [ GPS ] ) in advanced colorectal cancer , to explore a predictive pattern of plasma cytokines and their gene polymorphisms for clinical outcome , and to investigate which cytokines contribute to GPS . Inflammatory markers were measured at baseline in 52 patients with stage IV colorectal cancer . Germline DNA was genotyped for interleukin (IL)-1beta-511 , IL-1beta + 3954 , IL-6 - 174 , TNF-alpha-308 , IL-10 - 1082 , and IL-10 -592 using Sequenome mass spectrometry-based genotyping technology . Toxicity was grade d by the National Cancer Institute Common Toxicity Criteria version 2.0 . Response was assessed by the Response Evaluation Criteria in Solid Tumors . Glasgow Prognostic Score , carcinoembryonic antigen and hypoalbuminemia were predictive of overall survival ( OS ) . Hypoalbuminemia ( < or = 35 g/L ) and GPS were predictive of toxicity ; GPS 2 was predictive of increased grade 2/3 toxicity compared with patients with a GPS of 0 or 1 ( P < .05 ) . Interleukin-10 - 592AA and IL-10 -1082CC predicted for OS ( P < .05 ) . Elevated levels of circulating IL-4 and soluble glycoprotein 130 ( sgp130 ) were associated with increased grade 2/3 toxicity . Significantly elevated levels of IL-6 and sgp130 were observed in patients with a GPS of 2 ( P < .05 ) . In this patient group , inflammatory markers predict for clinical outcome . This could improve prognostication and allow for intervention strategies to reduce tumor-associated inflammation OBJECTIVES Postoperative delirium after cardiac surgery is associated with increased morbidity and mortality as well as prolonged stay in both the intensive care unit and the hospital . The authors sought to identify modifiable risk factors associated with the development of postoperative delirium in elderly patients after elective cardiac surgery in order to be able to design follow-up studies aim ed at the prevention of delirium by optimizing perioperative management . DESIGN A post hoc analysis of data from patients enrolled in a r and omized controlled trial was performed . SETTING A single university hospital . PARTICIPANTS One hundred thirteen patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass . INTERVENTIONS None . MEASUREMENTS AND MAINS RESULTS : Screening for delirium was performed using the Confusion Assessment Method ( CAM ) on the first 6 postoperative days . A multivariable logistic regression model was developed to identify significant risk factors and to control for confounders . Delirium developed in 35 of 113 patients ( 30 % ) . The multivariable model showed the maximum value of C-reactive protein measured postoperatively , the dose of fentanyl per kilogram of body weight administered intraoperatively , and the duration of mechanical ventilation to be independently associated with delirium . CONCLUSIONS In this post hoc analysis , larger doses of fentanyl administered intraoperatively and longer duration of mechanical ventilation were associated with postoperative delirium in the elderly after cardiac surgery . Prospect i ve r and omized trials should be performed to test the hypotheses that a reduced dose of fentanyl administered intraoperatively , the use of a different opioid , or weaning protocol s aim ed at early extubation prevent delirium in these patients BACKGROUND therapeutic use of cytokines can induce delirium , and delirium often occurs during infections associated with elevated levels of cytokines . This study examined the association of demographic , clinical and biological factors ( IL-1alpha , IL-1beta , IL-1RA , IL-6 , TNF-alpha , IFN-gamma , LIF , IGF-I , APOE genotype ) with the presence and severity of delirium . METHODS in an observational prospect i ve longitudinal study , patients aged 70 + were recruited from an elderly medical unit and assessed every 3 - 4 days ( maximum assessment s 4 ) . At each time , the scales MMSE , DRS , CAM , APACHEII were administered and blood was withdrawn to estimate the above biological factors . Mixed effects ( PQL ) and GEE were used to analyse the repeated measurements and investigate the associations at the individual and population average levels . RESULTS a total of 205 observations on 67 individuals were analysed . Lower levels of IGF-I , and lower levels of circulating IL-1RA , are significantly ( P < 0.05 ) associated with delirium , while the remaining of cytokines , severity of illness and possession of epsilon 4 allele had a non-significant effect . This has been shown by both statistical methods . Similarly lower levels of IGF-I , and high levels of IFN-gamma , are statistically significantly ( P < 0.05 ) associated with higher DRS scores ( more severe delirium ) . CONCLUSIONS this study finds that ( i ) low levels of both neuroprotective factors ( IGF-I , IL-1RA ) are associated with delirium , ( ii ) high IFN-gamma and low IGF-I have significant effects on delirium severity and ( iii ) otherwise the pro-inflammatory cytokines studied , APOE genotype and severity of illness do not appear to be associated , in older medically ill patients , with either delirium or severity of it Delirium is a common , serious , yet poorly understood syndrome . Growing evidence suggests cerebral metabolism is fundamentally disturbed ; however , it has not been investigated using 2 - 18F-fluoro-2-deoxyglucose ( FDG ) positron emission tomography ( PET ) in delirium . This prospect i ve study thus explored FDG PET patterns of cerebral glucose metabolism in older in patients with delirium . A particular emphasis was on the posterior cingulate cortex ( PCC ) , a key region for attention , which is a central feature of delirium . Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ ; 13 participants ( 8 female , median 84 y ) were scanned during delirium , and 6 scanned again after resolution . On visual analysis , cortical hypometabolism was evident in all participants during delirium ( 13/13 ) , and improved with delirium resolution ( 6/6 ) . Using NeuroQ , glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p < 0.05 ) . Greater metabolism in both PCCs correlated with better performance on a neuropsychological test of attention , the WAIS-IV Digit Span Test forwards , and with shorter delirium duration . This research found widespread , reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium Purpose : The purpose of this article was to investigate the influence of inflammatory cytokines , pro-cachectic ( interleukin [IL]-1 receptor agonist [ IL-1ra ] , IL-6 , and tumor necrosis factor-α [ TNF-α ] ) , immunomodulatory ( IL-10 and interferon-γ [ IFN-γ ] ) , and pro-angiogenic ( vascular endothelial growth factor [ VEGF ] ) , on resting energy expenditure ( REE ) , weight , and nutritional intake and to explore potential interactions between their circulating concentrations and colorectal cancer stage/histologic differentiation and response to radiotherapy ( RT ) . Patients and Methods : This was a prospect i ve longitudinal study in 101 patients evaluated before and after neoadjuvant RT , including REE ( indirect calorimetry ) , percent weight loss , usual/current diet ( diet history and 24-hour recall ) , serum concentrations of cytokines ( enzyme-linked immunosorbent assay ) , and RT response . Results : Stages III/IV were often associated with histologic grade s 2/3 ( P < 0.01 ) , albeit both characteristics independently were associated with higher concentrations of IL-1ra ( P ≤ 0.05 ) , IL-6 ( P ≤ 0.02 ) , TNF-α ( P ≤ 0.05 ) , IFN-γ ( P ≤ 0.05 ) , and VEGF ( P < 0.03 ) . Before and after RT , higher REE , weight loss ≥5 % , and intake reduction ≥25 % were associated with advanced stage , histologic grade s 2/3 , higher IL-1ra , IL-6 , TNF-α , IFN-γ , and VEGF , and nonresponse to RT ( P = 0.003 ) . A general linear model analysis showed that stages III/IV , histologic grade s 2/3 , and higher IL-1ra , IL-6 , TNF-α , IFN-γ , and VEGF were major determinants of REE increase , weight loss , and intake reduction . In predictive value analyses , higher baseline pro-cachectic cytokines ( IL-1ra + IL-6 + TNF-α ) by themselves predicted increased REE ( hazard ratio [ HR ] : 8.25 ; 95 % CI : 2.74–26.47 ; P < 0.002 ) , greater weight loss ( HR : 8.15 ; 95 % CI : 2.22–25.40 ; P < 0.002 ) , and intake reductions ( HR : 7.15 ; 95 % CI : 2.25–16.11 ; P < 0.004 ) after RT . Conclusion : This study confirms the fact that wasting in colorectal cancer is correlated with tumor burden and histologic aggressiveness and suggests that both characteristics lead to overproduction of IFN-γ , VEGF , and pro-cachectic cytokines , all of which may cause higher metabolic rates , poor intake , and nonresponse to RT OBJECTIVES This study aim ed to investigate the potential of C-reactive protein ( CRP ) as a predictor of death within 14 days in acutely symptomatic patients with advanced cancer admitted to the emergency department ( ED ) . METHODS A prospect i ve observational study was conducted of 126 consecutive patients with advanced cancer who were admitted to the ED because of acute symptoms . The patients were categorized into two groups according to serum CRP levels ( cutoff 9.2 mg/dL ) . Demographic characteristics , disease-related factors , clinical symptoms and signs , and laboratory data were collected . Univariate and multivariate analyses were performed to evaluate the relationship between clinical findings and 14-day mortality . RESULTS Median survival was 26.5 days ( interquartile range = 8.0 - 79.5 days ) . In univariate analysis , serum CRP level ( ≥9.2 mg/dL ) , chemotherapy , age ( ≥65 years ) , altered mental status , hypotension , and leukocytosis were significant . Multivariate regression analysis revealed that among these variables , serum CRP level ( hazard ratio [ HR ] = 2.444 , 95 % confidence interval [ CI ] = 1.298 to 4.603 , p = 0.006 ) and chemotherapy ( HR = 0.452 , 95 % CI = 0.236 to 0.863 , p = 0.016 ) were independent prognostic factors for 14-day mortality . CONCLUSIONS Serum CRP levels may provide information on death within 14 days after the ED visit in patients with advanced cancer BACKGROUND Biomarkers might help to predict the emergence of delirium . Advance warning of the threats of this condition could potentially reduce significant morbidity , mortality , and costs of hospitalizing patients . OBJECTIVE Our prospect i ve study investigates for the first time the impact of soluble interleukin-2 receptor ( sIL-2R ) as a biomarker of delirium after cardiac surgery with cardiopulmonary bypass ( CPB ) . METHOD A total of 34 patients who underwent elective cardiac surgery with CPB were enrolled . During the intensive care unit ( ICU ) stay and after discharge from the ICU , the delirious state was evaluated daily using the Delirium Rating Scale by Trzepacz . sIL-2R was assayed before CPB , 24 hours postoperatively , and on the day before discharge . RESULTS After CPB , 11 patients ( 32.4 % ) developed delirium . A short-term delirious state ( less than 1 day ) was observed in 3 patients and a prolonged delirious state in 8 patients . During the study period , sIL-2R levels decreased 24 hours postoperatively and increased afterward ( Friedman test ; p < 0.001 ) . As shown by the Spearman rank correlation , CPB patients with higher Delirium Rating Scale scores 72 hours , 96 hours , and 120 hours postoperatively had significant higher sIL-2R levels 24 hours postoperatively . In CPB patients with a prolonged postoperative delirious state , the sIL-2R level is statistically significantly elevated 24 hours postoperatively in comparison with CPB patients without a postoperative delirium ( Mann-Whitney U : 48.5 , p = 0.049 ) . CONCLUSION High levels of sIL-2R appear to be a useful biomarker to identify patients with high risk for a delirious state The knowledge of prognostic factors capable of subdividing cancer patients into groups having homogenous survival times is useful even in very advanced stages of illness . This prospect i ve multicenter study assessed these prognostic factors in 530 terminal patients with solid tumors who were undergoing only palliative care . Thirteen hematological and urinary parameters were assessed on admission and every 28 days thereafter . In 519 assessable patients with a median survival of 32 days , six biological parameters demonstrated a statistically significant predictive prognosis . A poor prognosis was predicted by high total white blood count ( WBC ) ( P < 0.0001 ) , high neutrophil percentage ( P < 0.0001 ) , low lymphocyte percentage ( P < 0.0001 ) , low serum albumin level ( P = 0.0015 ) , low pseudocholinesterase level ( P < 0.0001 ) , and high proteinuria ( P = 0.0064 ) . Multiple regression analysis showed that only WBC , lymphocyte percentage and pseudocholinesterase level were independent predictors of survival . The individualization of biological parameters having an independent prognostic capacity is a useful step in the attempt to identify subsets of patients with a homogeneous prognosis . The biological factors needed are easily detected by means of a simple blood test and do not require invasive operations on patients who are already debilitated OBJECTIVES To examine associations between the inflammatory marker C-reactive protein ( CRP ) measured preoperatively and on postoperative day 2 ( POD2 ) and delirium incidence , duration , and feature severity . DESIGN Prospect i ve cohort study . SETTING Two academic medical centers . PARTICIPANTS Adults aged 70 and older undergoing major noncardiac surgery ( N = 560 ) . MEASUREMENTS Plasma CRP was measured using enzyme-linked immunosorbent assay . Delirium was assessed from Confusion Assessment Method ( CAM ) interviews and chart review . Delirium duration was measured according to number of hospital days with delirium . Delirium feature severity was defined as the sum of CAM-Severity ( CAM-S ) scores on all postoperative hospital days . Generalized linear models were used to examine independent associations between CRP ( preoperatively and POD2 separately ) and delirium incidence , duration , and feature severity ; prolonged hospital length of stay ( LOS , > 5 days ) ; and discharge disposition . RESULTS Postoperative delirium occurred in 24 % of participants , 12 % had 2 or more delirium days , and the mean ± st and ard deviation sum CAM-S was 9.3 ± 11.4 . After adjusting for age , sex , surgery type , anesthesia route , medical comorbidities , and postoperative infectious complications , participants with preoperative CRP of 3 mg/L or greater had a risk of delirium that was 1.5 times as great ( 95 % confidence interval ( CI ) = 1.1 - 2.1 ) as that of those with CRP less than 3 mg/L , 0.4 more delirium days ( P < .001 ) , more-severe delirium ( 3.6 CAM-S points higher , P < .001 ) , and a risk of prolonged LOS that was 1.4 times as great ( 95 % CI = 1.1 - 1.8 ) . Using POD2 CRP , participants in the highest quartile ( ≥235.73 mg/L ) were 1.5 times as likely to develop delirium ( 95 % CI = 1.0 - 2.4 ) as those in the lowest quartile ( ≤127.53 mg/L ) , had 0.2 more delirium days ( P < .05 ) , and had more severe delirium ( 4.5 CAM-S points higher , P < .001 ) . CONCLUSION High preoperative and POD2 CRP were independently associated with delirium incidence , duration , and feature severity . CRP may be useful to identify individuals who are at risk of developing delirium OBJECTIVE Pathophysiological mechanisms leading to delirium are not clear . Age is a known risk factor and hypothesised to be accompanied by a low- grade inflammatory state . Previous studies have shown an association between delirium and circulating proinflammatory markers in acutely ill and postoperative patients . In light of the ageing/inflammation theory , we investigated the association of these markers with delirium in not acutely ill , elderly patients . METHODS In a prospect i ve nested case-control study levels of C-reactive protein ( CRP ) , interleukin 6 ( Il-6 ) , insulin growth factor 1 ( IGF-1 ) were measured pre-operatively in elderly patients admitted for hip-surgery . These levels were compared between patients who later developed a post-operative delirium and patients who did not . Patients were matched for age and disease severity . RESULTS Eighteen patients who developed delirium post-operatively were matched with 50 controls . Median APACHE-scores were below 16 in both groups . Pre-operative serum concentrations of CRP , Il-6 and IGF-1 did not differ between groups . IL-6 levels were associated with a measure of cognitive impairment . CONCLUSION In the present study no relationship was found between levels of pre-operative circulating pro-inflammatory markers and post-operative delirium in elderly patients , who were free from acute or severe disease BACKGROUND AND OBJECTIVES Optimal surgical decision-making and informed consent for palliative procedures is limited by a lack of appropriate outcomes data . Elevated C-reactive protein ( CRP ) may help guide patient selection for palliative surgery . METHODS Procedures to palliate symptoms of advanced cancer were identified from a prospect i ve palliative surgery data base . Patients with a recorded preoperative serum CRP were identified and observed for at least 180 days or until death . RESULTS Fifty patients were identified who underwent an elective palliative procedure from July 2006 to June 2012 . Presenting symptoms included gastrointestinal obstruction ( 40 % ) , tumor-related pain ( 38 % ) or bleeding ( 12 % ) , and other ( 10 % ) . Symptom improvement was documented for 37 patients ( 74 % ) . Palliative procedures were associated with 30-day postoperative morbidity ( 42 % ) and mortality ( 10 % ) . CRP ( range 1 - 144 mg/L , median 9.7 mg/L ) was elevated in 27 patients ( 54 % ) and was independently associated with developing a major complication ( P = 0.005 ) and decreased overall survival ( 166 vs. 659 days , P < 0.0001 ) . CONCLUSIONS Patients with advanced cancer can be afforded symptom improvement and the opportunity for improved quality of life following palliative procedures . Elevated preoperative CRP may help identify patients who are less likely to realize the benefits of palliative operations |
12,565 | 28,128,881 | There appears to be no clear for advantage continuous renal replacement in the hemodynamically unstable patient .
Currently , both modalities are safe and effective means of treating AKI in the critically ill adult | Critically ill adults with acute kidney injury ( AKI ) experience considerable morbidity and mortality .
Controversy remains regarding the optimal renal replacement intervention for these patients .
Our systematic review aim ed to determine the effect(s ) of sustained low-efficiency dialysis ( SLED ) compared with continuous renal replacement ( CRRT ) therapy on relevant patient outcomes . | Introduction Acute kidney injury ( AKI ) is associated with a high mortality of up to 60 % . The mode of renal replacement therapy ( intermittent versus continuous ) has no impact on patient survival . Sustained low efficiency dialysis using a single-pass batch dialysis system ( SLED-BD ) has recently been introduced for the treatment of dialysis-dependent AKI . To date , however , only limited evidence is available in the comparison of SLED-BD versus continuous veno-venous hemofiltration ( CVVH ) in intensive care unit ( ICU ) patients with AKI . Methods Prospect i ve , r and omized , interventional , clinical study at a surgical intensive care unit of a university hospital . Between 1 April 2006 and 31 January 2009 , 232 AKI patients who underwent renal replacement therapy ( RRT ) were r and omized in the study . Follow-up was assessed until 30 August 2009 . Patients were either assigned to 12-h SLED-BD or to 24-h predilutional CVVH . Both therapies were performed at a blood flow of 100 to 120 ml/min . Results 115 patients were treated with SLED-BD ( total number of treatments n = 817 ) and 117 patients with CVVH ( total number of treatments n = 877).The primary outcome measure , 90-day mortality , was similar between groups ( SLED : 49.6 % vs. CVVH : 55.6 % , P = 0.43 ) . Hemodynamic stability did not differ between SLED-BD and CVVH , whereas patients in the SLED-BD group had significantly fewer days of mechanical ventilation ( 17.7 ± 19.4 vs. 20.9 ± 19.8 , P = 0.047 ) and fewer days in the ICU ( 19.6 ± 20.1 vs. 23.7 ± 21.9 , P = 0.04 ) . Patients treated with SLED needed fewer blood transfusions ( 1,375 ± 2,573 ml vs. 1,976 ± 3,316 ml , P = 0.02 ) and had a substantial reduction in nursing time spent for renal replacement therapy ( P < 0.001 ) result ing in lower costs . Conclusions SLED-BD was associated with reduced nursing time and lower costs compared to CVVH at similar outcomes . In the light of limited health care re sources , SLED-BD offers an attractive alternative for the treatment of AKI in ICU patients .Trial registration Clinical Trials.gov We conducted a prospect i ve , r and omized study to compare conventional continuous venovenous hemodiafiltration ( CVVHDF ) with sustained hemodiafiltration ( SHDF ) using an acetate-free dialysate . Fifty critically ill patients with acute kidney injury ( AKI ) who required renal replacement therapy were treated with either CVVHDF or SHDF . CVVDHF was performed using a conventional dialysate with an effluent rate of 25 mL·kg−1 · h−1 , and SHDF was performed using an acetate-free dialysate with a flow rate of 300−500 mL/min . The primary study outcome , 30 d survival rate was 76.0 % in the CVVHDF arm and 88.0 % in the SHDF arm ( NS ) . Both the number of patients who showed renal recovery ( 40.0 % and 68.0 % , CVVHDF and SHDF , resp . ; P < .05 ) , and the hospital stay length ( 42.3 days and 33.7 days , CVVHDF and SHDF , resp . ; P < .05 ) , significantly differed between the two treatments . Although the total convective volumes did not significantly differ , the dialysate flow rate was higher and mean duration of daily treatment was shorter in the SHDF treatment arm . Our results suggest that compared with conventional CVVHDF , more intensive renal support in the form of post-dilution SHDF with acetate-free dialysate may accelerate renal recovery in critically ill patients with AKI BACKGROUND In postsurgical acute renal failure patients with moderate unstable hemodynamics or fluid overload , the choice of dialysis modality is difficult . This study was performed to compare the outcomes between the sustained low-efficiency dialysis ( SLED ) and continuous veno-venous hemofiltration ( CVVH ) in these patients . METHODS Sequential postsurgical acute renal failure patients undergoing acute dialysis with CVVH ( 2002 - 2003 ) , or SLED ( 2004 - 2005 ) as a result of severe fluid overload or moderately unstable hemodynamics were analyzed . Multivariate analyses of comorbidity , disease severity before initiating dialysis , biochemical measurements , and hemodynamic parameters for 3 days after the first dialysis session were performed by fitting multiple logistic regression models to predict patient 's 30-day after hospital discharge ( AHD ) mortality . RESULTS Among the 101 recruited patients , 38 received SLED and the rest received CVVH . The 30-day AHD mortality was 62.4 % . The independent risk factors of 30-day AHD mortality included older age ( P = .008 ) , lower first postdialysis mean arterial pressure ( MAP ) ( P = .021 ) , higher first postdialysis blood urea nitrogen level ( P = .009 ) , and absence of a history of hypertension ( P = .002 ) . A further linear regression analysis found that dialysis using SLED was associated with higher first postdialysis MAP ( P = .003 ) . CONCLUSIONS Among the postsurgical patients requiring acute dialysis with severe fluid overload or moderately unstable hemodynamics , the patients treated with SLED had a higher first postdialysis MAP than those treated with CVVH , which led to lower mortality . Further multicenter r and omized clinical trials of larger sample size are needed to compare the effects of SLED and CVVH on the outcomes of postsurgical acute dialysis patients Hemodialysis ( HD ) for critically ill patients with acute renal failure has been provided as intermittent hemodialysis ( IHD ) or continuous renal replacement therapy ( CRRT ) . IHD is often complicated by hypotension and inadequate fluid removal , and CRRT by high cost of solutions and problems with anticoagulation . Sustained low-efficiency daily dialysis ( SLED ) has been suggested as an alternative treatment . This is an observational , prospect i ve pilot study describing the introduction of SLED at our institution . We compared SLED ( 23 patients , 165 treatments ) with CRRT ( 11 patients , 209 days ) , focusing on cost , anticoagulation , and small solute removal . SLED consisted of 8 h of HD 6 days a week , with blood flow of 200 ml/min , dialysate flows of 350 ml/min , and hemofiltration with 1 l of saline/h . CRRT patients were anticoagulated with either heparin or citrate , and SLED patients with either heparin or saline flushes . The weekly costs to the hospital were $ 1431 for SLED , $ 2607 for CRRT with heparin , and $ 3089 for CRRT with citrate . Sixty-five percent of SLED treatments were heparin-free ; filter clotting occurred in 18 % of heparin treatments and 29 % of heparin-free treatments ( NS ) . Weekly Kt/V was significantly higher for SLED ( 8.4+/-1.8 ) and time-averaged serum creatinine was lower ; equivalent renal clearance ( EKRjc ) was 29+/-6 ml/min for SLED , similar to that for CRRT . In summary , SLED may be routinely performed without anticoagulation ; it provides solute removal equivalent to CRRT at significantly lower cost OBJECTIVE To assess the causes , the prognostic factors , and the outcome of patients with severe acute renal failure . DESIGN Prospect i ve , multicenter study . SETTING Twenty French multidisciplinary intensive care units ( ICUs ) . PATIENTS All patients with severe acute renal failure were prospect ively enrolled in the study for a 6-month period . Severe acute renal failure was defined by the following criteria : a ) a serum creatinine concentration of > or = 3.5 mg/dL ( > or = 310 mumol/L ) and /or a blood urea nitrogen concentration of > or = 100 mg/dL ( > or = 36 mmol/L ) ; or b ) an increase in blood urea nitrogen or serum creatinine concentration , such that the concentration is 100 % above the baseline value in patients with previous chronic renal insufficiency ( serum creatinine concentration of > 1.8 mg/dL [ > 150 mumol/L ] ) , excluding those patients with a basal serum creatinine concentration of > 3.4 mg/dL ( > 300 mumol/L ) . INTERVENTIONS None . MEASUREMENTS AND MAIN RESULTS Age , sex , previous health status and preexisting organ dysfunction , and type and origin of acute renal failure were recorded . The Simplified Acute Physiology Score , the Acute Physiology and Chronic Health Evaluation ( APACHE II ) score , and the number of Organ System Failures were calculated on ICU day 1 and at the time of inclusion in the study . Prognostic factors were determined by univariate methods and stepwise logistic regression analysis . There were 360 patients in the study ; 217 patients were admitted to the study at the time of ICU admission and 143 patients were admitted to the study after ICU admission . Only 41 % of these patients were in good health 3 months before ICU entry . The reason for admission was medical in 78 % of cases . The type of acute renal failure was prerenal ( n = 16 ) , renal ( n = 282 ) , or postrenal ( n = 17 ) . Renal replacement therapy was used in 174 patients . Two hundred ten ( 58 % ) patients died during the hospital stay . Using stepwide logistic regression , seven variables were predictive of death . These variables were advanced age , altered previous health status , hospitalization before ICU admission , delayed occurrence of acute renal failure , sepsis , oliguria , and severity of illness as assessed at the time of study inclusion by Simplified Acute Physiology Score , APACHE II , or Organ System Failure . CONCLUSIONS The hospital mortality rate of patients with severe acute renal failure in patients requiring intensive care remains high . In order to compare patient groups in further trials concerning acute renal failure , recorded characteristics of the population should include age , previous health status , disease characteristics ( initial or delayed acute renal failure , oliguria , sepsis ) , and the severity of the illness as assessed by physiologic scoring systems recorded at the time of study inclusion Objective : To investigate the efficacy , safety and cost of treating patients with acute kidney injury ( AKI ) and diabetic nephropathy ( DN ) with continuous renal replacement therapy ( CRRT ) or sustained low-efficiency daily diafiltration with hemofiltration ( SLEDD-f ) . Subjects and Methods : Medical records of patients with AKI/DN from January 2006 to December 2012 were review ed . Fifty-five patients who received CRRT and 52 who received SLEDD-f were included in the study . CRRT and SLEDD-f were performed for 20 - 72 h per session and 8 - 10 h per session , respectively . Mortality and renal function recovery rates were evaluated 30 days after the initiation of renal replacement therapy ( RRT ) and APACHE-II and SOFA scores , anticoagulant dose , inflammatory indices and cost were calculated at baseline and at the end of RRT . Results : Of the 55 patients treated with CRRT , 49 ( 89.1 % ) had a 30-day survival rate and 30 ( 54.5 % ) had a 30-day renal recovery rate . Of the 52 patients with SLEDD-f , these rates were 92.3 % ( n = 48 ) and 61.5 % ( n = 32 ) , respectively . The dosage of low-molecular-weight heparin in the CRRT and SLEDD-f groups was 15,230 ± 1,460 and 6,320 ± 490 U/day , respectively . The cost of hemopurification and the total cost for patients treated with CRRT was CNY 28,628 ± 5,576 ( USD 4,210 ± 820 ) and CNY 38,828 ± 6,324 ( USD 5,710 ± 930 ) , respectively . These were higher than those for patients treated with SLEDD-f at CNY 13,260 ± 1,564 ( USD 1,950 ± 230 ) and CNY 19,720 ± 2,652 ( USD 2,900 ± 390 ) , respectively . Conclusions : SLEDD-f offered a similar chance of renal recovery and also had further advantages such as a lower heparin dosage , a shorter therapy time and lower hospitalization costs for patients than CRRT . Studies with larger , r and omized sample sizes are needed to confirm these findings |
12,566 | 30,202,552 | Conclusion Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing | Background Vision encompasses a large component of the brain 's pathways , yet is not represented in current sideline testing .
Objectives We performed a meta- analysis of published data for a vision-based test of rapid number naming ( King-Devick [ K-D ] test ) . | CONTEXT The return-to-play decision after sport-related cerebral concussion depends in part on knowing when an athlete has fully recovered postural control after injury . OBJECTIVE To describe the postconcussion recovery of postural control using approximate entropy ( ApEn ) , a regularity statistic from nonlinear dynamics . DESIGN Retrospective case series analysis . SETTING Sports medicine research laboratory . PATIENTS OR OTHER PARTICIPANTS Collegiate athletes from whom center-of-pressure and symptom data were collected at preseason , less than 48 hours after injury , and 48 to 96 hours after injury . MAIN OUTCOME MEASURE(S ) Approximate entropy values reflecting the amount of r and omness contained in center-of-pressure oscillations were calculated for anterior-posterior ( AP ) and medial-lateral ( ML ) time series . Equilibrium scores reflecting the amplitude of center-of-pressure AP oscillations were used to indicate postural stability . The number and severity of symptoms were described . RESULTS Compared with the healthy preseason state , ApEn values for the AP and ML time series generally declined immediately after injury in both steady and unsteady injured athletes . At 48 to 96 hours after injury , ApEn values for the ML time series remained significantly depressed ( mean difference compared with preseason = -0.268 , st and ard error = 0.072 ) , even among athletes whose initial postural instability had resolved . We found few significant relationships between changes in ApEn values and changes in symptoms before and after injury . CONCLUSIONS The effects of cerebral concussion on postural control appear to persist for longer than 3 to 4 days , even among athletes with no signs of unsteadiness . Our results may reflect changes in neurophysiologic or mechanical constraints on postural control . Approximate entropy provides a theoretically distinct , valuable measurement alternative that may prove useful for reducing uncertainty in the return-to-play decision CONTEXT Approximately 300 000 sport-related concussions occur annually in the United States , and the likelihood of serious sequelae may increase with repeated head injury . OBJECTIVE To estimate the incidence of concussion and time to recovery after concussion in collegiate football players . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 2905 football players from 25 US colleges were tested at preseason baseline in 1999 , 2000 , and 2001 on a variety of measures and followed up prospect ively to ascertain concussion occurrence . Players injured with a concussion were monitored until their concussion symptoms resolved and were followed up for repeat concussions until completion of their collegiate football career or until the end of the 2001 football season . MAIN OUTCOME MEASURES Incidence of concussion and repeat concussion ; type and duration of symptoms and course of recovery among players who were injured with a concussion during the seasons . RESULTS During follow-up of 4251 player-seasons , 184 players ( 6.3 % ) had a concussion , and 12 ( 6.5 % ) of these players had a repeat concussion within the same season . There was an association between reported number of previous concussions and likelihood of incident concussion . Players reporting a history of 3 or more previous concussions were 3.0 ( 95 % confidence interval , 1.6 - 5.6 ) times more likely to have an incident concussion than players with no concussion history . Headache was the most commonly reported symptom at the time of injury ( 85.2 % ) , and mean overall symptom duration was 82 hours . Slowed recovery was associated with a history of multiple previous concussions ( 30.0 % of those with > or =3 previous concussions had symptoms lasting > 1 week compared with 14.6 % of those with 1 previous concussion ) . Of the 12 incident within-season repeat concussions , 11 ( 91.7 % ) occurred within 10 days of the first injury , and 9 ( 75.0 % ) occurred within 7 days of the first injury . CONCLUSIONS Our study suggests that players with a history of previous concussions are more likely to have future concussive injuries than those with no history ; 1 in 15 players with a concussion may have additional concussions in the same playing season ; and previous concussions may be associated with slower recovery of neurological function Diffuse axonal injury caused by mild closed head injury ( CHI ) is likely to affect the neural networks concerned with the planning and execution of sequences of memory-guided saccades . Thirty subjects with mild CHI and thirty controls were tested on 2- and 3-step sequences of memory-guided saccades . CHI subjects showed more directional errors , larger position errors , and hypermetria of primary saccades and final eye position . No deficits were seen in temporal accuracy ( timing and rhythm ) . These results suggest that computerized tests of saccade sequences can provide sensitive markers of cerebral dysfunction after mild CHI Following on from our earlier findings of a close relationship between motor function and outcome after mild traumatic brain injury ( mTBI ) , this study examined whether it might be possible to predict poor recovery in the form of postconcussion syndrome ( PCS ) based upon early eye and arm motor function . Within 1 week post-injury , we assessed 37 mTBI patients on measures of saccades , oculomotor smooth pursuit , upper-limb visuomotor function , neuropsychological status , and self-reported health condition . At 3 months , 8 patients met the criteria for PCS . Using discriminant function analyses , we examined whether this future PCS-group could be identified prospect ively based on motor function , neuropsychological status , and self-reported health condition at 1 week post-injury . Early eye movement function was the most effective in distinguishing between PCS and non-PCS patients , achieving a sensitivity and specificity of 100 % in the present sample . This was followed by self-reported early health condition ( sensitivity : 87 % , specificity : 97 % ) , early upper-limb motor performance ( 87 % , 97 % ) , neuropsychological function ( 62 % , 100 % ) , and age , gender , education and clinical measures of trauma severity ( 37 % , 87 % ) . Leave-one-out validation analyses confirmed eye movements as the most robust discriminator ( sensitivity : 62 % , specificity : 97 % ) . Assessment of eye movement function after mTBI may contribute to a prospect i ve identification of patients who develop PCS , supporting the targeting of early health-care intervention Background : Sports-related concussion commonly affects the visual pathways . Current sideline protocol s test cognition and balance but do not include assessment s of visual performance . We investigated how adding a vision-based test of rapid number naming could increase our ability to identify concussed athletes on the sideline at youth and collegiate levels . Methods : Participants in this prospect i ve study included members of a youth ice hockey and lacrosse league and collegiate athletes from New York University and Long Isl and University . Athletes underwent preseason baseline assessment s using : 1 ) the King – Devick ( K-D ) test , a < 2-minute visual performance measure of rapid number naming , 2 ) the St and ardized Assessment of Concussion ( SAC ) , a test of cognition , and 3 ) a timed t and em gait test of balance . The SAC and timed t and em gait are components of the currently used Sport Concussion Assessment Tool , 3rd Edition ( SCAT3 and Child-SCAT3 ) . In the event of a concussion during the athletic season , injured athletes were retested on the sideline/rink-side . Nonconcussed athletes were also assessed as control participants under the same testing conditions . Results : Among 243 youth ( mean age 11 ± 3 years , range 5–17 ) and 89 collegiate athletes ( age 20 ± 1 years , range 18–23 ) , baseline time scores for the K-D test were lower ( better ) with increasing participant age ( P < 0.001 , linear regression models ) . Among 12 athletes who sustained concussions during their athletic season , K-D scores worsened from baseline by an average of 5.2 seconds ; improvement by 6.4 seconds was noted for the nonconcussed controls ( n = 14 ) . The vision-based K-D test showed the greatest capacity to distinguish concussed vs control athletes based on changes from preseason baseline to postinjury ( receiver operating characteristic [ ROC ] curve areas from logistic regression models , accounting for age = 0.92 for K-D , 0.87 for timed t and em gait , and 0.68 for SAC ; P = 0.0004 for comparison of ROC curve areas ) . Conclusions : Adding a vision-based performance measure to cognitive and balance testing enhances the detection capabilities of current sideline concussion assessment . This observation in patients with mild traumatic brain injury reflects the common involvement and widespread distribution of brain pathways dedicated to vision Behavioral studies in monkeys and humans suggest that systematic and variable errors of memory-guided saccades reflect distinct neuronal computations in primate spatial memory . We recorded memory-guided saccades with a 2-s delay in three patients with unilateral ischemic lesions of the frontal eye field and in three patients with unilateral ischemic lesions of the frontal eye field and the dorsolateral prefrontal cortex . Results suggest that systematic errors of memory-guided saccades originate in the frontal eye field and variable errors in the dorsolateral prefrontal cortex . These data are the first human lesion data to support the hypothesis that these regions provide functionally distinct contributions to spatial short-term memory AIM To use the King-Devick ( KD ) test and Sports Concussion Assessment Tool 2 ( SCAT2 ) in amateur rugby union players to identify witnessed and unrecognised episodes of concussion that occurred from match participation . METHODS A prospect i ve observational cohort study was conducted on a premier club level amateur rugby union team during the 2012 competition in New Zeal and . Every player completed a pre-competition question naire on concussion history , a baseline PCSS and two trials of the KD before they participated in any match activities . RESULTS For players reporting a concussion in the previous three years there was an average of 4.0±2.8 concussions per player . There were 22 concussive incidents recorded over the duration of the competition ( 46 per 1000 match hours ) . Five concussive incidents were witnessed ( 11 per 1000 match hours ) and 17 unrecognised concussive incidents were identified with the KD ( 37 per 1000 match hours ) . Witnessed concussions recorded , on average , a longer KD on the day of injury ( 5.5±2.4s ) than unrecognised concussions ( 4.4±0.9s ) when compared with their baseline KD . DISCUSSION The KD was able to identify players that had not shown , or reported , any signs or symptoms of a concussion but who had meaningful head injury . The current rate of concussion reported was a ten-fold increase in previously reported concussion injury rates . This makes the KD suitable for rapid assessment in a limited time frame on the sideline such as a five-minute window to assess and review suspected concussed players in rugby union AIM To use the King-Devick ( K-D ) test in senior amateur rugby union and rugby league players over a domestic competition season to see if it could identify witnessed and unwitnessed episodes of concussion that occurred from participation in competition matches over three years . METHODS A prospect i ve observational cohort study was conducted on a club level senior amateur rugby union team ( n=36 players in 2012 and 35 players in 2013 ) and a rugby league team ( n=33 players in 2014 ) during competition seasons in New Zeal and . All 104 players completed two trials 10min apart of the K-D at the beginning of their competition season . Concussions ( witnessed or unwitnessed ) were only recorded if they were formally diagnosed by a health practitioner . RESULTS A total of 52 ( 8 witnessed ; 44 unwitnessed ) concussive events were identified over the duration of the study result ing in a concussion injury incidence of 44 ( 95 % CI : 32 to 56 ) per 1000 match participation hours . There was a six-fold difference between witnessed and unwitnessed concussions recorded . There were observable learning effects observed between the first and the second K-D test baseline testing ( 50 vs. 45s ; z=-8.81 ; p<0.001 ) . For every 1 point reduction in each of the post-injury SAC components there was a corresponding increase ( worsening ) of K-D test times post-match for changes in orientation ( 2.9s ) , immediate memory ( 1.8s ) concentration ( 2.8s ) , delayed recall ( 2.0s ) and SAC total score ( 1.7s ) . DISCUSSION The rate of undetected concussion was higher than detected concussions by using the K-D test routinely following matches . Worsening of the K-D test post-match was associated with reduction in components of the SAC . The appeal of the K-D test is in the rapid , easy manner of its administration and the reliable , objective results it provides to the administrator . The K-D test helped identify cognitive impairment in players without clinical ly observable symptoms Eye movements were recorded electro-oculographically in three patients with a small ischemic lesion affecting the left frontal eye field ( FEF ) and in 12 control subjects . Reflexive visually guided saccades ( gap and overlap tasks ) , antisaccades , predictive saccades , memory-guided saccades , smooth pursuit and optokinetic nystagmus ( OKN ) were studied in the three patients . Staircase saccades and double step saccades were also studied in one of the three patients . For both leftward and rightward saccades , latency in the overlap task ( but not in the gap task ) and that of correct antisaccades and of memory-guided saccades was significantly increased , compared with the results of controls . There was a significant decrease in the amplitude gain of all rightward saccades programmed using retinotopic coordinates ( gap and overlap tasks , predictive and memory-guided saccades ) , whereas the amplitude gain of corresponding leftward saccades was preserved . Such an asymmetry between leftward and rightward saccades was significant . In the staircase paradigm as well as for the first saccade in the double step paradigm ( with the use of retinotopic coordinates in both cases ) , the amplitude gain of rightward saccades was also significantly lower than that of leftward saccades . Moreover , in the double step paradigm , the amplitude gain of the first rightward saccade was significantly lower than that of the second rightward saccade ( programmed using extraretinal signals ) , which was preserved . The percentage of errors in the antisaccade task did not differ significantly from that of normal subjects . In the predictive saccade paradigm , the percentage of predictive rightward saccades was significantly decreased . The left smooth pursuit gain for all tested velocities , the right smooth pursuit gain for higher velocities , and the left OKN gain were significantly decreased . The results show , for the first time in humans , that the FEF plays an important role in ( 1 ) the disengagement from central fixation , ( 2 ) the control of contralateral saccades programmed using retinotopic coordinates , ( 3 ) saccade prediction and ( 4 ) the control of smooth pursuit and OKN , mainly ipsilaterally . In contrast , the left FEF did not appear to be crucial for the control of the only type of saccades programmed using extraretinal signals studied here Background : The association between antecedent head injury and AD is inconsistent . Objective : To examine the association between early adult head injury , as documented by military hospital records , and dementia in late life ; and to evaluate the interaction between head injury and APOE ε4 as risk factors for dementia . Methods : The study had a population -based prospect i ve historical cohort design . It included men who were World War II Navy and Marine veterans , and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition . In 1996 to 1997 , military medical records were abstract ed to document the occurrence and details of closed head injury . The entire sample was then evaluated for dementia and AD using a multistage procedure . There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study . The authors estimated risk of dementia , specifically AD , using proportional hazards models . Results : Both moderate head injury ( hazard ratio [ HR ] = 2.32 ; CI = 1.04 to 5.17 ) and severe head injury ( HR = 4.51 ; CI = 1.77 to 11.47 ) were associated with increased risk of AD . Results were similar for dementia in general . The results for mild head injury were inconclusive . When the authors stratified by the number of APOE ε4 alleles , they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more ε4 alleles . Conclusions : Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life . However , the authors can not exclude the possibility that other unmeasured factors may be influencing this association The goal of the current investigation was to detect clinical ly important axonal damage in cerebral white matter after mild traumatic brain injury ( TBI ) using diffusion tensor imaging ( DTI ) . To this end , we evaluated a prospect i ve , pilot study of six subjects with isolated mild TBI and six matched orthopedic controls . All subjects underwent DTI scanning , post-concussive symptom ( PCS ) assessment , and neurobehavioral testing within 72 h of injury . Fractional anisotropy ( FA ) and trace values in white matter voxels of whole brain and five preselected regions of interest ( ROI ) were compared in mild TBI and control subjects using a quantile approach . In addition , whole brain images were analyzed using voxel-based morphometry . All subjects underwent quality of life and repeat PCS assessment at 1 month . Whole brain images revealed significantly lower 1(st ) percentile trace values ( mean 0.465 vs. 0.488 , p = 0.049 ) among mild TBI subjects . These trace values correlated with PCS scores at both 72 h ( r = -0.57 , p = 0.05 ) and 1 month ( r = -0.61 , p = 0.04 ) . Analysis of ROIs showed mild TBI subjects to have significantly lower mean trace in the left anterior internal capsule ( 0.536 vs. 0.574 , p = 0.007 ) and higher maximum ROI-specific median FA values ( mean 0.801 vs. 0.756 , p = 0.035 ) in the posterior corpus callosum . These FA values correlated with 72-h PCS score ( r = -0.63 , p = 0.03 ) , and two neurobehavioral tests ( visual motor speed [ r = 0.63 , p = 0.03 ] and impulse control [ r = 0.59 , p = 0.04 ] ) . Collectively , DTI detected significantly lower trace and elevated FA values in mild TBI subjects compared to controls . These abnormalities correlated to poor clinical outcome . We believe these findings represent axonal swelling , an early step in the process of axonal injury AIM This study undertook to use the K-D sideline test with the SCAT2 to see if concussions could be identified in amateur rugby league players over a representative competition period . METHOD A prospect i ve cohort study was conducted on two teams participating in an amateur rugby league . All players were tested for signs of concussion utilising the K-D test and players with longer times than their baseline scores undertook a further concussion assessment with the SCAT2 . RESULTS Five athletes with suspected concussion were evaluated by K-D testing . Three concussions were associated with witnessed events during the matches and two athletes were identified by the team medic as having longer K-D time scores incidentally post-match compared to baseline . Post-match K-D scores for all concussed athletes were worse than baseline for those with reported or witnessed concussion events ( 7s ; 5.0 - 7.1 ; p=0.025 ) and for those identified incidentally ( > 5s ; 8.9 - 9.1s ) . Both groups also reported more symptoms on the PCSS ( a part of the SCAT2 ) post-match . DISCUSSION In this rugby cohort , the K-D test was not only useful in identifying changes in players with witnessed head trauma , but in identifying changes in players with an un-witnessed suspected concussion The effect of severe physical fatigue on the learning and performance of males and females was compared . The task used in the study was a stabilometer balance task , and fatigue was induced by walking on a treadmill . Thirty male and 30 female subjects were r and omly assigned to 2 experimental and 2 control groups . Each subject was pretested , received 20 trials , and was post-tested the following day . The experimental groups were fatigued to a heart rate between 175 and 180 bpm for 5 minutes prior to the first trial and for one minute following every second trial . The control groups were not fatigued . Both time on balance ( TOB ) and total error ( TE ) scores were recorded for each trial . The TOB data indicated that fatigue was detrimental to both performance and learning of this dynamic balance task . In addition , the TOB learning data revealed that learning is detrimentally affected by fatigue . Conclusions were that severe fatigue is detrimental to both performance and learning of stabilometer balance and that fatigue has similar effects on balance performance and learning of males and females AIM To determine whether the King-Devick ( K-D ) test used as a sideline test in junior rugby league players over 12 matches in a domestic competition season could identify witnessed and incidentally identified episodes of concussion . METHODS A prospect i ve observational cohort study of a club level junior rugby league team ( n=19 ) during the 2014 New Zeal and competition season involved every player completing two pre-competition season baseline trials of the K-D test . Players removed from match participation , or who reported any signs or symptoms of concussion were assessed on the sideline with the K-D test and referred for further medical assessment . Players with a pre- to post-match K-D test difference > 3s were referred for physician evaluation . RESULTS The baseline test-retest reliability of the K-D test was high ( rs=0.86 ; p<0.0001 ) . Seven concussions were medically identified in six players who recorded pre- to post-match K-D test times greater than 3s ( mean change of 7.4s ) . Post-season testing of players demonstrated improvement of K-D time scores consistent with learning effects of using the K-D test ( 67.7s vs. 62.2s ) . DISCUSSION Although no witnessed concussions occurred during rugby play , six players recorded pre- to post-match changes with a mean delay of 4s result ing in seven concussions being subsequently confirmed post-match by health practitioners . All players were medically managed for a return to sports participation . CONCLUSION The K-D test was quickly and easily administered making it a practical sideline tool as part of the continuum of concussion assessment tools for junior rugby league players |
12,567 | 27,077,334 | These studies yield evidence that nurse management in addition to st and ard general practitioner care leads to modest improvements in blood pressure and total cholesterol levels in adults with type 2 diabetes attending a general practice .
CONCLUSION Meta- analysis identified modest , significant improvements amongst participants in nurse management interventions ( NMIs ) in the following clinical outcomes : mean SBP , mean DBP and mean total cholesterol .
The majority of outcomes studied did not show any advantage to adding NMIs to general practitioner care . | AIM Using the methodology of the Joanna Briggs Institute , a systematic review of current research was performed to determine if the addition of management by nurses had been more effective in improving clinical outcomes of patients with type 2 diabetes attending a general practice compared with st and ard care . | OBJECTIVE To determine whether diabetes care directed by nurses following detailed protocol s and algorithms and supervised by a diabetologist results in meeting the evidence -based American Diabetes Association ( ADA ) process and outcome measures more often than care directed under usual care in a minority population . RESEARCH DESIGN AND METHODS Studies were mainly conducted in two Los Angeles County clinics . In clinic A , nurse-directed diabetes care was provided to 252 patients ( 92 % Hispanic and 2 % African-American ) referred by their primary care providers . These patients were hierarchically matched with 252 diabetic patients in clinic B ( 79 % Hispanic and 19 % African American ) . When nurse-directed care was abruptly discontinued in clinic A for administrative reasons , it was reestablished in clinic B. Those patients were r and omly selected from a teaching clinic , and the outcomes in 114 patients who completed 1 year were compared with outcomes derived the year before receiving nurses ' care . The following process and outcome measures were assessed in the study : 1 ) number of visits , 2 ) diabetes education , 3 ) nutritional counseling , 4 ) HbA(1c ) , 5 ) lipid profiles , 6 ) eye exams , 7 ) foot exams , 8) renal evaluations , and 9 ) ACE inhibitor therapy in appropriate patients . RESULTS For patients under nurse-directed diabetes care in both clinics A and B , almost all process measures were carried out significantly more frequently than for the appropriate control patients . Under the care of nurses in clinic A , HbA(1c ) levels fell 3.5 % from 13.3 to 9.8 % in the 120 patients who were followed for at least 6 months , as compared with a 1.5 % fall from 12.3 to 10.8 % under usual ( physician-directed ) care in clinic B. During the year before enrolling in nurse-directed care in clinic B , mean HbA(1c ) levels decreased from 10.0 to 8.5 % . At the end of a year under the nurses ' care , the values fell further to 7.1 % . The median value fell from 8.3 to 6.6 % . CONCLUSIONS Specially trained nurses who follow detailed protocol s and algorithms under the supervision of a diabetologist can markedly improve diabetes outcomes in a minority population . This approach could help blunt the increased morbidity and mortality noted in minority population AIMS To develop tables that report the life expectancy associated with levels of major modifiable risk factors for patients with type 2 diabetes . METHODS AND RESULTS A set of tables reporting life-expectancy stratified by age-sex groups for combinations of modifiable risk was constructed based on predictions from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) Outcomes Model . This model is based on a system of parametric proportional hazards risk equations for estimating mortality and vascular complications of diabetes that have been estimated from 3642 patients from the UKPDS . The tables show substantial potential gains in life expectancy within every age group from modifying major risk factors . The estimated life expectancy of men at age of 55 years with type 2 diabetes , 5 years after diagnosis , varies between 13.2 years for a patient who smokes , has systolic blood pressure of 180 mmHg , a total : HDL cholesterol ratio of 8 , and HbA(1c ) of 10 % , and 21.1 years for a non-smoker with SBP of 120 mmHg , total/HDL ratio of 4 , and HbA(1c ) of 6 % . CONCLUSION Life expectancy tables provide a potentially useful tool of conveying prognostic information to people with type 2 diabetes and suggest substantial scope for increasing longevity by improving modifiable risk factors OBJECTIVE —The Diabetes Care Protocol combines task delegation ( a practice nurse ) , computerized decision support , and feedback every 3 months . We studied the effect of the Diabetes Care Protocol on A1C and cardiovascular risk factors in type 2 diabetic patients in primary care . RESEARCH DESIGN AND METHODS —In a cluster r and omized trial , mean changes in cardiovascular risk factors between the intervention and control groups after 1 year were calculated by generalized linear models . RESULTS —Throughout the Netherl and s , 26 intervention practice s included 1,699 patients and 29 control practice s 1,692 patients . The difference in A1C change was not significant , whereas total cholesterol , LDL cholesterol , and blood pressure improved significantly more in the intervention group . The 10-year coronary heart disease risk estimate of the UK Prospect i ve Diabetes Study improved 1.4 % more in the intervention group . CONCLUSIONS —Delegation of routine diabetes care to a practice nurse combined with computerized decision support and feedback did not improve A1C but reduced cardiovascular risk in type 2 diabetes patients Objective To evaluate the effectiveness of goal focused telephone coaching by practice nurses in improving glycaemic control in patients with type 2 diabetes in Australia . Design Prospect i ve , cluster r and omised controlled trial , with general practice s as the unit of r and omisation . Setting General practice s in Victoria , Australia . Participants 59 of 69 general practice s that agreed to participate recruited sufficient patients and were r and omised . Of 829 patients with type 2 diabetes ( glycated haemoglobin ( HbA1c ) > 7.5 % in the past 12 months ) who were assessed for eligibility , 473 ( 236 from 30 intervention practice s and 237 from 29 control practice s ) agreed to participate . Intervention Practice nurses from intervention practice s received two days of training in a telephone coaching programme , which aim ed to deliver eight telephone and one face to face coaching episodes per patient . Main outcome measures The primary end point was mean absolute change in HbA1c between baseline and 18 months in the intervention group compared with the control group . Results The intervention and control patients were similar at baseline . None of the practice s dropped out over the study period ; however , patient attrition rates were 5 % in each group ( 11/236 and 11/237 in the intervention and control group , respectively ) . The median number of coaching sessions received by the 236 intervention patients was 3 ( interquartile range 1 - 5 ) , of which 25 % ( 58/236 ) did not receive any coaching sessions . At 18 months ’ follow-up the effect on glycaemic control did not differ significantly ( mean difference 0.02 , 95 % confidence interval −0.20 to 0.24 , P=0.84 ) between the intervention and control groups , adjusted for HbA1c measured at baseline and the clustering . Other biochemical and clinical outcomes were similar in both groups . Conclusions A practice nurse led telephone coaching intervention implemented in the real world primary care setting produced comparable outcomes to usual primary care in Australia . The addition of a goal focused coaching role onto the ongoing generalist role of a practice nurse without prescribing rights was found to be ineffective . Trial registration Current Controlled Trials IS RCT N50662837 We studied the impact of nurse case management ( NCM ) on blood pressure ( BP ) , hemoglobin A1C , lipids , and diabetes complication screening . A 1-year r and omized-controlled trial was conducted in two primary care clinics of the Penn State Hershey Medical Center . Diabetes patients were r and omized to control group ( CG ) ( n=182 ) who received usual care by their primary care provider and intervention group ( IG ) ( n=150 ) who received additional NCM care , including self-management education , and implementation of diabetes guidelines . Primary outcomes included BP , A1C , lipid , process measures , and secondary outcome was diabetes-related emotional distress as assessed by Problem Areas in Diabetes ( PAID ) . BP significantly decreased from 137/77 to 129/72 in IG as compared to an increase from 136/77 to 138/79 in CG after 1 year . PAID scores improved significantly in IG ( from 23 to 10 ) due to reduced emotional stress . A1C ( 7.4 ) and LDL ( 105 ) were unaffected . Complications screening significantly improved in IG compared to CG : opthalmologic exam 26 to 68 % , foot exam 47 to 64 % , and nephropathy screening 34 to 72 % . NCM improved BP , diabetes-related emotional distress , and process measures in primary care . Unchanged A1C and lipids might be due to a threshold effect . Intervention based upon initial risk assessment may prove more cost-effective AIM OF THE STUDY Assessment of effects on quality of care , in terms of patient outcomes , when tasks in the care for out patients with stable type 2 diabetes are transferred from internist to nurse specialist and from outpatient clinic to general practice . BACKGROUND For the management of chronic diseases with a high prevalence and requiring current monitoring , it is suggested that substitution of care may be an appropriate solution to safeguard high quality care . DESIGN AND METHODS A 12-month nonequivalent control group design was used . General practitioners ( GPs ) referring diabetes patients to the University Hospital Maastricht were asked to choose for the traditional model or the nurse specialist model . Informed consent was obtained from patients with stable diabetes type 2 attending these practice s. All patients received care according to the model chosen by their GP . Identified outcomes were : clinical status , health status , self-care behaviour , knowledge of diabetes , patient satisfaction , and consultation with care-providers . RESULTS In the control group ( n=47 ) no patients were treated with oral hypoglycaemic agents ( OHA ) only . The control group was compared with an intervention subgroup ( n=52 ) also without patients receiving OHA only . Clinical data were available for all patients . Patients without complete data from question naires had better mean concentration of HbA1c than patients with complete data ( P=0.004 ) . The traditional care model and the nurse specialist model achieved equal outcomes , while glycaemic control of patients in the nurse specialist model improved ( from 8.6 % to 8.3 % ) but deteriorated in the traditional model ( from 8.6 % to 8.8 % ; P-value between groups=0.001 ) . CONCLUSIONS The model with nurse specialists taking on roles and tasks beyond those traditionally regarded as their remit as well as new ones , is effective for the care of stable diabetic out patients The purpose of this study is to examine effects of a nurse-physician collaborative approach to care of patients with type 2 diabetes and to determine possible effect sizes for use in computing sample sizes for a larger study . Forty patients from a family practice clinic with type 2 diabetes were r and omly assigned to control or experimental groups . The control group received st and ard care , whereas the experimental group received st and ard care plus home visits from a nurse , as well as consultation with an exercise specialist and /or nutritionist . Follow-up continued for 3 months . Clinical end points included st and ard measures of diabetes activity as well as quality -of-life indicators . Focus group interviews were used to explore patients ’ responses to the program . Although findings were not statistically significant , a trend toward small to moderate positive effect sizes was found in glycosylated hemoglobin and blood pressure . Quality oflife measures also showed a trend toward small to moderate , but nonsignificant , improvements in physical functioning , bodily pain , vitality , social and global functioning , energy , impact of diabetes , and health distress . Focus group interviews indicated a very positive response from patients , who expressed feelings of empowerment . In this study , patients treated with nurse-physician collaboration demonstrated small , but nonsignificant , improvements in blood chemistry after only 3 months . Physical and social functioning , energy , and bodily pain also showed a small improvement . Changes in awareness of effects of diabetes on health and an expressed sense of self-efficacy suggest that effects could be sustainable over the longer term Background In Australia , diabetes was identified as a national health priority area in 1996 ; nevertheless the prevalence of type 2 diabetes has increased dramatically since then . Nurses have been working within Australian general practice s for several decades but only in recent years has the role of the practice nurse in primary health care increased . Objectives This review aims to identify the effectiveness of nurse‐led care in general practice as compared to general practitioner care on clinical outcomes in adults with type 2 diabetes . Inclusion criteria Types of participants Participants were adults ( aged > 18 years ) , with diabetes type 2 attending a general/family practice . Types of intervention Interventions of interest include nurse‐led care in general practice in which the nurse is identified as taking a lead role in the care of patients with type 2 diabetes compared to general practitioner‐led care . Types of studies To evaluate the effectiveness of nurse‐led diabetes care in general practice , this review sought r and omised controlled trials as the study design of choice . Other research design s such as controlled clinical trials , interrupted time series and controlled before and after design s were also considered . Types of outcomes The outcomes of interest were clinical outcomes including changes in systolic and diastolic blood pressure , body mass index , cholesterol levels , HbA1c ( glycated haemoglobin ) and fasting blood glucose . Search strategy A three step literature search was conducted for English language articles from January 1990 to December 2011 . Method ological quality Quantitative papers selected for retrieval were assessed by two independent review ers for method ological validity prior to inclusion in the review using st and ardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument . Data collection Quantitative data was extracted from papers included in the review using the st and ardised data extraction tool from the Joanna Briggs Institute . The data extracted included specific details about the interventions , population s , study methods and outcomes of significance to the review question and specific objectives . Data synthesis Data from quantitative papers , where possible , were pooled in statistical meta‐ analysis using the Meta‐ Analysis of Statistics Assessment and Review Instrument . Additionally , RevMan 5 was used for presenting forest plots of the meta‐ analysis . Results The electronic search yielded 804 potentially relevant papers of which 49 papers appeared to satisfy the criteria for inclusion and full texts of these papers were assessed against the inclusion criteria by two independent review ers . From these papers , five were included in the review , four r and omised control trials and one quasi‐experimental study . These articles provided evidence that nurse‐led care improves blood pressure and cholesterol levels for patients with type 2 diabetes attending a general practice . Conclusions There is some evidence to support the use of nurse‐led care in general practice for patients with type 2 diabetes . Implication s for Practice If nurse‐led care is implemented in the care of people with type 2 diabetes consideration needs to be given to the use of clinical algorithms , goal setting , individualised care plans , self management and follow up of lifestyle risk factors . Implication for Research More r and omised controlled trials are required to assess the efficacy of nurse‐led care including cost effectiveness OBJECTIVE This study evaluated the efficacy of a nurse-care management system design ed to improve outcomes in patients with complicated diabetes . RESEARCH DESIGN AND METHODS In this r and omized controlled trial that took place at Kaiser Permanente Medical Center in Santa Clara , CA , 169 patients with longst and ing diabetes , one or more major medical comorbid conditions , and HbA(lc ) > 10 % received a special intervention ( n = 84 ) or usual medical care ( n = 85 ) for 1 year . Patients met with a nurse-care manager to establish individual outcome goals , attended group sessions once a week for up to 4 weeks , and received telephone calls to manage medications and self-care activities . HbA(lc ) , LDL , HDL , and total cholesterol , triglycerides , fasting glucose , systolic and diastolic blood pressure , BMI , and psychosocial factors were measured at baseline and 1 year later . Annualized physician visits were determined for the year before and during the study . RESULTS At 1 year , the mean reductions in HbA(lc ) , total cholesterol , and LDL cholesterol were significantly greater for the intervention group compared with the usual care group . Significantly more patients in the intervention group met the goals for HbA(1c ) ( < 7.5 % ) than patients in usual care ( 42.6 vs. 24.6 % , P < 0.03 , chi(2 ) ) . There were no significant differences in any of the psychosocial variables or in physician visits . CONCLUSIONS A nurse-care management program can significantly improve some medical outcomes in patients with complicated diabetes without increasing physician visits Background : Logistic support to general practitioners improves the care processes for patients with diabetes but is not sufficient to meet all criteria . Aim : To introduce patient-oriented interventions by a practice nurse in general practice s which already use logistic support to improve the care processes for patients with diabetes . Design of study : A controlled before – after study with delayed intervention in the control group . Setting : 51 practice s ( n = 23 for the intervention and n = 28 for the control group ) in the south of The Netherl and s and 900 of their patients with type 2 diabetes . Methods : Data were collected on the results of the checkups ( fasting blood glucose , glycosylated haemoglobin ( HbA1C ) , cholesterol , cholesterol/high-density lipoprotein ratio , triglycerides , creatinine , blood pressure , fundus photo , foot exam and body mass index ) , smoking status , physical activity and medication use . The effect of the patient-oriented intervention was analysed in a mixed model with repeated measurement covariance structure . Results : The HbA1C improved in the intervention group ( from 7.3 to 7.1 ) , while that of the control group deteriorated ( from 7.2 to 7.3 ) . The percentage of patients with an HbA1C ⩾8.5 was halved after the intervention ( from 13 to 6 ) . Patients in the intervention group started to exercise more besides their daily activities compared with the control group . The need for medication increased more in the control group than in the intervention group ( more changes to insulin and more defined daily dose ( DDD ) oral medication ) . Conclusion : Patient-oriented interventions in addition to logistic support have a positive effect on diabetic patient outcomes M eeting the complex needs of patients with chronic illness or impairment is the single greatest challenge facing organized medical practice . Usual care is not doing the job ; dozens of surveys and audits have revealed that sizable proportions of chronically ill patients are not receiving effective therapy , have poor disease con- trol , and are unhappy with their care ( 1 ) . Results of r and omized trials also show that effective disease management programs can achieve substantially better outcomes than usual care , the control intervention . These trials , along with the ideas and efforts for improvement discussed in this issue , show that we can improve care and outcomes . As the articles suggest , these improvements will not come easily . If we are to improve care for most patients with chronic illness , the evidence strongly suggests that we reshape our ambulatory care systems for this purpose . Pri- mary care practice was largely design ed to provide ready access and care to patients with acute , varied problems , with an emphasis on triage and patient flow ; short appointments ; diagnosis and treatment of symptoms and signs ; reliance on laborato- ry investigations and prescriptions ; brief , didactic patient education ; and patient- initiated follow-up . Patients and families struggling with chronic illness have differ- ent needs , and these needs are unlikely to be met by an acute care organization and culture . They require planned , regular interactions with their caregivers , with a focus on function and prevention of exacerbations and complications . This interac- tion includes systematic assessment s , attention to treatment guidelines , and behav- iorally sophisticated support for the patient 's role as self-manager . These interactions must be linked through time by clinical ly relevant information systems and continu- ing follow-up initiated by the medical practice . Comprehensive System 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 |
12,568 | 17,077,101 | Patients treated with quinolones have a non-significant increase in colonization by quinolone-resistant bacteria .
There is no difference in the number of infections caused by pathogens resistant to quinolones .
As quinolone prophylaxis reduces the risk of death in neutropenic patients , the risk associated with colonization and infections caused by quinolone-resistant organisms does not outweigh the gain . | OBJECTIVES To assess the effect of quinolone prophylaxis following chemotherapy for malignancies on the emergence of resistant bacteria in neutropenic patients . | INTRODUCTION The use of fluoroquinolones as prophylaxis for bacterial infections in patients with chemotherapy induced neutropenia is debatable . The present study was conducted to assess the prophylactic efficacy of fluoroquinolones in adult neutropenic patients with hematologic malignancies . MATERIAL S AND METHODS For the period 1994 through 2000 a prospect i ve , r and omized trial was conducted at the University Clinic of Hematology ( Medical University , Plovdiv ) . Two groups of patients were included -- experimental group , consisting of 36 patients with 41 granulocytopenic episodes and a control group of 34 patients with 41 granulocytopenic episodes . Non parametrical and psi methods were used for statistical analysis . Kaplan-Meier test was employed to determine patients ' survival rate . Comparison of survival rates between the two groups was performed using the log-rank test . RESULTS A statistically significant difference between the two groups was found in the number of infection-free neutropenic episodes ( P < 0.001 ) , in infection-related mortality rate ( p = 0.001 ) and mortality rate within 1 month of the onset of infection ( p < 0.001 ) . Difference in long term survival rates was not statistically significant ( p > 0.05 ) . CONCLUSIONS Prophylaxis with fluoroquinolones reduced the occurrence of infection in adult neutropenic patients without affecting the long-term survival . Moreover , it is especially beneficial for patients with severe neutropenia and during the active phase of the disease We compared ciprofloxacin alone with ciprofloxacin plus rifampin ( C + R ) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support . No differences were found between groups in the time elapsed to the onset of fever , incidence of febrile episodes , amphotericin B use , and length of hospital stay . However , C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia ( five versus zero episodes ) but was associated with a higher incidence of drug-related side effects In neutropenic patients , quinolone-based oral antibacterial chemoprophylaxis has reduced morbidity and mortality attributable to aerobic gram-negative bacteria [ 1 - 3 ] . Gram-positive organisms , predominantly viridans streptococci and coagulase-negative staphylococci , have emerged as the most common pathogens isolated in association with infection among neutropenic persons receiving quinolone [ 4 - 7 ] . St and ard empiric antibacterial regimens that target aerobic gram-negative pathogens have required the addition of broader-spectrum gram-positive coverage to achieve a response [ 8 , 9 ] . Newer quinolone agents with broader in vitro gram-positive activity have recently emerged as possible c and i date s for antibacterial chemoprophylaxis regimens . Ofloxacin is a synthetic carboxyquinolone agent with in vitro activity against aerobic gram-negative bacilli similar to that of norfloxacin but with greater activity against gram-positive organisms , such as staphylococci and streptococci [ 10 ] . Early studies [ 11 - 15 ] suggested a promising role for this agent for antibacterial prophylaxis in neutropenic patients ; however , gram-positive infections have remained a problem . Strategies to reduce gram-positive infection by combining prophylactic trimethoprim-sulfamethoxazole or quinolones with other gram-positive agents , such as erythromycin [ 16 - 18 ] , roxithromycin [ 19 ] , or the penicillins [ 15 , 20 , 21 ] , have had variable success . Studies of prophylaxis with ofloxacin in neutropenic rats at the University of Manitoba [ 22 ] showed that adding rifampin to ofloxacin reduced both viridans streptococcal and staphylococcal bacteremia . Accordingly , the National Cancer Institute of Canada Clinical Trials Group design ed an open , r and omized , controlled phase III clinical trial to test the hypothesis that an increase in the gram-positive activity of an oral quinolone-based antibacterial prophylaxis regimen would have a clinical ly significant effect on the incidence of gram-positive infection in neutropenic patients with cancer receiving cytotoxic therapy . Methods Patients Patients between 18 and 70 years of age were eligible for inclusion in this trial if they 1 ) had acute myeloid leukemia or acute lymphocytic leukemia or had received an autologous bone marrow transplant ; 2 ) were receiving cytotoxic therapy for primary remission-induction , reinduction for first relapse , postremission consolidation , or conditioning for bone marrow autografting ; 3 ) had an absolute neutrophil count ( segmented plus b and neutrophils ) of 0.5 109/L or greater at study entry , with an expectation that severe neutropenia [ neutrophil count less than 0.5 109/L ] would occur at 14 days or thereafter ; 4 ) had a negative pregnancy test result [ a criterion applicable to women of child-bearing age ] ; and 5 ) provided informed written consent . Patients were excluded if they were febrile ( oral temperature more than 38 C ) ; had gastrointestinal conditions that might interfere with drug absorption ; were hypersensitive to any of the study agents ; had major renal ( serum creatinine level more than 180 mol/L ) , hepatic ( liver function test results more than twice normal ) , or cardiovascular ( uncontrolled hypertension or congestive failure ) disorders ; had received systemic antimicrobial therapy for more than 48 hours within 7 days before study entry ; or had previously been entered in this trial . Design The study was an open , r and omized , controlled phase III clinical trial . Before r and omization , patients were stratified according to diagnosis and intent of cytotoxic therapy ( primary remission-induction , reinduction , consolidation , or bone marrow autograft ) to ensure an even distribution of patients among the study groups . The r and omization list was generated by a computerized r and om-number generator . After patient eligibility was confirmed by telephone , assignments were allocated sequentially within the diagnostic grouping from the central office of the National Cancer Institute of Canada Clinical Trials Group . Equal numbers of patients were r and omly allocated to receive norfloxacin , 400 mg orally every 12 hours ; ofloxacin , 400 mg orally every 12 hours ; or ofloxacin , 400 mg orally every 12 hours , plus rifampin , 300 mg orally every 12 hours . Antibacterial prophylaxis was begun on the first day of the cytotoxic regimen and was continued until antimicrobial agents were administered parenterally for suspected infection , the neutrophil count increased to 0.5 109/L or greater , or the patient withdrew from the study for any reason . During the neutropenic period , infection was suspected if the patient 's oral temperature increased to more than 38 C on at least three occasions during a 12-hour period , if the patient 's oral temperature increased to more than 39 C on one occasion and was associated with chills or rigors , or if focal clinical signs of infection were present with a temperature greater than 38 C on one occasion . When an infection was suspected , a history was obtained , a physical examination was done , blood sample s were collected for culture , and , when appropriate , cultures were done on specimens obtained from sites of the suspected infection . Empiric antibacterial therapy with piperacillin and tobramycin was administered according to established guidelines [ 23 ] . Colonization Profiles Serial surveillance cultures of the nasopharynx , oropharynx , and rectum were taken twice weekly during the study at one participating center ( Winnipeg ) , as described elsewhere [ 24 ] , to examine the effect of allocation on clearance and acquisition of aerobic gram-negative bacilli and on acquisition and colonization by opportunistic fungi . Acquisition was defined by the isolation of a microorganism not present in baseline surveillance cultures . Colonization was defined by isolation of the same species of microorganism from at least two sequential surveillance cultures at a given site , as described elsewhere [ 24 ] . Cytotoxic Therapy Cytotoxic regimens were classified according to a cytotoxicity scale on the basis of cytarabine dosing : group 1 , cytarabine-containing regimens with a total cytarabine dose greater than 2 g/m2 body surface area ( n = 24 ; 21.6 % ) ; group 2 , cytarabine-containing regimens with a total cytarabine dose between 2 and 8 g/m2 ( n = 29 ; 26.1 % ) ; group 3 , cytarabine-containing regimens with total doses greater than 8 g/m2 [ n = 23 ; 20.7 % ] ; group 4 , regimens for acute myeloid leukemia not based on cytarabine consisting of 1 ) etoposide at total doses of 0.5 g/m2 or less plus idarubicin , mitoxantrone , or amacrine , 2 ) other high-dose etoposide-based regimens [ more than 0.5 g/m2 ] plus carboplatin or melphalan , or 3 ) a high-dose cyclophosphamide regimen ( 50 to 60 mg/kg of body weight per day ) ( n = 15 ; 13.5 % ) ; and group 5 , all other regimens ( n = 20 ; 18 % ) . Outcome Measures The primary end points were the incidence of suspected or documented infection and the spectrum of pathogens isolated . Infections were classified according to recommended guidelines [ 25 ] as microbiologically documented infections ( bacteremic or nonbacteremic ) , clinical infections , or unexplained fevers . The secondary end points included adverse events related to study drugs , infections correlated by cytotoxic regimen , the time from allocation to suspected infection , the time to response to empiric antibacterial therapy , the time to infection according to cytotoxic regimen , and the colonization profiles . Statistical Analysis Categorical variables were analyzed using the Pearson chi-square statistic or the Fisher exact test when the expected cell sizes were small . For patients who had an infection , the time from the start of prophylaxis until the beginning of parenteral therapy was used as an end point representing time to infection . For patients without an infection , the time was censored at the last date of prophylaxis . Time-to-event analyses were done using the Kaplan-Meier product-limit method [ 26 ] and were compared using the log rank test . The prognostic relation of cytotoxic therapy to bacteremic infection was examined using a Cox regression procedure [ 27 ] . A P value less than 0.05 was considered statistically significant . All tests were two sided . Results Eligibility and Evaluability One hundred twenty-seven patients were enrolled from 14 centers between 1 July 1989 and 30 June 1992 . The data set was frozen for analysis on 1 July 1994 . Seven patients were ineligible because their neutrophil counts were less than 0.5 109/L at r and omization ( n = 2 ) , they previously received systemic antibiotic therapy ( n = 3 ) , their chemotherapy was insufficiently myelosuppressive ( n = 1 ) , or the underlying diagnosis was unacceptable according to the protocol ( n = 1 ) . Of the remaining 120 patients , 9 were inevaluable because they never received the study agents ( n = 4 ) or because febrile events requiring parenteral antibiotics occurred within the first 24 hours after allocation ( n = 5 ) . Of the remaining 111 patients , 38 received norfloxacin , 38 received ofloxacin , and 35 received ofloxacin plus rifampin . All included patients had similar demographic characteristics ( Table 1 ) . Table 1 . Demographic Characteristics of Study Patients * Adverse Events Adverse events were grade d as none , mild , moderate , and severe , and the relations of these events to the study regimens were design ated as not related , possibly related , probably related , or definitely related . Gastrointestinal disturbance occurred in 28 % of norfloxacin recipients , 51 % of ofloxacin recipients , and 51 % of ofloxacin plus rifampin recipients ( p equals 0.07 ) . The incidence of gastrointestinal disturbances that were considered probably or definitely related to the study agents was very low ( 2.8 % ) and was independent of treatment allocation . No other clinical ly important side effects were seen . Compliance , measured by dose intensity , was similar in all three groups ( Table 1 ) . Five patients died during this trial . Three ( 2.7 % ) died of their presenting infections , one from each treatment group . Two others died The prophylactic efficacy of ofloxacin ( OFLX ) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospect i ve , r and omized , controlled trial . Oral administration of OFLX plus amphotericin-B ( AMPH ) and polymyxin-B ( PL ) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone ( p less than 0.01 ) , and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia ( p less than 0.01 ) . Furthermore , the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen ( p less than 0.05 ) . Clinical ly , the prophylactic efficacy was 92 % for the OFLX regimen and 40 % for the control regimen ( p less than 0.01 ) . These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy . Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy ABSTRACT The optimal oral antimicrobial prophylactic regimen for bone marrow transplant recipients remains to be eluci date d. We r and omized 84 patients to receive either oral ciprofloxacin or ciprofloxacin plus vancomycin at hospital admission . Patients were monitored for bacteremias and clinical parameters , and stool and throat swab surveillance cultures were performed . The addition of vancomycin result ed in a significant decrease in the frequency of patients with surveillance cultures positive for coagulase-negative staphylococci ( stool cultures , 44 versus 23 % ; throat swab cultures , 37 versus 19 % ) and alpha-hemolytic streptococci ( throat swab cultures , 90 versus 60 % ) . The frequencies of positivity for C and ida spp . and gram-negative organisms on surveillance cultures were comparable . Despite these results , no differences in the incidences of bacteremias ( 12 of 41 versus 12 of 43 patients ) or clinical parameters such as number of days to first fever , total number of febrile days , length of stay , and number of transfusions could be demonstrated . Because of a lack of efficacy of vancomycin and emerging problems with vancomycin-resistant isolates , vancomycin should not be used in oral antimicrobial prophylaxis regimens A r and omized , double-blind , placebo-controlled trial was conducted in eight hematologic units to determine the efficacy and safety of oral enoxacin for infection prevention in adult patients with acute nonlymphocytic leukemia . One hundred nineteen patients undergoing remission induction or consolidation chemotherapy were enrolled ; 62 of them received enoxacin ( 400 mg orally every 12 h ) . Patients received antifungal prophylaxis with oral mycostatin ( 1,000,000 U four times daily ) or clotrimazole ( 1 troche five times daily ) . Analysis was performed on an intent-to-treat basis . There was no significant difference between groups in race , age , or type and stage of leukemia , but there were more males in the placebo group ( P = 0.073 [ Fisher 's exact test ] ) . Fewer enoxacin patients had gram-negative bacteremia ( 1 versus 14 [ P < 0.001 ] ) , gram-negative infection at any site ( 2 versus 19 [ P < 0.001 ] ) , or bacterial and /or fungal infection ( 17 versus 26 [ P = 0.056 ] ) . There was no significant difference in the number of patients with gram-positive infection at any site ( 12 versus 16 ) , gram-positive bacteremia ( 9 versus 10 ) , deep fungal infection ( 6 versus 2 ) , death ( 2 versus 3 ) , other antimicrobial therapy required ( 48 versus 48 ) , therapy with amphotericin B ( 15 versus 7 [ P = 0.105 ] ) , any adverse event ( 45 versus 36 ) , or any study drug-associated adverse events ( 13 versus 6 ) . Logistic regression confirmed ( odds ratios and 95 % confidence intervals are given in parentheses ) that enoxacin reduced the risk of gram-negative infection ( 0.07 ; 0.01 to 0.30 ) , especially gram-negative bacillary bacteremia ( 0.05 ; 0.01 to 0.37 ) , without altering the risk of gram-positive bacterial ( 0.63 ; 0.26 to 1.5 ) , deep fungal ( 2.57 ; 0.47 to 13.9 ) , or Clostridium difficile ( 1.16 ; 0.3 to 4.56 ) infection . The median time to the onset of fever of more than or equal 102.8 F ( 39.3 degree C ) was 32 days for the enoxacin group versus 15 days for patients receiving placebo ( P=0.0007 [ Wilcoxon test ] ) . In patients with acute nonlymphocytic leukemia , oral enoxacin prevents gram-negative infections , delays the onset of fever , does not alter the incidence of gram-positive or proven deep fungal infections , and is well tolerated To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia , oral pefloxacin plus vancomycin ( PV ) ( n = 76 ) or gentamicin , colistin sulphate and vancomycin ( GCV ) ( n = 74 ) were administered in a r and omised double-blind study . Infections were significantly less severe in the PV than in the GCV group . Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV . Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV , because of fewer infections with Staphylococcus species and enterobacteriaceae . Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group . Thus , PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients , despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract PURPOSE To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy ( HDC ) with peripheral-blood stem-cell transplantation ( PBSCT ) decreases the incidence of neutropenia and fever , Gram-positive bacteremia , and infection-related morbidity . PATIENTS AND METHODS Patients with solid tumors undergoing HDC with PBSCT were r and omized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours . Prophylaxis was started 48 hours before stem-cell reinfusion . Patients were monitored to document the occurrence of neutropenia and fever , incidence and cause of bacterial infection , time to onset and duration of fever , requirement for intravenous antimicrobials , and length of hospital admission . RESULTS Sixty-five patients were r and omized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin , and from these groups , 62 and 61 were assessable , respectively . The proportion of patients who developed neutropenia and fever was 87 % in the group treated with ciprofloxacin and 78 % in the group treated with ciprofloxacin and rifampin ( P = .25 ) . Although there was a trend toward a reduction in the overall incidence of bacteremia ( 12 v 4 patients ) , and Gram-positive bacteremia ( 8 v 2 patients ) with the addition of rifampin , none of these comparisons was statistically significant ( P = .05 and P = .09 , respectively ) . CONCLUSION The results of this study , which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects , do not support the routine use of rifampin in this setting In order to evaluate whether the prophylactic use of fluoroquinolones diminishes the incidence of infections and /or mortality during neutropenia , we undertook a prospect i ve , aleatory and controlled study in non-hospitalized adult patients with acute leukemia and chemotherapy-induced neutropenia including twenty five episodes of neutropenia including twenty five episodes of neutropenia which had occurred in 14 patients who were r and omly selected either to receive or not quinolones ( norfloxacin 800 mg daily or ciprofloxacin 1000 mg daily ) . Both groups were similar in terms of sex , age , underlying disease , chemotherapy for hematologic malignancy , duration and severity of neutropenia . The use of quinolones was associated with a delay in the fever onset during neutropenia ( p = 0.0448 ) , a decrease in the proportion of neutropenic febrile days ( p = 0.0456 ) , a decrease of infections caused by gram-negative bacilli ( p = 0.037 ) and an increase of Streptococcus infections ( p = 0.0857 ) . There was no significant decrease in mortality , incidence of severe infections , proportion of neutropenic episodes without fever , empiric use of amphotericin B or fungal infections between both groups . The results of this study demonstrate that the prophylactic use of fluoroquinolones does not diminish the infectious morbidity and /or mortality in these patients Following a 2‐year study , the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance . During a 2‐year period ( 1987–1989 ) , we compared ciprofloxacin + colistin ( CIP + COL ) with neomycin + colistin ( NEO + COL ) in a r and omized trial – combinations chosen because of the potential for prophylaxis of Gram‐negative infection by ciprofloxacin , with colistin given to reduce the risk of emergence of resistance . Sixty‐four patients with similar demographics in each arm were evaluable for efficacy analysis . Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever ( P < 0·001 ) and neutropenic days on intravenous antibiotics ( P < 0·001 ) than patients on NEO + COL . A total of 54 ( 15 bacteriologically documented ) pyrexial episodes occurred in patients on CIP + COL and 77 ( 41 bacteriologically documented ) in patients on NEO + COL . Only two Gram‐negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm . No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients . Two CIP‐resistant Gram‐negative bacilli were isolated from patients on CIP + COL compared with 13 NEO‐resistant Gram‐negative bacilli from patients on NEO + COL . Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients , a 2‐year follow‐up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 350–400 neutropenic episodes . Eight of the 111 ( 7·2 % ) isolates were with ciprofloxacin‐resistant organisms , involving 2 % of the neutropenic episodes , indicating that the strategy of combining colistin with ciprofloxacin has been effective in the prevention of Gram‐negative sepsis in neutropenic patients without the emergence of significant resistance despite widespread concurrent hospital and community use of the quinolones Preliminary results are presented of an ongoing , prospect i ve , r and omized , study comparing ofloxacin , ciprofloxacin and co-trimoxazole/colistin for the prevention of infection in patients with acute leukaemia . The results for 59 patients ( median age 47 years , range 21 - 72 ) included 88 episodes of neutropenia , each associated with a course of cytotoxic therapy . The main factor measured was the time elapsed from the beginning of neutropenia ( neutrophils less than 500/microliter ) until the first infectious febrile episode . The median time for the period was 12 days ( range 1 - 56 ) for the cotrimoxazole/colistin group , 15 days ( range 1 - 38 ) for the ofloxacin group and 20 days ( range 1 - 36 ) for the ciprofloxacin group ( differences not significant ) . Microbiologically proven major infections occurred in 10/27 treatment courses with co-trimoxazole/colistin 7/31 courses with ofloxacin and 7/30 courses with ciprofloxacin ( P not significant ) . These were mostly due to Gram-positive cocci . There were no Gram-negative infections in the quinolone groups compared with one major Pseudomonas aeruginosa infection in the co-trimoxazole/colistin group . No Pneumocystis carinii infections were encountered . Adverse reactions associated with co-trimoxazole/colistin required discontinuation of medication in 11/27 treatment courses because of compliance problems , skin reactions or gastrointestinal intolerance . There were significantly fewer discontinuations in the ofloxacin ( n = 2 ) and in the ciprofloxacin groups ( n = 3 ) . Major side effects of the quinolones included persistent icterus in one patient receiving ofloxacin and psychiatric symptoms in one patient receiving ciprofloxacin . It is concluded from these data that there were no statistically significant differences between the three treatment groups in respect of the prevention of infection . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia . Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones , but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis . METHODS This prospect i ve observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia , after chemotherapy for hematologic malignancies . RESULTS After a 12-month baseline period of levofloxacin prophylaxis , a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks , because the mortality rate ( 33.3 % ) was higher than that with routine fluoroquinolone prophylaxis ( 2.9 % ) ( odds ratio [ OR ] , 16.6 ; 95 % confidence interval [ CI ] , 3.6 - 77.2 ) . Fewer patients had gram-negative bacteremia during the baseline period ( 4.8 % ; n=15 ) than during the discontinuation period ( 44.4 % ; n=4 ) ( OR , 16.9 ; 95 % CI , 4.1 - 70.0 ) . After levofloxacin therapy was reintroduced , the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period . Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro , whereas all E. coli isolates isolated during both prophylaxis periods were resistant . Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis , whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation . CONCLUSIONS These findings suggest that , despite increasing rates of antimicrobial resistance , levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality . Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis PURPOSE To compare the efficacy and safety of ciprofloxacin ( CIP ) and trimethoprim/sulfamethoxazole ( TMS ) for the prevention of bacterial infections in patients who received bone marrow transplantation ( BMT ) for the treatment of solid and hematopoietic neoplasms . PATIENTS AND METHODS Adult in patients about to undergo BMT for lymphoma , leukemia , or solid tumors were enrolled onto a prospect i ve , r and omized , double-blinded , controlled trial that compared CIP ( 750 mg orally twice per day ) with TMS ( 160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day ) . Subjects were stratified before r and omization according to tumor and BMT type . Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever , signs or symptoms of infection , serious adverse effects , or recovery of the absolute granulocyte count ( AGC ) to > or = to 400/microL. RESULTS Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy . No difference was noted between the two groups in occurrence of fever during neutropenia , time to onset of first fever , or overall infection rates . Ten bacteremias occurred in CIP recipients versus six in TMS recipients ( P = .43 ) . Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients ( P = .001 ) . Four infections caused by gram-negative bacilli , including one bacteremia , occurred in TMS recipients versus none in CIP recipients ( P = .06 ) . No differences were noted in the incidence of rash or organ toxicity . TMS recipients had longer duration s of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients ( P = .08 for both comparisons ) . Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis . CONCLUSION CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point . TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli , as well as a trend toward prolongation of granulocytopenia The effect of a combination regimen using norfloxacin ( NFLX ) and amphotericin B ( AMPH-B ) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a r and omized , controlled trial was studied . One hundred and six consecutive , evaluable patients were r and omly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily , or amphotericin B only . A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group ( 34.6 % vs 56.9 % ; P < 0.05 ) . The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group ( 23 days vs 30 days ; P < 0.05 ) . The percentage of patients with a gram-negative bacterial infection ( 9.6 % vs 27.5 % ; P < 0.05 ) or a fungal infection ( 17.3 % vs 37.3 % ; P < 0.05 ) was decreased in the study group . This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole . A total of 102 patients with hematological malignancies were r and omly selected to receive either co-trimoxazole or ofloxacin . All patients were monitored for compliance , occurrence of infection , and drug-related side effects . A surveillance culture of a rectal swab was performed regularly . A total of 25 of the 52 patients ( 48 % ) who received co-trimoxazole and 11 of the 50 patients ( 22 % ) who received ofloxacin developed fever during the study period ( P less than 0.025 ) . Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group ( 17 % ) but in only one patient ( 2 % ) in the ofloxacin group ( P less than 0.05 ) . No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection . Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia . The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin . Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment ( P less than 0.05 ) . Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a r and omized trial comparing ciprofloxacin with polymyxin B for prevention of infections . Both groups ( 12 patients each group ) received amphotericin B for antifungal prophylaxis . 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B. Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days , compared with 4.3 days for the polymyxin B group ( p less than 0.01 ) . Patients receiving ciprofloxacin also had fewer days of fever ( average 6.5 days versus 9.8 days for the polymyxin B group , p less than 0.02 ) . Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group ( p less than 0.001 ) . Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B , this did not reach statistical significance . These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia 230 leukaemic patients were entered into a r and omised , prospect i ve , multicentre trial of either ciprofloxacin ( 1 g/day ) or co-trimoxazole ( 1920 mg/day ) plus colistin ( 800 mg/day ) for the prevention of infection during granulocytopenia . Bacteraemia due to resistant gram-negative rods occurred only in the co-trimoxazole-colistin group though both regimens were effective for selective gastrointestinal tract decontamination . However , there were fewer patients without any infective complications ( 31 % vs. 18 % : P = 0.02 ) , fewer febrile days [ mean ( S.D. ) 5.9 ( 1.1 ) vs. 8.2 ( 1.4 ) : P = 0.0242 ] , a lower proportion of infective events ( 0.9 ( 0.16 ) vs. 1.2 ( 0.18 ) : P = 0.005 ) and fever occurred later ( median 19 vs. 14 days : 0.025 less than P less than 0.05 ) in the co-trimoxazole-colistin group . The choice of prophylactic regimen therefore appears to depend upon whether or not protection against gram-negative infection is required or better systemic prophylaxis overall Norfloxacin ( NOR ) or cotrimoxazole ( TMP/SMX ) were r and omly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections . Nineteen NOR patients ( 65 % ) and 22 TMP/SMX patients ( 73 % ) complained of febrile or infectious episodes during the study . The mean incidence of febrile complications per patient was higher in the TMP/SMX group : 1.05 vs 0.68 ( p less than 0.05 ) . Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli ( GNB ) . NOR recipients had fewer days of fever , fewer days on parenteral antibiotics and a lower proportion of time spent febrile . Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group ( resistant strains : 93 % ) and in 8/75 specimens in the NOR group ( 1 resistant strain ) . Overall , NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients 59 patients who had earlier developed an infection following antineoplastic chemotherapy were r and omised to receive either granulocyte colony-stimulating factor ( G-CSF ) alone or G-CSF+quinolone as prophylaxis during subsequent identical chemotherapy courses . 30 patients received 48 courses of G+CSF , while 29 patients received 44 courses of G-CSF+ofloxacin or ciprofloxacin . The overall infection rate was 23 % . Patients with WHO grade IV leukopenia at the onset of prophylactic treatment developed infection in 61 % of cases when on G-CSF , but only in 22 % when on G-CSF+quinolone ( P = 0.002 ) . Patients with initial leukopenia of grade WHO III-I had only a 11 % infection rate showing no significant difference between the treatment groups . The median duration of leukopenia < 1 x 10(9)/l was 4 days for patients receiving G-CSF alone and 3.5 days for those receiving additional quinolone . Patients developing infection had grade IV leukopenia for a median of 5 days . Both prophylactic treatments were well tolerated . We conclude that when prophylactic G-CSF is initiated at WHO grade IV leukopenia , addition of an oral quinolone reduces the risk of infection OBJECTIVE To compare the efficacy of norfloxacin and ciprofloxacin in preventing bacterial infection in neutropenic patients . DESIGN A r and omized , controlled , multicenter trial . SETTING Twenty-one hematologic units in tertiary care or university hospitals . PATIENTS Eight hundred and one consecutive , afebrile , adult patients who had hematologic malignancies or who had bone marrow transplantation and chemotherapy-induced neutropenia ( neutrophil count , less than 1000/mm3 ) expected to last more than 10 days . INTERVENTION Patients were r and omly assigned to receive orally every 12 hours norfloxacin , 400 mg , or ciprofloxacin , 500 mg . MEASUREMENTS Efficacy analysis was done for 619 patients : 319 treated with norfloxacin and 300 treated with ciprofloxacin . MAIN RESULTS More patients receiving ciprofloxacin did not develop fever during neutropenia and did not receive antibiotics ( 34 % ) compared with those receiving norfloxacin ( 25 % ) ( P = 0.01 ) . Patients receiving ciprofloxacin had a lower rate of microbiologically documented infection ( 17 % compared with 24 % ; P = 0.058 ) , particularly of infection from gram-negative bacilli ( 4 % compared with 9 % ; P = 0.03 ) . The interval to the first febrile episode was also longer in patients receiving ciprofloxacin ( 8.3 compared with 7.2 days ; P = 0.055 ) . The rates of clinical ly documented infection , fever of unknown origin , and mortality as well as compliance and tolerability were similar in the two groups . Patients who had neutropenia for less than 15 days , who had severe neutropenia for less than 7 days , and who received antifungal prophylaxis benefited most from ciprofloxacin therapy . CONCLUSION Ciprofloxacin should be used to prevent the development of infection in neutropenic patients with hematologic malignancies Summary Background : The objective of this study was to characterize the prevalence and clinical significance of ciprofloxacin-resistant Escherichia coli in perianal swabs of patients with hematologic malignancies in a German university hospital . Patients and Methods : Weekly surveillance cultures were performed for 26 weeks . 294 perianal swabs were obtained from 104 consecutive patients . Species discrimination , susceptibility testing and genotyping using pulsed-field gelelectrophoresis ( PFGE ) was performed for all E. coli isolates . Preceding antibiotic prophylaxis and treatment as well as the frequency and duration of the hospital stay in the 6 months prior to the study were analyzed . Results : A total of 31 patients ( 29.8 % ) were colonized with E. coli strains . Although 81.8 % of the patients colonized with ciprofloxacin-resistant E. coli had received former treatment with ciprofloxacin , this finding did not reach statistical significance , probably due to the small study population . During the surveillance period one of the colonized patients developed septicemia with a ciprofloxacin-resistant E. coli . Genotypic identity was demonstrated for the E. coli isolates from perianal swab and blood culture . Conclusion : We propose that selective gut decontamination with ciprofloxacin should be discontinued as a routine measure for all neutropenic patients in the department under investigation . We propose waiving oral decontamination in low-risk patients with neutropenia of only a few days duration . For all other patients , a regimen with alternating prophylactic treatments of cotrimoxazol and fluoroquinolone should be considered OBJECTIVE To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia . PATIENTS AND METHODS Oral pefloxacin plus vancomycin ( 48 patients ) , pefloxacin alone ( 51 patients ) , or placebo ( 52 patients ) were administered in a r and omized double-blind study . Evaluation was done by determining site and documentation of infections , organisms responsible for bacteriologically documented infections , organisms acquired in surveillance cultures and number of days with fever during aplasia . RESULTS Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae . No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive ( Gram+ ) infections and infections with gram-negative ( Gram- ) organisms usually resistant to pefloxacin . However , placebo gave similar results . There was no induction of resistance to pefloxacin during the study . Tolerance of treatment was excellent . Only a prolonged aplasia has been observed in patients receiving pefloxacin . CONCLUSION Thus , the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient . The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be question able Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection , but it is ineffective against gram-positive bacterial infections in the bloodstream , particularly those caused by streptococci and coagulase-negative staphylococci , which appear to have emerged as significant causes of morbidity , decreased treatment efficacy , and the increased costs of empiric antimicrobial therapy . In a prospect i ve , r and omized , open trial , we evaluated the efficacy and safety of oral roxithromycin ( 150 mg twice daily ) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin . In comparison with patients given ofloxacin alone , fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci ( incidence , 9 versus 0 % ; P = 0.03 ) , while the incidence of bacteremia caused by other organisms , the incidence of febrile episodes from any cause , the risk of infection-associated complications ( including prolonged or secondary fever , pneumonia , septic shock , need for mechanical ventilation , and /or infection-related death ) , and antimicrobial usage for therapy were comparable between both groups . Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment ( P = 0.05 ) . Although effective for the prevention of streptococcal bacteremia , the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia , but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications BACKGROUND The role of prophylactic antibacterial agents after chemotherapy remains controversial . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary , severe neutropenia ( fewer than 500 neutrophils per cubic millimeter ) . Patients were r and omly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period . The primary outcome was the incidence of clinical ly documented febrile episodes ( temperature of more than 38 degrees C ) attributed to infection . Secondary outcomes included the incidence of all probable infections , severe infections , and hospitalization but did not include a systematic evaluation of antibacterial resistance . RESULTS A total of 1565 patients underwent r and omization ( 784 to placebo and 781 to levofloxacin ) . The tumors included breast cancer ( 35.4 percent ) , lung cancer ( 22.5 percent ) , testicular cancer ( 14.4 percent ) , and lymphoma ( 12.8 percent ) . During the first cycle of chemotherapy , 3.5 percent of patients in the levofloxacin group had at least one febrile episode , as compared with 7.9 percent in the placebo group ( P<0.001 ) . During the entire chemotherapy course , 10.8 percent of patients in the levofloxacin group had at least one febrile episode , as compared with 15.2 percent of patients in the placebo group ( P=0.01 ) ; the respective rates of probable infection were 34.2 percent and 41.5 percent ( P=0.004 ) . Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group ( P=0.004 ) . The respective rate of severe infection was 1.0 percent and 2.0 percent ( P=0.15 ) , with four infection-related deaths in each group . An organism was isolated in 9.2 percent of probable infections . CONCLUSIONS Among patients receiving chemotherapy for solid tumors or lymphoma , the prophylactic use of levofloxacin reduces the incidence of fever , probable infection , and hospitalization The efficacy of oral prophylaxis with ciprofloxacin , ofloxacin or pefloxacin was assessed in preventing bacterial infection in neutropenic patients with treatment being allocated r and omly before beginning chemotherapy . Bacteraemia developed in six of 78 episodes ( 8 % ) treated with ciprofloxacin , in eight of 80 ( 10 % ) allocated to ofloxacin and in 12 of 77 ( 16 % ) when pefloxacin was given . However , there were no episodes involving Gram-negative bacilli among those given ciprofloxacin whereas three and seven episodes occurred in patients given ofloxacin or pefloxacin respectively ( P = 0.013 ) . With the exception of Pseudomonas aeruginosa , all potential pathogens isolated were resistant to all three fluoroquinolones . Faecal anaerobes were not affected by treatment with pefloxacin whereas their total numbers were reduced in 12 cases who had received ofloxacin and in nine cases who had been given ciprofloxacin ( P = 0.002 ) . Fourteen patients ( 18 % ) were colonized with pefloxacin resistant P. aeruginosa at the end of treatment with this agent compared with only two and five of those given ciprofloxacin or ofloxacin respectively . A similar trend was seen with other resistant Gram-negative bacilli colonizing 14 % , 20 % and 23 % of patients for ciprofloxacin , ofloxacin and pefloxacin , respectively . Ciprofloxacin was therefore superior to the other two fluoroquinolones in preventing infections due to Gram-negative bacteria in this population of neutropenic patients PURPOSE To study whether oral ciprofloxacin would be as effective in preventing bacterial infections in severely myelosuppressed patients as selective antibiotic modulation of the gut flora with neomycin/polymyxin B sulfate/nalidixic acid ( NPN ) . PATIENTS AND METHODS One hundred and five patients undergoing allogeneic or autologous bone marrow transplant , or induction therapy for acute leukemia in 1988 and 1989 were studied . Patients were stratified according to the type of therapy , and r and omized in a ratio of 2:1 to either oral ciprofloxacin 500 mg BID , or a combination of oral neomycin 250 mg QID , polymyxin-B 100 mg QID , and oral nalidixic acid 1,000 mg BID . Treatment began on admission and continued until the absolute granulocyte count was greater than 500/mm3 for 3 consecutive days . RESULTS The 96 evaluable patients were evenly distributed over the 3 treatment groups ; 63 patients received ciprofloxacin and 33 received NPN . Fever developed in 92 % of patients on ciprofloxacin and in 97 % of patients on NPN . ( P = 0.66 ) , 6.6 + /- 5.8 and 7.2 + /- 5.3 days from the start of prophylaxis , respectively . Twenty-five patients on ciprofloxacin developed 29 microbiologically documented infections , fewer than the 26 infections in the 22 patients on NPN ( P = 0.02 ) . Patients on ciprofloxacin had fewer bacteremias ( 33 % ) than did the NPN patients ( 55 % ) ( P = 0.05 ) . Gram-negative bacteremias were very rare ( 2 cases ; no Enterobacteriaceae ) , but streptococcal bacteremias were frequent in both arms ( 27 cases ) . Side effects were not significantly different , but compliance with ciprofloxacin was better . CONCLUSIONS Ciprofloxacin is at least as effective as the combination of neomycin/polymyxin/nalidixic acid in the prophylaxis of bacterial infections in myelosuppressed patients , and is better tolerated . Additional agents to prevent streptococcal infections are needed Ofloxacin ( 300 mg twice a day ) and trimethoprim-sulfamethoxazole ( TMP-SMZ ) ( 160 mg trimethoprim and 800 mg sulfamethoxazole twice a day ) were given prophylactically to 19 adult patients with acute leukemia undergoing induction chemotherapy . The influence of the two regimens on the bacterial aerobic flora was evaluated . Both of the prophylactic regimens conditioned the aerobic microflora of the patients . Both groups acquired new microorganisms , prevalently gram-positive cocci , but also gram-negative bacteria with the TMP-SMZ regimen . Both treatment groups acquired yeasts Bacterial infection is a common complication after allogeneic bone marrow transplantation . It is related to the toxic effects of the conditioning regimen on mucosal surfaces , to bone marrow aplasia and to the prolonged lymphopenia with immune deficiency that lasts for several weeks after bone marrow transplantation . We have performed a prospect i ve r and omized study comparing two methods of prophylaxis . Group I ( OA ) received a combination of ofloxacin 400 mg/day and amoxicillin 20 g/day ; group II ( VTC ) received the oral nonabsorbable antibiotics vancomycin 450 mg/day , tobramycin 450 mg/day and colistin 4.5.10(6 ) units daily , from day -15 to 15 days after discharge from laminar air flow ( LAF ) rooms . All patients were nursed in LAF rooms with a strict isolation procedure and sterile water and food . They were evaluated daily for clinical symptoms , and bacterial culture sample s were taken from the throat , stools and blood twice weekly . Forty-four patients were r and omized , 22 entered in group I ( OA ) and 22 in group II ( VTC ) . There were no differences between the two groups in age ( mean 33 years , range 11 - 54 ) , sex , diagnosis and mean duration of agranulocytosis ( 21.8 days , range 10 - 49 ) . Seven patients were excluded because of the selection of a resistant bacteria , 5 were in group I ( OA ) , and 2 were in group II ( VTC ) . The mean duration of fever was 9.2 + /- 7.1 days in group I ( OA ) and 13.7 + /- 6.8 days in group II ( VTC ; p = 0.05 ) . There were no significant differences between the two groups in graft-versus-host disease . ( ABSTRACT TRUNCATED AT 250 WORDS In this study the efficacy of norfloxacin and pefloxacin for the antibacterial prophylaxis of granulocytopenia was compared in cancer patients following cytostatic treatment . A total of 136 patients was r and omly selected to receive either norfloxacin or pefloxacin . Nineteen patients remained afebrile in the norfloxacin group compared with thirty one in the pefloxacin group ( p = 0.045 ) . Twenty four microbiologically documented infections ( twelve with and twelve without bacteraemia ) occurred in sixty seven patients taking norfloxacin , and twelve in sixty nine patients taking pefloxacin ( five with and seven without bacteraemia ) ( p = 0.015 ) . Only one infection caused by Gram-negative bacilli was observed in the pefloxacin group compared with seven in the norfloxacin group ( p = 0.019 ) . In conclusion , both microbiological and clinical results showed pefloxacin to be a better antibacterial agent than norfloxacin for these patients In a consecutive series of 65 patients treated by allogeneic bone marrow transplantation , we have compared the efficacy on prevention of bacterial infection of total gut decontamination with oral non absorbable antibiotics or with oral absorbable broad spectrum antibiotics . On day-8 , all patients were r and omly allocated to one group : Group I received orally pefloxacin 400 mg/day and penicillin 3 M UI/day . Group II received capsules containing cephalothin 250 mg , gentamicin 20 mg and bacitracin 150 UI . Each patient received 9 to 12 capsules per day according to body weight . Patients less than 5 years old or with severe hepatic abnormalities were excluded from the study . All patients were treated in LAF room with usual pre caution s of asepsis . They received sterile food . In addition , they were on ketoconazole for prophylaxis of fungal infections and acyclovir for prevention of herpes infections . Antibiotics were started on day-8 before bone marrow transplantation and stopped 15 days after discharge from the hospital . 32 patients were allocated to Group I and 33 in Group II . There was no difference between both groups according to age , sex , diagnosis . After transplant , the one year survival and the complications were similar in both groups . The median time of decontamination was 65 days , the mean number of days of agranulocytosis was 20 days , the mean number of days of fever was 7 days in both groups . The compliance was better in Group I but the treatment had to be modified in 9 patients of Group I because of liver abnormalities . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The results of a r and omised , prospect i ve trial to investigate the efficacy of prophylactic treatment with ofloxacin during granulocytopenia after cytostatic treatment are presented . 42 patients with metastasised testicular germ-cell tumours entered the study . Cytostatic treatment consisted of at least 4 courses , 2 of which were succeeded by prophylactic treatment with ofloxacin . Three patients undergoing prophylactic treatment developed fever . Fever occurred in 16 patients during control phases ( no ofloxacin prophylaxis ) of cytostatic treatment . Seven of the 19 infections could be documented microbiologically . No side effects that related to ofloxacin were noted . In conclusion , ofloxacin was highly effective in the prevention of infection and , therefore , should be given prophylactically to patients with granulocytopenia Sixty-five cancer patients pretreated with chemo or radiotherapy , with granulocytopenia less than 1000/mm3 and without fever , were entered into this study : 30 of them were su bmi tted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group . 20 % of the treated subjects versus 68.6 % of the controls presented a subsequent infection ( P less than 0.001 ) , the lung representing the most frequent site of the infectious disease in both groups ( 3/6 and 14/24 respectively ) . These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile , granulocytopenic cancer patients , especially as far as gram-negative infections are concerned . Because of the high prevalence of lung cancer in the patients of our study , and a related prevalence of lung infections , at the present time , a wider use of this antibiotic in every kind of solid tumor can not be generalized We evaluated the effect of norfloxacin , 400 mg given orally every 12 hours , on the prevention of bacterial infections in 68 adult patients who had acute leukemia throughout prolonged courses of granulocytopenia ( median , 32 days ) . Gram-negative infections were documented in 13 of the 33 patients receiving placebo , but only in 4 of the 35 patients receiving norfloxacin ; no effect on the frequency of gram-positive or fungal infections was noted . Norfloxacin administration result ed in the suppression of gastrointestinal tract colonization by aerobic bacteria without the development of norfloxacin resistance . Patients receiving norfloxacin developed first infectious fevers later than did those receiving placebo , had more rapid resolution of that fever after systemic antibiotic treatment , and spent less time febrile . Therefore , although no difference was seen in survival duration , we found that the prophylactic administration of oral norfloxacin led to decreases in overall morbidity and gram-negative infections , was well tolerated , and did not predispose to the development of multiply drug-resistant bacteria Summary Escherichia coli with high-level fluoroquinolone resistance were isolated from feces and /or various body sites of 16 cancer patients who were on oral fluoroquinolone prophylaxis . Population analysis of fecal isolates in 11 patients showed that fluoroquinoloneresistantE. coli was the only aerobic gram-negative bacillus present and exhibited a relatively homogenous fluoroquinolone MIC distribution . Molecular typing by pulsed field gel electrophoresis of chromosomal DNA digests or by r and om amplified polymorphic DNA fingerprinting confirmed the clonal nature of gastrointestinal tract colonization withE. coli . Genotyping of ten colonies picked from the same fecal culture demonstrated identical strains in four of four patients examined . Identical genotypes from the same patient were isolated over prolonged periods of time in 12 of 12 cases examined , with one patient ( with the longest follow-up of 14 months ) who lost his initial genotype and became persistently colonized with a new genotype . In the 11 patients who developed infection due to fluoroquinolone-resistantE. coli , molecular typing also indicated that fecal colonization was associated with , and presumably preceded infection due to an indistinguishable genotype of fluoroquinolone-resistantE. coli Summary In a prospect i ve r and omized study we evaluated the efficacy and safety of oral ofloxacin ( dosage : 200 mg three times daily ) versus trimethoprim-sulfamethoxazole ( dosage : 960 mg three times daily ) as antibacterial prophylaxis in 128 patients with acute leukemia who received aggressive cytotoxic chemotherapy and were granulocytopenic for a median duration of 30 days . Fewer patients receiving ofloxacin were colonized byEnterobacteriaceae ( 13 % versus 90 % , p<0.001 ) and Pseudomonas aeruginosa ( 3 % versus 14 % , p=0.025 ) , and developed gram-negative bacterial infection ( 4 % versus 26 % , p=0.002 ) , whereas the incidence of gram-positive bacterial ( 19 % versus 22 % ) and fungal ( 7 % versus 14 % ) infections was similar in both groups . Ofloxacin was significantly better tolerated than trimethoprim-sulfamethoxazole , and shortened the duration of fever ( p=0.02 ) and of parenteral antimicrobial therapy for presumed or documented acquired infection ( p=0.01 ) . Ofloxacin appears to be a safe , effective , well-tolerated alternative to trimethoprim-sulfamethoxazole for preventing gram-negative infection in acute leukemia , but more effective prophylaxis of gram-positive infections is still needed . ZusammenfassungIn einer prospektiven , r and omisierten Studie wurden die Wirksamkeit und Verträglichkeit von Ofloxacin ( dreimal 200 mg täglich ) i m Vergleich mit Trimethoprim-Sulfamethoxazol ( dreimal 960 mg täglich ) als antibakterielle Prophylaxe bei Patienten mit akuter Leukämie geprüft . Beurteilbar waren 128 Patienten , die eine aggressive cytostatische Chemotherapie erhielten , mit einer medianen Granulozytopeniedauer von 30 Tagen . In der Ofloxacin-Gruppe wurde eine Kolonisierung mitEnterobacteriaceae ( 13 % gegenüber 90 % , p<0.001 ) undPseudomonas aeruginosa ( 3 % gegenüber 14 % , p=0.025 ) wesentlich seltener beobachtet als in der Trimethoprim-Sulfamethoxazol-Gruppe . Patienten , die Ofloxacin erhielten , entwickelten auch weniger gram-negative Infektionen ( 4 % gegenüber 26 % , p=0.002 ) , während die Inzidenz von gram-positiven bakteriellen ( 19 % gegenüber 22 % ) und von Pilzinfektionen ( 7 % gegenüber 14 % ) in beiden Gruppen vergleichbar war . Ofloxacin war besser verträglich und verkürzte die Feiberdauer ( p=0.02 ) sowie die Dauer der parenteralen antimikrobiellen Beh and lung von vermuteten oder dokumentierten erworbenen Infektionen ( p=0.01 ) . In der Prophylaxe gramnegativer Infektionen bei Patienten mit akuter Leukämie erscheint Ofloxacin daher eine wirksamere und besser verträgliche Alternative zu Trimethoprim-Sulfamethoxazol zu sein . Möglichkeiten einer gezielten Prophylaxe gegen grampositive Infektionen sollten jedoch weiterhin überprüft werden INTRODUCTION The efficacy and safety of oral ofloxacin were compared with those of vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients undergoing chemotherapy for hematologic malignancy . PATIENTS AND METHODS Antimicrobial prophylaxis was begun at the time of initiation of chemotherapy . Thirty patients received ofloxacin tablets ( 300 mg orally every 12 hours ) plus a nystatin suspension . Thirty-two patients received vancomycin capsules ( 500 mg orally every eight hours ) and polymyxin capsules ( 100 mg orally every eight hours ) plus a nystatin suspension . RESULTS In the group of patients receiving ofloxacin , there were a lower number of acquired gram-negative bacillary organisms per patient ( 0.13 versus 1.37 , p less than 0.00005 ) , fewer patients with documented infection ( 11 of 30 versus 21 of 32 , p = 0.04 ) , and fewer cases of gram-negative septicemia ( zero of 30 versus five of 32 , p = 0.05 ) . Ofloxacin was also better tolerated ( 24 of 30 versus 10 of 32 patients highly compliant , p = 0.01 ) and associated with fewer gastrointestinal side effects ( one of 30 versus nine of 32 patients with gastrointestinal side effects , p = 0.01 ) than vancomycin/polymyxin . However , except for a reduction of Staphylococcus aureus colonization and infection by ofloxacin , neither ofloxacin nor vancomycin/polymyxin was effective in eliminating colonization or infection with viridans group streptococci , coagulase-negative staphylococci , or other gram-positive organisms . Only three isolates of ofloxacin-resistant gram-negative bacteria ( Pseudomonas fluorescens , Pseudomonas putida , and Enterobacter aerogenes ) were isolated from surveillance cultures , but none caused infection . CONCLUSION These results suggest that oral ofloxacin is a more tolerable and efficacious alternative to vancomycin/polymyxin for prevention of serious gram-negative bacillary infections in granulocytopenic patients . More effective prophylaxis of gram-positive infections , however , is still needed Summary Co-trimoxazole or norfloxacin were r and omly administered to 44 granulocytopenic children with malignancies in order to prevent bacterial infections . Although more patients in the co-trimoxazole group had febrile episodes ( p<0.01 ) , the mean of febrile days and the mean of days with systemic antibiotics did not differ significantly in the two groups . Five patients in the co-trimoxazole group had a microbiologically documented infection ( four with septicemia ) due toEscherichia coli (n=2),Klebsiella pneumoniae , Pseudomonas aeruginosa , Streptococcus sp. There were four septicemic episodes in the norfloxacin group due toP. aeruginosa , Streptococcus pneumoniae , Streptococcus mitis and Streptococcus faecalis . Compliance was good during administration of both drugs . No signs or symptoms of arthropathy were seen in the norfloxacin group . The number of gram-negative bacilli resistant to co-trimoxazole isolated from stools significantly increased during prophylaxis with co-trimoxazole ( p<0.001 ) . Norfloxacin did not select resistant strains and was very active in eradicating gram-negative bacilli from stools ( 27.5 % of positive cultures).Zusammenfassung44 Kinder , die an malignen Erkrankungen litten , erhielten zur Prävention bakterieller Infektionen während der granulozytopenischen Phase nach R and omverfahren entweder Co-trimoxazol oder Norfloxacin . Fieberzustände traten bei der mit Co-trimoxazol beh and elten Gruppe häufiger auf ( p<0,01 ) , aber die Anzahl der Tage mit Fieber und die Anzahl der Tage , an denen eine systemische Antibiotikatherapie durchgeführt werden mußte , wiesen i m Mittel keine signifikanten Unterschiede auf . Unter Co-trimoxazol-Prophylaxe traten fünf mikrobiologisch dokumentierte Infektionen auf ( vier mit Septikämie ) ; die Erreger warenEscherichia coli (n=2)Klebsiella pneumoniae , Pseudomonas aeruginosa undStreptococcus sp. In der Norfloxacin-Gruppe traten vier Septikämien auf , die durchP. aeruginosa , Streptococcus pneumoniae , Streptococcus mitis undStreptococcus faecalis verursacht wurden . Bei beiden Prophylaxeregimen war eine gute Compliance festzustellen . In der Norfloxacin-Gruppe waren keine Hinweise für eine Arthropathie zu finden . Unter Cotrimoxazol-Prophylaxe war eine signifikante Zunahme von gramnegativen Stuhlisolaten mit Resistenz gegen Co-trimoxazol festzustellen ( p<0,001 ) . Bei Norfloxacin war dagegen keine Selektion resistenter Stämme festzustellen , gramnegative Stäbchenbakterien wurden sehr effizient aus dem Stuhl eliminiert ( 27,5 % der positiven Kulturen ) The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a r and omized trial . Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded r and omized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6 ) U of penicillin intravenously ( i.v . ) every 6 h ( q6h ) ( if penicillin allergic , 750 mg of vancomycin i.v . q12h ) in addition to st and ard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day , 200 mg of fluconazole orally once a day , and 5 mg of acyclovir per kg of body weight i.v . q12h . The patients were being treated for germ cell cancer ( n = 15 ) , breast cancer ( n = 16 ) , Hodgkin 's disease ( n = 3 ) , non-Hodgkin 's lymphoma ( n = 4 ) , acute myeloid leukemia ( n = 1 ) , acute lymphoblastic leukemia ( n = 1 ) , and ovarian cancer ( n = 3 ) . The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis . There were significantly fewer overall infections ( 10 versus 3 ; P = 0.016 ) and streptococcal infections ( 9 versus 1 ; P = 0.0078 ) in the group receiving gram-positive prophylaxis . There were no significant differences in the numbers of deaths , duration of broad-spectrum antibiotics , or incidence of neutropenic fever between the two groups . Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant . However , this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin OBJECTIVE To determine the effect of oral penicillin V combined with a fluoroquinolone ( pefloxacin ) on the occurrence of fever and streptococcal and other gram-positive coccal bacteremic infections in granulocytopenic patients with cancer . DESIGN Prospect i ve r and omized double-blinded placebo-controlled prophylactic trial . SETTING Inpatient setting in multiple cooperating cancer centers . SUBJECTS Convenience sample with a total of 551 granulocytopenic patients , 95 % of whom had leukemia or underwent bone marrow transplantation . INTERVENTIONS Penicillin V ( 500 mg twice a day ) vs placebo given in combination with oral pefloxacin ( 400 mg twice a day ) . MAIN OUTCOME MEASURES Occurrence of fever and /or infection . RESULTS Fever or infection ( without fever ) developed in 190 ( 71 % ) of 268 evaluable patients in the penicillin arm compared with 213 ( 80 % ) of 268 evaluable patients in the placebo arm ( P = .03 ; 95 % confidence interval [ CI ] for the difference , -16 % to -1 % ) . Bacteremia occurred in 58 ( 22 % ) of 268 placebo-treated patients and in 38 ( 14 % ) of 268 penicillin-treated patients ( P = .03 ; 95 % CI for the difference , -14 % to -1 % ) , primarily due to a reduction in streptococcal bacteremic episodes that occurred in 14 penicillin-treated patients ( 5 % ) and in 27 placebo-treated patients ( 10 % ) ( P = .05 ; 95 % CI for the difference , -9 % to -0.3 % ) . Gram-negative rod bacteremias occurred in only two patients ( 1 % ) and in five patients ( 2 % ) , respectively . Logistic regression analysis also supported the treatment effect on the development of bacteremia . CONCLUSIONS These results demonstrate that the addition of penicillin V to fluoroquinolone prophylaxis in granulocytopenic patients with cancer effectively reduces febrile episodes and the incidence of bacteremia , especially that due to streptococcal species Seventy-three patients mainly receiving consolidation therapy for acute leukemia or autologous bone marrow transplantation were studied in a r and omized trial comparing nystatin with norfloxacin ( 800 mg ) given orally QID , for prevention of infection . Both groups were equally distributed in regard to age , disease , and duration of granulocytopenia , although far more patients entered the laminar air flow room in the norfloxacin group . Duration of more than a 39 degrees C fever was much longer in the nystatin group than in the norfloxacin group : Bacteremia , microbiologically documented infections , and fever of unknown origin were more frequently seen in the nystatin group , but there was no significant difference between the two groups . On the other h and , patients without fever during granulocytopenia were more numerous in the norfloxacin group than in the nystatin group ( p less than 0.05 ) . Furthermore , three deaths during granulocytopenia occurred in the nystatin group . In conclusion , prophylactic administration of norfloxacin during granulocytopenia showed a significant afebrile period Background Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia ( AML ) patients receiving chemotherapy . Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased . This study aim ed to access the effectiveness of antimicrobial prophylaxis ( AP ) with orally absorbable antibiotics . Methods Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were r and omly divided into the AP group ( 250 mg ciprofloxacin twice a day , 150 mg roxithromycin twice a day , 50 mg fluconazole once a day ) and the control group for a prospect i ve analysis . Results The incidence of fever was 82.6 % in the AP group and 91.6 % in the control group ( p = 0 . 15 ) . Though classification and sites of infections showed no difference between the two groups , the catheter associated infection occurred more frequently in the AP group in significance . The time interval between initiation of chemotherapy and onset of fever , white blood cell ( WBC ) count at the onset of fever , duration of leukopenia ( WBC < 1,000/mm3 ) , duration of systemic antibiotic therapy , mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups . Infections due to gram negative bacteria decreased to 33.3 % in the AP group ( vs. 92 % in the control group ) , but infections due to gram positive bacteria increased to 66.7 % ( vs. 8 % in the control group ) . Gram negative bacteria showed 100 % resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90–100 % resistance to erythromycin , regardless of the presence of AP . Conclusion The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy . On considering increased gram-positive infection and resistance to fluoroquinolone and macroiide , routine prescription of AP should be reconsidered . Further studies that assess the effectiveness of AP in other malignancies , aplastic anemia and bone marrow transplantation are required The objective of this study was to evaluate the efficacy of oral ciprofloxacin in preventing febrile morbidity superimposed on the neutropenia induced from a paclitaxel regimen in ovarian cancer patients . Eligible patients received paclitaxel at doses of 135 to 175 mg/m2 alone or in combination with a platinum agent . They were r and omized to either an observation ( control ) group or a ciprofloxacin prophylaxis group . Patients in the ciprofloxacin group received 500 mg ciprofloxacin orally twice a day once the absolute neutrophil count ( ANC ) was less than 500/mm3 and continued until the ANC was greater than 1000/mm3 . Ninety patients were enrolled between the control ( n = 45 ) and ciprofloxacin ( n = 45 ) groups . They received 371 cycles of a paclitaxel-based regimen with 177 and 194 cycles in the control and ciprofloxacin groups , respectively . Ciprofloxacin prophylaxis was prescribed for 138 ( 71 % ) of the cycles in the ciprofloxacin group and was given for a mean duration of 7.7 days per cycle . The groups were similar in disease status and risk factors for neutropenia . Fifteen patients in the control group developed febrile neutropenia versus 12 of those in the ciprofloxacin group ( P = 0.69 ) . The mean ANC and mean length of hospital stay for neutropenic fever were also similar between groups . There was a greater frequency of an ANC < 100 associated with those prophylaxed with ciprofloxacin ( P = 0.01 ) . Only 44 % of the febrile episodes were associated with a positive culture . Staphylococcus aureus was the most frequently reported organism isolated . Considering these results , it does not appear that febrile neutropenia is reduced by ciprofloxacin during grade IV neutropenia Twenty-six oncology patients , 25 of whom received bone marrow transplants , were enrolled in a prospect i ve , r and omized , double-blinded , placebo-controlled trial assessing the efficacy of ciprofloxacin , 750 mg p.o . b.i.d . , for preventing bacterial infections during prolonged neutropenia . Treatment was begun within 48 hr of initiation of chemotherapy and continued until the absolute granulocyte count recovered to greater than or equal to 500/microliters , or until the onset of fever ( greater than or equal to 38.3 degrees C ) . Seven evaluable subjects received ciprofloxacin , and 11 received placebo . Risk factors for infection were comparable in both groups . Fever occurred in all study subjects , but onset was delayed in ciprofloxacin recipients ( median = 6 days after the fall of the absolute granulocyte count to less than or equal to 500/microliters vs. 3 days for placebo recipients , P = 0.01 ) . No clinical ly or microbiologically documented infections occurred in ciprofloxacin recipients vs. 10 infections in placebo recipients ( 5 bacteremias , 4 skin/soft tissue infections , 1 urinary tract infection , P = 0.0003 ) . Ciprofloxacin recipients required fewer days of therapeutic antimicrobials ( median : 28 antibiotic-days vs. 49 , P0.02 ) . The bioavailability of ciprofloxacin appeared comparable to that found in previously published studies of normal volunteers and patients not receiving chemotherapy . Adverse effects and colonization by ciprofloxacin-resistant microorganisms were monitored , but the sample sizes were too small to permit meaningful conclusions about these safety parameters . Ciprofloxacin appears to be effective for preventing bacterial infections in neutropenic patients . Additional trials are needed to establish the optimal dose of ciprofloxacin and to compare its safety and efficacy with those of currently used prophylactic regimens Fifty-six patients receiving remission induction treatment for acute leukemia were studied in a r and omized trial comparing ciprofloxacin with trimethoprim-sulfamethoxazole plus colistin for prevention of infections . Both groups received amphotericin B for antifungal prophylaxis . Six major infections occurred in 28 patients receiving ciprofloxacin , and 11 major infections occurred in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin . No infections caused by gram-negative bacilli were seen in the ciprofloxacin group ( p less than 0.02 ) . Ciprofloxacin prevented colonization with resistant gram-negative bacilli , but 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole plus colistin ( p less than 0.01 ) . Ciprofloxacin was better tolerated : 23 of 28 patients were highly compliant to the drug , compared with 15 of 28 patients in the trimethoprim-sulfamethoxazole group ( p less than 0.05 ) . These results suggest that ciprofloxacin is a promising drug for the prevention of infection in patients with granulocytopenia A total of 63 neutropenic patients receiving cytotoxic therapy for acute leukemia were r and omly allocated to receive norfloxacin ( 400 mg every 12 hours ) or cotrimoxazole ( 160/800 mg every 12 hours ) to prevent bacterial infection . Compliance was more than 95 percent and no adverse effects attributable to the study drugs were observed . The overall incidence of febrile illness ( 67 percent ) was similar between the groups ; however , no gram-negative bacillary infections were observed in 31 norfloxacin recipients compared with four of 32 cotrimoxazole recipients . Furthermore , nine norfloxacin recipients had 17 gram-positive bacteremias compared with two in two cotrimoxazole recipients ( p = 0.0034 ) . Norfloxacin was more effective than cotrimoxazole for preventing acquisition of aerobic gram-negative bacilli in surveillance cultures . Neither study drug allocation nor the presence of an indwelling central venous catheter influenced outcome among the 42 patients who subsequently received empiric systemic antibiotics for suspected infection . Although gram-positive infection remains an unsolved problem , norfloxacin appears to be a safe , effective , well-tolerated alternative to cotrimoxazole for preventing gram-negative infection in neutropenic patients with acute leukemia BACKGROUND The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention . METHODS We r and omly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia ( < 1000 neutrophils per cubic millimeter ) was expected to occur for more than seven days to receive either oral levofloxacin ( 500 mg daily ) or placebo from the start of chemotherapy until the resolution of neutropenia . Patients were stratified according to their underlying disease ( acute leukemia vs. solid tumor or lymphoma ) . RESULTS An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis , as compared with 85 percent of those receiving placebo ( 243 of 375 vs. 308 of 363 ; relative risk , 0.76 ; absolute difference in risk , -20 percent ; 95 percent confidence interval , -26 to -14 percent ; P=0.001 ) . The levofloxacin group had a lower rate of microbiologically documented infections ( absolute difference in risk , -17 percent ; 95 percent confidence interval , -24 to -10 percent ; P<0.001 ) , bacteremias ( difference in risk , -16 percent ; 95 percent confidence interval , -22 to -9 percent ; P<0.001 ) , and single-agent gram-negative bacteremias ( difference in risk , -7 percent ; 95 percent confidence interval , -10 to -2 percent ; P<0.01 ) than did the placebo group . Mortality and tolerability were similar in the two groups . The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma . CONCLUSIONS Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia . The long-term effect of this intervention on microbial resistance in the community is not known Summary In a r and omized multicenter study , ciprofloxacin and norfloxacin , each in two different dose regimens and in combination with non-absorbable antimycotics , were administered to 51 patients with acute leukaemia undergoing aggressive remission induction chemotherapy for infection prevention . Both drugs showed an effective elimination of gram-negative potential pathogens and Staphylococcus aureus not affecting the anaerobic flora of the gastrointestinal tract . A low incidence of side effects and a satisfactory patient compliance could be observed . A daily dosage of 1,000 mg ciprofloxacin or 800 mg norfloxacin is recommended for infection prevention in severely granulocytopenic patients .ZusammenfassungIn einer r and omisierten multizentrischen Studie wurden 51 Patienten mit akuter Leukämie , die sich einer aggressiven Chemotherapie zur Remissionsinduktion unterzogen , mit Ciprofloxacin oder Norfloxacin , jeweils in zwei unterschiedlichen Dosierungen und in Kombination mit einem nicht resorbierbaren Antimykotikum , zur Infektionsprävention beh and elt . Mit beiden Substanzen wurde eine effektive Elimination potentiell pathogener gram-negativer Bakterien undStaphylococcus aureus erreicht , während die anaerobe Darmflora nicht beeinflußt wurde . Es wurde nur eine geringe Inzidenz von Nebenwirkungen bei zufriedenstellender Patientencompliance beobachtet . Als Tagesdosis zur Infektionsprävention bei schwer granulozytopenischen Patienten sollten 1000 mg Ciprofloxacin oder 800 mg Norfloxacin verabreicht werden Ciprofloxacin was compared to ciprofloxacin plus amoxicillin as antibacterial prophylaxis in 53 evaluable patients with neutropenic episodes , because an oral penicillin may help to decrease the incidence of gram-positive infections . The two groups were r and omized and evaluated in a number of febrile episodes , in days at fever/at risk , in mean interval of first febrile episode , in duration of antibiotic therapy and in causative organisms in febrile episodes . In conclusion , no significant difference was observed between the two groups in prevention of gram-positive bacteremias |
12,569 | 26,296,614 | Findings suggest a high prevalence of acute and posttraumatic stress symptoms in parents . | A systematic review of the literature investigating the early traumatic stress responses in parents of children diagnosed with a serious illness/injury .
This review integrates and compares early traumatic reactions in parents with children suffering a range of serious illnesses . | BACKGROUND Motor vehicle accidents ( MVAs ) are the main cause of Posttraumatic stress disorder ( PTSD ) in industrialized countries . This includes the frequently occurring but understudied situation of parents learning that their children were injured . However , unlike in other types of trauma survivors , little is known about the predictors of PTSD symptoms in mothers whose child has suffered an MVA . METHODS A group of 72 mothers and 28 fathers were prospect ively assessed for peritraumatic distress , peritraumatic dissociation , and PTSD symptoms 1 and 5 weeks after their child had suffered an MVA . RESULTS Levels of peritraumatic distress and dissociation were comparable to other trauma victims , 18 % of the mothers were considered to be suffering from probable PTSD . In mothers , significant positive correlations were found between PTSD symptoms and peritraumatic distress ( r=.34 ) and dissociation ( r=.37 ) , whereas mothers ' PTSD symptoms were associated with decreased peritraumatic dissociation in fathers ( r=-.37 ) . Even after controlling for covictim/witness status , peritraumatic distress was a predictor of mothers ' PTSD symptoms , explaining 14 % of the variance . CONCLUSIONS Peritraumatic response and PTSD symptoms should be routinely assessed among parents whose child has experienced a traumatic event OBJECTIVE To evaluate prospect ively the association between parental anxiety during treatment for childhood leukemia and posttraumatic stress symptoms ( PTSS ) after treatment ends . A secondary goal is to explore concurrent variables associated with parental avoidance after treatment ends . METHODS This is a longitudinal follow-up study of 113 parents of children treated for leukemia who previously participated in a study of procedural distress during treatment . Data included parental self-report question naires completed during treatment and after treatment . RESULTS Using hierarchical multiple regression , we found anxiety during treatment to be a significant predictor of later PTSS for mothers , but not fathers . Anxiety , self-efficacy , posttraumatic growth and length of time since treatment ended were associated with parental avoidance . CONCLUSIONS Highly anxious parents are at risk for PTSS and may benefit from approaches that decrease anxiety during treatment and afterward . Enhancing self-efficacy related to follow-up care and identifying positive aspects of the traumatic experiences are suggested as treatment approaches for families after cancer treatment OBJECTIVE The American Academy of Pediatrics highlights the important role of pediatricians in recognizing adverse child responses to tragic events , such as traffic crashes . One challenge in effectively identifying children and their parents with troubling psychological responses to trauma is that little is known about the normal range of acute psychological responses in children and their parents in the immediate aftermath of traumatic events , making identification of adverse child responses difficult . Within the first month after a traumatic event , individuals may display reexperiencing , avoidance , and hyperarousal symptoms as well as dissociation ( eg , feelings of unreality or emotional numbing ) . The presence of these responses , collectively known as acute stress disorder ( ASD ) , alerts providers to those who may be at risk for ongoing difficulties . For beginning to develop an evidence base to guide pediatric care providers in addressing acute traumatic responses , the aim of the current investigation was to describe systematic ally the range and type of symptoms of ASD in children and their parents after pediatric traffic injury . METHODS A prospect i ve cohort study was conducted of traffic-injured children , who were 5 to 17 years of age and admitted to the hospital for treatment of injuries from traffic crashes , and their parents . All children who met eligibility criteria between July 1999 and May 2000 were invited to participate in the study . After consent/assent was obtained , children and their custodial parents ( or guardians ) were interviewed within 1 month after injury via a structured assessment to determine the circumstances of the crash and the presence of ASD symptoms . Relevant demographic and clinical information ( eg , age , race , gender , date of injury ) was abstract ed from the medical records of subjects . A survey instrument to assess the presence of ASD symptoms was completed by both the child and his or her guardian . All children completed the Child Acute Stress Question naire , and all parents completed the Stanford Acute Stress Reaction Question naire . Responses were scored for the presence of dissociation , reexperiencing , avoidance , and /or hyperarousal symptoms as well as broad distress ( symptoms present in every category ) . RESULTS Symptoms of ASD were commonly observed in the children and parents . Eighty-eight percent of children and 83 % of parents reported having at least 1 clinical ly significant symptom ; this affected 90 % of the families . Broad distress was observed for a large minority : 28 % of children and 23 % of parents . No statistically significant association was found between child broad distress and either child age ( r = -0.12 ) or child injury severity score ( r = -0.05 ) . chi(2 ) analyses revealed no significant association between broad distress and child gender , child race , or mechanism of injury . No statistically significant association was found between parent broad distress and child age ( r = -0.06 ) or child injury severity score ( r = 0.09 ) . chi(2 ) analyses revealed no significant association between parent broad distress and child gender or parent presence at the crash scene . Associations were found between parent broad distress and race in that fewer white parents reported broad distress . In addition , mechanism of injury was associated with parent broad distress : more parents reported broad distress when their children were involved in pedestrian-motor vehicle crashes , and fewer parents reported broad distress when their children were injured in a bicycle fall . CONCLUSIONS Pediatric care providers can expect to see some ASD symptoms in most children and parents in the immediate aftermath of traffic-related injury . Brief education is appropriate to explain that these symptoms are normal reactions that are likely to resolve . If symptoms persist for > 1 month or are particularly distressing in their intensity , then referral for psychological care may be necessary for treatment of posttraumatic stress disorder . Given the high prevalence of pediatric traffic crashes and the underdiagnosis of posttraumatic stress disorder , probing for recent crash exposure might be appropriate during routine child health maintenance . The following are recommendations for pediatricians : 1 ) routinely call the family several days and 1 to 2 weeks after a traffic injury and ask about behavioral symptoms and family function ; 2 ) make use of the ongoing physician-patient relationship to explore symptom presence and intensity and any functional impairment in the injured child ; a brief office visit with the child and parents could serve this purpose ; 3 ) be sure to explore the effect that the child 's injury has had on the family ; remember that the parent 's experience posttraumatic stress symptoms after pediatric traffic-related injuries and these symptoms may limit the parent 's ability to support the child ; 4 ) provide supportive care and give families the opportunity to discuss the crash and their current feelings ; do not force families to talk about the crash ; 5 ) although any child in a traffic crash or his or her parent is at risk for posttraumatic symptomatology , regardless of injury severity , particular attention should be paid to the parents of child pedestrians who are struck by motor vehicles . These parents experience posttraumatic symptoms more commonly than parents of children in other traffic crashes OBJECTIVE To report acceptability , feasibility , and outcome data from a r and omized clinical trial ( RCT ) of a brief intervention for caregivers of children newly diagnosed with cancer . METHOD Eighty-one families were r and omly assigned following collection of baseline data to Intervention or Treatment as Usual ( TAU ) . Recruitment and retention rates and progression through the protocol were tracked . Measures of state anxiety and posttraumatic stress symptoms served as outcomes . RESULTS Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria ( 40 % ) and an unexpectedly low participation rate ( 23 % ) . However , movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback . Outcome data showed no significant differences between the arms of the RCT . CONCLUSIONS There are many challenges inherent in conducting a RCT shortly after cancer diagnosis . Consideration of alternative research design s and optimal timing for interventions are essential next steps Objectives : To examine children 's reports of their health-related quality of life ( HRQoL ) following paediatric traffic injury , to explore child and parental post-traumatic stress , and to identify children and parents with adverse outcomes . Design : Prospect i ve cohort study . Assessment s : shortly after the injury , three months and six months post injury . Setting : Department of Traumatology , University Hospital . Subjects : Fifty-one young traffic injury victims aged 8 - 15 years . Main measures : TNO-AZL Children 's Quality of Life question naire and the Impact of Event Scale . Results : Short-term adverse changes in the child 's HRQoL were observed for the child 's motor functioning and autonomy . At three months , 12 % of the children and 16 % of the parents reported serious post-traumatic stress symptoms . Increased stress at three months , or across follow-up , was observed among hospitalized children , children with head injuries , and children injured in a motor vehicle accident . Parental stress was related to low socioeconomic status and the seriousness of the child 's injury and accident ( hospitalization , head injury , serious injury , motor vehicle involved , others injured ) . Conclusions : The children reported only temporary effects in their motor functioning and autonomy . Post-traumatic stress symptoms following paediatric traffic injury were not only experienced by the children , but also by their parents OBJECTIVE To report initial feasibility and outcome from a pilot study of a new three-session intervention for caregivers of children newly diagnosed with cancer , Surviving Cancer Competently Intervention Program-Newly Diagnosed ( SCCIP-ND ) . METHOD Nineteen families ( 38 caregivers ) were r and omly assigned to SCCIP-ND or treatment as usual subsequent to learning of their child 's illness . The study design included pre- and 2-month postintervention assessment s , with state anxiety and posttraumatic stress symptoms as outcomes . Feasibility was based on therapist feedback and supervision , program evaluations , and data from study -tracking procedures . RESULTS SCCIP-ND appears to be an acceptable intervention that can be used successfully with caregivers over the first few months after diagnosis . Recruitment and retention data document feasibility but also highlight challenges . Preliminary outcome data show changes in the desired direction [ e.g. , reduced anxiety and parental posttraumatic stress symptoms ( PTSS ) ] . CONCLUSIONS The pilot data are supportive of the value and challenges of developing evidence -based family interventions in pediatric psychology OBJECTIVE To determine if maternal distress predicts child adjustment outcomes or if child adjustment outcomes predict maternal distress among children newly diagnosed with cancer , and if a parent-focused intervention has downstream effects on child adjustment . METHODS Mothers ( n = 52 ) were r and omly assigned to a clinic-based , interdisciplinary intervention for parents of children newly diagnosed with cancer . Measures of maternal distress and child adjustment were collected at baseline , posttreatment , and follow-up . RESULTS A lagged relationship was identified between maternal distress and child internalizing symptoms , but not externalizing symptoms . The parent intervention reduced child internalizing and externalizing symptoms at follow-up . Only the child internalizing symptoms effect was mediated by reduced maternal distress . The child externalizing symptoms effect was mediated by unobserved parent factors . CONCLUSIONS This study provides support for illness adjustment and coping models that emphasize the role of parent factors in driving child adjustment outcomes and is encouraging for future parent-focused intervention research Objective : To assess short-term changes in child and parent psychiatric status following meningococcal disease . Design : Prospect i ve cohort study ; 3-month follow-up using parent , teacher , and child question naires . Setting : Hospital admissions to three pediatric intensive care units and 19 general pediatric wards . Patients : Sixty children aged 3–6 yrs , 60 mothers , and 45 fathers . Interventions : We administered measures of illness severity ( Glasgow Meningococcal Septicaemia Prognostic Score , days in hospital ) and psychiatric morbidity ( Strengths and Difficulties Question naires , parent and teacher versions ; Impact of Event scales ; General Health Question naire-28 ) . Measurements and Main Results : In children admitted to pediatric intensive care units , parental reports at 3-month follow-up showed a significant increase in emotional and hyperactivity symptoms and in related impairment ; symptoms of posttraumatic stress disorder were present in four of 26 ( 15 % ) children > 8 yrs old . Regarding the parents , 26 of 60 ( 43 % ) mothers in the total sample had question naire scores indicative of high risk for psychiatric disorder and 22 of 58 ( 48 % ) for posttraumatic stress disorder . In fathers there was high risk for psychiatric disorder in 11 of 45 ( 24 % ) and for posttraumatic stress disorder in 8 of 43 ( 19 % ) . Severity of the child 's physical condition on admission was significantly associated with hyperactivity and conduct symptoms at follow-up . Length of hospital admission was associated with psychiatric symptoms in the child and posttraumatic stress disorder symptoms in parents . There were also significant associations between psychiatric symptoms in children and parents . Conclusions : Admission of children to pediatric intensive care units for meningococcal disease is associated with an increase in and high levels of psychiatric and posttraumatic stress disorder symptoms in children and parents . Length of admission is associated with psychiatric symptoms in children and posttraumatic stress disorder symptoms in parents . Pediatric follow-up should explore psychiatric as well as physical sequelae in children and parents BACKGROUND Traffic crashes are the leading health threat to children in the United States , result ing in nearly 1 million injuries annually . The psychological consequences of these injuries are primarily unknown . The aims of this study were to estimate the prevalence of posttraumatic stress disorder ( PTSD ) in traffic-injured children and their parents and to identify risk factors for PTSD development . METHODS A prospect i ve cohort study of traffic-injured children between 3 and 18 years of age was conducted at a level 1 Pediatric Trauma Center . The children were enrolled as part of an ongoing surveillance system of traffic-related injuries . Presence and severity of PTSD were determined in the children and their parents through a vali date d diagnostic question naire 7 to 12 months after child injury . RESULTS Twenty-five percent of the children and 15 % of the parents suffered diagnostic PTSD , but only 46 % of the parents of affected children sought help of any form ( including from friends ) for their child and only 20 % of affected parents sought help for themselves . Child PTSD was associated with older child age and parent PTSD . Parent PTSD was associated with younger child age , child PTSD , and parent witnessing the event . Injury severity was not predictive of PTSD . CONCLUSIONS PTSD in children and their parents is a common , yet overlooked , consequence of pediatric traffic-related injury with prevalence rates similar to those found in children exposed to violence . Physicians managing the pediatric trauma patient , regardless of injury severity or whether the injury was intentional , should screen for PTSD and refer for treatment where appropriate ABSTRACT . Mothers of children with serious illnesses have lower levels of well-being than mothers in the general population . Problem-solving therapy ( PST ) , a cognitive-behavioral intervention , has been shown to be effective in treating negative affectivity ( depression , anxiety ) and other manifestations of reduced well-being . This report describes a problem-solving skills training ( PSST ) intervention , based on problem-solving therapy , for mothers of newly diagnosed pediatric cancer patients . Ninety-two mothers were r and omly assigned to receive PSST or to receive st and ard psychosocial care ( Control Group ) . After the 8-week intervention , mothers in the PSST Group had significantly enhanced problem-solving skills and significantly decreased negative affectivity compared with controls . Analysis revealed that changes in self-reports of problem-solving behaviors accounted for 40 % of the difference in mood scores between the two groups . Interestingly , PSST had the greatest impact on improving constructive problem solving , whereas improvement in mood was most influenced by decreases in dysfunctional problem solving . The implication s of these findings for refinement of the PSST intervention and for extension to other groups of children with serious illnesses are discussed OBJECTIVE Acute stress disorder permits an early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder ( PTSD ) . This study aim ed to prevent PTSD by an early provision of cognitive behavior therapy . Specifically , this study indexed the relative efficacy of prolonged exposure and anxiety management in the treatment of acute stress disorder . METHOD Forty-five civilian trauma survivors with acute stress disorder were given five sessions of 1 ) prolonged exposure ( N = 14 ) , 2 ) a combination of prolonged exposure and anxiety management ( N = 15 ) , or 3 ) supportive counseling ( N = 16 ) within 2 weeks of their trauma . Forty-one trauma survivors were assessed at the 6-month follow-up . RESULTS Fewer patients with prolonged exposure ( 14 % , N = 2 of 14 ) and prolonged exposure plus anxiety management ( 20 % , N = 3 of 15 ) than supportive counseling ( 56 % , N = 9 of 16 ) met the criteria for PTSD after treatment . There were also fewer cases of PTSD in the prolonged exposure group ( 15 % , N = 2 of 13 ) and the prolonged exposure plus anxiety management group ( 23 % , N = 3 of 13 ) than in the supportive counseling group ( 67 % , N = 10 of 15 ) 6 months after the trauma . Chronic PTSD in the supportive counseling condition was characterized by greater avoidance behaviors than in the prolonged exposure condition or the prolonged exposure plus anxiety management condition . CONCLUSIONS These findings suggest that PTSD can be effectively prevented with an early provision of cognitive behavior therapy and that prolonged exposure may be the most critical component in the treatment of acute stress disorder OBJECTIVE Full and partial posttraumatic stress disorder ( PTSD ) following trauma exposure were examined in a community sample in order to determine their prevalence and their relative importance and functional significance . METHOD A st and ardized telephone interview with a series of trauma probes and a DSM-IV PTSD checklist was administered to a r and om sample of 1,002 persons in a midsized Midwestern Canadian city . The authors determined current ( i.e. , 1-months ) prevalence rates of full PTSD , i.e. , all DSM-IV criteria , and partial PTSD , i.e. , fewer than the required number of DSM-IV criterion C symptoms ( avoidance/numbing ) or criterion D symptoms ( increased arousal ) . Additional questions about interference with functioning were also posed . RESULTS The estimated prevalence of full PTSD was 2.7 % for women and 1.2 % for men . The prevalence of partial PTSD was 3.4 % for women and 0.3 % for men . Interference with work or school was significantly more pronounced in persons with full PTSD than in those with only partial symptoms , although the latter were significantly more occupationally impaired than traumatized persons without PTSD . CONCLUSIONS These findings in an epidemiologic sample underscore observations from patient and military groups that many traumatized persons suffer from a subsyndromal form of PTSD . These persons with partial PTSD , although somewhat less impaired than persons with the full syndrome , nonetheless exhibit clinical ly meaningful levels of functional impairment in association with their symptoms . This subthreshold form of PTSD may be especially prevalent in women . Additional study of partial PTSD is warranted OBJECTIVE To prospect ively assess the prevalence , course , and predictors of posttraumatic stress symptoms ( PTSSs ) in children after road traffic accidents ( RTAs ) . METHOD Sixty-eight children ( 6.5 - 14.5 years old ) were interviewed 4 - 6 weeks and 12 months after an RTA with the Child PTSD Reaction Index ( response rate 58.6 % ) . Their mothers ( n = 60 ) and fathers ( n = 53 ) were assessed with the Posttraumatic Diagnostic Scale . RESULTS The prevalence of moderate to severe PTSSs in children was 16.2 % at 4 - 6 weeks , and 17.6 % at 12 months . Mean PTSS scores did not decrease between the two assessment s. Five children showed a delayed onset of PTSSs . Twelve mothers ( 20 % ) and six fathers ( 11.3 % ) met criteria for posttraumatic stress disorder ( PTSD ) at 4 to 6 weeks . At 12 months , three mothers ( 5.7 % ) and no fathers met diagnostic criteria . Child PTSSs at 12 months was significantly predicted by PTSS at 4 - 6 weeks and by severity of father 's PTSD . Age , sex , injury severity , threat appraisal , and maternal PTSD did not significantly contribute to child PTSSs at follow-up . CONCLUSIONS There is a need for careful psychological assessment of children and their parents after an RTA . The possibility of delayed onset of PTSSs implies a monitoring beyond the first weeks after the accident . The impact of fathers ' PTSD on child PTSSs suggests that fathers ought to be actively involved in family-based prevention and treatment interventions of child PTSSs after RTAs Mothers of children with cancer experience significant distress associated with their children 's diagnosis and treatment . The efficacy of problem-solving skills training ( PSST ) , a cognitive-behavioral intervention based on problem-solving therapy , was assessed among 430 English- and Spanish-speaking mothers of recently diagnosed patients . Participants were r and omized to usual psychosocial care ( UPC ; n=213 ) or UPC plus 8 sessions of PSST ( PSST ; n=217 ) . Compared with UPC mothers , PSST mothers reported significantly enhanced problem-solving skills and significantly decreased negative affectivity . Although effects were largest immediately after PSST , several differences in problem-solving skills and distress levels persisted to the 3-month follow-up . In general , efficacy for Spanish-speaking mothers exceeded that for English-speaking mothers . Findings also suggest young , single mothers profit most from PSST Objective : To measure the prevalence of parental acute stress disorder ( ASD ) and posttraumatic stress disorder ( PTSD ) and to examine the relationship between ASD symptoms and PTSD symptoms in parents of infants and children admitted to the pediatric intensive care unit ( PICU ) . To examine the correlation between parental perceptions of illness severity and objective measures . To assess the association among demographic , situational , and illness factors and the severity of ASD and PTSD . Design : Prospect i ve cohort study . Setting : Thirty-eight bed PICU at an urban children ’s hospital . Patients : The parents of 272 children admitted to the PICU for > 48 hrs . Interventions : ASD symptoms were assessed using the Acute Stress Disorder Scale during the child ’s admission . PTSD symptoms were assessed using the PTSD Checklist at least 2 months after discharge . The severity of illness was measured using the Pediatric Risk of Mortality ( PRISM III ) score . Measurements and Main Results : Of the 272 parents completing the initial assessment , 87 ( 32 % ) met symptom criteria for ASD . Of the 161 parents completing follow-up , 33 ( 21 % ) met symptom criteria for PTSD . PTSD symptoms at follow-up were associated with ASD symptoms assessed in the PICU , unexpected admission , parent ’s degree of worry that the child might die , and the occurrence of another hospital admission or other traumatic event subsequent to the index admission . Neither ASD nor PTSD responses were associated with objective measures of a child ’s severity of illness ( PRISM III score ) . Conclusion : Traumatic stress symptoms are common among parents in the PICU and may persist long after discharge . There is strong support from these data for continued attention to supporting parents both during and after a child ’s PICU admission BACKGROUND Previous studies found notable rates of post-traumatic stress symptoms ( PTSS ) and post-traumatic stress disorder ( PTSD ) in pediatric patients and their parents and suggest a significant association between child and parent PTSS . However , little is known about mutual influences between child and parental PTSS over time . This study prospect ively examined the presence of PTSS and PTSD and the mutual influence of child and parental PTSS in a large sample of pediatric patients with different medical conditions . METHODS A total of 287 children ( aged 6.5 - 16 years ) and their mothers ( n = 239 ) and fathers ( n = 221 ) were assessed at 5 - 6 weeks and 1 year after an accident or a new diagnosis of cancer or diabetes mellitus type 1 in the child . RESULTS At the first assessment 11.1 % and at the second assessment 10.2 % of the children had moderate to severe PTSS . At 5 - 6 weeks 29.3 % of mothers and 18.6 % of fathers met criteria for PTSD . At 1 year the rates were 14.6 % for mothers and 7.9 % for fathers . There were considerable differences of PTSS among different medical diagnostic groups in children and parents . Mothers were more vulnerable than fathers . Structural equation analysis revealed that initially high PTSS in mothers and fathers were longitudinally related to poorer recovery from PTSS in the child . Cross-lagged effects from the child to the parents and from one parent to the other were not significant . CONCLUSIONS This study highlights the long-term influence of parental PTSS on the child 's recovery after trauma and calls for a family systems approach and for early interventions in the treatment of traumatized pediatric patients |
12,570 | 11,407,054 | Acute bacterial conjunctivitis is frequently a self-limiting condition but the use of antibiotics is associated with significantly improved rates of early clinical remission , and early and late microbiological remission . | There has been uncertainty about whether antibiotic therapy confers significant benefit in the treatment of acute bacterial conjunctivitis .
This study aim ed to assess the efficacy of antibiotic therapy in the management of acute bacterial conjunctivitis . | Two hundred eighty-eight cases of culture-proven bacterial conjunctivities were evaluated as part of two multicentered , r and omized , prospect i ve clinical studies comparing the antibacterial efficacy of topically administered ciprofloxacin 0.3 % either with a placebo or with tobramycin 0.3 % . In the first study , ciprofloxacin was significantly ( P less than .001 ) more effective than the placebo . It eradicated or reduced the various bacterial pathogens in 93.6 % of patients , compared to 59.5 % for the placebo . In the second study , ciprofloxacin ( 94.5 % ) and tobramycin ( 91.9 % ) were equally effective . Topically applied ciprofloxacin eradicated or reduced all isolated bacterial species , attesting to its broad antibacterial spectrum and its potential usefulness in treating external ocular infections Abstract Objective : To assess three prescribing strategies for sore throat . Design : R and omised follow up study . Setting : 11 general practice s in the South and West region . Subjects : 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat ; 84 % had tonsillitis or pharyngitis . Patients were r and omised to three groups : prescription for antibiotics for 10 days ( group 1 , 246 patients ) ; no prescription ( group 2 , 230 patients ) ; or prescription for antibiotics if symptoms were not starting to settle after three days ( group 3 ; 238 patients ) . Main outcome measures : Duration of symptoms ; satisfaction and compliance with and perceived efficacy of antibiotics ; time off school or work . Outcomes were documented in 582 subjects ( 81 % ) . Results : Median duration of antibiotic use differed significantly in the three groups ( 10 v 0 v 0 days , P<0.001 ) ; 69 % of patients in group 3 did not use their prescription . The proportion of patients better by day 3 did not differ significantly ( 37 % v 35 % v 30 % , P=0.28 ) , nor did the duration of illness ( median 4 v 5 v 5 days , P=0.39 ) , days off work or school ( median 2 v 2 v 1 , P=0.13 ) , or proportion of patients satisfied ( 96 % v 90 % v 93 % , P=0.09 ) , although group 1 had fewer days of fever ( median 1 v 2 v 2 days , P=0.04 ) . More patients in group 1 thought the antibiotics were effective ( 87 % v 55 % v 60 % , P<0.001 ) and intended coming to the doctor in future attacks ( 79 % v 54 % v 57 % , P<0.001 ) . “ Legitimation ” of illness — to explain to work or school ( 60 % ) or family or friends (37%)–was an important reason for consultation . Patients who were more satisfied got better more quickly , and satisfaction related strongly to how well the doctor dealt with patient 's concerns . Conclusion : Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription . Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness . Key messages Sore throat is one of the commonest presentations of upper respiratory illness to general practitioners , and attendance is increasing Prescribing antibiotics for sore throat does not reduce the extent and duration of symptoms Prescribing antibiotics enhances belief in antibiotics and intention to consult Legitimation of illness is an important reason for attending the doctor Satisfaction predicts duration of illness and closely relates to how well concerns are dealt with — unless patients are very ill , general practitioners should consider exploring concerns and should avoid or delay prescribing 48 patients witha diagnosis of presumptive bacterial conjunctivitis were assessed . They had been treated with either trimethoprim-polymyxin or neomycin-polymyxin-gramicidin eye drops in a r and omised double-blind trial . There were 24 patients in each treatment group . There were no significant differences between the two preparations proved with regard to the eradication of organisms or clinical improvement , and both preparations proved to be very effective . Patient compliance was good and no adverse reactions were encountered with either preparation Forty-five patients with presumed acute bacterial conjunctivitis were treated in an investigator-masked r and omized multicenter study with either lomefloxacin 0.3 % or fucidic acid 1 % eye drops twice daily . Clinical signs and symptoms were rated by slit-lamp examination and conjunctival swab cultures were performed to evaluate clinical and microbiological efficacy . A total of 57 ocular isolates were tested for susceptibility to nine antibiotics . A significant decrease in clinical symptomatology was achieved by both treatments with a gradual improvement over the treatment period of 7 - 9 days . Bacteriological recovery was frequently achieved already at the first control visit ( day 3 - 5 ) , but the recovery rate was statistically significant ( p = 0.014 ) only in the lomefloxacin group . The relatively high in vitro resistance rate ( 46 % ) to fucidic acid was not reflected by lower clinical efficacy . Two unrelated adverse events ( one in each treatment group ) and minimal local intolerance problems were observed in both treatment groups . A significantly higher incidence of burning sensation was observed with fucidic acid than with lomefloxacin ( p < 0.01 ) . All four treatment failures in the study occurred in the fucidic acid group . Lomefloxacin 0.3 % ophthalmic solution demonstrated a high efficacy and good tolerance in the management of acute bacterial conjunctivitis Abstract . Fusidic acid 1 % and chloramphenicol 0.5 % eye drops were in a r and omized , single‐blind manner given as a one‐week treatment to out‐ patients with acute , purulent conjunctivitis . A clinical success was recorded in 84 % ( 102/121 ) of patients receiving fusidic acid and in 81 % ( 104/129 ) of patients receiving chloramphenicol . More patients ( 14 % ) receiving chloramphenicol complained of trivial side effects such as stinging and local discomfort , compared with fusidic acid ( 5 % ) . No serious side effects were recorded . It is concluded that fusidic acid dispensed in a carbomer eye vehicle represents an effective and well tolerated new topical eye preparation with the advantage of being administered twice daily We studied 102 children aged 1 month to 18 years in a r and omized , double-blind trial design ed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial . Affected eyes were treated four times a day for 7 days with drug ( polymyxin-bacitracin ophthalmic ointment ) or placebo . Eighty-four patients had proved bacterial conjunctivitis ( Haemophilus influenzae 61 , Streptococcus pneumoniae 22 , both one ) ; 66 of these received only topical therapy . By 3 to 5 days , 21 of 34 ( 62 % ) patients receiving topical antibiotic were clinical ly cured , whereas only nine of 32 ( 28 % ) patients given placebo were cured ( P less than 0.02 ) . By 8 to 10 days , 31 ( 91 % ) of the patients given antibiotic and 23 ( 72 % ) of the placebo group were cured ( P = NS ) . The bacterial pathogen was eradicated by day 3 to 5 in 71 % and by day 8 to 10 in 79 % of patients given antibiotic , compared to 19 % and 31 % of the placebo group ( P less than 0.001 ) . Acute bacterial conjunctivitis is a self-limited disease , but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva One hundred fifty-eight patients , 21 years of age or less , presenting with culture-positive ( Haemophilus influenzae or Streptococcus pneumoniae ) conjunctivitis were treated with trimethoprim-polymyxin B ( TP ) , gentamicin sulfate ( GS ) or sodium sulfacetamide ( SS ) ophthalmic solution for 10 days . Clinical response at 3 to 6 days after start of therapy was similar for all test agents : 26 of 55 ( 47 % ) patients cured , 25 of 55 ( 45 % ) improved for TP ; 28 of 57 ( 49 % ) cured , 26 of 57 ( 46 % ) improved for GS ; and 19 of 46 ( 41 % ) cured , 22 of 46 ( 48 % ) improved for SS . Clinical response at 2 to 7 days after completion of therapy was also similar : 46 of 55 ( 84 % ) patients cured , 5 of 55 ( 9 % ) improved for TP ; 50 of 57 ( 88 % ) cured , 5 of 57 ( 9 % ) improved for GS ; and 41 of 46 ( 89 % ) cured , 2 of 46 ( 4 % ) improved for SS . Bacteriologic response at 2 to 7 days after completion of therapy was similar for all antimicrobials : 44 of 55 ( 83 % ) patients for TP ; 39 of 57 ( 68 % ) for GS ; and 33 of 46 ( 72 % ) for SS Forty patients with a diagnosis of presumptive bacterial conjunctivitis were treated with either trimethoprim-polymyxin or chloramphenicol ophthalmic solutions in a r and omized , double-blind trial . No significant differences could be demonstrated between the results of 7-days ' treatment with the two preparations and both solutions were found to be effective in improving the signs and symptoms of surface ocular bacterial infection . No adverse reactions were reported in either treatment group Two-hundred and thirty patients with a diagnosis of presumptive bacterial conjunctivitis were assessed in a r and omized double-blind multicentre trial . In two of the centres the patients had been treated with either trimethoprim-polymyxin B or neomycin-polymyxin B-gramicidin ophthalmic solution . In the other two centres the patients had been treated with either trimethoprim-polymyxin B or chloramphenicol ophthalmic solution . All of the preparations used were shown to be effective and very few adverse reactions were encountered . No significant difference in clinical efficacy could be demonstrated between trimethoprim-polymyxin B and neomycin-polymyxin B -gramicidin but trimethoprim-polymyxin B was found to be significantly better ( P = 0.03 ) than chloramphenicol in reducing signs and symptoms Forty-two patients with a clinical diagnosis of bacterial conjunctivitis were enrolled in a r and omized , double-blind trial . Patients were treated with either trimethoprim-polymyxin B sulphate or chloramphenicol ophthalmic ointments 4-times a day for 7 days . Analysis of clinical evaluation data showed that both treatments were effective and well tolerated , and that there were no statistically significant differences between them with regard to eradication of organisms or clinical improvement Summary We performed a prospect i ve , r and omised , investigator-masked and parallel-group study to compare topical lomefloxacin 0.3 % instilled twice daily with topical chloramphenicol instilled five times daily in the treatment of acute bacterial conjunctivitis . 191 patients ( lomefloxacin 96 , chloramphenicol 95 ) were enrolled in this study with clinical ly diagnosed acute bacterial conjunctivitis . The two treatment groups were similar at baseline . The treatments were equally effective and significantly ( p < 0.001 ) reduced the Cumulative Sum Score of the clinical signs and symptoms of bacterial conjunctivitis . At the end of the trial , there was no difference between the two treatments in the Cumulative Sum Score of signs and symptoms ( p = 0.63 ) , and the investigator ( p = 0.28 ) and patients ’ ( p = 0.50 ) assessment s of the success of therapy . The two drugs were equally well tolerated locally , with no serious systemic or local adverse drug reactions reported in any study patient . Bacteriological confirmation of acute conjunctivitis was possible in 96 patients ( lomefloxacin 47 , chloramphenicol 49 ) out of the 191 enrolled . Both treatments significantly ( p < 0.001 ) reduced the conjunctival bacterial colony count score with no difference ( p = 0.12 ) between the two treatment groups . In conclusion , lomefloxacin 0.3 % eye drops instilled twice daily were as effective and well tolerated as chloramphenicol 0.5 % eye drops instilled 5 times daily in the treatment of acute bacterial conjunctivitis Abstract Fucidic acid viscous eye drops 1 % given twice daily was compared with chloramphenicol eye drops 0.5 % given 6 times daily in patients with acute conjunctivitis . Patients were recruited from 38 general practitioners in Norway . The mean duration of treatment was 6.6 days for Fucidic acid , 6.2 days for chloramphenicol . There was no major differences between the two groups in the bacteriological findings , and there was no significant difference in response to treatment . The use of fusidic acid in a carbomer vehicle as in Fucithalmic , has proved to give a long‐lasting antibiotic concentration in the tear fluid , which allows the preferable twice daily application One hundred forty-three patients ( 207 eyes ) with conjunctivitis or blepharoconjunctivitis were investigated to determine ( 1 ) the safety of topical corticosteroid therapy and the relative efficacy of formulations of increasing potency and ( 2 ) the effectiveness of a steroid-antibiotic preparation compared to each of its components alone and to a placebo . The corticosteroids were equally effective in suppressing conjunctival inflammation ; all were more effective than the placebo . Active conjunctivitis was controlled more readily by those preparations containing a steroid , both alone and in combination . The corticosteroid alone ( dexamethasone ) was more effective in producing inactivation of conjunctivitis than the antibiotic alone ( a mixture of neomycin sulfate and polymyxin B sulfate ) . This observation remained unchanged when cases of Staphylococcus aureus conjunctivitis were analyzed separately . No serious complications result ed from any treatment regimen |
12,571 | 23,244,131 | Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC , and EGFR-TKI monotherapy was associated with less toxicity and better tolerability .
Moreover , our data also demonstrated that EGFR- TKI monotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with st and ard second-line chemotherapy . | PURPOSE To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitor monotherapy ( EFGR-TKIs : gefitinib or erlotinib ) with st and ard second-line chemotherapy ( single agent docetaxel or pemetrexed ) in previously treated advanced non-small-cell lung cancer ( NSCLC ) . | Background : Erlotinib ( Tarceva , OSI Pharmaceuticals , Melville , NY ) is an oral , epidermal growth factor receptor tyrosine kinase inhibitor that has antitumor activity and good tolerability in non-small cell lung cancer ( NSCLC ) . In particular , higher response rates have been reported in Asian patients than in Western patients . The aim of this study conducted by the Korean Cancer Study Group was to evaluate the efficacy and tolerability of erlotinib monotherapy as a palliative treatment for advanced NSCLC patients in Korea . Patients and Methods : Patients with histologically or cytologically confirmed stage IIIB or IV NSCLC including recurrent or metastatic disease , with performance status from 0 to 3 , were eligible either if they had received any anticancer treatment except epidermal growth factor receptor inhibitors or if they were unsuitable for chemotherapy because of poor performance status . Enrolled patients were treated with oral erlotinib at a dose of 150 mg daily until disease progression or development of intolerable toxicity . Results : A total of 120 patients were enrolled between January 2005 and May 2006 . Forty-four patients ( 36.7 % ) were female and 72 patients were current or former smoker . Fifty percent of patients had received one prior palliative chemotherapy regimens and 34.2 % had two or more prior palliative regimens . The overall tumor response rate was 24.2 % ( 95 % confidence interval [ CI ] , 16.8–32.8 % ) with 4 complete responses and 25 partial responses , and the disease control rate was 56.7 % . The favorable clinical variables for tumor response were female ( P = 0.001 ) , never smokers ( P = 0.041 ) , and adenocarcinoma ( P = 0.001 ) . The most common adverse event was skin rash ( 78 % of which grade 3 or 4 skin rash occurred in 13.3 % of the patients ) . With a median follow-up of 23.6 months , the median time to progression was 2.7 months ( 95 % CI , 2.2–3.2 ) , and the median overall survival was 12.9 months ( 95 % CI , 6.9–18.8 ) . By multivariate analysis , female and development of skin rash were significantly associated with longer time to progression and overall survival . Conclusion : Erlotinib monotherapy showed significant antitumor activity and an acceptable tolerability profile as a palliative treatment in advanced NSCLC patients in Korea , especially in females , never smokers , and patients with adenocarcinoma histology Purpose : The ISTANA ( IRESSA as Second-line Therapy in Advanced NSCLC — KoreA ) study compared gefitinib with docetaxel in patients with advanced or metastatic non – small cell lung carcinoma ( NSCLC ) pretreated with platinum-based chemotherapy . Experimental Design : We conducted a multicenter , r and omized , open-label phase III trial of gefitinib ( 250 mg/d ) versus docetaxel ( 75 mg/m2 day 1 every 3 weeks ) in patients with advanced or metastatic NSCLC treated with one previous platinum-based chemotherapy . The primary endpoint was progression-free survival . Results : A total of 161 patients ( male , 62 % ; never smoker , 41 % ; adenocarcinoma , 68 % ) were enrolled . Progression-free survival was longer for gefitinib compared with docetaxel ( hazard ratio , 0.729 ; 90 % confidence interval , 0.533 - 0.998 ; one-sided P = 0.0441 ) . Gefitinib significantly improved objective response rate ( 28.1 % versus 7.6 % ; two-sided P = 0.0007 ) . In the final analysis of overall survival , the hazard ratio was 0.870 ( 95 % confidence interval , 0.613 - 1.236 ; two-sided P = 0.4370 ) . No significant differences were seen in the quality of life or symptom improvement rates between the two treatment groups . Gefitinib was well tolerated , was consistent with previous data and disease , and had fewer serious adverse events and fewer Common Terminology Criteria for Adverse Events grade 3 or 4 adverse events than docetaxel . The incidence of interstitial lung disease – type events was 3.7 % ( n = 3 ) with gefitinib and 3.9 % ( n = 3 ) with docetaxel . Conclusions : The primary endpoint of progression-free survival was longer with gefitinib than docetaxel , and the secondary endpoints showed superior objective response rate , good tolerability , and similar quality of life improvement rates for gefitinib than docetaxel . Therefore , gefitinib is an important valid treatment option for second-line therapy for Korean NSCLC patients . Clin Cancer Res ; 16(4 ) ; PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy . Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel . Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks Our objective was to evaluate gefitinib ( IRESSA ) , an epidermal growth factor receptor tyrosine kinase inhibitor , versus docetaxel as second-line monotherapy for advanced non-small-cell lung cancer ( NSCLC ) . SIGN ( Second-line Indication of Gefitinib in NSCLC ; code 1839IL/0503 ) was a multicenter , r and omized , parallel-group , open-label , phase II trial that investigated oral gefitinib ( 250 mg/day ) or i.v . docetaxel ( 75 mg/m2 every 3 weeks ) in patients with advanced NSCLC who had previously received one chemotherapy regimen . The primary objective was assessment of symptom improvement ( using the FACT-L Lung Cancer Subscale ) . Secondary objectives included quality of life ( FACT-L total score ) , response rate ( using RECIST ) , overall survival and safety . This trial recruited 141 patients ( 68 to gefitinib and 73 to docetaxel ) who received treatment for a median duration of 3.0 ( gefitinib ) and 2.8 ( docetaxel ) months . Similar efficacy was observed with gefitinib and docetaxel , 36.8 and 26.0 % symptom improvement rates , 33.8 and 26.0 % quality -of-life improvement rates , 13.2 and 13.7 % objective response rates , and 7.5 and 7.1 months median overall survival , respectively . Fewer drug-related adverse events were observed with gefitinib compared with docetaxel ( all grade s : 51.5 versus 78.9 % ; Common Toxicity Criteria grade 3/4 : 8.8 versus 25.4 % ) . There were no withdrawals or deaths due to drug-related adverse events with gefitinib , while three patients withdrew and three died due to adverse events in the docetaxel group that were possibly drug related . We conclude efficacy with gefitinib was similar to docetaxel , but with a more favorable tolerability profile , in the second-line treatment of advanced NSCLC . These results support further investigation of gefitinib in this disease setting BACKGROUND Erlotinib , docetaxel , and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer ( NSCLC ) , but no head-to-head data from large clinical trials are available . We undertook the Tarceva In Treatment of Advanced NSCLC ( TITAN ) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC . METHODS TITAN was an international , r and omised multicentre , open-label , phase 3 study that was done at 77 sites in 24 countries . Chemotherapy-naive patients with locally advanced , recurrent , or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy , after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN . Enrolled patients were r and omly assigned ( 1:1 ) by a minimisation method to ensure balanced stratification , to receive erlotinib 150 mg/day or chemotherapy ( st and ard docetaxel or pemetrexed regimens , at the treating investigators ' discretion ) , until unacceptable toxicity , disease progression , or death . Patients were stratified by disease stage , Eastern Cooperative Oncology Group performance status , smoking history , and region of residence . The primary endpoint was overall survival in the intention-to-treat population . TITAN was halted prematurely because of slow recruitment . This study is registered with Clinical Trials.gov , number NCT00556322 . FINDINGS Between April 10 , 2006 , and Feb 24 , 2010 , 2590 chemotherapy-naive patients were treated with first-line platinum doublet chemotherapy , of whom 424 had disease progression and were enrolled into TITAN . 203 patients were r and omly assigned to receive erlotinib and 221 were assigned to receive chemotherapy . Median follow-up was 27·9 months ( IQR 11·0 - 36·0 ) in the erlotinib group and 24·8 months ( 12·1 - 41·6 ) in the chemotherapy group . Median overall survival was 5·3 months ( 95 % CI 4·0 - 6·0 ) with erlotinib and 5·5 months ( 4·4 - 7·1 ) with chemotherapy ( hazard ratio [ HR ] 0·96 , 95 % CI 0·78 - 1·19 ; log-rank p=0·73 ) . The adverse-event profile of each group was in line with previous studies . Rash ( 98/196 [ 50 % ] in the erlotinib group vs 10/213 [ 5 % ] in the chemotherapy group for all grade s ; nine [ 5 % ] vs none for grade 3 or 4 ) and diarrhoea ( 36 [ 18 % ] vs four [ 2 % ] for all grade s ; five [ 3 % ] vs none for grade 3 or 4 ) were the most common treatment-related adverse events with erlotinib , whereas alopecia ( none vs 23 [ 11 % ] for all grade s ; none vs one [ < 1 % ] for grade 3/4 ) was the most common treatment-related adverse event with chemotherapy . INTERPRETATION No significant differences in efficacy were noted between patients treated with erlotinib and those treated with docetaxel or pemetrexed . Since the toxicity profiles of erlotinib and chemotherapy differ , second-line treatment decisions should take into account patient preference and specific toxicity risk profiles . FUNDING F Hoffmann-La Roche 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 BACKGROUND We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer Gefitinib was compared with pemetrexed as second‐line therapy in a clinical ly selected population previously treated with platinum‐based chemotherapy PURPOSE Gefitinib and erlotinib are potent EGFR TKIs , with antitumor activity . In this r and omized , single-center , non-comparative phase II trial , the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with locally advanced , metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations ( female , adenocarcinoma histology , and never-smoker ) were eligible . RESULTS A total of 96 ( 48 per arm ) patients were r and omly assigned to gefitinib- or erlotinib-arm , respectively . Baseline characteristics were well-balanced between the two arms . The response rates ( RR ) were 47.9 % in the gefitinib arm and 39.6 % in the erlotinib arm . Median PFS was 4.9 months ( 95 % CI , 1.3 - 8.5 ) in the gefitinib arm and 3.1 months ( 95 % CI , 0.0 - 6.4 ) in the erlotinib arm . The most common grade 3/4 toxicity was skin rash . Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm ( RR ( % ) 47.9 vs. 39.6 , p=0.269 ; median survival ( months ) 4.9 vs. 3.1 , p=0.336 ) . There was no significant difference in QOL between the two arms . CONCLUSION Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC . We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population LBA7501 Background : While the benefit of EGFR tyrosine kinase inhibitors in the treatment of patients with NSCLC harboring EGFR mutations has been widely established , their value in treating patients with wt EGFR is still debated . To assess the role of erlotinib in these patients , we performed an independent multicenter phase III trial ( Tarceva Italian Lung Optimization Trial [ TAILOR ] NCT00637910 ) , comparing erlotinib to docetaxel in second line treatment , having overall ( OS ) and progression free survival ( PFS ) as principal and secondary endpoints , respectively . METHODS EGFR and KRAS mutational status were assessed by direct sequencing in all eligible patients ; only patients with wt EGFR NSCLC ( exons 19 and 21 ) at progression , and previously treated with a first line platinum-based regimen , were r and omized to receive either erlotinib 150 mg daily or docetaxel 75 mg/m2 ( 3-weekly ) or 35 mg/m2 ( weekly ) until disease progression or unacceptable toxicity occurred . To detect an hazard ratio of 0.67 ( 2-sided 5 % significance level for the log-rank test and a power of 80 % ) , 199 events were required for both OS and PFS evaluation . RESULTS On the planned analysis date ( March 30 , 2012 ) , 221 patients had been r and omized and 218 were evaluable ( docetaxel 110 , erlotinib 108 ; three major violations excluded ) . At a median follow-up of 20 months , 199 relapses and 157 deaths were recorded . The Kaplan-Meier PFS curves showed a highly significant increase favoring docetaxel ( HR 0.70 with 95 % CI 0.53 - 0.94 ; p = 0.016 ) over erlotinib regimen . The HR translated into an estimated absolute difference in 6-months PFS of 12 % ( 16 % vs 28 % ) . Data concerning toxicity were consistent with the literature . CONCLUSIONS In terms of PFS , our results indicate a clear superiority of docetaxel over erlotinib as second line treatment for patients without EGFR mutations in exons 19 or 21 . Analysis of OS will be conducted as far as the planned number of 199 deaths is reached BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo . At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin BACKGROUND Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy . We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy . METHODS We undertook an open-label phase III study with recruitment between March 1 , 2004 , and Feb 17 , 2006 , at 149 centres in 24 countries . 1466 patients with pretreated ( > /=one platinum-based regimen ) advanced non-small-cell lung cancer were r and omly assigned with dynamic balancing to receive gefitinib ( 250 mg per day orally ; n=733 ) or docetaxel ( 75 mg/m(2 ) intravenously in 1-h infusion every 3 weeks ; n=733 ) . The primary objective was to compare overall survival between the groups with co- primary analyses to assess non-inferiority in the overall per- protocol population and superiority in patients with high epidermal growth factor receptor (EGFR)-gene-copy number in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00076388 . FINDINGS 1433 patients were analysed per protocol ( 723 in gefitinib group and 710 in docetaxel group ) . Non-inferiority of gefitinib compared with docetaxel was confirmed for overall survival ( 593 vs 576 events ; hazard ratio [ HR ] 1.020 , 96 % CI 0.905 - 1.150 , meeting the predefined non-inferiority criterion ; median survival 7.6 vs 8.0 months ) . Superiority of gefitinib in patients with high EGFR-gene-copy number ( 85 vs 89 patients ) was not proven ( 72 vs 71 events ; HR 1.09 , 95 % CI 0.78 - 1.51 ; p=0.62 ; median survival 8.4 vs 7.5 months ) . In the gefitinib group , the most common adverse events were rash or acne ( 360 [ 49 % ] vs 73 [ 10 % ] ) and diarrhoea ( 255 [ 35 % ] vs 177 [ 25 % ] ) ; whereas in the docetaxel group , neutropenia ( 35 [ 5 % ] vs 514 [ 74 % ] ) , asthenic disorders ( 182 [ 25 % ] vs 334 [ 47 % ] ) , and alopecia ( 23 [ 3 % ] vs 254 [ 36 % ] ) were most common . INTERPRETATION INTEREST established non-inferior survival of gefitinib compared with docetaxel , suggesting that gefitinib is a valid treatment for pretreated patients with advanced non-small-cell lung cancer |
12,572 | 27,420,164 | Reported adverse effects were minor and similar in the sucrose and control groups .
Sucrose is not effective in reducing pain from circumcision .
The effectiveness of sucrose for reducing pain/stress from other interventions such as arterial puncture , subcutaneous injection , insertion of nasogastric or orogastric tubes , bladder catherization , eye examinations and echocardiography examinations are inconclusive .
Sucrose is effective for reducing procedural pain from single events such as heel lance , venipuncture and intramuscular injection in both preterm and term infants .
No serious side effects or harms have been documented with this intervention . | BACKGROUND Administration of oral sucrose with and without non-nutritive sucking is the most frequently studied non-pharmacological intervention for procedural pain relief in neonates .
OBJECTIVES To determine the efficacy , effect of dose , method of administration and safety of sucrose for relieving procedural pain in neonates as assessed by vali date d composite pain scores , physiological pain indicators ( heart rate , respiratory rate , saturation of peripheral oxygen in the blood , transcutaneous oxygen and carbon dioxide ( gas exchange measured across the skin - TcpO2 , TcpCO2 ) , near infrared spectroscopy ( NIRS ) , electroencephalogram ( EEG ) , or behavioural pain indicators ( cry duration , proportion of time crying , proportion of time facial actions ( e.g. grimace ) are present ) , or a combination of these and long-term neurodevelopmental outcomes . | Background : The analgesic effect of oral sucrose in newborn infants undergoing painful procedures is generally accepted . For blood sampling , some studies have shown that venepuncture ( VP ) is less painful than heel lance ( HL ) . Objective : To determine the least painful and most effective method among blood sampling by VP or HL with or without sucrose . Design : R and omised , double blind , placebo controlled trial . Subjects : A total of 100 healthy , full term newborn infants being screened for inborn errors of metabolism were r and omly allocated to one of four experimental groups ( 25 infants in each ) . Intervention and outcome measure : Seven specially trained nurses took turns to carry out blood sampling two minutes after administration of oral sucrose or water . Neonatal pain was assessed by the neonatal facial coding system ( NFCS ) , as well as by crying . Results : Without sucrose , the NFCS score was higher in the HL group than the VP group during blood sampling ( median 58 v 23 , p<0.001 ) . Oral sucrose significantly reduced the score of the HL group ( 58 v 47 , p<0.01 ) and also tended to reduce the score of the VP group ( 23 v 2 , p<0.1 ) . However , the HL with sucrose group still had a higher score than the VP without sucrose group ( 47 v 23 , p<0.01 ) . Crying and the total procedure time showed the same trends as the NFCS score . Conclusions : VP is less painful and more effective than HL for blood sampling in newborn infants . Although oral sucrose may have an additive analgesic effect , it is not necessarily required if VP is used for blood sampling OBJECTIVE To explore techniques that can be utilized in addition to the dorsal penile nerve block ( DPNB ) to further reduce the neonate 's stress and pain from routine circumcision , and thus make the procedure more humane . SETTING Level 1 nursery at a community hospital . SUBJECTS Eighty healthy , term , newborn male infants scheduled for routine neonatal circumcision . STUDY DESIGN Prospect i ve and r and omized ; double blind and placebo controlled for the study solutions . METHODS Four statistically similar groups of 20 were studied . The control group included infants circumcised using : a ) a rigid plastic restraint board ; b ) st and ard DPNB ; and c ) a pacifier dipped in water to comfort the infant . Each study group differed from the controls in one variable including : 1 ) using a specially design ed , physiologic circumcision restraint chair ; 2 ) pH buffering of lidocaine hydrochloride used for DPNB ; and 3 ) offering a pacifier dipped in a 24 % sucrose solution during the DPNB and circumcision . Behavioral observations were recorded and compared for each group starting before the injection of lidocaine hydrochloride and continuing through the completion of the circumcision . Plasma for cortisol levels were collected 30 minutes after the circumcision . RESULTS Neonates circumcised on the new restraint chair showed a significant decrease in distress scores ( > 50 % ) compared with the control group on the rigid molded-plastic restraint . The pacifier dipped in sucrose had a distress-reducing effect during both the post-DPNB injection and circumcision periods . The infants who were injected with the buffered lidocaine showed no differences in distress from the controls . The plasma cortisol levels were not significantly affected by any additional technique and were comparable to the levels previously reported . CONCLUSIONS When neonatal circumcisions are performed routinely , they should be done as humanely as possible . This study demonstrates that , when used in conjunction with DPNB , a pacifier dipped in 24 % sucrose and a more comfortable , padded , and physiologic restraint can be useful in decreasing distress and pain Intraoral sucrose induces rapid and sustained calm in crying newborns and transiently increases mouthing and h and -mouth contact . To determine whether these effects are specific to sucrose and to explore which properties of orogustatory stimuli might contribute to this effect , 60 crying newborns were r and omized to receive 250 ul of 24 % sucrose solution , 0.25 % quinine hydrochloride solution , or corn oil as well as water in a mixed parallel crossover design . Relative to water , sucrose persistently reduced crying , and transiently increased mouthing and h and -mouth contact as previously demonstrated . While quinine produces a " disgust " face in calm infants , in crying infants it transiently decreased crying and increased mouthing , but did not affect h and -mouth contact . Corn oil had no specific effect on crying , mouthing or h and -mouth contact . The results imply that crying newborns respond differentially to orogustatory stimuli , that taste " salience " rather than positive hedonic valence may account for initial crying reduction and increased mouthing , and that these behavioral effects are not induced by at least one lipid nutrient Abstract To study the patterns of supraspinal pain processing in neonates , we hypothesized that acute pain causes haemodynamic changes associated with activation of the primary somatosensory cortex . Forty preterm neonates at 28–36 weeks of gestation ( mean = 32.0 ) and at 25–42 h ( mean = 30.7 ) of age were studied following st and ardized tactile ( skin disinfection ) and painful ( venipuncture ) stimuli . Changes in regional cerebral haemodynamics were monitored by near infrared spectroscopy ( NIRS ) over both somatosensory cortices in 29 newborns , and over the contralateral somatosensory and occipital areas in 11 newborns . Heart rate ( HR ) and peripheral oxygen saturation ( SaO2 ) were recorded simultaneously with NIRS parameters : oxygenated [ HbO2 ] , deoxygenated , and total hemoglobin . Tactile stimulation produced no changes in HR or SaO2 . HR increased in the first 20 s ( p < 0.001 ) , while SaO2 decreased during the 40 s after venipuncture ( p < 0.0001 ) . Following tactile or painful stimulation , [ HbO2 ] increased bilaterally regardless of which h and was stimulated ( p < 0.0001 ) . Pain‐induced [ HbO2 ] increases in the contralateral somatosensory cortex ( p < 0.05 ) were not mirrored in the occipital cortex ( p > 0.1 ) . Pain‐related [ HbO2 ] increases were more pronounced in male neonates ( p < 0.05 on left , p < 0.001 on right ) , inversely correlated with gestational age ( r = −0.53 on left , p < 0.01 ; r = −0.42 on right , p < 0.05 ) and directly correlated with postnatal age ( r = 0.75 on left , p < 0.0001 ; r = 0.67 on right , p < 0.0001 ) . Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex , implying conscious sensory perception in preterm neonates . Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates or preterm neonates at lower gestational ages This experiment had three goals : 1 . To identify the basis of sucking-induced analgesia in healthy , term , newborn humans undergoing the painful , routine , procedure of heel lance and blood collection . 2 . To evaluate how taste-induced and sucking-induced analgesias combine to combat pain . 3 . To determine whether facial grimacing was an accurate index of diminished pain , or whether it was linked to tissue trauma . We report that : 1 . Sucking an unflavored pacifier was analgesic when and only when suck rate exceeded 30 sucks/min . 2 . The combination of sucrose and nonnutritive sucking was remarkably analgesic ; we saw no behavioral indication in nine of the ten infants that the heel lance had even occurred . 3 . Grimacing was reduced to almost naught by procedures that essentially eliminated crying and markedly reduced heart rate during the blood harvesting procedure There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive . Because sweet solutions such as sucrose , given orally , may relieve pain in neonates , we decided to compare the effects of two concentrations of glucose ( normally used for intravenous infusions ) and of breast milk in a r and omized controlled trial in 120 babies requiring heel‐prick tests . Glucose solutions and breast milk are readily available in the neonatal department . No other treatment was given . Our results strongly suggest that 1 ml of a 30 % glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns . Breast milk and 10 % glucose did not have a similar effect OBJECTIVE To determine whether milk and its components reduce crying in newborns during and after blood collection for phenylketonuria evaluation . METHODOLOGY Seventy-two normal newborns ingested 2 mL of milk ( Similac ) , Ross Special Formula , fat , protein , lactose , sucrose , or water for the 2 minutes preceding blood collection via heel lance . Crying duration during and for the 3 minutes after the procedure was determined by scorers who were blind to the ingestive substance . RESULTS Sucrose and Similac each reduced crying during the blood collection procedure . Sucrose , fat , protein , and Ross Special Formula were effective during the 3-minute recovery period . Neither water nor lactose were effective during or after blood collection . CONCLUSION Milk and some of its components are antinociceptive in human newborns . Based on previous studies , reduced crying during and after painful stimulation may be mediated through endogenous opioids . These findings are of potential clinical significance : natural protective mechanisms , normally engaged during suckling , may safely and noninvasively be activated to reduce newborn crying to painful stimulation The aim of this study was to evaluate the effectiveness of different oral carbohydrate solutions for alleviation of pain in healthy preterm babies . Thirty-one preterm infants who were having blood drawn by heel prick were given 2 ml of solution A ( 20 % sucrose ) , solution B ( 20 % glucose ) or solution C ( placebo , sterile water ) into the mouth , 2 min before lancing . Behavioural responses to this painful stimulus were measured by duration of crying and facial expressions ( Neonatal Facial Coding System , NFCS ) and physiological responses were measured by heart rate ( HR ) , respiratory rate ( RR ) , and oxygen saturation changes ( SaO2 ) . Infants had a mean birth weight ( ±SD ) of 1,401 g ( 406 ) , gestational age of 30.5 weeks ( 2.7 ) ; at the time of the procedure the postmenstrual age was 32.3 weeks ( 1.5 ) . There was no significant difference in the time spent squeezing the heel between the three groups ( P = 0.669 ) . After the heel prick of both the sucrose and glucose groups the duration of first cry and total crying time was significantly reduced ( P = 0.005 and P = 0.007 ) . When the babies received placebo they showed a significantly higher NFCS score at 4 and 5 min after the heel prick ( P = 0.009 and 0.046 respectively ) . Following painful stimulus HR increased significantly in the first 3 min compared with baseline , and at the first minute the mean of the HR was found to be significantly higher in the placebo group than in the sucrose and glucose groups ( P = 0.007 ) . We concluded that both sucrose and glucose administered orally before a heel prick reduce the pain response in preterm infants BACKGROUND : Eye examinations for retinopathy of prematurity ( ROP ) are painful to the neonate . The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit ( NICU ) , but does not completely suppress painful responses . Sweet solutions have been shown to reduce procedural pain in newborns . OBJECTIVE : To examine whether the addition of sucrose 24 % to topical anesthetic improves procedural pain control during the ROP eye examination . METHODS : Neonates born at ⩽30 weeks ' gestation were included in this placebo-controlled , double-blind , crossover study . Patients were r and omly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5 % plus 2 mL of sucrose 24 % or proparacaine HCl ophthalmic solution 0.5 % plus 2 mL of sterile water ( placebo ) prior to an eye examination . In a subsequent eye examination , each patient received the alternate treatment . Oral sucrose and sterile water were prepared in the pharmacy in identical syringes , and physicians , nurses , and pharmacists in the NICU were blinded to the treatment given . Pain was measured using the Premature Infant Pain Profile ( PIPP ) scoring system , which measures both physical and physiologic measures of pain , and the scores were simultaneously assessed by 2 study nurses . PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum . The same ophthalmologist performed all eye examinations . Several different definitions of a pain response were investigated . RESULTS : Twenty-three infants were studied , with 12 receiving sucrose and 11 receiving placebo as the first treatment . For 3 of the 5 definitions of pain response , patients experienced significantly less pain at speculum insertion with sucrose than with placebo . After the ROP examination , pain responses were similar with either sucrose or placebo . CONCLUSIONS : Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP OBJECTIVE To investigate interventions that affect pain reduction during vaccination in infants and children attending a well-child unit . STUDY DESIGN A consecutive sample of 243 children between age 0 and 48 months receiving their routine vaccinations was r and omly assigned to 1 of the study groups . A total of 158 infants under age 6 months were r and omly assigned to breast-feeding or no breast-feeding during immunization , and 85 children age 6 to 48 months were r and omly assigned to receive 12 % sucrose solution , lidocaine-prilocaine cream , or no intervention . All children were evaluated for crying time and pain score by a pediatrician using the Neonatal Infant Pain Scale ( NIPS ) for those under age 12 months and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) for those over age 12 months . RESULTS Breast-feeding in infants under age 6 months and use of sucrose or lidocaine-prilocaine in children age 6 to 48 months significantly reduced crying time and pain scores compared with controls . No difference in outcome was seen between the sucrose and lidocaine-prilocaine treatment groups . CONCLUSIONS Here we exp and on previous findings by demonstrating that breast-feeding may have an analgesic effect up to age 6 months and that in older children , both sucrose and lidocaine-prilocaine reduce vaccination pain The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two st and ard painful hospital procedures : blood collection via heel lance and circumcision . Infants who drank 2 mL of a 12 % sucrose solution prior to blood collection cried 50 % less during the blood collection procedure than did control infants who had received 2 mL of sterile water . Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline . Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision . Specifically , control infants who underwent a st and ard circumcision procedure without intervention cried 67 % of the time . A water-moistened pacifier reduced crying to 49 % ( P less than .01 ) . Crying was reduced further to 31 % ( P less than .05 ) by providing infants with a sucrose-flavored pacifier to suck . These findings , which parallel results obtained in studies of pain in infant rats , provide a potent yet simple , benign intervention to help alleviate stress and pain routinely experienced by human infants OBJECTIVE : To determine the relative effectiveness of liposomal lidocaine , sucrose , and their combination for reducing pain in term newborns . METHODS : Ours was a double-blind , r and omized , controlled , double-dummy trial of 330 healthy term newborns . Before venipuncture for the newborn screening test , neonates received ( 1 ) 1 g of liposomal lidocaine cream topically , ( 2 ) 2 mL of 24 % sucrose solution orally , or ( 3 ) sucrose and liposomal lidocaine . The facial grimacing score ( 0–100 ) was used to assess pain . Adverse events and lidocaine levels were used to assess safety . RESULTS : Infant characteristics did not differ among groups . Facial grimacing scores were lower in the sucrose group compared with those in the liposomal lidocaine group ( mean difference : −27 [ 95 % confidence interval ( CI ) : −36 to −19 ; P < .001 ) and for the sucrose plus liposomal lidocaine group compared with those in the liposomal lidocaine group ( mean difference : −23 [ 95 % CI : −31 to −14 ] ; P < .001 ) . The sucrose and sucrose plus liposomal lidocaine groups did not differ ( mean difference : −5 [ 95 % CI : −13 to 4 ] ; P = .3 ) . Local skin reactions were not observed , and the incidence of spitting up did not differ between sucrose-exposed and non – sucrose-exposed infants ( 1.4 % vs 2.7 % , respectively ; P = .22 ) . The mean ( SD ) plasma lidocaine level was 44.6 ( 55.3 ) ng/mL. CONCLUSIONS : Sucrose was more effective than liposomal lidocaine for reducing pain during venipuncture in newborns . The addition of liposomal lidocaine to sucrose did not confer any additional benefit to sucrose alone . There was no evidence of harm from liposomal lidocaine or sucrose OBJECTIVES : To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants . METHODS : A multicenter r and omized controlled trial in 3 NICUs in Switzerl and compared the effectiveness of oral sucrose , facilitated tucking ( FT ) , and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation . Data were collected during the first 14 days of their NICU stay . Three phases ( baseline , heel stick , recovery ) of 5 heel stick procedures were videotaped for each infant . Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in r and om order by using the Bernese Pain Scale for Neonates , a vali date d pain tool . RESULTS : Seventy-one infants were included in the study . Interrater reliability was high for the total Bernese Pain Scale for Neonates score ( Cronbach ’s α : 0.90–0.95 ) . FT alone was significantly less effective in relieving repeated procedural pain ( P < .002 ) than sucrose ( 0.2 mL/kg ) . FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores ( P = .003 ) compared with both the single-treatment groups . There were no significant differences in pain responses across gestational ages . CONCLUSIONS : Sucrose with and without FT had pain-relieving effects even in preterm infants of < 32 weeks of gestation having repeated pain exposures . These interventions remained effective during repeated heel sticks across time . FT was not as effective and can not be recommended as a nonpharmacologic pain relief intervention for repeated pain exposure Objective : The objective of this study was to evaluate and compare the efficacy of combined sucrose and non-nutritive sucking ( NNS ) for analgesia in newborn infants undergoing heel-stick procedures . Study Design : This r and omized control trial was conducted in the neonatal intensive care unit of a tertiary care hospital over a period of 1 year . One hundred and eighty full-term neonates with birth weight > 2200 g and age > 24 h were r and omized to one of four interventions administered 2 min before the procedure : 2 ml of 30 % sucrose ( group I , n=45 ) or NNS ( group II , n=45 ) or both ( group III , n=45 ) or none ( group IV , n=45 ) . Primary outcome was composite score based on Premature Infant Pain Profile ( PIPP ) score . Result : Baseline variables were comparable among the groups . Median ( interquartile range ) PIPP score was 3 ( 2 to 4 ) in group III as compared with 7 ( 6.5 to 8) in group I , 9 ( 7 to 11 ) in group II and 13 ( 10.5 to 15 ) in group IV . Group III had significant decrease in the median PIPP score compared with other groups ( P=0.000 ) . Median PIPP score also decreased significantly with any intervention as compared with no intervention ( P=0.000 ) . Conclusion : Sucrose and /or NNS are effective in providing analgesia in full-term neonates undergoing heel-stick procedures , with the combined intervention being more effective compared with any single intervention OBJECTIVE To determine the efficacy of sucrose analgesia for procedural pain during the first week of life in preterm neonates in neonatal intensive care units on enhancing later clinical outcomes . METHODS A total of 107 preterm neonates who were born at < 31 weeks ' postconceptional age ( PCA ) entered this double-blind , r and omized , controlled trial within 48 hours of birth at 3 level III university-affiliated neonatal intensive care units in Canada , and 103 completed the study . Sucrose ( 0.1 mL of 24 % ) or sterile water was administered orally up to 3 times , 2 minutes apart , for every invasive procedure during a 7-day period . Motor development and vigor , and alertness and orientation components of the Neurobehavioral Assessment of the Preterm Infant were measured at 32 , 36 , and 40 weeks ' PCA ; Score for Neonatal Acute Physiology was measured on the last day of intervention ; and Neuro-Biological Risk Score ( NBRS ) was measured at 2 weeks of age and at discharge . Primary analyses of covariance were applied for each outcome to compare group differences followed by secondary analyses using st and ard linear regression within each group to determine predictors of outcomes . RESULTS Although there were no differences between the groups on any outcomes , there were significant dose-related effects within each group . In the sucrose group only , higher number of doses of sucrose predicted lower scores on motor development and vigor , and alertness and orientation at 36 weeks ' , lower motor development and vigor at 40 weeks ' , and higher NBRS at 2 weeks ' postnatal age . Higher number of invasive procedures was predictive of higher NBRS both times in the water group . CONCLUSIONS Repeated use of sucrose analgesia in infants < 31 weeks ' PCA may put infants at risk for poorer neurobehavioral development and physiologic outcomes . Additional study is needed to determine the most appropriate age and duration of sucrose analgesia in preterm infants OBJECTIVE To determine the efficacy of 25 % oral sucrose in the reduction of pain during a heel lance procedure in sick hospitalized infants . METHODOLOGY In a blinded r and omized- controlled trial , hospitalized infants were given either 1 mL 25 % sucrose or 1 mL water 2 min prior to a heel lance procedure . Pain assessment comprised a four-point facial expression score , incidence and duration of crying , heart rate and oxygen saturation changes . RESULTS A total of 128 infants were included . Facial scores immediately upon heel lance , and at 1 and 2 min in the recovery period were reduced in the treatment ( sucrose ) group compared to the placebo ( water ) group ( P < 0.05 ) . At other observation points , the differences in facial scores between the two groups of infants did not reach statistical significance . Neither incidence nor duration of crying whilst the blood collection was in progress was significantly reduced by sucrose . In the 3-min recovery period following completion of the blood collection , incidence and duration of crying were significantly less in the treatment group of infants ( P < 0.05 ) . Physiological responses of heart rate and oxygen saturation were not attenuated by sucrose at any time point during or following the blood collection . CONCLUSION Oral sucrose was effective in reducing behavioural responses to pain upon heel lance and in the period following completion of a heel lance procedure in this group of sick hospitalized infants . This simple strategy can be promoted in institutions caring for sick babies , as a method of reducing behavioural responses to procedural pain CONTEXT Effective strategies to improve pain management in neonates require a clear underst and ing of the epidemiology and management of procedural pain . OBJECTIVE To report epidemiological data on neonatal pain collected from a geographically defined region , based on direct bedside observation of neonates . DESIGN , SETTING , AND PATIENTS Between September 2005 and January 2006 , data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospect ively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France ( 11.3 millions inhabitants ) for the Epidemiology of Procedural Pain in Neonates ( EPIPPAIN ) study . MAIN OUTCOME MEASURE Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy . RESULTS The mean ( SD ) gestational age and intensive care unit stay were 33.0 ( 4.6 ) weeks and 8.4 ( 4.6 ) calendar days , respectively . Neonates experienced 60,969 first-attempt procedures , with 42,413 ( 69.6 % ) painful and 18,556 ( 30.4 % ) stressful procedures ; 11,546 supplemental attempts were performed during procedures including 10,366 ( 89.8 % ) for painful and 1180 ( 10.2 % ) for stressful procedures . Each neonate experienced a median of 115 ( range , 4 - 613 ) procedures during the study period and 16 ( range , 0 - 62 ) procedures per day of hospitalization . Of these , each neonate experienced a median of 75 ( range , 3 - 364 ) painful procedures during the study period and 10 ( range , 0 - 51 ) painful procedures per day of hospitalization . Of the 42,413 painful procedures , 2.1 % were performed with pharmacological-only therapy ; 18.2 % with nonpharmacological-only interventions , 20.8 % with pharmacological , nonpharmacological , or both types of therapy ; and 79.2 % without specific analgesia , and 34.2 % were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons . Prematurity , category of procedure , parental presence , surgery , daytime , and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia , whereas mechanical ventilation , noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia . CONCLUSION During neonatal intensive care in the Paris region , large numbers of painful and stressful procedures were performed , the majority of which were not accompanied by analgesia Background Although sucrose has been accepted as an effective analgesic agent for procedural pain in neonates , previous studies are largely in the NICU population using the procedure of heel lance . This is the first report of the effect of sucrose , pacifier or the combination thereof for the procedural pain of venipuncture in infants in the pediatric emergency department population . Methods The study design was a double ( sucrose ) and single blind ( pacifier ) , placebo-controlled r and omized trial – factorial design carried out in a pediatric emergency department . The study population was infants , aged 0 – 6 months . Eighty-four patients were r and omly assigned to one of four groups : a ) sucrose b ) sucrose & pacifier c ) control d ) control & pacifier . Each child received 2 ml of either 44 % sucrose or sterile water , by mouth . The primary outcome measure : FLACC pain scale score change from baseline . Secondary outcome measures : crying time and heart rate change from baseline . Results Sucrose did not significantly reduce the FLACC score , crying time or heart rate . However sub-group analysis revealed that sucrose had a much greater effect in the younger groups . Pacifier use reduced FLACC score ( not statistically significant ) , crying times ( statistically significant ) but not heart rate . Subgroup analysis revealed a mean crying time difference of 76.52 seconds ( p < 0.0171 ) ( 0–1 month ) and 123.9 seconds ( p < 0.0029 ) ( 1–3 month ) . For subgroup age > 3 months pacifier did not have any significant effect on crying time . Age adjusted regression analysis revealed that both sucrose and pacifier had significant effects on crying time . Crying time increased with both increasing age and increasing gestational age . Conclusion Pacifiers are inexpensive , effective analgesics and are easy to use in the PED for venipuncture in infants aged 0–3 months . The benefits of sucrose alone as an analgesic require further investigation in the older infant , but sucrose does appear to provide additional benefit when used with a pacifier in this age group . Trial registration Current Controlled Trials IS RCT Objectives To determine if the addition of an inhaled equimolar mixture of nitrous oxide ( N2O ) and oxygen ( EMONO ) would produce superior pain relief to st and ard pharmacological and non-pharmacological measures during eye examination screening for retinopathy of prematurity ( ROP ) in premature infants . Study design A r and omised , double-blind controlled trial was conducted . Setting Royal Victoria Hospital , a tertiary neonatal intensive care unit in Montreal , Canada . Patients Stable spontaneously breathing premature infants with birth weights less than 1500 g or gestation of 30 weeks and less . Intervention During the eye examination , all infants were swaddled , received oral sucrose and topical anaesthetics . Control group infants received a mixture of 50 % oxygen and 50 % nitrogen ( n=18 ) administered by nasal cannula , while the intervention group received EMONO ( 50 % oxygen and 50 % N2O ) . Main outcome measures Pain was assessed by the premature infant pain profile ( PIPP ) . Results The mean PIPP score at speculum insertion in the control group ( 8.4 , 95 % CI 7.6 to 9.3 ) was comparable with the EMONO group ( 8.5 , 95 % CI 7.3 to 9.8 ) with a p value of 0.94 . There were no significant differences in heart rate or saturation between the two groups . EMONO inhalation was tolerated without any measured side effects . Conclusion EMONO does not produce any additional pain relief over currently used measures during ROP screening eye examinations . Systematic ally combining pharmacological and non-pharmacological treatment modalities appears to be the best option until newer treatments are proven effective . Clinical trials registration number Background Despite extensive research , institutional policies , and practice guidelines , procedural pain remains undertreated in hospitalized children . Knowledge translation ( KT ) strategies have been employed to bridge the research to practice gap with varying success . The most effective single or combination of KT strategies has not been found . A multifaceted KT intervention , Evidence -based Practice for Improving Quality ( EPIQ ) , that included tailored KT strategies was effective in improving pain practice s and clinical outcomes at the unit level in a prospect i ve comparative cohort study in 32 hospital units ( 16 EPIQ intervention and 16 St and ard Care ) , in eight pediatric hospitals in Canada . In a study of the 16 EPIQ units ( two at each hospital ) only , the objectives were to : determine the effectiveness of evidence -based KT strategies implemented to achieve unit aims ; describe the KT strategies implemented and their influence on pain assessment and management across unit types ; and identify facilitators and barriers to their implementation . Methods Data were collected from each EPIQ intervention unit on targeted pain practice s and KT strategies implemented , through chart review and a process evaluation checklist , following four intervention cycles over a 15-month period . Results Following the completion of the four cycle intervention , 78 % of 23 targeted pain practice aims across units were achieved within 80 % of the stated aims . A statistically significant improvement was found in the proportion of children receiving pain assessment and management , regardless of pre-determined aims ( p < 0.001 ) . The median number of KT strategies implemented was 35 and included reminders , educational outreach and material s , and audit and feedback . Units successful in achieving their aims implemented more KT strategies than units that did not . No specific type of single or combination of KT strategies was more effective in improving pain assessment and management outcomes . Tailoring KT strategies to unit context , support from unit leadership , staff engagement , and dedicated time and re sources were identified as facilitating effective implementation of the strategies . Conclusions Further research is required to better underst and implementation outcomes , such as feasibility and fidelity , how context influences the effectiveness of multifaceted KT strategies , and the sustainability of improved pain practice s and outcomes over time A r and omized study was done to compare non pharmacological methods to reduce the pain of heel pricks in 104 stable term neonates . Non-nutritive sucking ( NNS ) , rocking , massage , sucrose ( 20 percent ) , distilled water ( DW ) and expressed breast milk ( EBM ) were used as pain reducing agents . Duration of cry and Douleur Aiguë du Nouveau né ( DAN ) score were used to assess pain . Physiological parameters were also recorded before and after the stimulus . At 30 seconds after the stimulus , the pain scores were lowest in the sucrose group but this was not sustained at 1 , 2 and 4 minutes . At 2 and 4 minutes pain scores were lowest in the NNS and rocking groups as compared to sucrose , distilled water , expressed breast milk and massage . The total duration of crying was also lowest in the NNS and rocking groups . Physiological parameters were comparable in all groups . Babies who were in Prechtl State 1 and 2 ( sleeping ) at the time of stimulus showed significantly lesser response to pain compared to babies who were awake . This was seen in all the intervention groups . In conclusion , our study suggests that rocking or giving a baby a pacifier are more effective non-pharmacological analgesics than EBM , DW , sucrose or massage for the pain of heel pricks in neonates . A calm or sleeping state before a painful procedure also appears to decrease crying and pain scores Despite the recent increase in our underst and ing of the development of pain processing , it is still not known whether premature infants are capable of processing pain at a cortical level . In this study , changes in cerebral oxygenation over the somatosensory cortex were measured in response to noxious stimulation using real-time near-infrared spectroscopy in 18 infants aged between 25 and 45 weeks postmenstrual age . The noxious stimuli were heel lances performed for routine blood sampling ; no blood tests were performed solely for the purpose of the study . Noxious stimulation produced a clear cortical response , measured as an increase in total hemoglobin concentration [ HbT ] in the contralateral somatosensory cortex , from 25 weeks ( mean Δ[HbT ] = 7.74 μmol/L ; SE , 1.10 ) . Cortical responses were significantly greater in awake compared with sleeping infants , with a mean difference of 6.63 μmol/L [ 95 % confidence interval ( CI ) limits : 2.35 , 10.91 μmol/L ; mean age , 35.2 weeks ] . In awake infants , the response in the contralateral somatosensory cortex increased with age ( regression coefficient , 0.698 μmol/L/week ; 95 % CI limits : 0.132 , 1.265 μmol/L/week ) and the latency decreased with age ( regression coefficient , −0.9861 μmol/L/week ; 95 % CI limits : −1.5361 , −0.4361 μmol/L/week ; age range , 25–38 weeks ) . The response was modality specific because no response was detected after non-noxious stimulation of the heel , even when accompanied by reflex withdrawal of the foot . We conclude that noxious information is transmitted to the preterm infant cortex from 25 weeks , highlighting the potential for both higher-level pain processing and pain-induced plasticity in the human brain from a very early age BACKGROUND AND OBJECTIVE : Increasing data suggest that neonatal pain has long-term consequences . Nonpharmacologic techniques ( sucrose taste , pacifier suckling , breastfeeding ) are effective and now widely used to combat minor neonatal pain . This study examined the analgesic effect of sucrose combined with radiant warmth compared with the taste of sucrose alone during a painful procedure in healthy full-term newborns . METHODS : A r and omized , controlled trial included 29 healthy , full-term newborns born at the University of Chicago Hospital . Both groups of infants were given 1.0 mL of 25 % sucrose solution 2 minutes before the vaccination , and 1 group additionally was given radiant warmth from an infant warmer before the vaccination . We assessed pain by comparing differences in cry , grimace , heart rate variability ( ie , respiratory sinus arrhythmia ) , and heart rate between the groups . RESULTS : The sucrose plus warmer group cried and grimaced for 50 % less time after the vaccination than the sucrose alone group ( P < .05 , respectively ) . The sucrose plus warmer group had lower heart rate and heart rate variability ( ie , respiratory sinus arrhythmia ) responses compared with the sucrose alone group ( P < .01 ) , reflecting a greater ability to physiologically regulate in response to the painful vaccination . CONCLUSIONS : The combination of sucrose and radiant warmth is an effective analgesic in newborns and reduces pain better than sucrose alone . The ready availability of this practical nonpharmacologic technique has the potential to reduce the burden of newborn pain BACKGROUND Preterm infants manifest pain and stress by behavioural agitation and state change . Few studies have explored the effects of combining nonpharmacological interventions , i.e. non-nutritive sucking , oral sucrose , and facilitated tucking , on infants ' behaviours across painful procedures . OBJECTIVES To explore the effects of combined use of three nonpharmacological interventions ( non-nutritive sucking , oral sucrose , and facilitated tucking ) on infants ' pain- and stress-related behaviours during four assessment phases : baseline , intervention , heel stick , and recovery . DESIGN Prospect i ve , r and omised controlled trial . SETTING Level III neonatal intensive care unit in Taipei . METHOD A convenience sample of 110 infants ( gestational age 27 - 37 weeks ) needing heel sticks was r and omly assigned to five combinations of nonpharmacological treatments : ( 1 ) routine care , ( 2 ) non-nutritive sucking+facilitated tucking , ( 3 ) oral sucrose+facilitated tucking , ( 4 ) non-nutritive sucking+oral sucrose , and ( 5 ) non-nutritive sucking+oral sucrose+facilitated tucking . Outcomes were infants ' withdrawal or stress ( grimace , limb and trunk extension or squirming ) and approach or self-soothing ( sucking , sucking search , or mouthing ; h and holding or grasping ; and h and to mouth , face ) behaviours . RESULTS The frequency of infants ' withdrawal behaviours decreased significantly when they received combinations of nonpharmacological interventions before heel stick . Specifically , grimace frequency decreased by 32.2 % , 30.6 % , 19.7 % , and 13.8 % in infants receiving oral sucrose+non-nutritive sucking+facilitated tucking , non-nutritive sucking+oral sucrose , oral sucrose+facilitated tucking , and non-nutritive sucking+facilitated tucking , respectively , compared to those receiving routine care across assessment phases . Furthermore , infants ' frequency of limb and trunk extension or squirming decreased by 24.0 % when they received non-nutritive sucking+oral sucrose+facilitated tucking compared to those receiving routine care . Infants ' frequency of approach behaviours did not change significantly across all phases when they received non-nutritive sucking+oral sucrose+facilitated tucking , non-nutritive sucking+oral sucrose , and oral sucrose+facilitated tucking compared to those receiving routine care . CONCLUSIONS The combined use of nonpharmacological interventions ( non-nutritive sucking+oral sucrose+facilitated tucking ) effectively reduced the frequencies of infants ' withdrawal behaviours , i.e. grimace and limb and trunk extension or squirming . Our results provide evidence supporting clinicians ' incorporation of the combined use of facilitated tucking , oral sucrose , and non-nutritive sucking into clinical practice during painful procedures . Heel-stick procedures can be atraumatic when conducted while infants are stable and quiet , appropriately positioned , and stabilised and by offering facilitated tucking , oral sucrose , and non-nutritive sucking before gently sticking the heel and squeezing blood Background Procedural pain relief is sub-optimal in infants , especially small and vulnerable ones . Tetracaine gel 4 % ( Ametop ® , Smith-Nephew ) provides pain relief in children and larger infants , but its efficacy in smaller infants and for peripherally inserted central catheters ( PICC ) remains uncertain . The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight ( VLBW ) infants during insertion of a PICC . Methods Medically stable infants greater than or equal to 24 weeks gestation , requiring a non-urgent PICC , were included . Following r and omization and double blinding , 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes . The PICC was inserted according to a st and ard protocol . Pain was assessed using the Premature Infant Pain Profile ( PIPP ) . A 3-point change in the pain score was considered clinical ly significant , leading to a sample size of 54 infants , with 90 % statistical power . Local skin reactions and immediate adverse cardiorespiratory events were noted . The primary outcome , PIPP score at 1 minute , was analysed using an independent Student 's t-test . Results Fifty-four infants were included , 27 + /- 2 weeks gestation , 916 + /- 292 grams and 6.5 + /- 3.2 days of age . Baseline characteristics were similar between groups . The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group ( difference 0.86 , 95 % CI -1.86 , 3.58 ) . Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group ( difference -78 , 95 % CI -539 , 117 ) . Local skin erythema was observed transiently in 4 infants ( 3 in the treatment and 1 in the placebo group ) . No serious harms were observed . Conclusion Tetracaine 4 % when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants 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 BACKGROUND Pain of circumcision is only partially relieved by single modalities , such as penile nerve block , lidocaine-prilocaine cream , and sucrose pacifiers . OBJECTIVE To assess the effectiveness of a combination of interventions on the pain response of infants undergoing circumcision . METHODS Cohort study . Group 1 included infants circumcised using the Mogen clamp and combined analgesics ( lidocaine dorsal penile nerve block , lidocaine-prilocaine , acetaminophen , and sugar-coated gauze dipped in grape juice ) . Group 2 included infants circumcised using the Gomco clamp and lidocaine-prilocaine . Infants were videotaped during circumcision , and pain was assessed using facial activity scores and percentage of time spent crying . RESULTS There were 57 infants in group 1 and 29 infants in group 2 . Birth characteristics did not differ between groups . Infants in group 1 were older than infants in group 2 ( 17 days vs 2 days ) ( P < .001 ) . The mean duration of the procedure was 55 seconds and 577 seconds for infants in group 1 and 2 , respectively ( P < .001 ) . Facial action scores and percentage of time spent crying were significantly lower during circumcision for infants in group 1 ( P < .001 ) . The percentage of time spent crying was 18 % and 40 % for infants in groups 1 and 2 , respectively . No adverse effects were observed in infants in group 1 ; 1 infant in group 2 had a local skin infection . CONCLUSIONS Infants circumcised with the Mogen clamp and combined analgesia have substantially less pain than those circumcised with the Gomco clamp and lidocaine-prilocaine cream . Because of the immense pain during circumcision , combined local anesthesia and analgesia using the Mogen clamp should be considered ABSTRACT : In term infants sucrose given by mouth has been reported to reduce duration of crying after a heel prick . This study was design ed primarily to investigate the effect of sucrose administered orally immediately before heel lancing on the nociceptive reaction in preterm infants as assessed by change in heart rate and duration of crying . A secondary objective was to document changes in cerebral blood volume during acute pain . We used a r and omized , masked , placebo-controlled , crossover trial in a neonatal intermediate care unit in a level 3 perinatal center . The patients studied were 16 preterm infants ; birth weight , 900–1900 g ; gestational wk , 27–34 ; corrected postmenstrual age at time of investigation , 33–36 wk . Each infant was assessed twice receiving 2 mL of sucrose 50 % or 2 mL of distilled water in r and om order immediately before heel lance . Heart rate , thoracic movements , and transcutaneous blood gases were monitored continuously . Crying during the procedure was documented by a video-camera . A change in cerebral blood volume was assessed by near-infrared spectroscopy . We found the heart rate increased by a mean of 35 beats/min ( bpm ) after sucrose and 51 bpm after placebo ( median difference 16 bpm , interquartile range 1–30 bpm , p = 0.005 ) . Infants cried 67 % of time after sucrose and 88 % after placebo ( median difference 10 % , interquartile range 3–33 % , p = 0.002 ) . Cerebral blood volume decreased in 5 of 14 infants after sucrose and in 6 of 14 infants after placebo ( difference not significant ) . We concluded that sucrose administered orally before a heel lance reduces the pain reaction in preterm infants . Response of cerebral blood volume to pain does not seem to be altered by sucrose OBJECTIVE Inadequate assessment of pain in premature infants is a persistent clinical problem . The objective of this research was to develop and vali date a measure for assessing pain in premature infants that could be used by both clinicians and research ers . DESIGN The Premature Infant Pain Profile ( PIPP ) was developed and vali date d using a prospect i ve and retrospective design . Indicators of pain were identified from clinical experts and the literature . Indicators were retrospectively tested using four existing data sets . PATIENTS AND SETTING S Infants of varying gestational ages undergoing different painful procedures from three different setting s were utilized to develop and vali date the measure . METHODS AND RESULTS The largest data set ( n = 124 ) was used to develop the PIPP . The development process included determining the factor structure of the data , developing indicators and indicator scales and establishing internal consistency . The remaining three data sets were utilized to establish beginning construct validity . CONCLUSIONS The PIPP is a newly developed pain assessment measure for premature infants with beginning content and construct validity . The practicality and feasibility for using the PIPP in clinical practice will be determined in prospect i ve research in the clinical setting To assess the characteristics of sucrose as a pain-reducing substance , crying in 72 newborn humans during and after blood collection via heel prick was determined . In the first study infants drank 2 ml of water or 2 ml of a 0.17 - 0.34- or 0.51-M sucrose solution 1 min prior to blood collection . In the second experiment , a delay of 30 , 60 , 90 , 120 or 240 s was imposed between sucrose intake and the initiation of blood collection . The dose-response function for concentration was flat . The most effective time delay was 120 s. The effectiveness of the 2-min interval accords with previous findings of endogenous opioid release caused by sucrose taste . The flat dose-response function extends findings in rats and humans that the calming and pain-reducing effects of sucrose are not influenced by either concentration or volume , suggesting that the transduction from gustatory afferent to opioid-mediated efferent is of an on-off nature and not grade Premature infants are at risk for adverse motor outcomes , including cerebral palsy and developmental coordination disorder . The purpose of this study was to examine the relationship of antenatal , perinatal , and postnatal risk factors for abnormal development of the corticospinal tract , the major voluntary motor pathway , during the neonatal period . In a prospect i ve cohort study , 126 premature neonates ( 24 - 32 weeks ' gestational age ) underwent serial brain imaging near birth and at term-equivalent age . With diffusion tensor tractography , mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development . Generalized estimating equation models examined associations of risk factors on corticospinal tract development . The perinatal risk factor of greater early illness severity ( as measured by the Score for Neonatal Acute Physiology-II [ SNAP-II ] ) was associated with a slower rise in fractional anisotropy of the corticospinal tract ( P = 0.02 ) , even after correcting for gestational age at birth and postnatal risk factors ( P = 0.009 ) . Consistent with previous findings , neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract ( P = 0.03 and 0.02 , respectively ) . Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns Summary Background Many infants admitted to hospital undergo repeated invasive procedures . Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores . We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants . Methods In this double-blind , r and omised controlled trial , 59 newborn infants at University College Hospital ( London , UK ) were r and omly assigned to receive 0·5 mL 24 % sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinical ly required heel lance . R and omisation was by a computer-generated r and omisation code , and research ers , clinicians , participants , and parents were masked to the identity of the solutions . The primary outcome was pain-specific brain activity evoked by one time-locked heel lance , recorded with electroencephalography and identified by principal component analysis . Secondary measures were baseline behavioural and physiological measures , observational pain scores ( PIPP ) , and spinal nociceptive reflex withdrawal activity . Data were analysed per protocol . This study is registered , number IS RCT N78390996 . Findings 29 infants were assigned to receive sucrose and 30 to sterilised water ; 20 and 24 infants , respectively , were included in the analysis of the primary outcome measure . Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water ( sucrose : mean 0·10 , 95 % CI 0·04–0·16 ; sterile water : mean 0·08 , 0·04–0·12 ; p=0·46 ) . No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg . The PIPP score was significantly lower in infants given sucrose than in those given sterile water ( mean 5·8 , 95 % CI 3·7–7·8 vs 8·5 , 7·3–9·8 ; p=0·02 ) and significantly more infants had no change in facial expression after sucrose administration ( seven of 20 [ 35 % ] vs none of 24 ; p<0·0001 ) . Interpretation Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits , and therefore might not be an effective analgesic drug . The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief . Funding Medical Research Council Abstract Objectives : To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers . To determine the synergistic analgesic effect of sucrose and pacifiers . Design : R and omised prospect i ve study with vali date d behavioural acute pain rating scale . Setting : Maternity ward . Participants : 150 term newborns undergoing venepuncture r and omly assigned to one of six treatment groups : no treatment ; placebo ( 2 ml sterile water ) ; 2 ml 30 % glucose ; 2 ml 30 % sucrose ; a pacifier ; and 2 ml 30 % sucrose followed by a pacifier . Results : Median ( interquartile ) pain scores during venepuncture were 7 ( 5 - 10 ) for no treatment ; 7 ( 6 - 10 ) for placebo ( sterile water ) ; 5 ( 3 - 7 ) for 30 % glucose ; 5 ( 2 - 8 ) for 30 % sucrose ; 2 ( 1 - 4 ) for pacifier ; and 1 ( 1 - 2 ) for 30 % sucrose plus pacifier . Mann-Whitney U test P values for comparisons of 30 % glucose , 30 % sucrose , pacifier , and 30 % sucrose plus pacifier versus placebo ( sterile water ) were 0.005 , 0.01 , < 0.0001 , and < 0.0001 , respectively . Differences between group median pain scores for these comparisons were 2 ( 95 % confidence interval 1 to 4 ) , 2 ( 0 to 4 ) , 5 ( 4 to 7 ) , and 6 ( 5 to 8) , respectively . P values for comparisons of 30 % glucose , 30 % sucrose , and 30 % sucrose plus pacifier versus pacifier were 0.0001 , 0.001 , and 0.06 , respectively . Differences between group medians for these comparisons were 3 ( 2 to 5 ) , 3 ( 1 to 5 ) , and 1 ( 0 to 2 ) , respectively . Conclusion : The analgesic effects of concentrated sucrose and glucose and pacifiers are clinical ly apparent in newborns , pacifiers being more effective than sweet solutions . The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone . These simple and safe interventions should be widely used for minor procedures in neonates . Key messages The analgesic effects on newborn infants of sucrose , glucose , and pacifiers can be clearly detected by a behavioural pain rating scale Pacifiers had a better analgesic effect than sweet solutions A synergistic effect was found with a combination of sucrose and pacifiers Sweet solutions and pacifiers constitute simple and safe interventions that can be used to provide analgesia in newborns during minor OBJECTIVES To determine whether an oral sucrose solution improves pain response for infants undergoing bladder catheterization in an emergency department ( ED ) population . METHODS A r and omized , double-blinded study comparing the analgesic effects of a sucrose solution to placebo for infants < or = 90 days of age and requiring bladder catheterization . Infants with prior bladder catheterization , previous painful procedures that day , or neurological or genital abnormalities were excluded . Infants were assigned baseline pain scores and then given 2 mL of sucrose or water 2 minutes before catheterization . Trained pediatric ED nurses rated the infants for pain , presence of cry , and time to return to baseline . RESULTS Eighty-three patients were enrolled ; 40 were r and omized to sucrose , and 40 , to placebo . Baseline pain scores were similar within each age group . Overall , sucrose did not produce a significant analgesic effect . In subgroup analysis , infants 1 - 30 days of age receiving sucrose showed a smaller change in pain scores ( 2.9 vs. 5.3 , p = 0.035 ) , were less likely to cry with catheterization ( 29 % vs. 72 % , p = 0.008 ) , and returned to baseline more rapidly after catheter removal ( 10 seconds vs. 37 seconds , p = 0.04 ) compared with infants who received placebo . Infants older than 30 days of age who received sucrose did not show statistically significant differences in pain scores , crying , or time to return to baseline behavior . CONCLUSIONS There was no overall treatment effect when using an oral sucrose solution before bladder catheterization in infants younger than 90 days of age . However , infants younger than or equal to 30 days of age who received sucrose had smaller increases in pain scores , less crying , and returned to baseline more rapidly than infants receiving placebo . Older infants did not show an improved pain response with oral sucrose & NA ; The aim of the present study was to examine the efficacy and potential side effects of repeated doses of oral sucrose for pain relief during procedures in NICU . Thirty‐three preterm neonates were r and omly allocated in blind fashion into two groups , the sucrose group ( SG = 17 ) and the control group ( CG = 16 ) . The responses of neonates to pain and distress were assessed during blood collection on four consecutive assessment ( ass . ) days . For the first assessment , the neonates did not receive any solution before the blood collection procedure . During the next three days , the SG received oral sucrose ( 25 % ; 0.5 ml/kg ) and the CG received sterile water , 2 min before each minor acute painful procedure . The neonates were evaluated during blood collection each morning . The assessment was divided into five phases : Baseline ( BL ) , Antisepsis ( A ) , Puncture ( P ) , Dressing ( D ) , and Recovery ( R ) . The neonates ’ facial activity ( NFCS ) , behavioral state , and heart rate were evaluated . The data analysis used cut‐off scores for painful and distressful responses . No side effects of using sucrose were detected . There were significantly fewer SG neonates with facial actions signaling pain than CG neonates in P ( ass.2 ) and in A ( ass.3 ) . We found significantly fewer SG neonates in the awake state than CG neonates in P ( ass.2 and ass.4 ) . There were significantly fewer SG neonates crying during A ( ass.2 ) , P ( ass.2 and ass.4 ) , and D ( ass.3 ) . There was no statistical difference between‐groups for physiological response . The efficacy of sucrose was maintained for pain relief in preterm neonates with no side effects OBJECTIVES To evaluate the effect of sucrose solution given by mouth on infant crying times and measures of distress in the immunisation clinic . DESIGN R and omised , double blind , placebo controlled trial of sucrose solution 75 % wt/vol v sterile water as a control . SETTING The immunisation clinic of the Women ’s and Children ’s Hospital , Adelaide . PATIENTS A total of 107 healthy infants attending for 2 , 4 , or 6 month immunisations with polio by mouth ( Sabin ) , intramuscular diphtheria , tetanus , and pertussis ( DTP ) , and intramuscular Haemophilus influenzae type b were r and omised to receive 2 ml 75 % sucrose solution or sterile water by mouth before the two injections . METHODS The duration of infant crying was recorded during and immediately after two intramuscular immunisations and infant distress was assessed by a visual analogue scale ( Oucher scores ) independently by a nurse and a parent . RESULTS The administration of 2 ml 75 % sucrose solution by mouth reduced the infant crying time and Oucher distress scores after immunisation with DTP/H influenzae type b. CONCLUSIONS Infant immunisation by intramuscular injection is a distressing procedure for infants and parents . Sucrose solution at a high concentration reduces infant distress and is safe and clinical ly useful in this setting Background Skin-to-skin contact ( SSC ) between mother and infant , commonly referred to as Kangaroo Mother Care ( KMC ) , is recommended as an intervention for procedural pain . Evidence demonstrates its consistent efficacy in reducing pain for a single painful procedure . The purpose of this study is to examine the sustained efficacy of KMC , provided during all routine painful procedures for the duration of Neonatal Intensive Care Unit ( NICU ) hospitalization , in diminishing behavioral pain response in preterm neonates . The efficacy of KMC alone will be compared to st and ard care of 24 % oral sucrose , as well as the combination of KMC and 24 % oral sucrose . Methods / design Infants admitted to the NICU who are less than 36 6/7 weeks gestational age ( according to early ultrasound ) , that are stable enough to be held in KMC , will be considered eligible ( N = 258 ) . Using a single-blinded r and omized parallel group design , participants will be assigned to one of three possible interventions : 1 ) KMC , 2 ) combined KMC and sucrose , and 3 ) sucrose alone , when they undergo any routine painful procedure ( heel lance , venipuncture , intravenous , oro/nasogastric insertion ) . The primary outcome is infant ’s pain intensity , which will be assessed using the Premature Infant Pain Profile ( PIPP ) . The secondary outcome will be maturity of neurobehavioral functioning , as measured by the Neurobehavioral Assessment of the Preterm Infant ( NAPI ) . Gestational age , cumulative exposure to KMC provided during non-pain context s , and maternal cortisol levels will be considered in the analysis . Clinical feasibility will be accounted for from nurse and maternal question naires . Discussion This will be the first study to examine the repeated use of KMC for managing procedural pain in preterm neonates . It is also the first to compare KMC to sucrose , or the interventions in combination , across time . Based on the theoretical framework of the brain opioid theory of attachment , it is expected that KMC will be a preferred st and ard of care . However , current pain management guidelines are based on minimal data on repeated use of either intervention . Therefore , regardless of the outcomes of this study , results will have important implication s for guidelines and practice s related to management of procedural pain in preterm infants . Trial registration Clinical Trials.gov Identifier : NCT01561547 BACKGROUND Infants experience undue pain with multiple immunization injections . OBJECTIVE To assess the effectiveness , feasibility , and parental acceptance of a simple combination pain reduction intervention for infants receiving multiple immunization injections . DESIGN R and omized , controlled , clinical trial . SETTING Academic hospital-based primary care center . PARTICIPANTS Infants receiving their 2-month immunizations , consisting of 4 injections ( diphtheria and tetanus toxoids and acellular pertussis vaccine , inactivated poliovirus vaccine , Haemophilus influenzae b conjugate and hepatitis B vaccine [ Comvax ] , and heptavalent pneumococcal conjugate vaccine [ Prevnar ] ) . INTERVENTIONS Subjects were r and omly assigned to the intervention or control group for administration of 4 injections . The intervention group received sucrose and oral tactile stimulation ( with a pacifier or a bottle ) and were held by their parents during immunization . The control group did not receive these interventions ( st and ard practice ) . MAIN OUTCOME MEASURES Blinded assessment of audiotaped crying , heart rate , parent preference for future use of the injection technique , and nurse-rated ease of vaccine administration . RESULTS One hundred sixteen infants ( mean + /- SD age , 9.5 + /- 2.0 weeks ) participated . The median ( 25th-75th percentile range ) first cry duration was 19.0 ( 5.8 - 62.8 ) seconds for the intervention group compared with 57.5 ( 31.0 - 81.5 ) seconds for the control group ( P = .002 ) . Parents of the intervention group reported a stronger preference for future use of the injection procedure . For intervention vs control , the median ( 25th-75th percentile ) parent preference visual analog scale score was 97.0 ( 82.0 - 100.0 ) vs 44.0 ( 5.0 - 77.2 ) ( P<.001 ) ( 100 indicates definitely prefer ) . Nurse-rated ease of vaccine administration was equivalent for both treatment groups . CONCLUSIONS Combining sucrose , oral tactile stimulation , and parental holding was associated with significantly reduced crying in infants receiving multiple immunization injections . Parents stated a strong preference for future use of this method , and nurses found the intervention injection technique easy to apply Objective : Preterm neonates undergo numerous painful procedures in the neonatal intensive care unit ( NICU ) . Sucrose , with and without pacifiers , is effective and safe for relieving pain from single painful events . However , repeated use of sucrose for multiple painful procedures has not been adequately evaluated . The study objectives were to : 1 ) determine the efficacy and safety of consistent management of repeated procedural pain with sucrose ; and 2 ) explore the impact of consistent pain management on clinical outcomes and neurobiological risk status . Methods : Sixty-six preterm infants were r and omized to receive st and ard care ( positioning and swaddling ; n = 21 ) , sterile water plus pacifier ( n = 23 ) , or 24 % sucrose plus pacifier ( n = 22 ) prior to all painful procedures in the NICU during the first 28 days of life . Also , at a routine heel lance at 7 , 14 , 21 , and 28 days of life , data were collected to determine efficacy and immediate and long-term adverse events . Data on clinical outcomes and neurobiological risk status were collected at 28 days or NICU discharge . Results : There was no intervention by time interaction ( P = 0.60 ) . There was a significant main effect of intervention ( P = 0.03 ) between the sucrose plus pacifier group , and the st and ard care group ( P = 0.01 ) , but there was no main effect of time ( P = 0.72 ) . No group differences existed for adverse events , clinical outcomes , or neurobiological risk status . Discussion : Consistent management of painful procedures with sucrose plus pacifier was effective and safe for preterm neonates during their stay in the NICU . Further exploration of consistent pain management with sucrose on clinical , developmental , and neurobiological outcomes is required Objectives To study whether orogastric tube ( OGT ) insertion elicits a painful response in preterm neonates , and the role of oral sucrose in reducing this pain . Methods This double blinded , r and omized control trial was conducted in the neonatal intensive care units of Kalawati Saran Children 's Hospital . Clinical ly stable preterms within the first 7 postnatal days , who had not received painful stimulus 30 min prior to intervention , and who required routine OGT insertion were included . Lingual 24 % sucrose or distilled water ( 1 ml ) was administered 2 min before OGT insertion . The primary outcome was painful response assessed by Premature Infant Pain Profile scale ( PIPP ) , while the secondary outcomes were heart rate and SpO2 changes . The trial is registered with Clinical Trials.gov ( Registration number : NCT 00949104 ) Results Sixty preterms were r and omized in each group . Final analysis was carried out on 52 subjects in the placebo group and 53 in the sucrose group . The mean intra-procedure PIPP scores were significantly higher than the mean pre-procedure PIPP scores , in the gestational age groups of more than 34 wk , and 32 wk to 33 wk , 6 d , in both the placebo ( 7.25 vs. 3 , and 8.14 vs. 3.14 , respectively ) and sucrose arm ( 8.06 vs. 3.21 , and 7.18 vs. 4.18 , respectively ) . The mean PIPP scores assessed at 30 s post procedure in the sucrose group were significantly lower than the placebo group ( 4.32 vs. 5.6 , p = 0.014 ) . No significant adverse events were seen . Conclusions OGT insertion causes pain in preterms and single dose lingual 24 % sucrose may alleviate this pain OBJECTIVE To examine the effects of sucrose on pain and biochemical markers of adenosine triphosphate ( ATP ) degradation and oxidative stress in preterm neonates experiencing a clinical ly required heel lance . STUDY DESIGN Preterm neonates that met study criteria ( n = 131 ) were r and omized into 3 groups : ( 1 ) control ; ( 2 ) heel lance treated with placebo and non-nutritive sucking ; and ( 3 ) heel lance treated with sucrose and non-nutritive sucking . Plasma markers of ATP degradation ( hypoxanthine , xanthine , and uric acid ) and oxidative stress ( allantoin ) were measured before and after the heel lance . Pain was measured with the Premature Infant Pain Profile . Data were analyzed by the use of repeated- measures ANOVA and Spearman rho . RESULTS We found significant increases in plasma hypoxanthine and uric acid over time in neonates who received sucrose . We also found a significant negative correlation between pain scores and plasma allantoin concentration in a subgroup of neonates who received sucrose . CONCLUSION A single dose of oral sucrose , given before heel lance , significantly increased ATP use and oxidative stress in premature neonates . Because neonates are given multiple doses of sucrose per day , r and omized trials are needed to examine the effects of repeated sucrose administration on ATP degradation , oxidative stress , and cell injury Objectives To test the efficacy of oral sucrose in reducing pain/ stress during echocardiography as estimated by Premature Infant Pain Profile score . Design Double-blind , parallel-group , r and omized control trial . Setting Tertiary-care neonatal care unit located in Western India . Participants Neonates with established enteral feeding , not on any respiratory support and with gestational age between 32 and 42 weeks requiring echocardiography . Interventions Neonates in intervention group received oral sucrose prior to echocardiography . Main outcome measures Assessment was done using Premature Infant Pain Profile score . Results There were 104 examinations ; 52 in each group . Baseline characteristics like mean gestational age ( 37.6 vs. 37.1 ) , birth weight ( 2.20 vs. 2.08 ) , and feeding status ( Breastfeeding- 59.6 % vs. 44.2 % , paladai feeding- 13.5 % vs. 13.5 % , and gavage feeding- 26.9 % vs. 42.3 % ) were comparable . The mean ( SD ) premature infant pain profile score was significantly higher in control group [ ( 7.4 ( 3.78 ) vs. 5.2 ( 1.92 ) , P < 0.001 ] . Conclusion Oral sucrose significantly reduces pain , and is safe to administer to neonates BACKGROUND Safety of oral sucrose , commonly used procedural analgesic in neonates , is question ed . AIM To evaluate the effect of sucrose analgesia , for repeated painful procedures , on short-term neurobehavioral outcome of preterm neonates . METHODS Stable preterm neonates were r and omized to receive either sucrose or distilled water orally , for every potentially painful procedure during the first 7 days after enrollment . Neurodevelopmental status at 40 weeks postconceptional age ( PCA ) measured using the domains of Neurobehavioral Assessment of Preterm Infants scale . RESULTS A total of 93 newborns were analyzed . The baseline characteristics of the groups were comparable . No statistically significant difference was observed in the assessment at 40 weeks PCA , among the groups . Use of sucrose analgesia , for repeated painful procedures on newborns , does not lead to any significant difference in the short-term neurobehavioral outcome Abstract Feeding and carrying have been interventions used by caregivers throughout history in relieving distress in infants . Recent studies on the food substance sucrose have eluci date d the comforting effect of the taste component of feeding while studies of rocking have examined the comforting effect of the vestibular component of carrying . The purpose of this study was to determine the effectiveness of sucrose and simulated rocking alone and in combination on diminishing pain response in preterm neonates undergoing routine heelstick procedure in the neonatal intensive care unit ( NICU ) . Preterm infants ( n=85 ) between 25–34 weeks post‐conceptual age ( PCA ) and 2–10 days post‐natal age ( PNA ) were r and omly assigned to one of four conditions for routine heelstick procedure . The conditions were ( 1 ) sucrose alone : 0.05 ml of 24 % sucrose was placed on the anterior surface of the tongue just prior to the lancing of the heel ; ( 2 ) simulated rocking alone : 15 min prior to and during the heelstick procedure , the infant was swaddled and put on an oscillating mattress ; ( 3 ) combination of sucrose and simulated rocking ; and ( 4 ) placebo : 0.05 ml sterile water administered just prior to heelstick . Physiological ( heart rate ) and behavioural ( facial actions ) responses from baseline across 90 s following heelstick were scored second‐to‐second . Facial actions were analysed with repeated measures MANCOVA and heart rate with repeated measures ANCOVA . Behavioural state and gestational age were covariates . The groups that received sucrose alone or in combination with simulated rocking showed less facial actions indicative of pain than the rocking alone or control group . The addition of rocking to the sucrose condition tended to further blunt the facial expression of pain , but this enhancement did not reach a significant level . Heart rate was not decreased by any intervention compared to the control condition . Although the simulated rocking did promote quiet sleep , which has been reported in earlier studies to blunt pain response , there was no difference between simulated rocking and control groups in either facial expressions indicative of pain or heart rate . The implication of these results is that sucrose , but not simulated rocking may be a means of diminishing pain from minor procedures in preterm infants . Further research is needed on the use of sucrose for more than one procedure as well as examining the contact component of natural rocking , as opposed to simulated rocking Abstract Objective : To evaluate the effects of different sucrose concentrations on measures of neonatal pain . Design : R and omised , double blind , placebo controlled trial of sterile water ( control ) or one of three solutions of sucrose — namely , 12.5 % , 25 % , and 50 % wt/vol . Setting : Postnatal ward . Patients : 60 healthy infants of gestational age 37 - 42 weeks and postnatal age 1 - 6 days r and omised to receive 2 ml of one of the four solutions on to the tongue two minutes before heel prick sampling for serum bilirubin concentrations . Main outcome measure : Duration of crying over the first three minutes after heel prick . Results : There was a significant reduction in overall crying time and heart rate after three minutes in the babies given 50 % sucrose as compared with controls . This was maximal one minute after heel prick in the 50 % sucrose group and became statistically significant in the 25 % sucrose group at two minutes . There was a significant trend for a reduction in crying time with increasing concentrations of sucrose over the first three minutes . Conclusion : Concentrated sucrose solution seems to reduce crying and the autonomic effects of a painful procedure in healthy normal babies . Sucrose may be a useful and safe analgesic for minor procedures in neonates . Key messages Key messages Little is done to minimise the discomfort of these procedures Placing 2 ml of a 25 % or 50 % sucrose solution on the tongue before heel prick significantly reduces crying time There is a dose-response effect in the reduction of crying with increasing concentrations of sucrose Sucrose on the tongue may be a useful and safe form of analgesia in newborn Background : Screening is necessary for infants at risk of retinopathy of prematurity . Despite local anaesthetic drops , infants find eye examinations distressing , displaying behavioural and physiological changes indicating acute pain . Oral sucrose and non-nutritive sucking reduce pain responses associated with invasive procedures . Objective : To evaluate the use of oral sucrose and /or pacifier for reducing pain responses during eye examinations . Methods : Forty infants < 32 weeks gestation or < 1500 g birth weight , in two neonatal units , were r and omised to one of four interventions administered two minutes before their first screening examination : 1 ml sterile water as placebo ( group 1 , n = 10 ) , 1 ml 33 % sucrose solution ( group 2 , n = 10 ) , 1 ml sterile water with pacifier ( group 3 , n = 9 ) , or 1 ml 33 % sucrose solution with pacifier ( group 4 , n = 11 ) . Examinations were videotaped . Two observers , blind to the intervention , assessed recordings . Pain responses were scored using the premature infant pain profile ( PIPP ) . Results : The groups were similar in gestation , birth weight , and age at examination . Mean PIPP scores were 15.3 , 14.3 , 12.3 , and 12.1 for groups 1 , 2 , 3 , and 4 respectively . Analysis of variance showed a significant difference in PIPP score between groups ( p = 0.023 ) . Infants r and omised to pacifiers scored lower than those without pacifiers ( p = 0.003 ) . There was no difference between groups receiving sucrose and those receiving water ( p = 0.321 ) . Conclusions : Non-nutritive sucking reduced distress responses in infants undergoing screening for retinopathy of prematurity . The difference in response was large enough to be detected by a vali date d assessment tool . No synergistic effect of sucrose and pacifier was apparent in this group The potential of sucrose to reduce the pain response in a group of healthy premature infants was investigated . Fifteen infants of 32 - 34 weeks postmenstrual age were tested in a blind crossover manner on two separate occasions no more than two days apart . Either 1 ml of 25 % sucrose solution or sterile water was syringed into the baby 's mouth 2 minutes before routine heel lancing . Response to the painful stimuli was measured by duration of cry and by facial expression ( pain score ) . There was a significant reduction in the duration of first cry , the percentage of time spent crying in the 5 minutes after heel prick , and the pain score in the sucrose treated group . It is concluded that sucrose has analgesic effects in healthy premature infants OBJECTIVE To compare the effect of different types and concentrations of sweet solutions on neonatal pain during heel lance procedure . METHOD Totally 560 full term neonates ( male 295 , female 265 ) were r and omized into 7 groups : placebo group ( plain water ) , 10 % glucose , 25 % glucose , 50 % glucose , 12 % sucrose , 24 % sucrose and 30 % sucrose groups . In each group , 2 ml corresponding oral solutions were administered through a syringe by dripping into the neonate 's mouth 2 minute before heel lance . The procedure process was recorded by videos , from which to collect heart rate , oxygen saturation and pain score 1 min before puncture , 3 , 5 and 10 min after puncture . RESULT The average heart rate increase 3 , 5 and 10 min after procedure in the 25 % and 50 % glucose groups , 12 % and 24 % and 30 % sucrose groups was significantly lower than those in the placebo group ( P < 0.01 or 0.05 ) . The average heart rate increase 3 min after procedure in the sucrose group was lower than that in the glucose group ( P < 0.01).Neonates who received 30 % sucrose has a significantly lower average heart rate increase than those who received 12 % and 24 % sucrose 3 min after heel lance ( both P < 0.05 ) . The average oxygen saturation decrease 3 , 5 , 10 min after procedure was significantly lower than those in the placebo group ( P < 0.01 ) . The average oxygen saturation decrease 3 min after procedure in the sucrose groups was significantly lower than that in the glucose groups ( P < 0.01 ) . The average pain score 3 , 5 , 10 min after procedure was significantly lower than those in the placebo group ( P < 0.01 ) . The average pain score 3 min after procedure in the sucrose groups was significantly lower than that in the glucose groups ( P < 0.01 ) . CONCLUSION Oral administration of sweet solutions is an effective way to relieve neonatal pain on procedure , and sucrose has a better pain relief action than glucose , moreover , 30 % sucrose provides better effect in control of heart rate increase 3 min after heel lance , but the best concentration of sucrose for pain relief needs further study CONTEXT Newborns are subject to pain during routine invasive procedures . Pain caused by immunization injections is preventable , but remains untreated in neonates . OBJECTIVES The purpose of the study was to compare the effectiveness of three nonpharmacological pain relief strategies on newborns ' pain , physiological parameters , and cry duration before , during , and after hepatitis B intramuscular ( IM ) injection . METHODS In this prospect i ve , r and omized clinical trial , we enrolled 165 newborns ( gestational age , ≥36 weeks ) . The infants received IM injections and were r and omized to three treatment groups : nonnutritive sucking ( NNS ) , 20 % oral sucrose , or routine care . Pain was measured by the Neonatal Facial Coding System , physiological signals by electrocardiogram monitors , and cry duration using a stopwatch . RESULTS Pain was significantly lower among infants in the NNS ( B=-11.27 , P<0.001 ) and sucrose ( B=-11.75 , P<0.001 ) groups than that in controls after adjusting for time effects , infant sleep/wake state , number of prior painful experiences , and baseline pain scores . Infants in the NNS and sucrose groups also had significantly lower mean heart and respiratory rates than the controls . Cry duration of infants receiving sucrose was significantly shorter than those in the NNS ( Z=-3.36 , P<0.001 ) and control groups ( Z=-7.80 , P<0.001 ) . CONCLUSION NNS and oral sucrose can provide analgesic effects and need to be given before painful procedures as brief as a one-minute IM injection . Sucrose orally administered two minutes before injection more effectively reduced newborns ' pain during injection than NNS . Both nonpharmacological methods more effectively relieved newborns ' pain , stabilized physiological parameters , and shortened cry duration during IM hepatitis injection than routine care Abstract Objectives : To vali date spontaneous skin conductance variations as a specific reliable mean to measure pain in full-term healthy newborns during heel stick , comparing it with the ABC scale . To compare oral sucrose to wrapping effectiveness for non-pharmacological analgesia during the same procedure . Method : All recruited newborns ( n = 158 ) underwent a heel stick for metabolic screening at 48 h of life with non-pharmacological analgesia by oral sucrose ( group A ) or wrapping ( group B ) according to r and omization . Their pain was estimated by ABC scale score ( st and ard method ) and measured by skin conductance variations . Results : A positive correlation was founded between peaks per sec measure and ABC score ( rs = 0.303 , p < 0.005 ) . ABC score in group A was lower than in group B ( p < 0.001 ) . Difference in mean ABC score among newborn subgroups treated by different nurses was not statistically significant for wrapping while it was significant for sucrose ( p = 0.001 ) . Conclusions : Skin conductance measurement device is a reliable method to evaluate pain . Novel technological devices may be a useful support to clinical observation in this field . Oral sucrose is more effective than wrapping in reducing pain . Operators should be well periodically re-trained in performing non pharmacological analgesia during minor procedure on newborns This study evaluates the effects of colostrum , delivered via syringe or on a pacifier , on the pain and heart rate reactions of newborns undergoing routine heel-lance . This was achieved by following a quasi-r and omized , controlled trial in which 60 newborn infants at Boston Medical Center , Boston , MA , were r and omly assigned to receive colostrum , sucrose , or water , by syringe or on a pacifier , for a total of 6 groups ( n = 10 per group ) . The effectiveness of an intervention was determined by comparing crying , grimacing , and heart rate differences among groups during and following blood collection . We report that colostrum , delivered by syringe or on a pacifier , did not reduce crying or grimacing relative to control infants who received water . As has been previously reported , sucrose markedly reduced both crying and grimacing , and attenuated the rise in heart rate that normally accompanies blood collection ( p < .002 ) . Water , via syringe or on a pacifier , did not prevent the increase in heart rate , nor did colostrum via syringe . In contrast , colostrum delivered on a pacifier prevented the increase in heart rate despite pain reactivity and extreme crying . The implication s of this dissociation are discussed & NA ; The responses of preterm neonates to acute tissue‐damaging stimuli have been described . However , factors which influence these responses have received little attention . In this study , we observed 124 premature infants before , during and after a routine heel lance and determined how two context ual variables ( severity of illness and behavioral state ) influenced their behavioral responses . Significant changes in facial actions occurred between baseline and the most invasive phase of the heel lance procedure , stick . The fundamental frequency , harmonic structure and peak spectral energy of the infant 's cry were also significantly increased during the stick phase . Behavioral state was found to influence the facial action variables and severity of illness modified the acoustic cry variables . Accurate identification of pain in premature infants requires consideration of factors that influence their response A double-blind , r and omized controlled trial was conducted with infants born < 31 weeks of gestational age and recruited within 48 h of life . The infants were r and omized to receive up to three doses of 0.1 ml of either 24 % sucrose or sterile water ( placebo ) for every painful procedure during the 1st week of life . The purpose of this study was to test the efficacy of treating all procedural pain with sucrose on overall physiological stability . The hypotheses were that infants who received 24 % sucrose for all painful procedures would be less stressed as measured by salivary cortisol , and more physiologically stable as measured by pulse rate variability than those who received placebo . Salivary cortisol was measured before and 30 min after a painful procedure , whereas the pulse rate was continuously recorded , from second to second , from a pulse oximeter . There were no group differences in the cortisol response to a painful stimulus or in pulse rate variability over time . There was , however , a significant correlation between st and ard deviation of pulse rate and number of doses of sucrose only in the group who received high doses of sucrose To underst and how the ' caregiving context ' could affect responses to procedural pain , the authors sought to determine whether ( 1 ) the combined effects of sweet taste and holding ( caregiving contact ) were greater than the effects of either alone , ( 2 ) any combined effects were additive or interactive , and ( 3 ) the interventions had similar effects on behavioral ( crying and facial activity ) and physiological ( heart rate , vagal tone ) responses to the heel-stick procedure in newborn infants in a r and omized two-factorial intervention trial . Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life . Infants were r and omized in blocks of eight to receive ( 1 ) no holding and water taste ( control participants ) , ( 2 ) no holding and sucrose taste ( sucrose group ) , ( 3 ) holding and water taste ( holding group ) , or ( 4 ) holding and sucrose taste ( holding and sucrose group ) . Crying was reduced significantly by taste and holding , and the interventions combined additively . Facial activity was only significantly reduced by holding . For physiological measures , the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention . Consequently , sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences . The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants , and that no one measure captures these effects Background : The efficacy of oral sucrose in the reduction of single episodes of acute procedural pain in newborn infants has been demonstrated in a large number of well-conducted r and omized controlled trials . However , there are few studies that have examined the effectiveness of repeated doses of sucrose and there are no studies of prolonged sucrose use in sick infants over an entire period of hospitalization . Objective : The aim of this study was to evaluate the analgesic effectiveness of repeated doses of oral sucrose during heel lancing in sick infants over the course of a prolonged hospitalization . Methods : A prospect i ve longitudinal cohort study was conducted in a tertiary referral neonatal intensive care unit . Infants with a predicted length of stay of ≥28 days were eligible for inclusion . Oral sucrose was administered prior to and during all heel lance procedures observed . Pain outcomes consisted of facial expression scores , crying duration , heart rate , and oxygen saturation . Changes in sequential pain responses were analyzed , and weighted linear regression slopes for all assessed parameters were calculated to estimate the average regression slope . Results : There were 55 infants enrolled , and 443 pain assessment s during heel lancing were conducted . Behavioral responses to heel lancing were predominantly low , and there were minimal changes in behavioral and physiological parameters to successive heel lance procedures . The mean weighted regression slope over the period of hospitalization for the facial expression scores upon heel lance , on the 0 - 4 scale , was −0.0084 ( SD = 0.298 ; 95 % confidence interval [ CI ] = −0.076 to 0.093 ; p = .84 ) . The mean weighted regression slope for crying proportion during the procedure was −0.046 % ( SD = 4.247 % ; 95 % CI = −1.322 % to 1.230 % ; p = .943 ) and for heart rate change from baseline during the heel lance procedures was 0.541 % ( SD = 2.907 % ; 95 % CI = −0.299 % to 1.353 % ; p = .02 ) . Discussion : The predominantly low behavioral responses to heel lancing and the lack of increase in behavioral pain outcomes suggest the ongoing effectiveness of oral sucrose during painful procedures throughout the infants ' hospitalization . Further studies are recommended to ascertain the influence of factors such as adjunct analgesics , sedatives , and severity of illness OBJECTIVE : Infants undergoing eye exams to screen for retinopathy of prematurity ( ROP ) demonstrate physiologic and behavioral manifestations of pain and distress . Oral sucrose has analgesic properties that might reduce these effects . AIM : To determine the efficacy of oral sucrose in reducing the pain/distress of eye exams for ROP . METHODS : A total of 32 infants about to undergo ROP screening exams received either oral sucrose [ S ] ( N=16 ) or sterile water [ C ] ( N=16 ) in a r and omized , prospect i ve and blinded fashion . Outcome measures included HR , RR , O2 saturation , BP , pain ( premature infant pain profile ) and percent of time spent crying during the eye exam . RESULTS : The groups were similar in GA ( weeks ) ( 28±1.6 ) , BW ( kg ) ( 1.04±0.26 ) , postnatal age ( days ) 50.8±20.3 , and study weight ( kg ) 1.88±0.40 ) . Both groups demonstrated significant increases in HR , BP , and pain score in response to the exam . Infants in both groups spent the majority of time actively crying during the exam ( [ S ] 53±35 % vs [ C ] 63±31 % . Infants receiving [ S ] showed a small but significant drop in O2 saturation . No significant differences were seen between groups in physiologic or behavioral responses to the eye exam . CONCLUSION : Oral [ S ] was not effective in reducing pain/distress from the ROP screening exam . Alternative strategies should be considered to achieve adequate pain relief BACKGROUND Sucrose is an effective analgesic for procedural pain in preterm infants . It has been hypothesized that its analgesic effects are mediated by the release of endogenous opioid neurotransmitters such as beta-endorphin . OBJECTIVE To determine whether intraoral administration of sucrose was associated with an increase in serum beta-endorphin concentrations in preterm infants with a gestation period less than 29 weeks who were not exposed to a painful stimulus . METHODS We performed a prospect i ve open-label study in preterm infants admitted to 2 tertiary neonatal intensive care units . Each infant received a single dose of 30 % sucrose intraorally during a 1- to 2-minute period . A blood sample was obtained using an indwelling arterial catheter to determine beta-endorphin concentration immediately before and 2 to 5 minutes after the commencement of sucrose administration . RESULTS We enrolled 11 preterm infants with a mean + /- SD gestational age of 27.2 + /- 0.9 weeks and a mean + /- SD birth weight of 1018 + /- 238 g ( 1.02 + /- 0.24 kg ) at a mean + /- SD postnatal age of 3.0 + /- 2.5 days . The mean + /- SD beta-endorphin concentration before and after sucrose administration was 60.4 + /- 30.5 pg/mL and 57.4 + /- 22.4 pg/mL , respectively ( P = .45 ) . No adverse events were observed during the study procedures . CONCLUSION Intraoral administration of sucrose in preterm infants did not lead to an increase in serum beta-endorphin concentrations at a point in time when the analgesic effects of sucrose were presumed to be present To compare the relative efficacy of oral sucrose versus EMLA ® cream for pain relief during venepuncture , 51 full‐term newborns ( 38 M , 13F ; postnatal age < 4d ) in a stable condition were r and omly allocated to one of four treatment groups : placebo ( 2 ml spring water ) ; 2 ml sucrose 24 % w/v ; 1 g lidocaine‐prilocaine 5 % cream ( EMLA ) ; or EMLA plus sucrose . Water or a single dose of sucrose solution was administered orally 2 min before venepuncture . EMLA cream was applied in the antecubital fossa 45–60 min before venepuncture and covered by a Tegaderm ® dressing . A pacifier was given before skin puncture , but it was not actively held or replaced during the procedure or observation periods . In total , 55 venepunctures were performed blindly , always for clinical reasons . As indicators of pain , the total crying time was recorded and heart rate , respiratory rate and arterial oxygen saturation were measured blindly at baseline , immediately post‐venepuncture , and 2 and 4 min afterwards . The main effects observed were : ( i ) time spent crying decreased significantly in the sucrose alone ( p= 0.001 ) and EMLA plus sucrose ( p= 0.008 ) groups ; ( ii ) the above treatments attenuated significantly ( p < 0.05 ) the immediate heart rate response to pain ; and ( iii ) the concomitant use of EMLA did not increase further the analgesic efficacy of sucrose OBJECTIVE Our objective was to compare two methods of pain control during neonatal circumcision : a sucrose-dipped pacifier and an analgesic cream ( EMLA ) . STUDY DESIGN This study was conducted in our well-baby nursery where 80 male infants were placed into one of four groups : control ( water-dipped pacifier only ) , sucrose alone , EMLA alone , or sucrose and EMLA . Heart rate , oxygen saturation , systolic and diastolic blood pressure , and crying time were measured as indicators of pain . The primary data analysis was a 2 x 2 factorial analysis of variance with repeated measures . RESULTS Physiologic and behavioral parameters indicated significantly ( p < 0.05 ) decreased pain response in all treatment groups compared with that in the control group . The combination of sucrose and EMLA was most effective in reducing pain responses ; sucrose alone was significantly less effective . There were no side effects of treatment . CONCLUSION Pain during neonatal circumcision can be optimally ameliorated by combined use of a sucrose-dipped pacifier and a local analgesic cream Objective : To establish evidence of clinical validity and reliability of the Neonatal Pain , Agitation , and Sedation Scale ( N-PASS ) in neonates with acute heelstick pain . Study Design : Prospect i ve psychometric evaluation , r and omized crossover design . Two nurses administered the N-PASS simultaneously and independently during an actual and sham heelstick done in r and omized order . One nurse also administered the Premature Infant Pain Profile ( PIPP ) concurrently with the N-PASS . Heelsticks were videotaped for repeat analysis . Result : Construct ( discriminate ) validity was established through the Wilcoxon Signed-ranks test , comparing the distribution of the heelstick and sham N-PASS scores . The mean pain scores were 3.93 ( 2.30 ) and 0.81 ( 1.21 ) for the heelstick and sham procedures , respectively ( Z=−6.429 , P<0.0001 ) . Convergent validity was demonstrated by correlation with the PIPP scores ( Spearman rank correlation coefficient of 0.75 and 0.72 for raters 1 and 2 , respectively ) . Inter-rater reliability was high , measured by intra-class coefficients ; the ICC estimates ( 95 % CI ) of the pain scale were 0.86 ( 0.78 , 0.92 ) and 0.93 ( 0.88 , 0.96 ) for a single rating and average of two independent ratings , respectively ( P<0.0001 ) . Internal consistency , measured by Cronbach 's alpha , was evident ( 0.84 to 0.89 ) . Test – retest reliability was demonstrated by repeat scoring of videotaped heelsticks , measured by Spearman 's rho correlation ( 0.874 , P<0.0001 ) . Conclusion : This research provides beginning evidence that the N-PASS is a valid and reliable tool for assessing acute heelstick pain in infants 0 to 30 days of age , 23 to 40 weeks gestation It has been suggested that sucrose acts as an analgesic in the neonatal period . To evaluate this further , 52 infants received either 2 ml of 7.5 % sucrose or 2 ml of sterile water before heel stab blood sampling . The duration of crying in response to sampling did not differ in the two groups but was related to level of arousal at the time of stimulation A substance commercially described as ' sugar free , ' used as a sweetener for paracetamol suspension , was evaluated on measures of neonatal pain . Sixty infants were r and omly allocated to receive one of four solutions before heel stab blood sampling : sterile water ( placebo ) ; 25 or 50 % sucrose ( weight/volume ) ; and the commercial sweet-tasting solution . There was a significant reduction in crying time and pain score 3 minutes after the painful stimulus in all groups compared with the controls . It is concluded that this sweet-tasting solution has analgesic effects as potent as those of concentrated sucrose solutions Objective : To determine whether lingual sucrose modifies the pain response to nasogastric tube insertion in preterm infants . Design : R and omised , double-blind , placebo controlled clinical trial . Setting : Special care baby unit . Patients : 20 stable preterm infants who required nasogastric tube insertion for feeding , r and omised on 51 occasions . Intervention : Lingual 24 % sucrose or water placebo ( 0.5–2 ml varying with body weight ) administered 2 min before nasogastric tube insertion . Outcome measures : Heart rate , oxygen saturation ( SaO2 ) , Neonatal Facial Coding Score and presence or absence of cry . Results : Infants who received sucrose demonstrated a significantly lower Neonatal Facial Coding Score during nasogastric tube passage compared with the placebo group ( median 1 ( range 0–4 ) vs 3 ( 0–4 ) , p = 0.004 ) . There was a trend for sucrose-treated infants to have little change in heart rate during nasogastric tube passage compared with the placebo group ( mean ( SD ) −0.73 ( 23 ) vs + 11 ( 17 ) , p = 0.055 ) . Mean SaO2 did not change significantly . Pain response measurements quickly returned to baseline after nasogastric tube insertion . Adverse effects , such as apnoea or oxygen desaturation , were few and occurred equally in each group . Conclusions : Nasogastric tube insertion induces a pain response comparable with previously reported responses to heel lance in neonates . Single-dose lingual 24 % sucrose is effective in reducing the behavioural and physiological pain response to nasogastric tube insertion in preterm infants and it appears to be safe PURPOSE To examine the efficacy of pacifiers and sugar , alone and in combination , for pain management in neonates . METHODS An experimental design examined pain responses of 84 newborns undergoing heelstick . They were r and omly assigned to one of four groups : ( a ) water-moistened pacifier , ( b ) sugar-coated pacifier , ( c ) 2 cc of a 12 % oral sucrose solution , or ( d ) control . Pain measures were duration of cry , vagal tone , and salivary cortisol . RESULTS Multivariate analysis of variance ( MANOVA ) revealed that the sugar-coated pacifier group cried significantly less than the water-moistened pacifier and control groups . Repeated measures analysis of variance ( ANOVA ) revealed that the sugar-coated pacifier group demonstrated significantly lower vagal tone during heelstick than the oral sucrose solution and control groups . This difference between the sugar-coated pacifier and control groups persevered for 15 minutes after heelstick . CONCLUSIONS Offering a sugar coated pacifier during heelstick in healthy neonates reduces pain behaviors more effectively than a water-moistened pacifier , 2 cc of a 12 % sucrose solution , or no intervention Background Healthy term newborns commonly undergo painful procedures during routine follow-up visits . Non-pharmacological strategies have currently become more important than pharmacological analgesic agents in neonatal pain management . Acupuncture is a new non-pharmacological method for preventing pain in newborns . Objective We aim ed to investigate the effect of laser acupuncture ( LA ) at the Yintang point before heel lancing as a non-pharmacological intervention for procedural pain management in infants . Methods Forty-two term newborns , who were undergoing heel lancing between postnatal days 3 to 8 as part of routine neonatal screening , were r and omly assigned to the LA group or the oral sucrose group . In the LA group , 2 min before the heel lancing , 0.3 J of energy was applied to the Yintang point using a Laser PREMIO-30 unit for 30 s. In the sucrose group , each infant received 0.5 mL of 24 % sucrose orally via syringe 2 min before the heel lancing . Each baby 's behaviour was scored using the Neonatal Infant Pain Scale ( NIPS ) , assessed blinded to group . Results There were no significant differences between the LA and oral sucrose groups with respect to means for gestational week of age at birth , birth weight , actual weight , or Apgar score . Mean procedure time was significantly shorter in the LA group ; however , mean crying time was longer and NIPS score was lower compared to the oral sucrose group . Conclusions Our results indicate that 0.3 J of LA at the Yintang point before heel lancing is less effective than oral sucrose for reducing the discomfort of this procedure . Trial Registration Number KA14/09 Objective To investigate the analgesic effect ( measured with Neonatal Infant Pain Scale ( NIPS ) ) of breastfeeding ( BF ) in addition to skin-to-skin contact ( SSC ) versus other methods of non-pharmacological analgesia during blood sampling through heel lance in healthy term neonates . Design R and omised controlled trial . Setting Tertiary level maternity ward . Patients One hundred thirty-six healthy term newborns . Inclusion criteria : healthy term neonates , wish to breastfeed and absence of feeding during the previous 60 min . Intervention Neonates were r and omly assigned to four groups : Group breastfed with SSC ( BF+SSC Group ) ( n=35 ) ; Group sucrose with SSC ( Sucrose+SSC Group ) ( n=35 ) ; SSC Group ( n=33 ) ; or Sucrose Group ( n=33 ) . Babies were recorded with a video camera . Outcome measures Three observers watched the videos and measured NIPS score at three time points ( t0 : 2 min before heel prick ; t1 : During heel prick ; and t2 : 2 min after the heel prick ) . The influences of non-pharmacological methods on crying time , percentage of crying while sampling , heart rate , number of attempts and duration of sampling were also studied . Results BF+SSC Group achieved a significant lower median NIPS score ( value=1 ) compared with other groups ( value=2 , 4 and 4 , respectively ) . The percentage of neonates with moderate-to-severe pain was also lower in the BF+SSC Group . Both groups BF+SSC and Sucrose+SSC achieved a significant lower percentage of crying compared with SSC Group . Conclusions This study suggests that BF in addition to SSC provides superior analgesia to other kinds of non-pharmacological analgesia in healthy term neonates during heel prick . Trial registration number ( Clinical Trials.gov ) : OBJECTIVE : The goal of this study was to compare the analgesic effect of sucrose with that of the combination of sucrose and the local anesthetic cream EMLA during venipuncture in preterm neonates . METHODS : This r and omized , double-blind prospect i ve study included infants younger than 37 weeks ' gestational age during 1 routine venipuncture for blood sampling . Each child r and omly received either sucrose plus application of a placebo cream ( S group ) or sucrose plus EMLA cream ( S+E group ) before venipuncture . Venipuncture-induced pain was assessed through videotapes of the procedures by using the Douleur Aiguë Nouveau-né ( DAN ) behavioral scale . Pain was assessed at 2 phases : during venipuncture ( from needle introduction to its removal ) and during the recovery period ( 30 seconds after needle removal ) . Pain scores over time and between treatments were compared by using repeated- measures analysis of variance . RESULTS : The study included 76 children ( 37 in the S group , 39 in the S+E group ) . Mean ( SD ) DAN pain scores for the S group and the S+E group were 7.7 ( 2.1 ) and 6.4 ( 2.5 ) , respectively , during venipuncture and 7.1 ( 2.8 ) and 5.7 ( 3.3 ) during the postinjection period . A significant time and treatment effect in favor of the S+E group was observed . CONCLUSION : The combination of sucrose and EMLA cream revealed a higher analgesic effect than sucrose alone during venipuncture in these preterm infants This study was to evaluate the performed painful procedures among all sick neonates cared for at two university hospital neonatal intensive care units ( NICUs ) in the Republic of Korea . This prospect i ve study was done with all newborns admitted to the NICUs between 1 October and 20 November 2010 . Data collection was done with self-administered question naire by each nurse for the first 2 weeks of admission and discontinued if the neonate was discharged , transferred or died . The number of painful procedures , according to general characteristics of the neonates , were compared using Mann-Whitney U-test and Kruskal-Wallis test . Oral suctioning was the most frequently performed procedure , followed by tracheal suctioning and nasal suctioning . The number of painful procedures increased as the gestation period became shorter and birthweight decreased . In conclusion , nurses should reappraise the need for painful procedures , in particular , among neonates with a gestation period of ≤ 27 weeks and babies with ≤ 1000 g of birthweight , and execute their performance only if necessary Objectives To determine the incidence of and factors predicting management strategies used for procedural pain in Canadian neonatal intensive care units and to determine whether the incidence of procedures and their management has changed since our 1997 study . Patients Five hundred eighty-two neonates who were hospitalized in any of the participating study centers were included . Methods A prospect i ve observational study was conducted in 14 Canadian neonatal intensive care units ( level III A and III B ) . Infants were followed for 1 week regarding all invasive procedures . Data were collected prospect ively by unit staff using a checklist and verified by research assistants . Results A total of 3508 tissue damaging ( mean=5.8 , SD=15 ) and 14,085 ( mean=25.6 , SD=15 ) nontissue damaging procedures were recorded . Half of procedures ( 46 % tissue damaging and 57 % nontissue damaging ) had no analgesic interventions . Opiates were used for 14.5 % of tissue-damaging procedures and sweet taste was used for 14.3 % of the tissue-damaging procedures . Factors predicting use of pharmacologic management of tissue-damaging procedures were being less ill at birth , receiving high frequency ventilatory support , and being transferred to the study center . Parental presence predicted use of sweet taste or nonpharmacologic analgesia for tissue-damaging procedures . Study site practice s varied widely with 1 unit providing analgesia for 90 % of tissue-damaging procedures . InterpretationAlthough the number of tissue-damaging procedures has decreased from 1997 and the use of analgesics has increased , the management of these procedures falls far below the recommended guidelines of the Canadian Pediatric Society . That 1 unit reached a high level of analgesic use suggests that it is possible to achieve this goal . That parental presence had a positive influence on comfort strategies supports offering encouragement and support for parents to remain with their infant during procedures The analgesic effects of four solutions administered intra-orally ( 25 and 50 % sucrose solutions , hydrogenated glucose , and a sterile water placebo ) were tested in groups of babies receiving routine DTP ( diphtheria , tetanus , and pertussis ) and HIB ( Haemophilus influenzae type B ) injections at the first , second , or third immunization . The duration of the baby ’s cry during 3 min following DTP and HIB injections was measured as main outcome . For all three immunization groups , the babies receiving the placebo generally spent most time crying . For both the DTP and HIB injections , the difference between 50 % sucrose and placebo was most evident in the group receiving the 3rd immunization . Intra-oral administration of the 50 % sucrose solution , compared to placebo , appeared to reduce the cry response to painful experiences in babies beyond the neonatal period OBJECTIVE To assess the effectiveness of sucrose as an analgesic agent during routine immunization injections for infants ( age range , 2 weeks to 18 months ) . STUDY DESIGN Double-blind , r and omized control trial . SETTING Ambulatory care clinic of a large tertiary care center . PARTICIPANTS A consecutive sample of 285 infants were r and omly assigned to one of three treatment groups . INTERVENTION Subjects received either no intervention or drank 2 mL of sterile water or 2 mL or a 12 % sucrose solution 2 minutes before administration of the immunization . MAIN OUTCOME MEASURE Infants were videotaped during immunization for later interval recording of pain-induced vocalizations . RESULTS Results were analyzed by using two-way repeated measure analyses of variance . Two-week-old infants who received either the sterile water or sucrose solution cried significantly less than infants who received no intervention ( F=5.92,P<.005 ) . For older infants , those who received water or sucrose cried significantly less only if they were administered one injection rather than two injections ( F=3.36,P<.05 ) . CONCLUSIONS We found that when infants drank sucrose or sterile water , significantly fewer pain vocalizations were produced , but only for 2-week-old infants . For older infants , differences were found only when the number of injections was included in the analysis . We exp and on previous findings by demonstrating that both the age of the child and the number of painful exposures can attenuate calming effects . In addition , the results suggest that in the absence of nonnutritive sucking , the actual analgesic effects of sucrose may be nonspecific . Further study is needed of the possible analgesic effects of sucrose BACKGROUND Physiologic and behavioral responses to procedural pain are influenced by gestational age ( GA ) . Compared with term neonates , hospitalized preterm neonates are subjected to more painful procedures aim ed at improving their clinical outcome . Although several trials to determine the efficacy of sucrose for managing procedural pain have been conducted , none have examined the influence of GA . OBJECTIVES To examine the influence of GA on the efficacy and short-term safety of oral sucrose for relieving procedural pain associated with heel lances . To explore GA differences in behavioral and physiologic indicators of pain . METHODS As part of a larger r and omized controlled trial ( RCT ) to examine the efficacy and safety of sucrose during heel lance , 190 neonates were stratified by GA : ( a ) 27 to 31 6/7 weeks ( group 1 ; n = 63 ) , ( b ) 32 to 35 6/7 weeks ( group 2 ; n = 63 ) , and ( c ) > 36 weeks ( group 3 ; n = 64 ) . They were then r and omized to receive ( a ) oral sucrose and non-nutritive sucking ( NNS ) , ( b ) sucrose alone , or ( c ) sterile water and NNS ( control ) for a heel lance . The influence of GA was determined by examining the short-term safety , as defined by the number of associated adverse events ( choking , coughing or vomiting , sustained tachycardia , sustained tachypnea or dyspnea , or sustained oxygen desaturation ) . The efficacy was measured by changes in a vali date d pain measure , scored during each phase of the intervention and analyzed according to GA groups . RESULTS Significant differences in pain response existed in each GA group , with the lowest mean pain scores in the sucrose and NNS group . Significant GA differences in behavioral and physiologic responses were found , with the most mature neonates demonstrating the greatest magnitude of pain response . The greatest number of short-term adverse effects to treatment occurred in the lowest GA group . CONCLUSIONS In a secondary analysis of a larger RCT , sucrose and NNS was the most efficacious intervention for single heel lances in each of 3 GA groups . However , infants of lower GA experienced more adverse events . Research on the efficacy and safety of repeated doses of oral sucrose , tested in infants from a wide range of GA , is required Background : Neonatal circumcision is one of the oldest and most frequently performed surgical procedures on males . Newborns demonstrate strong endogenous reaction to pain and therefore modalities are being explored for optimum pain relief during circumcision . Pediatric nurses have a vital role for the use of these modalities and minimising the pain response during the neonatal minor procedures . Aim : The aim of this study was to assess the effectiveness of eutectic mixture of local anaesthetic ( EMLA ) cream compared with oral sucrose and both in alleviating pain in neonatal circumcision . Material s and Methods : This study was conducted in the Day Care Surgery Department of Maternity and Children Hospital , Dammam City , KSA . 90 full-term newborn males who underwent circumcision were divided r and omly into three groups ( 30 each ) . Each group was assigned to receive a different type of analgesics such as EMLA cream ( Group A ) , oral sucrose ( Group B ) or combination of EMLA cream and oral sucrose ( Group C ) . Neonatal pain agitation and sedation scale ( N-PASS ) was used 5 min before , during and 5 min after the circumcision procedure to assess the neonatal response to pain . Results : N-PASS scores were significantly lower in Group C ( median Group C = 5.2 , Group A = 5.8 , Group B = 8.5 ; P < 0.001 ) . The endogenous response to pain in terms of escalation of heart rate and reduction in O 2 saturation were minimal among Group C ( P < 0.0001 ) . Duration of crying was comparable among all the groups . Conclusion : The combination of sucrose and EMLA cream revealed a higher analgesic effect and minimal adverse response to pain than either EMLA cream or sucrose alone during neonatal circumcision A prospect i ve controlled blind study was carried out in the Special Care Unit for Newborns to assess the effect of commercially available sweetener on pain relief in newborns . Response to intramuscular injection and the pain stimulus was studied in twenty-five sick newborns , 13 preterm and 12 term , in a blinded fashion . Pain score , duration of cry , heart rate and oxygen saturations were studied . Basal response , responses with sterile water or sweetener were recorded in each baby . Responses to sweetener versus no solution and sweetener versus sterile water were compared by applying paired t-test . The reduction in pain score with sweetener was significant when compared with no solution . The difference was not significant when compared with sterile water . Similarly , duration of cry and heart rate with sweetener were significantly less when compared to sterile water or to no solution . However , the difference in oxygen saturation was not significantly different . Sweetener has an analgesic effect in sick babies . This can minimise adverse effects associated with painful procedures ABSTRACT . Reports that sweet taste calms crying in newborns and is analgesic against the pain caused by a heel lance served as the basis for this study . Electroencephalographic ( EEG ) activity , heart rate activity , and infants ’ facial behaviors were recorded before and after a noninvasive , but noxious , heelstroke ( procedure from the Brazelton Neonatal Behavior Assessment Scale ) . In a r and omized and controlled trial , 34 newborns were administered 2 mL of water or sucrose solution before the heelstroke . Frontal EEG asymmetry scores were computed , and power in the 3 to 6 Hz frequency b and was analyzed . Infants who received water showed increased relative right frontal EEG activation from baseline to the post-heelstroke phase , a pattern that typifies negative affect . The EEG of infants in the sucrose group did not change . Heart rate increased rapidly in both groups during the heelstroke phase . However , after the heelstroke , the heart rate of infants who received sucrose returned to baseline , whereas the heart rate of infants who tasted water remained elevated . During the heelstroke , the infants in the water group cried and grimaced twice as long as the infants in the sucrose group . These findings add to the growing literature showing that sucrose attenuates newborns ’ negative response to aversive or noxious stimuli To evaluate the effectiveness of oral sucrose in the prevention of pain‐induced crying in preterm infants , a sample of 28 healthy neonates ( 15 M , 13F ; gestational age at procedure less than 37 weeks ) who were having routine blood drawn by arm venipuncture was studied . Infants were r and omly allocated to receive by mouth , using a syringe , 2 ml of one of three solutions : spring water ( group W ) and sucrose 12 and 24 % w/v ( groups S12 and S24 , respectively ) , all in water vehicle . After 2 min , while awake , arm venipuncture was performed and duration of crying was measured . The time spent crying was reduced in the group treated with the sweetest solution ( S24 , n= 8 , mean = 19.1 s ) . No difference was observed between the S12 group ( n= 8 , mean = 63.1 s ) and W group ( n= 12 , mean = 72.9 s ) . Physiological measurements were recorded at different time points to evaluate excessive basal and procedural distress BACKGROUND Acute pain is a significant stressor for preterm infants in neonatal intensive care units ( NICU ) ; however , little is known about the effects of acute pain on subsequent motor responses during clusters of tactile h and ling . AIMS ( 1 ) To compare facial , body and heart rate reactivity in preterm infants at 32 weeks gestational age ( GA ) during routine care-giving tasks following a rest period ( RCC : diapering , measuring abdominal girth and axillary temperature , mouth care ) with their responses to Clustered Care following blood collection ( PCC ) . ( 2 ) To examine how GA at birth affects patterns of stress and self-regulatory behaviors during RCC and PCC . STUDY DESIGN Within-group crossover design ( r and om order ) . SUBJECTS Preterm infants , N=54 ( mean GA at birth 29.3 + /- 2.2 weeks ; mean birth weight 1257 + /- 423 g ) were assessed at 32 weeks GA in the NICU . OUTCOME MEASURES The Newborn Developmental Care and Assessment Program ( NIDCAP ) and Neonatal Facial Coding System ( NFCS ) were coded from continuous bedside video recordings . Changes in mean heart rate ( HR ) were computed using custom physiologic software . RESULTS All infants had heightened facial , body and HR responses when CC followed a painful procedure compared to when they had not been h and led prior to CC . Infants born at earlier GA ( < 30 weeks ) had equal numbers of stress cues during RCC and PCC , but dampened self-regulatory behaviors during PCC . CONCLUSION Prior pain induces heightened biobehavioral reactivity in preterm infants during subsequent tactile procedures . In addition , clustering care is particularly stressful for infants born at earlier GA OBJECTIVES . Sucrose has analgesic and calming effects in newborns . To date , it is not known whether the beneficial effects extend to caregiving procedures that are performed after painful procedures . Our objective was to determine the effect of sucrose analgesia for procedural pain on infant pain responses during a subsequent caregiving procedure . PATIENTS AND METHODS . We conducted a double-blind , r and omized , controlled trial . Healthy neonates within 2 strata ( normal infants and infants of diabetic mothers ) were r and omly assigned to a sucrose or placebo water group before all needle procedures after birth . Pain response during a diaper change performed after venipuncture for the newborn screening test was determined by using a vali date d multidimensional measure , the Premature Infant Pain Profile . RESULTS . The study was conducted between September 15 , 2003 , and July 27 , 2004 . Altogether , 412 parents were approached ; 263 consented . Twenty-three infants were not assigned , leaving 240 for participation ( n = 120 per group ) , with an equal number in each infant strata . Of those , 186 ( 78 % ) completed the study . There were no significant differences in birth characteristics between groups . During diaper change , sucrose-treated infants had lower pain scores than placebo-treated infants . The relative risk of having pain , defined as a Premature Infant Pain Profile score of ≥6 , was 0.64 with sucrose compared with placebo . CONCLUSIONS . This study demonstrates that when used to manage pain , sucrose reduces the pain response to a subsequent routine caregiving procedure . Therefore , the benefits of sucrose analgesia extend beyond the painful event to other aversive and potentially painful procedures As neonates are su bmi tted to pain , assessing the pain is crucial in effective pain control . The Premature Infant Pain Profile , an acute measurement tool combining physiological , behavioural and context ual indicators , was translated into Norwegian and tested clinical ly . The purpose was to establish construct validity , interrater reliability and internal consistency . In addition , the effect of sucrose as pain analgesia was tested in neonates > or= 36 weeks of gestational age . In a known-groups comparisons design with repeated measures , 111 consecutive neonates , preterm and term , were all observed at baseline , non-pain and pain event . Neonates in the neonatal unit received sucrose at pain event . A significant interaction effect of gestational age and events was found in the sucrose neonates . A significant interaction effect was detected from sucrose and event type for neonates from 36 weeks . The internal consistency of the six-item score was acceptable . A correlation coefficient of 0.89 - 0.97 was obtained for interrater reliability . The Norwegian version of the Premature Infant Pain Profile seems to be a reliable and valid instrument for pain assessment in neonates STUDY OBJECTIVE We sought to determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain score for children . METHODS We performed a prospect i ve , single-group , repeated- measures study of children between 8 and 15 years presenting to an urban pediatric emergency department with acute pain . On presentation to the ED , patients marked the level of their pain on a 100-mm nonhatched VAS scale . At 20-minute intervals thereafter , they were asked to give a verbal categoric rating of their pain as " heaps better , " " a bit better , " " much the same , " " a bit worse , " or " heaps worse " and to mark the level of pain on a VAS scale of the same type as used previously . A maximum of 3 comparisons was recorded for each child . The minimum clinical ly significant difference in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported " a bit worse " or " a bit better " pain . RESULTS Seventy-three children were enrolled in the study , yielding 103 evaluable comparisons in which pain was rated as " a bit better " or " a bit worse . " The minimum clinical ly significant difference in VAS score was 10 mm ( 95 % confidence interval 7 to 12 mm ) . CONCLUSION This study found the minimum clinical ly significant difference in VAS pain score for children aged 8 to 15 years ( on a 100-mm VAS scale ) to be 10 mm ( 95 % confidence interval 7 to 12 mm ) . In studies of population s , differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance Oral sucrose reduces pain during heel sticks and venipunctures in preterm infants , but no studies have been done to determine the effectiveness of sucrose during eye examinations for retinopathy of prematurity . Therefore , the purpose of this study was to determine the effectiveness of local anesthetic eye drops and a pacifier , plus repeated doses of 24 % sucrose , to relieve pain associated with eye examinations for retinopathy of prematurity . In this double-blind r and omized controlled trial , 30 preterm infants were r and omly assigned to one of two treatments , in which they received either local anesthetic eye drops , a pacifier , plus three doses of sterile water or local anesthetic eye drops , a pacifier , plus three doses of 24 % sucrose during the eye examination . Treatment effectiveness was determined using a vali date d infant pain measure , the Premature Infant Pain Profile ( PIPP ) , which includes measures of facial expressions , heart rate , and oxygen saturation and takes behavioral state and gestational age into consideration . Data were collected before , during , and following an examination of the left eye . Statistically significant differences in mean PIPP scores were found between the sucrose and water groups during the left eye examination . The mean PIPP score was 8.8 for the sucrose group and 11.4 for the water group ( t = 2.87 , p = .008 two-tailed ) . No significant differences were found in PIPP scores immediately following the procedure . Sucrose and a pacifier may be beneficial for minimizing pain during eye examinations in preterm infants and should be considered as a part of evidence -based guidelines for relieving pain during this procedure In this study we aim ed to assess and compare the analgesic effects of orally administered sucrose , dextrose , dextrose or sucrose followed by a pacifier , and sterile water during minor painful procedures in neonates . One hundred thirty-eight healthy term newborn infants were enrolled in this prospect i ve study . They received either sweet solutions or sweet solutions followed by pacifiers before the heel prick ( group 1 , dextrose 12.5 % ; group 2 , dextrose 12.5 % followed by a pacifier ; group 3 , sucrose 12.5 % ; group 4 , sucrose 12.5 % followed by a pacifier ; and group 5 , sterile water ) . The median values for crying time and the pain scores performed according to the neonatal facial coding system were recorded . The median crying times were 16.5 , 55 , 92.5 , 102 , and 132 seconds in groups 4 , 2 , 3 , 1 , and 5 , respectively ( P = .0001 ) . The pain scores showed that babies in group 4 had significantly lower scores followed by groups 2 , 3 , 1 , and 5 ( P = .0001 ) . Although group 4 had a lower pain score and shorter crying time than group 2 , the difference was not statistically significant ( P = .27 and P = .39 ) . In conclusion , 12.5 % dextrose or sucrose followed by a pacifier was found to be superior to dextrose only and sucrose only solutions in pain relief ; sucrose followed by a pacifier result ed in lower pain scores and shorter crying time than dextrose when combined with a pacifier . The antinociceptive effect of sweet solutions can be enhanced with a pacifier Clear benefit of sucrose analgesia for preterm neonates during venepuncture is shown Although studies of oral sucrose solution for procedure related pain in neonates have been subjected to a meta- analysis and a systematic review , several problems have been noted , and only one small trial focused on the role of oral sucrose for preterm venepuncture.1–3 We therefore performed a r and omised , double blinded , placebo controlled , crossover trial of 25 % sucrose solution in healthy preterm infants to assess its efficacy in reducing pain responses during routine venepuncture . All well infants , below gestational age 37 weeks , admitted to the neonatal intensive care unit at Leicester Royal Infirmary , who needed routine blood sampling on at least two occasions were eligible for the study . Exclusion criteria included unwell infants , need for oxygen or ventilation in the last seven days , intravenous feeding , five minute Apgar scores of 6 or less , neuromuscular dysfunction , grade 2 or more intraventricular haemorrhage , dysmorphic features , maternal opiate abuse , and need for analgesia or sedation within 48 hours of venepuncture . Written informed consent was obtained from a parent . The local hospital ethics committee approved the study . Infants received either 25 % sucrose solution ( S25 ) or water orally before two routine venepunctures . A hospital pharmacist used a table of r and om numbers to determine In this study , we aim ed to compare the analgesic effect of 30 % sucrose and 10 % and 30 % glucose in a group of healthy term newborns . A total of 113 infants whose heels were pricked for the guthrie test were included in the study . The babies were r and omized into 4 groups , receiving 2 ml of 30 % sucrose , 10 % glucose , 30 % glucose , or distilled water . Response to pain was assessed by mean crying time , recovery time , maximum heart rate , and percent change in heart rate at 1 , 2 , and 3 minutes . Mean crying times were 60 , 102 , 95 , and 105 seconds in the sucrose , 10 % glucose , 30 % glucose , and placebo groups , respectively ( P = .02 ) . Although mean recovery time was shorter in the sucrose group ( 102 seconds ) , there was neither a significant difference between the groups ( 10 % glucose , 121 seconds ; 30 % glucose , 109 seconds ; control group , 132 seconds [ P = .09 ] ) , Nor was there a difference in maximum heart rate and percent change in heart rate at 1 , 2 , and 3 minutes after heel prick ( P = .14 , P = .05 , P = .53 For the first , second , and third minutes , respectively ) . However , a statistically borderline difference existed at the end of 2 minutes favoring sucrose ( P = .05 ) . We conclude that 30 % sucrose is superior to 10 % and 30 % glucose solutions in relieving pain , showing its primary effect in crying time . As glucose solutions are readily available in neonatal intensive care units and easier to use in routine practice , further trials are needed to evaluate the antinociceptive effect of glucose when combined with other nonpharmacologic methods The aim of this study was to investigate whether repeated doses of hindmilk were effective for pain relief during routine heel stick in term neonates . Infants enrolled in this double-blind placebo-controlled study were r and omly assigned to hindmilk , 12.5 % sucrose and distilled water groups . Infants were given 1 ml of the test solution 1 minute prior to , immediately before and 1 minute after the heel stick . Pain responses were assessed by physiologic and behavioral parameters and also according to the Neonatal Facial Coding System ( NFCS ) . There were significant reductions in crying time , duration of the first cry and tachycardia , time needed for return to baseline heart rate , and the average and 1- and 5-minute NFCS scores in the hindmilk group when compared with the distilled water group . When the hindmilk group was compared to the sucrose group , only the NFCS scores at 1 and 2 minutes reached statistical significance in favor of the sucrose group . Repeated dose hindmilk administration is an effective analgesic intervention in term newborns during heel stick . Although the analgesic effect of 12.5 % sucrose is slightly superior , hindmilk may be considered as a physiologically suitable alternative to sucrose Background : Sucrose is widely used to manage procedural pain in term newborns despite a lack of evidence of its effectiveness for different procedures and infant population s. Our objectives were to evaluate the effectiveness and safety of sucrose in newborns undergoing various medical procedures within 2 days of birth . Methods : We performed a double-blind , r and omized controlled trial . We included newborns ( ≥ 36 weeks gestation ) of diabetic mothers and nondiabetic mothers . Each newborn received 2 mL of a 24%-sucrose or placebo solution before all procedures . We used the Premature Infant Pain Profile to assess pain during intramuscular injection of vitamin K , venipuncture for the newborn screening test and the first 3 heel lances for glucose monitoring ( newborns of diabetic mothers only ) . Scores ranged from from 0 ( no pain ) to 18 ( maximum pain ) . Results : We included 240 newborns ( 120 from diabetic mothers , 120 from nondiabetic mothers ) . The overall mean pain score was lower among newborns who received sucrose than among those who received a placebo ( mean difference –1.3 , 95 % confidence interval [ CI ] –2.0 to –0.6 ) . We found that pain scores during intramuscular injection did not differ significantly between the sucrose and placebo groups for newborns of diabetic or nondiabetic mothers ( newborns of nondiabetic mothers : mean difference –1.1 , 95 % CI –2.4 to 0.2 ; newborns of diabetic mothers : mean difference –1.0 , 95 % CI –2.4 to 0.4 ) . During venipuncture , newborns who received sucrose had lower pain scores compared with those who received a placebo ( newborns of nondiabetic mothers : mean difference –3.2 , 95 % CI –4.6 to –1.8 ; newborns of diabetic mothers : mean difference –2.4 , 95 % CI –3.8 to –1.0 ) . Among newborns of diabetic mothers , there was no difference in pain during the first 3 heel lances or mean glucose levels between the sucrose and placebo groups ( p = 0.94 and p = 0.29 respectively ) . Interpretation : We found a modest reduction of pain in newborns of both diabetic and nondiabetic mothers when sucrose was used for all medical procedures performed in the first 2 days after birth . However , when each procedure was analyzed separately , we found that the effectiveness of sucrose was limited to venipuncture for the newborn screening test . ( http:// Clinical trials.gov trial register no. NCT00213213 . Newborns endure many heel pricks and other uncomfortable procedures during their first hospital stay . The aim of this study was to investigate the effectiveness of breast-feeding in reducing pain in newborns undergoing heel prick tests . One hundred thirty healthy term infants requiring a heel prick blood sampling for the Guthrie test were studied . Infants were r and omly allocated to 1 of the following treatment groups : group 1 , 25 % sucrose ( n = 35 ) ; group 2 , breast milk ( n = 33 ) ; group 3 , sterile water ( n = 34 ) ; and group 4 , breast-feeding ( n = 28 ) . The median values of crying and recovery time and percent change in heart rate at 1 , 2 , and 3 minutes were recorded . A behavioral pain scale was applied according to the infant body coding system . The median crying time was 36 , 62 , 52 , and 51 seconds in groups 1 , 2 , 3 , and 4 , respectively ( P = .002 ) . Similarly , there was a significant overall difference among groups for the duration of recovery time ( P = .006 ) and the percent change in heart rate at 1 ( P = .03 ) , 2 ( P = .01 ) , and 3 ( P = .009 ) minutes favoring the sucrose group . But when we compared the groups , the significance remained for the sucrose versus breast milk ( P = .007 ) and water ( P = .001 ) groups for the recovery time and sucrose versus all other groups for the percent change in heart rate at 3 minutes . The infant body coding system showed that babies in the sucrose group had significantly lower scores followed by the breast-fed and breast milk groups ( P = .0001 ) . Our study revealed that 25 % sucrose is superior to breast-feeding in pain relief , which is reflected mainly in crying time and behavioral variables . The behavioral effects of breast-feeding did not provide any additional benefit Although comparison with a placebo is necessary to demonstrate the " true " effect of a drug , neonatologists are usually reluctant to use a placebo . The reason given is the lack of placebo effect in neonates . We studied heart and respiration rates and behaviour in normal neonates during heelstick for diagnosis of phenylketonuria . In this open r and omized study we compared no treatment with an " analgesic " treatment consisting of water and sucrose . There was no difference in heart and respiration rates and behaviour between the two groups . These results do not demonstrate a " suggested " placebo effect and can in part be explained by the model and tools used to measure pain . The results do not support the non-use of placebo in drug evaluation trials in children Background Preterm and acutely ill term neonates who are hospitalized in a neonatal intensive care unit are subjected to multiple frequent invasive and painful procedures aim ed at improving their outcome . Although several trials to determine the efficacy of sucrose for managing procedural pain in preterm and acutely ill term neonates have been developed , these have generally lacked method ological rigor and have not provided clinicians with clear practice guidelines . Objectives To compare the efficacy and safety of three interventions for relieving procedural pain associated with heel lances in preterm and term neonates , and to explore the influence of context ual factors including sex , severity of illness , and prior painful procedures on pain responses . Methods In a r and omized controlled trial , 190 neonates were stratified by gestational age and then r and omized to receive ( a ) sucrose and nonnutritive sucking ( n = 64 ) , ( b ) sucrose alone ( n = 62 ) , or ( c ) sterile water and nonnutritive sucking ( control ) ( n = 64 ) to evaluate the efficacy ( pain response as measured using the Premature Infant Pain Profile ) ( Stevens , Johnson , Petryshen , & Taddio , 1996 ) and safety ( adverse events ) following a scheduled heel lance during the first week of life . Stratification was used to control for the effects of age on pain response . Results Significant differences in pain response existed among treatment groups ( F = 22.49 , p < .001 ) , with the lowest mean Premature Infant Pain Profile scores in the sucrose and nonnutritive sucking group . Efficacy of sucrose following a heel lance was not affected by severity of illness , postnatal age , or number of painful procedures . Intervention group and sex explained 12 % of the variance in Premature Infant Pain Profile scores . Few adverse events occurred ( n = 6 ) , and none of them required medical or nursing interventions Conclusions The combination of sucrose and nonnutritive sucking is the most efficacious intervention for single heel lances . Research on the effects of gestational age on the efficacy and safety of repeated doses of sucrose is required OBJECTIVE To assess the effectiveness of oral sucrose via a nipple compared with no treatment and dorsal penile nerve block ( DPNB ) for alleviating pain in neonatal circumcision . DESIGN R and omized control trial . Data analysis performed by investigators blinded to the 3 treatment groups . SETTING University teaching hospital , General Care Nursery . PATIENTS One hundred nineteen full-term male , normal birth weight neonates , 12 hours old or older . INTERVENTIONS No treatment ( our st and ard care ) , DPNB , or oral sucrose prior to circumcision . MAIN OUTCOME MEASURES Differences between groups in heart rate and oxygen saturation changes from baseline during specified intervals of the circumcision procedure . Differences between groups in loss of data due to episodes of excessive motion . RESULTS Sucrose gave significant ( P < .001 ) pain relief compared with the no treatment control throughout most of the circumcision and particularly in the early stages of the procedure . Overall , the average difference in the elevation of heart rates during the circumcision operative procedure among the 3 groups and the 95 % confidence intervals ( CIs ) were as follows : control vs DPNB , 27.1 beats/min ( 17.6 , 36.6 ) and control vs sucrose , 9.7 beats/min ( 0.1 , 19.3 ) . Furthermore , newborns who received either DPNB or sucrose had less loss of oxygen saturation data due to excessive motion during the procedure than the no-treatment controls . The total percentages of lost data due to excessive motion in the 3 groups were 31 % for control , 10 % for DPNB , and 8 % for sucrose . Relative risk and 95 % CIs were : DPNB vs control , 0.32 ( 0.23 , 0.43 ) ; sucrose vs control , 0.26 ( 0.18 , 0.36 ) . Differences in oxygen saturation among the 3 groups during the circumcision operative procedure were statistically ( P < .001 ) , but perhaps not clinical ly , significant . However , the analysis did not include missing data due to excessive motion , which occurred predominantly in the no-treatment control group . CONCLUSION Sucrose on a pacifier is an inexpensive and effective method for pain relief in neonatal circumcision when DPNB is not desirable Objective To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck ( NNS ) as a method for reducing pain associated with retinopathy of prematurity ( ROP ) screening . Design R and omised placebo controlled study . Setting Tertiary level neonatal intensive care unit . Sample 40 infants undergoing primary eye examination for ROP screening . Intervention The control group were swaddled , and received 0.2 ml of sterile water given by mouth using a syringe and a soother . The intervention group were swaddled , and received 0.2 ml of sucrose 24 % given by mouth using a syringe and a soother . Results 40 infants were included in the study . There was no difference in mean gestational age at birth , mean birth weight or corrected gestational age at first examination between both groups . The sucrose group had a significantly lower median Neonatal Pain , Agitation and Sedation Scale ( N-PASS ) score during ROP screening , initially following insertion of the speculum ( 6.5 vs 5 , p=0.02 ) and subsequently during scleral indentation ( 9.5 vs 7.5 , p=0.03 ) . Fewer infants experienced episodes of desaturations or bradycardia in the intervention group ( 1 vs 4 , p=0.18 ) . Conclusion ROP screening is a necessary but recognised painful procedure . Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses . However , pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge OBJECTIVE . The purpose of this work was to compare the efficacy of breastfeeding versus orally administered sucrose solution in reducing pain response during blood sampling through heel lance . METHODS . We conducted an open-label , r and omized , controlled trial at a neonatal unit of a public hospital in northern Italy on 101 term neonates undergoing heel lance with an automated piercing device for routine neonatal screening for congenital disorders . Newborn infants were r and omly assigned to breastfeeding during blood sampling or to the oral administration of 1 mL of 25 % sucrose solution . We vali date d the multidimensional acute pain rating scale of the Premature Infant Pain Profile , heart rate increase , oxygen saturation decrease , crying behavior ( duration of first cry , cry percentage in 2 minutes , and during blood sampling ) , duration of sampling , and the number of performed heel lances . RESULTS . Median Premature Infant Pain Profile scores were lower in the breastfeeding group ( 3.0 ) than in the sucrose-solution group ( 8.5 ) , and the median group difference was −5.0 . The median heart rate increase , oxygen saturation decrease , and duration of first cry for the breastfeeding group were , respectively , 13.0 , −1 , and 3 and for sucrose group were 22 , −3 , and 21 . Medians were significantly different between the groups . There were no significant differences in the sampling duration and numbers of heel lances . CONCLUSIONS . This study suggests that breastfeeding provides superior analgesia for heel lance compared with oral sucrose in term neonates Abstract The aim of this study was to compare the analgesic effect of 2 ml 25 % sucrose and human milk in a group of healthy term newborns . Healthy infants ( n = 102 ) were r and omly allocated to receive one of three solutions ( sucrose , human milk , sterile water ) 2 min prior to taking a heel prick blood sample . The median values of crying time , recovery time and percentage change in heart rate at 1 , 2 and 3 min were recorded in response to the heel prick . Median crying times were 36 , 52 , and 62 s in the sucrose , placebo and human milk groups , respectively ( P = 0.0009 ) . In the sucrose group , there was a significant reduction in crying time compared to human milk and placebo groups . Similarly , the median recovery time in the sucrose group ( 72 s ) was shorter than that in the human milk ( 112 s ) and placebo groups ( 124 s ) ( P = 0.004 ) . The percentage change in heart rate at 1 , 2 and 3 min was also significantly lower in the sucrose group ( P = 0.008 , P = 0.01 , P = 0.002 at 1 , 2 , and 3 min respectively ) . Conclusion The orosensorial antinociceptive effect of human milk is not as effective as an analgesic as a 25 % sucrose solution Objectives : To assess pain burden in neonates during their hospitalization in China and thus provide evidence for the necessity of neonatal pain management . Patients and Methods : The Neonatal Facial Coding System was used to evaluate pain in neonates . We prospect ively collected data of all painful procedures performed on 108 neonates ( term , 62 ; preterm , 46 ) recruited from admission to discharge in a neonatal intensive care unit of a university-affiliated hospital in China . Results : We found that during hospitalization each preterm and term neonate was exposed to a median of 100.0 ( range , 11 to 544 ) and 56.5 ( range , 12 to 249 ) painful procedures , respectively . Most of the painful procedures were performed within the first 3 days . Preterm neonates , especially those born at 28 and 29 weeks ’ gestational age , experienced more pain than those born at 30 weeks ’ gestation or later ( P<0.001 ) . Among those painful procedures , tracheal aspiration was the most frequently performed on preterm neonates , and intravenous cannulation was the most common for term neonates . Moreover , tracheal intubations and femoral venous puncture were found to be the most painful . Notably , none of the painful procedures was accompanied by analgesia . Conclusions : Neonates , particularly preterm neonates , were exposed to numerous invasive painful procedures without appropriate analgesia in hospitals in China . The potential long-term impacts of poorly treated pain in neonates call for a change in pediatric practice in China and in countries with similar practice In this nonr and omized , prospect i ve cohort study , the construct validity of the Neurobehavioral Assessment of the Preterm Infant ( NAPI ) was examined by comparing it with measures of neonatal physiological status . A cohort of preterm infants ( n = 37 ) was tested repetitively at 32 and 36 weeks post-conceptional age ( PCA ) to determine whether there was a correlation between physiological status and NAPI scores at these ages . We anticipated fair , clinical ly significant correlations ( r = 0.25–0.50 ) between physiological and neurobehavioral status . This was found using Pearson Product Moment correlational analysis between components of the neurobehavioral performance repertoire at 32 weeks PCA , the degree of medical intervention and the early biological risks that contribute to developmental status . The finding was less marked at 36 weeks PCA when the subjects were physiologically more stable PURPOSE : The purpose of this study was to determine the effect of oral sucrose solution on pain responses of neonates to arterial puncture compared with neonates who did not receive a sucrose solution . SUBJECTS : Convenience sample of 47 neonates , 31 to 35 weeks ' gestational age . DESIGN : Double-blind , r and omized controlled trial . MAIN OUTCOME MEASURE : Changes in pain response during and after an arterial puncture . METHODS : Infants were r and omly assigned to receive a 24 % sucrose solution or usual care ( comfort measures only ) 2 minutes before an arterial puncture . Pain , heart rate , and oxygen saturation were measured before , during , and after an arterial puncture . Chi-square analysis was used to determine group differences , with P < .05 considered significant . RESULTS : Forty-seven subjects were studied during arterial puncture ( sucrose , 24 ; no sucrose , 23 ) . Neonates receiving sucrose solution had significantly less crying than the no sucrose group , both during and immediately after an arterial puncture ( P = .006 and .022 , respectively ) . No significant changes in other pain subscales , heart rate , or oxygen saturation were found during or after the arterial puncture ( P > .05 ) . CONCLUSION : This study found a significant reduction in the crying subscale of the Neonatal Infant Pain subscale immediately after the introduction of an arterial needle in neonates receiving a 24 % sucrose solution , compared with those who did not receive sucrose solution . While prior studies found a similar reduction in pain scores after heel and venipuncture needlesticks , this is the first study evaluating a high concentration of oral sucrose to blunt the pain associated with an arterial puncture Objective : The aim of the study was to determine if pain and distress during the retinopathy of prematurity ( ROP ) screening examination could be ameliorated by providing comfort care . Study Design : This study was a prospect i ve , r and omized , controlled trial of 30 stable preterm infants who underwent initial ROP screening examinations . Fourteen study infants were swaddled , held , and given 24 % sucrose solution during the examination . Sixteen controls were examined while lying in their cribs . Vital signs ( i.e. , pulse rate , respiratory rate , and oxygen saturation ) , crying time , and time for the vital signs to return to baseline values were recorded at different times during the examination . Results : The vital signs did not vary significantly between the two groups . The participants in the control group had a trend of longer crying time , but this trend did not reach a level of statistical significance . In addition , The time required for the vital signs to return to their baseline values did not vary significantly . Conclusion : ROP screening is very distressful for preterm infants . The routine use of comfort care to reduce pain during the examination could not be supported by this study The effects of behavioral interventions in reducing the stress of infant pain are not well documented . Two comfort interventions , rocking and pacifiers , were compared with routine care administered to 60 newborn infants r and omly assigned to the three conditions following a neonatal screening heelstick . Heart rate , state of arousal , and crying were recorded continuously . Both pacifiers and rocking reduced crying , but pacifiers predominantly produced sleep states and rocking predominantly produced alert states . Pacifiers reduced heart rate levels significantly more than did rocking . Thus , newborns clearly benefit from both comforting methods . Several mechanisms are proposed to account for these findings BACKGROUND To evaluate the effect of different oral glucose or sucrose solutions on the pain response to heelstick in newborns . METHODS DESIGN r and omised double blind placebo controlled trial of water ( control ) versus one of three solutions of glucose - namely 5 , 33 and 50 % - or one of two solutions of sucrose ( 33 % and 50 % ) or nothing . SETTING postnatal ward . PATIENTS seven groups of 20 healthy newborns ( gestational age 38 - 41 , weighing over 2500 g ) were r and omised to receive 2 ml of one of the six solutions on the tongue inmediately before heelstick procedure . MAIN OUTCOME MEASURE heart rate before , during and three minutes after the procedure . RESULTS Even if the trend of the cardiac rates did not reach statistic significance , glucose solution 33 and 50 % proved to be the most effective in reducing pain response . CONCLUSIONS Sweet solutions may be an easy , useful , safe and cheap analgesic for minor invasive procedures in newborns The purpose of this r and omized clinical trial was to test the efficacy of repeated versus single dose sucrose to decrease pain from routine heel stick procedures in preterm neonates . Infants ( n = 48 ) in the first week of life with a mean gestational age of 31 weeks received 0.05 ml of 24 % sucrose solution or sterile water by mouth ( 1 ) 2 min prior to actual lancing of the heel ; ( 2 ) just prior to lancing , and ( 3 ) 2 min after lancing . The single-dose group received sucrose for the first dose and water for the second and third dose ; the repeated-dose group received sucrose three times , and the placebo group received only water . The Premature Infant Pain Profile ( PIPP ) scores were obtained for five 30-second blocks from lancing . Both sucrose groups had lower PIPP scores ( single sucrose pain scores , 6.8–8.2 , p = 0.07 ; repeated sucrose pain scores , 5.3–6.2 , p < 0.01 ) than water ( pain scores 7.9–9.1 ) , and in the last block , the repeated dose had lower scores than the single dose ( 6.2 vs. 8.2 , p < 0.05 ) To investigate the soothing effect of feeding on infants in distress , the effects of 2mL 15 % and 1 mL 25 % sucrose given orally 2 min before heel prick in fasting preterms to reduce the pain response were assessed . The effects of milk intake by nasogastric tube were also assessed once during the last hour before heel prick , and the effects of milk intake by nasogastric tube once during the last hour before heel prick together with 1 mL 25 % sucrose given orally 2 min before heel prick . The pain response was measured as changes in crying time , behavioural state , skin conductance and heart rate . Each group included 12 healthy preterm infants with a median gestational age of 32 wk and a median postnatal age of 14 d. These infants were r and omly studied twice ; one in connection with the intervention and once after being given sterilized water . Differences in the measured variables before and during heel prick showed that only the crying time was reduced when the infants received milk or 25 % sucrose prior to heel prick ( p > 0.05 ) . If the infants received milk and 25 % sucrose before heel prick , the crying time and the level of behavioural state were reduced ( p > 0.05 ) . The increase from before to during heel prick in skin conductance ( number and amplitude of the waves ) and heart rate correlated with the crying time ( p > 0.01 ) OBJECTIVE : The purpose of this trial was to investigate whether breast milk ( either breastfed or bottle-fed ) has a better analgesic effect than sucrose in newborns born at a postmenstrual age between 32 and 37 weeks . METHODS : We conducted a r and omized controlled trial at a secondary care neonatal unit in the Netherl and s on 71 preterm neonates ( postmenstrual age at birth 32–37 weeks ) , undergoing heel lance with an automated piercing device . Newborns were r and omly assigned to breast milk ( either breastfed or bottle-fed ) administered during heel lance or oral sucrose administered before heel lance . We assessed the Premature Infant Pain Profile ( PIPP ) score ( range , 0–21 ) to investigate whether there was a difference in pain score between neonates receiving breast milk and those receiving sucrose solution . RESULTS : There was no significant difference in mean PIPP score between neonates receiving breast milk ( 6.1 ) and those receiving sucrose ( 5.5 ) , with a mean difference of 0.6 ( 95 % confidence interval −1.6 to 2.8 ; P = .58 ) . CONCLUSIONS : From this study , it can not be concluded that breast milk has a better analgesic effect than sucrose in late preterm infants . From the results , it follows with 95 % confidence that the analgesic effect of breast milk is not > 1.6 points better and not > 2.8 points worse on the PIPP scale ( SD 3.7 ) than the analgesic effect of sucrose in late preterm infants It remains unclear whether “ sucrose analgesia ” is related to a pre- or postabsorptive mechanism . In a double blind cross over study sucrose reduced the pain response of preterm infants exposed to heel prick blood sample s only when it was administered into the mouth . It was ineffective when administered intragastrically BACKGROUND Procedural pain management for very low birth weight ( VLBW ) neonates has been minimal or nonexistent in most neonatal intensive care units ( NICUs ) . OBJECTIVES To compare the efficacy of developmentally sensitive behavioral interventions ( nonnutritive sucking via a pacifier , positioning ) and sucrose for relieving procedural pain in VLBW infants and to determine the influence of context ual factors ( gestational age , postnatal age , birth weight , severity of illness , frequency of painful procedures ) on pain response . METHOD In a prospect i ve r and omized crossover trial , pain was assessed in 122 VLBW neonates using the Premature Infant Pain Profile following four r and omly ordered interventions during consecutive routine heel lance procedures . RESULTS Significant differences in pain existed among treatment interventions ( F = 16.20 , p < .0001 ) . The pacifier with sucrose ( F = 24.09 , p < .0001 ) and pacifier with sterile water ( F = 9.00 , p = .003 ) significantly reduced pain . Prone positioning did not decrease pain ( F = 2.24 , p = .137 ) . Frequency of painful procedures approached significance in influencing pain response ( F = 3.59 , p = .01 ) . CONCLUSIONS The most efficacious interventions for reducing pain from single painful events were the pacifier with sucrose and the pacifier with sterile water . Research on the efficacy and safety of implementing these interventions , alone and in combination , for repeated painful procedures is needed . In addition , research is needed on the influence of implementing these interventions on pain response and clinical outcomes ( e.g. , health status and neurodevelopmental status ) in VLBW neonates in the NICU In human newborns , small amounts of sucrose reduce crying with procedural pain by about 50 % . To determine whether “ sucrose analgesia ” could be extended to painful procedures beyond the newborn period , 57 infants were r and omly assigned to receive three 250-$mUl doses of 50 % sucrose solution ( g/100 mL ) or water before their diphtheria-tetanus-pertussis immunizations at 2 and 4 months of age . Crying during and after injection was measured separately to determine whether sucrose modified crying during the noxious stimulus , recovery from the stimulus , or both . Sucrose was effective in reducing crying only from 83 to 69 % , and the reduction was limited to the postinjection period . We conclude that , although sucrose continues to have some effect beyond the newborn period , the effect is limited to recovery from the noxious stimulus , is clinical ly modest , and is probably smaller than in the newborn period BACKGROUND Pain and stress agitate preterm infants , interrupting their sleep . Frequent high arousal states may affect infants ' brain development and illness recovery . Preserving infants ' sleep and relieving their pain during painful procedures are both important for their health . OBJECTIVES To compare the effectiveness of different combinations of non-nutritive sucking ( sucking ) , oral sucrose , and facilitated tucking ( tucking ) with routine care on infants ' sleep-wake states before , during , and after heel-stick procedures . DESIGN Prospect i ve , r and omised controlled trial . SETTING Level III Neonatal Intensive Care Unit in Taipei . METHOD A convenience sample of 110 infants ( gestational age 26.4 - 37 weeks ) needing heel sticks were r and omly assigned to five combinations of non-pharmacological treatments : sucking-oral sucrose-tucking ; sucking-oral sucrose ; oral sucrose-tucking ; sucking-tucking ; and routine care . Infant states , measured by a state-coding scheme , included quiet sleep , active sleep , transition , quiet awake , active awake , and fussing or crying . All states were recorded at 1-min intervals during four phases : baseline , intervention , heel-stick procedures , and recovery . RESULTS Infants receiving sucking-oral sucrose-tucking or sucking-oral sucrose experienced 52.8 % ( p=0.023 ) and 42.6 % ( p=0.063 ) more quiet-sleep occurrences than those receiving routine care after adjusting for phase , baseline states , non-treatment sucking during baseline and recovery , positioning , and infants ' characteristics . Infants receiving oral sucrose-tucking , sucking-oral sucrose , sucking-oral sucrose-tucking , and sucking-tucking experienced 77.3 % ( p<0.001 ) , 72.1 % ( p=0.008 ) , 51.5 % ( p=0.017 ) , and 33.0 % ( p=0.105 ) fewer occurrences of fussing or crying , respectively , than those receiving routine care after adjusting for related factors . CONCLUSIONS The four treatment combinations differentially reduced infants ' high arousal across heel-stick procedures . The combined use of oral sucrose-tucking , sucking-oral sucrose , and sucking-oral sucrose-tucking more effectively reduced occurrences of infant fussing or crying than routine care . Treatment combinations of sucking-oral sucrose-tucking and sucking-oral sucrose also better facilitated infants ' sleep than routine care . To preserve infants ' sleep , clinicians should use combinations of non-nutritive sucking , oral sucrose , and facilitated tucking to reduce agitation during painful procedures Objectives : To evaluate the effect of oral sucrose on skin blood flow ( SBF ; perfusion units ; PU ) measured by Laser Doppler Imager ( LDI ) in term newborns and pain response ( Neonatal Infant Pain Scale score ; NIPS score ) during heel lance ; ( 2 ) determine SBF changes during heel lance ; and ( 3 ) the relationship between SBF and NIPS . Material s and Methods : Term infants ⩽7 days old ( n=56 ) undergoing routine heel lance were r and omized to pretreatment with 2.0 mL oral 24 % sucrose ( n=29 ) or sterile water ( n=27 ) in a double-blinded , placebo-controlled trial . SBF was assessed by LDI scans and NIPS scores at 10 minutes before lance , immediately after lancing , and 5 minutes after blood extraction . Mean SBF and median NIPS scores were compared between groups using General Linear Model or Kruskal-Wallis . Regressions examined the relationship between SBF immediately after heel lance and NIPS score . Results : Mean SBF and median NIPS scores immediately after heel lance were lower in sucrose-treated infants ( 167.9±15.5 vs. 205.4±16.0 PU , P=0.09 ; NIPS 1 [ interquartile range 0 to 4 ] vs. NIPS 3 [ interquartile range 0 to 6 ] , P=0.02 ) , although no significant difference in mean SBF . During heel lance NIPS score was predictive of SBF . An increase of 1 in NIPS score was associated with 11 PU increase in SBF ( R2=0.21 ; P=0.09 ) for sucrose , and 16 PU increase for placebo-treated infants ( R2=0.20 ; P=0.014 ) . Conclusions : Increased SBF assessed by LDI is a pain response among term neonates after routine heel lance , which was not completely attenuated by oral sucrose administration . Increased SBF is associated with NIPS scores . Sucrose analgesic efficacy evidence d by decreased NIPS scores for the sucrose group . Association of SBF with NIPS scores suggests that LDI is potentially useful for assessing newborn procedural pain The purpose of this study was to investigate if cries from preterm neonates would reflect changes in pain intensity following interventions . The cries from 25 preterm neonates from an original sample of 122 were audiorecorded while the infant was undergoing heelstick during a r and omized crossover design testing the efficacy of : pacifier with sucrose or water , or prone position as compared to st and ard care . Both pacifier conditions reduced procedural pain according to a vali date d composite pain measure ( the Premature Infant Pain Profile ) . There were proportionately fewer cries in the two pacifier groups compared to the prone positioning and st and ard care groups , and cry duration was positively correlated with PIPP scores . However , neither cry duration nor fundamental frequency reflected group differences . Further research is needed to determine if cry is a sensitive and valid indicator of pain in preterm infants We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria . In addition , the influences of gender , gestational age , postnatal age , ponderal index and behavioural state of the infant before the heel prick were studied , as judged by the neonatal infant pain scale ( NIPS ) score , on crying time ( CT ) and subsequent NIPS score . 100 healthy full-term infants were enrolled in this double-blind , r and omized controlled trial . Before the heel prick , the newborns , when cuddled by the parent(s ) , were either given 2 ml 50 % sucrose solution or 2 ml sterile water . The sessions were videotaped and analyzed for determination of CT and NIPS scores . The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups . Sucrose significantly reduced CT and NIPS scores after the heel prick . No influence of gender , gestational age , postnatal age or ponderal index on CT was found . NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups . Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever . Furthermore , the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration A sub- analysis was conducted of data from a study of prolonged use of sucrose for hospitalized infants ( N=50 infants ) during heel lancing . Results showed that pain responses differed when opioid analgesics were administered concomitantly with sucrose ( n=79 pain assessment s ) , than when sucrose was administered alone ( n=364 pain assessment s ) OBJECTIVE The purpose of this study was to identify the least painful circumcision method . STUDY DESIGN The infants were circumcised with either the Mogen or the Gomco procedure and were given a sweetened pacifier or a pacifier dipped in water . All infants had a eutectic mixture of local anesthetic cream applied before circumcision . The duration of the crying and grimacing were measured . RESULTS The Gomco procedure took 1.9 times longer to complete . Infants who were circumcised with the Mogen procedure cried and grimaced far less than infants who were circumcised with the Gomco procedure ( P = .0001 ) . Sucrose on a pacifier was far more analgesic than water on a pacifier for infants in the Gomco group . CONCLUSION On the basis of these and other findings on pain prevention and amelioration , we recommend that a local anesthetic be administered in advance of circumcision and that the Mogen procedure be used , unless contraindicated . We also recommend that infants be given a sweetened pacifier before , during , and after circumcision if the Gomco method is used PURPOSE To describe current newborn circumcision pain interventions and to identify which forms of analgesia were most effective . METHOD Each male newborn was assessed for pain during the circumcision procedure and at 15-minute intervals after the procedure using the FLACC pain scale . The type and combination of analgesia was also recorded on the pain assessment record . RESULTS Pain scores were highest for newborns receiving no analgesia during circumcision . Newborns circumcised with the dorsal block and the ring block in combination with the concentrated oral sucrose had the lowest pain scores . The sucrose alone did not provide sufficient analgesia ; however , it did reduce the FLACC score somewhat when used in conjunction with other analgesics/anesthesia . CONCLUSIONS Information obtained from this project facilitated a change in policy wherein newborn circumcision is performed only with the use of analgesia and not concentrated oral sucrose alone BACKGROUND Sucrose has been shown to have an analgesic effect in preterm and term neonates . Sucrose , however , has a high osmolarity and may have deleterious effects in infants with fructose intolerance . Furthermore , it may favour caries . We therefore investigated the effects of a commercially available artificial sweetener ( 10 parts cyclamate and 1 part saccharin ) , glycine ( sweet amino acid ) or breast milk in reducing reaction to pain as compared with a placebo . SUBJECTS Eighty healthy term infants , four days old , with normal birth weight . INTERVENTIONS The infants were r and omly assigned to one of four groups : 2 ml sweetener , glycine , expressed breast milk or water were given 2 min before a heel prick for the Guthrie test . The procedure was filmed with a video camera and analysed by two observers who did not know which medication the infant had received . RESULTS Using a multivariate regression analysis , the following variables had significant correlation with relative crying time and recovery time : behavioural state before the intervention , the pricking nurse , and the type of medication . Relative crying time and recovery time were significantly less in the sweetener group but not in the glycine and the breast milk group . CONCLUSIONS The artificial sweetener used in our study reduces pain reaction to a heel prick in term neonates , and thus provides an alternative to sucrose . In contrast , glycine tends to increase pain reaction whereas breast milk has no effect Background and Objectives : Previous r and omized trials of the analgesic effects of sucrose , glucose , and a pacifier in term neonates have shown that the pacifier result ed in lower pain scores than glucose or sucrose , but the pacifier with and without sucrose did not differ . The current study was design ed to assess the analgesic effect of pharmacologic ( sucrose , water ) and a non-pharmacologic measures ( pacifier ) in preterm infants and to find whether there is any synergism between these intervention in relieving pain during painful procedures . Patients and Methods : In this double-blind , r and omized , controlled study , 36 preterm infants ( mean 31 weeks gestational age , range 27 to 36 weeks ) were r and omly allocated to six different regimens ( 0.5 mL sterile water with pacifier , 0.5 mL sterile water without pacifier , 0.5 mL sucrose 24 % with pacifier , 0.5 mL sucrose 24 % without pacifier , pacifier alone and control group ) during a stay in intensive care of up to 15 days . Pain scores were measured with the Premature Infant Pain Profile ( PIPP ) , a vali date d behavioral acute pain scale . Results : Of all the regimens , the lowest pain scores occurred with the use of 24 % sucrose solution combined with pacifier . The mean pain score for the combination of sucrose with pacifier was 0.7 as compared to 1.4 for the sterile water with pacifier group ( P < .05 ) . Conclusion : The synergistic effect of the combination of sucrose and non-nutritive sucking was clinical ly effective and safe in relieving the pain of simple procedures such as venipuncture or heel stick in preterm and term infants , but further research is needed on these interventions alone and in combination with other behav -- ioral interventions in neonates Objectives : To describe revisions to the Premature Infant Pain Profile ( PIPP ) and initial construct validation and feasibility of the Premature Infant Pain Profile-Revised ( PIPP-R ) . Methods : The PIPP was revised to enhance validity and feasibility . To vali date the PIPP-R , data from 2 r and omized cross-over studies were utilized to : ( 1 ) calculate and compare PIPP and PIPP-R scores in extremely low gestational age infants undergoing a painful and nonpainful event ( N=52 ; data set # 1 ) and ( 2 ) calculate and compare PIPP and PIPP-R scores in assessing the effectiveness of ( a ) sucrose , ( b ) non-nutritive sucking (NNS)+sucrose , and ( c ) facilitated tucking+NNS+sucrose during heel lance ( N=85 ; data set # 2 ) . Pearson correlations between PIPP and PIPP-R scores were calculated , and Student t tests and 1-way analysis of variance were used to determine construct validity during painful and nonpainful events . To establish feasibility , a survey of 31 Neonatal Intensive Care Unit nurses was conducted . Results : PIPP-R scores were significantly lower during nonpainful ( mean , 8.3 ; SD=2.9 ) compared with painful ( mean , 9.9 ; SD=3.1 ; t95=4.51 , P=0.036 ) events in extremely low gestational age infants in data set # 1 . In data set # 2 , PIPP-R scores were significantly lower in infants 25 to 41 weeks gestation in the group receiving NNS+sucrose compared with the other 2 groups ( F2,79=2.9 , P<0.05 ) . Overall , nurses rated the PIPP-R as feasible . Discussion : Initial construct validation and feasibility of the PIPP-R was demonstrated . Further testing with infants of varying gestational ages , diagnoses , and pain conditions is required ; as is exploration of PIPP-R in relation to other types of physiological and cognitive responses BACKGROUND : Gavage feeding is required in preterm infants who can not feed by themselves . Insertion of the feeding tube is painful , and reducing the discomfort in these patients is desirable . OBJECTIVE : The aim of this study was to assess pain and discomfort during nasal insertion of a feeding tube , and to evaluate different measures for pain relief . METHODS : We included 24 preterm infants with postmenstrual age 28 to 32 weeks ' who were in stable condition . Each infant acted as his or her own control over a 3-week period during which the tube was changed 6 times . On these occasions , 6 different treatment combinations were given in r and omized order : pacifier or no pacifier , combined with no fluid , sterile water , or 30 % sucrose . Pain and discomfort were assessed by at least 2 independent and experienced observers using a pain assessment tool , the Premature Infant Pain Profile ; score range : 0 to 21 . In general , scores of 4 to 6 are interpreted as normal or no discomfort ; ≥12 usually signals significant pain and distress . RESULTS : The median Premature Infant Pain Profile score during the procedure was 9 and decreased gradually toward 4 after 5 minutes . The lowest pain score was achieved by combining a pacifier with oral sucrose . Sterile water without a pacifier gave the highest score . CONCLUSIONS : Insertion of a feeding tube in preterm infants leads to a measurable degree of pain and discomfort , according to the Premature Infant Pain Profile assessment tool . Pain relief was best achieved by combining a pacifier with 30 % sucrose TOC Summary Providing natural warmth to newborn infants during a painful procedure decreases crying and grimacing and ranks first compared to the st and ard treatments of sucrose or pacifier . ABSTRACT This study identifies a behavioral and nonpharmacologic means of preventing and reducing newborn pain . Our objective was to determine whether warmth is analgesic in newborn infants undergoing vaccination — a routine painful hospital procedure . We used a prospect i ve r and omized controlled trial of 47 healthy full‐term newborn infants . Infants were r and omized into 1 of 3 conditions prior to vaccination : warmth exposure , pacifier suckling , or sucrose taste . Crying , grimacing , and heart rate differences were analyzed between groups before , during , and after vaccination as outcome measures . Warmer infants cried significantly less than sucrose taste or pacifier suckling after vaccination . Heart rate patterns reflected this analgesia . Core temperature did not differ between study groups . Providing natural warmth to newborn infants during a painful procedure decreases the crying and grimacing on par with the “ gold ” st and ard treatments of sucrose or pacifier Objective : To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the results of our previous study in 2001 . Design : A prospect i ve observational study . Setting : Level III NICU of the Erasmus MC-Sophia Children 's Hospital , Rotterdam . Participants : Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h. Main Outcome Measures : Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay . Results : A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days ( mean 12.2 ) . The mean number of painful procedures per neonate per day was 11.4 ( SD 5.7 ) , significantly lower than the number of 14.3 ( SD 4.0 ) in 2001 ( p < 0.001 ) . The use of analgesics was 36.6 % compared to 60.3 % in 2001 . Sixty-three percent of all peripheral arterial line insertions failed versus 37.5 % in 2001 and 9.1 % venipunctures failed versus 21 % in 2001 . Conclusions : The mean number of painful procedures per NICU patient per day declined . Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management . As further reduction of the number of painful procedures is unlikely , we should apply more nonpharmacological interventions and explore newer pharmacological agents |
12,573 | 30,810,641 | Yet , long-term studies have shown the favorable progression of this condition , with no pain and /or jaw locking occurring in most of the patients | Disc displacement with reduction ( DDWR ) is one of the most common intra-articular disorders of the temporom and ibular joint ( TMJ ) .
Factors related to the etiology , progression and treatment of such condition is still a subject of discussion .
This literature review aim ed to address etiology , development , related factors , diagnosis , natural course , and treatment of DDWR .
DDWR is usually asymptomatic and requires no treatment , since the TMJ structures adapt very well and painlessly to different disc positions . | BACKGROUND The authors compared the efficacy of bilateral balanced and canine guidance ( occlusal ) splints in the treatment of temporom and ibular joint ( TMJ ) pain in subjects who experienced joint clicking with a nonoccluding splint in a double-blind , controlled r and omized clinical trial . METHODS The authors r and omly assigned 57 people with signs of disk displacement and TMJ pain into three groups according to the type of splint : bilateral balanced , canine guidance and nonoccluding . The authors followed the groups for six months using analysis of a visual analog scale ( VAS ) , palpation of the TMJ and masticatory muscles , m and ibular movements and joint sounds . They used repeated analysis of variance and a chi(2 ) test to test the hypothesis . RESULTS The type of guidance used did not influence the pain reduction , yet both occlusal splints were superior to the nonoccluding splint , on the basis of the VAS . Despite similar outcomes in relation to opening , left lateral and protrusive movements , TMJ and muscle pain on palpation , subjects who used the occlusal splints had improved clinical outcomes . The frequency of joint noises decreased over time , with no significant differences among groups . Subjects in the groups using the occlusal splints reported more comfort . CONCLUSION The type of lateral guidance did not influence the subjects ' improvement . All of the subjects had a general improvement on the VAS , though subjects in the occlusal splint groups had better results that did subjects in the nonoccluding splint group ABSTRACT Therapeutic exercise is a new concept of treatment for patients with clicking due to anterior disk displacement with reduction ( ADDWR ) . In order to investigate the efficacy of the exercise , we design ed a r and omized controlled clinical trial to compare with no-treatment controls . The subjects were patients who complained of painless unilateral reciprocal clicking and were diagnosed as having ADDWR by Magnetic Resonance Imaging ( MRI ) . Forty-two patients were r and omly assigned . Three months after the r and omization , the success rate was 61.9 % ( 13/21 joints ) in the exercise group and 0 % ( 0/21 joints ) in the control group , with a significant difference between the two groups ( p=0.0001 ) . However , captured disks in the successful cases were seen in only 23.1 % on MRI examination . In conclusion , the therapeutic exercise for clicking due to ADDWR is significantly effective in reducing the clicking , and thought to be much more conservative and cost-effective than splint therapy or surgery PURPOSE Hyaluronic acid ( HA ) injections and occlusal splints have been suggested in the treatment of temporom and ibular joint ( TMJ ) derangements , but no sufficient data are available from controlled clinical trials comparing HA injection with another treatment modality . This study compared the effectiveness of a single HA injection , a double HA injection , and splint therapy for the treatment of TMJ disc displacement with reduction ( DDR ) . MATERIAL S AND METHODS A prospect i ve clinical trial was design ed . The study sample included patients with TMJ DDR . The primary predictor variable was treatment method . Patients were divided into 4 groups : control , single HA injection , double HA injection , and stabilization splint therapy . Patients were r and omly assigned to 1 of 3 treatment groups . The control group was self-selected . The primary outcome variable was pain at rest and during mastication . The secondary outcome variables were TMJ noise , quality of life , and level of jaw movements . Clinical symptoms and jaw movements were evaluated at baseline and at 6-month follow-up . Descriptive , comparative , correlation , and multivariate analyses were conducted . RESULTS The sample included 51 patients ( 66 TMJs ) 18 to 48 years old . All treatment groups showed significant improvement compared with baseline values for pain , TMJ noise , quality of life , and maximum mouth opening ( MMO ) at 6-month follow-up ( P < .05 ) . However , the 2 HA injection groups indicated superior improvement for pain , MMO , and quality of life compared with the stabilization splint group ( P < .05 ) . CONCLUSIONS The results of this study showed that HA injection and stabilization splinting are acceptably successful treatment modalities to alleviate the clinical signs and symptoms of TMJ DDR Objective The benefit of the use of some intraoral devices in arthrogenous temporom and ibular disorders ( TMD ) patients is still unknown . This study assessed the effectiveness of the partial use of intraoral devices and counseling in the management of patients with disc displacement with reduction ( DDWR ) and arthralgia . Material s and Methods A total of 60 DDWR and arthralgia patients were r and omly divided into three groups : group I ( n=20 ) wore anterior repositioning occlusal splints ( ARS ) ; group II ( n=20 ) wore the Nociceptive Trigeminal Inhibition Clenching Suppression System devices ( NTI-tss ) ; and group III ( n=20 ) only received counseling for behavioral changes and self-care ( the control group ) . The first two groups also received counseling . Follow-ups were performed after 2 weeks , 6 weeks and 3 months . In these sessions , patients were evaluated by means of a visual analogue scale , pressure pain threshold ( PPT ) of the temporom and ibular joint ( TMJ ) , maximum range of motion and TMJ sounds . Possible adverse effects were also recorded , such as discomfort while using the device and occlusal changes . The results were analyzed with ANOVA , Tukey ’s and Fisher Exact Test , with a significance level of 5 % . Results Groups I and II showed improvement in pain intensity at the first follow-up . This progress was recorded only after 3 months in Group III . Group II showed an increased in joint sounds frequency . The PPT values , m and ibular range of motion and the number of occlusal contacts did not change significantly . Conclusion The simultaneous use of intraoral devices ( partial time ) plus behavioral modifications seems to produce a more rapid pain improvement in patients with painful DDWR . The use of NTI-tss could increase TMJ sounds . Although intraoral devices with additional counseling should be considered for the management of painful DDWR , dentists should be aware of the possible side effects of the intraoral device ’s design PURPOSE This study was design ed to investigate the efficacy of arthrocentesis with and without injection of sodium hyaluronate ( SH ) into the upper joint space in the treatment of temporom and ibular joint ( TMJ ) internal derangements . PATIENTS AND METHODS Forty-one TMJs in 5 males and 26 females aged 14 to 53 years comprised the study material . The patients ' complaints were limited mouth opening , TMJ pain and tenderness , and joint noises during function . Patients were r and omly divided into 2 groups in which only arthrocentesis was performed in 1 group and arthrocentesis plus intra-articular injection of sodium hyaluronate was performed in the other group . Both groups contained patients with disc displacement with reduction and with closed lock . Clinical evaluation of the patients was done before the procedure , immediately after the procedure , on postoperative day 1 , and at 1 , 2 , 3 , 4 , 5 , 6 , 9 , 12 , 18 , and 24 months postoperatively . Intensity of TMJ pain , jaw function , and clicking sounds in the TMJ were assessed using visual analog scales . Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit . RESULTS Both techniques increased maximal mouth opening , lateral movements , and function , while reducing TMJ pain and noise . CONCLUSIONS Although patients benefitted from both techniques , arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone Temporom and ibular dysfunction ( TMD ) has been established as a therapeutic challenge in the plastic and maxillofacial clinics . The current treatment recommendations for TMD include resting the jaw , soft diet , and pain medication with nonsteroidal analgesic agents . If conservative and noninvasive techniques do not work , more invasive techniques may be considered . The main goal of this study was to assess the safety and clinical utility of intraarticular injection of sodium hyaluronate for the treatment of symptoms associated with internal derangement of the temporom and ibular joint ( TMJ ) . In this prospect i ve study , 40 TMJs of 33 patients who have TMD were treated with intraarticular sodium hyaluronate injections at weekly intervals for 3 weeks . Pre- and postinjection pain intensity , the presence of joint sounds , and interincisial distance were documented . The follow-up period was 12 months . There was a statistically significant reduction of pain intensity ( P < 0.01 ) and joint sound ( P < 0.05 ) in all patients . This study shows that intraarticular hyaluronic acid injection for the treatment of reducing and nonreducing disc displacement of TMJ is an effective and safe management The severity of symptoms of craniom and ibular disorders was studied during a 2-year period in 195 patients treated with conservative therapeutic schemes . Results revealed a continuing improvement and a statistically significant tendency for the great majority of patients to become asymptomatic or show a decrease in the severity of symptoms . By the end of the 2 years , 66.7 % of the patients were symptom free , 25.6 % presented with slight symptomatology , and 3.1 % were recorded with a fluctuating recurrence of symptoms . This investigation provided the data to develop an exponential model for the hypothesis that stabilization of effectiveness of conservative treatment is achieved between 6 months and 1 year after the initiation of treatment |
12,574 | 31,142,548 | We summarised the strength of review level evidence for interventions as " sufficient " , " tentative " , " insufficient " or " no " using a framework based on the consistency of evidence within and between review s. RESULTS We found sufficient review level evidence for direct effects on TB incidence/case prevention of vaccination and treatment of latent TB infection .
We also found sufficient evidence of beneficial indirect effects attributable to drug susceptibility testing and adverse indirect effects ( measured as sub-optimal treatment outcomes ) in relation to use of st and ardised first-line drug regimens for isoniazid-resistant TB and intermittent dosing regimens .
We found insufficient review level evidence for direct or indirect effects of interventions in other areas , including screening , adherence , multidrug-resistant TB , and healthcare-associated infection . | AIMS What is the evidence base for the effectiveness of interventions to reduce tuberculosis ( TB ) incidence in countries which have low TB incidence ? | Background Evidence of protection from childhood Bacillus Calmette-Guerin ( BCG ) against tuberculosis ( TB ) in adulthood , when most transmission occurs , is important for TB control and re source allocation . Methods We conducted a population -based case-control study of protection by BCG given to children aged 12 - 13 years against tuberculosis occurring 10 - 29 years later . We recruited UK-born White subjects with tuberculosis and r and omly sample d White community controls . Hazard ratios and 95 % confidence intervals ( CIs ) were estimated using case-cohort Cox regression , adjusting for potential confounding factors , including socio-economic status , smoking , drug use , prison and homelessness . Vaccine effectiveness ( VE = 1 - hazard ratio ) was assessed at successive intervals more than 10 years following vaccination . Results We obtained 677 cases and 1170 controls after a 65 % response rate in both groups . Confounding by deprivation , education and lifestyle factors was slight 10 - 20 years after vaccination , and more evident after 20 years . VE 10 - 15 years after vaccination was 51 % ( 95 % CI 21 , 69 % ) and 57 % ( CI 33 , 72 % ) at 15 - 20 years . Subsequently , BCG protection appeared to wane ; 20 - 25 years VE = 25 % ( CI -14 % , 51 % ) and 25 - 29 years VE = 1 % ( CI -84 % , 47 % ) . Based on multiple imputation of missing data ( in 17 % subjects ) , VE estimated in the same intervals after vaccination were similar [ 56 % ( CI 33 , 72 % ) , 57 % ( CI 36 , 71 % ) , 25 % ( -10 , 48 % ) , 21 % ( -39 , 55 % ) ] . Conclusions School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years , which is longer than previously thought . This has implication s for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines The number of published systematic review s of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions . Systematic review s are subject to a range of biases and increasingly include non-r and omised studies of interventions . It is important that users can distinguish high quality review s. Many instruments have been design ed to evaluate different aspects of review s , but there are few comprehensive critical appraisal instruments . AMSTAR was developed to evaluate systematic review s of r and omised trials . In this paper , we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic review s that include r and omised or non-r and omised studies of healthcare interventions , or both . With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic review s , including those based on non-r and omised studies of healthcare interventions The authors developed and tested a framework for identifying evidence gaps and prioritizing comparative effectiveness research by using a combination of clinical practice guidelines and systematic review s. In phase 1 of the project , reported elsewhere , 45 clinical questions on the management of primary open-angle glaucoma were derived from practice guidelines and prioritized by using a 2-round Delphi survey of clinicians . On the basis of the clinicians ' responses , 9 questions were classified as high-priority . In phase 2 , reported here , systematic review s that addressed the 45 clinical questions were identified . The review s were classified as at low , high , or unclear risk of bias , and evidence gaps ( in which no systematic review was at low risk of bias ) were identified . The following comparative effectiveness research agenda is proposed : Two of the 9 high-priority questions require new primary research ( such as a r and omized , controlled trial ) and 4 require a new systematic review . The utility and limitations of the framework and future adaptations are discussed Background Help and treatment seeking behavior of men and women suffering from tuberculosis is largely determined by how he/she and those around them perceive the causes , regard the diagnosis , accept the treatment , and adhere to the treatment . Objectives To critically appraise and synthesize the best available evidence on gender‐based determinants of help and treatment seeking behavior of tuberculosis patients . Inclusion criteria Male and female tuberculosis patients ( > = 15 years ) living in developed and developing countries were included . Quantitative studies examining gender differences in help and treatment seeking among tuberculosis patients with cross‐sectional , retrospective and prospect i ve cohort were included . Types of primary outcomes Outcomes related to determinants of help seeking : pattern of distress , perceived cause of tuberculosis and stigma related to tuberculosis patients and determinants of treatment seeking : delay in diagnosis , health service utilization , and consequence of treatment seeking ; treatment outcomes . Search strategy The review considered both published and unpublished studies in the English language published between January 1990 and December 2010 . Data bases of the Joanna Briggs Institute , PubMed , Popline , Cochrane Library , CINAHL and MedNar were search ed . The search focused on key elements of objectives ( participants , comparator , and outcome ) and a thorough search was undertaken utilizing a st and ardized three step approach . Method ological quality Considered papers were critically appraised by two independent review ers using st and ardized Joanna Briggs Institute tools . Data was extracted using the Joanna Briggs Institute Meta Analysis of Statistical Assessment and Review Instrument data extraction tool . Data was analyzed using Revman 5.1 software from the Cochrane collaboration . Results Nine cross‐sectional , two retrospective and one prospect i ve cohort studies were included in the review . Males were 49 % less likely to have psychological distress than females ( OR=0.51 , 95 % CI=0.32‐0.83 ) . Males were 46 % less likely to perceive health , illness and injuries as a cause of tuberculosis infection than females ( OR=0.54 , 95 % CI=0.31‐0.96 ) . Males were 78 % less likely to use a traditional healer as health service utilization than females ( OR=0.22 , 95 % CI=0.07‐0.66 ) . Males were almost twice more likely to be diagnosed within 30 days in a health institution than females ( OR=1.76 , 95 % CI=1.09‐2.84 ) however , they were 23 % less likely to successfully complete tuberculosis treatment ( OR=0.77 , 95 % CI=0.68‐0.87 ) . Conclusions Gender differences were observed on determinants of help seeking such as distress , perceived causes of tuberculosis infection and stigma components . Determinants of treatment seeking that showed significant gender differences were utilization of health services for diagnosis and treatment , patient delay in seeking health service and treatment outcome of tuberculosis . Implication s for Practice Gender specific strategies for behavioral change should be implemented by health professionals on causes of tuberculosis , early treatment seeking , signs/symptoms , related stigma and adherence of treatment to raise awareness in the community . Practitioners should suspect tuberculosis among women at early stages of their visits to health facilities and screen for tuberculosis . Special efforts should be made by practitioners for male tuberculosis patients to complete the treatment . Implication s for Research Further research with gender perspective should be conducted using behavioral change models on screening of patients and sensitizing communities to uptake of tuberculosis facilities for tuberculosis control BACKGROUND A vaccine to interrupt the transmission of tuberculosis is needed . METHODS We conducted a r and omized , double‐blind , placebo‐controlled , phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya , South Africa , and Zambia . Human immunodeficiency virus (HIV)–negative adults 18 to 50 years of age with latent M. tuberculosis infection ( by interferon‐γ release assay ) were r and omly assigned ( in a 1:1 ratio ) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart . Most participants had previously received the bacille Calmette – Guérin vaccine . We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease . Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase‐chain‐reaction test , mycobacterial culture , or both . RESULTS We report the primary analysis ( conducted after a mean of 2.3 years of follow‐up ) of the ongoing trial . A total of 1786 participants received M72/AS01E and 1787 received placebo , and 1623 and 1660 participants in the respective groups were included in the according‐to‐ protocol efficacy cohort . A total of 10 participants in the M72/AS01E group met the primary case definition ( bacteriologically confirmed active pulmonary tuberculosis , with confirmation before treatment ) , as compared with 22 participants in the placebo group ( incidence , 0.3 cases vs. 0.6 cases per 100 person‐years ) . The vaccine efficacy was 54.0 % ( 90 % confidence interval [ CI ] , 13.9 to 75.4 ; 95 % CI , 2.9 to 78.2 ; P=0.04 ) . Results for the total vaccinated efficacy cohort were similar ( vaccine efficacy , 57.0 % ; 90 % CI , 19.9 to 76.9 ; 95 % CI , 9.7 to 79.5 ; P=0.03 ) . There were more unsolicited reports of adverse events in the M72/AS01E group ( 67.4 % ) than in the placebo group ( 45.4 % ) within 30 days after injection , with the difference attributed mainly to injection‐site reactions and influenza‐like symptoms . Serious adverse events , potential immune‐mediated diseases , and deaths occurred with similar frequencies in the two groups . CONCLUSIONS M72/AS01E provided 54.0 % protection for M. tuberculosis – infected adults against active pulmonary tuberculosis disease , without evident safety concerns . ( Funded by GlaxoSmithKline Biologicals and Aeras ; Clinical Trials.gov number , NCT01755598 . |
12,575 | 29,511,005 | Clinical pathways , multidisciplinary teams and multifaceted interventions were most consistently successful in increasing physician uptake of guidelines .
Among r and omised controlled trials ( RCT ) ( n=10 ) , pharmacist and nurse-led interventions improved target dose prescriptions .
Baseline assessment of barriers , staff training , iterative intervention development , leadership commitment and policy/financial incentives were associated with intervention effectiveness .
Clinical pathways , multidisciplinary teams and multifaceted interventions appear to be most consistent in increasing guideline uptake .
However , improvements in process outcomes were rarely accompanied by improvements in clinical outcomes . | Background The uptake of guideline recommendations that improve heart failure ( HF ) outcomes remains suboptimal .
We review ed implementation interventions that improve physician adherence to these recommendations , and identified context ual factors associated with implementation success . | The methods of evaluating change and improvement strategies are not well described . The design and conduct of a range of experimental and non-experimental quantitative design s are considered . Such study design s should usually be used in a context where they build on appropriate theoretical , qualitative and modelling work , particularly in the development of appropriate interventions . A range of experimental design s are discussed including single and multiple arm r and omised controlled trials and the use of more complex factorial and block design s. The impact of r and omisation at both group and individual levels and three non-experimental design s ( uncontrolled before and after , controlled before and after , and time series analysis ) are also considered . The design chosen will reflect both the needs ( and re sources ) in any particular circumstances and also the purpose of the evaluation . The general principle underlying the choice of evaluative design is , however , simple — those conducting such evaluations should use the most robust design possible to minimise bias and maximise generalisability OBJECTIVES We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure ( CHF ) hospital readmissions and mortality over a six-month period . BACKGROUND Hospital admission for CHF is an important problem amenable to improved outpatient management . METHODS Two hundred patients hospitalized with CHF at increased risk of hospital readmission were r and omized to a multidisciplinary program or usual care . A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient 's primary physician before r and omization . The intervention team consisted of a cardiologist , a CHF nurse , a telephone nurse coordinator and the patient 's primary physician . Contact with the patient was on a prespecified schedule . The CHF nurse followed an algorithm to adjust medications . Patients in the nonintervention group were followed as usual . The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months , compared by using a log transformation t test by intention-to-treat analysis . RESULTS The median age of the study patients was 63.5 years , and 39.5 % were women . There were 43 CHF hospital admissions and 7 deaths in the intervention group , as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group ( p = 0.09 ) . The quality -of-life score , percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group . Cost per patient , in 1998 U.S. dollars , was similar in both groups . CONCLUSIONS This study demonstrates that a six-month , multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF Objective : To evaluate the effects of a nurse based outpatient management programme for elderly patients discharged with heart failure from a university hospital . Design : Patients with heart failure ( New York Heart Association class II – IV ) and left ventricular systolic dysfunction aged 60 years or more were r and omly assigned to follow up within the management programme or to conventional follow up , usually in primary care . Of the 208 participants , 58 % were men , mean age was 75 years , and mean ejection fraction 34 % . All patients were scheduled for three observational study visits at six month intervals . The primary end point was quality of life ( QoL ) and secondary end points were hospitalisation and mortality . Results : More patients achieved target doses of angiotensin converting enzyme ( ACE ) inhibitors in the intervention group than in the control group ( 82 % v 69 % , 88 % v 69 % , and 88 % v 74 % of recommended target doses at 6 , 12 , and 18 months of follow up , respectively , p < 0.05 for all ) . Patients with initial low QoL had a poor prognosis . After a mean 1122 days of follow up , 82 % of all patients had been readmitted . There were on average 4.7 readmissions per patient and 66 % were due to non-cardiac diagnoses . There were no differences in QoL or health care consumption between the two study groups during follow up . Conclusion : A nurse based management programme is more effective than follow up in primary care in optimising medication for elderly patients with heart failure . However , such a programme does not seem to have a favourable influence on QoL or readmission rate during long term follow up Objective : To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners ( GPs ) in cardiovascular care . Design : Pragmatic cluster controlled trial with r and omisation of practice s to support ( intervention group ) or no special attention ( control group ) ; analysis after 2 years . Setting : 124 general practice s in The Netherl and s. Participants : 185 GPs . Main outcome measures : Compliance rates for 12 evidence -based indicators for the management of patients with hypertension , hypercholesterolaemia , angina pectoris , or heart failure . The evaluation relied on the prospect i ve recording of patient encounters by the participating GPs . Results : The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention . A significant improvement was seen for five of the 12 indicators : assessment of risk factors in patients with hypercholesterolaemia ( odds ratio 2.04 ; 95 % CI 1.44 to 2.88 ) or angina pectoris ( 3.07 ; 1.08 to 8.79 ) , provision of information and advice to patients with hypercholesterolaemia ( 1.58 , 1.17 to 2.13 ) or hypertension ( 1.55 , 1.35 to 1.77 ) , and checking for clinical signs of deterioration in patients with heart failure ( 4.11 , 2.17 to 7.77 ) . Single h and ed practice s , non-training practice s , and practice s with older GPs gained particular benefit from the intervention . Conclusions : Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care . The effect is small and the strategy needs further development Introduction The uptake of Clinical Practice Guideline ( CPG ) recommendations that improve outcomes in heart failure ( HF ) remains suboptimal . We will conduct a systematic review to identify implementation strategies that improve physician adherence to class I recommendations , those with clear evidence that benefits outweigh the risks . We will use American , Canadian and European HF guidelines as our reference . Methods and analysis We will conduct a literature search in the data bases of MEDLINE , EMBASE , HEALTHSTAR , CINAHL , Cochrane Library , Campbell Collaboration , Joanna Briggs Institute Evidence Based Practice , Centre for Review s and Dissemination and Evidence Based Practice Centres . We will include prospect i ve studies evaluating implementation interventions aim ed at improving uptake of class I CPG recommendations in HF . We will extract data in duplicate . We will classify interventions according to their level of application ( ie , provider , organisation , systems level ) and common underlying characteristics ( eg , education , decision-support , financial incentives ) using the Cochrane Effective Practice and Organisation of Care Taxonomy . We will assess the impact of the intervention on adherence to the CPGs . Outcomes will include proportion of eligible patients who were : prescribed a CPG-recommended pharmacological treatment ; referred for device consideration ; provided self-care education at discharge ; and provided left ventricular function assessment . We will include clinical outcomes such as hospitalisations , readmissions and mortality , if data is available . We will identify the common elements of successful and failing interventions , and examine the context in which they were applied , using the Process Re design context ual framework . We will synthesis e the results narratively and , if appropriate , will pool results for meta- analysis . Discussion and dissemination In this review , we will assess the impact of implementation strategies and context ual factors on physician adherence to HF CPGs . We will explore why some interventions may succeed in one setting and fail in another . We will disseminate our findings through briefing reports , publications and presentations . Trial registration number CRD42015017155 Background — A treatment gap exists between heart failure ( HF ) guidelines and the clinical care of patients . The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting ( IMPROVE HF ) prospect ively tested a multidimensional practice -specific performance improvement intervention on the use of guideline -recommended therapies for HF in outpatient cardiology practice s. Methods and Results — Performance data were collected in a r and om sample of HF patients from 167 US outpatient cardiology practice s at baseline , longitudinally after intervention at 12 and 24 months , and in single-point-in-time patient cohorts at 6 and 18 months . Participants included 34 810 patients with reduced left ventricular ejection fraction ( ≤35 % ) and chronic HF or previous myocardial infa rct ion . To quantify guideline adherence , 7 quality measures were assessed . Interventions included clinical decision support tools , structured improvement strategies , and chart audits with feedback . The performance improvement intervention result ed in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline : & bgr;-blocker ( 92.2 % versus 86.0 % , + 6.2 % ) , aldosterone antagonist ( 60.3 % versus 34.5 % , + 25.1 % ) , cardiac resynchronization therapy ( 66.3 % versus 37.2 % , + 29.9 % ) , implantable cardioverter-defibrillator ( 77.5 % versus 50.1 % , + 27.4 % ) , and HF education ( 72.1 % versus 59.5 % , + 12.6 % ) ( each P<0.001 ) . There were no statistically significant improvements in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use or anticoagulation for atrial fibrillation . Sensitivity analyses at the patient level and limited to patients with both baseline and 24-month quality measure data yielded similar results . Improvements in the single-point-in-time cohorts were smaller , and there were no concurrent control practice s. Conclusions — The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting , a defined and scalable practice -specific performance improvement intervention , was associated with substantial improvements in the use of guideline -recommended therapies in eligible patients with HF in outpatient cardiology practice s. Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00303979 AIMS To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure ( HF ) are adopted in clinical practice . METHODS AND RESULTS The ESC-HF Long-Term Registry is a prospect i ve , observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries , members of the European Society of Cardiology ( ESC ) . From May 2011 to April 2013 , a total of 12,440 patients were enrolled , 40.5 % with acute HF and 59.5 % with chronic HF . Intravenous treatments for acute HF were heterogeneously administered , irrespective of guideline recommendations . In chronic HF , with reduced EF , renin-angiotensin system ( RAS ) blockers , beta-blockers , and mineralocorticoid antagonists ( MRAs ) were used in 92.2 , 92.7 , and 67.0 % of patients , respectively . When reasons for non-adherence were considered , the real rate of undertreatment accounted for 3.2 , 2.3 , and 5.4 % of the cases , respectively . About 30 % of patients received the target dosage of these drugs , but a documented reason for not achieving the target dosage was reported in almost two-thirds of them . The more relevant reasons for non-implantation of a device , when clinical ly indicated , were related to doctor uncertainties on the indication , patient refusal , or logistical/cost issues . CONCLUSION This pan-European registry shows that , while in patients with acute HF , a large heterogeneity of treatments exists , drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines , when the reasons for non-adherence are taken into account . Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written BACKGROUND Treatment with specific beta-blockers and doses recommended by guidelines is often not achieved in practice . We evaluated an intervention directed to the pharmacy to improve prescribing . METHODS AND RESULTS We conducted a pragmatic cluster-r and omized trial , where facilities ( n = 12 ) with patients ( n = 220 ) were the clusters . Eligible patients had a beta-blocker prescription that was not guideline concordant . Level 1 intervention included information to a pharmacist on facility guideline concordance . Level 2 also provided a list of patients not meeting guideline goals . Intervention and follow-up periods were each 6 months . Achievement of full concordance with recommendations was low ( 4%-5 % ) in both groups , primarily due to lack of tolerability . However , compared with level 1 , the level 2 intervention was associated with 1.9-fold greater odds of improvement in prescribing ( 95 % confidence interval [ CI ] 1.1 - 3.2 ) . Level 2 patients also had greater odds of a higher dose ( 1.9 , 95 % CI 1.1 - 3.3 ) . The intervention was aided by the patient lists provided , the electronic medical record system , and staff support . CONCLUSIONS In actual practice , full achievement of guideline goals was low . However , a simple intervention targeting pharmacy moved patients toward guideline goals . As health care systems incorporate electronic medical records , this intervention should have broader feasibility RATIONALE , AIMS AND OBJECTIVES The efficacy of angiotensin-converting enzyme ( ACE ) inhibitors in treating heart failure is well established , but there is concern that these agents are underutilized . This study aim ed to evaluate the effect of developing and implementing Clinical Practice Guidelines ( CPGs ) on the quality of care given to patients receiving ACE inhibitors for systolic heart failure . METHODS Twenty cardiology units in Lorraine ( France ) were r and omized to an experimental ( n = 10 ) or a control group ( n = 10 ) . In each experimental unit , doctors were involved in drafting and implementing CPGs ; those at control units were not . Practice surveys were conducted in all units before and after the intervention ; 723 patients with heart failure and less than 75 years old were included . The main outcome was compliance with the CPGs . RESULTS Before intervention , clinicians in both groups were already compliant with CPGs relating to indications and contra-indications , adverse effects management , concomitant therapy and monitoring of biologic factors . After intervention , adherence to others CPGs was generally better in the experimental group . Compliance with the CPG relating to ACE inhibitor dose on discharge was higher in the experimental group ( P = 0.003 ) . Compliance with CPGs relating to increasing ACE inhibitors doses ( P < 0.0001 ) and the contents of the discharge letter ( P = 0.02 ) improved in all units between the two periods . CONCLUSIONS These results suggest that doctors involved in drafting and implementing CPGs are more likely to comply with them Abstract Clinical systolic heart failure ( HF ) guidelines specify recommendations for ACE inhibitors ( ACEI ) , angiotensin receptor blockers ( ARB ) , and beta blockers according to doses used in clinical trials . However , many HF patients remain suboptimally treated . We sought to determine which provider type , between an interprofessional HF team , non-HF cardiologists , and primary care physicians ( PCP ) , most optimally manages HF medications and doses . A retrospective chart review was performed on adult patients at an academic county hospital with an ejection fraction ≤40 % and a diagnosis of HF , seen by a single provider type ( HF team , cardiologist , or PCP ) at least twice within a 12-month period . Utilization rates of any ACEI/ARB and any beta blocker were robust across provider types , though evidence -based ACEI/ARB and beta blocker were greatest from the HF team . Doses of evidence -based therapies dropped markedly in the non-HF team groups . The percent of patients prescribed optimal doses of an evidence -based ACEI/ARB AND beta blocker was 69 % , 33 % , and 25 % for the HF team , cardiologists and PCPs , respectively ( p < 0.0167 ) . Patients followed by the HF team were more frequently prescribed evidence -based medications at optimal doses . This supports using specialized interprofessional HF teams to attain greater adherence to evidence -based recommendations in treating systolic HF BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure . It is unclear , however , if low doses and high doses of ACE inhibitors have similar benefits . METHODS AND RESULTS We r and omly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction < or = 30 % to double-blind treatment with either low doses ( 2.5 to 5.0 mg daily , n=1596 ) or high doses ( 32.5 to 35 mg daily , n=1568 ) of the ACE inhibitor , lisinopril , for 39 to 58 months , while background therapy for heart failure was continued . When compared with the low-dose group , patients in the high-dose group had a nonsignificant 8 % lower risk of death ( P=0.128 ) but a significant 12 % lower risk of death or hospitalization for any reason ( P=0.002 ) and 24 % fewer hospitalizations for heart failure ( P=0.002 ) . Dizziness and renal insufficiency was observed more frequently in the high-dose group , but the 2 groups were similar in the number of patients requiring discontinuation of the study medication . Conclusions -These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor ( unless these are the only doses that can be tolerated ) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor ( if any ) is likely to be very small Background —The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence . This study evaluated interventions for implementing a new practice guideline advocating the use of & bgr;-blockers for heart failure patients . Methods and Results —This was a r and omized controlled trial involving heart failure patients ( n=169 ) with an ejection fraction ≤45 % and no contraindications to & bgr;-blockers . Patients ’ primary providers were r and omized in a stratified design to 1 of 3 interventions : ( 1 ) control : provider education ; ( 2 ) provider and patient notification : computerized provider reminders and patient letters advocating & bgr;-blockers ; and ( 3 ) nurse facilitator : supervised nurse to initiate and titrate & bgr;-blockers . The primary outcome , the proportion of patients who were initiated or uptitrated and maintained on & bgr;-blockers , analyzed by intention to treat , was achieved in 67 % ( 36 of 54 ) of patients in the nurse facilitator group compared with 16 % ( 10 of 64 ) in the provider/patient notification and 27 % ( 14 of 51 ) in the control groups ( P < 0.001 for the comparisons between the nurse facilitator group and both other groups ) . The proportion of patients on target & bgr;-blocker doses at the study end ( median follow-up , 12 months ) was also highest in the nurse facilitator group ( 43 % ) compared with the control ( 10 % ) and provider/patient notification groups ( 2 % ) ( P < 0.001 ) . There were no differences in adverse events among groups . Conclusions —The use of a nurse facilitator was a successful approach for implementing a & bgr;-blocker guideline in heart failure patients . The use of provider education , clinical reminders , and patient education was of limited value in this setting HEART Failure Effectiveness & Leadership Team ( HEARTFELT ) is a multifaceted intervention design ed to improve adherence with the American College of Cardiology/American Heart Association practice guidelines for heart failure ( HF ) . The purpose of this study was to assess differences in clinician adherence with clinical practice guidelines before and after implementation of HEARTFELT . A quasi-experimental , untreated control group design with separate pretest/posttest sample s was employed at a community hospital in Connecticut . The untreated historical control group included patients aged 65 years or older with HF and a nonequivalent comparison group of patients with stroke . The posttest sample s included patients with the diagnosis of HF and stroke admitted after implementation of the HEARTFELT intervention . The HEARTFELT intervention included automated pathway in electronic medical record ( order sets , interdisciplinary plan of care , self-management plan ) , access to evidence for clinicians and patients , HF self-management education tools , and ongoing discipline-specific feedback regarding adherence . Data were analyzed using parametric and nonparametric methods . The HEARTFELT intervention significantly improved clinician adherence with addressing all self-management categories in the electronic medical record ( P = .000 ) and adherence with self-management education given to the patient in writing at discharge ( P = .000 ) . There were no significant differences in adherence with medical interventions ( P = .39 ) . While guideline adherence is associated with less practice variation and improved processes , methods of integration into practice in community hospital setting s have been largely unexplored . The multifaceted HEARTFELT intervention is promising for its potential to integrate evidence at the point of care , to reduce unwarranted variation in practice , and ultimately to improve the outcomes of individuals with HF BACKGROUND It is unknown if physician education through heart failure ( HF ) patient-specific quality -of-care report cards ( HFRC ) impacts outpatient HF guideline adherence . METHODS A prospect i ve pre-post design study was performed to test the hypothesis that a one-time , patient-specific HFRC delivered to physicians after HF patient ( ejection fraction < or = 40 % ) discharge would lead to improved HF guideline adherence compared with control practitioners . Patients were contacted at 1 , 3 , and 6 months after discharge to assess medication usage and intolerances . Six month quality score ( QS ) was the primary end point , calculated as the sum of adherence to 4 medication performance measures ( angiotensin-converting enzyme inhibitors/angiotensin receptor blockers , beta-blockers , aldosterone inhibitors , and warfarin for atrial fibrillation ) . RESULTS The mean QS at discharge was 3.10 + /- 0.78 in controls ( n = 189 ) and 3.25 + /- 0.79 in the HFRC group ( n = 76 , P = .11 ) . Controlling for discharge QS , the HFRC result ed in a significantly improved QS at 3 months ( beta = .11 , P = .023 ) but not at the 6-month primary end point ( beta = .084 , P = .14 ) . Controlling for baseline medication use , patients of practitioners receiving the HFRC were 32.5 ( P = .019 ) and 8.5 ( P = .030 ) times more likely to receive , or have a documented contraindication to , an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker at 3 and 6 months , respectively . There were no significant differences in indicated beta-blocker , aldosterone inhibitor , or warfarin prescriptions at any follow-up . CONCLUSIONS Although one-time patient-specific report cards result in short-term statistically significant improvements in outpatient evidence -based HF care , the gain does not translate into sustained improvements in quality of care RATIONALE , AIMS AND OBJECTIVES Peer review groups are considered helpful for quality improvement in primary care . An interactive educational programme for small peer groups was developed , focusing on the implementation of newly developed treatment guidelines . The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice . METHODS A cluster r and omized trial using a balanced incomplete block design was used ; one arm received a programme on treatment of chronic heart failure ( CHF ) , the other on hypertension treatment in diabetes mellitus type 2 ( T2DM ) . A r and om sample of 10 CHF and 10 T2DM patients per GP was drawn , for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention . The outcomes were prescribing of ACE inhibitors , and antihypertensive treatment in T2DM . The effect was analysed separately for both programmes using multilevel regression models . RESULTS All 27 peer review groups in one region in the Netherl and s were r and omized , of which 16 participated . No significant effects were observed in the CHF group or in the T2DM group . The opportunity for change was limited , as only 53 % of the CHF patients and 60 % of the T2DM patients had a contact with their GP between the intervention and follow-up measurement . CONCLUSION The peer review programme was not successful for changing the treatment of chronic patients , although the programme focused on dealing with barriers perceived by the participants . Not all problems perceived can be solved in a peer group discussion BACKGROUND Angiotensin-receptor blockers ( ARBs ) are effective treatments for patients with heart failure , but the relation between dose and clinical outcomes has not been explored . We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure . METHODS This double-blind trial was undertaken in 255 sites in 30 countries . 3846 patients with heart failure of New York Heart Association class II-IV , left-ventricular ejection fraction 40 % or less , and intolerance to angiotensin-converting-enzyme ( ACE ) inhibitors were r and omly assigned to losartan 150 mg ( n=1927 ) or 50 mg daily ( n=1919 ) . Allocation was by block r and omisation stratified by centre and presence or absence of beta-blocker therapy , and all patients and investigators were masked to assignment . The primary endpoint was death or admission for heart failure . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00090259 . FINDINGS Six patients in each group were excluded because of poor data quality . With 4.7-year median follow-up in each group ( IQR 3.7 - 5.5 for losartan 150 mg ; 3.4 - 5.5 for losartan 50 mg ) , 828 ( 43 % ) patients in the 150 mg group versus 889 ( 46 % ) in the 50 mg group died or were admitted for heart failure ( hazard ratio [ HR ] 0.90 , 95 % CI 0.82 - 0.99 ; p=0.027 ) . For the two primary endpoint components , 635 patients in the 150 mg group versus 665 in the 50 mg group died ( HR 0.94 , 95 % CI 0.84 - 1.04 ; p=0.24 ) , and 450 versus 503 patients were admitted for heart failure ( 0.87 , 0.76 - 0.98 ; p=0.025 ) . Renal impairment ( n=454 vs 317 ) , hypotension ( 203 vs 145 ) , and hyperkalaemia ( 195 vs 131 ) were more common in the 150 mg group than in the 50 mg group , but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group . INTERPRETATION Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure , reduced left-ventricular ejection fraction , and intolerance to ACE inhibitors compared with losartan 50 mg daily . These findings show the value of up-titrating ARB doses to confer clinical benefit . FUNDING Merck ( USA ) RATIONALE AND AIMS Clinical practice guidelines ( CPG ) reflect the evidence of effective pharmacotherapy of chronic ( systolic ) heart failure ( CHF ) which needs to be implemented . This study aim ed to evaluate the effect of a new , multifaceted intervention ( educational train-the-trainer course plus pharmacotherapy feedback = TTT ) compared with st and ard education on guideline adherence ( GA ) in general practice . METHOD Thirty-seven participating general practitioners ( GPs ) were r and omized ( 18 vs. 19 ) and included 168 patients with ascertained symptomatic CHF [ New York Heart Association ( NYHA ) II-IV ] . Groups received CPG , the TTT intervention consisted of four interactive educational meetings and a pharmacotherapy feedback , while the control group received a usual lecture ( St and ard ) . Outcome measure was GA assessed by prescription rates and target dosing of angiotensin converting enzyme ( ACE ) inhibitors ( ACE-I ) or angiotensin receptor blockers ( ARB ) , beta-blockers ( BB ) and aldosterone antagonists ( AA ) at baseline and 7-month follow-up . Group comparisons at follow-up were adjusted to GA , sex , age and NYHA stage at baseline . RESULTS Prescription rates at baseline ( n = 168 ) were high ( ACE-I/ARB 90 , BB 79 and AA 29 % ) in both groups . At follow up ( n = 146 ) , TTT improved compared with St and ard regarding AA ( 43 % vs. 23 % , P = 0.04 ) and the rates of reached target doses of ACE-I/ARB ( 28 % vs. 15 % , P = 0.04 ) . TTT group achieved significantly higher mean percentages of daily target dose ( 52 % vs. 42 % , mean difference 10.3 % , 95 % CI 0.84 - 19.8 , P = 0.03 ) . CONCLUSION Despite of pre-existing high GA in both groups and an active control group , the multifaceted intervention was effective in quality of care measured by GA . Further research is needed on the choice of interventions in different provider population |
12,576 | 10,796,593 | REVIEW ER 'S CONCLUSIONS Low molecular weight heparin is at least as effective as unfractionated heparin in preventing recurrent venous thromboembolism , and significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at the end of follow-up . | BACKGROUND Low molecular weight heparins have been shown to be effective and safe for prevention of venous thromboembolism .
There is accumulating evidence that these new anticoagulants are also effective and safe for treatment of venous thromboembolism .
OBJECTIVES The objective of this review was to determine the effect of fixed-dose , subcutaneous low molecular weight heparins compared with adjusted-dose , intravenous or subcutaneous , unfractionated heparin for initial treatment of acute deep venous thrombosis or pulmonary embolism . | Two anticoagulant regimens , similar except for the timing of warfarin therapy , were compared in patients with clinical ly submassive venous thromboembolism ( VTE ) . Warfarin was begun after 7 days of continuous intravenous heparin infusion in group L ( 127 patients ) or within 3 days ( average 1 day ) of starting heparin in group S ( 139 patients ) , with similar outcomes . The frequency of symptomatic VTE recurrence during the hospital stay was 4.7 % in group L and 3.6 % in group S , and that of symptomless new perfusion defects 8.5 % in group L and 3.9 % in group S. On routine iodine-125-fibrinogen leg scanning of patients presenting with distal thrombosis ( in the calf , popliteal , or distal femoral veins ) 3.6 % of group S but no group L patients had symptomless proximal extension . The incidence of bleeding was similar with both regimens . Outpatient follow-up showed no excess recurrent VTE in either treatment group . Early warfarin treatment significantly shortened hospital stay by an average of 3.9 days ( 30 % ) in patients admitted solely because of VTE BACKGROUND Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home Intravenous heparin followed by oral anticoagulant therapy ( e. g. with coumarin ) is still the most widely used treatment for deep venous thromboembolism . Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin , but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease . Certainly , long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans . This study aim ed to compare the efficacy and safety of unfractionated ( UF ) heparin with that of a low molecular weight heparin ( Fragmin , Kabi Pharmacia ) in the prevention of recurrent deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) in a consecutive series of patients with contraindications to coumarin therapy . The patients comprised 40 men and 40 women , aged between 19 and 92 years ( mean age , 68 years ) . They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital . All patients had at least one of the following conditions : recent blood loss ( either spontaneous or during admission while receiving heparin therapy ) ; active gastroduodenal ulcer disease ; psychological or physical inability or unwillingness to underst and and accept the need for regular laboratory monitoring during coumarin treatment ; chronic alcoholism ; dementia ; pregnancy ; recent neurosurgery , and pericardial effusion ; or were over 80 years of age . They were r and omly allocated to receive either UF heparin , 10,000 IU s.c . b.d . , or Fragmin , 5000 IU anti-Factor Xa s.c . b.d . , for a period of 3 - 6 months . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Body weight-adjusted subcutaneous low-molecular-weight heparin ( LMWH ) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin ( UFH ) for the treatment of patients with venous thromboembolism . However , body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing . Therefore a fixed LMWH dose , independent of body-weight , might rationalize initial treatment for venous thromboembolism . METHODS Patients with proven proximal deep-vein thrombosis were r and omly assigned to fixed dose subcutaneous LMWH Certoparin ( 8,000 anti-factor Xa U b.i.d . ; 265 patients ) or to adjusted dose i.v . UFH ( 273 patients ) for 12 days . Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months . The primary outcome measure was a 30 percent or greater improvement in the Marder Score , as revealed by repeated venography on day 12 ( end of the initial treatment ) . The secondary composite outcome measure included death , recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee . RESULTS The Marder score improved by 30 % or more in 30.3 % and 25.0 % of patients assigned to LMWH ( 198 paired venograms ) and UFH ( 192 paired venograms ) , respectively ( 2p = 0.26 ) . At the end of the initial treatment , the composite outcome was observed in 4 of the 265 patients ( 1.5 % ) r and omized to LMWH , as compared with 14 of the 273 patients ( 5.1 % ) r and omized to UFH ( 2p = 0.03 ) . At 6 months these figures were 6.8 % and 12.8 % , respectively ( risk reduction 0.53 , confidence interval 0.31 - 0.90 , 2p = 0.02 ) . CONCLUSION Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis We performed a prospect i ve , r and omized , double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin ( Fragmin ) compared with st and ard heparin as the initial treatment of acute venous thromboembolism . Ninety-eight patients received continuous intravenous heparin , and 96 patients received Fragmin for 5 - 10 days . Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding . Treatment was stopped when a therapeutic level of anticoagulation ( International Normalized Ratio greater than 3.5 ) was reached with coumarins . Thirteen patients in the heparin group and 10 patients in the Fragmin group had a major bleeding complication . The incidence of major and minor bleeding complications combined decreased from 48.9 % to 38.5 % ( 95 % confidence interval for the difference , -3.5 % to + 24.2 % ) , corresponding with a relative bleeding risk reduction of 21.2 % . There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients : six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects ( 95 % confidence interval for the difference , -9.4 % to + 17.8 % ) . We conclude that low molecular weight heparin ( Fragmin ) given in adjusted , continuous , and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin . There is a trend in risk reduction for bleeding in favor of low molecular weight heparin , a trend , however , that is smaller than expected compared with animal studies BACKGROUND An intravenous course of st and ard ( unfractionated ) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the st and ard initial in-hospital treatment for patients with deep-vein thrombosis , but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe . Because the latter treatment can be given on an outpatient basis , we compared the two treatments in symptomatic out patients with proximal-vein thrombosis but no signs of pulmonary embolism . METHODS We r and omly assigned patients to adjusted-dose intravenous st and ard heparin administered in the hospital ( 198 patients ) or fixed-dose subcutaneous low-molecular-weight heparin administered at home , when feasible ( 202 patients ) . We compared the treatments with respect to recurrent venous thromboembolism , major bleeding , quality of life , and costs . RESULTS Seventeen of the 198 patients who received st and ard heparin ( 8.6 percent ) and 14 of the 202 patients who received low-molecular-weight heparin ( 6.9 percent ) had recurrent thromboembolism ( difference , 1.7 percentage points ; 95 percent confidence interval , -3.6 to 6.9 ) . Major bleeding occurred in four patients assigned to st and ard heparin ( 2.0 percent ) and one patient assigned to low-molecular-weight heparin ( 0.5 percent ; difference , 1.5 percentage points ; 95 percent confidence interval , -0.7 to 2.7 ) . Quality of life improved in both groups . Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin . Among the patients in that group , 35 percent were never admitted to the hospital at all , and 40 percent were discharged early . This treatment was associated with a mean reduction in hospital days of 67 percent , ranging from 29 percent to 86 percent in the various study centers . CONCLUSIONS In patients with proximal-vein thrombosis , treatment with low-molecular-weight heparin at home is feasible , effective , and safe BACKGROUND Enoxaparin , a low-molecular-weight heparin administered to hospitalized patients once or twice daily , has shown efficacy and safety equivalent to unfractionated heparin in the treatment of acute venous thromboembolic disease . Although the cost of either enoxaparin regimen is greater than that of unfractionated heparin , the overall cost of care for each of these 3 treatment strategies is unknown . METHODS A cost minimization analysis of a 3-month , partially blinded , r and omized , controlled efficacy and safety trial of anticoagulant therapy for deep vein thrombosis . Three hundred thirty-nine hospitalized patients with symptomatic lower extremity deep vein thrombosis were r and omly assigned to initial therapy with subcutaneous enoxaparin either once ( n = 112 ) or twice ( n = 123 ) daily , or with dose-adjusted intravenous unfractionated heparin ( n = 104 ) , followed by long-term oral anticoagulant therapy . Estimated 1997 total cost from a third-party payer perspective for the 3-month episode of care was calculated by assigning st and ard unit costs to counts of medical re sources used by each patient in the clinical trial . RESULTS Average total cost for the 3-month episode of care was similar across all 3 treatment regimens : once-daily dose of enoxaparin , $ 12,166 ( 95 % confidence interval [ CI ] , $ 10,744-$13,588 ) ; twice-daily dose of enoxaparin , $ 11,558 ( 95 % CI , $ 10,201-$12,915 ) ; and unfractionated heparin , $ 12,146 ( 95 % CI , $ 10,670-$12,622 ) . Bootstrapped estimates and sensitivity analyses did not significantly change findings . CONCLUSIONS There was no significant difference in the overall cost for the 3-month episode of care for patients treated with either enoxaparin or unfractionated heparin . Additional acquisition costs for anticoagulant medication among patients treated with enoxaparin were offset by savings associated with lower incidence of hospital readmission and shorter duration of venous thromboembolism-related readmissions In view of the potential of low-molecular-weight heparins ( LMWH ) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis , we undertook a r and omised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous st and ard heparin in the initial treatment of this disorder . Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinical ly important bleeding . Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis , 85 received st and ard heparin ( to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value ) and 85 LMWH ( adjusted only for body weight ) for 10 days . Oral coumarin was started on day 7 and continued for at least 3 months . The frequency of recurrent venous thromboembolism diagnosed objective ly did not differ significantly between the st and ard-heparin and LMWH groups ( 12 [ 14 % ] vs 6 [ 7 % ] ; difference 7 % [ 95 % confidence interval -3 % to 15 % ] ; p = 0.13 ) . Clinical ly important bleeding was infrequent in both groups ( 3.5 % for st and ard heparin vs 1.1 % for LMWH ; p greater than 0.2 ) . We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis . Since there is no need for laboratory monitoring with the LMWH regimen , patients with venous thrombosis can be treated at home Summary Two studies have been done to establish recommendations for dosage and dose adjustment in the treatment of deep vein thrombosis ( DVT ) with low molecular weight heparin ( LMWH ) . In the first , 56 patients were r and omized in a double blind study to be treated either with unfractionated heparin ( UFH ) or LMWH s. c. every 12 h. Initial doses were given according to age and sex , disregarding bodyweight , and the dose was then adjusted when the peak plasma heparin concentration fell outside the desired range of 0.5–0.8 anti-FXa U/ml . There were fewer dose adjustments in the LMWH group . The correlation between injected dose ( U/kg bodyweight ) and the heparin concentration was higher in the LMWH group ( r=0.59 ) than in the UFH group ( r=0.38 ) . The results suggest that , in order to obtain the desired heparin concentration , the initial dose of LMWH should be about 100 U/kg bodyweight every 12 h . In the second , open study , this dosage plan was followed in 15 patients . The peak heparin concentration on Day 2 ranged from 0.40 to 0.75 anti-FXa U/ml and adjustment was only required in 3 patients . Day to day variation in peak heparin activity in the individual patient varied little ( CV 11–22 % ) , and there was no accumulation . The results indicate that plasma heparin concentration is more predictable using LMWH than UFH , and they point to definite advantages in the use of LMWH in a bodyweight adjusted dosage BACKGROUND The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate . METHODS Using a two-by-two factorial design , we r and omly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter ( 200 patients ) or no filter ( 200 patients ) , and to receive low-molecular-weight heparin ( enoxaparin , 195 patients ) or unfractionated heparin ( 205 patients ) . The rates of recurrent venous thromboembolism , death , and major bleeding were analyzed at day 12 and at two years . RESULTS At day 12 , two patients assigned to receive filters ( 1.1 percent ) , as compared with nine patients assigned to receive no filters ( 4.8 percent ) , had had symptomatic or asymptomatic pulmonary embolism ( odds ratio , 0.22 ; 95 percent confidence interval , 0.05 to 0.90 ) . At two years , 37 patients assigned to the filter group ( 20.8 percent ) , as compared with 21 patients assigned to the no-filter group ( 11.6 percent ) , had had recurrent deep-vein thrombosis ( odds ratio , 1.87 ; 95 percent confidence interval , 1.10 to 3.20 ) . There were no significant differences in mortality or the other outcomes . At day 12 , three patients assigned to low-molecular-weight heparin ( 1.6 percent ) , as compared with eight patients assigned to unfractionated heparin ( 4.2 percent ) , had had symptomatic or asymptomatic pulmonary embolism ( odds ratio , 0.38 ; 95 percent confidence interval , 0.10 to 1.38 ) . CONCLUSIONS In high-risk patients with proximal deep-vein thrombosis , the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis , without any difference in mortality . Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism Low molecular weight heparin ( LMWH ) is effective in the treatment of acute deep vein thrombosis ( DVT ) in adults . This has not been demonstrated for one LMWH alone . The relationship between venographic changes due to LMWH therapy and clinical outcome in the initial treatment period has not been reported . A pooled analysis of two clinical trials was performed . The trials compared a fixed-dose , body weight-independent , subcutaneous LMWH , certoparin ( 8000 antifactor Xa [ aXa ] U twice a day [ b.i.d . ] ) , with an adjusted-dose intravenous unfractionated heparin ( UFH ) with respect to venographic changes expressed as Marder score and occurrence of recurrent venous thromboembolism , major bleeding , and mortality . The Marder score was 23.2 + /- 8.4 in patients r and omized to LMWH ( n = 299 paired phlebograms ) and 23.9 + /- 8.9 in patients allocated to UFH ( n = 297 paired phlebograms ) at entry ( 2p = 0.23 ) and 18.9 + /- 9.7 and 20.5 + /- 9.9 at the end of the initial therapy ( 2p = 0.04 ) , respectively . The composite outcome of recurrent venous thromboembolism , major bleeding , and mortality occurred less frequently during treatment with LMWH ( n = 393 ) than it did with UFH ( n = 404 , 1.3 % versus 5.0 % , risk reduction [ RR ] 0.26 , 95 % confidence interval [ CI ] 0.11 to 0.63 , 2p = 0.004 ) . Single events of recurrent thromboembolism ( 2p = 0.12 ) , major bleeding ( 2p = 0.03 ) , and mortality ( 2p = 0.12 ) were observed less frequently with LMWH . A trend toward a lack of regression of thrombus size was observed in recurrent venous thromboembolism ( 2p = 0.08 ) . Body weight-independent LMWH significantly reduces thrombus size and the incidence of composite outcome during the initial treatment of acute proximal venous thrombosis compared with adjusted dose intravenous UFH . The data indicate a relation between an unimproved Marder score and a recurrent venous thromboembolism BACKGROUND A low-molecular-weight heparin , enoxaparin sodium , has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery . We conducted a controlled , r and omized trial with enoxaparin in the treatment of established deep vein thrombosis . METHODS In a multicenter trial , we compared fixed-dose subcutaneous enoxaparin , given twice daily , with adjusted-dose intravenous unfractionated heparin ( UFH ) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis . The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10 . The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment . RESULTS There were 67 patients in each group . Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority ( P < .002 ) of enoxaparin over the reference treatment with UFH . Moreover , the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher ( P < .002 ) in the UFH group ( seven of 67 ) than in the enoxaparin group ( one of 67 ) . There were no serious bleeding complications in either group . CONCLUSIONS Enoxaparin is at least as effective and safe as UFH under the conditions of this study . Moreover , it is more comfortable for patients and less time-consuming for nurses and laboratories . Thus , our study confirmed , with the use of enoxaparin , other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis BACKGROUND Low-molecular-weight heparin appears to be at least as effective and safe as st and ard , unfractionated heparin for the treatment of deep-vein thrombosis , but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism . METHODS We r and omly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin ( tinzaparin ) given once daily in a fixed dose or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months . We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism , major bleeding , and death . RESULTS In the first eight days of treatment , 9 of 308 patients assigned to receive unfractionated heparin ( 2.9 percent ) reached at least one of the end points , as compared , with 9 of 304 patients assigned to low-molecular-weight heparin ( 3.0 percent ; absolute difference , 0.1 percentage point ; 95 percent confidence interval , -2.7 to 2.6 ) . By day 90 , 22 patients assigned to unfractionated heparin ( 7.1 percent ) and 18 patients assigned to low-molecular-weight heparin ( 5.9 percent ) had reached at least one end point ( P=0.54 ; absolute difference , 1.2 percentage points ; 95 percent confidence interval , -2.7 to 5.1 ) . The risk of major bleeding was similar in the two treatment groups throughout the study . CONCLUSIONS Under the conditions of this study , initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism UNLABELLED A total of 164 patients were recruited from a r and omized trial comparing a low molecular weight heparin , dalteparin , given subcutaneously once daily with a continuous intravenous infusion of unfractionated heparin in the initial treatment of acute deep vein thrombosis . The primary objective of this follow-up study was to investigate whether there were any differences between the two treatment groups with respect to Marder score changes 6 months after the initial diagnosis using repeated venography . The secondary objectives were to analyse whether certain haemostatic and acute phase parameters or patient characteristics influenced the venographic outcome . RESULTS Complete lysis of the thrombus was observed in 38.4 % of the patients and a partial lysis in another 54.3 % assessed by venography 6 months after the acute event . Extension of the thrombus was seen in 7.3 % of the patients . There were no significant differences in the change in mean Marder score before treatment and at the 6 month follow-up between the two treatment groups , irrespective of thrombus localisation . In a regression model , male gender , low levels of orosomucoid and increased levels of d-dimer in plasma on day 5 were independently associated ( p < 0.05 ) with an enhanced absolute resolution of the thrombus at 6 months . No differences in symptoms and signs in the thrombotic leg at follow-up , comparing the treatment given , or thrombus extension at diagnosis and 6 months later , were demonstrated . CONCLUSION Dalteparin given once daily subcutaneously was as effective as continuous intravenous infusion of unfractionated heparin in the initial treatment of deep vein thrombosis assessed by Marder score evaluation 6 months after the acute event BACKGROUND Low-molecular-weight heparins are frequently used to treat venous thromboembolism , but optimal dosing regimens and clinical outcomes need further definition . METHODS In this multicenter , open-label study with blinded adjudication of end points , we r and omly assigned patients with acute deep-vein thrombosis to one of three treatment regimens : intravenous administration of unfractionated heparin ; subcutaneous administration of a low-molecular-weight heparin , reviparin , twice a day for one week ; or subcutaneous administration of reviparin once a day for four weeks . The primary end point was evidence of regression of the thrombus on venography on day 21 ; secondary end points were recurrent venous thromboembolism , major bleeding within 90 days after enrollment , and death . RESULTS Of the patients receiving unfractionated heparin , 40.2 percent ( 129 of 321 ) had thrombus regression , as compared with 53.4 percent ( 175 of 328 ) of patients receiving reviparin twice daily and 53.5 percent ( 167 of 312 ) of the patients receiving reviparin once daily . With regard to thrombus regression , reviparin administered twice daily was significantly more effective than unfractionated heparin ( relative likelihood of thrombus regression , 1.28 ; 97.5 percent confidence interval , 1.08 to 1.52 ) , as was reviparin administered once daily ( relative likelihood , 1.29 ; 97.5 percent confidence interval , 1.08 to 1.53 ) . Mortality and the frequency of episodes of major bleeding were similar in the three groups . CONCLUSIONS In acute deep-vein thrombosis , reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus . Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis ( DVT ) were r and omised either to a low molecular weight heparin , Fragmin , administered subcutaneously ( s.c . ) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin ( UFH ) . The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre . Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin , given from day 1 , was established ( i.e. an Internation Normalised Ratio , of 2.0 - 3.0 ) . A second venogram was obtained after Fragmin or UFH treatment . There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups , irrespective of thrombus localisation . No major bleeding events , symptomatic pulmonary embolism , symptomatic thrombosis progression or death occurred during hospitalisation . Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after r and omisation : 5 in patients treated with Fragmin and 3 in those treated with UFH . Six of these events occurred after cessation of warfarin treatment . In conclusion Fragmin given s.c . once daily in a fixed dose adjusted for body weight , is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT In order to avoid selective biases and to minimize r and om errors , inference about the effects of treatment on serious endpoints needs to be based not on one , or a few , of the available trial results , but on a systematic overview of the totality of the evidence from all the relevant unconfounded r and omized trials . But , only where coverage of all , or nearly all , r and omized patients in all relevant trials ( or a reasonably unbiased sample of such trials ) can be assured , is a systematic overview of trials reasonably trustworthy , for then any selective biases are likely to be small in comparison with any moderate effects of treatment . Checks for the existence of such biases can best be conducted if reasonably detailed data are available from each trial . Future trials should take into account the results of any relevant overviews in their design , and should plan to obtain sufficient numbers of events to contribute substantially to such overviews . In many cases , this implies the need for r and omized trials that are much larger than is currently st and ard We performed a r and omized double-blind trial comparing continuous intravenous heparin with intermittent subcutaneous heparin in the initial treatment of 115 patients with acute proximal deep-vein thrombosis . Intermittent subcutaneous heparin as administered in this trial was inferior to continuous intravenous heparin in preventing recurrent venous thromboembolism . The subcutaneous heparin regimen induced an initial anticoagulant response below the target therapeutic range in the majority of patients and result ed in a high frequency of recurrent venous thromboembolism ( 11 of 57 patients , 19.3 percent ) , which was virtually confined to patients with a subtherapeutic anticoagulant response . In contrast , continuous intravenous heparin induced a therapeutic anticoagulant response in the majority of patients and a low frequency of recurrent events ( 3 of 58 patients , 5.2 percent ; P = 0.024 ) ; the recurrences were limited to patients with an initial subtherapeutic anticoagulant response . The results of this trial establish the efficacy of intravenous heparin in the treatment of proximal venous thrombosis and suggest a relation between the effectiveness of heparin and the levels of anticoagulation achieved ; such a relation could explain the observed failure of the subcutaneous regimen Danaparoid ( Org 10172 ; Organon Scientific Development Group , Oss , the Netherl and s ) , a heparinoid with a mean molecular weight of 5500 d , is obtained from the intestinal mucosa of the pig after removal of heparin . It is a mixture of sulfated glycosaminoglycans with low molecular weight : heparan sulfate ( 84 % ) , dermatan sulfate ( 12 % ) , and chondroitin sulfate ( 4 % ) [ 1 , 2 ] . Only a subfraction ( 4 % ) of heparan sulfate contains the pentasaccharide sequence , common to heparin and to low-molecular-weight heparins , that has a high affinity to antithrombin III . This subfraction acts through the selective inhibition of factor Xa through antithrombin III , which leads to the inhibition of thrombin generation . The fraction of heparan sulfate with a low affinity for antithrombin III does not affect coagulation factors Xa and IIa but contributes substantially to antithrombotic activity , probably through an endothelial cellular mechanism [ 3 ] . The dermatan sulfate component of danaparoid activates heparin cofactor II , which acts at the level of factor IIa . The synergistic activity of these three components determines the antithrombotic profile . As reflected in its anti-factor Xa : anti-factor IIa inhibitory ratio of more than 28:1 , danaparoid is a more selective inhibitor of factor Xa than heparin or the low-molecular-weight heparins . The dose-related response to danaparoid remains gradual and linear over a wide dosing range , which may contribute to its safety as an antithrombotic drug . Compared with heparin and low-molecular-weight heparins , danaparoid has almost no effect on physiologic platelet function and has low cross-reactivity with heparin-induced antibodies against platelets . The wide therapeutic range of danaparoid and its minimal effect on platelets may render it a safer anticoagulant than heparin or low-molecular-weight heparins . Treatment with unfractionated heparin is limited by the drug 's pharmacokinetic , biophysical , and antihemostatic ( nonanticoagulant ) properties . Heparin must be given in sufficient quantities under frequent monitoring , its dose-response curve is nonlinear and unpredictable in individual persons , and the risk for bleeding increases with increasing doses and duration of treatment . Danaparoid has been shown in animal studies to be more effective than st and ard heparin or two different low-molecular-weight heparin preparations in preventing the extension of experimentally induced venous thrombi [ 4 ] . It has been both safe and effective in the prophylaxis of deep venous thrombosis in patients having cancer surgery [ 5 ] , hip-fracture surgery [ 6 ] , or hip-replacement surgery [ 7 ] and in patients with nonhemorrhagic stroke [ 8 ] . It has been used as an anticoagulant during hemodialysis [ 9 , 10 ] and in patients with heparin-induced thrombocytopenia [ 11 , 12 ] or disseminated intravascular coagulation [ 13 ] . Data from studies of the treatment of deep venous thrombosis in patients with hemorrhagic stroke indicate that treatment with danaparoid can prevent the extension of venous thromboembolism without aggravating cerebral bleeding [ 14 ] . No study has yet assessed the efficacy and safety of danaparoid in the treatment of patients presenting with acute deep venous thrombosis or pulmonary embolism . Danaparoid has a bioavailability of 100 % after subcutaneous administration ; the bioavailability of unfractionated heparin after subcutaneous injection is only 20 % to 30 % . Therefore , danaparoid is particularly suitable for subcutaneous administration , much like the low-molecular-weight heparin preparations [ 15 - 19 ] , which have a bioavailablity of approximately 90 % . Our study was design ed to assess the efficacy and safety of two doses of subcutaneously administered danaparoid and of continuous intravenous administration of unfractionated heparin as initial treatment in patients presenting with acute proximal deep venous thrombosis of the leg , pulmonary embolism , or both . Methods Study Design Our study was a r and omized , open , parallel-group clinical trial done in one university hospital and two university-affiliated hospitals in the Netherl and s. The study protocol and forms giving informed consent were approved by the institutional review board at each hospital . Patients All patients gave witnessed informed consent before being entered into the study . Men and women 18 years of age or older who presented with clinical symptoms of acute proximal deep venous thrombosis of the leg or pulmonary embolism of no more than 7 days duration were eligible . Patients were excluded if they had had intracranial bleeding within 2 months or resuscitation by external chest compression within 48 hours ; if they were allergic to heparin ; if they were pregnant ; if they were receiving treatment with coumarin derivatives ; if they had been treated with thrombolytic drugs within 7 days ; or if they were receiving ongoing treatment with aspirin , nonsteroidal anti-inflammatory drugs , dextran , or fibrinolytic drugs . The provisional diagnosis of venous thrombosis or pulmonary embolism had to be confirmed within 48 hours after the start of study treatment by compression ultrasonography or contrast venography ( whichever could be done soonest ) or by ventilation-perfusion lung scan . Treatment was discontinued and the patient was excluded from the study if the clinical diagnosis was not confirmed . Enrollment began in March 1991 and continued through August 1992 . Dosing Schedule The efficacy and safety of two dosing schedules of danaparoid were compared with the efficacy and safety of continuous intravenous unfractionated heparin . The schedule for low-dose danaparoid was 1250 anti-factor Xa units given as an intravenous bolus , followed by subcutaneous doses of 1250 anti-factor Xa units every 12 hours . The schedule for high-dose danaparoid was 2000 anti-factor Xa units given as an intravenous bolus , followed by subcutaneous doses of 2000 anti-factor Xa units every 12 hours . The first subcutaneous injection was simultaneous with the intravenous bolus injection . The second subcutaneous injection was given at the time of the first of the routine twice-daily injections , unless this was within 6 hours of the first injection . Unfractionated heparin was given intravenously as a loading dose of 2500 U and was followed by an initial maintenance dose of 30 000 U every 24 hours . This maintenance dose was adjusted to reach activated partial thromboplastin 2.5 to 3.5 times the control values ; these times were equivalent to a heparin level of 0.25 to 0.40 U/mL. This was measured daily and 4 hours after any dose adjustment . Study treatment was given for at least 5 days and was continued until an international normalized ratio of at least 3.0 was achieved with oral anticoagulation therapy , which was started 48 hours after the initiation of study treatment . The oral anticoagulant dose was calculated daily using the Thrombotest ( Nyegaard and Co. , Oslo , Norway ; international sensitivity index , 0.94 ) ; this was done each morning using plasma sample s taken before the morning dose had been given . If the international normalized ratio was below the target level after 8 days of study treatment , the attending physician decided whether to continue heparin therapy , continue danaparoid therapy , or switch patients being treated with danaparoid to intravenous heparin . Study treatment was r and omized as follows . Consecutively numbered , identical boxes were kept in each hospital pharmacy ; each box contained one of the three treatments , r and omized per hospital . After giving informed consent , a patient was treated with medication from the next consecutive box . The investigators were blinded to the r and omization schedule . Only when the study medication for one individual patient was delivered did the treatment become known . After being assigned to treatment , patients were excluded from the efficacy analysis only if diagnosis of deep venous thrombosis or pulmonary embolism could not be confirmed within 48 hours of admission . Evaluations and Scheduling The primary method of assessment for recurrence or extension was repeated ultrasonography of the leg , contrast venography , ventilation-perfusion scanning , or both contrast venography and ventilation-perfusion scanning . Assessment was done after at least 5 days and at most 8 days of study treatment , within 24 hours after stopping treatment , or if clinical ly indicated . Institutional physicians , who were blinded to treatment assignments , interpreted venograms , ultrasonograms , and lung scans . Clinical evidence of recurrence or extension was defined as documented clinical circumstances suggestive of venous thromboembolic disease leading to the discontinuation of study treatment . A daily physical examination ( including tests for hemoglobin level , platelet count , and leukocyte count ) and a urinalysis to test for erythrocyte count were done . Liver function tests were done and creatinine levels were measured before and at the end of study treatment . Plasma used to measure amidolytic anti-factor Xa activity was collected at the time of screening and at treatment days 2 and 4 ( before and 2.5 hours after the morning injection on both days ) . This plasma was frozen at 20C and stored until assay . Plasma sample s were collected at the time of screening for determination of activated partial thromboplastin times before study treatment . Follow-up assessment was done 2 months after the initiation of study treatment to gather information on state of health , recurrence or extension of venous thromboembolism , and bleeding complications . Compression Ultrasonography To establish the extent of thrombosis using ultrasonography [ 20 ] , the deep venous system was divided into six segments : lower popliteal , upper popliteal , inferior femoral , mid-femoral , upper femoral , and common femoral veins . Each patient was first examined in the supine position so that the superficial femoral , common femoral , and iliac vein segments could be assessed . Patients were then examined in the prone position In a prospect i ve , r and omized , open study 119 consecutive patients with phlebographically verified deep venous thrombosis ( DVT ) of the leg ( 36 % distal and 64 % proximal ) were treated either with a low molecular weight heparin ( Fragmin , Kabi-Vitrum ) subcutaneously ( 120 anti-FXa U/kg ) twice daily or st and ard heparin ( SH ) as continuous intravenous infusion ( 480 IU kg-1 day-1 ) . The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2 - 0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection . The SH dose was modified to prolong the APTT 2 - 3 times . Repeat phlebography after 5 - 7 days showed improvement in 34/45 patients ( 76 % ) in the Fragmin group and in 30/49 patients ( 61 % ) in the SH group and progress in 2/45 ( 4 % ) and 3/49 ( 6 % ) , respectively . The mean Marder scores decreased from 18.7 + /- 12.1 to 15.7 + /- 12.7 in the Fragmin group and from 16.9 + /- 12.0 to 14.4 + /- 11.8 in the SH group ( ns ) . Two patients in the SH group and none in the Fragmin group had major bleedings . After 22 + /- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group . Postthrombotic signs and symptoms were similar in both groups . We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg BACKGROUND In patients with venous thromboembolism ( VTE ) , identifying clinical risk factors for recurrence during the initial 3 months of anticoagulant therapy and knowledge of the time course of recurrence may help clinicians decide about the frequency of clinical surveillance and the appropriateness of outpatient treatment . METHODS Analysis of a r and omized controlled trial data base involving 1021 patients with VTE ( 750 with deep vein thrombosis [ DVT ] and 271 with pulmonary embolism [ PE ] ) who were followed up for 3 months after the start of anticoagulant therapy . All patients received initial treatment with unfractionated heparin or a low-molecular-weight heparin ( reviparin ) and a coumarin derivative starting the first or second day of treatment , with a target international normalized ratio of 2.0 to 3.0 . RESULTS Four independent clinical risk factors for recurrent VTE were identified : ( 1 ) cancer ( odds ratio [ OR ] , 2.72 ; 95 % confidence interval [ CI ] , 1 . 39 - 5.32 ) , ( 2 ) chronic cardiovascular disease ( OR , 2.27 ; 95 % CI , 1 . 08 - 4.97 ) , ( 3 ) chronic respiratory disease ( OR , 1.91 ; 95 % CI , 0.85 - 4 . 26 ) , and ( 4 ) other clinical ly significant medical disease ( OR , 1.79 ; 95 % CI , 1.00 - 3.21 ) . Older age was associated with a decreased risk for recurrent VTE ( OR , 0.76 ; 95 % CI , 0.64 - 0.92 ) . Previous VTE , sex , and idiopathic VTE were not risk factors for recurrence . In patients with DVT or PE , there was no significant difference in the rates of recurrent nonfatal VTE ( 4.8 % vs 4.1 % ; P = .62 ) , major bleeding ( 2.9 % vs 2.2 % ; P = .53 ) , and non-VTE death ( 6.4 % vs 7.8 % ; P = .45 ) , but recurrent fatal PE was more frequent in patients with PE than DVT ( 2 . 2 % vs 0 % ; P<.01 ) . There was a clustering of recurrent VTE episodes during the initial 2 to 3 weeks after the start of treatment . CONCLUSIONS During the initial 3 months of anticoagulant therapy , recurrent VTE is more likely to occur in patients with cancer , chronic cardiovascular disease , chronic respiratory disease , or other clinical ly significant medical disease . Patients with PE are as likely to develop recurrent VTE as those with DVT ; however , recurrence is more likely to be fatal in patients who initially present with PE . Arch Intern Med . 2000;160:3431 - 3436 BACKGROUND Ardeparin sodium has recently received approval by the Food and Drug Administration for prophylaxis against venous thromboembolism in patients undergoing elective total knee replacement . However , this low-molecular-weight heparin has not been previously evaluated in a r and omized controlled trial for treatment of established acute deep venous thrombosis . METHODS The study included patients with ultrasound-documented acute symptomatic deep venous thrombosis of the legs . They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular-weight heparin . Patients were r and omized to receive ardeparin with a 2-day hospitalization or unfractionated heparin sodium with a 5-day hospitalization . Both groups received warfarin sodium . Follow-up ultrasound examinations were undertaken at 6 weeks . RESULTS Of the 80 patients enrolled , 75 had follow-up ultrasonography . Evaluation of baseline vs 6-week venous scans demonstrated that , overall , 31 of the 39 ardeparin-treated patients improved , compared with 21 of the 36 patients assigned to receive unfractionated heparin ( P=.05 ) . The 95 % confidence interval for the difference in improvement was 0.6 % to 42 % in favor of ardeparin . Median charges for ardeparin and unfractionated heparin were $ 2815 and $ 6500 , respectively ( P<.001 ) . There were no differences in bleeding or patient satisfaction between the 2 groups . CONCLUSIONS The results of this small preliminary trial suggest that ardeparin can be administered effectively and safely to selected patients with acute deep venous thrombosis and that , with proper nursing and home services , it can help decrease the duration of hospitalization In this study , 294 patients with acute proximal DVT ( deep venous thrombosis ) were r and omly assigned to receive intravenous st and ard heparin in the hospital ( 98 patients ) or low-molecular-weight heparin ( LMWH ) ( nadroparin 0.1 mL [ equivalent to 100 AXa IU ] per kg of body weight subcutaneously twice daily ) administered primarily at home ( out patients ) or alternatively in hospital ( 97 patients ) or subcutaneous calcium heparin ( SCHep ) ( 99 patients , 0.5 mL bid ) administered directly at home . The study design allowed out patients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early . Patients treated with st and ard heparin or LMWH received the oral anticoagulant starting on the second day , and heparin was discontinued when the therapeutic range ( INR 2 - 3 ) had been reached . Anticoagulant treatment was maintained for 3 months . Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants . Patients were evaluated for inclusion and follow-up with color duplex scanning . Venography was not used . In case of suspected pulmonary embolism ( PE ) a ventilatory-perfusional lung scan was performed . Endpoints of the study were recurrent or extension of DVT , bleeding , the number of days spent in hospital , and costs of treatments . Of the 325 patients included , 294 completed the study . Dropouts totaled 31 ( 10.5 % ) ; six of the 325 included patients ( 1.8 % ) died from the related , neoplastic illness . Recurrence or extension of DVT was observed in 6.1 % of patients in the LMWH group , in 6.2 % in the st and ard heparin group , and in 7.1 % in the SCHep group . Most recurrences ( 11/17 ) were in the first month in all groups . Bleedings were all minor , mostly during hospital stay . Hospital stay in patients treated with LMWH was 1.2 ± 1.4 days in comparison with 5.4 ± 1.2 in those treated with st and ard heparin . There was no hospital stay in the SCHep group . Average treatment costs in 3 months in the st and ard heparin group ( US $ 2,760 ) were considered to be 100 % ; in comparison costs in the LMWH group was 28 % of the st and ard heparin and 8 % in the SCHep group . This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost The st and ard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin . This entails hospitalisation , nursing care , immobility and repeated laboratory tests ( e.g. activated partial thromboplastin time [ APTT ] , platelet count ) . In addition approximately 10 % of patients suffer major haemorrhages . The potential advantages of a low molecular weight heparin ( CY 216 ) given subcutaneously were explored in a r and omised trial with blind quantitative evaluation of venograms . The study included 166 patients and both " therapeutic efficacy " and " intention to-treat " analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i.v . st and ard heparin with daily dose adjustment according to results of coagulation tests . There was no increase in the risks of pulmonary embolism , haemorrhage or clot extension In order to study whether a low molecular weight heparin ( LMWH ) of mw 4000 D is effective in the treatment of deep venous thrombosis ( DVT ) , patients with DVT verified by phlebography were r and omized to treatment by continuous intravenous infusion of either unfractionated heparin ( UFH ) or LMWH . The initial dose was 240 U ( anti F Xa)/kg/12 h. This study ( study I ) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated . The heparin activity measured as F Xa inhibition assayed in retrospect , was found to be much higher in the LMWH group ( mean 1.6 - 2.0 anti F Xa U/ml ) than in the UFH group ( mean 0.5 - 0.8 anti F Xa U/ml ) . A second study was therefore initiated in which the DVT patients were r and omly given UFH ( 240 U/kg/12 h ) or LMWH only 120 U ( anti F Xa)/kg/12 h , as initial doses ( study II ) . In this study 27 patients could be evaluated , the mean heparin activity still being higher in the LMWH group ( 0.9 - 1.2 anti F Xa U/ml ) than in the UFH group ( 0.5 - 0.7 anti F Xa U/ml ) . A second phlebographic investigation showed progression of thrombus size in 3 ( 11 % ) of the UFH patients of studies I and II ( n = 29 ) and improvement in 14 ( 48 % ) . There was no progression in any LMWH patient , 6 ( 50 % ) had improved in study I and 10 ( 77 % ) in study II . The mean decrease of thrombus size score ( according to Marder ) during treatment did not differ between the 3 groups . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Two hundred and thirty-four patients treated with continuous intravenous infusions of heparin were studied prospect ively to seek a relation between the activated partial thromboplastin tim Two clinical trials in patients with acute deep venous thrombosis have indicated that the outpatient management with fixed-dose , subcutaneous low-molecular-weight heparin is at least as effective and safe as inpatient treatment with unfractionated intravenous heparin with respect to recurrent venous thromboembolism and major bleeding . We performed an economic evaluation alongside one of these trials to assess the cost consequences of the outpatient management strategy . Data were collected through case record forms , complemented by a prospect i ve question naire in 78 consecutive patients , interviews with health care providers , and hospital data bases . Our study demonstrated that seventy-five percent of patients allocated to low-molecular-weight heparin received treatment either entirely at home or after a brief hospital stay . Fifteen percent of these patients required professional domiciliary care . Within-centre comparisons of re source utilisation in terms of natural units showed that outpatient management with low-molecular-weight heparin reduced the average number of hospital days in the initial treatment period in nine centres by 59 percent ( 95 % CI : 43 to 71 percent ) accompanied by a limited increase in outpatient and professional domiciliary care . The average reduction in hospital days at the end of follow up was 40 percent ( 95 % CI : 25 to 54 percent ) . A cost-minimisation analysis , focusing on re source utilisation directly related to the treatment of deep venous thrombosis and associated costs in one centre demonstrated a cost reduction of 64 percent ( 95 % CI : 56 to 72 percent ) with the outpatient management with low-molecular-weight heparin . These data suggest that outpatient management of patients with proximal venous thrombosis using low-molecular-weight heparin reduces re source utilisation and total treatment cost . Implementation should be preceded by a cautious evaluation of a potential cost shifting and organisational prerequisites It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin , with warfarin added on day 5 to 10 and continued for several months . We performed a r and omized , double-blind trial comparing a shorter course of continuous intravenous heparin ( 5 days , with warfarin sodium begun on the first day ) with the conventional 10-day course of heparin ( with warfarin sodium begun on the fifth day ) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography . The frequency of objective ly documented recurrent venous thromboembolism was low and essentially the same in the two groups ( 7.1 percent in the short-course group vs. 7.0 percent in the long-course group ) . Because the observed difference between the groups was 0.1 percent in favor of the long-course group , it is unlikely ( P less than 0.05 ) that a true difference in favor of this group would be greater than 7.5 percent ; the difference could be as much as 7.3 percent in favor of the short-course group . Major bleeding episodes were infrequent , and the rate was similar in both groups . We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis . Furthermore , using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings In a prospect i ve multicenter trial , 149 consecutive patients with phlebographically proven proximal and /or distal deep vein thrombosis of the leg were r and omly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 ( Fraxiparine ) in a fixed dose or unfractionated heparin ( UFH ) in doses adjusted according to the activated partial thromboplastin time . Pre- and post-treatment phlebograms were assessed blindly using the Arnesen 's score system in 134 patients available for analysis of the treatment efficacy . The mean phlebographic score after 10 days of treatment was significantly decreased in both groups ( p less than 0.001 ) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant . There was an improvement in 45/68 patients ( 66 % ) in the Fraxiparine group and in 32/66 patients ( 48 % ) in the UFH group , and an increase in the thrombus size in 10/68 ( 15 % ) and 12/66 ( 18 % ) , respectively . One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group . During a follow-up period of 3 months , two rethromboses had occurred in the UFH group and none in the Fraxiparine group . It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis BACKGROUND In most countries , heparin is used in the initial treatment of patients with deep-vein thrombosis . Well- design ed studies establishing the efficacy of heparin therapy are lacking , however . Treatment with acenocoumarol alone , according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin , is considered an effective alternative in some countries . METHODS In a r and omized , double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of out patients with proximal-vein thrombosis . The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up . In addition , we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment . The incidence of major bleeding was determined during three months of follow-up . RESULTS The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone ( in 12 of 60 patients [ 20 percent ] , as compared with 4 of 60 patients [ 6.7 percent ] in the combined-therapy group by intention-to-treat analysis ; P = 0.058 ) . Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol ( P < 0.001 ) . Major bleeding complications were infrequent and comparable in the two groups . CONCLUSIONS Patients with proximal-vein thrombosis require initial treatment with full-dose heparin , which can safely be combined with acenocoumarol therapy Venous thromboembolic disease causes significant morbidity and mortality in both hospitalized and nonhospitalized patients . The mean annual incidence in the United States is 48 per 100 000 for deep venous thrombosis and 23 per 100 000 for pulmonary embolism , according to an epidemiologic study conducted in Massachusetts ( 1 ) . A similar study in Sweden showed an annual incidence of 160 new cases of deep venous thrombosis per 100 000 inhabitants ( 2 ) . Five to 10 days of unfractionated heparin is a common recommended initial treatment for deep venous thrombosis . This treatment maintains the activated partial thromboplastin time above 1.5 times its control value ( 3 , 4 ) , as calibrated by protamine titration or an antifactor Xa assay . Another recommended initial treatment is 5 to 10 days of weight-adjusted low-molecular-weight heparin followed by at least 3 months of oral anticoagulant therapy ( 3 - 7 ) . Low-molecular-weight heparins are now frequently being used in place of unfractionated heparin for both prevention and treatment of venous thromboembolism ( 3 , 8) . R and omized trials and meta-analyses have shown subcutaneously administered low-molecular-weight heparins to have antithrombotic efficacy equal to ( 9 - 12 ) or greater than ( 13 - 16 ) that of continuously infused unfractionated heparin in the initial treatment of deep venous thrombosis and equal to that of unfractionated heparin in the treatment of pulmonary embolism ( 17 , 18 ) . However , many of these studies enrolled small numbers of patients ( 9 - 13 , 15 , 16 ) , used primarily venographic plethysmographic or scintigraphic end points ( 9 - 11 , 13 , 16 ) , and sometimes excluded patients with pulmonary embolism ( 11 , 15 ) . Most trials of twice-daily low-molecular-weight heparin adjusted treatment regimens according to patient weight without laboratory monitoring . However , several studies suggest that once-daily weight-adjusted dosage of a low-molecular-weight heparin is as effective in the treatment of proximal deep venous thrombosis as adjusted dosages of intravenous unfractionated heparin ( 14 , 19 ) or twice-daily low-molecular-weight heparin ( 20 ) . Since low-molecular-weight heparins differ in their physicochemical and pharmacologic characteristics , study results that apply to one can not be extended to another ( 21 , 22 ) . We conducted the present study to determine whether enoxaparin administered subcutaneously once or twice per day is as effective as continuously infused unfractionated heparin in the treatment of patients with acute , symptomatic venous thromboembolic disease . Methods Study Description This parallel-group , r and omized , partially blinded , international , multicenter clinical trial compared continuously infused unfractionated heparin ( adjusted to maintain activated partial thromboplastin time within a defined range ) with two weight-adjusted dosages of enoxaparin administered subcutaneously once or twice daily . The study was conducted in 74 hospitals in 16 countries , including the United States , several European countries , Australia , and Israel , and was approved by the institutional review board or ethics committees at each location . Written informed consent was obtained from each patient . Four committees participated in this study : an Advisory Committee ; an Outcome Adjudication Committee , which provided blinded outcome assignments for incidence of recurrent venous thromboembolic disease , major or minor hemorrhage , immune thrombocytopenia , and cause of death ; an independent Safety Committee ; and a Vascular Imaging Committee , which review ed all baseline venograms and all vascular imaging studies in a blinded manner to determine whether deep venous thrombosis was present at baseline and whether objective evidence of recurrence existed . Patient Characteristics Patients were required to be at least 18 years of age and willing to remain hospitalized during r and omized therapy . The primary inclusion criteria were symptomatic lower-extremity deep venous thrombosis confirmed by venography or ultrasonography ( if venography was inconclusive ) , symptomatic pulmonary embolism confirmed by high-probability ventilationperfusion scanning , or positive pulmonary angiography with confirmation of lower-extremity deep venous thrombosis . All eligible patients underwent baseline lung scanning or angiography . Exclusion criteria were more than 24 hours of previous treatment with heparin or warfarin ; need for thrombolytic therapy ; known hemorrhagic risk , including active hemorrhage , active intestinal ulcerative disease , known angiodysplasia , or eye , spinal , or central nervous system surgery within the previous month ; renal insufficiency ( serum creatinine concentration>180 mol/L [ 2.03 mg/dL ] ) ; severe hepatic insufficiency ; allergy to heparin , protamine , porcine products ( both heparin and enoxaparin are derived from pork intestinal mucosa ) , iodine , or contrast media ; history of heparin-associated thrombocytopenia or heparin- or warfarin-associated skin necrosis ; treatment with other investigational therapeutic agents within the previous 4 weeks ; inferior vena cava interruption ; or known pregnancy or lactation . Treatments Within each center , consecutive eligible patients were r and omly assigned sequentially to one of three treatment groups . R and omization was done without stratification in blocks of six , according to ascending r and omization number . The numbers were affixed to sealed treatment kits that contained study medication and were provided by the study sponsor . Patients assigned to enoxaparin received a weight-adjusted subcutaneous dose . Two blinded regimens were tested : 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily . Several clinical trials have shown the twice-daily regimen to be effective and safe ( 16 , 23 , 24 ) . The once-daily dosage was chosen on the basis of results of pharmacokinetic studies that showed it to have a suitable pharmacokinetic profile in healthy volunteers and to be well tolerated in the treatment of patients with venous thromboembolism ( 25 , 26 ) . In these previous studies , therapeutic antifactor Xa levels were present for up to 18 hours in both volunteers and patients , and measurable levels were present for up to 24 hours . A total of three injections , study drug and placebo , were given each day to maintain blinding for volume of solutions and frequency of administration . Patients assigned to the nonblinded unfractionated heparin group received an intravenous bolus dose and infusion on the basis of an approved institution-specific nomogram . In most cases , administration was as follows : Six hours after the initial bolus , the activated partial thromboplastin time was measured and the dose was adjusted to maintain the specified value , which was between 55 and 80 seconds in most centers ( 4 - 7 ) . Activated partial thromboplastin time was measured at least daily during unfractionated heparin treatment . Enoxaparin and heparin treatments were continued for at least 5 days , and warfarin was started within 72 hours of initial study drug administration . Forty-three patients received phenprocoumon in place of warfarin sodium . Prothrombin time was measured daily , and patients could be discharged from the hospital after the international normalized ratio was found to be between 2.0 and 3.0 on 2 consecutive days . Oral anticoagulation was continued for at least 3 months . Study Assessment s Observers who were aware of treatment assignment assessed patients daily and monthly during the 3-month follow-up for worsening or recurrence of deep venous thrombosis or pulmonary embolism , hemorrhage , adverse events , changes in concomitant medications and adequacy of warfarin use , and warfarin adherence . For patients receiving unfractionated heparin , adherence was defined as an activated partial thromboplastin time within or above the therapeutic range on the second day of treatment . For patients receiving enoxaparin , adherence was defined as at least 10 doses of study medication given with no dosing errors . Adherence to warfarin therapy was defined as having at least one international normalized ratio value greater than or equal to 2.0 between day 4 and the last dose of study treatment during the initial treatment period . These definitions of treatment adherence were established before the analysis of the study outcomes . Efficacy Analysis The efficacy analysis was performed on two study sample s : all treated patients , who received at least one dose of study medication , and evaluable patients , which excluded all patients who met at least one of the criteria for nonevaluability . These criteria were no confirmed deep venous thrombosis at baseline , insufficient study therapy , placement of an inferior vena cava filter , two r and om assignments , and no 3-month follow-up . Insufficient study therapy was defined as one or more missed enoxaparin doses among at least eight consecutive enoxaparin doses or less than 4 consecutive days of heparin infusion . The definition of insufficient study therapy was established before analysis of study outcomes . These two study sample s were analyzed to strengthen the conclusion of equivalence among the treatment groups . The homogeneity of the results of the two analyses is considered to be more supportive of the conclusion of equivalence than the results of either analysis alone . Primary clinical end points were recurrent deep venous thrombosis or pulmonary embolism within 3 months of r and omization . Patients with symptoms of recurrent thrombosis underwent confirmatory testing with venography , ultrasonography , or both . Patients presenting with signs or symptoms of pulmonary embolism underwent lung perfusion scanning , pulmonary angiography , or both . Clinical symptoms and supportive findings on objective tests ; extension of existing thrombi or new thrombi for venography , angiography , or ultrasonography ; or high-probability defect patterns on perfusion scans were required to confirm recurrent thrombosis . Prespecified subgroup analyses were performed on the basis of patient Inherent contradictions in current diagnostic recommendations for pulmonary embolism have created considerable confusion and controversy . To resolve these contradictions , we did a prospect i ve study of ventilation-perfusion scanning , pulmonary angiography , and venography in consecutive patients with clinical ly suspected pulmonary embolism and abnormal perfusion scans . Ventilation scanning increased the probability of pulmonary embolism in patients with large perfusion defects and ventilation mismatch , but a ventilation-perfusion match was not helpful in ruling out pulmonary embolism . Small perfusion defects with mismatch had neither sufficiently high nor low probability to be of diagnostic value . The observed frequency of proximal vein thrombosis ( 19 % to 51 % ) and its association with the range of ventilation-perfusion defects have important implication s for management of pulmonary embolism . Pulmonary angiography is required in combination with venography in most patients with perfusion abnormalities because the probability of pulmonary embolism is neither sufficiently high nor low to confirm or exclude pulmonary embolism Background : Low-molecular-weight heparin ( LMWH ) appears to be as effective as unfractionated heparin ( UFH ) for both treatment and prophylaxis of deep vein thrombosis ( DVT ) , but limited data are available for its use in acute pulmonary thromboembolism ( PTE ) . Objective : To determine whether enoxaparin , a LMWH , was clinical ly as efficient and safe as UFH in patients with a diagnosis of acute PTE . Material and Methods : After exclusion of those with massive forms , 59 patients with acute PTE were r and omly assigned to either subcutaneous enoxaparin given twice daily ( 1 mg/kg/dose ) or adjusted dose intravenous UFH . Oral anticoagulant treatment was begun on the second day and was given for at least 6 months . We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding , recurrent venous thromboembolism ( VTE ) , and death . Results : In the first 8 days of treatment , 1 of 30 patients assigned to receive UFH ( 3.3 % ) reached one of the end points ( recurrence ) , as compared with none of 29 patients assigned to enoxaparin . Statistically this difference was not significant ( p = 0.508 ) . By day 90 , 3 patients assigned to UFH ( 10 % ) had symptomatic recurrent VTE , as compared with 1 patient assigned to enoxaparin ( 3.4 % ) . There was neither major bleeding nor death in the study groups . There was an absolute difference of 6.4 percentage points between the two treatment groups , but the difference was statistically not significant ( p = 0.318 ) . Conclusion : Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin , a low molecular weight heparin , with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis ( DVT ) . Patients were included if they had deep venous thrombosis distal to inguinal ligament and were r and omised either before , if it was considered necessary , or after phlebographic verification of the diagnosis . There was no pre- inclusion treatment with unfractionated heparin . One hundred and twenty patients received dalteparin , administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg , and 133 patients received a continuous intravenous infusion of unfractionated heparin ( UFH ) . Oral anticoagulation was started on the first or second day , and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range ( 2 < INR < 3 ) on two consecutive days . Control phlebograms were taken within 4 days , thereafter . There were no significant differences between the two initial treatment groups in improvements in Marder score . Two major bleeding events occurred in the UFH group versus none in the dalteparin group . One patient in each group experienced clinical ly significant pulmonary embolism . During a mean follow-up period of 6.9 + /- 1.5 months , recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group . These results confirm those of a previous study on dalteparin in the initial treatment of DVT , and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament . The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH . Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised , studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted BACKGROUND Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis . However , its application to pulmonary embolism or previous episodes of thromboembolism has not been studied . METHODS We r and omly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose , subcutaneous low-molecular-weight heparin ( reviparin sodium ) or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks . Approximately one third of the patients had associated pulmonary embolism . The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism , major bleeding , and death . We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism . RESULTS Twenty-seven of the 510 patients assigned to low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolic events , as compared with 25 of the 511 patients assigned to unfractionated heparin ( 4.9 percent ) . The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence . Sixteen patients assigned to low-molecular-weight heparin ( 3.1 percent ) and 12 patients assigned to unfractionated heparin ( 2.3 percent ) had episodes of major bleeding ( P= 0.63 ) , and the mortality rates in the two groups were 7.1 percent and 7.6 percent , respectively ( P=0.89 ) . CONCLUSIONS Fixed-dose , subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose , intravenous unfractionated heparin for the initial management of venous thromboembolism , regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism We have performed a prospect i ve , r and omized , controlled trial comparing continuous intravenous unfractionated heparin with twice-daily subcutaneous ( s.c . ) high-dose low-molecular-weight ( LMW ) heparin in the initial treatment of 50 patients with acute proximal deep vein thrombosis . In this article we analyze the relationship between the dosage of the heparins , the anticoagulant effects on aPTT , and thrombin and factor Xa inhibition to the improvement of the Marder score after a 10-day treatment period . Improvement of the Marder score was observed in about 70 % of patients without regard to administration of unfractionated or LMW heparin . Patients in both treatment categories were divided into two groups , namely , those who showed an improvement of the Marder score and those who did not . In the group of patients with unfractionated heparin and regression of thrombus size the mean dosage was 33,000 U/day , whereas the mean dosage was 37,000 U/day in the patients with status idem of the Marder score after the 10-day treatment period . Thrombin clotting time values were in contrast to the dosage . Patients with regression of thrombosis showed higher thrombin clotting time values compared with those with status idem . These results were also seen with aPTT and the Heptest coagulation assay , but the differences between the two groups were less pronounced . No differences between these two groups of patients were seen or detected with the S2222 chromogenic anti-factor Xa method . Patients receiving 2 x 12,000 IU s.c./day LMW heparin did not show these differences , the dosage being adjusted by the anti-Xa levels , ranging from 0.6 to 1.0 U/mL 4 hours after the s.c . injection . The groups of patients categorized as to improvement or not of the Marder score did not show differences in the daily dose . The anti-Xa activity was higher in patients with regression of thrombosis compared with patients without regression . The other coagulation parameters did not show any relation to the clinical outcome of thrombus regression . The relationship between the change of the Marder score at day 10 and the anticoagulant effect on the different coagulation systems correlated weakly for patients receiving unfractionated heparin . The highest correlation was found for the improvement of Marder score and thrombin inhibition in the heparin group with r = 0.42 . For LMW heparin no correlation could be detected . Heptest coagulation values were in the same range for patients receiving unfractionated and LMW heparin . In contrast to the chromogenic anti-Xa assay , aPTT , thrombin clotting time , and prothrombin time values differed substantially in the two treatment regimens . Treatment of recent deep vein thrombosis with unfractionated heparin profits from laboratory monitoring , whereas monitoring of the anticoagulant effect during the treatment with s.c . LMW heparin does not influence the outcome on thrombus regression OBJECTIVES To compare the efficacy and safety of the low molecular weight heparin ( LMWH ) dalteparin with unfractionated heparin ( UFH ) in the acute treatment of DVT patients who had not previously received UFH . DESIGN An open r and omized multicentre trial with blinded analysis of venograms . SETTING Seven hospitals in Sweden , Finl and and the USA . SUBJECTS A total of 330 patients , of 20 years or older , with suspected DVT , verified using venography . INTERVENTIONS Fixed-dose dalteparin ( 200 IU kg-1 ) given as a once-daily subcutaneous injection , or aPTT adjusted i.v . UFH infusion for 6 to 10 days . MAIN OUTCOME MEASURES Change in Marder score in patients with confirmed DVT and two evaluable venograms ; PE , bleeding events and follow-up . RESULTS Marder scores improved in 51 % ( 95 % CI 42 - 60 % ) of 92 patients treated with dalteparin and in 62 % ( 95 % CI 53 - 70 % ) of 98 patients treated with UFH ( P = 0.152 ) . One dalteparin-treated patient had a PE confirmed by V/Q scan ; another had progressive thrombosis with swelling in the affected limb . Bleeding complications occurred in six patients in each group . One patient treated with dalteparin and five treated with UFH died during the 6-month follow-up period as a result of underlying malignancy or heart disease . The 6-month recurrence rate was low with both treatments ( dalteparin , 3/97 ; UFH , 2/103 ) . CONCLUSIONS Fixed-dose subcutaneous dalteparin given once daily from the start of treatment is of equivalent efficacy and safety to conventional UFH therapy in the routine management of DVT |
12,577 | 18,378,417 | The pooled sensitivity , pooled specificity and AUC showed no statistical significance between PET alone and PET-CT .
PET-CT might be a useful supplement to current surveillance techniques , particularly for those patients with an increasing CA 125 level and negative CT or MR imaging .
However , regarding to diagnostic accuracy , interpreted CT images may have limited additional value on PET in detecting recurrent ovarian cancer | BACKGROUND AND PURPOSE Ovarian cancer is the commonest tumor in female patients with a propensity for recurrence even after primary chemotherapy in early stage .
The accuracy of CA 125 , PET alone , PET-CT , CT and MRI in diagnosing the recurrent ovarian carcinoma has never been systematic ally assessed , and present systematic review was aim ed at this issue . | PURPOSE To determine the accuracy of breath-hold gadolinium- and perflubron-enhanced magnetic resonance ( MR ) imaging , immunoscintigraphy with indium-111-CYT-103 ( planar and single photon emission computed tomography [ CT ] ) , and contrast material -enhanced CT for the detection of ovarian cancer prior to laparotomy . MATERIAL S AND METHODS Sixteen patients with primary ( n = 3 ) or treated ( n = 13 ) ovarian cancer underwent imaging of the abdomen and pelvis with each modality . All images were review ed prospect ively for tumor location , and results were compared with findings at surgery . RESULTS With CT or MR imaging , tumor was detected in 11 of 13 ( 85 % ) patients compared with 11 of 12 patients ( 92 % ) with immunoscintigraphy . Per patient accuracy for CT was 81 % compared with 75 % for MR imaging and 86 % for immunoscintigraphy . For detection of individual sites of tumor , the sensitivity of MR imaging was highest ( 81 % ) compared with CT ( 51 % , P < .001 ) and immunoscintigraphy ( 50 % , P < .01 ) . The combination of MR imaging and immunoscintigraphy depicted 89 % of sites of tumor involvement confirmed at laparotomy . CONCLUSION MR imaging and immunoscintigraphy show promise for the evaluation of patients with ovarian cancer The aim of this study was to compare the prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography ( FDG PET ) with that of second-look laparotomy ( SLL ) in patients with advanced ovarian carcinoma following primary chemotherapy . Fifty-five patients who had undergone cytoreductive surgery and adjuvant chemotherapy for advanced ovarian carcinoma were enrolled in the study . Thirty patients underwent SLL after primary treatment ( SLL group ) , while 25 underwent FDG PET after primary treatment without SLL ( PET group ) . We retrospectively review ed the medical records of the 55 patients for comparison of progression-free interval and disease-free interval between the two groups . Ovarian carcinomas recurred in 37 of the 55 patients . When the progression-free interval and the disease-free interval in patients in the PET group were compared with those in the SLL group , no significant differences were observed . The progression-free interval in the PET and SLL groups were 28.8±12.7 months and 30.6±13.7 months , respectively ( P=0.29 ) . The disease-free interval in the negative PET group was 40.5±11.6 months , and that in the negative SLL group was 48.6±12.1 months ( P=0.12 ) . In conclusion , FDG PET has a similar prognostic value to SLL , and can substitute for SLL in the follow-up of patients who have had ovarian carcinoma , especially when there is a high risk for recurrence OBJECTIVE Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer . This prospect i ve study was undertaken to evaluate the clinical contribution of positron emission tomography ( PET ) using (18)F-fluorodeoxyglucose ( FDG ) for recurrent ovarian cancer . SUBJECTS AND METHODS Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study . Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements ( group A ) . Clinical findings for the remaining 12 women showed them to be disease-free ( group B ) . PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up . The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment . RESULTS PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging , and treatment was affected in five patients . On the other h and , in group B , additional information was obtained in only three of 12 patients , and treatment of only one patient was affected . Overall sensitivity , specificity , and accuracy of conventional imaging modalities were 72.7 % , 75.0 % , and 73.3 % , respectively , and these rates improved to 92.3 % , 100.0 % , and 94.4 % , respectively , by considering both conventional imaging modalities and PET findings . CONCLUSION Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer , especially patients believed to be at risk for recurrence PURPOSE To assess magnetic resonance ( MR ) imaging in depiction of ovarian tumor recurrence and for identification of patients who may not benefit from surgical reexploration . MATERIAL S AND METHODS In a prospect i ve study , 34 patients ( mean age , 57.07 years ) with surgically staged ovarian cancer underwent MR imaging before reexploration . Findings at MR imaging and surgery were correlated . MR imaging tumor depiction was correlated with tumor size , presence of ascites , and CA-125 levels . RESULTS Tumor recurrence was identified in 29 patients at surgery . MR imaging depicted tumor in 20 patients . Accuracy for lesions smaller than 2 cm was 35 % and increased to 82 % for lesions larger than 2 cm ( P < .01 ) . MR imaging had low sensitivity for depiction of implants in the peritoneum and mesentery . Ascites improved depiction of smaller lesions ( < 2 cm ) . MR imaging in combination with CA-125 levels improved detection of recurrent disease ( CA-125 measurement alone 53 % vs CA-125 measurement and MR imaging 75 % , P = .048 ) . CONCLUSION MR imaging is a useful adjunct to the clinical examination to identify patients with recurrent disease and those in whom reexploration may not be beneficial Purpose To evaluate the accuracy of integrated positron emission tomography ( PET ) and computed tomography ( CT ) for depiction of suspected recurrent ovarian carcinoma after treatment , with use of clinical or histological findings as the reference st and ard . Methods Seventy-seven women ( median age , 51 years ) with ovarian carcinoma treated with primary cytoreductive surgery followed by platinum-based combination chemotherapy were included , and [18F]fluorodeoxyglucose ( FDG ) PET/CT was performed for suspected recurrence . In all patients , imaging findings were compared with results of histological examination after surgical exploration or clinical follow-up to determine the diagnostic accuracy of PET/CT in the evaluation of disease status . Fisher ’s exact test was used to measure the ability of PET/CT to predict recurrent lesions . Results Forty-five ( 58.4 % ) of the 77 patients had documented recurrence during surgical exploration or clinical follow-up , while 32 ( 41.6 % ) had no evidence of recurrent tumour . Of the 45 patients with recurrent disease , 27 ( 60 % ) were confirmed to have recurrence by surgical biopsy . A correlation was found between PET/CT and histological or clinical analyses ( κ = 0.894 ) . The overall sensitivity , specificity , accuracy , positive predictive value and negative predictive value of PET/CT were 93.3 % , 96.9 % , 94.8 % , 97.7 % and 91.2 % , respectively . PET/CT modified the diagnostic or treatment plan in 19 ( 24.7 % ) patients , by leading to the use of previously unplanned therapeutic procedures in 11 ( 57.9 % ) patients and the avoidance of previously planned diagnostic procedures in eight ( 42.1 % ) patients . Conclusion Integrated FDG PET/CT is a sensitive post-therapy surveillance modality for the detection of recurrent ovarian cancer ; it aids decisions on treatment plans and may ultimately have a favourable impact on prognosis Background Recurrent ovarian cancer is refractory and resistant to treatment in most patients , and no effective treatment for it has been established . Starting a treatment when tumors still consist of micro foci may contribute to improvement of prognosis . Therefore , the early diagnosis of relapse is important . Methods Among patients with epithelial ovarian cancer in whom initial treatment achieved remission between April 1998 and December 2003 , those patients in whom the cancer-related antigen (CA)125 level was increased during the subsequent follow-up period , or those who showed abnormal computed tomography (CT)/magnetic resonance imaging ( MRI ) findings despite normal CA125 levels , were examined by 18F-fluoro-2-deoxyglucose – positron emission tomography ( FDG-PET ) . We compared the rates of accurate diagnosis of recurrence achieved using CT/MRI , CA125 , and FDG-PET in patients with a definitive diagnosis of relapse . Results We investigated 29 patients with epithelial ovarian cancer . The sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and accuracy of FDG-PET were 84.6 % ( 22/26 ) , 100 % ( 3/3 ) , 100 % ( 22/22 ) , 42.9 % ( 3/7 ) , and 86.2 % ( 25/29 ) , respectively . These values were higher than the corresponding values obtained using CT/MRI or CA125 levels . Conclusion FDG-PET may be very useful for identifying sites of recurrent ovarian cancer , although this procedure had a low NPV because of the high rate of false-negative findings for micro or cystic lesions PURPOSE To prospect ively evaluate the accuracy of integrated positron emission tomography ( PET ) and computed tomography ( CT ) for depiction of persistent ovarian carcinoma after first-line treatment , with use of histologic findings as the reference st and ard . MATERIAL S AND METHODS Thirty-one women ( mean age , 55.9 years ) with ovarian carcinoma treated with primary cytoreductive surgery and followed up with platinum regimen chemotherapy were included . All 31 patients were scheduled for surgical second-look . Before surgical second-look , all patients underwent fluorodeoxyglucose ( FDG ) PET/CT . At PET/CT , three main categories of persistent disease were considered for data analysis : lymph nodal lesion , peritoneal lesion , and pelvic lesion . In all patients , imaging findings were compared with results of histologic examination after surgical second-look to determine the diagnostic accuracy of PET/CT in the evaluation of disease status . The kappa statistic ( Cohen kappa ) was used for statistical analysis . RESULTS Seventeen ( 55 % ) of 31 patients had persistent tumor at histologic analysis after surgical second-look , and fourteen ( 45 % ) had no histologically proved tumor . The total number of lesions that was positive for tumor cells at histologic analysis was 41 ( lymph nodes , n = 16 ; peritoneal lesions , n = 21 ; pelvic lesions , n = 4 ) ; maximum diameter of these lesions was 0.3 - 3.2 cm ( mean , 1.7 cm ) . A correlation was found between PET/CT and histologic analysis ( kappa = 0.48 ) . The overall lesion-based sensitivity , specificity , accuracy , positive predictive value , and negative predictive value of PET/CT were 78 % , 75 % , 77 % , 89 % and 57 % , respectively . In the detection of a tumor , a size threshold could be set at 0.5 cm , as this was the largest diameter of a lesion missed at PET/CT . CONCLUSION Integrated PET/CT depicts persistent ovarian carcinoma with a high positive predictive value BACKGROUND Borderline ovarian tumors often affect women of childbearing age and the prognosis is outst and ing . Given the young age of several patients and the good prognosis , fertility-sparing surgery is considered adequate for stage I tumors . However , women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique . METHODS From 1981 to 1997 , 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospect ively . After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter . Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor . RESULTS With a median follow-up of 71 , months 28 women treated with fertility-sparing surgery ( 28/164 = 17 % ) had either recurrence of borderline tumor ( 23 ) or recurrence with carcinoma . Complete details of follow-up procedures are available for 24 women and they represent the study population . An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor . One patient had diagnosis due to persistent free fluid . All five women with invasive carcinoma had diagnosis of a complex adnexal mass . Gynecologic examination was suspicious ( palpable mass ) in 7 cases and obviously abnormal ( large mass or nodules ) in another 7 . CA 125 serum levels were elevated in 8 cases . CONCLUSION Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor PURPOSE To evaluate whether gadolinium-enhanced magnetic resonance ( MR ) imaging can demonstrate clinical ly occult tumors in women with treated ovarian cancer and to compare the diagnostic accuracy of MR imaging , serum CA-125 ( ovarian cancer antigen ) level , and physical examination . MATERIAL S AND METHODS From 1992 to 1997 , a longitudinal study comparing MR imaging findings , CA-125 values , and physical examination results with eventual clinical outcome in 69 women with treated ovarian cancer was performed . Tumor presence was determined with surgery , by an elevated CA-125 value , or with follow-up of patients longitudinally to assess for tumor recurrence . Absence of tumor was accepted with a disease-free interval of at least 2 years . RESULTS Twenty-three of 39 patients in clinical remission with a normal CA-125 level and physical examination result had sub clinical tumor proved at laparotomy or clinical follow-up . Gadolinium-enhanced MR imaging correctly demonstrated residual tumor in 20 of 23 patients . In all 69 patients , MR images had a 91 % sensitivity , 87 % specificity , 90 % accuracy , and 72 % negative predictive value and were superior to serum CA-125 level ( 53 % , 94 % , 63 % , and 38 % , respectively ) ( P < .001 ) and physical examination ( 26 % , 94 % , 43 % , and 29 % , respectively ) ( P < .001 ) in the depiction of residual tumor . CONCLUSION Gadolinium-enhanced MR imaging is a valuable clinical tool in patients with ovarian cancer . An abnormal MR examination with a normal CA-125 value is a strong indication of residual or recurrent tumor OBJECTIVES To evaluate the impact of PET/CT on the restaging and management of recurrent ovarian cancer . METHODS From January 2002 to July 2003 , all women undergoing either surveillance or investigation of possible recurrent ovarian cancer at the Centre for Molecular Imaging , The Peter MacCallum Cancer Centre , were invited to take part in a prospect i ve evaluation of the clinical impact of PET/CT . RESULTS Fifty-six women having 66 scans were available for analysis . All patients had at least 12months follow-up after the PET/CT unless they died before that time . Apart from one equivocal scan , all scans performed in women with a CA125 higher than 35IU/ml had a positive PET/CT . PET/CT altered the known disease distribution in 40 scans ( 64 % ) . Overall , PET/CT showed less disease in six scans ( 9 % ) and more disease in 34 scans ( 52 % ) . Regardless of the value of CA125 , PET/CT identified a sub group of women with apparently localized disease or no definite evidence of disease . This group showed improved survival compared with women shown to have systemic disease . PET/CT result ed in a major change of management plan in 34 patients ( 58 % ) . CONCLUSION PET/CT modifies the assessment of the distribution of recurrent ovarian cancer and alters patient management in a substantial proportion of patients . PET/CT appears to offer prognostic information Reports which analyzed the effects of secondary cytoreductive surgery at second-look laparotomy have often included small numbers of patients who have been treated with a variety of first-line chemotherapy regimens and those who may have progressed on first-line therapy . The purpose of this study was to analyze survival following secondary cytoreductive surgery at second-look laparotomy in patients with advanced ovarian cancer . Review of the surgical data of 153 patients allowed classification of tumor size found at second-look laparotomy and tumor size remaining after cytoreduction . Multivariate analysis evaluated multiple risk factors for survival . Of 153 patients , 124 had macroscopic tumor at second-look laparotomy and 29 had microscopic disease only . Fifteen of 69 ( 22 % ) patients were found to have tumor > 1 cm in diameter and were cytoreduced to microscopic residual and 18/69 ( 26 % ) were left with 1 cm tumor . Twenty-one of 55 ( 38 % ) patients with < or = 1 cm tumor were debulked to microscopic residual . The shortest survival relative to patients found to have microscopic disease at second-look laparotomy was observed among patients whose maximum tumor size remained > 1 cm following second-look laparotomy ( relative risk = 3.1 , P = 0.0004 ) . No difference in survival was seen between patients found to have microscopic disease and those cytoreduced to microscopic disease ( P = 0.24 ) . The risk of death was lower among patients debulked to a lower category ( < or = 1 cm debulked to microscopic , relative risk = 0.48 , P = 0.02 ; > 1 cm reduced to < or = 1 cm , relative risk = 0.49 , P = 0.02 ; > 1 cm reduced to microscopic , relative risk = 0.44 , P = 0.01 ) . Whether this apparent beneficial effect of cytoreductive surgery at second-look laparotomy reflects the biology of the tumor which allows surgical cytoreduction or the effects of cytoreduction can only be addressed in a r and omized prospect i ve trial Abstract . This study was design ed to assess the value of whole-body positron emission tomography ( PET ) using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ( FDG ) for the diagnosis of recurrent ovarian cancer . Twenty-five patients who had previously undergone surgery for ovarian cancer were imaged using whole-body FDG-PET . During the 4 weeks preceding the PET study , conventional imaging , comprising computed tomography ( CT ) and magnetic resonance ( MR ) imaging of the abdomen and /or pelvis , was performed and serum CA125 levels were measured . PET imaging was commenced at 60 min after the intravenous administration of FDG in all patients . PET results were compared with the results of conventional imaging and CA125 levels , and related to pathological findings and clinical follow-up for more than 6 months . FDG-PET showed a sensitivity of 80 % ( 16/20 ) , a specificity of 100 % ( 5/5 ) and an accuracy of 84 % accuracy ( 21/25 ) for the diagnosis of recurrent ovarian cancer . The sensitivity , specificity and accuracy of conventional imaging were 55 % ( 11/20 ) , 100 % ( 5/5 ) and 64 % ( 16/25 ) , respectively . PET could detect recurrent lesions in seven of nine patients in whom conventional imaging was falsely normal , while conventional imaging was true positive in two of four patients with false-negative PET results . The CA125 results showed a sensitivity of 75 % ( 15/20 ) , a specificity of 100 % ( 5/5 ) and an accuracy of 80 % accuracy ( 20/25 ) . Among the 15 patients with true-positive CA125 results , PET correctly detected abnormal foci of recurrence in 13 patients ( 86.7 % ) whereas conventional imaging showed recurrent lesions in only eight patients ( 53.3 % ) . In conclusion , our preliminary study demonstrates that FDG-PET may be accurate and useful for the detection of tumour recurrence when conventional imaging is inconclusive or negative , especially in patients with abnormal CA125 levels AIM To determine the additional value of [(18)F]FDG-PET in combination with computed tomography ( CT ) over CT used alone , for evaluating ovarian cancer patients after primary treatment . METHODS Twenty-five women ( mean age : 53.6 years ) had primary debulking surgery followed by chemotherapy for histologically proven ovarian carcinoma . At initial diagnosis , the tumor types were papillary serous adenocarcinoma ( n=20 ) , endometroid carcinoma ( n=3 ) , mixed mullerian tumor ( n=1 ) , and granulosa cell tumor ( n=1 ) . All patients underwent [(18)F]FDG-PET and contrast enhanced CT examinations , within 30 days of the completion of chemotherapic treatment . [(18)F]FDG-PET images were interpreted with the knowledge of CT findings ( PET+CT ) ; conversely , CT images were evaluated with no knowledge of the [(18)F]FDG-PET results . Within 7 day of imaging studies , 2(nd)-look laparoscopy ( n=7 ) or laparotomy ( n=18 ) was performed for histological confirmation . In all cases , imaging findings were then correlated with results of histopathologic examination . RESULTS Of the 23 neoplastic viable lesions , all histologically confirmed , 16 could be detected by CT alone and 19 by PET+CT . An inflammatory lymph-node was misdiagnosed as viable tumor with both PET+CT and CT alone ; an area of scar tissue in the presacral region was also misinterpreted as malignant tissue with CT alone . Overall lesion-based sensitivity , specificity and accuracy in assessing focal areas of residual tumor were as follows : 69.56 % , 83.33 % , 74.28 % for CT , and 82.60 % , 91.67 % , 85.71 % for PET+CT . The negative predictive value of PET+CT was markedly higher ( 73.33 % ) , compared to that of CT alone ( 58.82 % ) . CONCLUSION PET used in combination with CT allows to accurately assess tumor response . A major advantage of PET+CT over CT alone is in excluding the presence of residual viable lesions after treatment Abstract . The aim of this study was to compare prospect ively the accuracy of whole-body positron emission tomography ( PET ) , CT and MRI in diagnosing primary and recurrent ovarian cancer . Nineteen patients ( age range 23–76 years ) were recruited with suspicious ovarian lesions at presentation ( n = 8) or follow-up for recurrence ( n = 11 ) . All patients were scheduled for laparotomy and histological confirmation . Whole-body PET with FDG , contrast-enhanced spiral CT of the abdomen , including the pelvis , and MRI of the entire abdomen were performed . Each imaging study was evaluated separately . Imaging findings were correlated with histopathological diagnosis . The sensitivity , specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions ( n = 7 ) were , respectively : 100 , 67 and 86 % for PET ; 100 , 67 and 86 % for CT ; and 100 , 100 and 100 % for MRI . For the diagnosis of recurrent disease ( n = 10 ) , PET had a sensitivity of 100 % , specificity of 50 % and accuracy of 90 % . The PET technique was the only technique which correctly identified a single transverse colon metastasis . Results for CT were 40 , 50 and 43 % , and for MRI 86 , 100 and 89 % , respectively . No statistically significant difference was seen . Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease . No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease ; thus , the methods are permissible alternatives . The PET technique , however , has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI Objective The aim of this prospect i ve study was to evaluate the accuracy of clinical examinations ( palpation/determination of serum tumor-associated antigen CA125 level ) , CT , and MRI in the detection of tumor recurrence in patients with treated ovarian cancer . Material s and Methods Twenty-four patients who had been treated for ovarian carcinoma were prospect ively examined by clinical means ( palpation/serum tumor-associated antigen CA125 level ) , CT , and MRI to assess their accuracy in detecting recurrent disease ; results were correlated with surgical/bioptic/pathoanatomic findings . Nine patients had relapse ; 15 women were disease-free . Results Examinations were true-negative in 14 patients ( on palpation/CA125 , CT , and MRI ) and true-positive in 9 on palpation/CA125 , in 6 on CT , and in 7 patients on MRI . False-positive examinations occurred in one patient on palpation/CA125 , CT , and MRI and false-negative in zero on palpation/CA125 , in three on CT , and in two on MRI , a sensitivity of 100 % for palpation/CA125 , 66.6 % for CT , and 77.7 % for MRI and a specificity of 93.3 % for palpation/CA125 , CT , and MRI . Accuracy of palpation/CA125 examinations was 95.8 % in comparison with 83.3 % for CT and 87.5 % for MRI . Conclusion Our results suggest that in the follow-up of ovarian cancer patients , assessment of serum tumor-associated antigen CA125 level is accurate in the determination of patients with tumor recurrence . Computed tomography is the primary imaging modality to prove macroscopic disease recurrence and can spare these patients from invasive restaging second-look laparotomy ; MRI should be performed in women with question able macroscopic recurrent tumor and negative CT examination . Neither CT nor MRI can confidently exclude microscopic disease This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests . This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures ( the conversions of these clinical questions into appropriate research design s ) used to answer them . As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide ( BNP ) in the diagnosis of left ventricular dysfunction.1 R and omised controlled trials are dealt with elsewhere . As in other forms of clinical research , there are several different ways study ing the potential or real diagnostic value of a physical sign or laboratory test , and each is appropriate to one kind of question and inappropriate for others . Among the possible questions about the relation between a putative diagnostic test and a target disorder ( for example , the concentration of BNP and left ventricular dysfunction ) , four are most relevant . # # # # Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary , |
12,578 | 29,391,776 | Theophylline was not significantly different from other drugs in its effects on respiratory rate , forced vital capacity ( FVC ) , peak expiratory flow rate , admission rate , use of rescue medication , oxygen saturation , or symptom score .
Conclusion Given the low cost of theophylline , and its similar efficacy and rate of side effects compared with other drugs , we suggest that theophylline , when given with bronchodilators with or without steroids , is a cost-effective and safe choice for acute asthma exacerbations | Background and objective Theophylline has been used for decades to treat both acute and chronic asthma .
Despite its longevity in the practitioner 's formulary , no detailed meta- analysis has been performed to determine the conditions , including concomitant medications , under which theophylline should be used for acute exacerbations of asthma .
We aim ed to quantify the usefulness and side effects of theophylline with or without ethylene diamine ( aminophylline ) in acute asthma , with particular emphasis on patient subgroups , such as children , adults , and concomitant medications . | Our investigation supports the use of intravenous salbutamol as an alternative to aminophylline in the early stages of acute severe asthma . Salbutamol proved to be a marginally better bronchodilator and is likely to cause less gastrointestinal side effects than aminophylline , but tachycardia and generalized tremor are more frequent with this drug The role of bronchodilator regimens combining a sympathomimetic and a methylxanthine in the treatment of acute exacerbations of asthma remains controversial . This report describes the outcome of 157 emergency room visits for asthma in which patients were r and omly assigned to single-drug therapy with intravenous aminophylline , subcutaneous epinephrine , or inhaled isoproterenol or to one of three regimens combining a sympathomimetic and a methylxanthine . The increase in one-second forced expiratory volume after one hour of treatment with the two-drug combinations ( 0.79 + /- 0.07 liter ) was significantly greater than for epinephrine alone ( 0.57 + /- 0.08 liter ; p less than 0.05 ) but did not differ significantly from that occurring with therapy with isoproterenol alone ( 0.72 + /- 0.09 liter ; p = NS ) . This disparity reflects the greater bronchodilation effected by isoproterenol as a single agent than by epinephrine , in the dosing schedules and routes of administration chosen . Among patients presenting with severe airflow obstruction ( one-second forced expiratory volume 35 percent or less of normal ) , the bronchodilator response to isoproterenol alone was 0.88 + /- 0.14 liter versus 0.51 + /- 0.11 for epinephrine alone ( p less than 0.05 ) . It is concluded that the observed benefit derived from use of combination therapy depends on the dosage and potency of the particular sympathomimetic to which a methylxanthine is added , and on the severity of the airflow obstruction at presentation In patients with acute exacerbations of asthma , the intravenous administration of bronchodilators , such as salbutamol , entails the potential risk of worsening pulmonary gas exchange , despite an amelioration of airflow obstruction . The present study was design ed to investigate the effect of intravenous aminophylline on pulmonary gas exchange in patients hospitalized with a severe exacerbation of asthma . We studied 12 patients ( aged 41 + /- 13 yrs ) admitted to the hospital because of an exacerbation of asthma . The study was of a r and omized , double-blind , placebo-controlled design . Six patients were treated with intravenous aminophylline and six received placebo , in addition to st and ard treatment with inhaled salbutamol and intravenous corticosteroids . Forced spirometry , respiratory gas exchange , ventilation-perfusion relationships assessed with the multiple inert gas elimination technique , and systemic haemodynamics were measured at baseline and 60 min after treatment started . In the aminophylline-treated group , mean theophylline plasma levels increased to 15.2 + /- 3.6 micrograms.ml-1 , forced expiratory volume ( FEV1 ) increased by 17 + /- 12 % , and forced vital capacity ( FVC ) by 16 + /- 10 % . The mean changes in FEV1 and FVC in the aminophylline-treated group were significantly higher than in the placebo-treated group . Likewise , minute ventilation increased by 23 + /- 14 % and arterial carbon dioxide tension ( PaCO2 ) decreased by 0.4 + /- 0.3 kPa ( 3 + /- 2 mmHg ) during aminophylline infusion . No significant changes in arterial oxygen tension ( PaO2 ) or in ventilation-perfusion distributions were shown in aminophylline-treated patients . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The role of aminophylline ( ethylene diamine salt of theophylline ) in the treatment of acute exacerbation of asthma has not been well established in children . OBJECTIVE The aim of the study was to determine the additional therapeutic benefit of intravenous aminophylline in the treatment of children hospitalized for acute asthmatic exacerbation and treated with inhaled bronchodilators and glucocorticoid therapy . METHODS Thirty-eight children aged from 2 to 16 years ( mean age 5.64 + /- 3.31 ) , admitted for acute exacerbation of asthma , participated in a prospect i ve , r and omized , double-blind , placebo-controlled study . All the subjects received methylprednisolone , administered intravenously , and nebulized salbutamol . The treatment group received intravenous aminophylline therapy and the placebo group received 0.9 % saline solution for 24 hours . RESULTS The number of salbutamol nebulizations needed and the clinical asthma scoring were recorded both at onset and at the end of 24 hours . There was no significant difference in either the mean number of nebulizations or the clinical asthma scores between the two groups ( P = .7843 , P = .8452 ) . CONCLUSION Intravenous aminophylline ( ethylene diamine salt of theophylline ) demonstrated no additional beneficial effect to the combination of beta adrenergic agonists and glucocorticoid treatment in acute asthma attack in children Twenty-one patients admitted to hospital with acute severe asthma were allocated in a r and om , single-blind manner to receive intravenous infusions for 24 hours or either aminophylline or salbutamol or a combination of the two drugs . Infusions were administered by a slow infusion pump with an initial loading dose given over 15 minutes , followed by a continuous lower dose of the drug 24 hours as follows : 1 . Aminophylline 0.285 mg/kg/min for 15 min followed by 0.014 mg/kg/min ( 20 mg/min . followed by 1 mg/min for a 70 kg subject ) . 2 . Salbutamol 0.285 microgram/kg/min for 15 min followed by 0.057 microgram/kg/min ( 20 microgram/min followed by 4 microgram/min for a 70 kg subject ) . 3 . Combined regimen of the above infusions . In addition each patient received intravenous hydrocortisone ( 4 g ) and potassium chloride ( 4 g ) in 2 litres of 5 % dextrose infused over 24 hours amd 35 % oxygen given via a Ventimask . Peak expiratory flow rates showed a significant improvement after 15 minutes treatment with aminophylline and the combined infusion , but this was not seen until 60 minutes with the salbutamol infusion . No synergistic bronchodilator effect was seen with the combined infusion . The results show that intravenous aminophylline is superior to intravenous salbutamol in the doses given in the initial treatment of acute asthma and that the combination when given intravenously is not better than aminophylline alone BACKGROUND The purpose of this study was to test the contribution of aminophylline in improving peak expiratory flow rate ( PEFR ) during emergency department treatment of acute asthma when metaproterenol sulfate and steroid therapy are also provided . METHODS In a prospect i ve , r and omized , double-blind , and placebo-controlled trial at a municipal hospital emergency department , 44 patients with acute asthma , aged 18 to 45 years , with theophylline levels below 28 mumol/L , who had failed to achieve a PEFR of 40 % predicted after one nebulized metaproterenol treatment , were recruited . An aminophylline or placebo loading dose and maintenance infusion were administered . All patients received hourly nebulized metaproterenol and initial methylprednisolone sodium succinate . The PEFR was measured hourly for 5 hours . Two-factor repeated- measures analysis of variance of improvement in PEFR ( [ final-initial PEFR]/predicted PEFR ) was assessed . RESULTS There was no difference in improvement of PEFR at any hour between the treatment and placebo groups . After 5 hours , the difference in improvement ratio was 0.40 ( aminophylline ) vs 0.36 ( placebo ) ( P = .30 ; n = 22 in each group ) . The treatment group suffered more tremor , nausea or vomiting , and palpitations ( P < .05 ) . CONCLUSION In the emergency department setting , aminophylline contributes no significant improvement in PEFR when beta 2-agonists and corticosteroids are being provided , while causing more side effects Acute , severe exacerbations of asthma present a challenge due to the significant morbidity associated with this presentation . For exacerbations that are refractory to initial treatments with inhaled and oral therapies , there is still doubt about which intravenous therapies are most likely to be helpful . β-2 agonists and aminophylline have differing mechanisms of action that also affect their adverse effects profiles and these are considered . A review of the available r and omised control trials suggests that a bolus of intravenous salbutamol may reduce symptoms and hasten recovery . Aminophylline infusions may improve lung function , and in some studies have been shown to improve symptoms , but the evidence is not clear cut . Decisions about which treatment to use should include risk management considerations such as ease of prescription , preparation and administration factors and availability of high-dependency beds 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 : There is a lack of consensus regarding second-line therapy in children with acute asthma who fail to the st and ard therapy . Ketamine had bronchodilator property and may be useful in the treatment of acute asthma . Objective : The objective of this study was to evaluate the efficacy and safety of ketamine as compared to aminophylline in children with acute asthma who respond poorly to the st and ard therapy . Methods : This r and omized controlled trial included patients with acute asthma having Pediatric Respiratory Assessment Measure ( PRAM ) score ≥5 at 2 h of st and ard therapy . The enrolled patients received either intravenous ( IV ) ketamine or IV aminophylline . Primary outcome measure was change in PRAM score at the end of intervention . Secondary outcome measures included adverse effects , change in PO2 and PCO2 , need for mechanical ventilation , and duration of hospital stay . Results : The trial included 24 patients each in ketamine and aminophylline groups . The baseline parameters were similar between the groups . The primary outcome was similar in both the groups with a change in PRAM score of 4.00 ± 1.25 and 4.17 ± 1.68 ( P = 0.699 ) in ketamine and aminophylline groups , respectively . The secondary outcomes were not different between the groups . Conclusion : Ketamine and aminophylline were equally effective for children with acute asthma who responded poorly to the st and ard therapy Severe asthma is the most common respiratory emergency treated in casualty departments of most hospitals . Intravenous aminophylline has been the mainstay of bronchodilator treatment for several years , although sudden death may occur after rapid administration,1 2 and it may be cardiotoxic.3 We thought that a selective adrenoceptor agonist might therefore be worthy of trial , and we report here our results with single and double-blind comparative trials of intravenous aminophylline and salbutamol on 50 patients with severe asthma Thirty-seven patients with severe asthma were r and omized into three groups and treated double-blindly with either aminophylline , epinephrine , or a combination of these two for one hour and then with both drugs for an additional hour . All patients began with plasma theophylline levels less than 10 µg/ml and all achieved 17 µg/ml . Epinephrine produced 134 % improvement in FEV1 in one hour compared to 38 % improvement produced by aminophylline . Epinephrine and combination therapy produced the same amount of bronchodilatation in one hour . Patients whose initial PEFR was ≦100 l/min failed to improve with aminophylline alone . After two hours of treatment , there was no difference in FEV1 or PEFR among the three groups . Arrhythmias and vomiting occurred more frequently when aminophylline was used and these adverse responses did not correlate with plasma theophylline levels STUDY OBJECTIVE To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma . DESIGN R and omized , double-blind , placebo-controlled trial throughout the study . SETTING University Hospital Clinical Research Center . PATIENTS Forty-four patients admitted from the emergency room with a primary diagnosis asthma ; 39 patients completed the study . INTERVENTIONS Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol ; prednisone 0.5 mg/kg body weight every 6 h orally ; and supplemental oxygen . Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml . Changes were made in placebo infusion rates to maintain the double blind design . MEASUREMENTS AND RESULTS Forced expiratory volume in 1 s ( FEV1 ) and other spirometric measurements every 8 h by a blinded investigator or trained respiratory therapist . Subjective patient response and duration of hospitalization were compared . No difference in spirometric measurements was observed between the two groups at any time point . On admission to the study , FEV1 in the placebo group was 41.5 ( + /- 2.9 ) percent predicted and in the aminophylline group 34.7 ( + /- 2.3 ) percent predicted ( p = 0.08 ) . At discharge , FEV1 was 70.4 ( + /- 2.9 ) percent predicted in the placebo group and 63.7 ( + /- 2.8 ) percent predicted in the theophylline group ( p = 0.10 ) . There was no difference in subjective patient rating or duration of hospitalization between the two groups ( placebo 1.95 days and aminophylline 1.78 days , p = 0.51 ) . CONCLUSIONS Our results suggest that aminophylline therapy does not add significant benefit to other st and ard therapies in hospitalized adult asthmatic patients . Because of the risks and cost of aminophylline treatment in the hospital setting , further research is needed to determine if there are subgroups of adult asthmatics who may benefit from the addition of aminophylline to other st and ard optimal therapies Forty-eight patients who presented with acute episodes of asthma were r and omized to treatment with subcutaneously administered epinephrine , inhaled isoproterenol , or intravenously administered aminophylline . The patients ' couses were followed clinical ly and with spirometry . Although there were no significant differences between the groups before treatment for any measured variable , at the end of 1 hour , the mean improvement inforced expiratory volume in one second ( FEV1 ) was significantly greater for patients treated with epinephrine ( 0.76 L ) or nebulized isoproterenol ( 0.79 L ) than for those given aminophylline ( 0.23 L ) . Similarly , the mean duration of therapy required before discharge from the emergency room was significantly longer for patients receiving aminophylline ( 5.4 h ) than for patients treated with either epinephrine ( 3.5 h ) or isisoproeternol ( 3.0 h ) . There was no significant differences between the effects of the 2 beta agonists . These results demonstrated that short-acting sympathomimtic agents produce more rapid and potent bronchodilatation in acutely ill asthmatics than that provided by intravenously administered methylxanthines , and that there are no disadvantages to using an inhaled beta agonist rather than one administered parenterally OBJECTIVE To evaluate the effects of aminophylline ( Am ) in children hospitalized with asthma . METHODS Prospect i ve , r and omized , double-blind , placebo-controlled trial . Subjects were children between the ages of 5 and 18 years admitted for asthma exacerbation to either a tertiary care children 's hospital or an inner-city general hospital in New York . Exclusion criteria were admission to the intensive care unit , initial theophylline level > 5 micrograms/dL , or the presence of other systemic disorders . All patients received nebulized albuterol therapy and intravenous glucocorticosteroids in st and ardized doses . Thirty-one patients were r and omized to receive either an Am bolus followed by continuous Am infusion or placebo ( P ) bolus and infusion . The outcome variables were : duration of hospitalization , percent of predicted peak expiratory flow rates recorded at 12-hour intervals , number of albuterol treatments required , and adverse effects . RESULTS There were no significant differences at study entry in age , sex , race , number of previous hospital admissions , prior medications used , clinical symptom scores , or initial peak flow rates for the two groups . For 26 patients who completed this study , 15 patients in the P group were hospitalized for a mean duration of 2.33 + /- 1.3 days , whereas 11 patients in the Am group required 2.58 + /- 1.5 days . There were no significant differences between the two groups for hospital days , peak flow rates at any time interval , or amount of albuterol therapy required ( P > .2 ) . In the Am group , 6 of the 14 patients who entered the study experienced significant adverse effects consisting of nausea , emesis , headache , abdominal pain , and palpitations . Only 1 of 17 patients in the P group had an adverse effect ( P < .05 ) . CONCLUSIONS There is no benefit and considerable risk of adverse effects associated with the use of Am in hospitalized asthmatic children OBJECTIVES To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol , inhaled ipratropium , and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously . STUDY DESIGN R and omised , double blind , placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol . RESULTS The placebo and treatment groups of children were similar at baseline . The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours . Five subjects in the placebo group were intubated and ventilated after enrolment compared with none in the aminophylline group . CONCLUSIONS Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment PURPOSE To determine whether intravenously administered theophylline , when added to frequently nebulized albuterol and intravenously administered methylprednisolone , benefits children hospitalized with severe asthma . DESIGN Prospect i ve , r and omized , placebo-controlled , parallel-group , double-blind study . SETTING Inpatient pediatric service at a tertiary-care teaching hospital . PATIENTS Twenty-one children 5 to 18 years of age . INTERVENTIONS All patients received 2.5 to 5.0 mg of nebulized albuterol every 20 minutes to every 6 hours , intravenously administered methylprednisolone ( 1 mg/kg every 6 hours ) , and either intravenously administered theophylline ( as aminophylline ) or placebo for 36 hours . Serum theophylline concentrations were maintained between 55 and 110 mumol/L ( between 10 and 20 micrograms/ml ) by adjusting loading doses and continuous infusion rates . MEASUREMENTS AND MAIN RESULTS Forced expired volume in 1 second ( FEV1 ) and clinical score were measured at 0 , 1 , 3 , 6 , 12 , 24 , and 36 hours after the start of each individual study . The total number of nebulizations , total albuterol dosage , adverse effects , and duration of hospital stay were recorded . Twelve children received theophylline and nine received placebo . The two groups did not differ significantly in age , sex , or baseline FEV1 . In both groups , clinical score significantly improved from baseline by 12 hours , and FEV1 by 24 hours ( p < 0.05 ) . There were no significant differences between the groups in FEV1 or clinical score at any of the measured time points . There were no significant differences in rate of improvement in FEV1 , total number of nebulizations , total albuterol dosage , or duration of hospital stay . Adverse effects were mild and infrequent and did not differ significantly between the two groups . CONCLUSIONS Theophylline , at therapeutic concentrations , did not additionally benefit children hospitalized with severe asthma who were being treated frequently with nebulized albuterol and with methylprednisolone intravenously No uniform guidelines currently exist for the initial drug therapy of asthma or for the criteria to assess efficacy of initial therapy . A study with 71 subjects aged between 15 and 40 years was conducted to compare the usefulness of three commonly used asthma treatment regimes , viz subcutaneous adrenaline , nebulised salbutamol and intravenous aminophylline . Parameters used to monitor response were pulse rate ( PR ) , respiratory rate ( RR ) , Peak Expiratory Flow Rate ( PEFR ) and Patient 's Subjective Assessment Scale ( PSAS ) . All patients in the three treatment groups were comparable at pre-treatment , except for the Salbutamol group which appeared to have asthma of a milder severity based on PSAS scores alone . Following treatment , improvements were noted in Peak Flow Rate and PSAS . These improvements were greatest in those groups treated with salbutamol and adrenaline ( p = 0.04 for PEFR and 0.01 for PSAS ) . Salbutamol treated patients also had significant improvements in Respiratory Rate ( p < 0.05 ) . The results were not conclusive as to whether adrenaline or salbutamol was the superior drug . Salbutamol and adrenaline are preferred to aminophylline in the initial treatment of acute bronchial asthma In a r and omized double-blind trial an intravenous injection of salbutamol ( 100mug ) was compared with an intravenous injection of aminophylline ( 250 mg ) in 23 patients with acute exacerbations of asthma . Salbutamol ( 11 cases ) and aminophylline ( 12 ) produced a mean proportionate increase in FEV of 26 % and 23 % respectively . Blood gas pressures showed a trend to improvement with a mean rise in oxygen tension of 2 mm Hg(0 - 2kPa ) in the aminophylline group and of 6 mm Hg ( 0 - 8kPa ) in the salbutamol group . Electrocardiogram patterns also showed overall improvement , and mean decreases in pulse rate of 8 beats per minute and 2 beats per minute were noted in the aminophylline and salbutamol groups respectively . Differences in results did not reach conventional levels of significance and no serious side effects were noted . It was concluded that in the doses and routes of administration compared , salbutamol was as effective as aminophylline We conducted a r and omized , double-blind , placebo-controlled study to determine if intravenous aminophylline adds any benefit to high doses of inhaled salbutamol in patients who presented for treatment of acute asthma . We studied 94 patients ( mean age , 35.6 + /- 11.2 years ) with moderate to severe acute asthma . All patients received therapy with salbutamol delivered with metered-dose inhaler ( MDI ) into a spacer device ( Volumatic ) in four puffs ( 400 micrograms ) at 10-min interval , and intravenous hydrocortisone ( 500 mg ) . Patients were r and omly assigned to receive either a loading dose of intravenous aminophylline followed by a routine infusion ( n = 45 ) or an equal volume of placebo as a loading dose and infusion ( n = 49 ) . The two groups showed no differences in measurements of peak expiratory flow , FEV1 , and FVC at baseline and at the end of treatment . However , the patients treated with aminophylline had significantly more adverse effects ( p < 0.05 ) . There were no differences in the final mean dose of salbutamol ( 6.3 + /- 44.5 mg for the placebo group and 5.8 + /- 4.2 mg for the aminophylline group ) , hospital admission rate ( 10.2 percent for the placebo group and 9.0 percent for the aminophylline group ) , and mean duration of Emergency Department treatment ( 2.5 + /- 1.83 h for the placebo group and 2.37 + /- 1.75 h for the aminophylline group ) . The results were similar when the patients were divided in accord with the degree of respiratory obstruction ( baseline FEV1 < 30 percent of predicted ) and theophylline level at 30 min of treatment ( placebo group patients with theophylline level < 10 mg/L vs aminophylline group patients with theophylline level > or = 10 mg/L ) . We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled salbutamol in the treatment of acute exacerbations of asthma BACKGROUND --The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently . METHODS --In an open r and omised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol ( 5 mg/dose ) and aminophylline infusion ( 0.6 - 0.9 mg/kg/hour ) , or nebulised salbutamol alone . RESULTS --The responses to treatment as measured by peak expiratory flow ( PEF ) and the time taken to achieve maximum PEF were similar in both groups . Side effects were observed more commonly in patients receiving the combined treatment . CONCLUSIONS --Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline In a previous paper ( 9 ) the plasma concentration of three different theopylline derivatives was studied following parenteral , oral and rectal administration . In connection with these studies the authors made the present observations in patients with bronchial asthma on the effect on the pulmonary ventilation after intravenous administration of these derivatives . Comparable groups of patients were simultaneously studied after subcutaneously injected adrenaline , inhaled isoprenaline and for the comparison parenteral administration of a placebo . Further studies concerning the effects on the pulmonary circulation in patients with induced bronchial asthma after administration of adrenaline and theophylline-derivatives is to be published ( 7 ) OBJECTIVES Evaluate the efficacy of adding two intravenous bolus of aminophylline to the st and ard treatment of acute asthma episode in children admitted to the pediatric emergency room ( PER ) . METHODS Between March 2001 and February 2002 , 60 children ( 2 - 5 years old ) , admitted to the PER at Hospital de Clínicas de Porto Alegre ( Brazil ) , due to an episode of acute asthma , refractory to conventional therapy ( an oral dose of steroids and at least three doses of inhaled albuterol , associated or not with oxygen ) were enrolled in a r and omized , double blind , placebo controlled clinical trial . The r and omization was performed in blocks of 10 patients , who received a " bronchodilator solution " ( either saline or aminophylline ) , in two doses : on arrival at the PER and again 6h later . The intervention group received aminophylline 5mg/kg/dose diluted in normal saline ( NS ) solution up to a 20 mL volume , while the placebo group received plain NS , both in an infusion rate of 1 cc/min . The main outcomes were total length of hospital stay , length of supplemental oxygen use , number of bronchodilator nebulizations and /or aerosol inhalations performed and patient destination . The groups were compared using the Students t-test , Mann-Whitney test and Chi-Square test , accepting p<0.05 as significant . RESULTS Comparing the main outcomes , we did not find differences between the placebo and aminophylline groups : 29.0+/-14.7 versus 26.2+/-13.4 beta-agonist nebulizations per patient ( p=0.46 ) ; 2.4+/-10.6 versus 5.6+/-14.2 aerosol inhalations per patient ( p=0.32 ) ; 24.7+/-30.0 versus 26.0+/-25.2h for oxygen supplement ( p=0.86 ) ; 43.2+/-30.0 versus 43.6+/-23.7h for length of hospital stay ( p=0.95 ) . We also did not find differences between the two groups related to the blood pressure , heart rate , respiratory rate and oxygen saturation . CONCLUSION In children aged 2 - 5 years admitted to a PER with asthma , two intravenous doses of 5mg/kg of aminophylline given 6h apart did not change the length of stay in hospital , the number of nebulizations given or the duration of oxygen therapy required . We are unable to tell whether there would be benefit with higher doses of aminophylline design ed to give levels in the usual therapeutic range During a prospect i ve 10-week assessment period , 3238 children aged 1–16 years presented with acute wheeze to Paediatric Emergency Research in the UK and Irel and centres . 110 ( 3.3 % ) received intravenous bronchodilators . Intravenous magnesium sulfate ( MgSO4 ) was used in 67 ( 60.9 % ) , salbutamol in 61 ( 55.5 % ) and aminophylline in 52 ( 47.3 % ) of cases . In 35 cases ( 31.8 % ) , two drugs were used together , and in 18 cases ( 16.4 % ) , all three drugs were administered . When used sequentially the most common order was salbutamol , then MgSO4 , then aminophylline . Overall , 30 different intravenous treatment regimens were used varying in drugs , dose , rate and duration Intravenous theophylline ( aminophylline ) has been used for more than 50 years to treat acute exacerbations of asthma [ 1 ] . However , in the emergency department treatment of acute exacerbations of asthma , it has not been shown to be as effective as inhaled -agonists [ 2 ] and may increase minor adverse side effects when combined with -agonists [ 3 ] . Consequently , the National Heart , Lung , and Blood Institute ( NHLBI ) Expert Panel on the diagnosis and management of asthma has not recommended its routine use in the treatment of asthma in the emergency department [ 4 ] . In contrast , both the Expert Panel [ 4 ] and the British Thoracic Society [ 5 ] recommend the routine use of oral or intravenous theophylline in adults admitted to the hospital for acute exacerbation of asthma , despite the lack of controlled studies . Because theophylline has a narrow therapeutic index and its use can result in serious adverse effects when dosage is not carefully adjusted on the basis of serum concentration measurements [ 6 ] , its use can be justified only if a benefit is clear , especially since the advent of inhaled 2-selective agonists and the early use of high-dose corticosteroids [ 7 ] . Because the observation periods in two of the studies question ing aminophylline 's efficacy were 3 hours or less [ 2 , 3 ] , we postulated that the drug 's benefit may occur later in the course of therapy . Thus , the purpose of our study was to determine whether the addition of intravenous aminophylline ( during a 48-hour period ) improves pulmonary function faster than frequent nebulizations of albuterol and intravenous methylprednisolone alone . Methods Study Design and Patient Selection We did a r and omized , placebo-controlled , double-blind study in patients admitted to the medical service of a tertiary-care university teaching hospital . The study protocol was approved by the Institutional Review Board of the University of Florida , and each patient gave written informed consent . Eligible persons included adults 18 to 50 years old who were admitted to the hospital with an acute exacerbation of asthma by the emergency department physician . Each patient met the American Thoracic Society criteria for the diagnosis of asthma [ 8 ] and had failed to respond to three or more doses of inhaled albuterol ( with or without the addition of subcutaneous terbutaline ) and a loading dose of intravenous corticosteroids . Chest radiographs , arterial blood gas values , and serum theophylline concentrations measured by fluorescence polarization immunoassay ( Abbott TDx ; Abbott Diagnostics , Irving , Texas ) [ 9 ] were obtained from each patient . Entry into the study ( design ated as time 0 ) was identified by the first spirometric measurement done by the investigators ( after treatment in the emergency department and at hospital admission ) . Patients were excluded if they were unable to perform spirometry correctly or consistently ; were intubated ; were pregnant ; had a lower respiratory tract infection ( lobar consolidation or new pulmonary infiltrate on chest radiograph ) ; had a Pco 2 greater than 50 mm Hg after three consecutive nebulized albuterol treatments ; had chronic cardiopulmonary disease , chronic bronchitis , or emphysema ; or if the patient had a forced expiratory volume in 1 second ( FEV1 ) greater than 80 % of the predicted value at time zero . Interventions All patients received routine intravenous fluids ; supplemental oxygen to keep oxygen saturation greater than 92 % by pulse oximetry ; intravenous methylprednisolone , 125 mg , in the emergency department , followed by 60 mg every 6 hours ; nebulized albuterol treatments ; and either intravenous aminophylline or placebo . The dose and frequency of administration of as-needed albuterol nebulizations were titrated to clinical response , FEV1 , and adverse effects . The dose ( 2.5 or 5.0 mg ) was selected by the internal medicine housestaff based on their judgment of the adequacy of the clinical response , the occurrence of adverse effects on heart rate or blood pressure , or if tremor or headache was intolerable . The frequency of nebulizations was based on the last measured FEV1 . The following criteria for as-needed albuterol administration were used . If the FEV1 was less than 30 % ( of the predicted value ) , albuterol treatments were given every half hour . If FEV1 was 30 % to 50 % , treatment was given every 1 to 2 hours ( the choice between 1 and 2 hours was based on the physician 's assessment of the severity of symptoms and presence of adverse effects ) . If FEV1 was more than 50 % , albuterol was given every 4 hours . This individualization of albuterol administration is consistent with recommendations in the NHLBI Expert Panel Report [ 4 ] . Albuterol ( Proventil 5 % solution ; Schering Corporation , Kenilworth , New Jersey ) was diluted to a final volume of 4 mL with normal saline and delivered by a Whisper Jet h and -held nebulizer ( Marquest , Englewood , Colorado ) driven by 100 % oxygen at a flow rate of 8 L/min . Under these conditions , 85 % of the dose of albuterol is aerosolized [ 10 ] . Patients were selected r and omly to receive an intravenous loading dose of either aminophylline or placebo , which was prepared by an unblinded clinical pharmacist . Aminophylline was added to a commercial plastic intravenous bag containing 5 % dextrose in water , whereas the intravenous solution alone was used for placebo . The intravenous bags were identical in appearance and labeling . In the patients treated with aminophylline , the loading dose was based on the serum theophylline concentration measured in the emergency department and was infused for 30 minutes . One milligram per kilogram of theophylline was administered for each 2 g/mL desired increase in serum theophylline concentration to achieve a target concentration of 15 g/mL [ 11 ] . Thereafter , a continuous infusion of aminophylline ( starting at 0.6 mg/kg hour ) or placebo was begun . The infusion rate of aminophylline was adjusted by the clinical pharmacist to maintain theophylline concentrations between 10 and 20 g/mL. To assure double-blinding , patients receiving placebo infusions had sham theophylline concentrations measured , followed by adjustment of the placebo infusion rate . The r and omization code was not revealed until the last patient completed the study . Measurements and End Points Spirometry was done using a water-sealed Collins spirometer attached to an Eagle 1 microprocessor and printer ( W.E. Collins , Braintree , Massachusetts ) . Each spirometric maneuver ( the better of two efforts ) was done approximately 1 hour after a nebulized albuterol treatment . The spirometer was calibrated each day with a 3-L syringe . Forced expiratory volume in 1 second was measured at 0 ( entry point ; baseline ) , 1 , 3 , 6 , 12 , 24 , 36 , and 48 hours . For each patient at each time point , FEV1 was converted to a percentage of the predicted value based on age , height , sex , and race [ 12 ] ( Appendix ) . Our primary outcome measure was relative improvement in FEV1 from hour 0 . The change in FEV1 from baseline to time t was st and ardized relative to the difference between the baseline value and the 100 % predicted value for that patient [ 12 ] ( Appendix ) . This measurement , when plotted against the log of time , provides a good linear fit for assessing rate of improvement in FEV ( 1 ) . It measures the improvement in FEV1 in a way that adjusts for intersubject differences in baseline severity of airway obstruction and it is also independent of body size . Some investigators have suggested that this is the best clinical method for assessing bronchodilator response [ 13 , 14 ] . Adverse effects , vital signs , and an asthma symptom score were measured at the same times as FEV1 . The symptom score was the sum of the subjective rating of the patient 's sensation of dyspnea plus the study physician 's assessment of the severity of wheezing based on auscultation . The following was the basis for the symptom score : absent = 0 , mild = 1 , moderate = 2 , and severe = 3 . The maximum possible score at each time point was 6 points . Also recorded was the number of as-needed nebulizations of albuterol and the total dose of albuterol given during the 48-hour study period . Whole-blood theophylline concentration was measured from a fingerstick at the bedside by an unblinded clinical pharmacist using an AccuLevel kit ( Syntex Medical Diagnostics , Palo Alto , California ) [ 15 ] at 0.5 hours and 8 hours after completion of the intravenous bolus of aminophylline or placebo and then approximately every 24 hours thereafter . The coefficient of variation for measurement of a 10-grams/mL control solution by the pharmacists participating in the study was 11 % ( n = 31 ) . This method of measuring theophylline concentration was used to avoid unblinding by the hospital laboratory computer system . The study drug infusion and intravenous methylprednisolone were discontinued at 48 hours or before if the patients became relatively asymptomatic and were ready for discharge . At that time , both aminophylline- and placebo-treated patients were converted to oral prednisone , 40 to 60 mg daily , and to oral slow-release theophylline . Patient discharge decisions were made blinded by housestaff physicians . Because patients were charged for all hospital costs , we considered it to be unethical to keep them in the study if they became asymptomatic before 48 hours . Data Analysis Mean differences between aminophylline- and placebo-treated patients on quantitative demographic and outcome variables were assessed by ordinary two- sample Student t-tests and Wilcoxon rank-sum tests . Because the two methods produced similar conclusions , only the results of the two- sample Student t-tests are reported , along with their associated CIs . The Fisher exact test was used to analyze categorical variables such as sex , race , smoking status , and incidence of adverse effects . For computing CIs for differences in proportions , we used the exact method of Conlon and Thomas [ 16 ] . The robust tests of O'Brien [ 17 ] and Brown and Forsythe [ 18 ] were used to compare the group 's This study was conducted to determine whether intravenous theophylline , added to inhaled albuterol and intravenous methylprednisolone , provides a clinical ly significant benefit in the treatment of pediatric status asthmaticus . Patients aged 2 to 10 years were r and omized to receive either intravenous theophylline or placebo . All patients received aerosolized albuterol and intravenous methylprednisolone . There was no difference between groups in the improvement of a clinical asthma score over time , in oxygen requirement , or in the number of albuterol treatments required . Theophylline group patients experienced more nausea , emesis , and insomnia . We conclude that there is no benefit in adding theophylline to treatment with methylprednisolone and albuterol for pediatric status asthmaticus . Furthermore , there are significantly more adverse effects associated with the use of theophylline STUDY OBJECTIVE To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma . DESIGN R and omized , prospect i ve , placebo-controlled , double-blind trial . SETTING Tertiary-care children 's hospital . PATIENTS Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study . The treatment and placebo groups were similar in age , gender , race , illness severity , and emergency department treatment . INTERVENTIONS All patients received intravenously administered methylprednisolone and nebulized albuterol . The treatment group received intravenous theophylline therapy and the placebo group dextrose in water . When intravenously administered medications were discontinued , therapy continued with oral administration of theophylline ( or placebo ) and of prednisone . MEASUREMENTS AND MAIN RESULTS Twice-daily assessment s of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate , inspiratory/expiratory ratio , wheeze , and accessory muscle use . Time required to reach study discharge criteria ( asthma score < or = 2 ) ( 30.4 + /- 16.8 vs 27.0 + /- 10.3 hours ; p = 0.51 ) and the rate of improvement of the clinical asthma score ( -0.10 + /- 0.05 unit/hr vs -0.11 + /- 0.09 unit/hr ; p = 0.88 ) were not significantly different between the theophylline and placebo groups . The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups . CONCLUSION When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma , addition of theophylline may not be justified OBJECTIVE To determine if the use of intravenous theophylline , in the form of aminophylline , when added to systemic corticosteroids and aerosolized beta 2-agonists , enhances the improvement of children with acute asthma exacerbations . DESIGN A double-blind , placebo-controlled , r and omized , clinical trial . SETTING The University of Maryl and Medical Center , Baltimore , an urban primary - and tertiary-care pediatric medical center . PATIENTS Forty-two children , aged 2 to 18 years , admitted to the hospital for acute exacerbations of asthma . METHODS Patients were r and omized to receive either intravenous theophylline to maintain a serum level greater than 55 mumol/L or a placebo infusion . All patients received methylprednisolone and nebulized albuterol . A clinical severity score was assessed twice daily . RESULTS The mean length of stay for the treatment and control groups was 52.3 + /- 32.3 hours and 48.2 + /- 26.6 hours , respectively ( t = 0.45 , P = .65 ) . The rate of improvement of clinical scores was similar . CONCLUSION These data suggest that the addition of theophylline to albuterol and corticosteroids does not enhance improvement of children admitted to the hospital with asthma A double-blind test to compare IV aminophylline with salbutamol in the treatment of acute , uncontrolled asthma showed that both drugs were equally effective during the first 24 hours . Salbutamol caused a relative tachycardia . Hydrocortisone was given after 2 hours , but did not appear to affect the rate of recovery STUDY OBJECTIVE To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists , inhaled ipratropium , and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU ( PICU ) . DESIGN A prospect i ve , r and omized , controlled trial . Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment . SETTING The PICU of an urban , university-affiliated , tertiary-care children 's hospital . PATIENTS Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress , as indicated by a modified Wood-Downes clinical asthma score ( CAS ) of > or = 5 . INTERVENTIONS All subjects initially received continuous albuterol nebulizations ; intermittent , inhaled ipratropium ; and IV methylprednisolone . The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily . MEASUREMENTS AND RESULTS Forty-seven children ( median age , 8.3 years ; range , 13 months to 17 years ) completed the study . Twenty-three children received theophylline . The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group . All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion . Among the 41 subjects who were not receiving mechanical ventilation , those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects ( 18.6 + /- 2.7 h vs 31.1 + /- 4.5 h ; p < 0.05 ) . Theophylline had no effect on the length of PICU stay or the total incidence of side effects . Subjects receiving theophylline had more emesis ( p < 0.05 ) , and control patients had more tremor ( p < 0.05 ) . CONCLUSIONS Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol , ipratropium , and methylprednisolone . The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined The aim of the present study was to investigate the efficacy of iv aminophylline as a supplemental therapy for wheezy infants and preschool children who still present moderate broncho-obstruction after treatment with nebulized fenoterol . A prospect i ve r and omized , double blind , placebo-controlled trial was conducted in a Paediatric Emergency Room . The major selection criteria for patients > > inclusion were age between 1 and 7 years , a wheezy episode lasting less than 2 days which failed to respond to three sequential fenoterol nebulizations , a Wood-Downes score between 3 and 6 , and a history of at least two similar episodes . Exclusion criteria were radiologically-identified pulmonary condensation , recent use of corticosteroid and /or theophylline drugs , and previous diagnosis of chronic conditions . A sample of 43 cases was selected : 24 in Group A and 19 in Control Group B. All patients were su bmi tted to nebulization with fenoterol and intravenous hydrocortisone for a maximum period of 24 h. Only Group A patients received iv aminophylline ( 6 mg/kg in bolus and 1.2 mg/kg per h for maintenance schedule ) . Treatment efficacy parameters established for the two groups were based on the Wood-Downes clinical score . Throughout the study , the average clinical scores and the discharge rate were similar for both groups . The average stay in the Emergency Room was 12.5 h for Group A and 14.6 h for Control Group B. In conclusion , the use of supplemental iv aminophylline for moderate broncho-obstructive crisis in wheezy infants and preschool children did not add therapeutically significant results to the usually prescribed combination of nebulized beta-adrenergic and intravenous corticosteroid drugs Objective : To compare the efficacy of theophylline , terbutaline , or theophylline combined with terbutaline treatment in critically ill children with status asthmaticus who are already receiving continuous nebulized albuterol and intravenous corticosteroids . Design : R and omized , prospect i ve , controlled , double-blind trial . Setting : Pediatric intensive care unit of a tertiary-care children ’s medical center . Patients : Forty critically ill children between the ages of 3 and 15 yrs with impending respiratory failure secondary to status asthmaticus . Interventions : All patients received intravenous methylprednisolone and continuous nebulized albuterol . The three study groups received theophylline plus placebo ( group 1 ) , terbutaline plus placebo ( group 2 ) , or theophylline and terbutaline together ( group 3 ) . Measurements and Main Results : Differences in baseline characteristics , change in clinical asthma score over time , length of pediatric intensive care unit stay , and incidence of adverse events were determined . The three study groups were similar in age , gender , race , asthma severity , and treatment . There were no differences in clinical asthma score over time , length of pediatric intensive care unit stay , or incidence of adverse events between the three groups , with the exception of a higher incidence of nausea in children in group 3 . The median hospital cost of medication and theophylline blood levels was significantly lower in group 1 compared with groups 2 and 3 ( $ 280 vs. $ 3,908 vs. $ 4,045 , respectively , p < .0001 ) . Conclusions : Theophylline , when added to continuous nebulized albuterol therapy and intravenous corticosteroids , is as effective as terbutaline in treating critically ill children with status asthmaticus . The addition of theophylline to baseline therapy is more cost-effective when compared with terbutaline alone or terbutaline and theophylline together . Theophylline should be considered for use early in the management of critically ill asthmatic children We studied 40 patients with acute exacerbations of asthma to determine the efficacy of a 3-h intravenous infusion of aminophylline in patients who were already being treated with an inhaled beta-adrenergic agonist ( metaproterenol ) . Each patient was treated with inhaled metaproterenol at hourly intervals for 3 h. In addition , patients were r and omly assigned to therapy with either intravenous aminophylline or placebo . Neither the patient nor the house officers and nurses caring for the patient knew whether aminophylline or placebo was given . The FEV1 improved continually throughout the study to a similar extent in both treatment groups , but the patients treated with aminophylline had significantly more adverse effects ( p less than 0.025 , Mann-Whitney ) . There was no apparent benefit from aminophylline even in patients who presented to the emergency room with severe airway obstruction ( FEV1 less than 0.8L ) or with plasma theophylline levels less than 10 mg/L. We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled metaproterenol in the treatment of acute exacerbations of asthma OBJECTIVE To assess the role of aminophylline in the treatment of acute exacerbations of bronchospastic disease when used in addition to inhaled beta-agonists and intravenous corticosteroids . DESIGN R and omized , double-blind , placebo-controlled intervention study . PATIENTS One hundred thirty-three adult patients with either asthma or chronic obstructive pulmonary disease who presented to the emergency department with asthma or wheezing . INTERVENTIONS All patients received therapy with both aerosolized metaproterenol and intravenous methyl-prednisolone . Patients were r and omly assigned to receive either a loading dose of aminophylline followed by a routine infusion ( n = 65 ) or an equal volume of placebo as a loading dose and infusion ( n = 68 ) . MEASUREMENTS AND MAIN RESULTS At discharge from the emergency department , the median serum theophylline concentration for the aminophylline group was 54 mumol/L ( 9.7 mg/L ) . The two groups showed no differences ( P greater than 0.2 ) in measurements of forced expiratory volume at 1 second ( FEV1 ) , forced vital capacity ( FVC ) , or peak expiratory flow rate ( PEFR ) at baseline or at 60 or 120 minutes after aminophylline administration . Neither patient satisfaction nor physician assessment of response to therapy differed between the two groups . There was no difference ( P greater than 0.2 ) in the frequency of side effects , except for a trend toward a higher frequency of nausea ( P = 0.13 ) in the aminophylline group . There was , however , a threefold decrease in the hospital admission rate for patients treated with aminophylline ( 6 % ) compared with placebo recipients ( 21 % ) ( P = 0.016 ) . CONCLUSION Aminophylline , in doses producing levels just below the commonly accepted therapeutic range , appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease . This finding , if confirmed in larger studies , may represent a substantial cost savings BACKGROUND The role of intravenous aminophylline in acute asthma is unclear despite meta- analysis of many studies comparing aminophylline with other bronchodilator therapies . AIMS The aim of this study is to determine whether continuous aminophylline infusion confers any benefit in acute severe asthmatics treated with intravenous steroids and inhaled bronchodilators . METHODS The study was r and omised , double-blind and placebo-controlled . All patients received nebulised salbutamol ( 1 mL of 0.5 % ) and ipratropium bromide ( 1 mL of 0.025 % ) with glycol diluent ( 1 mL ) at 0 , two , four , six , eight and 12 hours , and six-hourly thereafter . In addition all patients were given intravenous hydrocortisone 250 mg six-hourly and oxygen to maintain normoxia . Aminophylline infusions were adjusted to maintain therapeutic levels . Peak expiratory flow rate ( PEFR ) was measured before and after nebulised bronchodilator on a two-hourly basis in the Emergency Department ( ED ) and six-hourly on the inpatient wards . RESULTS Thirty-one patients were clinical ly sufficiently improved within 12 hours to be discharged home from the ED . The remaining 28 patients were admitted to the inpatient ward for a total trial duration of 48 hours . No significant difference was found between the placebo and treatment groups for measurements of PEFR , or for the duration of stay of the patients in hospital . The power of the study was 80 % for a 25 % to 33 % difference at a 5 % level of significance . Presentation values of PEFR and arterial blood gases did not predict which patients would require inpatient admission and which could be safely discharged home from the ED A double-blind , r and omized study was performed to determine the occurrence of ventricular arrhythmias in acute asthma patients treated with epinephrine , aminophylline , or both in combination . Sixty patients were studied with Holter monitoring during the 90-minute study period . There was no statistical difference among the study groups in frequency or grade of ventricular arrhythmia . Combination treatment of acute asthma with these drugs is as safe as treatment with either alone |
12,579 | 27,919,096 | She said that if we test for vitamin D deficiency , she could almost guarantee that my level would not be in the normal range because of living in the Northeast , where we do n't get a lot of sunshine over the winter .
Your bone density is better if you exercise regularly .
I do some weights and play tennis a lot and walk regularly .
People with low vitamin D levels have an increased risk for osteoporosis .
Context , Evidence , and Guidelines Sub clinical vitamin D deficiency is common in the United States , especially in winter , and has been associated with an increased risk for falls and bone disorders .
Decreased intake of dairy products in adulthood may also be a contributing factor in some patients .
In summary , the USPSTF found that treatment of vitamin D deficiency in asymptomatic persons might reduce mortality risk in institutionalized elderly persons and risk for falls but not fractures .
This study and similar meta-analyses ( 10 ) constitute good evidence that vitamin D plus calcium ( but not vitamin D alone ) prevents fractures .
These studies have consistently shown no effect of supplementation with vitamin D and calcium on vertebral fractures ( 10 ) .
Vitamin D supplementation has also been reported | About Beyond the Guidelines Beyond the Guidelines is an educational feature based on recent guidelines .
Each considers a patient who falls between the cracks of available evidence and for whom the optimal clinical course in unclear .
Moderator : Eileen E. Reynolds , MD Discussants : Alan O. Malabanan , MD , and Gordon J. Strewler , MD Available at www.annals.org Patient interview video Gr and Rounds video Supplement slides CME/MOC activity Questions and comments Ms. X is a healthy 55-year-old woman who presents for an annual visit .
She had her last menstrual period about 1.5 years ago and reports mild hot flashes and vaginal dryness .
Family medical history is noteworthy for lung cancer in her father and breast and thyroid cancers in a sister .
slide set ) Ms. X 's Story I 'm a fairly healthy person , eat a good diet , and exercise regularly .
I reached menopause just in the last year .
I used to work as a dietitian in a variety of setting s but more recently have been at home raising our children .
I take a multivitamin and am now on a vitamin D supplement .
Vitamin D is important for bone health .
My underst and ing is that it helps with the absorption of calcium into the cells and bones .
However , the issues of how to measure vitamin D , the optimal serum level for good health , and whether to screen for deficiency ( and , if so , in which population s ) or whether to recommend that all at-risk patients take a daily vitamin D supplement remain controversial .
The U.S. Preventive Services Task Force ( USPSTF ) recently published a systematic review on screening for vitamin D deficiency ( 1 ) ( Figure 1 ) .
The National Academy of Medicine ( formerly the Institute of Medicine ) does not have formal guidelines on screening for vitamin D deficiency but published a report of the recommended dietary allowance , which is 600 IU/d for adults aged 19 to 70 years and 800 IU/d for adults older than 70 years ( 5 ) .
What is the evidence that supplementation is clinical ly beneficial ?
2 .
What are the pros and cons of screening for vitamin D deficiency versus recommending vitamin D supplementation without screening ?
3 .
What would you recommend for Ms. X and why ?
Vitamin D is really a hormone , which is normally made in the skin in response to ultraviolet light .
Its best understood effect is to increase calcium absorption from the gut and thereby assure bone health .
We know from mutations inactivating the nuclear receptor for vitamin D that severe cartilage and bone diseaserickets and osteomalaciaoccur in the absence of vitamin D action ( 6 ) .
We also know that these bone diseases can be prevented by administering large amounts of intravenous calcium , demonstrating that it is defective calcium absorption , not some direct effect of vitamin D on bone or other tissues , that is responsible for bone disease .
Despite the powerful biological argument for efficacy of vitamin D and calcium to prevent bone disease , the USPSTF concluded that there was no evidence that vitamin D supplementation prevented fractures ( 2 ) . | Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies . Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [ 25(OH)D ] . Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2 ) vitamin D form . Thus , 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology . We conducted a prospect i ve nested case-control study in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention cohort of male Finnish smokers , ages 50 to 69 years at baseline , to test whether more adequate vitamin D status , as determined by prediagnostic serum 25(OH)D concentrations , was associated with lower pancreatic cancer risk . Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 ( up to 16.7 years of follow-up ) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using conditional logistic regression . Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer ( highest versus lowest quintile , > 65.5 versus < 32.0 nmol/L : OR , 2.92 ; 95 % CI , 1.56 - 5.48 , P(trend ) = 0.001 ) that remained after excluding cases diagnosed early during follow-up . Contrary to expectations , subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status . Our findings need to be replicated in other population s and caution is warranted in their interpretation and implication . Our results are intriguing and may provide clues that further the underst and ing of the etiology of this highly fatal cancer Summary The Women 's Health Initiative ( WHI ) double-blind , placebo-controlled clinical trial r and omly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo , with average intervention period of 7.0 years . The trial was design ed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture , and secondarily , total fracture and colorectal cancer . Introduction This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data , with emphasis on fractures , cardiovascular disease , cancer , and total mortality . Methods WHI calcium and vitamin D r and omized clinical trial ( CT ) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation , and these data were contrasted and combined with corresponding data from the WHI prospect i ve observational study ( OS ) . Results Among women not taking personal calcium or vitamin D supplements at baseline , the hazard ratio [ HR ] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 ( 95 % confidence interval ( CI ) , 0.38–1.00 ) . In combined analyses of CT and OS data , the corresponding HR was 0.65 ( 95 % CI , 0.44–0.98 ) . Supplementation effects were not apparent on the risks of myocardial infa rct ion , coronary heart disease , total heart disease , stroke , overall cardiovascular disease , colorectal cancer , or total mortality , while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive . Conclusion Though based primarily on a subset analysis , long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women . Other health benefits and risks of supplementation at doses considered , including an elevation in urinary tract stone formation , appear to be modest and approximately balanced Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease ( CVD ) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention . The VITamin D and Omega-A 3 TriaL ( VITAL ) is an ongoing nationwide , r and omized , double-blind , placebo-controlled clinical trial design ed to fill this knowledge gap . The study population consists of 25,874 U.S. adults without cancer or CVD at baseline , who were selected only on age ( men aged ≥50 and women aged ≥55 ) , with an oversampling of African Americans ( n=5,107 ) . In a 2 × 2 factorial design , participants were r and omized to one of four supplement groups : [ 1 ] active vitamin D3 ( cholecalciferol ; 2000 IU/d ) and active marine omega-3 fatty acids ( Omacor ® fish oil , eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] , 1g/d ) ; [ 2 ] active vitamin D and omega-3 placebo ; [ 3 ] vitamin D placebo and active marine omega-3 fatty acids ; or [ 4 ] vitamin D placebo and omega-3 placebo . The mean length of the r and omized treatment period will be 5 years . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed . VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice BACKGROUND Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons . Calcium and vitamin D supplements reduce this secondary hyperparathyroidism , but whether such supplements reduce the risk of hip fractures among elderly people is not known . METHODS We studied the effects of supplementation with vitamin D3 ( cholecalciferol ) and calcium on the frequency of hip fractures and other nonvertebral fractures , identified radiologically , in 3270 healthy ambulatory women ( mean [ + /- SD ] age , 84 + /- 6 years ) . Each day for 18 months , 1634 women received tricalcium phosphate ( containing 1.2 g of elemental calcium ) and 20 micrograms ( 800 IU ) of vitamin D3 , and 1636 women received a double placebo . We measured serial serum parathyroid hormone and 25-hydroxyvitamin D ( 25(OH)D ) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women . RESULTS Among the women who completed the 18-month study , the number of hip fractures was 43 percent lower ( P = 0.043 ) and the total number of nonvertebral fractures was 32 percent lower ( P = 0.015 ) among the women treated with vitamin D3 and calcium than among those who received placebo . The results of analyses according to active treatment and according to intention to treat were similar . In the vitamin D3-calcium group , the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months ( P < 0.001 ) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value ( P < 0.001 ) . The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group ( P < 0.001 ) . CONCLUSIONS Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment BACKGROUND Epidemiologic and pre clinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia . To further study the chemopreventive potential of these nutrients , we conducted a r and omized , double-blind , placebo-controlled trial of supplementation with vitamin D , calcium , or both for the prevention of colorectal adenomas . METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy . We r and omly assigned 2259 participants to receive daily vitamin D3 ( 1000 IU ) , calcium as carbonate ( 1200 mg ) , both , or neither in a partial 2 × 2 factorial design . Women could elect to receive calcium plus r and om assignment to vitamin D or placebo . Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations , according to the endoscopist 's recommendation . The primary end point was adenomas diagnosed in the interval from r and omization through the anticipated surveillance colonoscopy . RESULTS Participants who were r and omly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter , relative to participants given placebo . Overall , 43 % of participants had one or more adenomas diagnosed during follow-up . The adjusted risk ratios for recurrent adenomas were 0.99 ( 95 % confidence interval [ CI ] , 0.89 to 1.09 ) with vitamin D versus no vitamin D , 0.95 ( 95 % CI , 0.85 to 1.06 ) with calcium versus no calcium , and 0.93 ( 95 % CI , 0.80 to 1.08 ) with both agents versus neither agent . The findings for advanced adenomas were similar . There were few serious adverse events . CONCLUSIONS Daily supplementation with vitamin D3 ( 1000 IU ) , calcium ( 1200 mg ) , or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00153816 . ) |
12,580 | 23,680,414 | This meta- analysis shows no evidence of a significant difference in patient-reported and objective cure/improvement rates between RP-TVT and TO-TVT in the surgical treatment of women with R-SUI . | CONTEXT Recurrent stress urinary incontinence ( R-SUI ) represents a management dilemma ; however , only a limited number of r and omised controlled trials ( RCTs ) have assessed the various surgical procedures used for its treatment .
OBJECTIVE To assess the effectiveness and complications of various surgical procedures for the treatment of female R-SUI . | OBJECTIVE To compare peri-operative complications , pain , and the immediate functional results of the sub-urethral sling procedure for urinary stress incontinence by the retropublic and transobturator routes , using a non-elastic polypropylene sub-urethral sling . PATIENTS AND METHODS This prospect i ve , multicentre study involved 88 women undergoing the sub-urethral sling procedure for stress urinary incontinence ( SUI ) . The retropubic route ( RPR ) and the transobturator route ( TOR ) were used in respectively 42 and 46 cases . The characteristics of the women in the RPR and TOR groups were as follows : mean age ( + /-st and ard deviation ) 56.8+/-12 years and 53.4+/-10 years , respectively ; mean BMI : 25+/-4 and 26+/-4 ; mean parity : 2.1+/-0.9 and 2+/-1 children ; post-menopausal status : 66.7 % and 58.7 % ; prior surgery for SUI : 7.1 % and 6.5 % ; and prior hysterectomy : 21.4 % and 26.1 % . None of these characteristics differed significantly between the groups . Likewise , pre-operative urinary functional status ( SUI stage , and pollakiuria , nocturia and urgency rates ) was similar in the two groups . RESULTS Mean hospital stay and overall morbidity rate were not significantly different between the RPR and TOR groups . Mean operating time was longer in the RPR group . Bladder injury was significantly more frequent in the RPR group and vaginal injury was significantly more frequent in the TOR group . Pain scores were significantly lower in the TOR group . The objective functional results at one month did not differ between the groups . Quality of life , evaluated with question naires and numerical rating scales , was similarly improved in the two groups . DISCUSSION The suburethral sling procedure was less painful by the TOR route than by the RPR route . Bladder injury , haematomas and abscesses were only observed in the RPR group , while vaginal injury only occurred in the TOR group . The immediate functional results of the two approaches were similar Introduction and hypothesisThis study aims to analyze comparatively the efficacy and safety of synthetic transobturatory and aponeurotic retropubic slings , in the treatment of stress urinary incontinence ( SUI ) in women . Methods Patients were separated in a r and omized way . Twenty-one patients were su bmi tted to the operatory correction by the transobturatory sling technique , whereas 20 patients were operated by the retropubic sling technique . All patients were su bmi tted to complete physical exam and urodynamic test . The “ T ” test and the Mann – Whitney U test were applied to establish comparisons between the two groups . Patients were followed-up for 12 months . Results Healing rate was 90.5 % ( 19/21 ) and 95 % ( 19/20 ) , respectively after 12 months . The transobturatory group presented lesser complications rate than the retropubic group . Conclusions The transobturatory and the aponeurotic slings techniques were equally effective for the treatment of SUI . The transobturatory sling has shown fewer complications and lesser surgical time than the aponeurotic sling technique Introduction and hypothesisThe aim of this study is to compare a modified inside-out transobturator procedure with its original counterpart [ inside-out transobturator ( TVT-O ) ] for the treatment of female stress urinary incontinence ( SUI ) . Methods A prospect i ve , r and omized trial in women suffering from SUI was used . The modified procedure consisted of a shorter tape whilst the scissors or guide no longer perforated the obturator membrane . The primary outcome was the resolution of subjective and objective SUI at 1 year . Secondary outcome measures included adverse events , quality of life measures , and groin pain . Results One hundred seventy-five patients were r and omized . No intraoperative complications were recorded . The SUI cure rate was 91.7 % versus 90.7 % ( original versus modified , respectively ; p = 0.824 ) . Incidence and intensity of groin pain was higher in the original TVT-O group on day 0 and 1 ( p < 0.05 ) , requiring more analgesics ( p = 0.015 ) but not thereafter . Conclusions At 1 year follow-up , the modified inside-out transobturator tape procedure was as efficient and safe as the original technique but associated with less immediate postoperative groin pain OBJECTIVE The purpose of this study was to prospect ively and r and omly compare tension-free vaginal tape ( TVT ) with transobturator suburethral tape ( T.O.T. ) for the surgical treatment of stress urinary incontinence ( SUI ) in women . STUDY DESIGN Sixty-one women with SUI were r and omly assigned to either TVT ( n=31 ) or T.O.T. ( n=30 ) . The preoperative evaluation included a quality -of-life question naire and a comprehensive urodynamic examination . The 1-year outcome included a detrusor pressure-uroflow study to compare bladder outlet obstruction . RESULTS Patient characteristics , preoperative quality of life , and urodynamic evaluation were similar in the 2 groups . Mean operative time was significantly shorter in the T.O.T. group ( 15 min+/-4 vs 27 min+/-8 , P<.001 ) . No bladder injury occurred in the T.O.T. group versus 9.7 % ( n=3 ) in the TVT group ( P>.05 ) . The rate of postoperative urinary retention was 25.8 % ( n=8 ) in the TVT group versus 13.3 % ( n=4 ) in the T.O.T. group ( P>.05 ) . The rates of cure ( 83.9 % vs 90 % ) , improvement ( 9.7 % vs 3.3 % ) , and failure ( 6.5 % vs 6.7 % ) were similar for the TVT and T.O.T. groups , respectively . The 1-year outcome data were collected in 29 women of the TVT group and 27 women of the T.O.T. group . No vaginal erosion occurred in either of the groups . In terms of bladder outlet obstruction , no differences were found after TVT and T.O.T. CONCLUSION T.O.T. appears to be equally efficient as TVT for surgical treatment of stress urinary incontinence in women , with no reduction of bladder outlet obstruction at 1-year follow-up The purpose of our study was to compare the two st and ard routes of urethral bulking injection in a prospect i ve r and omized trial . Forty women with genuine stress incontinence ( n=36 ) , or mixed incontinence with a minor and controlled urge component ( n=4 ) , participated in a urethral bulking agent trial . All patients had a st and ardized preoperative evaluation which included history , physical examination , assignment of incontinence status on a Stamey grading scale , postvoid residual ( PVR ) determination , Valsalva leak-point pressure , maximal urethral closure pressure , functional urethral length , Q-tip excursion angle , quantitative pad test , and completion of a quality of life question naire . On the day of injection they were r and omly assigned to a periurethral or transurethral route of injection based on a computer-generated block r and omization scheme . An ultrasound-determined PVR was obtained on all patients after injection . If self-catheterization was necessary , and the PVR was > 200 ml , urinary retention was diagnosed . Postoperative assessment included a patient interview , subjective assessment of improvement , PVR , voiding diary , and assignment of incontinence grade . At the screening visit there were no significant differences between the groups for any variables except type of stress incontinence . With short-term follow-up both transurethral and periurethral routes of injection seem to be equally efficacious . In the periurethral injection group there was a higher rate of postoperative retention ; this group had a significantly higher volume of injectable agent used . There was no significant difference in risk of urinary tract infections between the two groups . We conclude that both periurethral and transurethral methods of bulking agent injection for stress urinary incontinence are equally efficacious , with minimal morbidity OBJECTIVE The treatment of women with mixed urinary incontinence still poses a great challenge . This study evaluated surgical outcomes of combined trans-obturator tension-free vaginal tape ( TVT-O ) and modified Ingelman-Sundberg ( IS ) procedure for the treatment of mixed urinary incontinence . METHODS A r and omized controlled trial was conducted . Ninety-six women diagnosed with mixed incontinence were r and omized , with 49 allocated to TVT-O plus IS and 47 to TVT-O alone . A baseline urodynamic study and evaluation of quality of life ( QOL ) was conducted . The primary outcome measure was objective assessment of surgical outcomes , and the secondary outcome measure was warning time . RESULTS Objective surgical response rate was significantly higher in the TVT-O plus IS group than in the TVT-O alone group ( 84.8 % vs. 62.8 % ; p=0.019 ) . Furthermore , a significant increase in warning time was observed in the TVT-O plus IS group ( from 3.9 to 9.4 min ; p=0.006 ) , but the increase in warning time within the TVT-O alone group was not statistically significant ( from 4.3 to 4.5 min ; p=0.695 ) . Postoperative complications were similar in the two study groups with respect to pelvic hematoma , nerve injury , sepsis , mesh erosion , and fistula formation . However , fever occurred more frequently in the TVT-O plus IS group ( 30.4 % vs. 20.9 % ; p=0.026 ) . CONCLUSIONS Mixed urinary incontinence can potentially be treated with a one-step combined surgery using trans-obturator sling plus modified IS procedure . Although surgical time and blood loss were significantly increased in the TVT-O plus IS group , overall morbidity was not significantly increased The aim of this study was to prospect ively compare the efficacy and safety of ‘ inside – out ’ ( TVT-O ) and ‘ outside – in ’ ( TOT ) transobturator tape procedures for treatment of female stress urinary incontinence ( SUI ) . One hundred women with SUI were alternately assigned to TVT-O ( n = 50 ) or TOT ( n = 50 ) . About 1 year after surgery , we compared surgical outcomes in the two groups . TVT-O and TOT showed similar rates of cure ( 86 vs 92 % ) . Approximately 1 year after surgery , Incontinence Quality of Life question naire parameters improved significantly in both groups ( p < 0.05 ) , but the two groups did not differ ( p > 0.05 ) . The rates of patient satisfaction with TVT-O and TOT ( 96 vs 98 % ) were similar . These preliminary results suggest that TVT-O and TOT are equally effective and safe procedures for women with SUI . However , this study was unable to identify a difference between the two procedures due to the underpowered nature of the study Introduction and hypothesisSynthetic mid-urethral slings are currently considered the treatment of choice for stress urinary incontinence ( SUI ) . In this study , two types of slings are compared : TVT vs. TOT . Methods In a prospect i ve r and omized study , 40 patients underwent either TVT ( 19 patients ) or TOT ( 21 patients ) . Stress-specific and overall success was evaluated . Perioperative complications were classified according to Clavien ’s classification . Results Mean duration of follow-up was 20 months . At last follow-up , stress-specific success rate was 94.6 % in TVT vs. 81 % in TOT . No significant difference was detected in terms of post-void residual urine , symptom score , and filling and voiding parameters . Thigh pain represented the main complication in the TOT group . Conclusions Both TVT and TOT are effective procedures for treatment of SUI . When compared to each other , TOT seems to be inferior to TVT in terms of efficacy , causing less serious complications Our objective was to compare monofilament and multifilament tapes positioned without tension at the midurethra for postoperative complications and cure rate . One hundred patients with stress urinary incontinence were r and omly allocated into two study groups . Using identical surgical methodology , 50 patients had a monofilament tape inserted at the midurethra using the TVT delivery instrument , and another 50 a multifilament tape using the IVS delivery instrument . The only significant difference between the groups was in the incidence of postoperative urinary retention ( p=0.023 ) . Ten patients from the monofilament group required longer than normal ( ‘ normal ’ means to the morning of the next day ) catheterization , in contrast to only two from the multifilament group . The clinical efficacy of both procedures was equally high . Conclusions were that both tapes appear to be equally effective in the surgical treatment of SUI . The higher incidence of postoperative urinary retention in the monofilament group was most likely caused by the elastic feature of this tape OBJECTIVES The aim of this study was to compare the long-term success rates , complication rates and patient satisfaction rates for Pelvicol pubovaginal sling ( Bard ) versus TVT ( Gynecare ) in surgical treatment of urodynamic stress incontinence ( USI ) in women . DESIGN Prospect i ve r and omized cohort trial . SETTING District General Hospital , South West of Engl and . METHODS One hundred and forty-two women with urodynamic stress incontinence were r and omized to either surgical procedure ( Pelvicol = 74 , TVT = 68 ) with median follow-up of 36 month . A postal question naire was sent to all women and the response rate was excellent at approximately 90 % in both groups . RESULTS Cure of incontinence , as identified by a quality of life improvement > 90 % , and /or patient-determined continent status as dry , were comparable in both groups . When the cure rates were adjusted assuming the non-respondents as failures the figures were almost identical ( p > 0.05 ) . Preoperative continence pad usage was similar for both groups . Overall , a postoperative significant decrease in pad score was noted in both groups ( p = 0.01 ) but there was no significant difference between the groups ( p > 0.05 ) . Statistical analysis failed to detect significant differences between both groups as regards complication rates such as frequency , nocturia , de-novo urgency or dyspareunia . CONCLUSION Pelvicol sling is a safe procedure in the surgical management of USI with similar success rate and patient satisfaction rate to TVT up to three years of follow-up Objective To compare the outcomes of tension- free vaginal tape ( TVT ) and transobturator tape ( TOT ) in the treatment of female stress urinary incontinence with or without concomitant pelvic organ prolapse ( POP ) . Methods One hundred and forty patients with SUI were r and omly allocated to TVT ( n = 70 ) or TOT ( n = 70 ) . The objective outcomes were assessed with a stress test , 1-h pad test . Subjective outcomes were assessed with UDI-6/(IIQ-7 ) question naires . Results The surgical outcomes revealed no significant difference between TVT and TOT surgical route . Both the subjective and objective cure rates were 91.4 % in the TOT group , while 90 and 92.8 % in the TVT group , respectively . The results showed the association to pelvic floor surgical techniques did not diminish a year later . TOT procedure has a shorter operative time for patients without concomitant surgery . Conclusion The efficacy and safety of TVT procedure were similar to that of TOT procedure for female stress urinary incontinence with or without concomitant POP Abstract : In a prospect i ve long-term follow-up study we evaluated the results of TVT surgery in 34 women with recurrent stress urinary incontinence in whom previous traditional surgical procedures had failed . The women were followed for a mean of 4 years ( range 3–5 ) after TVT surgery . The mean age was 58.9 ± 10 years and the mean parity 2 ( 0–4 ) . Pre- and postoperative evaluation was performed according to a protocol which included gynecologic examination , urodynamic investigations , quality of life evaluation and 24-hour pad test . According to the protocol 28 patients ( 82 % ) were cured , 3 ( 9 % ) were significantly improved , and the operation failed in 3 cases ( 9 % ) . There were no significant intra- or postoperative complications . All patients were operated on under local anesthesia with a short hospitalization and had no long-term postoperative voiding problems Objectives . This study evaluates the long-term clinical success of Durasphere ( Carbon Metal Technologies , St. Paul , MN ) compared with Contigen ( C. R. Bard , Covington , GA ) in the treatment of stress urinary incontinence caused by intrinsic sphincter deficiency ( ISD ) . Methods . Fifty-two women diagnosed with stress urinary incontinence caused by ISD were treated between March and November of 1998 in a r and omized , double-blinded trial comparing Durasphere and Contigen . Pad testing , Stamey Continence Grading , and urodynamics , including abdominal leak point pressures , were performed during the initial evaluation . All patients were diagnosed with ISD and displayed abdominal leak point pressures of ≤ 90 cm of H2O . Results . Of 26 patients in each group , 25/26 ( 96 % ) Durasphere patients and 21/26 ( 81 % ) Contigen patients were available for this follow-up of 2.6 and 2.8 years , respectively , post initial injection . A total of 80 % of Durasphere patients and 62 % of Contigen patients demonstrated an improvement of ≥1 continence grade at this follow-up . Of these patients , 10/25 ( 40 % ) Durasphere patients and 3/21 ( 14 % ) Contigen patients are dry . Conclusions . Long-term follow-up demonstrated that Durasphere had greater success than Contigen in providing improved continence grade UNLABELLED The objective of this study was to compare TVT ( tension-free vaginal tape ) and TVT-O ( tension-free vaginal tape obturator from inside to outside ) procedures for the female surgical treatment of stress urinary incontinence : results , complications , and effectiveness after 1 year . MATERIAL AND METHODS A prospect i ve r and omized study was carried out . The patients were followed up for 12 months . A total of 114 patients were operated on using TVT procedure and 150 patients - TVT-O procedure . There was no significant difference in age , body mass index , parity , menopausal status , and prolapse ( no patients had cystocele greater than stage II ) comparing both groups . RESULTS The mean time in surgery was significantly shorter in the TVT-O group ( 19+/-5.6 min ) as compared with the TVT group ( 27+/-7.1 min ) . No differences in the effectiveness of both procedures were found : TVT - 94.6 % and TVT-O - 94.6 % after one year , respectively . Hospital stay was significantly shorter in the TVT-O group ( 1.5+/-0.5 days ) than in the TVT group ( 4.0+/-1.6 days ) . Significantly fewer complications were observed in the TVT-O group . CONCLUSION TVT and TVT-O operations are equally effective for the surgical treatment of female stress urinary incontinence . TVT-O group had shorter time in surgery and showed a lower rate of complications BACKGROUND Midurethral slings are increasingly used for the treatment of stress incontinence , but there are limited data comparing types of slings and associated complications . METHODS We performed a multicenter , r and omized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence . The primary outcome was treatment success at 12 months according to both objective criteria ( a negative stress test , a negative pad test , and no retreatment ) and subjective criteria ( self-reported absence of symptoms , no leakage episodes recorded , and no retreatment ) . The predetermined equivalence margin was + /-12 percentage points . RESULTS A total of 597 women were r and omly assigned to a study group ; 565 ( 94.6 % ) completed the 12-month assessment . The rates of objective ly assessed treatment success were 80.8 % in the retropubic-sling group and 77.7 % in the transobturator-sling group ( 3.0 percentage-point difference ; 95 % confidence interval [ CI ] , -3.6 to 9.6 ) . The rates of subjectively assessed success were 62.2 % and 55.8 % , respectively ( 6.4 percentage-point difference ; 95 % CI , -1.6 to 14.3 ) . The rates of voiding dysfunction requiring surgery were 2.7 % in those who received retropubic slings and 0 % in those who received transobturator slings ( P=0.004 ) , and the respective rates of neurologic symptoms were 4.0 % and 9.4 % ( P=0.01 ) . There were no significant differences between groups in postoperative urge incontinence , satisfaction with the results of the procedure , or quality of life . CONCLUSIONS The 12-month rates of objective ly assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence ; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence . Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence . ( Clinical Trials.gov number , NCT00325039 . OBJECTIVE The aim of this study was to compare a modified Burch procedure with a suburethral sling for the treatment of stress incontinence complicated by a low-pressure urethra . STUDY DESIGN Thirty-six women with stress incontinence , low-pressure urethra , and urethral hypermobility ( straining cotton swab angle > /=30 degrees ) were r and omly assigned to undergo either a modified Burch procedure ( n = 19 ) or a suburethral sling ( n = 17 ) . Objective and subjective cure rates at 3 months after the operation were the primary outcome measures . Comparisons of group means were performed with the Student t test for independent groups , and proportions were compared with the Fisher exact test . RESULTS After the operation the 2 groups had statistically similar cure rates and voiding function . Urethral closure pressure , pressure transmission ratios , and maximum detrusor pressure during voiding were significantly higher in the sling group . CONCLUSION At 3 months there were no clinical ly significant differences between the groups treated with suburethral sling and modified Burch procedures OBJECTIVE To compare the efficacy and safety of the tension-free vaginal tape ( TVT ) and transobturator suburethral tape ( TVT-O ) procedures for the treatment of mild and moderate stress urinary incontinence ( SUI ) . METHODS A total of 56 women were r and omly selected to undergo the TVT-O or the TVT procedure . In some patients , vaginal repair or vaginal hysterectomy was done simultaneously for associated indications . RESULTS Mean blood loss and hospital stay duration were the same for the 2 groups , but mean + /- SD operative time was significantly shorter in the TVT-O than in the TVT group ( 16+/-4 min vs 27+/-6 min ; P<0.001 ) . On the second day following surgery a residual urine volume less than 100 mL was noted in 86 % and 89 % of the patients in the TVT-O and TVT groups , respectively ; cure was achieved in 92.9 % and 92.6 % of the patients . No serious complications occurred in either group . Outcome was subjectively assessed , with the patients followed-up for a mean of 27.6 months . CONCLUSION No significant differences in rates of cure , postoperative urine retention , or operative complications were found following the TVT-O or the TVT procedure STUDY OBJECTIVE To compare laparoscopic Burch colposuspension and tension-free vaginal tape ( TVT ) procedure in women with genuine stress incontinence . DESIGN R and omized clinical study ( Canadian Task Force classification I ) . SETTING Tertiary care university hospital . PATIENTS Forty-six consecutive women . INTERVENTION Laparoscopic Burch colposuspension ( 23 ) and TVT procedure ( 23 ) . MEASUREMENTS AND MAIN RESULTS Valsalva leak-point pressure increased after surgery in both groups , but TVT substantially decreased maximum urinary flow rate . Other urodynamic studies showed no statistical differences . The groups did not differ significantly with respect to intraoperative complications or objective and subjective cure rates . Operating time was significantly longer for laparoscopic Burch ( p = 0.001 ) , and three patients in that group required conversion to laparotomy . Length of hospital stay ( p = 0.003 ) and duration of catheterization ( p = 0.003 ) were shorter in the TVT group . CONCLUSION TVT holds promise in women with genuine stress incontinence , with several advantages over laparoscopic Burch PURPOSE We evaluated the effectiveness of periurethral autologous fat injection as treatment for female stress urinary incontinence . MATERIAL S AND METHODS Women with stress incontinence were r and omized in a double-blind fashion to receive periurethral injections of autologous fat ( treatment group ) or saline ( placebo group ) . After injection patients were evaluated monthly for 3 months by a vali date d st and ardized incontinence question naire , 1-hour pad test and cough test . Patients who remained incontinent were offered repeat injection using the same initial agent to a maximum of 3 injections . Every 3 months after injection patients were assessed by a st and ardized question naire , pad test , cough test and urodynamics . Those who did not qualify for repeat injection at 3 months were then followed 6 , 9 , 12 , 18 and 24 months or until failure . RESULTS Of the 68 women enrolled 35 received fat and 33 received saline injections . The groups were comparable in terms of baseline parameters . A total of 56 patients completed the study , including 27 in the fat and 29 in the placebo group , for a total of 189 injections ( 91 fat and 98 saline ) . At 3 months 6 of 27 ( 22.2 % ) and 6 of 29 ( 20.7 % ) women were cured or improved in the fat and saline groups , respectively . Complications included cystitis in 9 of 189 injections , urinary retention in 6 in the fat injection group , urge incontinence in 9 of 68 patients and pulmonary fat embolism result ing in death in 1 of 189 procedures . CONCLUSIONS In this study periurethral fat injection did not appear to be more efficacious than placebo for treating stress incontinence STUDY OBJECTIVE To compare results of laparoscopic Burch colposuspension with those of classic Burch colposuspension , and to assess complications , results , and morbidity associated with each procedure . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING Minimal access surgery unit . PATIENTS Seventy-four women with genuine stress incontinence . INTERVENTION Laparoscopic and classic Burch colposuspensions . MEASUREMENTS AND MEAN RESULTS : Mean operating times for laparoscopic and open surgery were 70.18 + /- 16.54 and 53+/- 10.05 minutes , respectively ( p < 0.001 ) . Mean blood loss was 42.75 + /- 7.2 and 240.5 + /- 35.5 ml , respectively ( p < 0.001 ) . Postoperative analgesia requirement was significantly less with laparoscopy ( p < 0.001 ) . Mean postoperative hospital stay was 36 + /- 6.3 hours for the laparoscopic group and 76+/- 10.4 hours for the open group p<0.001 ) . Average time to return to light work was 8.5 and 31.5 days , respectively . Success rates were 90.9 % at 6 months and 87.9 % at 18 months in the laparoscopic group , compared with 90 % and 85 % , respectively , in the open group . CONCLUSION Given equal efficacy of the two procedures , we prefer the laparoscopic approach since it is associated with lower morbidity , shorter hospital stay , and fewer complications . ( J Am Assoc Gynecol Laparosc 8(1):99 - 106 , 2001 OBJECTIVES This prospect i ve , multicentre , r and omised study compared the safety and success rate of tension-free vaginal tape ( TVT ) and transobturator tape ( TOT ) in treatment of female stress urinary incontinence . METHODS Of 148 women , 73 were r and omised to TVT and 75 to TOT . Preoperative workups included case history , clinical examination , Urogenital Distress Inventory and Impact Incontinence Quality of life question naires , 1-h pad test , pelvic ultrasound , and urodynamics . Intra- and postoperative complications were the primary end point ; subjective and objective changes in SUI , and postoperative voiding dysfunctions were secondary end points . Patients were classified into two main categories : dry ( no leakage during clinical and /or stress test and /or reported by patients ) versus wet . Patients who referred being wet were separated into " improved " or " failure " on subjective analysis . Other outcome variables were quality of life question naires and VAS scale . Clinical checkups were conducted at 3 , 6 , 12 mo , and then annually . RESULTS Both techniques are safe and no significant differences emerged in intra- and postoperative complications . At a mean follow-up of 31 mo , the overall objective cure ( dry ) was 71.4 % for TVT and 77.3 % for TOT ( p = ns ) . When one considered " dry " plus " wet but improved , " these values increased to 90 % and 90.6 % , respectively ( p = ns ) . Median satisfaction rate was 9 ( range : 1 - 10 ) for both procedures . Postoperative storage symptoms are a controversial issue ; they persisted in 44 % of patients in TVT group versus 24 % in TOT group ( p<0.053 ) . CONCLUSIONS TOT appears as safe and effective as TVT in surgery for female SUI , with minimal complications at mean follow-up of 31 mo Voiding dysfunction following sling procedures for correction of genuine stress urinary incontinence ( GSI ) is a frequently reported complication . This study sought to determine if voiding dysfunction could be reduced by eliminating sling tension against the urethra . Participants were diagnosed with GSI and r and omized to one of two surgical groups . One received a conventional suburethral sling and the other received a modified sling placed at the mid-urethra without tension . Voiding trials after surgery monitored for voiding dysfunction . Multichannel urodynamic studies were performed pre- and post-operatively . Cure rates for GSI were similar for the two groups ( 91.7 vs. 88.5 % ) . The 27 patients in the modified group voided an average of 5 days earlier than the 21 patients in the conventional group . Conventional group patients were more likely to have urinary retention ( 125 vs. 49 cc , p=0.03 ) . The modified group had a lesser change in average closure pressure following surgery . Results suggested a higher increase in urethral resistance in the conventional group ( 0.72 vs. 1.88 cm H2O ml-2 sec2 ) . No differences were seen in symptomatic urinary urgency or urge incontinence following surgery . This study demonstrated a no-tension sling at the mid-urethra to afford equivalent cure of GSI with significant reduction of voiding dysfunction This r and omised control trial compares full-length autologous slings ( Group A : 81 women ) with a modified “ sling-on-a-string ” ( Group B : 84 women ) technique for the treatment of stress urinary incontinence ( SUI ) . Primary outcomes are quality of life ( QoL ) scores ; Group A/Group B. The IIQ-7 scores decrease from 1.91/1.85 at baseline to 0.65/0.72 at 12 months and 0.85/0.92 at + 5 years . The UDI-6 scores decrease from 1.85/1.61 at baseline to 0.66/0.62 at 12 months and 1.22/1.08 at + 5 years . The incidence of SUI is 13 % at 3 months but averages 53 % at + 5 years . Both techniques offer similar improvements . The shorter sling is quicker , less painful and with less hospital readmissions . The ‘ sling-on-a-string ’ technique is as effective as the st and ard technique with better short-term sequelae . The incidence of SUI post-autologous slings rises over the long term OBJECTIVE This study measured the 10-year risk of reoperation for surgically treated pelvic organ prolapse and urinary incontinence ( POPUI ) in a community population . STUDY DESIGN We conducted a prospect i ve cohort analysis of 374 women who were > 20 years old and who underwent surgery for POPUI in 1995 . RESULTS The 10-year reoperation rate was 17 % by Kaplan Meier analysis . Previous POPUI surgery at the time of index surgery conferred a hazard ratio of 1.9 ( 95 % CI , 1.1 - 3.2 ; P = .018 ) . The abdominal approach was protective against reoperation compared with the vaginal approach ( hazard ratio , 0.37 ; 95 % CI , 0.17 - 0.83 ; P = .02 ) With the use of Cox regression , no association was observed for age , vaginal parity , previous hysterectomy , body mass index , prolapse severity , ethnicity , chronic lung disease , smoking , estrogen status , surgical indication , or anatomic compartment . CONCLUSION A reoperation rate of 17 % is unacceptably high and likely represents an underestimate of the true rate . Most of the factors that influence reoperation have not yet been identified Objective To compare the pubovaginal sling and transurethral Macroplastique in the treatment of female stress urinary incontinence ( SUI ) and intrinsic sphincter deficiency ( ISD ) Objective To assess the effectiveness and late postoperative morbidity of the Burch procedure and the sling procedure for the treatment of recurrent urinary stress incontinence after vaginal hysterectomy and anterior repair . Methods Clinical , urodynamic , and sonographic examinations were done on 77 women suffering with recurrent urinary stress incontinence . The women were r and omized to two groups , modified Burch colposuspension and lyophilized dura mater sling surgery ; 72 women were reexamined 32–48 months after these procedures . Results The cure rate at 32–48 months ' follow-up was 86 % for the Burch procedure and 92 % for the sling . Women who had had the sling procedure demonstrated a clear decrease in maximal bladder capacity , from 330 to 240 mL ( P < .05 ) . In both groups , stress profiles demonstrated a shift of maximal pressure point toward the proximal urethra and a significant improvement in pressure transmission ( P < .05 ) . The post-operative patients who had persistent incontinence were found to have insufficient elevation of the bladder neck ( less than 10 mm ) . The uroflow examination showed an increase of urination time in both groups . The incidence of bladder problems was 10 % with the Burch procedure and 29 % with the sling procedure ; however , 13 % of the Burch group developed rectoceles . Conclusion Both procedures offer a high rate of success . We believe that the sling surgery should be used only in certain special cases because of its higher rate of complications , but that posterior vaginal repair should be considered after modified Burch colposuspension because of the possibility of rectocele and enterocele Please cite this paper as : Abdel‐fattah M , Ramsay I , Pringle S , Hardwick C , Ali H , Young D , Mostafa A. R and omised prospect i ve single‐blinded study comparing ‘ inside‐out ’ versus ‘ outside‐in ’ transobturator tapes in the management of urodynamic stress incontinence : 1‐year outcomes from the E‐TOT study . BJOG 2010;117:870–878 OBJECTIVES Obtape and DUPS are modifications of the original TVT procedure . To test these new products in terms of safety and efficacy , we design ed a prospect i ve clinical trial with a follow-up of at least 1 yr . METHODS We r and omized 190 consecutive females with SUI for this study . They were evaluated by history , ICIQ-SF , physical examination , cystoscopy , UDS , and the 1-h pad test . Patients were reevaluated at 1 , 6 , and 12 mo . The ICIQ-SF and pad test were repeated at 1-yr follow-up . RESULTS There were 78 , 32 , and 80 patients in the Obtape , DUPS , TVT arms , respectively . An interim analysis after 32 patients in each arm indicated postoperative retention rates of 3 ( 9.4 % ) , 6 ( 18.8 % ) , and 4 ( 12.5 % ) patients in Obtape , DUPS , and TVT groups , respectively . Because of higher retention rate and suprapubic discomfort , DUPS was discontinued . At the end of the study , complete retention rates were 6 ( 7.8 % ) , 6 ( 18.8 % ) , and 6 ( 7.5 % ) in Obtape , DUPS , and TVT , respectively . TVT was the only procedure with bladder perforations at a rate of 14 % . However , Obtape and DUPS were associated with more postoperative complications including complete retention , urethrolysis , hematoma , mesh erosion , UTI , and wound infection ( 13 % , 28 % , and 8 % ; p < or = 0.025 ) . At 1 yr , 83 % , 94 % , and 86 % of patients in the Obtape , DUPS , and TVT groups were objective ly cured ( p>0.05 ) . CONCLUSIONS TVT was the only procedure associated with bladder perforation , but there were more postoperative complications with Obtape and DUPS . No statistically significant differences in cure rates were observed at 1-yr follow-up . Longer follow-up is needed to confirm these results The aim of this study was to evaluate the results of tension-free vaginal tape ( TVT ) surgery in women with recurrent stress urinary incontinence ( SUI ) . Fifty-one women with recurrent SUI were treated with TVT and followed prospect ively for a minimum of 2 years according to a protocol . Twenty percent of the women had already undergone two previous continence procedures , whereas 80 % had undergone only one . The mean follow-up period was 25.3 months . The objective cure rate was 89.6 % , and the subjective cure rate 80.4 % . No serious complications occurred . The majority of the patients were discharged in the afternoon of the operation day . No significant difference was observed between pre- and postoperative residual urine , maximal urethral closure pressure , and total and maximum voided urine volume values . However , the changes in urinary frequency , minimum voided volume , pad test results , and visual analog scale scores were highly significant . TVT appears to be a safe and suitable treatment for recurrent SUI The objective of this study was to compare the efficacy of porcine dermal implant injection ( Permacol ) and silicone injection ( Macroplastique ) in the treatment of female urodynamic stress incontinence ( USI ) in a prospect i ve r and omized trial . Fifty women with urodynamically proven stress incontinence were recruited and r and omised to receive either Permacol or Macroplastique injection . Twenty-five patients were enrolled in each case . An International Continence Society ( ICS ) st and ard 1-h pad test was carried out prior to the injection and a subjective analysis of incontinence made using a Stamey scoring system . In addition , a Kings College Hospital Quality of Health Question naire ( KCQ ) was completed . The women were followed up at 6 weeks and 6 months and the same methods used to gauge the success or failure of the operation . Preoperatively there were no significant differences in pad losses , Stamey score or King ’s score between the two groups . The mean age of the women was 61 years ( range 28–80 years ) . At 6 weeks there were significant reductions in the mean and median values in pad losses , Stamey score and King ’s score in both Permacol and Macroplastique patients but the effects were more pronounced in Permacol patients than Macroplastique patients . Of the Permacol patients , 64 % were improved on quantified pad losses out of which 60 % were dry whereas 54 % of Macroplastique patients were improved on pad losses of which 41.6 % were dry . Of the Permacol patients , 64 % and 60 % had reduction in Stamey and KCQ score , respectively , whereas Macroplastique patients had 46 % reduction in one or more grade s of Stamey scores and 42 % reduction in KCQ scores . At 6 months the results in the Permacol patients appeared to be sustained but not for Macroplastique patients . This study has shown that Permacol injection when used as a urethral bulking agent appears to have a higher cure rate for urodynamic stress incontinence than Macroplastique and these results persist until the follow-up period of 6 months . The use of Permacol injection is an attractive alternative in the treatment of urodynamic stress incontinence BACKGROUND Many surgical procedures are available for women with urinary stress incontinence , yet few r and omized clinical trials have been conducted to provide a basis for treatment recommendations . METHODS We performed a multicenter , r and omized clinical trial comparing two procedures --the pubovaginal sling , using autologous rectus fascia , and the Burch colposuspension -- among women with stress incontinence . Women were eligible for the study if they had predominant symptoms associated with the condition , a positive stress test , and urethral hypermobility . The primary outcomes were success in terms of overall urinary-incontinence measures , which required a negative pad test , no urinary incontinence ( as recorded in a 3-day diary ) , a negative cough and Valsalva stress test , no self-reported symptoms , and no retreatment for the condition , and success in terms of measures of stress incontinence specifically , which required only the latter three criteria . We also assessed postoperative urge incontinence , voiding dysfunction , and adverse events . RESULTS A total of 655 women were r and omly assigned to study groups : 326 to undergo the sling procedure and 329 to undergo the Burch procedure ; 520 women ( 79 % ) completed the outcome assessment . At 24 months , success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure , for both the overall category of success ( 47 % vs. 38 % , P=0.01 ) and the category specific to stress incontinence ( 66 % vs. 49 % , P<0.001 ) . However , more women who underwent the sling procedure had urinary tract infections , difficulty voiding , and postoperative urge incontinence . CONCLUSIONS The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension . ( Clinical Trials.gov number , NCT00064662 [ Clinical Trials.gov ] . ) OBJECTIVES To evaluate the safety and effectiveness of soft-tissue augmentation of the urethral sphincter with calcium hydroxylapatite ( CaHA ; Coaptite ) compared with glutaraldehyde cross-linked bovine collagen ( Contigen ) in female patients with stress urinary incontinence due to intrinsic sphincter deficiency and without associated urethral hypermobility . METHODS This 12-month prospect i ve , r and omized , comparative , multicenter , single-blind , parallel , clinical trial of CaHA and collagen for soft-tissue augmentation of the urethral sphincter in the treatment of stress urinary incontinence enrolled 296 women . Up to five injections were performed in the first 6 months of the trial . Twelve-month postinjection efficacy data were available for 231 patients . RESULTS The results indicated that CaHA and collagen were both well tolerated in this study . No systemic adverse events were observed with either product . We used the Stamey Urinary Incontinence Scale to grade the improvement , which was the primary endpoint of the study . At 12 months , 83 ( 63.4 % ) of 131 CaHA patients compared with 57 ( 57.0 % ) of 100 collagen patients showed improvement of one Stamey grade or more ( P = 0.34 ) . More CaHA patients required only one injection ( n = 60 ; 38.0 % ) during the study compared with the Contigen patients ( n = 36 ; 26.1 % ; P = 0.034 ) . Also , the average total volume of material injected during the course of the study was less for CaHA than for collagen ( 4.0 mL versus 6.6 mL , respectively ; P < 0.0001 ) . CONCLUSIONS The results of the study have demonstrated that Coaptite is an appropriate and well-tolerated treatment for patients with incontinence due to intrinsic sphincter deficiency . This new soft-tissue augmentation material has a good safety profile and appears to provide durable improvement PURPOSE We prospect ively compared the efficacy and safety of tension-free vaginal tape and transobturator vaginal tape inside-out for female stress urinary incontinence . MATERIAL S AND METHODS A total of 120 women with stress urinary incontinence were alternately assigned to the tension-free vaginal tape group ( 60 ) or the transobturator vaginal tape inside-out group ( 60 ) . Preoperative evaluation included urodynamic study and a Korean version of the incontinence quality of life question naire . One year after operation the surgical result , patient satisfaction , incontinence quality of life question naire , long-term complications and uroflowmetry were evaluated in the 2 groups . RESULTS Patient characteristics were comparable in the 2 groups . Mean + /- SD operative time was significantly shorter in the transobturator vaginal tape inside-out vs the tension-free vaginal tape group ( 11 + /- 1.4 vs 15 + /- 1.8 minutes ) . In the transobturator vaginal tape inside-out and the tension-free vaginal tape groups the rates of cure ( 86.8 % and 86.8 % ) , improvement ( 6.6 % and 8.2 % ) and failure ( 6.6 % and 5.0 % , respectively ) were similar . Incontinence quality of life question naire parameters 1 year after surgery were improved significantly in each group and there was no difference between the 2 groups ( p < 0.001 and > 0.05 , respectively ) . There was no long-term complication in either group . Preoperative urge incontinence resolved in 80 % of the tension-free vaginal tape group and in 100 % of the transobturator vaginal tape inside-out group . De novo urgency developed in 4 patients ( 6.6 % ) in the transobturator vaginal tape inside-out group . CONCLUSIONS The tension-free vaginal tape and transobturator vaginal tape inside-out procedures were minimally invasive and similar in operation related morbidity . Transobturator vaginal tape inside-out appeared to be as effective and safe as tension-free vaginal tape for the surgical treatment of stress urinary incontinence in women at 1-year followup To compare the safety and efficacy of the transobturator tape ( Monarc ® ) with the retropubic tape ( tension-free vaginal tape , TVT ® ) for the treatment of urodynamic stress incontinence ( USI ) a prospect i ve , single-blinded , multi-centre r and omised clinical controlled trial was undertaken in four urogynaecology units in Australia . One hundred and eighty-seven women with USI were r and omly allocated to undergo surgery with either the Monarc sling ( n = 80 ) or TVT ( n = 107 ) . Outcome measures were intra-operative complications ( especially bladder injury ) , as well as peri-operative complications , symptomatology , quality of life and urodynamic outcomes . At 3 months , data were available on 140 women , 82 ( 59 % ) TVT and 58 ( 42 % ) Monarc . The TVT group was significantly more likely to be complicated by bladder injury ( 7 TVT , 0 Monarc , p < 0.05 ) . Blood loss and operative time were significantly less in the Monarc group , which was 49 mls ( 31 ) vs that of the TVT group , which was 64 mls ( 41 ) p < 0.05 ; 18.5 min ( 6.5 ) TVT vs 14.6 min ( 6 ) Monarc ( p < 0.001 ) . The subjective and objective stress incontinence cure rates were 86.6 % ( 71 ) vs 72.4 % ( 42 ) p = 0.77 and 79.3 vs 84.5 % , p = 0.51 for the TVT and Monarc groups , respectively . Both groups reported similar improvement in incontinence impact and satisfaction with their operation , although return to activity was significantly quicker with the transobturator route ( p = 0.029 ) . The transobturator tape appears to be as effective as the retro-pubic tape in the short term , with a reduction in the risk of intra-operative bladder injury , shorter operating time , decreased blood loss , and quicker return to usual activities PURPOSE The incidence of urinary incontinence in women of childbearing age is about 30 % . Around half have stress incontinence . Many treatment modalities have been eluci date d to treat stress incontinence , and among the most popular are rectus fascia sling and tension-free vaginal tape ( TVT ) . The introduction of TVT to the urological armamentarium put a multiplicity of synthetic material s into use in the correction of stress urinary incontinence . A comparison of the impact of these 2 commonly used techniques is needed . MATERIAL S AND METHODS A total of 53 female patients older than 21 years ( mean age 45.09 ) were r and omized , using closed envelopes , to undergo TVT or rectus fascia sling . R and omization was performed after patients received spinal anesthesia . One surgeon performed the 2 types of treatment . Associated grade 2 cystocele was simultaneously corrected . Patients with bladder or urethral pathology , as well as those with cystocele greater than grade 2 , were excluded from analysis . RESULTS All 53 patients completed 6 months of followup and all had stress urinary incontinence . There were 15 patients who underwent sling surgery and 17 who underwent TVT who had concomitant grade 1 or 2 cystocele . No statistically significant difference was found between the 2 groups at baseline . Cure was accomplished in 23 of 25 ( 92 % ) with sling and in 26 of 28 ( 92.9 % ) with TVT at first followup visit ( 1 week ) . There were 7 patients who needed at least 1 extra week of catheterization in the sling group and 3 in the TVT group . No significant difference was detected in terms of post-void residual urine , symptom score , and filling and voiding parameters . At 6 months 1 patient had de novo detrusor overactivity and 7 had wound pain . Compared to those with TVT , 2 cases of sling were considered treatment failures , none had de novo overactivity and 2 had wound pain . None of the patients had symptoms suggestive of urethral erosion . CONCLUSIONS Rectus fascia sling and TVT seem to be equally effective regarding primary outcome measure ( ie cure of stress incontinence ) . Symptom score related to incontinence surgery as well as simultaneous correction of cystocele are comparable in the 2 groups . Fascial sling is a longer treatment process yet it is more economical . Longer followup is vital before rigorous conclusions can be drawn Objective : To compare the safety and efficacy of three types of suburethral slings for the treatment of urodynamic stress incontinence OBJECTIVE To evaluate the use of Goretex pubovaginal sling and compare the results with a typical indigenous material graft made of rectal fascia . METHODS We have prospect ively evaluated 48 consecutive patients in a r and omized fashion in whom a sling procedure was performed to treat their type III incontinence . Sixteen women had a vesicourethral suspension ( VUS ) by a Goretex sling and another group of 32 patients , comparable in age range and medium age with the previous group , had a similar VUS by a sling from the rectus abdominis fascia . Both groups were evaluated urodynamically 6 and 30 months later . RESULTS In the first group , cure of incontinence was observed in 87.5 % and in the remaining patients it was significantly improved . In 2 patients there was an erosion of the urethra and the Goretex sling had to be removed 3.5 years later . Three other women remained dry but complained of occasional irritative symptoms . In the remaining 11 there was no erosion and the excellent postoperative result was maintained . In the group with fascial slings there was no erosion observed and in general they had less irritative symptoms . Cure or improvement of incontinence was comparable with the first group when studied 6 months after surgery , but there was a significant difference in the 30 months postoperative evaluation . CONCLUSIONS Use of a Goretex sling provides better long-term results even though it is associated with somewhat increased morbidity OBJECTIVE To compare the efficacy and safety of the tension-free vaginal tape ( TVT ) and inside-out transobturator tape ( TVT-O ) procedures for the treatment of stress urinary incontinence ( SUI ) . METHODS A total of 315 women with or without concomitant pelvic organ prolapse repairs were r and omly allocated to undergo a TVT or TVT-O procedure . Demographic data , intra- and postoperative complications , and surgical outcomes were analyzed . RESULTS Fifteen patients were lost to follow-up . There were no significant differences in cure rates between the 2 groups at 6 , 12 , 24 , and 36 months ' follow-up . Hematomas occurred in 4 patients and there were 6 vaginal tape erosions . Urinary retention and de novo urinary urgency were similar in both groups . The operative time was significantly shorter for TVT-O than for TVT without other procedures ( P<0.001 ) and postoperative groin/thigh pain was higher ( P<0.05 ) in the TVT-O group . CONCLUSION Both techniques appear equally effective for the treatment of SUI . However , TVT-O had a shorter operative time and a higher rate of groin/thigh pain PURPOSE In a pivotal trial we evaluated the effectiveness and safety of Macroplastique(R ) as minimally invasive endoscopic treatment for female stress urinary incontinence primarily due to intrinsic sphincter deficiency . MATERIAL S AND METHODS A total of 247 females with intrinsic sphincter deficiency were r and omized 1:1 and treated with a transurethral injection of Macroplastique or Contigen . The latter group served as the control . Repeat treatment was allowed after the 3-month followup . Effectiveness was determined 12 months after the last treatment using Stamey grade , pad weight and Urinary Incontinence Quality of Life Scale scores . Safety assessment was recorded throughout the study . RESULTS After 12 patients were excluded from study 122 patients received Macroplastique injection and 125 received Contigen injection . Mean patient age was 61 years and the average history of incontinence was 11.2 years . Of the patients 24 % had undergone prior incontinence surgery . At 12 months after treatment 61.5 % of patients who received Macroplastique and 48 % of controls had improved 1 Stamey grade . In the Macroplastique group the dry/cure rate was 36.9 % compared to 24.8 % in the control group ( p < 0.05 ) . In the Macroplastique and control groups the 1-hour pad weight decrease was 25.4 and 22.8 ml from baseline ( p = 0.64 ) , and the mean improvement in Urinary Incontinence Quality of Life Scale score was 28.7 and 26.4 ( p = 0.49 ) , respectively . CONCLUSIONS Macroplastique injection was statistically more effective than Contigen for stress urinary incontinence primarily due to intrinsic sphincter deficiency with a 12.1 % cure rate difference . Macroplastique can be administered on an outpatient basis . It should be considered a primary or secondary treatment option for stress urinary incontinence OBJECTIVE : To compare the safety and efficacy of the transobturator tape to tension-free vaginal tape ( TVT ) in the treatment of stress urinary incontinence in patients with and without concurrent pelvic organ prolapse . METHODS : One-hundred seventy women with urodynamic stress incontinence , including those with and those without pelvic organ prolapse , from three academic medical centers were r and omized to receive TVT or transobturator tape . Subjects with detrusor overactivity or previous sling surgery were excluded . The primary outcome was the presence or absence of abnormal bladder function , a composite outcome defined as the presence of any the following : incontinence symptoms of any type , a positive cough stress test , or retreatment for stress incontinence or postoperative urinary retention assessed 1 year after surgery . This study is a noninferiority study design . RESULTS : Of 180 women who enrolled in the study , 170 underwent surgery and 168 returned for follow-up , with a mean follow-up of 18.2±6 months . Mean operating time , length of stay , and postoperative pain scores were similar between the two groups . Bladder perforations occurred more frequently in the TVT group ( 7 % compared with 0 % , P=.02 ) ; otherwise , the incidence of perioperative complications was similar . Abnormal bladder function occurred in 46.6 % of TVT patients and 42.7 % of transobturator tape patients , with a mean absolute difference of 3.9 % favoring transobturator tape ( 95 % confidence interval –11.0 % to 18.6 % . ) . The P value for the one-sided noninferiority test was .006 , indicating that transobturator tape was not inferior to TVT . CONCLUSION : The transobturator tape is not inferior to TVT for the treatment of stress urinary incontinence and results in fewer bladder perforations . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00475839 LEVEL OF EVIDENCE : Objectives : To compare two different procedures , tension-free vaginal tape ( TVT ) and autologous rectus fascia sling , according to their medium-term subjective and objective outcomes and satisfaction rates in the treatment of urinary stress incontinence in women . Subjects and Methods : One hundred women with type II urinary stress incontinence were r and omized to be treated with either TVT or autologous rectus fascia sling . They were evaluated by means of a cough-induced stress test , 1-hour pad test , Incontinence Impact Question naire ( IIQ ) , and urodynamic study . They were reevaluated postoperatively every 6 months , and the collected data of more than 1 year ’s follow-up were compared with preoperative assessment s. Results : All patients completed the full 6-month postoperative assessment . However , of the 100 patients , only 61 ( 25 in the TVT and 36 in the sling group ) were followed for more than 1 year . Mean follow-up time was 38.5 and 40 months in the TVT and sling group , respectively . Objective cure was achieved in 22 ( 88 % ) of the TVT group and in 30 ( 83 % ) of the sling group ( p = 0.78 ) using a cough-induced stress test , and in 76 and 75 % of the women in the TVT versus sling group ( p = 0.83 ) , respectively , using a 1-hour pad test . Postoperative mean IIQ scores were 44.3 ( range 35.5–61.5 ) and 48.5 ( range 38.5–69.7 ) in the TVT versus sling group ( p = 0.46 ) . Five ( 20 % ) and 11 ( 30 % ) of the TVT and sling group , respectively , reported some changes in the voiding pattern or posture at more than 1 year ’s follow-up . Conclusion : There is no significant difference between the TVT and autologous rectus fascia sling procedures in the treatment of urinary stress incontinence at medium-term follow-up . There were changes in the voiding pattern for patients in both groups at more than 1 year postoperatively , which were not evident at early follow-up |
12,581 | 31,220,835 | We conclude that FV showed a modest and uncertain anticaries effect in preschoolers . | The aim of this study was to assess the effectiveness of fluoride varnish ( FV ) in reducing dentine caries at the patient , tooth , and surface levels as well as caries-related hospitalizations in preschoolers . | Sound evidence on the effectiveness of fluoride varnishes ( FV ) to reduce caries incidence in preschool children is lacking . Objective : To assess whether the application of FV in preschool children at 6-month intervals decreases the incidence of caries and produces any adverse effects . Methods : A r and omized , examiner- and patient-blind , placebo-controlled , parallel-group design , clinical trial , comprising 1- to 4-year-old children , 100 in each group ( FV or placebo varnish , PV ) , was conducted in Rio de Janeiro , Brazil . Two trained pediatric dentists performed the clinical examinations ( kappa = 0.85 ) . Dental caries was recorded at the d2 ( cavitated enamel ) and d3 ( dentine ) levels using the International Caries Diagnosis and Assessment System . Results : At baseline , the mean age of the participants was 2.4 years ( SD 0.9 ) and the mean d3mfs was 0.8 ( SD 1.9 ) . Most of the children brushed their teeth with fluoride toothpaste and consumed fluori date d tap water . After 24 months , 89 and 92 children of the test and the control groups were analyzed , respectively . A total of 32 ( 35.9 % ) children in the FV group and 43 ( 46.7 % ) in the PV group presented new dentine caries lesions ( χ2 test ; p = 0.14 ) , showing relative and absolute risk reductions of 23 % ( 95 % CI : -9.5 to 45.9 ) and 11 % ( 95 % CI : -3.5 to 25.0 ) . The mean caries increment differences between the test and control groups were -0.8 ( 95 % CI : -2.0 to 0.4 ) at the d2 level and -0.7 ( 95 % CI : -1.9 to 0.4 ) at the d3 level . Only 2 minor complaints regarding the intervention were reported . Conclusion : Although safe and well accepted , twice-yearly professional FV application , during 2 years , did not result in a significant decrease in caries incidence Objectives We tested a dental health program in remote Aboriginal communities of Australia 's Northern Territory , hypothesizing that it would reduce dental caries in preschool children . Methods In this 2-year , prospect i ve , cluster-r and omized , concurrent controlled , open trial of the dental health program compared to no such program , 30 communities were allocated at r and om to intervention and control groups . All residents aged 18–47 months were invited to participate . Twice per year for 2 years in the 15 intervention communities , fluoride varnish was applied to children 's teeth , water consumption and daily tooth cleaning with toothpaste were advocated , dental health was promoted in community setting s , and primary health care workers were trained in preventive dental care . Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child ( d3mfs ) . A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered r and omization design ; four other models used additional variables for adjustment . Results At baseline , 666 children were examined ; 543 of them ( 82 % ) were re-examined 2 years later . The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child ( 95 % CI = 1.2 , 4.9 ) , a prevented fraction of 31 % . Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36 % . Conclusions These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children Early childhood caries , a serious health problem among young children , can be prevented with effective intervention . The aim of this study was to evaluate the efficacy of oral health education and a fluoride varnish in the prevention of caries in children under the age of 3 years . For this single-blind r and omized parallel group 1-year clinical trial in Shiraz , 300 children aged 12 - 24 months with sound primary teeth were selected and r and omly divided into three groups ( n = 100 ) : ( 1 ) control : no preventive intervention ; ( 2 ) oral health counseling , and ( 3 ) oral health counseling and fluoride varnish at baseline and 6 months later . At baseline and 4 , 8 and 12 months after the intervention , caries risk reduction was recorded as the primary outcome . The mothers ' knowledge and performance regarding oral health in children was used as a secondary outcome . A total of 260 children ( mean age : 20.49 ± 7.33 months ) completed the study . Compared to group 1 , caries risk reduction in group 2 was 28 % ( 95 % CI : -39.05 to -17.45 ) and 31 % in group 3 ( 95 % CI : -41.88 to -21.73 ) . However , there was no significant difference between groups 2 and 3 ( 95 % CI : -8.58 to 1.47 ) . In all groups , mothers ' knowledge and performance at baseline were low ; however , they increased significantly in follow-up appointments in groups 2 and 3 ( p < 0.001 ) . Oral health education increased mothers ' knowledge and performance regarding oral health in children . Oral health counseling alone or associated with the use of fluoride varnish reduced the caries incidence in young children We conducted a parallel group r and omized controlled trial of children initially aged 2 to 3 y who were caries free , to prevent the children becoming caries active over the subsequent 36 mo . The setting was 22 dental practice s in Northern Irel and , and children were r and omly assigned by a clinical trials unit ( CTU ) ( using computer-generated r and om numbers , with allocation concealed from the dental practice until each child was recruited ) to the intervention ( 22,600-ppm fluoride varnish , toothbrush , 50-mL tube of 1,450 ppm fluoride toothpaste , and st and ardized , evidence -based prevention advice ) or advice-only control at 6-monthly intervals . The primary outcome measure was conversion from caries-free to caries-active states . Secondary outcome measures were number of decayed , missing , or filled teeth ( dmfs ) in caries-active children , number of episodes of pain , and number of extracted teeth . Adverse reactions were recorded . Calibrated external examiners , blinded to the child ’s study group , assessed the status of the children at baseline and after 3 y. In total , 1,248 children ( 624 r and omized to each group ) were recruited , and 1,096 ( 549 intervention , 547 control ) were included in the final analyses . Eighty-seven percent of intervention and 86 % of control children attended every 6-mo visit ( P = 0.77 ) . A total of 187 ( 34 % ) in the intervention group converted to caries active compared to 213 ( 39 % ) in the control group ( odds ratio , 0.81 ; 95 % confidence interval , 0.64–1.04 ; P = 0.11 ) . Mean dmfs of those with caries in the intervention group was 7.2 compared to 9.6 in the control group ( P = 0.007 ) . There was no significant difference in the number of episodes of pain between groups ( P = 0.81 ) or in the number of teeth extracted in caries-active children ( P = 0.95 ) . Ten children in the intervention group had adverse reactions of a minor nature . This well-conducted trial failed to demonstrate that the intervention kept children caries free , but there was evidence that once children get caries , it slowed down its progression ( EudraCT No : 2009 - 010725 - 39 ; IS RCT N : IS RCT N36180119 ) Objective : We aim ed to evaluate the efficacy of oral hygiene instruction , fluoride varnish and casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) for remineralizing white spot lesions ( WSL ) , and the effect of these on the dmft index in primary teeth . Subjects and Methods : In this 1-year , r and omized clinical trial , 140 children aged 12 - 36 months with WSL in the anterior maxillary teeth were selected and r and omly divided into 4 groups of 35 children each . Group 1 ( control ) received no preventive intervention . In group 2 , there was oral hygiene and dietary counseling . In group 3 , there was oral hygiene and the application of fluoride varnish at 4 , 8 and 12 months after baseline . In group 4 , there was oral hygiene and tooth mousse was applied by the parents twice a day over a 12-month period . At baseline and 4 , 8 and 12 months after the intervention , the size of WSL in millimeters and the dmft index were recorded . One hundred and twenty-two children completed the study . Data were analyzed using the repeated- measures ANOVA test . Results : In group 1 , the mean percent WSL area and dmft index values had increased significantly at 12 months after baseline ( p < 0.001 ) . The interventions led to significant decreases in the size of the WSL ; the greatest reduction was in group 4 ( 63 % ) followed by group 3 ( 51 % ) and group 2 ( 10 % ) after 12 months . The smallest increase in the dmft index was in group 4 ( 0.17 ) , followed by groups 3 ( 0.3 ) and 2 ( 0.42 ) . However , there were no significant differences between the groups ( p < 0.001 ) . Conclusions : Oral hygiene along with four fluoride varnish applications or constant CPP-ACP during the 12- month period reduced the size of WSL in the anterior primary teeth and caused a small increase in dmft index values OBJECTIVE To measure the effectiveness of fluoride varnish ( FV ) ( Duraflor ) , 5 % sodium fluoride , Pharmascience Inc. , Montréal , QC , Canada ) and caregiver counseling in preventing early childhood caries ( ECC ) in Aboriginal children in a 2-year community-r and omized controlled trial . METHODS Twenty First Nations communities in the Sioux Lookout Zone ( SLZ ) , Northwest Ontario , Canada were r and omized to two study groups . All caregivers received oral health counseling , while children in one group received FV twice per year and the controls received no varnish . A total of 1275 , 6 months to 5-year-old children from the SLZ communities were enrolled . In addition , a convenience sample of 150 primarily non-Aboriginal children of the same age were recruited from the neighboring community of Thunder Bay and used as comparisons . Longitudinal examinations for the dmft/s indices were conducted by calibrated hygienists in 2003 , 2004 and 2005 . RESULTS Aboriginal children living in the SLZ or in Thunder Bay had significantly higher caries prevalence and severity than non-Aboriginal children in Thunder Bay . FV treatment conferred an 18 % reduction in the 2-year mean ' net ' dmfs increment for Aboriginal children and a 25 % reduction for all children , using cluster analysis to adjust for the intra-cluster correlation among children in the same community . Adjusted odds ratio for caries incidence was 1.96 times higher in the controls than in the FV group ( 95 % CI = 1.08 - 3.56 ; P = 0.027 ) . For those caries-free at baseline , the number ( of children ) needed to treat ( NNT ) equaled 7.4 . CONCLUSIONS Findings support the use of FV at least twice per year , in conjunction with caregiver counseling , to prevent ECC , reduce caries increment and oral health inequalities between young Aboriginal and non-Aboriginal children The authors tested the effectiveness of a community-based , tribally delivered oral health promotion ( OHP ) intervention ( INT ) at reducing caries increment in Navajo children attending Head Start . In a 3-y cluster-r and omized trial , we developed an OHP INT with Navajo input that was delivered by trained Navajo lay health workers to children attending 52 Navajo Head Start classrooms ( 26 INT , 26 usual care [ UC ] ) . The INT was design ed as a highly personalized set of oral health – focused interactions ( 5 for children and 4 for parents ) , along with 4 fluoride varnish applications delivered in Head Start during academic years of 2011 to 2012 and 2012 to 2013 . The authors evaluated INT impact on decayed , missing , and filled tooth surfaces ( dmfs ) increment compared with UC . Other outcomes included caries prevalence and caregiver oral health – related knowledge and behaviors . Modified intention-to-treat and per- protocol analyses were conducted . The authors enrolled 1,016 caregiver-child dyads . Baseline mean dmfs/caries prevalence equaled 19.9/86.5 % for the INT group and 22.8/90.1 % for the UC group , respectively . INT adherence was 53 % ( i.e. , ≥3 child OHP events , ≥1 caregiver OHP events , and ≥3 fluoride varnish ) . After 3 y , dmfs increased in both groups ( + 12.9 INT vs. + 10.8 UC ; P = 0.216 ) , as did caries prevalence ( 86.5 % to 96.6 % INT vs. 90.1 % to 98.2 % UC ; P = 0.808 ) in a modified intention-to-treat analysis of 897 caregiver-child dyads receiving 1 y of INT . Caregiver oral health knowledge scores improved in both groups ( 75.1 % to 81.2 % INT vs. 73.6 % to 79.5 % UC ; P = 0.369 ) . Caregiver oral health behavior scores improved more rapidly in the INT group versus the UC group ( P = 0.006 ) . The dmfs increment was smaller among adherent INT children ( + 8.9 ) than among UC children ( + 10.8 ; P = 0.028 ) in a per- protocol analysis . In conclusion , the severity of dental disease in Navajo Head Start children is extreme and difficult to improve . The authors argue that successful approaches to prevention may require even more highly personalized approaches shaped by cultural perspectives and attentive to the social determinants of oral health ( Clinical Trials.gov NCT01116739 ) A 2-arm parallel-group r and omized controlled trial measured the cost-effectiveness of caries prevention in caries-free children aged 2 to 3 y attending general practice . The setting was 22 dental practice s in Northern Irel and . Participants were central ly r and omized into intervention ( 22,600 ppm fluoride varnish , toothbrush , a 50-mL tube of 1,450 ppm fluoride toothpaste , and st and ardized prevention advice ) and control ( advice only ) , both provided at 6-monthly intervals during a 3-y follow-up . The primary outcome measure was conversion from caries-free to caries-active states assessed by calibrated and blinded examiners ; secondary outcome measures included decayed , missing , or filled teeth surfaces ( dmfs ) ; pain ; and extraction . Cumulative costs were related to each of the trial ’s outcomes in a series of incremental cost effectiveness ratios ( ICERs ) . Sensitivity analyses examined the impact of using dentist ’s time as measured by observation rather than that reported by the dentist . The costs of applying topical fluoride were also estimated assuming the work was undertaken by dental nurses or hygienists rather than dentists . A total of 1,248 children ( 624 r and omized to each group ) were recruited , and 1,096 ( 549 in the intervention group and 547 in the control group ) were included in the final analyses . The mean difference in direct health care costs between groups was £ 107.53 ( £ 155.74 intervention , £ 48.21 control , P < 0.05 ) per child . When all health care costs were compared , the intervention group ’s mean cost was £ 212.56 more than the control group ( £ 987.53 intervention , £ 774.97 control , P < 0.05 ) . Statistically significant differences in outcomes were only detected with respect to carious surfaces . The mean cost per carious surface avoided was estimated at £ 251 ( 95 % confidence interval , £ 454.39–£79.52 ) . Sensitivity analyses did not material ly affect the study ’s findings . This trial raises concerns about the cost-effectiveness of a fluoride-based intervention delivered at the practice level in the context of a state-funded dental service ( EudraCT No : 2009 - 010725 - 39 ; IS RCT N : IS RCT N36180119 ) The aim was to study the effect of substitution of invert sugar for sucrose , in combination with fluoride varnish ( Duraphat ) treatment twice a year , on caries development in preschool children . One hundred and eighty-seven 4-years-olds were divided r and omly into four sugar groups : ( 1 ) sucrose ( S ) , ( 2 ) sucrose-Duraphat ( SD ) , ( 3 ) invert sugar ( I ) , and ( 4 ) invert sugar-Duraphat ( ID ) . All families were asked to buy beverages , biscuits , breakfast cereals , marmalade , ice cream , jam , ketchup , sweets and table sugar , totally 32 different food items , sweetened with invert sugar or sucrose . The substitution was , thus , restricted to a number of sugar-rich between-meal products . The study was carried out double-blind for 2 years . The children of those parents who did not want to participate in the sugar groups were divided r and omly into one of the following two groups : ( 5 ) Duraphat ( D ) , and control ( C ) . Because of lack of cooperation , only 114 of the 187 children ( 61 % ) were considered to have completed the study . The mean caries increment , including initial lesions , was 3.86 dmfs in the combined groups S and SD ( n = 63 ) and 3.10 dmfs in the combined groups I and ID ( n = 51 ) during the 2 years ( p = 0.34 ) . The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs , respectively ( p = 0.09 ) . The mean caries increment was 2.86 dmfs in group D ( n = 113 ) and 4.10 dmfs ( p = 0.08 ) in group C ( n = 93 ) . If initial caries lesions were excluded from the index , the difference between groups D and C was significant ( p = 0.008 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES Early childhood caries ( ECC ) constitutes a serious public health issue , especially in communities without water fluoridation . We assessed the effectiveness of biannual fluoride varnish applications to prevent ECC in children from nonfluori date d rural areas . METHODS A triple-blind r and omized control trial with two parallel arms was conducted with 275 two- to three-year-old children without cavitated carious lesions from 28 rural public preschools in Chile . The preschools were located in areas of low socioeconomic status without access to fluori date d water . An oral health education component was administered to children , parents and educators . A new toothbrush and toothpaste for each child was delivered to the parents at baseline and at four follow-up visits . The participants were r and omly allocated to receive fluoride varnish or placebo applications every six months . Trained , calibrated dentists blind to the treatment arm performed visual dental assessment s at 6 , 12 , 18 and 24 months . The primary endpoint was the development of cavitated carious lesions in children during the 24-month follow-up period using WHO criteria , and the secondary outcomes were an increase in caries measured as a change in the index of decayed , missing or filled teeth ( dmft ) since the beginning of the study and the development of adverse effects . An intention-to-treat ( ITT ) approach was used for the primary analysis . RESULTS We included 131 participants in the intervention group and 144 participants in the placebo group ; of these children , 89 ( 67.9 % ) in the intervention group and 100 ( 69.4 % ) in the control group completed the protocol . The comparative ITT analysis of caries incidence after 24 months of follow-up showed a between-group prevention fraction of 18.9 % ( -2.9%-36.2 % ) . Caries incidence was 45.0 % for the experiment group and 55.6 % for the control group ( P = .081 ) , with a mean dmft of 1.6 ( SD = 2.4 ) and 2.1 ( SD = 2.5 ) , respectively . No adverse effects were reported . CONCLUSIONS In conclusion , biannual fluoride varnish application is not effective in preschool children from rural nonfluori date d communities at a high risk of caries UNLABELLED Navajo Nation children have the greatest prevalence of early childhood caries in the United States . This protocol describes an innovative combination of community-based participatory research and clinical trial methods to rigorously test a lay native Community Oral Health Specialists-delivered oral health intervention , with the goal of reducing the progression of disease and improving family knowledge and behaviors . METHODS / DESIGN This cluster-r and omized trial design ed by research ers at the Center for Native Oral Health Research at the University of Colorado in conjunction with members of the Navajo Nation community compares outcomes between the manualized 2-year oral health fluoride varnish-oral health promotion intervention and usual care in the community ( child-caregiver dyads from 26 Head Start classrooms in each study arm ; total of 1016 dyads ) . Outcome assessment includes annual dental screening and an annual caregiver survey of knowledge , attitudes and behaviors ; collection of cost data will support cost-benefit analyses . DISCUSSION The study protocol meets all st and ards required of r and omized clinical trials . Aligned with principles of community-based participatory research , extended interaction between members of the Navajo community and research ers preceded study initiation , and collaboration between project staff and a wide variety of community members informed the study design and implementation . We believe that the benefits of adding CBPR methods to those of r and omized clinical studies outweigh the barriers and constraints , especially in studies of health disparities and in challenging setting s. When done well , this innovative mix of methods will increase the likelihood of valid results that communities can use This study evaluated whether toddlers in an extended preventive program of semiannual fluoride varnish applications from 1 year of age had a lower incidence of caries than those undergoing a st and ard program . A cohort of 1-year-old children ( n = 3,403 ) living in multicultural areas of low socioeconomic st and ing in Stockholm participated in a cluster-r and omized controlled field trial with two parallel arms . The children attended 23 dental clinics . Using the ICDAS II criteria , the examiners recorded caries at baseline and after 1 and 2 years . The children in the reference group received a st and ardized oral health program once yearly between 1 and 3 years of age . The children in the test group received the same st and ard program supplemented with topical applications of fluoride varnish every 6 months . We compared the test group and the reference group for the prevalence and increment of caries . At baseline , 5 % of the children had already developed caries ( ICDAS II 1 - 6 ) . We reexamined the children after 1 year ( n = 2,675 ) and after 2 years ( n = 2,536 ) . Neither prevalence nor caries increment differed between the groups . At 3 years of age , 12 % of the children had developed moderate and severe carious lesions ( ICDAS II 3 - 6 ) , with a mean increment of 0.5 ( SD 2.4 ) in the test group and 0.6 ( SD 2.2 ) in the reference group . In conclusion , semiannual professional applications of fluoride varnish , as a supplement to a st and ard oral health program , failed to reduce caries development in toddlers from high-risk communities OBJECTIVE To evaluate the clinical effect of fluoride varnish in preventing caries of primary teeth , and to compare the caries prevention effects of fluoride varnish with two different concentrations . METHODS 150 children whose ages were three year-old were r and omly chosen from one of nurseries of Chongqing , and were r and omly divided into four groups with 37 children in 0.5 % fluoride varnish group , 38 children in 0.1 % fluoride varnish group , 39 children in 0.5 % sodium fluoride group and 36 children in blank group . The groups included 71 ' girls and 79 boys . Protective measure was applied every half an year and the research has lasted for two years . The research was design ed by double-blinded methods , and was carried out with the dental caries st and ard suggested by World Health Organization . All the data were collected and the clinical effects of four groups were compared . RESULTS The average caries index and caries surface index of 0.1 % fluoride varnish group and those of control groups were significantly higher than that of 0.5 % fluoride varnish group . There were no significant difference between the average caries index and caries surface index of 0.1 % fluoride varnish group and those of control groups . CONCLUSION 0.5 % fluoride varnish was effective in preventing caries of primary teeth PURPOSE To compare the prevalence and severity of fluorosis in the permanent maxillary incisors of children who had participated in a two-year r and omized placebo-controlled clinical trial on fluoride varnish application in the primary dentition and to assess children 's esthetic perception of their teeth . METHODS Parents of 200 one- to four-year-old children who had received biannual applications of fluoride or placebo varnish were contacted four years after the end of the trial . Two calibrated examiners assessed dental fluorosis using the Thylstrup and Fejerskov index ( TF ) and interviewed the children regarding their perceptions of teeth appearance . RESULTS Fluorosis ( TF equals at least one ) and esthetically objectionable fluorosis ( TF equals at least three ) were observed in 38 ( 30.9 percent ) and eight ( 6.5 percent ) children , respectively . There was no statistically significant difference in fluorosis prevalence between children who had received fluoride or placebo varnish . Children 's responses regarding the esthetic perceptions of their teeth showed no statistically significant difference between children with and without fluorosis . CONCLUSIONS Fluoride varnish applications in preschoolers were not associated with any level of fluorosis in their permanent maxillary incisors . The fluorosis found in this study did not influence the children 's esthetic perception of their teeth AIM The aim of the study was to assess the caries inhibition effect of fluoride varnishes among preschool children with high caries risk . At the same time , the suitability of this measure should be examined in the frame of group prevention programmes in kindergartens . METHOD This was an examiner-blind , clinical ly controlled 2-year study with 200 r and omly selected 2- to 4-year-old preschool children with high caries risk . At the baseline , caries-free surfaces , initial caries lesions as well as the caries status ( dmfs ) were recorded . After the baseline , all subjects were divided into 3 groups . Subjects of group A received every 6 months ( altogether four times ) applications with the fluoride varnish Fluoridin N5 ( VOCO GmbH , Cuxhaven , Germany ) , children of the group B received every 6 months ( altogether four times ) applications with Duraphat ( Colgate Palmolive GmbH , Hamburg , Germany ) , while the subjects of group C did not receive any fluoride varnish applications and constituted the control group . A final examination was performed after two years similar to the baseline . Statistical analysis was based on the SPSS programme at a significance level of 95 % . RESULTS AND CONCLUSIONS The results confirmed the caries inhibition efficacy of both fluoride varnishes . This is shown as well in the almost constant number of caries-free surfaces and initial caries lesions in the two F-groups during the observation period . The caries-free surfaces in group C were significantly reduced along with an increase of initial caries lesions . The caries reduction , based on the control group , amounted in group A to 56 % and in group B to 57 % . The results documented the caries inhibition effect of both fluoride varnishes which are suitable for intensive group prevention programmes for pre-school children To determine the efficacy of fluoride varnish ( 5 % NaF , Duraphat ® , Colgate ) added to caregiver counseling to prevent early childhood caries , we conducted a two-year r and omized , dental-examiner-masked clinical trial . Initially , 376 caries-free children , from low-income Chinese or Hispanic San Francisco families , were enrolled ( mean age ± st and ard deviation , 1.8 ± 0.6 yrs ) . All families received counseling , and children were r and omized to the following groups : no fluoride varnish , fluoride varnish once/year , or fluoride varnish twice/year . An unexpected protocol deviation result ed in some children receiving less active fluoride varnish than assigned . Intent-to-treat analyses showed a fluoride varnish protective effect in caries incidence , p < 0.01 . Analyzing the number of actual , active fluoride varnish applications received result ed in a dose-response effect , p < 0.01 . Caries incidence was higher for ‘ counseling only ’ vs. ‘ counseling + fluoride varnish assigned once/year ’ ( OR = 2.20 , 95 % CI 1.19–4.08 ) and ‘ twice/year ’ ( OR = 3.77 , 95 % CI 1.88–7.58 ) . No related adverse events were reported . Fluoride varnish added to caregiver counseling is efficacious in reducing early childhood caries incidence OBJECTIVE The aim of this two-year community demonstration trial was to study the caries inhibitory effects of semiannual applications of a fluoride varnish in preschool children . METHODS Twenty-four public dental health clinics in the county of Hall and , Sweden , with 5,137 preschool children , 4 and 5 years of age , were matched and equally allocated to a fluoride varnish group ( n = 2,535 ) and a reference group ( n = 2,602 ) . The children in the fluoride varnish group were treated every six months with topical applications of a silane fluoride varnish , Fluor Protector ( 0.1 % F ) , while no fluoride varnish was used in the reference group . Both groups received a basic preventive program at annual checkups consisting of dietary counseling and instructions to parents to brush their children 's teeth at least once daily with fluori date d dentifrice . Caries data were collected by clinical examinations at baseline and after one and two years . RESULTS Caries prevalence at baseline did not differ significantly between the groups . After two years , the mean caries incidence was low and no statistical difference was found in the total number of carious and filled surfaces ( dfs ) between the two groups . However , the incidence of approximal lesions ( dfsa ) was significantly lower ( P < .05 ) in the fluoride varnish group than the reference group . Children in the fluoride varnish group with dfs scores of 1 - 4 and > or = 5 at the start of the study exhibited a statistically significant ( P < .05 ) reduction in approximal caries incidence of 19 percent and 25 percent , respectively , when compared with the reference group . CONCLUSION Preschool children 4 and 5 years of age with clinical caries who receive semiannual applications of a silane fluoride varnish containing 0.1 percent F experience a reduced incidence of approximal caries over two years OBJECTIVES The total body of evidence finds fluoride varnish effective to prevent caries . However , most trials were conducted in high-risk population s , with more recent trials on low-risk groups finding a lower efficacy . We aim ed to assess the cost-effectiveness of fluoride varnish application in clinic setting in population s with different caries risk . METHODS A mixed public-private-payer perspective in the context of German health care was performed using a lifetime Markov model . Effectiveness data were derived from an up date of the most recent systematic Cochrane review and synthesized in three different risk groups according to control group caries increment via r and om-effects meta- analysis . Varnish was assumed to be applied twice yearly between age 6 and 18 years . Teeth with carious defects would be treated restoratively and could experience further follow-up treatments . Costs were deduced from German fee item catalogues . Monte Carlo microsimulations were used for to analyse lifetime treatment costs and caries increment ( Euro/Decayed , Missing , Filled Teeth ( DMFT ) ) . RESULTS In low-risk groups , fluoride varnish was nearly twice as costly and minimally more effective ( 293 Euro , 8.1 DMFT ) than no varnish ( 163 Euro , 8.5 DMFT ) . The incremental cost-effectiveness ratio ( ICER ) was 343 Euro spent per avoided DMFT . The ICER was lower in medium-risk ( ICER 93 Euro/DMFT ) and high-risk groups ( 8 Euro/DMFT ) . CONCLUSIONS Application of fluoride varnish in the clinic setting is unlikely to be cost-effective in low-risk population s. There is the need to either target high-risk groups or to provide fluoride varnish at lower costs , possibly in nonclinic setting OBJECTIVES To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste . METHODS 424 preschool children , 2 - 5 year of age , from 10 different pre schools in Athens were invited to this double-blind r and omized controlled trial and 328 children completed the 2-year programme . All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily . The test group was treated with fluoride varnish ( 0.9 % diflurosilane ) biannually while the control group had placebo applications . The primary endpoints were caries prevalence and increment ; secondary outcomes were gingival health , mutans streptococci growth and salivary buffer capacity . RESULTS The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years , respectively . There was a reduced number of new pre-cavitated enamel lesions during the second year of the study ( p=0.05 ) but the decrease was not statistically significant . The secondary endpoints were unaffected by the varnish treatments . CONCLUSIONS Under the present conditions , biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste . CLINICAL SIGNIFICANCE In community based , caries prevention programmes , for high caries risk preschool children , a fluoride varnish may add little to caries prevention , when 1000ppm fluoride toothpaste is used daily OBJECTIVES To investigate the effectiveness of h and s-on training in parental toothbrushing , with or without semi-annual applications of 5 % sodium fluoride varnish in preventing ECC . METHODS Study was conducted in Hong Kong where water is optimally fluori date d. Children aged 8 - 23 months were recruited and r and omly allocated to one of three groups : Gp 1 - control , one-off oral health education talk to parents ; Gp 2 - oral health education talk and parental toothbrushing training , reinforced every 6 months ; Gp 3 - semi-annual application of fluoride varnish onto child 's teeth in addition to the intervention provided to Gp 2 . Clinical examinations of the children and interviews were conducted at baseline and after 24 months to assess the children 's dental caries status and toothbrushing behaviour . RESULTS Out of the 450 child-parent dyads recruited at baseline , 415 ( 92 % ) remained after 24 months . At baseline , 2 % of the children had non-cavitated enamel caries lesions and the mean dmft score was 0.03 ± 0.24 . Most of the children did not have daily parental toothbrushing ( 65 - 73 % ) and self toothbrushing ( 86 - 90 % ) . At 24-month follow-up , including both non-cavitated and cavitated carious lesions , the incidences of ECC in Gp 1 to Gp 3 were 11.9 % , 11.8 % , and 17.5 % , respectively ( p>0.05 ) ; and the mean new dmft scores in Gp 1 to Gp 3 were 0.3 , 0.2 , and 0.3 , respectively ( p>0.05 ) . Proportions of parents who practice d parental toothbrushing twice daily were 62.7 % , 60.4 % , and 65.7 % in Gp 1 to Gp 3 , respectively ( p>0.05 ) . CONCLUSIONS In a water fluori date d area , h and s-on training in parental toothbrushing , with or without semi-annual application of 5 % sodium fluoride varnish may not have additional effect on preventing ECC in young children with low risk of dental caries compared to provision of oral health education to parents . CLINICAL SIGNIFICANCE In a water fluori date d area , provision of individual oral health education to parents may be sufficient for preventing ECC in young children below age 3 . Supplemental training in parental toothbrushing and semi-annual applications of fluoride varnish may not have additional caries prevention effect in young children with low risk of dental caries |
12,582 | 31,479,532 | We found evidence that the alpha2 agonist dexmedetomidine may shorten delirium duration , although this small effect ( compared with placebo ) was seen in pairwise analyses based on a single study and was not seen in the NMA results .
Alpha2 agonists also ranked best for duration of mechanical ventilation and length of ICU stay , whereas the CHE inhibitor rivastigmine was associated with longer ICU stay .
We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days , days with coma , physical restraint use , length of stay , long-term cognitive outcomes , or mortality . | BACKGROUND Although delirium is typically an acute reversible cognitive impairment , its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients .
Advances in our underst and ing of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions .
However , considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population .
OBJECTIVES Primary objective 1 .
To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of delirium Secondary objectives To assess the following:1 .
effects of pharmacological interventions on delirium-free and coma-free days ; days with coma ; delirium relapse ; duration of mechanical ventilation ; intensive care unit ( ICU ) and hospital length of stay ; mortality ; and long-term outcomes ( e.g. cognitive ; discharge disposition ; health-related quality of life ) ; and 2 .
the safety of such treatments for critically ill adult patients . | Introduction We hypothesized that delirium symptoms may respond differently to antipsychotic therapy . The purpose of this paper was to retrospectively compare duration and time to first resolution of individual delirium symptoms from the data base of a r and omized , double-blind , placebo-controlled study comparing quetiapine ( Q ) or placebo ( P ) , both with haloperidol rescue , for critically ill patients with delirium . Methods Data for 10 delirium symptoms from the eight-domain , intensive care delirium screening checklist ( ICDSC ) previously collected every 12 hours were extracted for 29 study patients . Data between the Q and P groups were compared using a cut-off P- value of ≤0.10 for this exploratory study . Results Baseline ICDSC scores ( 5 ( 4 to 7 ) ( Q ) vs 5 ( 4 to 6 ) ) ( median , interquartile range ( IQR ) ) and % of patients with each ICDSC symptom were similar in the two groups ( all P > 0.10 ) . Among patients with the delirium symptom at baseline , use of Q may lead to a shorter time ( days ) to first resolution of symptom fluctuation ( 4 ( Q ) vs. 14 , P = 0.004 ) , inattention ( 3 vs. 8 , P = .10 ) and disorientation ( 2 vs. 10 , P = 0.10 ) but a longer time to first resolution of agitation ( 3 vs. 1 , P = 0.04 ) and hyperactivity ( 5 vs. 1 , P = 0.07 ) . Among all patients , Q-treated patients tended to spend a smaller percent of time with inattention ( 47 ( 0 to 67 ) vs. 78 ( 43 to 100 ) , P = 0.025 ) , hallucinations ( 0 ( 0 to 17 ) vs. 28 ( 0 to 43 ) , P = 0.10 ) and symptom fluctuation ( 47 ( 19 to 67 ) vs. 89 ( 33 to 00 ) , P = 0.04 ] and there was a trend for Q-treated patients to spend a greater percent of time at an appropriate level of consciousness ( 26 % ( 13 to 63 % ) vs. 14 % ( 0 to 33 % ) , P = 0.17 ] . Conclusions Our exploratory analysis suggests that quetiapine may resolve several intensive care unit ( ICU ) delirium symptoms faster than the placebo . Individual symptom resolution appears to differ in association with the pharmacologic intervention ( that is , P vs Q , both with as needed haloperidol ) . Future studies evaluating antipsychotics in ICU patients with delirium should measure duration and resolution of individual delirium symptoms and their relation to long-term outcomes 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 Introduction Delirium is a common , serious and potentially preventable condition with devastating impact on the quality of life prompting a proliferation of interventional trials . Core outcome sets aim to st and ardise outcome reporting by identifying outcomes perceived fundamental for measurement in trials of a specific interest area . Our aim is to develop international consensus on two core outcome sets for trials of interventions to prevent and /or treat delirium , irrespective of study population . We aim to identify additional core outcomes specific to the critically ill , acutely hospitalised patients , palliative care and older adults . Methods and analysis We will conduct a systematic review of published and ongoing delirium trials ( 1980 onwards ) and one-on-one interviews of patients who have experienced delirium and family members . These data will inform Delphi round 1 of a two-stage consensus process . In round 2 , we will provide participants their own response , summarised group responses and those of patient/family participants for rescoring . We will r and omise participants to receive feedback as proportion scoring the outcome as critical or as group mean responses . We will hold a consensus meeting using nominal group technique to finalise outcomes for inclusion . We will repeat the Delphi process and consensus meeting to select measures for each core outcome . We will recruit 240 Delphi participants giving us 80 % power to detect a 1.0–1.5 point ( 9-point scale ) difference by feedback method between rounds . We will analyse differences for subsequent scores , magnitude of opinion change , items retained and level of agreement . Ethics and dissemination We are obtaining research ethics approvals according to local governance . Participation will be voluntary and data deidentified . Support from three international delirium organisations will be instrumental in dissemination and core outcome set uptake . We will disseminate through peer- review ed open access publications and present at conferences selected to reach a wide range of knowledge users BACKGROUND Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge . Pre clinical and observational studies suggest that the use of statins might reduce delirium in intensive care . We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a r and omised controlled trial . METHODS We did this ancillary study within the SAILS trial , a r and omised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome . This study was done at 35 hospitals in the USA . Patients were r and omly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin ( 40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care , study day 28 , or death ) or placebo . Patients and investigators were masked to treatment assignment . Delirium was assessed with the vali date d Confusion Assessment Method for intensive care . Cognitive function was assessed with tests for executive function , language , verbal reasoning and concept formation , and working , immediate , and delayed memory . We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms . The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months . This trial is registered with Clinical Trials.gov ( NCT00979121 and NCT00719446 ) . FINDINGS 272 patients were assessed for delirium daily in intensive care . The mean proportion of days with delirium was 34 % ( SD 30 % ) in the rosuvastatin group versus 31 % ( 29 % ) in the placebo group ; hazard ratio 1·14 , 95 % CI 0·92 - 1·41 , p=0·22 . At 6 months , 19 ( 36 % ) of 53 patients in the rosuvastatin group versus 29 ( 38 % ) of 77 in the placebo group had cognitive impairment , with no significant difference between groups ( treatment effect 0·93 , 95 % CI 0·39 - 2·22 ; p=0·87 ) . At 12 months , 20 ( 30 % ) of 67 patients versus 23 ( 28 % ) of 81 patients had cognitive impairment , with no significant difference between groups ( treatment effect 1·1 , 95 % CI 0·5 - 2·6 ; p=0·82 ) . INTERPRETATION Most patients had delirium , with around a third of survivors having cognitive impairment over 1 year of follow-up . Despite encouraging pre clinical and observational studies , this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority . Thus , there is continued need to evaluate interventions aim ed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population . FUNDING National Heart , Lung and Blood Institute ; Johns Hopkins Institute for Clinical and Translational Research ; the SAILS trial was also supported by AstraZeneca BACKGROUND Delirium in critically ill patients is associated with poor clinical outcomes . Neuroinflammation might be an important mechanism in the pathogenesis of delirium , and since simvastatin has anti-inflammatory properties it might reduce delirium . We aim ed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma . METHODS We undertook this r and omised , double-blind , placebo-controlled trial in a general adult intensive care unit ( ICU ) in Watford General Hospital ( Watford , UK ) . We enrolled critically ill patients ( ≥18 years ) needing mechanical ventilation within 72 h of admission . We r and omly assigned patients ( 1:1 ratio ) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days , irrespective of coma or delirium status . We assessed delirium using the Confusion Assessment Method for the ICU ( CAM-ICU ) . The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being r and omly allocated to receive treatment or placebo . ICU clinical and research staff and patients were masked to treatment . We did intention-to-treat analyses with no extrapolation . This trial is registered with the International St and ard R and omised Controlled Trial Registry , number IS RCT N89079989 . FINDINGS Between Feb 1 , 2013 , and July 29 , 2016 , 142 patients were r and omly assigned to receive simvastatin ( n=71 ) or placebo ( n=71 ) , and were included in the final analysis . The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups ( 5·7 days [ SD 5·1 ] with simvastatin and 6·1 days [ 5·2 ] with placebo ; mean difference 0·4 days , 95 % CI -1·3 to 2·1 ; p=0·66 ) . The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal ( eight [ 11 % ] in the simvastatin group vs three [ 4 % ] in the placebo group p=0·208 ) . No patient had a serious adverse event related to the study drug . INTERPRETATION These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients . FUNDING National Institute for Health Research Objective : To compare the efficacy and safety of scheduled quetiapine to placebo for the treatment of delirium in critically ill patients requiring as-needed haloperidol . Design : Prospect i ve , r and omized , double-blind , placebo-controlled study . Setting : Three academic medical centers . Patients : Thirty-six adult intensive care unit patients with delirium ( Intensive Care Delirium Screening Checklist score ≥4 ) , tolerating enteral nutrition , and without a complicating neurologic condition . Interventions : Patients were r and omized to receive quetiapine 50 mg every 12 hrs or placebo . Quetiapine was increased every 24 hrs ( 50 to 100 to 150 to 200 mg every 12 hrs ) if more than one dose of haloperidol was given in the previous 24 hrs . Study drug was continued until the intensive care unit team discontinued it because of delirium resolution , therapy ≥10 days , or intensive care unit discharge . Measurements and Main Results : Baseline characteristics were similar between the quetiapine ( n = 18 ) and placebo ( n = 18 ) groups . Quetiapine was associated with a shorter time to first resolution of delirium [ 1.0 ( interquartile range [ IQR ] , 0.5–3.0 ) vs. 4.5 days ( IQR , 2.0–7.0 ; p = .001 ) ] , a reduced duration of delirium [ 36 ( IQR , 12–87 ) vs. 120 hrs ( IQR , 60–195 ; p = .006 ) ] , and less agitation ( Sedation-Agitation Scale score ≥5 ) [ 6 ( IQR , 0–38 ) vs. 36 hrs ( IQR , 11–66 ; p = .02 ) ] . Whereas mortality ( 11 % quetiapine vs. 17 % ) and intensive care unit length of stay ( 16 quetiapine vs. 16 days ) were similar , subjects treated with quetiapine were more likely to be discharged home or to rehabilitation ( 89 % quetiapine vs. 56 % ; p = .06 ) . Subjects treated with quetiapine required fewer days of as-needed haloperidol [ 3 [ ( IQR , 2–4 ) ] vs. 4 days ( IQR , 3–8 ; p = .05 ) ] . Whereas the incidence of QTc prolongation and extrapyramidal symptoms was similar between groups , more somnolence was observed with quetiapine ( 22 % vs. 11 % ; p = .66 ) . Conclusions : Quetiapine added to as-needed haloperidol results in faster delirium resolution , less agitation , and a greater rate of transfer to home or rehabilitation . Future studies should evaluate the effect of quetiapine on mortality , re source utilization , post-intensive care unit cognition , and dependency after discharge in a broader group of patients Background : The aim of this r and omized , parallel-arm trial was to study the effect of treating subsyndromal delirium with risperidone on the incidence of clinical delirium in elderly patients who underwent on-pump cardiac surgery . Methods : One hundred one patients aged 65 yr or older who experienced subsyndromal delirium after on-pump cardiac surgery were r and omized using a computer-generated list to receive 0.5 mg risperidone ( n = 51 ) or placebo ( n = 50 ) every 12 h by mouth . Patients were assessed at 8 h by a blinded observer using the Intensive Care Delirium Screening Checklist , and those scoring more than 3 were evaluated by a blinded psychiatrist to confirm delirium . Patients in either group who experienced delirium were treated according to the same algorithm . Initially , risperidone was administered and if symptoms were not controlled , haloperidol was administered . The primary outcome was the proportion of patients who experienced delirium in either group . Results : Seven ( 13.7 % ) patients in the risperidone group experienced delirium versus 17 ( 34 % ) in the placebo group ( P = 0.031 ) Competing-risks regression analysis showed that failure to treat subsyndromal delirium with risperidone was an independent risk factor for delirium ( subhazard ratio , 3.83 ; 95 % CI , 1.63–8.98 ; P = 0.002 ) . Two ( 3.9 % ) patients in the risperidone group experienced extrapyramidal manifestations versus one ( 2 % ) in the placebo group ( P = 1.0 ) . Conclusion : Administration of risperidone to elderly patients who experienced subsyndromal delirium after on-pump cardiac surgery was associated with significantly lower incidence of delirium . Larger studies are required to determine whether early administration of risperidone during the subsyndromal phase of delirium would influence the clinical course of such patients Background Delirium often has a poor outcome , but why some people have incomplete recovery is not well understood . Our objective was to identify factors associated with short-term ( by discharge ) and long-term ( by 6 month ) incomplete recovery of function following delirium . Methods In a prospect i ve cohort study of elderly patients with delirium seen by geriatric medicine services , function was assessed at baseline , at hospital discharge and at six months . Results Of 77 patients , vital and functional status at 6 months was known for 71 , of whom 21 ( 30 % ) had died . Incomplete functional recovery , defined as ≥10 point decline in the Barthel Index , compared to pre-morbid status , was present in 27 ( 54 % ) of the 50 survivors . Factors associated with death or loss of function at hospital discharge were frailty , absence of agitation ( hypoactive delirium ) , a cardiac cause and poor recognition of delirium by the treating service . Frailty , causes other than medications , and poor recognition of delirium by the treating service were associated with death or poor functional recovery at 6 months . Conclusion Pre-existing frailty , cardiac cause of delirium , and poor early recognition by treating physicians are associated with worse outcomes . Many physicians view the adverse outcomes of delirium as intractable . While in some measure this might be true , more skilled care is a potential remedy within their grasp 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 Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia . Contribution This large , population -based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia . New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days . Conventional agents were associated with higher risks than were atypical agents . Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations . Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia . The Editors Various challenging behavioral and psychological symptoms commonly develop in older adults with dementia and predispose them and their caregivers to poor outcomes ( 1 ) . Nonpharmacologic strategies are recommended as first-line management for these symptoms ( 2 ) , but they may be difficult to implement in clinical practice ( 3 ) . For many reasons , antipsychotic medications are routinely prescribed in this setting ( 4 , 5 ) . Conventional antipsychotics , such as haloperidol , have been available since the 1950s . Meta-analyses of clinical trials evaluating conventional antipsychotics to treat agitation in dementia show that these agents have modest efficacy and important adverse effects compared with placebo ( 6 , 7 ) . In the past decade , use of newer atypical antipsychotics has been rapidly increasing in clinical practice because these agents were thought to produce fewer adverse effects than conventional agents ( 2 ) . A Canadian study found that the prevalence of antipsychotic use in older adults increased from 2.2 % in 1993 to 3.0 % at the end of 2002 . In that study , atypical antipsychotics , which were unavailable in 1993 , accounted for 82.5 % of all antipsychotics dispensed in 2002 ( 8) . Short-term r and omized , controlled trials ( RCTs ) have studied the role of atypical antipsychotics in the management of behavioral and psychological symptoms of dementia ( 2 , 9 ) . An RCT involving 421 out patients with Alzheimer disease and psychosis , aggression , or agitation concluded that the adverse effects of these newer drugs offset their advantages ( 10 ) . As a result , improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers ( 11 ) . In April 2005 , the U.S. Food and Drug Administration ( FDA ) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo ( 12 ) . In June 2005 , Health Canada issued a similar warning and additional data ( 13 ) . These warnings stem from review s of RCTs that involve the atypical agents risperidone , olanzapine , quetiapine , and aripiprazole . The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials review ed by the U.S. FDA ( 12 ) . The warnings extend to all currently available atypical antipsychotics . Other publications have provided support for these warnings and have raised further safety concerns about older conventional antipsychotics ( 1416 ) . Important questions remain unanswered . Although RCTs provide the best evidence of treatment efficacy and harm , the individual RCTs in this case had low event rates . Reliable estimates of the mortality risk were generated only when data were combined by meta- analysis ( 14 ) . Furthermore , these RCTs were generally short in duration and could not provide information about the long-term effect of antipsychotics on mortality ( 14 , 17 ) . Finally , these trials provide estimates of harm primarily for atypical antipsychotics . Relatively few data are available on harms associated with older conventional antipsychotics . Studies suggest that important differences may exist in the safety profiles of conventional and atypical agents ( 15 , 16 , 18 , 19 ) . Using population -based data , we sought to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotics , conventional antipsychotics , or no antipsychotic . Because important baseline differences exist among these groups , we used propensity score matching to improve their comparability . We also evaluated the effect of duration of treatment with antipsychotics on the risk for death . Methods Data Sources Ontario is Canada 's most populous province . During our study , Ontario had a population of approximately 12 million people , of whom 1.4 million were 65 years of age or older . A universally funded health program covers nearly all physician services , medications , and hospital services for patients 65 years of age or older in Ontario . Information from 4 administrative health care data bases was linked to develop the study cohort : pharmacy records from the Ontario Drug Benefit program , hospitalization records from the Canadian Institute for Health Information Discharge Abstract Data base , physician billing information for inpatient and outpatient services from the Ontario Health Insurance Plan , and basic demographic information and vital statistics from the Registered Persons Data base . We used encrypted unique identifiers that are common among data bases to link anonymous information on demographic characteristics and health services utilization for patients in our study . Little basic information on patients is missing in these data bases . For example , the coding accuracy of drug cl aims in the Ontario Drug Benefit program data base is excellent , with an error rate of only 0.7 % ( 20 ) . The study was approved by the ethics review board of Sunnybrook and Women 's College Health Sciences Centre , Toronto , Ontario , Canada . Dementia Cohort We identified a cohort of all Ontario residents 66 years of age or older with a diagnosis of dementia ( in the Ontario Health Insurance Plan or Discharge Abstract Data base ) between 1 April 1997 and 31 March 2002 . To focus on antipsychotic drug treatment for behavioral and psychological symptoms of dementia , we excluded patients who had evidence of other psychotic disorders ( such as schizophrenia ) or were receiving palliative care services . To reduce the potential for selection bias , we studied only new users of antipsychotics and excluded those who had received antipsychotics in the year before cohort entry ( 21 ) . Exposure to Antipsychotics We identified new use of antipsychotics if any agent available through the Ontario Drug Benefit program was dispensed after cohort entry . Cohort entry ( that is , the index date ) was defined as the date of the first dispensed antipsychotic drug . Available atypical drugs included olanzapine , quetiapine , and risperidone , and available conventional drugs included chlorpromazine , flupenthixol , fluphenazine , haloperidol , loxapine , pericyazine , perphenazine , pimozide , thioridazine , and trifluoperazine . Clozapine was rarely used in Ontario during the study period , and we therefore excluded patients who were receiving this medication . Other atypical antipsychotics ( such as aripiprazole and ziprasidone ) are not licensed for use in Canada . We decided that exposure to an antipsychotic was discontinued ( and we censored follow-up ) if the patient did not refill his or her antipsychotic prescription within an interval composed of the days of drug supply plus a grace period of 20 % . For example , we censored follow-up for a patient who did not refill his or her 60-day antipsychotic prescription within 72 days . We also censored follow-up for patients who switched from atypical to conventional antipsychotics ( or vice versa ) . However , we continued follow-up for patients who switched from 1 atypical antipsychotic to another , because data suggest no statistically significant difference in the risk for death associated with individual drugs in this class ( 13 , 14 , 16 ) . We applied the same rules to conventional antipsychotics . All-Cause Mortality The primary outcome was all-cause mortality , as recorded in the Registered Persons Data base ( for patients who were not hospitalized at the time of death ) or the Discharge Abstract Data base ( for patients who died while hospitalized ) . To assess the influence of the duration of antipsychotic exposure on the outcome , we evaluated the risk for death at 30 , 60 , 120 , and 180 days after the initial dispensing of antipsychotic medication . Cohort Matching We stratified the dementia cohort to support separate analyses among persons living in the community and those residing in long-term care at cohort entry . Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities ( 4 ) . Furthermore , long-term care residents typically carry a greater burden of comorbid disease and are more vulnerable to adverse drug events than are their counterparts in the community ( 22 , 23 ) . Our first objective was to determine the risk for death among older adults with dementia who received atypical antipsychotics compared with those who were not exposed to any antipsychotic . Because antipsychotic use was not r and omly assigned in the study cohorts , we addressed potential confounding and selection biases by developing a propensity score for antipsychotic use . We then applied this score to match users of atypical antipsychotics with nonusers in the dementia cohort . The rationale and methods underlying the use of a propensity score for a proposed causal exposure variable are described elsewhere ( 24 ) . Recent studies provide guidance on the selection of variables to include in the propensity score ( 25 , 26 ) . We developed a logistic regression model by using 42 covariates describing patient characteristics . Tables 1 and 2 list many of the characteristics included in the propensity score . After a structured and iterative assessment of the balance of measured covariates Background To investigate the controlling efficacy of ondasetron and haloperidol in regard to the postcardiotomy delirium . Methods We included in this prospect i ve , r and omized , double-blinded study 80 patients who developed delirium after heart surgery with the application of heart lung-machine . The patients were divided into two , equally-sized groups , which on detection of delirium received ondasetron 8 mg iv or haloperidol 5 mg iv respectively . The statistical analysis compared the baseline and demographic characteristics of the two groups ( age , gender , comorbidities , years of education , type of surgery etc . ) . Results Both ondasetron and haloperidol had very good delirium controlling effects , without statistically significant differences . Discussion - Conclusions Ondasetron and haloperidol are efficient agents as far as the treatment of postcardiotomy delirium is concerned . As , in addition , ondasetron bares milder side-effects , we believe this could be the agent of choice in patients developing postcardiotomy delirium in the future 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 RATIONALE Delirium is a frequent occurrence in older intensive care unit ( ICU ) patients , but the importance of the duration of delirium in contributing to adverse long-term outcomes is unclear . OBJECTIVES To examine the association of the number of days of ICU delirium with mortality in an older patient population . METHODS We performed a prospect i ve cohort study in a 14-bed ICU in an urban acute care hospital . The patient population comprised 304 consecutive admissions 60 years of age and older . MEASUREMENTS AND MAIN RESULTS The main outcome was 1-year mortality after ICU admission . Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a vali date d chart review method . The median duration of ICU delirium was 3 days ( range , 1 - 46 d ) . During the follow-up period , 153 ( 50 % ) patients died . After adjusting for relevant covariates , including age , severity of illness , comorbid conditions , psychoactive medication use , and baseline cognitive and functional status , the number of days of ICU delirium was significantly associated with time to death within 1 year post-ICU admission ( hazard ratio , 1.10 ; 95 % confidence interval , 1.02 - 1.18 ) . CONCLUSIONS Number of days of ICU delirium was associated with higher 1-year mortality after adjustment for relevant covariates in an older ICU population . Investigations should be undertaken to reduce the number of days of ICU delirium and to study the impact of this reduction on important health outcomes , including mortality and functional and cognitive status CONTEXT Delirium is a common problem in the intensive care unit ( ICU ) . Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a vali date d delirium instrument for use in the ICU . OBJECTIVES To vali date a delirium assessment instrument that uses st and ardized nonverbal assessment s for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients . DESIGN AND SETTING Prospect i ve cohort study testing the Confusion Assessment Method for ICU Patients ( CAM-ICU ) in the adult medical and coronary ICUs of a US university-based medical center . PARTICIPANTS A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1 , 2000 , to July 15 , 2000 , of whom 96 ( 86.5 % ) were evaluable for the development of delirium and 15 ( 13.5 % ) were excluded because they remained comatose throughout the investigation . MAIN OUTCOME MEASURES Occurrence rate of delirium and sensitivity , specificity , and interrater reliability of delirium assessment s using the CAM-ICU , made daily by 2 critical care study nurses , compared with assessment s by delirium experts using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS A total of 471 daily paired evaluations were completed . Compared with the reference st and ard for diagnosing delirium , 2 study nurses using the CAM-ICU had sensitivities of 100 % and 93 % , specificities of 98 % and 100 % , and high interrater reliability ( kappa = 0.96 ; 95 % confidence interval , 0.92 - 0.99 ) . Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older , 0.99 for those with suspected dementia , or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 ( all P<.001 ) . Comparing sensitivity and specificity between patient subgroups according to age , suspected dementia , or severity of illness showed no significant differences . The mean ( SD ) CAM-ICU administration time was 2 ( 1 ) minutes . Reference st and ard diagnoses of delirium , stupor , and coma occurred in 25.2 % , 21.3 % , and 28.5 % of all observations , respectively . Delirium occurred in 80 ( 83.3 % ) patients during their ICU stay for a mean ( SD ) of 2.4 ( 1.6 ) days . Delirium was even present in 39.5 % of alert or easily aroused patient observations by the reference st and ard and persisted in 10.4 % of patients at hospital discharge . CONCLUSIONS Delirium , a complication not currently monitored in the ICU setting , is extremely common in mechanically ventilated patients . The CAM-ICU appears to be rapid , valid , and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purpose BACKGROUND Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes . Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness . The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma . METHODS We did this double-blind , placebo-controlled r and omised trial in a general adult intensive care unit ( ICU ) . Critically ill patients ( ≥18 years ) needing mechanical ventilation within 72 h of admission were enrolled . Patients were r and omised ( by an independent nurse , in 1:1 ratio , with permuted block size of four and six , using a central ised , secure web-based r and omisation service ) to receive haloperidol 2.5 mg or 0.9 % saline placebo intravenously every 8 h , irrespective of coma or delirium status . Study drug was discontinued on ICU discharge , once delirium-free and coma-free for 2 consecutive days , or after a maximum of 14 days of treatment , whichever came first . Delirium was assessed using the confusion assessment method for the ICU ( CAM-ICU ) . The primary outcome was delirium-free and coma-free days , defined as the number of days in the first 14 days after r and omisation during which the patient was alive without delirium and not in coma from any cause . Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma . ICU clinical and research staff and patients were masked to treatment throughout the study . Analyses were by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Registry , number IS RCT N83567338 . FINDINGS 142 patients were r and omised , 141 were included in the final analysis ( 71 haloperidol , 70 placebo ) . Patients in the haloperidol group spent about the same number of days alive , without delirium , and without coma as did patients in the placebo group ( median 5 days [ IQR 0 - 10 ] vs 6 days [ 0 - 11 ] days ; p=0.53 ) . The most common adverse events were oversedation ( 11 patients in the haloperidol group vs six in the placebo group ) and QTc prolongation ( seven patients in the haloperidol group vs six in the placebo group ) . No patient had a serious adverse event related to the study drug . INTERPRETATION These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients . Although haloperidol can be used safely in this population of patients , pending the results of trials in progress , the use of intravenous haloperidol should be reserved for short-term management of acute agitation . FUNDING National Institute for Health Research Background Delirium prevalence in the intensive care unit ( ICU ) is high . Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms . Methods / Design This is a r and omized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis . Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium ( PMD ) and those assigned to the control group will receive no change in their usual ICU care . The primary outcomes of the trial are ( 1 ) delirium severity as measured by the Delirium Rating Scale revised-98 ( DRS-R-98 ) and ( 2 ) delirium duration as determined by the Confusion Assessment Method for the ICU ( CAM-ICU ) . The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients : dopamine , acetylcholine , and gamma-aminobutyric acid . The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines , and introduce a low-dose of haloperidol at 0.5 - 1 mg for 7 days . The protocol will be delivered by a combination of computer ( artificial intelligence ) and pharmacist ( human intelligence ) decision support system to increase adherence to the PMD protocol . Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU.Trial Registration Clinical Trials.gov : PURPOSE The purpose was to describe characteristics and outcomes of restrained and nonrestrained patients enrolled in a r and omized trial of protocol ized sedation compared with protocol ized sedation plus daily sedation interruption and to identify patient and treatment factors associated with physical restraint . METHODS This was a post hoc secondary analysis using Cox proportional hazards modeling adjusted for center- and time-varying covariates to evaluate predictors of restraint use . RESULTS A total of 328 ( 76 % ) of 430 patients were restrained for a median of 4 days . Restrained patients received higher daily doses of benzodiazepines ( 105 vs 41 mg midazolam equivalent , P < .0001 ) and opioids ( 1524 vs 919 μg fentanyl equivalents , P < .0001 ) , more days of infusions ( benzodiazepines 6 vs 4 , P < .0001 ; opioids 7 vs 5 , P = .02 ) , and more daily benzodiazepine boluses ( 0.2 vs 0.1 , P < .0001 ) . More restrained patients received haloperidol ( 23 % vs 12 % , P = .02 ) and atypical antipsychotics ( 17 % vs 4 % , P = .003 ) . More restrained patients experienced unintentional device removal ( 26 % vs 3 % , P < .001 ) and required reintubation ( 8 % vs 1 % , P = .01 ) . In the multivariable analysis , alcohol use was associated with decreased risk of restraint ( hazard ratio , 0.22 ; 95 % confidence interval , 0.08 - 0.58 ) . CONCLUSIONS Physical restraint was common in mechanically ventilated adults managed with a sedation protocol . Restrained patients received more opioids and benzodiazepines . Except for alcohol use , patient characteristics and treatment factors did not predict restraint use Objective : To test for an association between apolipoprotein E ( APOE ) genotypes and duration of intensive care unit delirium . Design : Prospect i ve , observational cohort study . Setting : A 541‐bed , community‐based teaching hospital . Patients : Fifty‐three mechanically ventilated intensive care unit patients . Interventions : None . Measurements and Main Results : All patients were managed with st and ardized sedation and ventilator weaning protocol s as part of an ongoing clinical trial and were evaluated prospect ively for delirium with the Confusion Assessment Method for the Intensive Care Unit ( CAM‐ICU ) . DNA was extracted from whole blood sample s obtained on enrollment , and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information . Delirium occurred in 47 ( 89 % ) patients at some point during the intensive care unit stay . Of the 53 patients , 12 ( 23 % ) had an APOE4 allele ( APOE4 + ) and 41 ( 77 % ) had only APOE2 or APOE3 alleles ( APOE4− ) . APOE4 + patients were younger ( 53.2 ± 21.9 vs. 65.4 ± 13.4 , p = .08 ) and less often admitted for pneumonia ( 0 % vs. 29.3 % , p = .05 ) compared with APOE4− patients , yet they had a duration of delirium that was twice as long : median ( interquartile range ) , 4 ( 3 , 4.5 ) vs. 2 ( 1 , 4 ) days ( p = .05 ) . No other clinical outcomes were significantly different between the APOE4 + and APOE4− patients . Using multivariable regression analysis to adjust for age , admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia , severity of illness , and duration of coma , the presence of APOE4 allele was the strongest predictor of delirium duration ( odds ratio , 7.32 ; 95 % confidence interval , 1.82–29.51 , p = .005 ) . Conclusions : APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans Objective To compare the safety and estimate the response profile of olanzapine , a second-generation antipsychotic , to haloperidol in the treatment of delirium in the critical care setting . Design Prospect i ve r and omized trial Setting Tertiary care university affiliated critical care unit . Patients All admissions to a medical and surgical intensive care unit with a diagnosis of delirium . Interventions Patients were r and omized to receive either enteral olanzapine or haloperidol . Measurements Patient ’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium . Main results Delirium Index decreased over time in both groups , as did the administered dose of benzodiazepines . Clinical improvement was similar in both treatment arms . No side effects were noted in the olanzapine group , whereas the use of haloperidol was associated with extrapyramidal side effects . Conclusions Olanzapine is a safe alternative to haloperidol in delirious critical care patients , and may be of particular interest in patients in whom haloperidol is contraindicated 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 Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . OBJECTIVES Patients who undergo cardiac surgery have an increased risk of delirium . Currently , there are few choices of treatment for postoperative hyperactive delirium in cardiac surgical patients . The aim of this study was to assess the effect of morphine compared with a haloperidol-based regimen in hyperactive-type delirium in patients after cardiac surgery . DESIGN A prospect i ve , r and omized clinical study . SETTING A single community hospital . PARTICIPANTS Fifty-three consecutive , adult , delirious patients . INTERVENTIONS Patients were r and omized into 2 groups ; in group 1 , patients received 5 mg of haloperidol intramuscularly and in group 2 , patients received 5 mg of morphine sulfate intramuscularly to control delirium symptoms . MEASUREMENTS AND MAIN RESULTS During the second and third hour of the morphine treatment , statistically low Richmond Agitation and Sedation Scale scores were found and the target Richmond Agitation and Sedation Scale scores percentages were statistically higher than those of the haloperidol group ( p = 0.042 and p = 0.028 , respectively ) . The number of patients requiring additive sedatives was significantly more in the haloperidol group when compared with the morphine group ( p = 0.011 ) . CONCLUSION During the treatment of patients , it was determined that the patients who were receiving morphine treatment responded more quickly compared with the patients receiving haloperidol treatment . Morphine was found to be a reasonable alternative to haloperidol in the treatment of postoperative hyperactive delirious patients after cardiac surgery BACKGROUND Simulated family presence has been shown to be an effective nonpharmacological intervention to reduce agitation in persons with dementia in nursing homes . Hyperactive or mixed delirium is a common and serious complication experienced by hospitalized patients , a key feature of which is agitation . Effective nonpharmacological interventions to manage delirium are needed . OBJECTIVES To examine the effect of simulated family presence through pre-recorded video messages on the agitation level of hospitalized , delirious , acutely agitated patients . DESIGN Single site r and omized control trial , 3 groups × 4 time points mixed factorial design conducted from July 2015 to March 2016 . SETTING Acute care level one trauma center in an inner city of the state of Connecticut , USA . PARTICIPANTS Hospitalized patients experiencing hyperactive or mixed delirium and receiving continuous observation were consecutively enrolled ( n=126 ) , with 111 participants completing the study . Most were older , male , Caucasian , spouseless , with a pre-existing dementia . METHODS Participants were r and omized to one of the following study arms : view a one minute family video message , view a one minute nature video , or usual care . Participants in experimental groups also received usual care . The Agitated Behavior Scale was used to measure the level of agitation prior to , during , immediately following , and 30min following the intervention . RESULTS Both the family video and nature video groups displayed a significant change in median agitation scores over the four time periods ( p<0.001 ) , whereas the control group did not . The family video group had significantly lower median agitation scores during the intervention period ( p<0.001 ) and a significantly greater proportion ( 94 % ) of participants experiencing a reduction in agitation from the pre-intervention to during intervention ( p<0.001 ) than those viewing the nature video ( 70 % ) or those in usual care only ( 30 % ) . The median agitation scores for the three groups were not significantly different at either of the post intervention time measurements . When comparing the proportion of participants experiencing a reduction in agitation from baseline to post intervention , there remained a statistically significant difference ( p=0.001 ) between family video(60 % ) and usual care ( 35.1 % ) immediately following the intervention CONCLUSION : This work provides preliminary support for the use of family video messaging as a nonpharmacological intervention that may decrease agitation in selected hospitalized delirious patients . Further studies are necessary to determine the efficacy of the intervention as part of a multi-component intervention as well as among younger delirious patients without baseline dementia 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 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 ; Abstract . Study objective : To determine the relationship between delirium in the intensive care unit ( ICU ) and outcomes including length of stay in the hospital . Design : A prospect i ve cohort study . Setting : The adult medical ICU of a tertiary care , university-based medical center . Participants : The study population consisted of 48 patients admitted to the ICU , 24 of whom received mechanical ventilation . Measurements : All patients were evaluated for the development and persistence of delirium on a daily basis by a geriatric or psychiatric specialist with expertise in delirium assessment using the Diagnostic Statistical Manual IV ( DSM-IV ) criteria of the American Psychiatric Association , the reference st and ard for delirium ratings . Primary outcomes measured were length of stay in the ICU and hospital . Results : The mean onset of delirium was 2.6 days ( S.D.±1.7 ) , and the mean duration was 3.4±1.9 days . Of the 48 patients , 39 ( 81.3 % ) developed delirium , and of these 29 ( 60.4 % ) developed the complication while still in the ICU . The duration of delirium was associated with length of stay in the ICU ( r=0.65 , P=0.0001 ) and in the hospital ( r=0.68 , P<0.0001 ) . Using multivariate analysis , delirium was the strongest predictor of length of stay in the hospital ( P=0.006 ) even after adjusting for severity of illness , age , gender , race , and days of benzodiazepine and narcotic drug administration . Conclusions : In this patient cohort , the majority of patients developed delirium in the ICU , and delirium was the strongest independent determinant of length of stay in the hospital . Further study and monitoring of delirium in the ICU and the risk factors for its development are warranted Purpose : Investigate the relationship between psychoactive drugs and delirium . Material s and methods : Prospect i ve observational study of 520 critically ill adult patients admitted ≥ 24 h to 6 intensive care units ( ICUs ) . Data were collected on psychoactive drug exposure , use of sedation administration strategies , and incident delirium ( Intensive Care Delirium Screening Checklist score ≥ 4 ) . Results : Delirium was detected in 260 ( 50 % ) patients , median ( IQR ) duration 2 ( 1–5 ) days , and time to onset 3 ( 2–5 ) days . Delirious patients received more low‐potency anticholinergic ( P < 0.0001 ) , antipsychotic ( P < 0.0001 ) , benzodiazepine ( P < 0.0001 ) and non‐benzodiazepine sedative ( P < 0.0001 ) , and opioid ( P = 0.0008 ) drugs . Primary regression ( 24‐hours preceding drug exposure ) revealed no association between any psychoactive drug and delirium . Post‐hoc analysis ( extended 48‐hour exposure ) revealed an association between delirium and high‐potency anticholinergic ( HR 2.45 , 95 % CI 1.08–5.54 ) and benzodiazepine ( HR 1.08 per 5 mg midazolam‐equivalent increment , 95 % CI 1.04–1.12 ) drugs . Delirious patients had longer ICU ( P < 0.0001 ) and hospital ( P < 0.0001 ) length of stay , and higher ICU and hospital mortality ( P = 0.003 and P = 0.007 , respectively ) . Conclusions : The identification of psychoactive drugs as modifiable delirium risk factors plays an important role in the management of critically ill patients . This is particularly important given the burden of exposure and combinations of drugs used in this vulnerable patient population 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 and transient neurologic dysfunctions ( TND ) often complicate the postoperative course after surgery for acute type-A aortic dissection ( AAD ) . We evaluated the role of clonidine on neurological outcome and respiratory function in 30 consecutive patients undergoing surgery for AAD . Patients were prospect ively r and omized to receive either clonidine ( 0.5 microg/kg bolus , followed by continuous infusion at 1 - 2 microg/kg/h ) or placebo ( NaCl 0.9 % ) in on starting and throughout the weaning period from the mechanical ventilation . Incidence of delirium and TND , Delirium Detection Score ( DDS ) , weaning parameters [ respiratory rate to tidal volume ratio - f/VT ; pressure-frequency product ( PFP ) ; partial pressure of arterial oxygen to fractional inspired oxygen concentration ( PaO(2)/FiO(2 ) ) ; partial pressure of carbon dioxide ( PaCO(2 ) ) ] , weaning duration and intensive care unit ( ICU ) length of stay were recorded . The two groups were similar for preoperative and operative variables and also for the incidence of postoperative complications . DDS was lower in the clonidine group ( P<0.001 ) . Patients weaned with clonidine showed lower f/VT and PFP , higher PaO(2)/FiO(2 ) and PaCO(2 ) , lower DDS , weaning period and the related ICU length of stay ( P<0.001 ) . This was further confirmed in patients developing delirium/TND . Intravenous clonidine after surgery for AAD reduces the severity of delirium , improves the respiratory function , shortens the weaning duration and the ICU length of stay Objectives : To revali date a means of assessing delirium in intensive care unit patients and to investigate the independent effect of delirium on the mortality of mechanically ventilated patients . Design : A prospect i ve cohort study . Setting : A 37-bed medical intensive care unit of a tertiary care hospital . Patients : Subjects were 102 of 131 consecutive mechanically ventilated patients . Measurements : All the enrolled patients were assessed for delirium using the Confusion Assessment Method for the Intensive Care Unit ( CAM-ICU ) . Mortality rate were compared between patients with or without delirium , and the predictors of death were investigated . Results : The two CAM-ICU assessors ’ sensitivities in diagnosing delirium compared with reference st and ard were 91 % and 95 % , whereas their specificities were both 98 % . They also demonstrated high interrater reliability with kappa statistics of 0.91 . Delirium was present in 22 of 102 ( 22 % ) patients in the first 5 days . The delirious patients had higher intensive care unit mortality rate than nondelirious patients ( 63.6 % vs. 32.5 % , respectively ) , with a hazard ratio of 2.57 ( 95 % confidence interval , 1.56–8.15 ) . In multivariate analysis , delirium ( odds ratio , 13.0 ; 95 % confidence interval , 2.69–62.91 ) , shock ( odds ratio , 12.91 ; 95 % confidence interval , 2.93–56.92 ) , and illness severity ( odds ratio , 9.61 ; 95 % confidence interval , 2.24–41.18 ) were independent predictors of mortality . Conclusions : This study confirms previous work showing that delirium is an independent predictor for increased mortality among mechanically ventilated patients Objective To determine the costs associated with delirium in mechanically ventilated medical intensive care unit patients . Design Prospect i ve cohort study . Setting A tertiary care academic hospital . Patients Patients were 275 consecutive mechanically ventilated medical intensive care unit patients . Interventions We prospect ively examined patients for delirium using the Confusion Assessment Method for the Intensive Care Unit . Measurements and Main Results Delirium was categorized as “ ever vs. never ” and by a cumulative delirium severity index . Costs were determined from individual ledger-level patient charges using cost-center-specific cost-to-charge ratios and were reported in year 2001 U.S. dollars . Fifty-one of 275 patients ( 18.5 % ) had persistent coma and died in the hospital and were excluded from further analysis . Of the remaining 224 patients , delirium developed in 183 ( 81.7 % ) and lasted a median of 2.1 ( interquartile range , 1–3 ) days . Baseline demographics were similar between those with and without delirium . Intensive care unit costs ( median , interquartile range ) were significantly higher for those with at least one episode of delirium ( $ 22,346 , $ 15,083–$35,521 ) vs. those with no delirium ( $ 13,332 , $ 8,837–$21,471 , p < .001 ) . Total hospital costs were also higher in those who developed delirium ( $ 41,836 , $ 22,782–$68,134 vs. $ 27,106 , $ 13,875–$37,419 , p = .002 ) . Higher severity and duration of delirium were associated with incrementally greater costs ( all p < .001 ) . After adjustment for age , comorbidity , severity of illness , degree of organ dysfunction , nosocomial infection , hospital mortality , and other potential confounders , delirium was associated with 39 % higher intensive care unit ( 95 % confidence interval , 12–72 % ) and 31 % higher hospital ( 95 % confidence interval , 1–70 % ) costs . Conclusions Delirium is a common clinical event in mechanically ventilated medical intensive care unit patients and is associated with significantly higher intensive care unit and hospital costs . Future efforts to prevent or treat intensive care unit delirium have the potential to improve patient outcomes and reduce costs of care Objective : To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma . Design : R and omized , double-blind , placebo-controlled trial . Setting : Six tertiary care medical centers in the US . Patients : One hundred one mechanically ventilated medical and surgical intensive care unit patients . Intervention : Patients were r and omly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days . Twice each day , frequency of study drug administration was adjusted according to delirium status , level of sedation , and side effects . Measurements and Main Outcomes : The primary end point was the number of days patients were alive without delirium or coma . During the 21-day study period , patients in the haloperidol group spent a similar number days alive without delirium or coma ( median [ interquartile range ] , 14.0 [ 6.0–18.0 ] days ) as did patients in the ziprasidone ( 15.0 [ 9.1–18.0 ] days ) and placebo groups ( 12.5 [ 1.2–17.2 ] days ; p = 0.66 ) . No differences were found in secondary clinical outcomes , including ventilator-free days ( p = .25 ) , hospital length of stay ( p = .68 ) , and mortality ( p = .81 ) . Ten ( 29 % ) patients in the haloperidol group reported symptoms consistent with akathisia , compared with six ( 20 % ) patients in the ziprasidone group and seven ( 19 % ) patients in the placebo group ( p = .60 ) , and a global measure of extrapyramidal symptoms was similar between treatment groups ( p = .46 ) . Conclusions : A r and omized , placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible . Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma , nor did it increase adverse outcomes . Thus , a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate . Trial Registration : Clinical Trials.gov , number NCT00096863 RATIONALE Intensive care unit ( ICU ) delirium is associated with ventilator , ICU , and hospital days ; discharge functional status ; and mortality . Whether rapidly reversible , sedation-related delirium ( delirium that abates shortly after sedative interruption ) occurs with the same frequency and portends the same prognosis as persistent delirium ( delirium that persists despite a short period of sedative interruption ) is unknown . OBJECTIVES To compare rapidly reversible , sedation-related delirium and persistent delirium . METHODS This was a prospect i ve cohort study of 102 adult , intubated medical ICU subjects in a tertiary care teaching hospital . Confusion Assessment Method for the ICU evaluation was performed before and after daily interruption of continuous sedation ( DIS ) . Investigators were blinded to each other 's assessment s and as to whether evaluations were before or after DIS . The primary outcome was proportion of days with no delirium versus rapidly reversible , sedation-related delirium versus persistent delirium . Secondary outcomes were ventilator , ICU , and hospital days ; discharge disposition ; and 1-year mortality . MEASUREMENTS AND MAIN RESULTS The median proportion of ICU days with delirium was 0.57 before versus 0.50 after DIS ( P < 0.001 ) . The Confusion Assessment Method for the ICU indicated patients are 10.5 times more likely to have delirium before DIS versus after ( P < 0.001 ) . Rapidly reversible , sedation-related delirium showed fewer ventilator ( P < 0.001 ) , ICU ( P = 0.001 ) , and hospital days ( P < 0.001 ) than persistent delirium . Subjects with no delirium and rapidly reversible , sedation-related delirium were more likely to be discharged home ( P < 0.001 ) . Patients with persistent delirium had increased 1-year mortality versus those with no delirium and rapidly reversible , sedation-related delirium ( P < 0.001 ) . CONCLUSIONS Rapidly reversible , sedation-related delirium does not signify the same poor prognosis as persistent delirium . Degree of sedation should be considered in delirium assessment s. Coordinating delirium assessment s with daily sedative interruption will improve such assessment s ' ability to prognosticate ICU delirium outcomes . Clinical trial registered with www . clinical trials.gov ( NCT 00919698 ) BACKGROUND Delirium exemplifies the interface between medicine and psychiatry . The mainstay of treatment of delirium are the antipsychotic drugs . These are efficacious and safe for the treatment of delirium . In the last decade the use of second generation antipsychotics has been advocated at the expense of the classical drugs , particularly haloperidol . We thus aim ed to compare the outcome of delirium treatment in a large , university-affiliated general hospital . METHODS We used retrospective medical charts analysis over a one-year period . Those included were all patients who had been admitted to an acute internal medicine ward for delirium or who had developed delirium during their hospital stay . RESULTS 191 patients ' records were analysed . Mean age for the group was 78.8 + /- 1.1 years . There were 108 males ( 56.5 % ) and 83 ( 43.5 % ) female patients . The most frequent co-morbid psychiatric diagnosis was that of dementia ( 106 ; 56 % ) . The most common physical conditions were : cardiovascular ( 75 patients ) and sepsis ( 24 patients ) . Patients suffering from delirium were mostly treated with an antipsychotic : 147 ( 77 % ) were treated either with risperidone ( 73 patients ) or classical antipsychotics ( 74 patients ) . The most frequently used classical antipsychotic was haloperidol ( 59/74 ) . Mean risperidone dose was 1.7 + /- 0.4 mg/daily . Mean haloperidol dose was 7.8 + /- 1.9 mg/daily . Mean duration of antipsychotic treatment was 3.8 days for the classical antipsychotics group and 2.6 for the risperidone group ( p = 0.04 ) . In the untreated group , mean delirium episodes lasted 5.6 days - significantly longer than that of either treated groups , p = 0.02.Mean hospital stay ( days ) for the group was 12.8 + /- 1.4 . In the risperidone treated group the mean stay was 10.8 days while in the classical antipsychotics group it was 13.5 and in the untreated group it was 15.5 ( p = 0.008 ) . Fourteen patients ( 7.3 % ) died during the delirium episode : 10 untreated , 3 treated by classical antipsychotics and 1 risperidone treated ( p = 0.04 ) . The majority of patients ( 65 % ) were discharged to the community . CONCLUSIONS The present study adds to the growing body of evidence favoring risperidone as the drug of choice for the treatment of delirium . However , due to the limitations inherent in a retrospective analysis , prospect i ve large-scale trials are needed to support this recommendation Purpose Our aim was to describe analgo-sedation and antipsychotic and neuromuscular blocking drug ( NMBD ) use in critically ill patients , management strategies , and variables associated with these practice patterns . Methods This prospect i ve observational study in 51 intensive care units ( ICUs ) included all patients who underwent invasive mechanical ventilation ( MV ) over a two-week period during 2008 - 2009 . Results We included 712 patients representing 3,620 patient-days . Median MV duration was 3.0 days ( interquartile range 2 - 6 ) . During MV , 92 % of patients received analgo-sedation , 32 % an adjunct agent ( e.g. , acetaminophen ) , 18 % NMBDs , and 10 % antipsychotics . Opioids were used more frequently than benzodiazepines or propofol ( 84.8 % vs 62.2 % vs 10.1 % patients , respectively , P < 0.0001 ) . Independent predictors of opioid and benzodiazepine use were a longer MV duration , assessment scales , physical restraints , and university-affiliated hospital . Although more than 50 % of ICUs reported that assessment tools , protocol s , and daily sedation interruption ( DSI ) were available for use , application was modest : sedation scale 53.0 % , pain scale 19.1 % , delirium scale 5.2 % , protocol 25.0 % , DSI 42.1 % . Accidental device removal occurred in 4.6 % of patients , with 75.8 % of events during DSI . Daily sedation interruption was associated with protocol use , physical restraints , university-affiliated hospital , and short- duration MV . Variables associated with protocol use included assessment scales , longer MV duration , lack of physical restraints , and admission to a community hospital . Conclusion Nearly all MV patients received analgo-sedation . Opioids were used more often than sedatives despite infrequent use of pain scales . Few patients received antipsychotic therapy , but physical restraint was common . Protocol use was poor compared to DSI . Duration of MV predicted the use of either . RésuméObjectifNotre objectif était de décrire l’utilisation des médicaments antalgiques-sédatifs et bloqueurs neuromusculaires ( NMBD ) chez des patients dans un état critique , les stratégies de prise en charge et les variables associées aux pratiques habituelles . MéthodesCette étude observationnelle prospect i ve menée dans 51 unités de soins intensifs ( USI ) a inclus tous les patients ayant bénéficié d’une ventilation mécanique ( VM ) invasive sur une période de deux semaines au cours des années 2008 - 2009.RésultatsNous avons inclus 712 patients représentant 3 620 jours- patients . La durée médiane de VM a été de 3,0 jours ( intervalle interquartile : 2 - 6 ) . Au cours de la VM , 92 % des patients ont reçu une analgésie-sédation , 32 % ont reçu un médicament d’appoint ( par exemple : acétaminophène ) , 18 % des NMBD , et 10 % des antipsychotiques . Les morphiniques ont été utilisés plus souvent que les benzodiazépines ou le propofol ( respectivement , 84,8 % contre 62,2 % et 10,1 % des patients , P < 0,0001 ) . Les facteurs prédictifs indépendants de l’utilisation des morphiniques et des benzodiazépines étaient une plus longue durée de VM , les échelles d’évaluation , la contention physique et l’affiliation universitaire de l’hôpital . Bien que plus de 50 % des USI aient indiqué la disponibilité d’outils d’évaluation , de protocol es et d’interruptions quotidiennes de la sédation ( DSI ) , leur utilisation pratique a été modeste : échelle de sédation 53,0 % , échelle de douleur 19,1 % , échelle d’évaluation du délire 5,2 % , protocol e 25,0 % , DSI 42,1 % . Un retrait accidentel du dispositif est survenu chez 4,6 % des patients , 75,8 % de ces événements survenant au cours d’une DSI . L’interruption quotidienne de la sédation était associée à l’utilisation d’un protocol e , une contention physique , l’affiliation universitaire de l’hôpital et la courte durée de la VM . Les variables associées à l’utilisation d’un protocol e incluaient les échelles d’évaluation , une plus longue durée de VM , l’absence de contrainte physique et l’hospitalisation dans un hôpital général . Conclusion Presque tous les patients sous VM ont reçu une analgésie-sédation . Les morphiniques ont été utilisés plus souvent que les sédatifs en dépit de l’utilisation rare des échelles de douleur . Peu de patients ont reçu un traitement antipsychotique , mais les dispositifs de contention étaient courants . L’utilisation d’un protocol e a été faible par rapport à la DSI . La durée de la VM a prédit l’utilisation des deux Objective : To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium ( Intensive Care Delirium Screening Checklist ≥ 4 ) administered to critically ill adults with subsyndromal delirium ( Intensive Care Delirium Screening Checklist = 1–3 ) . Design : R and omized , double-blind , placebo-controlled trial . Setting : Three 10-bed ICUs ( two medical and one surgical ) at an academic medical center in the United States . Patients : Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions , cardiac surgery , or requiring deep sedation . Interventions : Patients were r and omly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred ( Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation ) , 10 days of therapy had elapsed , or ICU discharge . Measurements and Main Results : Baseline characteristics were similar between the haloperidol ( n = 34 ) and placebo ( n = 34 ) groups . A similar number of patients given haloperidol ( 12/34 [ 35 % ] ) and placebo ( 8/34 [ 23 % ] ) developed delirium ( p = 0.29 ) . Haloperidol use reduced the hours per study day spent agitated ( Sedation Agitation Scale ≥ 5 ) ( p = 0.008 ) , but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma ( Sedation Agitation Scale ⩽ 2 ) or delirium ( p = 0.36 ) , the time to first delirium occurrence ( p = 0.22 ) , nor delirium duration ( p = 0.26 ) . Days of mechanical ventilation ( p = 0.80 ) , ICU mortality ( p = 0.55 ) , and ICU patient disposition ( p = 0.22 ) were similar in the two groups . The proportion of patients who developed corrected QT-interval prolongation ( p = 0.16 ) , extrapyramidal symptoms ( p = 0.31 ) , excessive sedation ( p = 0.31 ) , or new-onset hypotension ( p = 1.0 ) that result ed in study drug discontinuation was comparable between the two groups . Conclusions : Low-dose scheduled haloperidol , initiated early in the ICU stay , does not prevent delirium and has little therapeutic advantage in mechanically ventilated , critically ill adults with subsyndromal delirium Background Delirium during intensive care unit ( ICU ) stay is frequent and associated with significant morbidity , mortality and healthcare-related costs . International guidelines suggest its prevention . However , curative treatment remains unclearly established . Despite contradictory and ambiguous academic literature , international guidelines suggest the use of second-generation ( atypical ) antipsychotics over haloperidol . However , haloperidol remains the most widely used neuroleptic worldwide as a first-line treatment of agitation and /or delirium . Dexmedetomidine , an alpha2-adrenergic receptors agonist , has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention . Dexmedetomidine represents a widely used alternative to haloperidol . Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first-line curative treatment of delirium . The main objective of the 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo . Methods / design The 4D trial is an investigator-initiated , prospect i ve , multicenter , r and omized , double-blinded , two-arm trial , r and omizing 300 non-intubated ICU patients with a diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure . In case of agitation ( RASS≥ + 2 ) , immediate haloperidol administration will be allowed , to protect patient and staff in charge , while waiting for study treatment action . The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation . Secondary outcomes include mortalities at 7 and 30 days , ICU length of stay and occurrence of adverse effects related to dexmedetomidine use ( bradycardia or hypotension requesting any treatment ; or haloperidol use ( neuroleptic malignant syndrome , extrapyramidal syndrome , prolonged QTc ) . The sample size will allow the detection of a 50 % decrease of agitation duration ( 120 min ) , of an absolute reduction of delirium duration ( 1 day ) and of a 50 % relative decrease of intubation and mechanical ventilation , with a type 1 error rate of 1.8 % ( error risk inflation due to components of composite ) and power of 90 % , assuming a 15 % incidence of intubation and mechanical ventilation requirements , an agitation duration of 240 min and a delirium duration of 3 days . One hundred and ten patients by group will be needed . An intermediate analysis is scheduled and requires the inclusion of 150 patients . Discussion The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium . Trial registration Clinical Trials.gov , ID : NCT 03317067 . Registered on 23 October 2017 BACKGROUND Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome . Impaired cholinergic neurotransmission seems to have an important role in the development of delirium . We aim ed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients . METHODS Patients ( aged ≥18 years ) who were diagnosed with delirium were enrolled from six intensive care units in the Netherl and s , and treated between November , 2008 , and January , 2010 . Patients were r and omised ( 1:1 ratio ) to receive an increasing dose of rivastigmine or placebo , starting at 0·75 mL ( 1·5 mg rivastigmine ) twice daily and increasing in increments to 3 mL ( 6 mg rivastigmine ) twice daily from day 10 onwards , as an adjunct to usual care based on haloperidol . The trial pharmacist generated the r and omisation sequence by computer , and consecutively numbered bottles of the study drug according to this sequence to conceal allocation . The primary outcome was the duration of delirium during hospital admission . Analysis was by intention to treat . Duration of delirium was censored for patients who died or were discharged from hospital while delirious . Patients , medical staff , and investigators were masked to treatment allocation . Members of the data safety and monitoring board ( DSMB ) were unmasked and did interim analyses every 3 months . This trial is registered with Clinical Trials.gov , number NCT00704301 . FINDINGS Although a sample size of 440 patients was planned , after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis ( n=54 on rivastigmine , n=50 on placebo ) , the DSMB recommended that the trial be halted because mortality in the rivastigmine group ( n=12 , 22 % ) was higher than in the placebo group ( n=4 , 8 % ; p=0·07 ) . Median duration of delirium was longer in the rivastigmine group ( 5·0 days , IQR 2·7 - 14·2 ) than in the placebo group ( 3·0 days , IQR 1·0 - 9·3 ; p=0·06 ) . INTERPRETATION Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients . FUNDING ZonMw , the Netherl and s Brain Foundation , and Novartis BACKGROUND There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit ( ICU ) . METHODS In a r and omized , double‐blind , placebo‐controlled trial , we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol ( maximum dose , 20 mg daily ) , ziprasidone ( maximum dose , 40 mg daily ) , or placebo . The volume and dose of a trial drug or placebo was halved or doubled at 12‐hour intervals on the basis of the presence or absence of delirium , as detected with the use of the Confusion Assessment Method for the ICU , and of side effects of the intervention . The primary end point was the number of days alive without delirium or coma during the 14‐day intervention period . Secondary end points included 30‐day and 90‐day survival , time to freedom from mechanical ventilation , and time to ICU and hospital discharge . Safety end points included extrapyramidal symptoms and excessive sedation . RESULTS Written informed consent was obtained from 1183 patients or their authorized representatives . Delirium developed in 566 patients ( 48 % ) , of whom 89 % had hypoactive delirium and 11 % had hyperactive delirium . Of the 566 patients , 184 were r and omly assigned to receive placebo , 192 to receive haloperidol , and 190 to receive ziprasidone . The median duration of exposure to a trial drug or placebo was 4 days ( interquartile range , 3 to 7 ) . The median number of days alive without delirium or coma was 8.5 ( 95 % confidence interval [ CI ] , 5.6 to 9.9 ) in the placebo group , 7.9 ( 95 % CI , 4.4 to 9.6 ) in the haloperidol group , and 8.7 ( 95 % CI , 5.9 to 10.0 ) in the ziprasidone group ( P=0.26 for overall effect across trial groups ) . The use of haloperidol or ziprasidone , as compared with placebo , had no significant effect on the primary end point ( odds ratios , 0.88 [ 95 % CI , 0.64 to 1.21 ] and 1.04 [ 95 % CI , 0.73 to 1.48 ] , respectively ) . There were no significant between‐group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms . CONCLUSIONS The use of haloperidol or ziprasidone , as compared with placebo , in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium . ( Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center ; MIND‐USA Clinical Trials.gov number , NCT01211522 . BACKGROUND Long-term complications of critical illness include intensive care unit (ICU)-acquired weakness and neuropsychiatric disease . Immobilisation secondary to sedation might potentiate these problems . We assessed the efficacy of combining daily interruption of sedation with physical and occupational therapy on functional outcomes in patients receiving mechanical ventilation in intensive care . METHODS Se date d adults ( > /=18 years of age ) in the ICU who had been on mechanical ventilation for less than 72 h , were expected to continue for at least 24 h , and who met criteria for baseline functional independence were eligible for enrolment in this r and omised controlled trial at two university hospitals . We r and omly assigned 104 patients by computer-generated , permuted block r and omisation to early exercise and mobilisation ( physical and occupational therapy ) during periods of daily interruption of sedation ( intervention ; n=49 ) or to daily interruption of sedation with therapy as ordered by the primary care team ( control ; n=55 ) . The primary endpoint-the number of patients returning to independent functional status at hospital discharge-was defined as the ability to perform six activities of daily living and the ability to walk independently . Therapists who undertook patient assessment s were blinded to treatment assignment . Secondary endpoints included duration of delirium and ventilator-free days during the first 28 days of hospital stay . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00322010 . FINDINGS All 104 patients were included in the analysis . Return to independent functional status at hospital discharge occurred in 29 ( 59 % ) patients in the intervention group compared with 19 ( 35 % ) patients in the control group ( p=0.02 ; odds ratio 2.7 [ 95 % CI 1.2 - 6.1 ] ) . Patients in the intervention group had shorter duration of delirium ( median 2.0 days , IQR 0.0 - 6.0 vs 4.0 days , 2.0 - 8.0 ; p=0.02 ) , and more ventilator-free days ( 23.5 days , 7.4 - 25.6 vs 21.1 days , 0.0 - 23.8 ; p=0.05 ) during the 28-day follow-up period than did controls . There was one serious adverse event in 498 therapy sessions ( desaturation less than 80 % ) . Discontinuation of therapy as a result of patient instability occurred in 19 ( 4 % ) of all sessions , most commonly for perceived patient-ventilator asynchrony . INTERPRETATION A strategy for whole-body rehabilitation-consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness-was safe and well tolerated , and result ed in better functional outcomes at hospital discharge , a shorter duration of delirium , and more ventilator-free days compared with st and ard care . FUNDING None CONTEXT Gamma-aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit ( ICU ) patients , yet preliminary evidence indicates that the alpha(2 ) agonist dexmedetomidine may have distinct advantages . OBJECTIVE To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients . DESIGN , SETTING , AND PATIENTS Prospect i ve , double-blind , r and omized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours . Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale ( RASS ) and the Confusion Assessment Method for the ICU . INTERVENTIONS Dexmedetomidine ( 0.2 - 1.4 microg/kg per hour [ n = 244 ] ) or midazolam ( 0.02 - 0.1 mg/kg per hour [ n = 122 ] ) titrated to achieve light sedation ( RASS scores between -2 and + 1 ) from enrollment until extubation or 30 days . MAIN OUTCOME MEASURES Percentage of time within target RASS range . Secondary end points included prevalence and duration of delirium , use of fentanyl and open-label midazolam , and nursing assessment s. Additional outcomes included duration of mechanical ventilation , ICU length of stay , and adverse events . RESULTS There was no difference in percentage of time within the target RASS range ( 77.3 % for dexmedetomidine group vs 75.1 % for midazolam group ; difference , 2.2 % [ 95 % confidence interval { CI } , -3.2 % to 7.5 % ] ; P = .18 ) . The prevalence of delirium during treatment was 54 % ( n = 132/244 ) in dexmedetomidine-treated patients vs 76.6 % ( n = 93/122 ) in midazolam-treated patients ( difference , 22.6 % [ 95 % CI , 14 % to 33 % ] ; P < .001 ) . Median time to extubation was 1.9 days shorter in dexmedetomidine-treated patients ( 3.7 days [ 95 % CI , 3.1 to 4.0 ] vs 5.6 days [ 95 % CI , 4.6 to 5.9 ] ; P = .01 ) , and ICU length of stay was similar ( 5.9 days [ 95 % CI , 5.7 to 7.0 ] vs 7.6 days [ 95 % CI , 6.7 to 8.6 ] ; P = .24 ) . Dexmedetomidine-treated patients were more likely to develop bradycardia ( 42.2 % [ 103/244 ] vs 18.9 % [ 23/122 ] ; P < .001 ) , with a nonsignificant increase in the proportion requiring treatment ( 4.9 % [ 12/244 ] vs 0.8 % [ 1/122 ] ; P = .07 ) , but had a lower likelihood of tachycardia ( 25.4 % [ 62/244 ] vs 44.3 % [ 54/122 ] ; P < .001 ) or hypertension requiring treatment ( 18.9 % [ 46/244 ] vs 29.5 % [ 36/122 ] ; P = .02 ) . CONCLUSIONS There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients . At comparable sedation levels , dexmedetomidine-treated patients spent less time on the ventilator , experienced less delirium , and developed less tachycardia and hypertension . The most notable adverse effect of dexmedetomidine was bradycardia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00216190 Published online February 2 , 2009 ( doi:10.1001/jama.2009.56 ) 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 |
12,583 | 31,618,443 | It is unclear whether CVVH has any effect on mortality or complications in patients with severe acute pancreatitis .
It is also unclear whether high-volume CVVH is superior , equivalent or inferior to st and ard CVVH in patients with severe acute pancreatitis | BACKGROUND Severe acute pancreatitis is associated with high rates of mortality and life-threatening complications .
Continuous veno-venous hemofiltration ( CVVH ) has been used in some centers to reduce mortality and avoid local or systemic complications , however its efficiency and safety is uncertain .
OBJECTIVES To assess the benefits and harms of CVVH in patients suffering from severe acute pancreatitis ; to compare the effects of different CVVH techniques ; and to evaluate the optimal time for delivery of CVVH . | BACKGROUND Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients , but a clear definition of an adequate treatment dose has not been established . We undertook a prospect i ve r and omised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival . METHODS We enrolled 425 patients , with a mean age of 61 years , in intensive care who had acute renal failure . Patients were r and omly assigned ultrafiltration at 20 mL h(-1 ) kg(-1 ) ( group 1 , n=146 ) , 35 mL h(-1 ) kg(-1 ) ( group 2 , n=139 ) , or 45 mL h(-1 ) kg(-1 ) ( group 3 , n=140 ) . The primary endpoint was survival at 15 days after stopping haemofiltration . We also assessed recovery of renal function and frequency of complications during treatment . Analysis was by intention to treat . RESULTS Survival in group 1 was significantly lower than in groups 2 ( p=0.0007 ) and 3 ( p=0.0013 ) . Survival in groups 2 and 3 did not differ significantly ( p=0.87 ) . Adjustment for possible confounding factors did not change the pattern of differences among the groups . Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors . 95 % , 92 % , and 90 % of survivors in groups 1 , 2 , and 3 , respectively , had full recovery of renal function . The frequency of complications was similarly low in all groups . INTERPRETATION Mortality among these critically ill patients was high , but increase in the rate of ultrafiltration improved survival significantly . We recommend that ultrafiltration should be prescribed according to patient 's bodyweight and should reach at least 35 mL h(-1 ) kg(-1 ) Abstract Systemic inflammatory response syndrome ( SIRS ) prevention is key to severe acute pancreatitis ( SAP ) treatment and the assessment of high-volume hemofiltration ( HVHF ) for treating SAP accompanying multiple organ dysfunction syndromes . In this prospect i ve controlled study , 40 SAP patients were divided into 2 groups : control ( n = 22 , treated with fasting , decompression , and intravenous somatostatin ) and HVHF ( n = 18 , HVHF administration in addition to the treatment in the control group ) groups ; and were assessed for serum and urine amylase , WBC , C-reactive protein ( CRP ) , and hepatic and renal functions . Vital signs and abdominal symptoms were recorded , and complications and mortality were analyzed . APACHE II scores in the HVHF group were significantly lower than in the control group at 3 and 7 days ( 6.3 ± 1.7 vs 9.2 ± 2.1 and 3.3 ± 0.8 vs 6.2 ± 1.7 , respectively ) . Compared with controls , serum , and urine amylase , WBC , CRP , and organ functions significantly improved after HVHF treatment . Meanwhile , mortality ( 16.7 % vs 31.8 % ) and complication ( 11.1 % vs 40.9 % ) rates were significantly reduced . The other clinical parameters were significantly ameliorated by HVHF . HVHF rapidly reduces abdominal symptoms and improves prognosis , reducing mortality in SAP patients ; and is likely through systemic inflammatory response syndrome attenuation in the early disease stage BACKGROUND AND OBJECTIVES The evidence for high-volume hemofiltration plus hemoperfusion ( HVHF&HP ) for hyperlipidemic severe acute pancreatitis ( HL-SAP ) is anecdotal . The purpose of our study was to evaluate the efficacy of HVHF&HP for HL-SAP in a prospect i ve controlled study . DESIGN AND SETTING Prospect i ve controlled pilot study between May 2010 and May 2013 in a hospital intensive care unit . PATIENTS AND METHODS HL-SAP patients chose conventional treatment alone ( the control group ) or conventional treatment combined with the experimental protocol ( the HVHF&HP group ) and were prospect ively followed in our hospital . APACHE II score , SOFA score , ICU and hospital stay duration , and serum biomarkers were considered endpoints . RESULTS Ten HL-SAP patients accepted conventional treatment alone ( the control group ) and 10 patients underwent HVHF&HP combined with conventional treatment ( the HVHF&HP group ) . The APACHE II score , SOFA score , systolic blood pressure , diastolic blood pressure , heart rate , serum amylase , and serum creatinine were significantly reduced after the HVHF&HP treatment . The changes in these variables were significantly different between the HVHF&HP and control group at 48 hours after the initiation of treatment . Patients in the HVHF&HP group had a significantly shorter ICU stay ( P=.015 ) . The reduction in serum triglyceride and cholesterol in the HVHF&HP group after 2 , 6 , 12 , 24 , and 48 hours was greater than the control group . All of the tested serum cytokines were significantly decreased after HVHF&HP treatment ( P<.05 ) . However , in patients who underwent conventional treatment alone , there was no significant change in the serum cytokines . CONCLUSION This study suggests that the addition of HVHF&HP to conventional treatment for HL-SAP patients may be superior to conventional treatment alone for the improvement of serum biomarkers and clinical outcomes Objective : Our aim was to study the therapeutic effects and the mechanism of combination of hemofiltration ( HF ) and peritoneal dialysis ( PD ) in the treatment of severe acute pancreatitis ( SAP ) . Methods : Fifty-one cases of SAP were r and omly divided into the HF+PD group ( treated group , 36 patients ) and the non-HF+PD group ( control group , 15 patients ) . Both groups were treated by the same traditional methods . The relief time of abdominal pain and abdominal distension , computed tomographic scores , acute physiology and chronic health enquiry II scores , length of stay , cost of hospitalization , operability , and recovery rate of the 2 groups were compared . The concentration of tumor necrosis factor-&agr ; , IL-6 , and IL-8 in serum and ascites volumes was determined before and after treatment . Results : The mean time of abdominal pain relief , amelioration of abdominal distension , decrease of computed tomographic scores , acute physiology and chronic health enquiry II scores , the mean length of stay , and cost of hospitalization of the treated group were significantly shorter or less than those of the control group . The aforementioned inflammatory cytokines , detected at the end of 1 day and 2 days after HF+PD treatment , were decreased significantly compared with those observed in pretherapy and the control group . Conclusions : Inflammatory cytokines , which overproduced in SAP , can be eliminated effectively from the blood and the ascites by HF+PD treatment A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients . Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies , but so far without important effects on their serum concentrations . Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies . In the present study , 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration ( CVVH ) with an AN69 membrane . After 12 h , the hemofilter was replaced and the blood flow rate ( QB ) was switched from 100 ml/min to 200 ml/min or vice versa . Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance . Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane ( ranging from 25 to 43 % of the prefilter amount ) , corresponding with a significant fall in the serum concentration of all cytokines . The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines . Adsorption to the AN69 membrane appeared to be the main clearance mechanism , being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter , indicating rapid saturation of the membrane . A QB of 200 ml/min was associated with a 75 % increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min . The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes AIM To investigate whether continuous veno-venous hemofiltration ( CVVH ) in different filtration rate to eliminate cytokines would result in different efficiency in acute pancreatitis , whether the saturation time of filter membrane was related to different filtration rate , and whether the onset time of CVVH could influence the survival of acute pancreatitis . METHODS Thirty-seven patients were classified into four groups r and omly . Group 1 underwent low-volume CVVH within 48 h of the onset of abdominal pain ( early CVVH , n = 9 ) . Group 2 received low-volume CVVH after 96 h of the onset of abdominal pain ( late CVVH , n = 10 ) . Group 3 underwent high-volume CVVH within 48 h of the onset of abdominal pain ( early CVVH , n = 9 ) . Group 4 received high-volume CVVH after 96 h of the onset of abdominal pain ( late CVVH , n = 9 ) . CVVH was sustained for at least 72 h. Blood was taken before hemofiltration , and ultrafiltrate was collected at the start of CVVH and every 12 h during CVVH period for the purpose of measuring the concentrations of TNF-alpha , IL-1beta and IL-6 . The concentrations of TNF-alpha , IL-1beta and IL-6 were measured by swine-specific ELISA . The Solartron 1 255 B frequency response analyzer ( British ) was used to observe the resistance of filter membrane . RESULTS The survival rate had a significant difference ( 94.44 % vs 68.42 % , P<0.01 ) high-volume and low-volume CVVH patients . The survival rate had also a significant difference ( 88.89 % vs 73.68 % , P<0.05 ) between early and late CVVH patients . The hemodynamic deterioration ( MAP , HR , CVP ) was less severe in groups 4 and 1 than that in group 2 , and in group 3 than in group 4 . The adsorptive saturation time of filters membranes was 120 - 180 min if the filtration rate was 1 000 - 4 000 mL/h . After the first , second and third new hemofilters were changed , serum TNF-alpha concentrations had a negative correlation with resistance ( r : -0.91 , -0.89 , and -0.86 , respectively in group 1 ; -0.89 , -0.85 , and -0.76 , respectively in group 2 ; -0.88 , -0.92 , and -0.82 , respectively in group 3 ; -0.84 , -0.87 , and -0.79 , respectively in group 4 ) . The decreasing extent of TNF-alpha , IL-1beta and IL-6 was significantly different between group 3 and group 1 ( TNF-alpha P<0.05 , IL-1beta P<0.05 , IL-6 P<0.01 ) , between group 4 and group 2 ( TNF-alpha P<0.05 , IL-1beta P<0.05 , IL-6 P<0.01 ) , between group 1 and group 2 ( TNF-alpha P<0.05 , IL-1beta P<0.05 , IL-6 P<0.05 ) , and between group 3 and group 4 ( TNF-alpha P<0.01 , IL-1beta P<0.01 , IL-6 P<0.05 ) , respectively during CVVH period . The decreasing extent of TNF-alpha and IL-1beta was also significantly different between survival patients and dead patients ( TNF-alpha P<0.05 , IL-1beta P<0.05 ) . In survival patients , serum concentration of TNF-alpha and IL-1beta decreased more significantly than that in dead patients . CONCLUSION High-volume and early CVVH improve hemodynamic deterioration and survival in acute pancreatitis patients . High-volume CVVH can eliminate cytokines more efficiently than low-volume CVVH . The survival rate is related to the decrease extent of TNF-alpha and IL-1beta . The adsorptive saturation time of filter membranes are different under different filtration rate condition . The filter should be changed timely once filter membrane adsorption is saturated Background Convective dialysis modalities ( haemofiltration ( HF ) , haemodiafiltration ( HDF ) , and acetate-free biofiltration ( AFB ) ) removed excess body fluid across the dialysis membrane with positive pressure and accumulated middle- and larger-size accumulated solutes more efficiently than haemodialysis ( HD ) . This increased larger solute removal combined with use of ultra-pure dialysis fluid in convective dialysis is hypothesised to reduce the frequency and severity of symptoms during dialysis as well as improve clinical outcomes . Convective dialysis therapies ( HDF and HF ) are associated with lower mortality compared to diffusive therapy ( HD ) in observational studies . This is an up date of a review first published in 2006 . Objectives To compare convective ( HF , HDF , or AFB ) with diffusive ( HD ) dialysis modalities on clinical outcomes ( mortality , major cardiovascular events , hospitalisation and treatment-related adverse events ) in men and women with end-stage kidney disease ( ESKD ) . Search methods We search ed the Cochrane Renal Group 's Specialised Register ( to 18 February 2015 ) through contact with a Trials ' Search Co-ordinator using search terms relevant to this review . Selection criteria We included r and omised controlled trials comparing convective therapy ( HF , HDF , AFB ) with another convective therapy or diffusive therapy ( HD ) for treatment of ESKD . Data collection and analysis Two independent authors identified studies , extracted data and assessed study risk of bias . We summarised treatment effects using the r and om effects model . We reported results as a risk ratio ( RR ) for dichotomous outcomes and mean difference ( MD ) for continuous data together with 95 % confidence intervals ( CI ) . We assessed for heterogeneity using the Chi2 test and explored the amount of variation in treatment estimates beyond that expected by chance using the I2 statistic . Main results Twenty studies comprising 667 participants were included in the 2006 review . In that review , there was insufficient evidence of treatment effects on major clinical outcomes to draw clinical ly meaningful conclusions . Search ing to February 2015 identified 40 eligible studies comprising 3483 participants overall . In total , 35 studies ( 4039 participants ) compared HF , HDF or AFB with HD , three studies ( 54 participants ) compared AFB with HDF , and three studies ( 129 participants ) compared HDF with HF . Risks of bias in all studies were generally high result ing in low confidence in estimated treatment effects . Convective dialysis had no significant effect on all-cause mortality ( 11 studies , 3396 participants : RR 0.87 , 95 % CI 0.72 to 1.05 ; I2 = 34 % ) , but significantly reduced cardiovascular mortality ( 6 studies , 2889 participants : RR 0.75 , 95 % CI 0.61 to 0.92 ; I2 = 0 % ) . One study reported no significant effect on rates of nonfatal cardiovascular events ( 714 participants : RR 1.14 , 95 % CI 0.86 to 1.50 ) and two studies showed no significant difference in hospitalisation ( 2 studies , 1688 participants : RR 1.23 , 95 % CI 0.93 to 1.63 ; I2 = 0 % ) . One study reported rates of hypotension during dialysis were significantly reduced with convective therapy ( 906 participants : RR 0.72 , 95 % CI 0.66 to 0.80 ) . Adverse events were not systematic ally evaluated in most studies and data for health-related quality of life were sparse . Convective therapies significantly reduced predialysis levels of B2 microglobulin ( 12 studies , 1813 participants : MD -5.55 mg/dL , 95 % CI -9.11 to -1.98 ; I2 = 94 % ) and increased dialysis dose ( Kt/V urea ) ( 14 studies , 2022 participants : MD 0.07 , 95 % CI -0.00 to 0.14 ; I2 = 90 % ) compared to diffusive therapy , but results across studies were very heterogeneous . Sensitivity analyses limited to studies comparing HDF with HD showed very similar results . Directly comparative data for differing types of convective dialysis were insufficient to draw conclusions . Studies had important risks of bias leading to low confidence in the summary estimates and were generally limited to patients who had adequate dialysis vascular access . Authors ' conclusions Convective dialysis may reduce cardiovascular but not all-cause mortality and effects on nonfatal cardiovascular events and hospitalisation are inconclusive . However , any treatment benefits of convective dialysis on all patient outcomes including cardiovascular death are unreliable due to limitations in study methods and reporting . Future studies which assess treatment effects of convection dose on patient outcomes including mortality and cardiovascular events would be informative Introduction Severe acute pancreatitis ( AP ) is associated with high morbidity and mortality . Early prediction of severe AP is needed to improve patient outcomes . The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease . Methods We performed a prospect i ve study of 163 nonconsecutive patients with AP , of whom 25 had severe AP according to the revised Atlanta criteria . Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels . Admission plasma levels of C-reactive protein ( CRP ) , creatinine and calcium were measured for comparison . In subgroup analyses , we assessed the cytokine profiles of patients with severe AP ( n = 14 ) who did not have organ dysfunction ( OD ) upon admission ( modified Marshall score < 2 ) . Results Of 14 cytokines elevated in the severe AP group , interleukin 6 ( IL-6 ) and hepatocyte growth factor ( HGF ) levels were independent prognostic markers of severe AP . IL-6 , HGF and a combination of them predicted severe AP with sensitivities of 56.0 % , 60.0 % and 72.0 % , respectively , and specificities of 90.6 % , 92.8 % and 89.9 % , respectively . The corresponding positive likelihood ratio ( LR+ ) values were 5.9 , 8.3 and 7.1 , respectively . The predictive values of CRP , creatinine and calcium were comparable to those of the cytokines . In subgroup analyses of patients with severe AP and without OD upon admission , we found that IL-8 , HGF and granulocyte colony-stimulating factor ( G-CSF ) levels predicted the development of severe AP , with G-CSF being the most accurate cytokine at a sensitivity of 35.7 % , a specificity of 96.1 % and a LR+ of 9.1 . Conclusions IL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP , creatinine and calcium . Although IL-6 and HGF , as either single or combined markers , were not perfect in identifying patients at risk for severe AP , the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied . The accuracy of IL-8 , HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies Objectives This study aim ed to conduct a single-center prospect i ve trial of short-term continuous high-volume hemofiltration ( HVHF ) in patients with predicted severe acute pancreatitis ( SAP ) . Methods Patients with acute pancreatitis with Acute Physiology and Chronic Health Evaluation II scores of greater than 15 on admission between January 2008 and December 2010 were allocated to receive either optimal st and ard therapy or 72 hours of continuous HVHF on an alternate basis , beginning as soon as possible after admission . Biomarkers and clinical outcomes were compared between the 2 groups . Results A total of 61 patients received either conventional therapy ( n = 29 ) or HVHF ( n = 32 ) . High-volume hemofiltration treatment was associated with a significant reduction in the incidence of renal failure ( P = 0.013 ) , infected pancreatic necrosis ( P = 0.048 ) , length of hospitalization ( P = 0.005 ) , mortality ( P = 0.033 ) , as well as duration of renal ( P < 0.001 ) , respiratory ( P = 0.002 ) , and hepatic failure ( P = 0.001 ) . Acute Physiology and Chronic Health Evaluation II score and C-reactive protein and interleukin 6 levels were significantly reduced after the start of HVHF on days 1 , 3 , and 7 ( all , P < 0.05 ) . Conclusions This study suggests that short-term HVHF may reduce local and systemic complications and mortality in patients with SAP with Acute Physiology and Chronic Health Evaluation score of greater than 15 Objectives : To compare the value of emergent triglyceride (TG)-lowering therapies between early high-volume hemofiltration ( HVHF ) and low – molecular-weight heparin ( LMWH ) combined with insulin ( LMWH+insulin ) as well as their effects on the outcomes of hypertriglyceridemic pancreatitis ( HTGP ) patients . Methods : In this r and omized controlled trial , 66 HTGP patients presenting within 3 days after the onset of symptoms from August 2011 to October 2013 were assigned r and omly to receive either HVHF or LMWH+insulin as an emergent TG-lowering therapy . Thirty-three patients were included in each group , and the therapy was started as soon as possible after admission . TG levels , clinical outcomes , and inflammatory biomarkers were compared between the 2 groups . Results : Thirty-two individuals in the HVHF group and 34 in the LMWH+insulin group were included in the final analysis . Characteristics of the patients in both groups were roughly comparable . HVHF could remove TG from the plasma and achieve its target ( < 500 mg/dL ) in approximately 9 hours , whereas the target was not achieved within 48 hours in patients receiving the LMWH+insulin treatment ( P<0.05 ) . However , no differences were found in terms of the majority of the clinical outcomes , including local pancreatic complications ( P>0.05 ) , the requirement of surgical intervention ( P=0.49 ) , mortality ( P=0.49 ) , and the duration of hospitalization ( P=0.144 ) . Furthermore , an unexpectedly higher incidence of persistent organ failure was observed in the HVHF group compared with the LMWH+insulin group ( risk ratio with HVHF , 2.42 ; 95 % confidence interval , 1.15 - 5.11 ; P=0.01 ) . Hospital charges for patients in the HVHF group were approximately 2-fold higher than those for patients in the LMWH+insulin group ( 5.20±4.90 vs. 2.92±3.21 , P=0.03 ) . We selected a systemic inflammatory response syndrome score of at least 2 at baseline as a predictor of SAP patients , and the subgroup analyses showed that HVHF can not improve the prognosis of the predicted SAP patients compared with the LMWH+insulin group . Conclusions : HVHF can lower TG levels more efficiently than LMWH+insulin therapy , but it is not superior in terms of clinical outcomes and costs . Further multicenter studies with large sample s are required to clarify the feasibility of administering the HVHF treatment to HTGP patients ( ChiCTR-TRC-13003274 ) Objective The aim of this study was to investigate the effect of high-volume hemofiltration ( HVHF ) on ameliorating immune dysfunction in patients with severe acute pancreatitis ( SAP ) . Methods Twelve patients diagnosed with SAP admitted to the intensive care unit of general surgery , Jinling Hospital , from January 2004 to December 2006 were included in this study . They were assigned to the st and ard medical therapy group ( SMT group , n=4 ) or HVHF group ( n=8 ) immediately after enrollment , in a 1:2 ratio . The SMT group were given st and ard treatment for SAP , while the HVHF group were given st and ard as well as 72-hour HVHF treatment initiated within 2 hours after enrollment . Patients in the 2 groups were comparable for the baseline clinical parameters . All patients were monitored over a 72-hour observation period for continuous clinical status , blood cell counts including monocytes , CD4 + and CD8 + T cells , and HLA-DR expression on monocytes . Blood sample s were collected from those patients at 0 , 6 , 12 , 24 , 48 , and 72 hour after enrollment for measurement of plasma Th1-type cytokines ( interleukin-1 [ IL-1 ] , IL-2 , interferon-γ [ IFN-γ ] , and tumor necrosis factor-α [ TNF-α ] ) and Th2-type cytokines ( IL-4 , IL-5 , IL-6 , IL-10 , and IL-13 ) using ELISA . Results Within 72 hours , all measured cytokines except IL-4 were maintained at high levels , accompanied with a low level of peripheral monocytes , CD4 + and CD8 + T cell counts , and HLA-DR expression . Seventy-two hours later , plasma cytokines IFN-γ , IL-1 , IL-2 , IL-5 , IL-10 , and IL-13 ( p<0.05 ) , but not TNF-α and IL-6 , in patients in the HVHF group were significantly reduced , while there was no change for these parameters in the SMT group . Plasma levels of IFN-γ , TNF-α , IL-1 , IL-2 , IL-5 , and IL-13 in the HVHF group were significantly lower than those in the SMT group . Peripheral CD4 + and CD8 + T cells , monocyte count , and HLA-DR expression were increased significantly ( p<0.05 ) only in the HVHF group , not in the SMT group . HLA-DR expression in the HVHF group was significant higher than that in the SMT group ( p<0.05 ) . Conclusions HVHF significantly reduced plasma inflammatory cytokine concentrations including those of IFN-γ , TNF-α , IL-1 , IL-2 , IL-5 , and IL-13 , while it increased monocyte HLA-DR expression in patients with SAP . The association of plasma cytokine reduction and cellular immune function recovery and clinical outcome needs further investigation |
12,584 | 19,001,059 | The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 ( 95 % CI , 0.57 to 0.78 ) , with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors .
Antidepressants are effective in the treatment of IBS .
There is less high- quality evidence for routine use of psychological therapies in IBS , but available data suggest these may be of comparable efficacy | OBJECTIVE Irritable bowel syndrome ( IBS ) is a chronic functional gastrointestinal disorder .
Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting . | Twenty patients with irritable bowel syndrome ( IBS ) were r and omly assigned either to intensive , individualized cognitive therapy ( 10 sessions over 8 weeks ) or to 8 weeks of daily gastrointestinal ( GI ) symptom monitoring . Pre- to posttreatment evaluations showed significantly ( p = .005 ) greater GI symptom reduction for those receiving cognitive therapy than for those in symptom monitoring . At posttreatment , 80 % of the cognitive therapy group showed clinical ly significant improvement , whereas only 10 % of the monitoring group showed this . Results held up well at a 3-month follow-up . Within the cognitive therapy group , GI symptom reductions correlated significantly with increases in positive and reductions in negative automatic thoughts BACKGROUND Irritable bowel syndrome ( IBS ) prevalence estimates are essential for measuring the importance of the problem and the burden of the illness . However , IBS diagnosis is based on clinical criteria which have changed over time . The aim of this study was to assess how the use of different diagnostic criteria influences estimated IBS prevalence and , in particular , to compare how this prevalence varies using the new Rome II criteria and previous diagnostic criteria . METHODS An epidemiological survey was conducted in the general population using personal interviews in a home setting . Two thous and individuals stratified by gender , age , social class and geographic location were r and omly selected from the general population of Spain . Participants were classified as ' potential IBS subjects ' ( n = 281 ) or ' non-potential IBS subjects ' ( n = 1719 ) as a result of their response to a screening question regarding the presence of abdominal pain , constipation or diarrhoea . Thus , we estimated IBS prevalence according to the following diagnostic criteria : Manning , Rome I , Rome II , Drossman , Talley and Kay & Jorgensen . RESULTS Prevalences of IBS according to the Manning and Rome I criteria were 10.3 % and 12.1 % , respectively . These were higher than the prevalences obtained with the other criteria used , which varied from 2.1 % to 4.9 % . IBS was more prevalent in females than males irrespective of the criteria used ( the female : male ratio ranged from 2.33 to 4.33 ) . Subjects who fulfilled the Rome II , Drossman , Talley or Kay & Jorgensen criteria also fulfilled the Rome I and Manning criteria . However , between 44 % and 80 % of subjects who fulfilled the Rome I or Manning criteria did not fulfil the more stringent diagnostic criteria . CONCLUSIONS The prevalence of IBS varies enormously depending on the diagnostic criteria employed . Criteria based on the frequency of symptoms , such as the Rome II criteria , produce much lower prevalence values compared to criteria based solely on the presence of symptoms . In fact , more than two-thirds of subjects who fulfilled the Rome I criteria would not have been diagnosed with IBS if Rome II criteria had been employed OBJECTIVES : Psychological treatments are considered to be useful in the irritable bowel syndrome ( IBS ) , although the evidence is based on small , often flawed trials . Although cognitive behavior therapy ( CBT ) and relaxation therapy have both been promising , we hypothesized that CBT would be superior to relaxation and st and ard care alone in IBS patients . The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS . METHODS : Patients ( n = 105 ) with Rome I criteria for IBS were recruited from advertisement ( n = 51 ) and outpatient clinics ( n = 54 ) ; those patients with resistant IBS were not included . A r and omized controlled trial with three arms ( st and ard care for all groups plus either CBT or relaxation ) for 8 wk was conducted , which applied blinded outcome assessment s using vali date d measures with 1 yr of follow-up . The primary outcome for this study was bowel symptom severity . RESULTS : Of 105 patients at the commencement of treatment , the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1 ; this persisted at the 52-wk follow-up , with a significant linear trend for scores to change over time ( F= 39.57 p < 0.001 ) . However , there were no significant differences among the three treatment conditions . Significant changes over time were found for physical functioning ( F= 4.37 , p < 0.001 ) , pain ( F= 3.12 , p < 0.05 ) , general health ( F= 2.71 , p < 0.05 ) , vitality ( F= 2.94 , p < 0.05 ) , and the social functioning scales on the Medical Outcomes Study Short Form 36 ( F= 4.08 , p < 0.05 ) ; however , all three arms showed similar improvement . There were significant reductions in anxiety , depression , and locus of control scales , but no significant differences among the treatment groups were detected . CONCLUSION : Cognitive behavior and relaxation therapy seem not to be superior to st and ard care alone in IBS OBJECTIVES : It has been suggested that the variation in the prevalence of irritable bowel syndrome ( IBS ) may be due to the application of different diagnostic criteria . New criteria for IBS have been proposed ( Rome II ) . It is unknown whether persons meeting different criteria for IBS have similar psychological and symptom features . The aim of this study was to measure the prevalence of IBS according to Manning and Rome definitions of IBS and to evaluate the clinical and psychological differences between diagnostic categories . METHODS : A total of 4500 r and omly selected subjects , with equal numbers of male and female subjects aged ≥18 yr and representative of the Australian population , took part in this study . Subjects were mailed a question naire ( response rate , 72 % ) . Characteristics measured were gastrointestinal symptoms over the past 12 months , neuroticism and extroversion ( Eysenck Personality Question naire ) , anxiety and depression ( Delusions-Symptoms-States Inventory ) , mental and physical functioning ( SF-12 ) , and somatic distress ( Sphere ) . RESULTS : The prevalence for IBS according to Manning , Rome I , and Rome II was 4.4 % ( 95 % confidence interval [ CI ] = 3.5–5.1 % ) , 6.9 % ( CI 6.0–7.8 % ) , and 13.6 % ( CI 12.3–14.8 % ) , respectively . Only 12 persons with Rome I did not also meet Rome II criteria ; 196 persons with Manning criteria did not meet Rome II cut-offs . Having IBS regardless of which criteria were used was significantly associated with psychological morbidity , but psychological factors were not important in discriminating between diagnostic categories . However , pain and bowel habit severity independently discriminated between diagnostic groups . CONCLUSIONS : IBS is a relatively common disorder in the community . The new Rome II criteria may be unnecessarily restrictive in practice Background Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists . Although several r and omized‐controlled trials have assessed the therapeutic role of antidepressant drugs , there is insufficient evidence to support their use One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment Objective Postpr and ial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response . We investigated whether this response can be affected by hypnotherapy . Methods We included 28 patients with irritable bowel syndrome refractory to other treatments . They were r and omized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks ( N = 14 ) or were provided with supportive therapy ( control group ; N = 14 ) . Before r and omization and after 3 months , all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion . Colonic sensory thresholds and tonic and phasic motor activity were assessed . Results Before r and omization , reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations . At 3 months , the colonic sensitivity before duodenal lipids did not differ between groups . Controls reduced their thresholds after duodenal lipids for gas ( 22 ± 1.7 mm Hg vs. 16 ± 1.6 mm Hg , p < .01 ) , discomfort ( 29 ± 2.9 mm Hg vs. 22 ± 2.6 mm Hg , p < .01 ) , and pain ( 33 ± 2.7 mm Hg vs. 26 ± 3.3 mm Hg , p < .01 ) , whereas the hypnotherapy group reduced their thresholds after lipids only for pain ( 35 ± 4.0 mm Hg vs. 29 ± 4.7 mm Hg , p < .01 ) . The colonic balloon volumes and tone response at r and omization were similar in both groups . At 3 months , baseline balloon volumes were lower in the hypnotherapy group than in controls ( 83 ± 14 ml vs. 141 ± 15 ml , p < .01 ) . In the control group , reduced balloon volumes during lipid infusion were seen ( 141 ± 15 ml vs. 111 ± 19 ml , p < .05 ) , but not after hypnotherapy ( 83 ± 14 ml vs. 80 ± 16 ml , p > .20 ) . Conclusion Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome . These effects may be involved in the clinical efficacy of hypnotherapy in IBS Background The efficacy of antidepressants in irritable bowel syndrome ( IBS ) is controversial . No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor . Our aim was to determine whether imipramine and citalopram are efficacious in IBS . Methods This was a r and omized , double-blind , placebo-controlled , parallel group pilot trial with imipramine ( 50 mg ) and citalopram ( 40 mg ) . Results Of 51 IBS patients r and omized , baseline characteristics were comparable among the treatment arms ; the majority was diarrhea-predominant . Adequate relief of IBS symptoms ( primary endpoint ) was similar for each treatment arm . Improvements in bowel symptom severity rating for interference ( P = 0.05 ) and distress ( P = 0.02 ) were greater with imipramine versus placebo , but improvements in abdominal pain were not . There was a greater improvement in depression score ( P = 0.08 ) and in the SF-36 Mental Component Score ( P = 0.07 ) , with imipramine . Citalopram was not superior to placebo . Approximately 20 % of the variance in scores was explained by treatment differences for abdominal pain , bowel symptom severity disability , depression and the mental component of the SF-36 . Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome ( IBS ) . The current study provides a systematic replication of this work in the United States . Six matched pairs of IBS patients were r and omly assigned to either a gut-directed hypnotherapy ( n=6 ) or to a symptom monitoring wait-list control condition ( n=6 ) in a multiple baseline across subjects design . Those assigned to the control condition were later crossed over to the treatment condition . Subjects were matched on concurrent psychiatric diagnoses , susceptibility to hypnosis , and various demographic features . On a composite measure of primary IBS symptoms , treatment was superior ( p=.016 ) to symptom monitoring . Results from the entire treated sample ( n=11 ; one subject was removed from analysis ) indicate that the individual symptoms of abdominal pain , constipation , and flatulence improved significantly . State and trait anxiety scores were also seen to decrease significantly . Results at the 2-month follow-up point indicated good maintenance of treatment gains . No significant correlation was found between initial susceptibility to hypnosis and treatment gain . A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement Despite the accumulation of efficacy data for cognitive-behavioral treatment of Irritable Bowel Syndrome ( IBS ) , efforts to investigate methods for increasing access to psychological treatments are in their infancy . The current study examined the efficacy of self-administered treatment in comparison to a wait list control . Twenty-eight participants monitored gastrointestinal ( GI ) symptoms and completed measures of quality of life ( QOL ) and psychological distress prior to r and omized assignment to self-help treatment or wait list . Wait listed participants later received treatment . A 3 month post-treatment follow-up was included . Seven participants completed immediate treatment ; nine the wait list . The self-help treatment significantly decreased composite GI symptom scores in comparison to the wait list , but did not lead to significant improvements in QOL or distress . In the entire treated sample , including wait list crossovers , analyses showed significant improvement in abdominal pain , average GI symptoms , and perceived health and well-being . Interpretation of these results should be considered in the context of several limitations , including small sample size , brief baseline symptom monitoring , and high drop out rate . Despite these limitations , this study is an important first step in empirically validating low-cost , self-administered treatments as a first line psychological intervention for IBS OBJECTIVE : The impact of functional gastrointestinal disorders ( FGIDs ) on quality of life is unknown . We aim ed to evaluate whether FGIDs impair quality of life in terms of mental and physical functioning in patients and non patients . METHODS : A r and om sample of 4500 subjects , representative of the Australian population , were mailed a question naire on gastrointestinal symptoms in the past 12 months . Quality of life was assessed using the valid SF-12 , in which the lower the scores , the greater the impairment of quality of life . The response rate was 72 % . RESULTS : Among those fulfilling Rome I criteria for a diagnosis of a FGID ( n = 1006 ) versus those not having a FGID ( n = 1904 ) ( healthy controls ) , there was a significant association with impaired mental ( 43.9 vs 48.1 ) and physical ( 47.7 vs 51.6 ) functioning . Mental functioning ( 43.3 vs 44.9 ) and physical functioning ( 46.0 vs 50.5 ) was significantly more impaired in patients versus non patients with a FGID . Furthermore , non patients with a FGID had more impaired mental and physical functioning than healthy controls . CONCLUSION : FGIDs impair quality of life , particularly in those that consult for health care Thirty-four patients with irritable bowel syndrome were r and omly assigned to 1 of 3 treatment conditions : individualized cognitive treatment ( CT ) , self-help support group ( SG ) , or symptom-monitoring waiting-list control ( WL ) . Each of the 3 conditions lasted approximately 8 weeks . Pre- to posttreatment analyses revealed significantly greater reductions in both individual gastrointestinal ( GI ) symptoms and in a composite index for GI symptom change for the CT condition than for the SG or WL conditions . When compared with the SG and WL conditions , the CT condition also showed significant improvement on psychological measures of depression and anxiety . At 3-month follow-up , the results for the CT condition were maintained and revealed further numerical improvements We report two controlled comparisons of a previously vali date d multicomponent ( relaxation , thermal biofeedback , and cognitive therapy ) treatment for irritable bowel syndrome ( IBS ) to an ostensible attention-placebo control ( pseudo-meditation and EEG alpha suppression biofeedback ) and to a symptom-monitoring control . In Study 1 ( n = 10 per condition ) there were nonsignificant trends for the multicomponent treatment to be superior to the attention-placebo condition . In Study 2 ( n = 30 per condition ) , we found no advantage for the multicomponent treatment over the attention-placebo condition . Subjects in both treatment conditions showed significant reductions in GI symptoms , as measured by daily symptom diaries , and significant reductions in trait anxiety and depression . The GI symptom reductions held up over a 6 month follow-up . Possible explanations for the results are explored Background : Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness BACKGROUND & AIMS Studies of antidepressants and psychological treatments in functional bowel disorders ( FBD ) are method ologically limited . The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy ( CBT ) against education ( EDU ) and desipramine ( DES ) against placebo ( PLA ) in female patients with moderate to severe FBD ( irritable bowel syndrome , functional abdominal pain , painful constipation , and unspecified FBD ) . We also evaluated the amenability of clinical ly meaningful subgroups to these treatments . METHODS This r and omized , comparator-controlled , multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD . Participants received psychological ( CBT vs. EDU ) or antidepressant ( DES vs. PLA ) treatment for 12 weeks . Clinical , physiologic , and psychosocial assessment s were performed before and at the end of treatment . RESULTS The intention-to-treat analysis showed CBT as significantly more effective than EDU ( P = 0.0001 ; responder rate , 70 % CBT vs. 37 % EDU ; number needed to treat [ NNT ] , 3.1 ) . DES did not show significant benefit over PLA in the intention-to-treat analysis ( P = 0.16 ; responder rate , 60 % DES vs. 47 % PLA ; NNT , 8.1 ) but did show a statistically significant benefit in the per- protocol analysis ( P = 0.01 ; responder rate , 73 % DES vs. 49 % PLA ; NNT , 5.2 ) , especially when participants with nondetectable blood levels of DES were excluded ( P = 0.002 ) . Improvement was best gauged by satisfaction with treatment . Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms , abuse history , no depression , and diarrhea-predominant symptoms ; CBT was beneficial over EDU for all subgroups except for depression . CONCLUSIONS For female patients with moderate to severe FBD , CBT is effective and DES may be effective when taken adequately . Certain clinical subgroups are more or less amenable to these treatments BACKGROUND & AIMS A r and omized clinical trial was used to test the effectiveness of an 8-session multicomponent program ( Comprehensive ) compared to a Brief ( single session ) version and Usual Care for women with irritable bowel syndrome . METHODS Menstruating women , ages 18 - 48 years , were recruited from a health maintenance organization as well as community advertisements . Psychiatric nurse practitioners delivered both programs . The primary outcomes were improved symptoms , psychological distress , health-related quality of life , and indicators of stress-related hormones . Outcome indicators were measured at 3 points : ( 1 ) immediately after the Comprehensive program or 9 weeks after entry into the Usual Care and Brief Self-Management groups , ( 2 ) at 6 months , and ( 3 ) at 12 months . RESULTS Compared to Usual Care , women in the Comprehensive program had reduced gastrointestinal symptoms , psychological distress indicators , interruptions in activities because of symptoms , and enhanced quality of life that persisted at the 12-month follow-up evaluation . Women in the Brief group also demonstrated statistically significant improvements in quality of life and smaller nonsignificant improvements in other outcome variables than observed in the Comprehensive group . There were no group differences in urine catecholamines and cortisol levels . CONCLUSIONS A comprehensive self-management program is an important therapy approach for women with irritable bowel syndrome . The Brief 1-session version is also moderately helpful for some women with IBS BACKGROUND & AIMS Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome ( IBS ) , but the cost-effectiveness of either treatment in routine practice has not been established . METHODS Patients with severe IBS were r and omly allocated to receive 8 sessions of individual psychotherapy , 20 mg daily of the specific serotonin reuptake inhibitor ( SSRI ) antidepressant , paroxetine , or routine care by a gastroenterologist and general practitioner . Primary outcome measures of abdominal pain , health-related quality of life , and health care costs were determined after 3 months of treatment and 1 year later . RESULTS A total of 257 subjects ( 81 % response rate ) from 7 hospitals were recruited ; 59 of 85 patients ( 69 % ) r and omized to psychotherapy and 43 of 86 ( 50 % ) of the paroxetine group completed the full course of treatment . Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life ( SF-36 physical component score improvement , 5.2 [ SEM , 1.26 ] , 5.8 [ SEM , 1.0 ] , and -0.3 [ SEM , 1.17 ] ; P < 0.001 ) , but there was no difference in the psychological component . During the follow-up year , psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual ( psychotherapy , $ 976 [ SD , $ 984 ] ; paroxetine , $ 1252 [ SD , $ 1616 ] ; and treatment as usual , $ 1663 [ SD , $ 3177 ] ) . CONCLUSIONS For patients with severe IBS , both psychotherapy and paroxetine improve health-related quality of life at no additional cost BACKGROUND & AIMS Although widely prescribed , the evidence for the use of antidepressants for the treatment of irritable bowel syndrome ( IBS ) is limited . In this study , we hypothesized that fluoxetine ( Prozac ) , a selective serotonin reuptake inhibitor , has visceral analgesic properties , leading to increased sensory thresholds during rectal distention and improvement of symptoms , in particular in IBS patients with visceral hypersensitivity . METHODS Forty non-depressed IBS patients underwent a rectal barostat study to assess the sensitivity to rectal distention before and after 6 weeks of treatment with fluoxetine 20 mg or placebo . Abdominal pain scores , individual gastrointestinal symptoms , global symptom relief , and psychologic symptoms were assessed before and after the intervention . RESULTS At baseline , 21 of 40 patients showed hypersensitivity to rectal distention . Fluoxetine did not significantly alter the threshold for discomfort/pain relative to placebo , either in hypersensitive ( 19 + /- 3 vs. 22 + /- 2 mm Hg above MDP ) or in normosensitive ( 34 + /- 2 vs. 39 + /- 4 mm Hg above MDP ) IBS patients . Overall , 53 % of fluoxetine-treated patients and 76 % of placebo-treated patients reported significant abdominal pain scores after 6 weeks ( not significant ) . In contrast , in hypersensitive patients only , fluoxetine significantly reduced the number of patients reporting significant abdominal pain . Gastrointestinal symptoms , global symptom relief , and psychologic symptoms were not altered . CONCLUSIONS Fluoxetine does not change rectal sensitivity in IBS patients . Possible beneficial effects on pain perception need to be confirmed in larger trials BACKGROUND & AIMS Functional gastrointestinal disorders ( FGID ) are common in the community . The natural history of FGID is unknown because of a lack of prospect i ve population -based studies and the indistinct nature of the phenotype . We sought to report the natural history of FGID in a US population . METHODS This prospect i ve cohort study used data from multiple vali date d surveys of r and om sample s of Olmsted County , MN , residents over a mean of a 12-year period between 1988 and 2003 ( n = 1365 ) . The surveys measured gastrointestinal symptoms experienced during the past year . Each subject received a minimum of 2 surveys . Point prevalence , onset , and disappearance rates and transition probabilities were calculated for individual FGIDs . RESULTS Between the initial and final surveys , the point prevalences ( per 100 residents ) were stable for irritable bowel syndrome ( 8.3 % and 11.4 % , respectively ) and functional dyspepsia ( 1.9 % and 3.3 % , respectively ) . The onset of each of the disorders studied was greater than the disappearance rate , but the transition probabilities varied across the different subgroups . Among people with symptoms at baseline , approximately 20 % had the same symptoms , 40 % had no symptoms , and 40 % had different symptoms at follow-up . CONCLUSIONS Although the prevalence of the FGID was stable over time , the turnover in symptom status was high . Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution . This transition between different FGIDs suggests a common etiopathogenesis Until recently many clinical trials of functional gastrointestinal disorders ( FGIDs ) suffered from important weaknesses in trial design , study execution , and data analysis . This makes it difficult to determine whether truly efficacious therapies exist for these disorders . One of the important method ologic problems is the absence of vali date d outcome measures and lack of consensus among stakeholders on how to measure outcome . Currently much of the effort is being put into the development of vali date d outcome measures for several of the FGIDs . The r and omized , controlled trial with parallel groups is the design of choice . In this report , guidelines are given for the basic architecture of intervention studies of FGIDs . Further studies on design issues are required to ensure the recommendations will become evidence based in the future After organic disease had been excluded as far as possible by clinical examination , including laboratory tests , analysis of faeces , and X-ray examination or endoscopy of the upper and lower gastrointestinal tract , 61 patients were given either 50 mg trimipramine at bedtime or identically looking coded placebo in a prospect i ve study for 4 weeks . The complaints were grade d on an analogue scale by both the patients and the physicians . The results showed that the complaint scores were significantly reduced to about half in the placebo group . In the group treated with trimipramine a significantly greater reduction was found for the scores of vomiting , sleeplessness , depression , and for the mucus content of stools . The scores for tiredness during treatment had decreased less in the group receiving trimipramine than in the one receiving placebo . These improvements occurred already during the first week of treatment . No adverse side effect was recorded OBJECTIVE : The purpose of the trial was to determine whether a high-fiber diet ( HFD ) alone or in combination with paroxetine or placebo was effective treatment for patients with irritable bowel syndrome ( IBS ) . METHODS : Design : Trial of HFD alone ( Group 1 ) followed by a r and omized , double-blind trial of HFD with paroxetine or placebo ( Group 2 ) . Setting : Gastroenterology office in a 524-bed university-affiliated community hospital in Pittsburgh . Patients : Men and women , aged 18–65 yr , previously diagnosed with IBS but otherwise healthy . Intervention : Institution of HFD in 98 participants consuming low- or average-fiber diets . Allocation of paroxetine to 38 and placebo to 43 symptomatic participants consuming HFDs . Measurements : Overall well-being , abdominal pain , and abdominal bloating ( Groups 1 and 2 ) ; food avoidance , work functioning , and social functioning ( Group 2 ) . RESULTS : In Group 1 , overall well-being improved in 26 % patients , and abdominal pain and bloating decreased in 22 % and 26 % patients , respectively , with an HFD . In Group 2 , overall well-being improved more with paroxetine than with placebo ( 63.3%vs 26.3 % ; p= 0.01 ) , but abdominal pain , bloating , and social functioning did not . With paroxetine , food avoidance decreased ( p = 0.03 ) and work functioning was marginally better ( p = 0.08 ) . Before unblinding , more paroxetine recipients than placebo recipients wanted to continue their study medication ( 84%vs 37 % ; p < 0.001 ) . CONCLUSIONS : The difference in overall well-being found in our paroxetine/placebo trial is greater than that found in previously published drug/placebo trials for IBS . Moreover , the difference in well-being applied to nondepressed recipients of paroxetine BACKGROUND Irritable bowel syndrome ( IBS ) is commonly thought to be associated with psychologic distress . However , in some studies only persons who had sought medical care for IBS ( IBS patients ) showed an increased frequency of psychiatric symptoms , and non patients did not differ significantly from normal subjects . Our aims were 1 ) to estimate the prevalence of IBS in the population aged 18 - 45 years , 2 ) to find the proportion seeking medical care for IBS , and 3 ) to compare IBS subjects with normals , and IBS patients with IBS non patients with regard to mental health . METHODS Question naires on IBS symptoms and the General Health Question naire ( GHQ ) were mailed to 5000 r and omly sample d persons aged 18 - 45 years . The response rate was 58 % . RESULTS IBS was found in 7.4 % of the men and 13.3 % of the women . Those who had sought medical attention had more severe symptoms . The Likert mean score on the GHQ was 4.7 ( 95 % confidence interval , 4.4 - 5.0 ) points higher for the IBS group than for normals ( P < 0.001 ) . There was no difference in GHQ scores between IBS patients and non patients . CONCLUSIONS The results indicate that IBS per se is associated with more psychiatric distress , regardless of medical care-seeking . Seeking medical care is associated with more severe IBS symptoms In this study , Herbert Benson 's ( 1975 ) Relaxation Response Meditation program was tested as a possible treatment for Irritable Bowel Syndrome ( IBS ) . Participants were 16 adults who were matched into pairs based on presence of Axis I disorder , primary IBS symptoms and demographic features and r and omized to either a six week meditation condition or a six week wait list symptom monitoring condition . Thirteen participants completed treatment and follow-up . All subjects assigned to the Wait List were subsequently treated . Patients in the treatment condition were taught the meditation technique and asked to practice it twice a day for 15 minutes . Composite Primary IBS Symptom Reduction ( CPSR ) scores were calculated for each patient from end of baseline to two weeks post-treatment ( or to post wait list ) . One tailed independent sample t-tests revealed that Meditation was superior to the control ( P=0.04 ) . Significant within-subject improvements were noted for flatulence ( P=0.03 ) and belching ( P=0.02 ) by post-treatment . By three month follow-up , significant improvements in flatulence ( P<0.01 ) , belching ( P=0.02 ) , bloating ( P=0.05 ) , and diarrhea ( P=0.03 ) were shown by symptom diary . Constipation approached significance ( P=0.07 ) . Benson 's Relaxation Response Meditation appears to be a viable treatment for IBS Abstract Objective To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome . Design R and omised controlled trial . Setting 10 general practice s in London . Participants 149 patients with moderate or severe irritable bowel syndrome resistant to the antispasmodic mebeverine . Interventions Cognitive behaviour therapy delivered by trained primary care nurses plus 270 mg mebeverine taken thrice daily compared with mebeverine treatment alone . Main outcome measures Primary measures were patients ' scores on the irritable bowel syndrome symptom severity scale . Secondary measures were scores on the work and social adjustment scale and the hospital anxiety and depression scale . Results Of 334 referred patients , 72 were r and omised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine alone . Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone , with a mean reduction in score of 68 points ( 95 % confidence interval 103 to 33 ) , with the benefit persisting at three months and six months after therapy ( mean reductions 71 points ( 109 to 32 ) and 11 points ( 20 to 3 ) ) but not later . Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy ( mean reduction 2.8 points ( 5.2 to 0.4 ) ) , but had an inconsistent effect on the hospital anxiety and depression scale . Conclusion Cognitive behaviour therapy delivered by primary care nurses offered additional benefit over mebeverine alone up to six months , although the effect had waned by 12 months . Such therapy may be useful for certain patients with irritable bowel syndrome in primary care Abstract Numerous attempts have been made to relate specific emotional conflicts to colonic symptoms in the irritable colon syndrome . Depression has been described as an accompaniment of the illness . This paper investigates the relationship between irritable colon and depression using self-rating symptom scales and the Zung Self-Rating Depression Scale . Thirty-one subjects were followed for two months in a double-blind study employing a tricyclic antidepressant and an inactive placebo . The study demonstrates the frequency of depression in patients with the syndrome ; it shows a clearly positive treatment effect with placebo alone for both depressive symptoms and gastrointestinal complaints , and suggests that tricyclic antidepressant therapy results in moderately greater improvement in symptoms than does treatment with placebo alone Thirty-five patients with irritable bowel syndrome were r and omized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin . The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to underst and the nature of their symptoms , their relationship to stress and were taught relaxation exercises . Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity . This benefit was maintained for at least 12 months . Few of those given conventional management had any benefit . A stress management programme would appear to be of value for patients with irritable bowel syndrome |
12,585 | 18,288,311 | Conclusions The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action . | Background Male reproductive tract abnormalities such as hypospadias and cryptorchidism , and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology result ing from the disruption of gonadal development during fetal life , the testicular dysgenesis syndrome ( TDS ) .
The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993 .
The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago , and other systematic review s of the association between estrogenic compounds , other than the potent pharmaceutical estrogen diethylstilbestrol ( DES ) , and TDS end points have remained inconclusive . | This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind , placebo-controlled investigation during 1951 and 1952 aim ed at determining the effect of DES on pregnancy . Epididymal cysts , hypotrophic testes , and capsular in duration were the more common genital lesions found in 25 % of 163 DES-exposed males as compared to 6 % in 168 control males . Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26 % of the DES-exposed group produced an ejaculate volume under 1.5 ml ; no such cases were observed in the control group . The average values for sperm density and total motile spermatozoa per ejaculate , although in the normal range , were more than two times lower in the DES-exposed group as compared to the controls . A quality score of > 10 ( “ severely pathologic semen ” ) was found in 28 % of the DES-exposed group as compared to 0 in the control group . An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group . Two cases of azoospermia , one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group . Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles ( oligomenorrhea ) as compared to 10 % of 136 controls . The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group ( 18 % ) than in the control group ( 33 % ) . Circumferential ridges of the vagina and cervix were seen in 40 % of 229 DES-exposed females but in none of 136 controls . Colposcopic findings in the vagina revealed adenosis in 66.8 % of the DES-exposed females and in 3.6 % of the control group . Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects . No cases of cancer were observed in either the male or female offspring Increasing rates of cryptorchidism and hypospadias in human population s may be caused by exogenous environmental agents . We conducted a case – control study of serum levels of p , p′-dichlorodiphenyltrichloroethane ( DDT ) and its major metabolite , p , p′-dichlorodiphenyldichloroethylene ( DDE ) , and cryptorchidism and hypospadias in the Child Health and Development Study , a longitudinal cohort of pregnancies that occurred between 1959 and 1967 , a period when DDT was produced and used in the United States . Serum was available from the mothers of 75 male children born with cryptorchidism , 66 with hypospadias , and 4 with both conditions . We r and omly selected 283 controls from the cohort of women whose male babies were born without either of these conditions . Overall , we observed no statistically significant relationships or trends between outcomes and serum measures . After adjusting for maternal race , triglyceride level , and cholesterol level , compared with boys whose mothers had serum DDE levels < 27.0 ng/mL , boys whose mothers had serum DDE levels ≥61.0 ng/mL had odds ratios of 1.34 [ 95 % confidence interval ( CI ) , 0.51–3.48 ] for cryptorchidism and 1.18 ( 95 % CI , 0.46–3.02 ) for hypospadias . For DDT , compared with boys whose mothers had serum DDT levels < 10.0 ng/mL , boys whose mothers had serum DDT levels ≥20.0 ng/mL had adjusted odds ratios of 1.01 ( 95 % CI , 0.44–2.28 ) for cryptorchidism and 0.79 ( 95 % CI , 0.33–1.89 ) for hypospadias . This study does not support an association of DDT or DDE and hypospadias or cryptorchidism The 27-year follow-up is reported of 136 children whose mothers were involved in a r and omised trial of high doses of stilboestrol and ethisterone therapy during pregnancy . The children were not contacted directly . Information about them was obtained from hospitals , general practitioners , and other official sources ; and the persons who responded to our inquiries were unaware of who had been exposed to hormones in utero and whose mothers had received an inactive tablet . All children were traced . Urogenital anomalies were reported more frequently in the hormone-exposed than the unexposed children ( 14 % and 9 % respectively ) . The earlier in pregnancy the therapy began , the higher the prevalence rate of abnormalities ( X2 for trend , p less than 0.02 ) . No malignant tumours were reported . For males , the proportion reported to be married or living as married was lower in the exposed than in the unexposed group ( 32 % and 62 % respectively ) . The proportion was lower the earlier in pregnancy hormonal exposure occurred and the higher the total hormone dose to which they were exposed ( X2 for trend , p less than 0.02 ) . These findings suggest that some interference with sexual function may not be uncommon in males exposed to high doses of stilboestrol and ethisterone while in utero Synthetic hormone-disrupting chemicals may play a role in the increased frequency of cryptorchidism observed in some studies . We used a spatial ecological design to search for variations in orchidopexy rates in the province of Granada in Spain and to search for relationships between these differences and geographical variations in exposure to pesticides . Orchidopexy rates were estimated for the period from 1980 to 1991 in all municipalities and health care districts served by the University of Granada Hospital . A r and om sample of males of the same age ( 1 - 16 years ) admitted for any reason during the same period was used to estimate inpatient control rates . Each municipality was assigned to one of four levels of pesticide use . We used Poisson homogeneity tests to detect significant differences in rates of orchidopexy between districts and between levels of pesticide use . Poisson and logistic regression models were also used to estimate the strength of association between orchidopexy and level of pesticide use . Orchidopexy rates tended to be higher in districts near the Mediterranean coast where intensive farming is widespread . The city of Granada , where the reference hospital is located , also had higher figures both for orchidopexy and inpatient control rates . Regression models showed that the strength of association between orchidopexy and level of pesticide use tended to increase with higher levels of use , with the exception of level 0 ( mainly in the city of Granada ) . Our results are compatible with a hypothetical association between exposure to hormone-disruptive chemicals and the induction of cryptorchidism . Several method ological limitations in the design make it necessary to evaluate the results with caution . ImagesFigure 1.Figure 2.Figure 3 Epididymal cysts and /or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero , compared to 7.8 per cent of 307 placebo-exposed controls . Analyses of the spermatozoa have revealed severe pathological changes ( Eliasson score greater than 10 ) in 134 diethylstilbestrol-exposed men ( 18 per cent ) and 87 placebo-exposed men ( 8 per cent ) . Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism . Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent . Although none of our Diekmann 's lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid . A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma ) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism BACKGROUND Several investigators have shown striking differences in semen quality and testicular cancer rate between Denmark and Finl and . Since maldescent of the testis is a shared risk factor for these conditions we undertook a joint prospect i ve study for the prevalence of congenital cryptorchidism . METHODS 1068 Danish ( 1997 - 2001 ) and 1494 Finnish boys ( 1997 - 99 ) were consecutively recruited prenatally . We also established prevalence data for all newborns at Turku University Central Hospital , Finl and ( 1997 - 99 , n=5798 ) . Testicular position was assessed by a st and ardised technique . All subtypes of congenital cryptorchidism were included , but retractile testes were considered normal . FINDINGS Prevalence of cryptorchidism at birth was 9.0 % ( 95 % CI 7.3 - 10.8 ) in Denmark and 2.4 % ( 1.7 - 3.3 ) in Finl and . At 3 months of age , prevalence rates were 1.9 % ( 1.2 - 3.0 ) and 1.0 % ( 0.5 - 1.7 ) , respectively . Significant geographic differences were still present after adjustment for confounding factors ( birthweight , gestational age , being small for gestational age , maternal age , parity , mode of delivery ) ; odds ratio ( Denmark vs Finl and ) was 4.4 ( 2.9 - 6.7 , p<0.0001 ) at birth and 2.2 ( 1.0 - 4.5 , p=0.039 ) at three months . The rate in Denmark was significantly higher than that reported 40 years ago . INTERPRETATION Our findings of increasing and much higher prevalence of congenital cryptorchidism in Denmark than in Finl and contribute evidence to the pattern of high frequency of reproductive problems such as testicular cancer and impaired semen quality in Danish men . Although genetic factors could account for the geographic difference , the increase in reproductive health problems in Denmark is more likely explained by environmental factors , including endocrine disrupters and lifestyle Summary . In the early 1950s , a r and omized , double‐blind , controlled trial of the value of prophylactic stilboestrol therapy given antenatally to reduce the incidence of late pregnancy toxaemia and to improve perinatal mortality was conducted at University College Hospital , London . Women expecting their first baby were allocated to one or other of two groups . Those in the stilboestrol group started treatment at the 12th week of pregnancy on average and received a mean dose of about 11.5 g of the drug while those in the control group received placebo tablets . In spite of the fact that the original trial documentation was lost , it was possible to be fairly certain which was the treated group and follow‐up data from 650 mothers and 660 offspring were obtained from death certificates , cancer registration s and question naires sent to general practitioners . We found no indication of any harmful long‐term effect of stilboestrol exposure during pregnancy on the mothers — in particular 10 out of 331 women in the untreated group and 9 out of 319 women in the treated group were found to have developed breast cancer . Amongst the daughters , those in the treated group suffered an excess of minor benign lesions of the cervix uteri and an excess ( not statistically significant ) of unfavourable pregnancy outcomes . None of the daughters had developed clear cell adenocarcinoma of the vagina or cervix uteri . Amongst the sons , we discovered no evidence of any significant excess of genital tract disorders or of impaired reproductive performance in the treated group but one son developed a ( fatal ) teratoma of the testis . Unexpectedly , psychiatric disease ( especially depression and anxiety ) was reported by general practitioners about twice as often in the treated group offspring ( sons and daughters ) as in the untreated group . This result can not be due to bias , and is unlikely to be due to confounding or chance , and may thus represent an adverse effect of exposure to stilboestrol in utero BACKGROUND An association between prenatal diethylstilbestrol ( DES ) exposure and cancer in men , especially testicular cancer , has been suspected , but findings from case-control studies have been inconsistent . This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospect i ve follow-up . METHODS A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994 . The overall and site-specific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population -based rates . The relative rate ( RR ) was used to assess the strength of the association between prenatal DES exposure and cancer development . All statistical tests were two-sided . RESULTS Overall cancer rates among DES-exposed men were similar to those among unexposed men ( RR = 1.07 ; 95 % confidence interval [ CI ] = 0.58 to 1.96 ) and to national rates ( RR = 0.99 ; 95 % CI = 0.65 to 1.44 ) . Testicular cancer may be elevated among DES-exposed men , since the RRs for testicular cancer were 3.05 ( 95 % CI = 0.65 to 22.0 ) times those of unexposed men in the study and 2.04 ( 95 % CI = 0.82 to 4.20 ) times those of males in the population -based rates . The higher rate of testicular cancer in the DES-exposed men is , however , also compatible with a chance observation . CONCLUSIONS To date , men exposed to DES in utero do not appear to have an increased risk of most cancers . It remains uncertain , however , whether prenatal DES exposure is associated with testicular cancer With the objective of identifying whether hypospadias in infants is associated with maternal use of oral contraceptives before pregnancy or in early pregnancy , 846 case-control pairs were collected from eight different malformation monitoring programs around the world and mothers were interviewed using structured question naires administered after the birth of the infants . There was no difference in the preconceptional use of oral contraceptives between cases and controls , neither with respect to the number of years of oral contraceptive usage nor the time between stopping oral contraceptives and the present pregnancy . To this material was added data on oral contraceptive usage in early pregnancy from two other sources : an ongoing case-control study in Spain ( 725 infants with hypospadias ) and a population -based study in Sweden ( 631 infants with hypospadias ) . There was no statistically significant difference in oral contraceptive exposure in early pregnancy between cases and controls . There is no demonstrable association between oral contraceptive use and infant hypospadias Previous epidemiological studies of cryptorchidism have led to the hypothesis that the risk of undescended testis is associated with excess oestrogen exposure during pregnancy . A case-control study was undertaken to test this hypothesis , comparing mothers of affected boys ( 244 ) and normal male births ( 488 ) born within six months of a case selected r and omly from the British Columbia population . Information was collected on the mother 's reproductive history , family history , and past medical history , and events surrounding all pregnancies ending in a birth . The results were analysed using both the population -based sample of male births and the male sibs of cases as control groups . Neither exogenous oestrogen exposure , nor any of the pregnancy-related variables hypothesized to be indirect indicators of endogenous oestrogen exposure , including bleeding and nausea and /or vomiting , were found to be significantly associated with risk of undescended testes in either comparison . More mothers with later index births reported menstrual irregularity greater than half the time , and smoking , thought to have a protective effect , was more prevalent among case mothers than control mothers . No other variables were significantly different between case and control mothers . The results of this study do not support the hypothesis that elevated exogenous or endogenous oestrogen exposure during pregnancy increases the risk of undescended testis in male children In a prospect i ve study of some 20,000 pregnancies in the Child Health and Development Studies in the San Francisco East Bay area , 226 gravidas were tested for pregnancy with estrogen/progestogen preparations . The two control groups were women who were tested for pregnancy by either a serum or urine test . There were no statistically differences ( p greater than 0.05 ) in the rates of severe congenital anomalies between the hormone test group and the two control groups . The relative risks and the 95 % confidence intervals were 1.01 ( 0.47 - 2.19 ) for the hormone/serum test comparison and 1.60 ( 0.60 - 4.18 ) for the hormone/urine test comparison A case-referent study of birth defects was nested in a prevalence survey of adverse reproductive outcomes carried out among 8867 floriculture workers in Bogotá , Colombia . A total of 535 children born to these workers and reported by their parents as malformed and 1070 children selected at r and om as referents were invited to a medical examination including consultation with a geneticist and a clinical teratologist and a review of the medical records . Seventy-six percent of both groups attended the examination . Of 403 children reported as malformed , a birth defect was confirmed for only 154 ( 38 % ) . On the other h and , of the 817 children reported as normal , 735 ( 90 % ) were normal , but 68 had a birth defect and 14 had other conditions . A case-referent analysis was then carried out including 222 children with birth defects and 443 referents . An increased risk was found only for birthmarks , and specifically for hemangiomas , for children with parents exposed to pesticides in the floriculture industry The in utero effects of diethylstilbestrol on the human male genital tract are reported in our followup study of male offspring of mothers treated with diethylstilbestrol . Anatomical and functional abnormalities were significantly greater in male patients exposed to diethylstilbestrol compared to male controls whose mothers were all participants in a prospect i ve , r and omized double-blind study on the effects of diethylstilbestrol on pregnancy at our hospital during the early 1950s . Epididymal cysts , hypotrophic testes and capsular in duration of the testes were among the more common genital lesions found in more than 25 per cent of 159 male patients exposed to diethylstilbestrol compared to a 6.8 per cent incidence in 161 male controls . Spermatozoal analysis revealed severe pathological changes ( Eliasson score more than 10 ) in 32 per cent of 31 patients exposed to diethylstilbestrol and 0 per cent of 20 male controls . Abnormal findings on physical examination combined with severe sperm abnormalities ( Eliasson score more than 10 ) were found in 23 per cent of the male patients exposed to diethylstilbestrol versus none of the male controls . Cytologic examinations revealed no malignant cells from urine sample s before and after prostatic massage or ejaculation , prostatic fluids and aspirates from epididymal cysts |
12,586 | 11,226,105 | Review s in perioperative medicine tended to evaluate prophylactic or therapeutic interventions .
No differences were seen in quality between review s published in anesthesia and nonanesthesia journals .
IMPLICATION S The quality of systematic review s relating to perioperative medicine was examined systematic ally and found to be similar in quality to those in other specialties . | UNLABELLED Systematic review s are structured review s that use scientific strategies to reduce bias in the collection , appraisal , and interpretation of relevant studies . | In an effort to identify the types of articles published in anaesthesia literature , a stratified r and om sample of articles published in North America between 1977 and 1986 was analyzed ( N = 571 ) . Human studies constituted 63 per cent of the total , with case reports and case series constituting over half . Study design s classed as descriptive in nature were remarkably rare in the anaesthesia literature , with prevalence and case-control studies constituting 0.8 and 3.3 per cent of the total respectively . Cohort studies ( 7.8 per cent ) , non-r and omized intervention studies ( 12.8 per cent ) , and r and omized controlled trials ( 17.8 per cent ) were more numerous , but many suffered major contamination of experimental design . Frequently identified concerns in assessing the applicability of a given study to general anaesthetic practice were a bias induced by selection of the study subjects , application of the results from tertiary care hospitals to community hospitals , and contamination of the study protocol . These factors were identified as present in the majority of articles . The results suggest that growth of the speciatty of anaesthesia is constrained by the narrow spectrum of study design s , as well as major problems affecting generalizability of the published results .RésuméAfin ďidentifier le genre ďarticles publiés dans la littérature anesthésique , un échantillon r and omisé et stratifié des articles publiés en Amérique du Nord entre 1977 et 1986 a été analysé ( N = 571 ) . Les études cliniques constituaient 63 pour cent du total , avec des histoires de cas et des séries de cas constituant plus que la moitié . Les études descriptives étaient rares alors que les études de prévalence et les études cliniques formaient respectivement 0.8 et 3.3 pour cent du total . Les études de cohortes ( 7.8 pour cent ) , des études ďintervention non r and omisée ( 12.8 pour cent ) et des études contrôlées et r and omisées ( 17.8 pour cent ) étaient plus nombreuses mais plusieurs souffraient de problèmes majeurs de planification expérimentale . Les points fréquemment identifiés dans ľévaluation de ľapplicabilité ďune étude donnée à la pratique anesthésique générale était : un biais induit par la sélection de ľétude , ľapplication des résultats ďun centre de soin tertiaire à des hôpitaux communautaires , et des problèmes de protocol e de ľétude . Ces problèmes ont été identifiés dans la majorité des articles . Ces résultats suggèrent que la croissance de la spécialité anesthésique est contrainte par un spectre étroit de la planification des études ainsi que par des problèmes majeurs affectant la généralisation des résultats publiés Simple criteria were used to evaluate the statistical analyses in 243 articles from two American anesthesia journals published in the latter six months of 1981 and 1983 . Eighty-two percent of the articles reported the use of control measures and 37 % reported r and omization of treatment , where they were possible . Data were classified as nominal , ordinal , or interval ; as independent or related sample s ; as two- sample or more-than-two- sample cases . The descriptive , inferential , and correlative tests used were evaluated for appropriate application and primary errors were identified . Nine percent of the 722 descriptive statistics had major errors , most of which were a description of ordinal data as though they were interval . The incidence of erroneous applications of 394 inferential statistical tests was 78 % . Nearly three-quarters of the 308 primary inferential statistical errors involved either use of a test for independent sample s on related data ( and vice versa ) or multiple applications of an uncorrected test to the same data . Only 4 % of the 113 statistics of association were considered erroneous , most because the method was not identified . No differences were detected in the incidence of errors in either experimental design or statistical analysis across time or across the two anesthesia journals . Fifteen percent of the 243 articles in both journals at both times were without major errors in statistical analysis . Recognition of potential sources of error should make it easier for investigators to use experimental design s and statistical analyses appropriate to their needs 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 Background Controversy exists as to the risk for postoperative apnea in former preterm infants . The conclusions of published studies are limited by the small number of patients . Methods The original data from eight prospect i ve studies were subject to a combined analysis . Only patients having inguinal herniorrhaphy under general anesthesia were included ; patients receiving caffeine , regional anesthesia , or undergoing other surgical procedures were excluded . A uniform definition for apnea was used for all patients . Eleven risk factors were examined : gestational age , postconceptual age , birth weight , history of respiratory distress syndrome , bronchopulmonary dysplasia , neonatal apnea , necrotizing enterocolitis , ongoing apnea , anemia , and use of opioids or nondepolarizing muscle relaxants . Results Two hundred fifty-five of 384 patients from eight studies at four institutions fulfilled study criteria . There was significant variation in apnea rates and the location of apnea ( recovery room and postrecovery room ) between institutions ( P < 0.001 ) . There was considerable variation in the duration and type of monitoring , definitions of apnea , and availability of historical information . The incidence of detected apnea was greater when continuous recording devices were used compared to st and ard impedance pneumography with alarms or nursing observations . Despite these limitations , it was determined that : ( 1 ) apnea was strongly and inversely related to both gestational age ( P = 0.0005 ) and postconceptual age ( P < 0.0001 ) ; ( 2 ) an associated risk factor was continuing apnea at home ; ( 3 ) small-for-gestational-age infants seemed to be somewhat protected from apnea compared to appropriate- and large-for-gestational-age infants ; ( 4 ) anemia was a significant risk factor , particularly for patients > 43 weeks ' postconceptual age ; ( 5 ) a relationship to apnea with history of necrotizing enterocolitis , neonatal apnea , respiratory distress syndrome , bronchopulmonary dysplasia , or operative use of opioids and /or muscle relaxants could not be demonstrated . Conclusions The analysis suggests that , if it is assumed that the statistical models used are equally valid over the full range of ages considered and that the average rate of apnea reported across the studies analyzed is accurate and representative of actual rates in all institutions , the probability of apnea in non-anemic infants free of recovery-room apnea is not less than 5 % , with 95 % statistical confidence until postconceptual age was 48 weeks with gestational age 35 weeks . This risk is not less than 1 % , with 95 % statistical confidence , for that same subset of infants , until postconceptual age was 56 weeks with gestational age 32 weeks or postconceptual age was 54 weeks and gestational age 35 weeks . Older infants with apnea in the recovery room or anemia also should be admitted and monitored . The data do not allow prediction with confidence up to what age this pre caution should continue to be taken for infants with anemia . The data were insufficient to allow recommendations regarding how long infants should be observed in recovery . There is additional uncertainty in the results due to the dramatically different rates of detected apnea in different institutions , which appear to be related to the use of different monitoring devices . Given the limitations of this combined analysis , each physician and institution must decide what is an acceptable risk for postoperative apnea OBJECTIVE To assess the extent to which hypotheses about potential adverse effects of epidural analgesia during labour can be tested using evidence from controlled comparisons of epidural with non-epidural forms of pain relief . INCLUSION CRITERIA Prospect i ve studies in which an attempt had been made to use r and om allocation to generate comparable groups of women receiving epidural and non-epidural forms of pain relief during labour . IDENTIFICATION OF RELEVANT STUDIES : Systematic h and search of a total of 36 anaesthetic , obstetric and general journals , and more than 30 other journals ( 1950 - 1990 ) , and a search of MEDLINE ( 1966 - 1990 ) . DATA COLLECTION Data were abstract ed from published reports of 9 controlled trials , involving a total of 600 women . It was possible to obtain some missing information and data from the investigators . RESULTS Very few postulated effects of epidural block during labour can be confirmed or rejected on the basis of the evidence generated by the small number of controlled trials . Evidence derived from these trials confirms that epidural block provides more effective relief of pain than alternatives ; and that if it is continued during the second stage of labour , it can cause a substantial increase in the use of instrumental delivery . CONCLUSIONS Considering the very widespread use of epidural block during labour , remarkably little is known about its short-term and long-term effects . In view of hypotheses about potentially important adverse effects , there is still a need to conduct larger , better design ed r and omised controlled trials Abstract R and omised controlled trials ( RCTs ) alone are unlikely to provide reliable estimates of the incidence of rare events because of their limited size . Cohort , case control , and other observational studies have large numbers but are vulnerable to various kinds of bias . Wanting to estimate the risk of death from bleeding or perforated gastroduodenal ulcers with chronic usage of non‐steroidal anti‐inflammatory drugs ( NSAIDs ) with greater precision , we developed a model to quantify the frequency of rare adverse events which follow a biological progression . The model combined data from both RCTs and observational studies . We search ed systematic ally for any report of chronic ( ≥2 months ) use of NSAIDs which gave information on gastroduodenal ulcer , bleed or perforation , death due to these complications , or progression from one level of harm to the next . Fifteen RCTs ( 19 364 patients exposed to NSAIDs for 2–60 months ) , three cohort studies ( 215 076 patients redeeming a NSAID prescription over a 3–12 month period ) , six case‐control studies ( 2957 cases ) and 20 case series ( 7406 ) , and case reports ( 4447 ) were analysed . In RCTs the incidence of bleeding or perforation in 6822 patients exposed to NSAIDs was 0.69 % ; two deaths occurred . Of 11 040 patients with bleeding or perforation with or without NSAID exposure across all reports , 6–16 % ( average 12 % ) died ; the risk was lowest in RCTs and highest in case reports . Death from bleeding or perforation in all controls not exposed to NSAIDs occurred in 18 out of 849 489 ( 0.002 % ) . From these numbers we calculated the number‐needed‐to‐treat for one patient to die due to gastroduodenal complications with chronic ( ≥2 months ) NSAIDs as 1/((0.69 × {6–16 % , average 12%})−0.002%))=909–2500 ( average 1220 ) . On average 1 in 1200 patients taking NSAIDs for at least 2 months will die from gastroduodenal complications who would not have died had they not taken NSAIDs . This extrapolates to about 2000 deaths each year in the UK Summary Hyperventilation is a st and ard method of treating patients with intracranial hypertension . I review ed all the relevant peer- review ed literature to identify the documented benefits of hyperventilation as treatment for cerebral disease . Studies were identified by search es of the Medline data base between 1966 and September 1996 , interviews with experts , and review s of reference lists . Retained manuscripts reported results of a human or animal controlled trial that tested effect of hyperventilation and /or systemic hypocapnia on mortality , histopathology , or neurologic examination . Studies could be either r and omized or observational and need not have been blinded . I found that for no clinical studies of cerebral disease , other than in acute head injury patients , was there any suggestion of a clinical benefit from hyperventilation . Three controlled , observational studies examined effects of airway management and ventilatory support in head-injured patients . These studies found that maintaining such patients hypocapnic , versus spontaneously breathing without ventilatory support , decreased mortality . However , by design the studies could not establish whether hypocapnia itself contributed to the decreased mortality . Two clinical studies examined the effect of P3CO2 itself in patients with head injury . In both , hypocapnic patients did not have better neurologic outcome . In conclusion , securing the airway and supporting ventilation probably reduces mortality in unconscious , neurosurgical patients . However , there are virtually no clinical data that hypocapnia improves outcome in patients with cerebral disease |
12,587 | 29,575,036 | CONCLUSIONS This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects .
It confirms that malignant mesothelioma is associated with the physical , emotional , and social functioning of patients , while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress , despair , and mental health difficulties | BACKGROUND The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people . | Purpose People with lung cancer report a higher burden of unmet needs , specifically psychological and daily living unmet needs . They experience more psychological distress and more physical hardship than other tumour sites . This study examined the levels of unmet need and psychological distress in inoperable lung cancer patients at the start of treatment . Methods A cross-section survey methodology was employed using baseline data from a r and omised controlled trial design ed to evaluate a supportive care intervention . Eligible lung cancer patients were approached to participate at the start of treatment . Consenting patients completed question naires prior to or just after the commencement of treatment . Reliable and valid measures included Needs Assessment for Advanced Lung Cancer Patients , Hospital Anxiety and Depression Scale and Brief Distress Thermometer . Results Of the 108 patients participating , the top unmet need was ‘ Dealing with concerns about your family ’s fears and worries ’ ( 62 % ) ; with the next four also coming from the psychological/emotional domain , but , on average , most needs related to medical communication . Thirty two percent of patients reported clinical or sub clinical anxiety and 19 % reported HADS scores suggestive of clinical or sub clinical depression . Moreover , 39.8 % of the sample reported distress above the cut-off on the distress thermometer and this was associated with higher needs for each need subscale ( p < 0.05 ) . Conclusions People with lung cancer have high levels of unmet needs especially regarding psychological/emotional or medical communication . People with lung cancer who are classified as distressed have more unmet needs Abstract Purpose To examine the effect of knowledge of radiographic abnormalities on the mental health of asbestos-exposed people with and without pleural abnormalities . Methods Subjects were former asbestos mine and mill workers and residents of the mining town who had participated in an annual health review program . Pleural abnormalities ( pleural plaques , diffuse pleural thickening and asbestosis ) were determined from plain chest X-rays . All Participants completed a question naire on mental health status ( SF-12 ) and locus of control ( LOC ) . Results There were no significant differences between asbestos-exposed people with and without radiographic abnormalities for either the SF-12 mental health score or LOC . However , the asbestos-exposed cohorts had lower mental health scores compared with a r and om sample of the local population . Conclusion The presence of pleural abnormalities did not further affect the mental health of asbestos-exposed people beyond a decrement associated with exposure per se Purpose Malignant pleural mesothelioma ( MPM ) is a highly aggressive and symptomatic disease . We examined the relationship between health-related quality of life ( HRQoL ) and inflammatory markers , and the prognostic role of HRQoL in MPM patients . Methods MPM patients from two parallel phase II studies ( thalidomide alone or thalidomide with chemotherapy ) were included . HRQoL was assessed at baseline using the modified Lung Cancer Symptom Scale ( LCSS ) . Baseline inflammatory markers and cytokines were measured . Spearman correlation was used to examine the relationship between inflammatory markers and HRQoL measures . The prognostic value of the HRQoL domains was examined using Cox proportional hazard model . Results Sixty-three patients were included : median age 61 years ( range 44–79 ) ; 82 % male ; 77 % Eastern Cooperative Oncology Group ( ECOG ) performance status 0–1 ; 44 % epithelial histology subtype . Baseline systemic symptoms of anorexia and fatigue , the summation symptoms of overall symptomatic distress , interference with normal activity and global QoL and the aggregate score of total LCSS score were all associated with elevated neutrophil-to-lymphocyte ratio , C-reactive protein and vascular endothelial growth factor levels at baseline ( rho ≥ 0.25 ; p < 0.05 ) . Baseline anorexia , fatigue , cough , dyspnoea , pain , overall symptomatic distress , interference with normal activity , global QoL and total LCSS score were all significantly related to survival ( p < 0.05 ) after adjusting for established prognostic factors ( age , gender , histological subtype and performance status ) and treatment effect . Conclusions In conclusion , HRQoL seems to relate to a patient 's systemic inflammatory status and is associated with survival in MPM patients BACKGROUND In patients with malignant pleural mesothelioma undergoing a multimodality therapy , treatment toxicity may outweigh the benefit of progression-free survival . The subjective experience across different treatment phases is an important clinical outcome . This study compares a st and ard with an individual quality of life ( QoL ) measure used in a multi-center phase II trial . PATIENTS AND METHODS Sixty-one patients with stage I-III technically operable pleural mesothelioma were treated with preoperative chemotherapy , followed by pleuropneumonectomy and subsequent radiotherapy . QoL was assessed at baseline , at day 1 of cycle 3 , and 1 , 3 and 6 months post-surgery by using the Rotterdam Symptom Checklist ( RSCL ) and the Schedule for the Evaluation of Quality of Life-Direct Weighting ( SEIQoL-DW ) , a measure that is based on five individually nominated and weighted QoL-domains . RESULTS Completion rates were 98 % ( RSCL ) and 92 % ( SEIQoL ) at baseline and 98%/89 % at cycle 3 , respectively . Of the operated patients ( N=45 ) RSCL and SEIQoL were available from 86%/72 % , 93%/74 % , and 94%/76 % at months 1 , 3 , and 6 post-surgery . Average assessment time for the SEIQoL was 24min compared to 8min needed for the RSCL . Median changes from baseline indicate that both RSCL QoL overall score and SEIQoL index remained stable during chemotherapy with a clinical ly significant deterioration ( change > or=8 points ) 1 month after surgery ( median change of -66 and -14 for RSCL and SEIQoL , respectively ) . RSCL QoL overall scores improved thereafter , but remained beneath baseline level until 6 months after surgery . SEIQoL scores improved to baseline-level at month 3 after surgery , but worsened again at month 6 . RSCL QoL overall score and SEIQoL index were moderately correlated at baseline ( r=.30 ; p < or=.05 ) and at 6-month follow-up ( r=.42 ; p < or=.05 ) but not at the other time points . CONCLUSION The SEIQoL assessment seems to be feasible within a phase II clinical trial , but may require more effort from staff . More distinctive QoL changes in accordance with clinical changes were measured with the RSCL . Our findings suggest that the two measures are not interchangeable : the RSCL is to favor when mainly information related to the course of disease- and treatment is of interest |
12,588 | 28,383,375 | We did not identify any patient characteristics precluding a vaginal approach ; chlorhexidine or povidone is appropriate for vaginal antisepsis ; vasopressin decreases blood loss by 130 cc ; tissue-sealing devices decrease blood loss by 44 cc and operative time by 15 minutes with uncertain complication implication s ; vertical cuff closure results in 1-cm increased vaginal length ; either peritoneum or epithelium can be used for colpotomy closure ; and routine vaginal packing is not advised . | OBJECTIVE To create evidence -based clinical practice guidelines based on a systematic review of published literature regarding the risks and benefits of available preoperative , intraoperative , and postoperative technical steps and interventions at the time of vaginal hysterectomy for benign indications . | One hundred and twelve vaginal hysterectomies were perormed over a 2.8-year period . Five different techniques ofcuff closure were performed , and evaluated for their preservation of vaginal depth . We have concluded that all five methods are acceptable ways to close the vaginal cuff at the time of transvaginal hysterectomy as long as there is proper vault support . Each surgical closure is pictorially illustrated . Morbidity was minimal , and vaginal dcpth was retained The commonest complication associated with vaginal hysterectomy is vault hematoma ( 1 ) , which has been detected by ultrasound in 34–59 % cases postoperatively ( 1,2 ) . This has been shown to increase febrile morbidity , need for blood transfusions , longer hospital stay , and higher readmission rate ( 2 ) . We therefore design ed a r and omized , controlled trial to determine whether nonclosure of the vaginal vault reduced the risk of febrile morbidity Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas , which were the size of 14 to 18 weeks ' gestation , were r and omized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy . The control group ( group A ; n = 25 ) did not receive preoperative gonadotropin-releasing hormone agonist , but patients in Group B ( n = 25 ) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy . Patients in the two groups were similar with respect to age , gravidity , parity , pretreatment uterine size , and hemoglobin and hematocrit levels . Patients in group B had an increase in hemoglobin levels ( 10.75 to 12.12 gm/dl , p less than 0.05 ) and a decrease in uterine volume ( 1086.7 to 723.4 ml , p less than 0.05 ) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy ( 76.0 % vs 16 % ) . Patients in group B also had shorter hospitalizations ( 5.2 vs 3.8 days , p less than 0.05 ) . We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas OBJECTIVE : To compare blood loss , operative time , postoperative pain medication requirements , and complication rates in patients undergoing vaginal hysterectomy who were r and omly assigned to receive preoperative intracervical vasopressin or no intracervical injection . METHODS : Fifty-eight women undergoing vaginal hysterectomy were r and omly allocated to receive either eight units of vasopressin intracervically or nothing preoperative from January 2004 to January 2005 . A research er blinded to the study group determined blood loss . The surgeries were performed using uniform steps by senior residents under the direction of two attending surgeons . Multiple preoperative and postoperative values were evaluated , including time to specific points in surgery and use of postoperative pain medication . Independent sample t tests , Fisher exact test , and Pearson & khgr;2 tests were used to analyze the data . RESULTS : The two groups were similar in terms of age , weight , parity , and ethnicity . There was also no difference in indication for surgery or estimated uterine size . The vasopressin group lost significantly less blood ( 145.3 mL compared with 266.4 mL control ; P=.022 ) . There was a significant difference in the increase in mean blood pressure at 5 minutes after injection ( 10.4 for the vasopressin group compared with . 2.5 for the control group , P=.043 ) . There was no significant difference in immediate recovery room morphine requirements , but patient-controlled anesthesia usage was significantly higher in the vasopressin group . CONCLUSION : The preoperative injection of intracervical vasopressin leads to decreased blood loss during vaginal hysterectomy . There was , however , a significant increase in postoperative morphine use in patients receiving vasopressin . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00799292 LEVEL OF EVIDENCE : Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE This study was undertaken to compare the use of bipolar vessel sealing system ( BVSS ) with conventional suture ligature in vaginal hysterectomy ( VH ) on a non-prolapsed uterus . STUDY DESIGN Women referred for VH for uterine myoma were r and omized to BVSS ( n=45 ) or conventional suture ligature VH ( n=45 ) . Exclusion criteria were uterine prolapse and indication associated surgical procedures . Main outcome measures were operative time , blood loss , hospital stay , pain status , peri and post-operative complications . Data of patients were collected prospect ively . Statistical analysis was performed using chi-square and Student 's t-test as appropriate . RESULTS There were no differences in patients ' mean age , parity and uterine size between groups . Patients in the BVSS group had a significantly reduced operating time ( 29.2+/-2.1 min vs. 75.2+/-5 min ; p<0.001 ) , operative blood loss ( 84+/-5.9 mL vs. 136.4+/-89.1 mL ; p=0.001 ) , requirement of surgical sutures ( 1.2+/-0.6 units vs. 7.4+/-0.3 units ; p<0.001 ) , pain status ( 1.6+/-0.4 vs. 3.6+/-0.4 ; p<0.001 ) and hospital stay ( 25.6+/-0.9h vs. 33.2+/-1.7h ; p<0.001 ) compared to the control group . The overall complication rate in the study was 7.8 % ( 7/90 ) , and did not differ between patients of the BVSS and control group . CONCLUSION Bipolar vessel sealing for vaginal hysterectomy appears to be an effective and safe haemostatic control method , with reduced operating time , peri-operative blood losses , post-operative pain and hospital stay OBJECTIVE This study compared 3 surgical methods of prophylaxis against enterocele formation employed at the time of vaginal hysterectomy . STUDY DESIGN One hundred consecutive women undergoing total vaginal hysterectomy for various reasons were r and omly assigned to have 1 of 3 surgical methods applied to the posterior superior aspect of the vagina for prophylaxis against enterocele formation . The first procedure involved closing the cul-de-sac and bringing the uterosacral-cardinal complex together in the midline in a vaginal Moschcowitz-type operation . The second procedure was a McCall-type culdeplasty to obliterate the cul-de-sac , plicate the uterosacral-cardinal complex , and elevate any redundant posterior vaginal apex . The third technique used only the peritoneum to close the cul-de-sac , allowing passive movement of the uterosacral-cardinal complex to the midline , no obliteration per se , and no elevation of the posterior vagina . Postoperative findings on pelvic examination were evaluated at 6 weeks , 3 months , and 1 , 2 , and 3 years . Statistical analysis was performed with the chi2 test of independence . RESULTS At 6 weeks ' follow-up and at 3 months ' follow-up there were no prolapses involving the posterior superior segment of the vagina . At 1 year of follow-up 11 patients had stage 1 or 2 posterior superior segment prolapse . At 2 years ' follow-up this number was 16 . At 3 years ' follow-up the McCall-type method was statistically better ( chi2 = 11.27 with 2 degrees of freedom , P = . 004 ) than the other 2 in preventing postoperative enterocele ( n = 2 of 32 with McCall-type procedure , n = 10 of 33 with vaginal Moschcowitz-type procedure , and n = 13 of 33 with peritoneal closure only ) . CONCLUSION When applied at the time of vaginal hysterectomy the McCall-type culdeplasty is superior to a vaginal Moschcowitz-type procedure and to simple peritoneal closure in preventing subsequent enterocele OBJECTIVE The purpose of this study was to compare the efficacy of chlorhexidine and povidone iodine for cleansing the operative field for vaginal surgery . STUDY DESIGN This was a r and omized controlled trial that compared 10 % povidone iodine and 4 % chlorhexidine gluconate as surgical scrubs . Our primary end point was the proportion of contaminated specimens ( defined as total bacterial colony counts of > /=5000 colony-forming units ) per group found throughout the surgical procedures . All patients received st and ard infection prophylaxis that included preoperative intravenous antibiotics . Immediately before antibiotic administration and baseline aerobic and anaerobic cultures of the vaginal flora were obtained , which were followed by cultures at 30 minutes after the surgical scrub and hourly thereafter throughout each patient 's surgery . RESULTS A total of 50 patients were enrolled between October 2002 and September 2003 . There were no differences between the povidone iodine ( n = 27 ) and chlorhexidine ( n = 23 ) groups with respect to age , race , exogenous hormone use , body mass index , gravity , parity , preoperative mean colony counts , or operative time . Among the first set of intraoperative specimens ( which were obtained 30 minutes after the surgical scrub ) , 63 % of the cultures ( 17/27 ) from the povidone iodine group and 22 % of the cultures ( 5/23 ) from the chlorhexidine group were classified as contaminated ( P = .003 ; relative risk , 6.12 ; 95 % CI , 1.7 , 21.6 ) . Subsequent cultures failed to demonstrate significant differences . CONCLUSION Chlorhexidine gluconate was more effective than povidone iodine in decreasing the bacterial colony counts that were found in the operative field for vaginal hysterectomy STUDY OBJECTIVE To explore attitudes and hysterectomy practice s among gynecologists in the United States and to identify potential barriers to offering minimally invasive hysterectomies . DESIGN Mixed-mode ( online and on-paper ) survey of a r and om sample of 1500 practicing obstetrician-gynecologists . SETTING Nationwide survey in the United States . PARTICIPANTS Nonretired obstetrician-gynecologists identified through a physician list from the American Medical Association . INTERVENTIONS Postal and online survey . MEASUREMENTS & MAIN RESULTS : We received a response from 376 physicians ( 25.8 % response rate ) . The average age of respondents was 47.9 years , and 87 % were generalists . Participants performed on average 4 surgical cases per week and 32 hysterectomies per year , most of which were abdominal hysterectomies . When asked for preferred mode of access for themselves or their spouse , 55.5 % chose vaginal hysterectomy ( VH ) , 40.6 % chose laparoscopic hysterectomy ( LH ) , and 8 % chose abdominal hysterectomy ( AH ) . Younger physicians ( < 40 ) and high surgical volume physicians were significantly more likely to chose a laparoscopic approach and identified significantly fewer barriers for performing LH . The main barriers to performing VH were technical difficulty , potential for complications , and caseload of VH . The main barriers for performing LH were training during residency , technical difficulty , personal surgical experience and operating time . The majority of gynecologists wanted to decrease their AH rates and increase their LH rates . The most significant identified contraindications to VH were prior laparotomy , a uterus larger than 12 weeks , narrow introitus , adnexal mass , and minimal uterine descent . CONCLUSIONS While a large majority of gynecologists would prefer a VH or LH for themselves or their spouse , AH remains the most common hysterectomy method in the United States . A generation gap appears to be brewing with younger gynecologist more in favor of the laparoscopic approach . More emphasis should be placed on training gynecologists in performing minimally invasive hysterectomies , given their desire to change their surgical mode of access Purpose The medical and economic benefits of the transvaginal approach over the abdominal and laparoscopic methods are demonstrated in many studies . Vaginal hysterectomy with bipolar vessel sailing ( BiClamp ® ) represents an example of mininvasive surgery and could be a valid and cost-benefit alternative in the surgical treatment of benign gynaecologic disease . BiClamp ® may be carried out according to Clavè ’s technique with a good result in postoperative pain . Methods Prospect i ve r and omized study ( Canadian Task Force classification I ) . We compared the vaginal hysterectomy with salpingo-oophorectomies with BiClamp ® and multimodal anaesthesia ( group A 30 patients ) with vaginal hysterectomy with salpingo-oophorectomies and spinal anaesthesia ( group B 30 patients ) . Results The median operating time was 33.5 min for group A and 54.5 min for group B ( p < 0.0001 ) . The median blood loss was 59.25 ml in group A and 81.75 ml in group B. The median hospital stay was 1.6 ± 0.58 days for group A and 2.55 ± 0.66 days for group B. Postoperative pain was statistically different between groups in the immediate postoperatory times , at 2 and at 6 h from the surgery and at 10 p.m. ( p < 0.0001 ) . Analyses of cost-effectiveness have stated advantages in terms of costs and indirect – direct benefits but also in earlier resumption of working . Conclusions BiClamp ® technique with multimodal anaesthesia has advantages from surgical , anaesthesiology and economic point of view . It is a minimally invasive surgery characterised by lower morbidity , quicker surgery times and reduced costs when compared to classical vaginal hysterectomy . BiClamp ® technique represents a new border in vaginal surgery This report concerns the indications , technique , and safety of vaginal hysterectomy among 213 women . It further examines the comparative risks of complications and costs between 107 patients whose operations were performed with the use of the new retractor during the 5-year period ended June 1991 and 106 other patients whose surgeries were done during 4 preceding years when the retractor was not available . The selected characteristics of the patients undergoing vaginal hysterectomy in the two groups were largely similar . When the retractor was used , suturing the cuff and pedicles was easier , as the retractor facilitated good exposure and better visibility . In no case was there any injury or the need for transfusion . Of 7 patients with morbidity , 1 had no demonstrable cause , 3 had urinary tract infection , and 3 had cuff cellulitis of which one progressed into abscess requiring transvaginal drainage 6 days postoperation . My experience with 107 vaginal hysterectomies using the self-retaining retractor demonstrates that the retractor was instrumental in significantly reducing operative time , blood loss , and morbidity STUDY OBJECTIVE To compare operating time , intraoperative blood loss , postoperative analgesia , and length of hospital stay using ultrasonic shears vs traditional suture ligature in vaginal hysterectomy . DESIGN R and omized controlled trial ( Canadian Task Force classification I ) . SETTING Gynecology units within a single health network , university hospital . PATIENTS Forty women requiring vaginal hysterectomy because of benign disease . INTERVENTIONS Vaginal hysterectomy performed using either ultrasonically activated shears ( USS ) or traditional suture ligatures . MEASUREMENTS AND MAIN RESULTS Twenty-one patients were r and omized to the USS arm , and 19 patients to the traditional suture ligature arm . Patient characteristics were comparable . Mean ( SD ) hysterectomy time and was similar in both the USS and traditional arms , 28.66 ( 4.0 ) minutes vs 32.37 ( 3.18 ) minutes ( p = .47 ) , as was total operating time , 97.38 ( 8.9 ) minutes vs 91.63 ( 7.69 ) minutes ( p = .63 ) . Operative blood loss was significantly decreased in the USS group : 62.63 ( 12.46 ) mL vs 136.05 ( 21.54 ) mL ( p = .006 ) . There was , however , no significant change in hemoglobin concentration between the 2 groups : 19.53 ( 1.79 ) g/L vs -16.72 ( 2.5 ) g/L. There was no significant difference in mean oxycodone use : 9.29 ( 2.66 ) mg vs 8.06 ( 3.19 ) mg ( p = .77 ) . Length of hospital stay was similar in both groups : 58.98 ( 3.27 ) hours vs 60.05 ( 6.48 ) hours ( p = .88 ) . There was no significant difference in overall complication rates between the groups . CONCLUSION Although the Harmonic scalpel system , compared with the traditional suture ligation method , seems to be a safe alternative for securing the pedicles in vaginal hysterectomy , it offers no benefit insofar as operative time , reduction in clinical ly significant blood loss , and analgesic requirements Purpose To compare bipolar vessel sealing ( BVS ; BiClamp ® ) versus conventional suture ligation in vaginal hysterectomy . Methods A multicenter , single-blind r and omized controlled trial ( RCT ) was conducted at eight women ’s hospitals in Germany . One hundred and seventy-five patients with benign uterine disease underwent vaginal hysterectomy using BVS ( n = 88 ) or conventional suture ligation ( n = 87 controls ) . Data analysis was based on intention-to-treat . Results Postoperative pain ( primary endpoint ) was decreased in the BVS group , but not significantly . Intraoperative blood loss was significantly lower in this group , with < 100 mL recorded in 79/88 versus 52/86 patients ( P < 0.001 ) . Hemoglobin decrease indicated non-significantly lower blood loss in the BVS group . Operating time was significantly shorter in the BVS group than in the controls ( 38.0 ± 18.6 vs. 48.0 ± 24.9 min ; P = 0.001 ) . On average , 7.8 sutures/operation were saved with bipolar coagulation ( P < 0.0001 ) . Ease of use ratings were significantly higher for BVS . Hospital stay was similar for both groups . Adverse event rates did not differ significantly . Conclusions The BiClamp ® procedure proved superior or similar to conventional ligation , particularly with regard to intraoperative blood loss , operating time and postoperative pain , although statistical significance was not attained for postoperative pain . Moreover , BVS was easier to use and more cost effective OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with GRADE and other experts . RESULTS Up date d guidance continues to be conceptually similar to GRADE . Review ers are to evaluate SOE separately for each major treatment comparison for each major outcome . We added reporting bias as a required domain and retained study limitations ( risk of bias ) , consistency , directness , and precision ( and three optional domains ) . Additional guidance covers scoring consistency , precision , and reporting bias , grading bodies of evidence with r and omized controlled trials and observational studies , evaluating single study bodies of evidence , using studies with high risk of bias , and presenting findings with greater clarity and transparency . SOE is grade d high , moderate , low , or insufficient , reflecting review ers ' confidence in the findings for a specific treatment comparison and outcome . CONCLUSION No single approach for grading SOE suits all review s , but a more consistent and transparent approach to reporting summary information will make review s more useful to the broad range of audiences that AHRQ 's work aims to reach . EPC working groups will consider ongoing challenges and modify guidance as needed , on issues such as combining trials and observational studies in bodies of evidence , weighting domains , and combining qualitative and quantitative syntheses OBJECTIVE This study compares the postoperative outcomes of patients in whom indwelling bladder catheterization or no catheter was used after vaginal hysterectomy . STUDY DESIGN One hundred women undergoing inpatient vaginal hysterectomy were r and omly assigned to have an indwelling Foley catheter for 24 hours or no catheter after the procedure . Data regarding postoperative morbidity were recorded , and a clean voided urine specimen for urinalysis and culture was obtained 48 hours and 2 weeks after surgery . RESULTS The study groups were similar with respect to demographics and surgical indications . Two patients in the catheterized group required recatheterization after the catheters were removed . None of the subjects in the no-catheter group required a catheter . There was a significantly higher incidence of fever in the catheter group . No differences were found in the incidence of positive urine cultures between the study groups at 48 hours ( 8 vs 14 , p = 0.227 ) and 2 weeks ( 6 vs 1 , p = 0.111 ) , respectively . CONCLUSION Indwelling catheterization appears unnecessary after routine vaginal hysterectomy . However , catheter placement for 24 hours does not contribute significantly to postoperative morbidity OBJECTIVE To compare electrosurgical bipolar vessel sealing ( EBVS ) with traditional suturing during vaginal hysterectomy . METHODS In a r and omized controlled trial involving 68 women undergoing vaginal hysterectomy for benign disease , 37 procedures were performed using EBVS and 31 using traditional suturing . The end points were procedure time , blood loss , number of ligatures used , postoperative pain score , and number of days in hospital . RESULTS The procedure duration was shorter using EBVS ( median duration , 32 vs. 40 min ; P=.0003 ) , with fewer ligatures ( 1 vs. 7 ; P<.0001 ) and less pain ( median score , 4 vs. 6 ; P<.0001 ) . There were no significant differences regarding blood loss ( median , 100 vs. 160 mL ; P=.36 ) and days in hospital ( median , 2 vs. 2 ; P=.03 ) . CONCLUSION The EBVS system provided advantages over traditional suturing with regard to procedure time , number of ligatures used , and postoperative pain score Summary This r and omised prospect i ve study in 53 women having vaginal hysterectomy for benign conditions compared a closed vault technique with an open technique . Twenty-seven had the vault closed ( group A ) whereas 26 patients had an open vault ( group B ) . The primary outcomes include , vault haematoma ( as detected by ultrasound on day 3 ) and fever . Secondary outcomes are haemorrhage , urinary tract infection , urinary retention and vault granulation tissue . The study did not show any statistical difference between either group . Prolapse of the fallopian tube was recorded in one case in the open vault group . A r and omised controlled study on a larger scale is recommended Purpose The aim of this study is to compare vaginal hysterectomy performed with st and ard technique versus the one performed with LigaSure . Methods Observational-longitudinal-cohort study on 42 women c and i date s to vaginal hysterectomy because of benign uterine pathology . Outcome variables , methods of analysis , inclusion and exclusion criteria were determined prospect ively . Eligible patients were subdivided in Group-A ( LigaSure-21 patients ) , or in Group-B ( classical-21 patients ) . Group-A was divided into Subgroup-A1 ( 10 patients ) and Subgroup-A2 ( 11 patients ) , depending on the point where the stump of the uterosacral-ligament was transfixed : Subgroup-A1 at cervical portion , Subgroup-A2 at intermediate portion . For all patients were reported : pre-post surgery haemoglobin and hematocrit , number of sutures , duration of intervention and blood loss , NRS-score on first/third post-operative days . All patients underwent gynaecological examination 30 and 180 days after surgery . Results General characteristics did not show significant differences between the two groups . Statistically significant differences emerged from the comparison between Group-A versus Group-B in terms of : intraoperative bleeding , post-operative value of haemoglobin , Δ-Hb , number of sutures , surgical time , pain at first and third post-operative day . The 180 days follow-up demonstrated four cases of vaginal vault prolapse , only in the Subgroup-A1 related to thermal damage of the uterosacral ligament . Conclusion LigaSure vessel sealing system is a safe alternative for securing pedicles in vaginal hysterectomy with significant improvement in patients outcome . Following vaginal vault prolapse , we determined the optimal fixation-site to perform the colposuspension in the intermediate portion of the uterosacral-ligament , especially if the cervical portion received a thermal damage , as occurs during the LigaSure use Introduction and hypothesisThe objective of this study was to evaluate the effect of vaginal packing following pelvic floor surgery with regard to post-operative pain , bleeding and infection . This was a double-blind r and omised study of women undergoing vaginal hysterectomy and /or pelvic floor repair at a tertiary urogynaecology unit . Methods The primary outcome of day 1 post-operative pain was assessed using the short-form McGill Pain score . Secondary outcomes were haematological and infective morbidity , evaluated using changes in full blood count , and cultures of midstream urine and high vaginal swabs . A transvaginal ultrasound scan to exclude pelvic haematoma was performed at 6 weeks in all women who underwent vaginal hysterectomy with or without a pelvic floor repair . Results In total , 190 women were recruited : mean age 58.3 years ( 27–91 years ) , mean body mass index 27.4 kg/m2 and median parity 3 . Women were r and omised into the ‘ pack ’ ( n = 86 ) and ‘ no pack ’ ( n = 87 ) arms with no demographic differences between the groups . No statistically significant differences in the post-operative pain scores or secondary outcome measures were demonstrated . Incidence of haematoma formation ( 14.8 % no pack , 7.3 % pack , p = 0.204 ) was not statistically significant . There were three clinical ly significant complications in the no pack group and none in the pack group . Conclusions This is the first study to examine pain in association with post-operative vaginal packing . There is no evidence to suggest that packing increases pain scores or post-operative morbidity . A trend towards increased haematoma and significant complications was seen in the no pack group . As vaginal packing does no harm and may be of some benefit it may be argued that packing should be recommended as routine clinical practice Objective To evaluate the clinical outcome of patients who underwent vaginal hysterectomy with or without peritoneal closure . Methods This study was a r and omized trial . Using computer-generated numbers , all patients undergoing vaginal hysterectomy without oophorectomy were r and omized to either no peritoneal closure ( n = 57 ) or routine peritoneal closure ( n = 49 ) . Patients were followed-up for a minimum of 1 year for development of complications and postoperative dyspareunia . At 4–6 postoperative weeks , the distance between the ovaries and the vaginal cuff was measured by ultrasound . Results Postoperative complications were similar in both groups . The incidence of deep-thrust dyspareunia at 6 and 12 months was also similar . No statistical differences between the two groups were noted in the ovary to vaginal cuff distances either overall or when patients with dyspareunia were considered separately . Conclusion The data in this study do not support the use of reperitonealization on a routine basis . However , because of a lack of statistical power , larger studies will be required to confirm this theory OBJECTIVE To compare blood loss and procedure time of vaginal hysterectomy using an electrosurgical bipolar vessel sealer versus using sutures . METHODS Sixty patients scheduled for vaginal hysterectomy in a single surgical practice were r and omized to either electrosurgical bipolar vessel sealer or sutures as the hemostasis technique . Procedure time was defined as time from initial mucosal injection to closure of the vaginal cuff with satisfactory hemostasis . Blood loss was estimated by the anesthesia service . Statistical methodology included the Student t and Wilcoxon rank-sum tests , and all comparisons were two tailed , with P < .05 considered significant . RESULTS Use of an electrosurgical bipolar vessel sealer result ed in shorter procedure times : The mean procedure time in the electrosurgical bipolar vessel sealer arm was 39.1 minutes ( range 22–93 ) versus 53.6 minutes ( range 37–160 ) for the suture arm ( P = .003 ) . Mean estimated blood loss was also statistically less with electrosurgical bipolar vessel sealer : 68.9 mL ( range 20–200 ) versus 126.7 mL ( range 25–600 ) for the suture arm ( P = .005 ) . Complication rate and length of stay did not differ by hemostasis technique . Seventy-eight percent of all cases were outpatient . CONCLUSION Electrosurgical bipolar vessel sealer is an effective alternative to sutures in vaginal hysterectomy , result ing in significantly reduced operative time and blood loss BACKGROUND Electrical acustimulation can reduce postoperative nausea and vomiting ( PONV ) . The primary purpose of this study was to investigate the effectiveness of acustimulation in relation to known risk factors for PONV . We also tested the secondary hypothesis that pre- or post-induction application of acustimulation results in differences in PONV reduction . METHODS Two hundred women undergoing vaginal hysterectomy were enrolled in this prospect i ve , observer-blind , r and omized controlled trial . Patients received r and omly for 24 h acustimulation ( n=101 ) , subdivided into groups of pre-induction ( n=48 ) and post-induction ( n=53 ) , or sham stimulation ( n=99 ) , subdivided into groups of pre-induction ( n=49 ) or post-induction ( n=50 ) . Nausea and vomiting/retching was recorded for 24 h after operation in the whole group and stratified by risk factors ( female gender , non-smoker , history of PONV/motion sickness , and postoperative morphine usage ) . RESULTS The incidence of PONV and need for rescue therapy was significantly lower in the acustimulation than in the sham group ( PONV , 33 % vs 63 % , P<0.001 ; rescue therapy , 39 % vs 61 % , P=0.001 ) . The risk ratio for acustimulation and PONV was 0.29 [ 95 % confidence interval ( CI ) 0.16 - 0.52 ] and for rescue therapy , it was 0.38 ( 95 % CI 0.21 - 0.66 ) . Subgroup analyses according to the simplified risk score by Apfel and colleagues revealed a reduction in high-risk patients , that is , when three or four risk factors were present . Binary logistic regression analysis revealed that no history of PONV and usage of acustimulation were independent predictors for risk reduction of all PONV qualities . No significant difference in PONV reducing effects could be detected between pre- and post-induction . CONCLUSIONS Continuous 24 h acustimulation decreases PONV , particularly in patients at high risk Please cite this paper as : Dua A , Galimberti A , Subramaniam M , Popli G , Radley S. The effects of vault drainage on postoperative morbidity after vaginal hysterectomy for benign gynaecological disease : a r and omised controlled trial . BJOG 2011 ; DOI : 10.1111/j.1471‐0528.2011.03170.x Abstract . Micturition difficulties and urinary retention are common complications after abdominal or vaginal hysterectomy . Adrenergic receptors are located in the bladder neck and proximal urethra , and blocking these receptors with al‐pha‐blockers such as phenoxybenzamine ( Dibenzyline ) may improve micturition and prevent postoperative urinary retention . In a r and omized clinical trial , 51 patients who underwent total abdominal hysterectomy , received a prophylactic dose of Dibenzyline 10 μg orally 6‐8 hours after operation and again the next day about 18 hours later . Only 2 of the 51 patients were found to have urinary retention , in comparison with 9 of 48 patients in the control group ( p>0.05 ) . Another group of patients who underwent vaginal hysterectomy were treated according to the same protocol . Eight of the 30 patients in this study group required catheterization to drain the overdistended bladder , in comparison with 16 of 26 patients in the control group ( p>0.025 ) . It seems from this clinical trial that prophylactic treatment with Dibenzyline is recommended after abdominal hysterectomy or vaginal operation in order to improve micturition and prevent urinary retention STUDY OBJECTIVE To compare the effects of horizontal and vertical vaginal cuff closure techniques on vagina length after vaginal hysterectomy . DESIGN Prospect i ve r and omized study ( Canadian Task Force classification I ) . SETTING Teaching and research hospital , a tertiary center . PATIENTS Fifty-two women with POP-Q stage 0 or 1 uterine prolapse were r and omized into 2 groups using vertical ( n = 26 ) or horizontal ( n = 26 ) vaginal cuff closure . INTERVENTIONS All patients underwent vaginal hysterectomy . MEASUREMENTS AND MAIN RESULTS Vagina length in the 2 groups was compared preoperatively , immediately after surgery , and at 6 weeks postoperatively . Mean ( SD ) preoperative vagina length in the horizontal and vertical groups was similar ( 7.87 [ 0.92 ] cm vs 7.99 [ 0.78 ] cm ; p = .41 ) . Immediately postoperatively , the vagina was significantly shorter in the horizontal group than in the vertical group ( 6.61 [ 0.89 ] cm vs 7.51 [ 0.74 ] cm ; p < .001 ) . At 6 weeks postoperatively , the vagina was still significantly shorter in the horizontal group ( 6.55 [ 0.89 ] cm vs 7.42 ( 0.73 ) cm ; p < .001 ) . The mean difference in vagina length before and after surgery was also significantly higher in the horizontal group than in the vertical group ( -1.26 [ 0.12 ] cm vs 0.49 [ 0.11 ] cm ; p < .001 ) . CONCLUSION Vertical cuff closure during vaginal hysterectomy seems to preserve vagina length better than does horizontal cuff closure OBJECTIVE The purpose of this study was to evaluate the risk of pelvic infection with the use of vasopressin at time of vaginal hysterectomy with a r and omized controlled trial . STUDY DESIGN Women who underwent vaginal hysterectomy and agreed to participate were r and omly assigned to pericervical injections of vasopressin or normal saline solution . Surgeons and patients were blinded to the injected substance . Power analysis revealed that a sample size of 116 patients would be sufficient to detect a 4-fold difference in pelvic infection rates between the 2 groups , with 90 % power and a probability value of.05 . RESULTS Analysis with 117 patients found no difference in infection rate between the normal saline solution group and the vasopressin groups ( 7.3 % vs 1.6 % ; P = .19 ) . Estimated blood loss ( 312 + /- 222 mL vs 446 + /- 296 mL ; P = .006 ) and change in hemoglobin and hematocrit levels ( 2.1 + /- 1.4 gm vs 2.9 + /- 1.4 gm ; P : = .02 ; and 6.7 % + /- 3.4 % vs 8.5 % + /- 3.8 % ; P = .01 ; vasopressin versus normal saline solution , respectively ) were significantly less in the vasopressin group . There were no significant differences in interval blood pressure measurements after vasopressin administration between the 2 groups . CONCLUSION The use of vasopressin during vaginal hysterectomy does not increase the risk of pelvic infection , does decrease operative blood loss , and does not significantly affect blood pressure OBJECTIVE To assess the efficacy of electrosurgical bipolar vessel sealing using the LigaSure system during vaginal hysterectomy in comparison with conventional suture ligation method . STUDY DESIGN 103 patients undergoing vaginal hysterectomy for benign conditions were r and omised to either LigaSure or Suture groups . Each group was divided into two subgroups according to the degree of surgical difficulty . RESULTS Participants in the LigaSure had shorter procedure time ( 52.5 min vs. 90 min ; p<0.001 ) and less blood loss ( 230 ml vs. 360 ml ; p<0.001 ) . Complication rates were not statistically different between the two groups . The advantage of the LigaSure system in reducing the operative blood loss was more pronounced in the more difficult procedures . CONCLUSION The LigaSure system reduces the operating time ( by reducing pedicle-securing time ) and blood loss without increasing the post-operative complication rates of vaginal hysterectomy . This beneficial effect was found to be more pronounced in difficult procedures The aim of this study was to assess the efficacy of PGE2 in enhancing bladder function after vaginal hysterectomy . A total of 110 women with or without urinary incontinence underwent vaginal hysterectomy and cystourethropexy surgery because of grade II or III genital prolapse . Preoperatively the patients were r and omly assigned to two groups : group 1 ( n = 50 ) received on the fourth post-operative day , before removal of the bladder catheter , an intravesicular solution of 1.50 mg PGE2 ( 2 × 0.75 mg ) ; group 2 ( n = 60 ) did not receive any prophylaxis for urinary retention . In the PGE2-treated group significantly fewer patients had urinary retention for 3 days or more ( 10 % , P < 0.05 ) than in the control group ( 27 % ) . The use of intravesicular PGE2 reduced the time taken to restore detrusor function Objective To assess the efficacy of prostagl and ins in enhancing bladder function after vaginal hysterectomy Objective Placement of vaginal packing after pelvic reconstructive surgery is common ; however , little evidence exists to support the practice . Furthermore , patients have reported discomfort from the packs . We describe pain and satisfaction in women treated with and without vaginal packing . Methods This institutional review board – approved r and omized-controlled trial enrolled patients undergoing vaginal hysterectomy with prolapse repairs . The primary outcome was visual analog scales ( VASs ) for pain on postoperative day 1 . Allocation to “ packing ” ( “ P ” ) or “ no-packing ” ( “ NP ” ) arms occurred intraoperatively at the end of surgery . Visual analog scales regarding pain and satisfaction were completed early on postoperative day 1 before packing removal . Visual analog scale scores for pain , satisfaction , and bother attributable to packing were recorded before discharge . All packing and perineal pads were weighed to calculate a “ postoperative vaginal blood loss . ” Perioperative data were collected from the hospital record . Our sample size estimation required 74 subjects . Results Ninety-three women were enrolled . After exclusions , 77 were r and omized ( P , 37 ; NP , 40 ) . No differences were found in surgical information , hemoglobin levels , or narcotic use between groups . However , “ postoperative vaginal blood loss ” was greater in packed subjects ( P < 0.001 ) . Visual analog scale scores for pain before removal of packing ( P , 41.6 vs NP , 46.3 ; P = 0.43 ] and before discharge ( P , 35.0 vs NP , 40.0 ; P = 0.43 ] were not significantly different between treatment arms . Likewise , VAS scores for satisfaction before removal of packing ( P , 81.0 vs NP , 90.0 ; P = 0.08 ] and before discharge ( P , 90.0 vs NP , 90.5 ; P = 0.60 ] were not significantly different . Packed patients noted lower nursing verbal pain scores ( P = 0.04 ) and used less ketorolac ( P = 0.01 ) . Bother from packing was low overall . Conclusions Although there was no difference based on VAS , women receiving vaginal packing had lower nursing documented pain and used less ketorolac than packed women . Vaginal packing may provide benefit and can remain part of the surgical practice |
12,589 | 24,501,548 | Conclusion This review suggests that simulation-based training is one effective way to teach VL skills . | Introduction A review of the literature was conducted to analyze the impact of simulation-based training for direct and video laryngoscopy ( VL ) skills for health care professionals and health care students .
This current review addresses the question of whether airway management simulation-based training improves the acquisition of resuscitation skills for health care profession learners . | Background —Early defibrillation is considered the most important factor for restoring spontaneous circulation in cardiac arrest patients with ventricular fibrillation . Recent studies have shown that , after prolonged ventricular fibrillation , the rates of return of spontaneous circulation ( ROSC ) and survival are improved if defibrillation is delayed so that CPR can be given first . To examine whether CPR improves myocardial readiness for defibrillation , we analyzed whether CPR causes changes in predictors of defibrillation success calculated from the ventricular fibrillation waveform . Methods and Results —ECG recordings were retrieved for 105 patients from an original study of 200 patients receiving CPR or defibrillation first . Altogether , 267 CPR sequences from 77 patients were identified on which the effect of CPR could be evaluated . Five predictors of ROSC ( spectral flatness measure , energy , centroid frequency , amplitude spectrum relationship , and estimated probability of ROSC ) were determined from a spectral analysis of the ventricular fibrillation waveform immediately before and immediately after each of the 267 sequences . CPR increased spectral flatness measure , centroid frequency , and amplitude spectrum relationship ( P < 0.05 , P < 0.001 , P < 0.01 ) . In an analysis of the effect of the duration of CPR , the probability of ROSC and amplitude spectrum relationship showed a positive change for CPR sequences lasting > 3 minutes ( P < 0.001 , P < 0.05 ) . Conclusions —During resuscitation from ventricular fibrillation , changes in the predictors calculated from the ventricular fibrillation waveform indicated a positive effect of CPR on the myocardium This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer Background When airway management is difficult , various measures can be taken to facilitate tracheal intubation . The Bullard and Airtraq laryngoscopes were developed for this purpose . We hypothesised that the Bullard and Airtraq laryngoscopes would perform better than a conventional laryngoscope in the management of a simulated difficult airway . We also hypothesised that the indirect laryngoscopes would perform comparably . Methods In a r and omised controlled study , 60 anaesthetists ( 30 with no or little experience and 30 with broader experience in the use of the Bullard laryngoscope , referred to as beginners and experts , respectively ) performed three successive intubation attempts using conventional , Bullard and Airtraq laryngoscopes in two simulated difficult airway scenarios : neck immobilisation ( scenario A ) and neck immobilisation with additional tongue oedema ( scenario B ) . The primary endpoint was overall intubation success rate . Secondary endpoints were time required for successful intubation , the amount of dental stress exerted during laryngoscopy and satisfaction with each airway device . Results In scenario A , intubation success rates were 97–100 % with all devices . In scenario B , all participants failed to intubate the trachea using the conventional laryngoscope . When using the Bullard laryngoscope , intubation success rates of 87–97 % did not differ significantly ( P > 0.05 ) from those during scenario A and between groups ( beginners vs. experts ) . In contrast , when using the Airtraq laryngoscope , the overall intubation success rate was significantly lower ( P < 0.05 ) compared with scenario A and compared with use of the Bullard laryngoscope , and differed between beginners and experts ( 20 and 50 % , respectively ) . In cases of successful intubation , intubation times were comparable between devices and groups . Intubation times were longer during scenario B. Dental stress was always lower ( P < 0.05 ) during use of the Bullard and Airtraq laryngoscopes compared with the conventional laryngoscope , lowest ( P < 0.05 ) during use of the Bullard laryngoscope and ( with the exception of use of the conventional laryngoscope by the experts ) higher during scenario B than during scenario A. In scenario A , participants preferred both video laryngoscopes to the conventional laryngoscope . Conclusion In a moderately difficult airway scenario , all laryngoscopes performed equally well . However , in a more difficult airway scenario , the Bullard and Airtraq laryngoscopes performed better than the conventional laryngoscope , with the Bullard device performing better than the Airtraq . This may be in part related to differing prior experiences of operators with the respective airway devices Objective . To investigate the effectiveness of the Karl Storz BERCI DCI Macintosh video laryngoscope ( MVL ) via the TELE PACK system for facilitating intubation by novice paramedic students in a simulation environment . We assessed the laryngeal view , measured by percentage of glottic opening ( POGO ) , when intubating the SimMan manikin airway in different setting s. The primary endpoint was the best POGO achieved by the student . Secondary endpoints included intubation times and success rate . Method . We enrolled 25 novice paramedic students to intubate SimMan manikins . Students were r and omized to use either a conventional Macintosh 3 ( Mac3 ) blade alone or the MVL with a Mac3 blade . Students attempted their first intubation with the manikin on a stretcher in a normal neck position and reattempted intubation with the manikin 's neck stiffened . The groups then crossed over using the alternate device to repeat the attempts in the manikin with a normal neck and with a stiffened neck . The students then attempted the same sequence of four intubations with the manikin on the floor . Results . The MVL significantly improved POGO in all scenarios ( p < 0.05 ) . The MVL improved mean POGO 16 % ± 6 % in the manikin with a normal neck position on a stretcher and 33 % ± 7 % in the manikin with a stiff neck on the floor . The improvement was significantly greater in simulated difficult scenarios . The intubation success rate ( 94 % ) was equal in the two groups , and the POGO was significantly worse in the failures . In some subgroups , intubation times were longer with the MVL . Conclusion . The MVL improves the laryngeal view for novice laryngoscopists in a simulated setting , and this improvement is greatest in simulated difficult Objective Emergency airway situations are relatively rare events in pediatrics with most graduating residents having little exposure to intubate . Newer video technology offers the promise of reducing complications associated with intubation . This study proposes that video laryngoscopy ( VL ) should aid less skilled residents to intubate an infant mannequin with greater success and speed as compared with traditional direct laryngoscopy ( DL ) . Methods Pediatric ( PED ) and emergency medicine ( EM ) residents were r and omized in a prospect i ve controlled study . A st and ard respiratory failure scenario was conducted using SimBaby with an uncomplicated airway . Residents who inadvertently performed esophageal intubation were made aware as part of the scenario and allowed to reattempt until successful . Results Sixty-nine residents voluntarily participated , 49 % EM and 51 % PED . Seven subjects in the DL group required multiple attempts ( 21 % ) , compared with 6 subjects in the VL group ( 17 % ) ( P = 0.718 ) . Median time to intubation was 30 seconds ( 95 % confidence interval [ CI ] , 19–41 seconds ) for DL and 39 seconds ( 95 % CI , 36–42 seconds ) for VL ( P = 0.111 ) . Comparison of programs revealed a 77 % PED success rate versus 85 % EM success rate ( P = 0.578 ) and median time to intubation of 38 seconds ( 95 % CI , 31–45 seconds ) for PED compared with 32 seconds ( 95 % CI , 23–41 seconds ) for EM residents ( P = 0.316 ) . In a sub analysis , subjects successful at first attempt revealed a 13-second median difference ( DL , 23 seconds [ 95 % CI , 18–28 seconds ] vs. VL , 36 seconds [ 95 % CI , 29–43 seconds ; P = 0.01 ) . Conclusions In a simulated respiratory failure scenario involving residents , VL provided no additional success over DL with slightly longer time to intubation OBJECTIVES This study assesses intubation times and potential trauma with two new portable video laryngoscopes , the GlideScope Ranger ( GSR ) and the Venner A.P. Advance ( APA ) , in a simulated difficult prehospital airway . The GSR has a hockey stick shape and is inserted by a different ( midline ) technique compared with direct laryngoscopy and requires the use of a stylet . The APA has a h and le similar to a direct laryngoscope , but with an angulated difficult airway blade . The APA is design ed to have an intuitive insertion technique somewhat similar to that of direct laryngoscopy ( lateral tongue displacement ) and has a guiding mechanism that foregoes the need for a stylet . METHODS Thirty qualified paramedics received a short demonstration of each device and were asked to intubate a modified Grade III difficult laryngoscopy mannequin in a r and om order ( closed envelope technique ) . Optimal view and tracheal intubation times were recorded , and potential trauma assessed by the number of additional discrete forward advances and by visual analog scale ( VAS ) . Direct laryngoscopy was used as a comparator . The Wilcoxon rank sum test was used for intubation times , optimal view times , percentage of glottis opening ( POGO ) seen , and objective trauma assessment . Student 's paired t-test was used for subjective trauma assessment and a Bonferroni correction was used for the primary outcome measures . RESULTS Participants declared a median of 60 ( range 20 to 300 ) previous intubations . Time to achieve optimal view between APA and GSR was not different ( 20 seconds vs. 19 seconds ; p = 0.19 ) , but tracheal intubation was significantly faster with the APA ( 25 seconds vs. 46 seconds ; p < 0.0001 ) . Intubation success was ultimately 97 % in both groups . Participants judged subjective trauma to be less for the APA than GSR on a VAS ( 1.6 cm vs. 3.3 cm ; p < 0.001 ) . More than three additional forward advances were required in 43 % of GSR and 0 % of APA intubations . CONCLUSIONS Following a brief demonstration to paramedics naïve to video laryngoscopy , the APA demonstrated earlier intubation , fewer additional discrete forward advances of the tube , and less participant-judged subjective trauma when compared to the GSR in this simulation model Background The National Confidential Enquiry into Patient Outcome and Death ( NCEPOD ) report on trauma management , published in 2007 , defined st and ards for United Kingdom ( UK ) hospitals dealing with trauma . This study compared the NCEPOD st and ards with the performance of a UK military field hospital in Afghanistan . Setting UK military field hospital , Camp Bastion , Helm and Province , Afghanistan . Material s and methods Data were collected prospect ively for all patients fulfilling the trauma team activation criteria during the 3 months of Operation Herrick IXa ( from mid October 2008 to mid January 2009 ) and combined with a retrospective review of prehospital documentation , trauma resuscitation notes , operations notes and transfer notes for these patients . Results During the study period , there were 226 trauma team activations . Of those patients brought to the medical facility at Camp Bastion by UK assets , 93.7 % were accompanied by a doctor with advanced airway skills , although only 6.2 % of the patients required such an intervention . Consultants in emergency medicine and anaesthesia were present in 100 % of cases and were directly involved ( in either leading the team or performing airway management ) in 63.5 % and 77.6 % of cases respectively . Of those patients requiring operative intervention , 98.1 % had this performed by a consultant surgeon . Of those patients requiring CT , 93.6 % of cases had this performed within 1 h of arrival . Conclusions Trauma patients presenting to the medical facility at Camp Bastion during Operation Herrick IXa , irrespective of their nationality or background , received a high st and ard of medical care when compared with the NCEPOD st and ards Background Many healthcare professionals are trained in direct laryngoscopic tracheal intubation ( LEI ) , which is a potentially lifesaving procedure . This study attempts to determine the number of successful LEI exposures required during training to assure competent performance , with special emphasis on defining competence itself . Methods Analyses were based on a longitudinal study of novices under training conditions in the operating room . The progress of 438 LEIs performed by the 20 nonanesthesia trainees was monitored by observation and videotape analysis . Eighteen additional LEIs were performed by experienced anesthesiologists to define the st and ard . A generalized linear , mixed-modelling approach was used to identify key aspects of effective training and performance . The number of tracheal intubations that the trainees were required to perform before acquiring expertise in LEI was estimated . Results Subjects performed between 18 and 35 laryngoscopic intubations . However , statistical modeling indicates that a 90 % probability of a “ good intubation ” required 47 attempts . Proper insertion and lifting of the laryngoscope were crucial to “ good ” or “ competent ” performance of LEI . Traditional features , such as proper head and neck positions , were found to be less important under the study conditions . Conclusions This study determined that traditional LEI teaching for nonanesthesia personnel using manikin alone is inadequate . A reevaluation of current st and ards in LEI teaching for nonanesthesia is required The GlideScope ® is a new video laryngoscope developed for management of the difficult airway . We compared the GlideScope with the Macintosh laryngoscope in simulated easy and difficult laryngoscopy . Twenty anaesthetists were allowed three attempts to intubate in each of four laryngoscopy scenarios in a high fidelity simulator . In the simulated easy laryngoscopy scenarios , the anaesthetists took longer to intubate using the GlideScope than the Macintosh laryngoscope ( mean ( SD ) 19.0 ( 9.7 ) s vs. 12.7 ( 5.9 ) s , respectively ; p = 0.006 ) . There was no difference in the number of successful intubations , ease of intubation or choice of intubating device . In the simulated difficult laryngoscopy scenarios , the anaesthetists took less time to intubate using the GlideScope ( 23.5 ( 12.7 ) s vs. 70.5 ( 101.2 ) s , respectively ; p = 0.001 ) . The slightly higher success rate with the GlideScope was not statistically significant ( 20/20 vs. 18/20 , respectively ; p = 0.5 ) . However , the anaesthetists found it easier to intubate using the GlideScope ( median ( interquartile range [ range ] ) 1 ( 1–2 [ 1–2 ] ) vs. 2 ( 2–3 [ 1–3 ] ) , respectively ; p < 0.0001 ) Background : Videolaryngoscopy has been developed mainly to assist difficult airway intubation . However , there is a lack of studies demonstrating the real efficacy of its use in children . In this study , we tested the hypothesis that GlideScope ( Verathon Inc , Bothell , Wash ) videolaryngoscope improves tracheal intubation when used by pediatric residents in an advanced patient simulation model . Methods : Pediatric residents who passed a pediatric advanced life support course were eligible for the study . An advanced infant simulator was used , and 4 scenarios were proposed : normal airway ( NA ) , tongue edema ( TE ) , tongue edema and oropharyngeal edema , and cervical collar . No participant had prior experience with any videolaryngoscope . After a brief instruction in GlideScope technique , each participant performed the 4 scenarios using both the st and ard Miller and GlideScope laryngoscopes , in a r and om sequence . Results : Sixteen residents were included . The number of failed intubations was higher with GlideScope in NA and TE scenarios ( 3 vs 0 , in both cases ) . Mean ( SD ) time to successful intubation was significantly longer with GlideScope in the NA scenario ( GlideScope , 38 [ SD , 13 ] vs Miller , 26 [ SD , 16 ] seconds ; P = 0.043 ) . The number of maneuvers was significantly higher with GlideScope in the tongue edema and oropharyngeal edema scenario ( 2.3 [ SD , 1.5 ] vs 1.5 [ SD , 1 ] ; P = 0.04 ) . Upper jaw injury index was significantly lower with GlideScope in NA ( 2.0 [ SD , 1 ] vs 2.6 [ SD , 0.8 ] ; P = 0.008 ) and cervical collar ( 2.1 [ SD , 1.0 ] vs 2.8 [ SD , 0.5 ] ; P = 0.011 ) scenarios . Participants considered GlideScope technique more difficult than st and ard Miller in NA ( 5 [ SD , 2.0 ] vs 3 [ SD , 1.3 ] ; P = 0.04 ) and TE ( 5.9 [ SD , 2.5 ] vs 3.9 [ SD , 1.7 ] ; P = 0.02 ) scenarios . Conclusions : In simulated scenarios of infant NA and difficult airway , when used by pediatric residents , GlideScope did not improve intubation performance when compared with the st and ard laryngoscope . Nevertheless , GlideScope may be safer for upper jaw injury and could have advantages in the management of complicated airway . Further studies are needed to assess if specific training will improve GlideScope intubation performance and whether the " in simulator " results translate into clinical practice Context : This translational research initiative focused on the physiology of cardiopulmonary resuscitation ( CPR ) initiated by a clinical observation of consistent hyperventilation by professional rescuers in out-of-hospital cardiac arrest . This observation generated scientific hypotheses that could only ethically be tested in the animal laboratory . Objective : To examine the hypothesis that excessive ventilation rates during performance of CPR by overzealous but well-trained rescue personnel causes a significant decrease in coronary perfusion pressure and an increased likelihood of death . Design and Setting : In the in vivo human aspect of the study , we set out to objective ly and electronically record rate and duration of ventilation during performance of CPR by trained professional rescue personnel in a prospect i ve clinical trial in intubated , adult patients with out-of-hospital cardiac arrest . In the in vivo animal aspect of the study , to simulate the clinical ly observed hyperventilation , nine pigs in cardiac arrest were ventilated in a r and om order with 12 , 20 , or 30 breaths/min , and physiologic variables were assessed . Next , three groups of seven pigs in cardiac arrest were ventilated at 12 breaths/min with 100 % oxygen , 30 breaths/min with 100 % oxygen , or 30 breaths/min with 5 % Co2/95 % oxygen , and survival was assessed . Main Outcome Measures : Ventilation rate and duration in humans ; mean intratracheal pressure , coronary perfusion pressure , and survival rates in animals . Results : In 13 consecutive adults ( average age , 63 ± 5.8 yrs ) receiving CPR ( seven men ) the average ventilation rate was 30 ± 3.2 breaths/min ( range , 15 to 49 breaths/min ) and the average duration of each breath was 1.0 ± 0.07 sec. The average percentage of time in which a positive pressure was recorded in the lungs was 47.3 ± 4.3 % . No patient survived . In animals treated with 12 , 20 , and 30 breaths/min , the mean intratracheal pressures and coronary perfusion pressures were 7.1 ± 0.7 , 11.6 ± 0.7 , 17.5 ± 1.0 mm Hg/min ( p < .0001 ) and 23.4 ± 1.0 , 19.5 ± 1.8 , 16.9 ± 1.8 mm Hg ( p = .03 ) with each of the different ventilation rates , respectively ( p = comparison of 12 breaths/min vs. 30 breaths/min for mean intratracheal pressure and coronary perfusion pressure ) . Survival rates were six of seven , one of seven , and one of seven with 12 , 30 , and 30 + Co2 breaths/min , respectively ( p = .006 ) . Conclusions : Despite seemingly adequate training , professional rescuers consistently hyperventilated patients during out-of-hospital CPR . Subsequent hemodynamic and survival studies in pigs demonstrated that excessive ventilation rates significantly decreased coronary perfusion pressures and survival rates , despite supplemental Co2 to prevent hypocapnia . This translational research initiative demonstrates an inversely proportional relationship between mean intratracheal pressure and coronary perfusion pressure during CPR . Additional education of CPR providers is urgently needed to reduce these newly identified and deadly consequences of hyperventilation during CPR . These findings also have significant implication s for interpretation and design of resuscitation research , CPR guidelines , education , the development of biomedical devices , emergency medical services quality assurance , and clinical practice OBJECTIVES Advanced cardiac life support ( ACLS ) skills tend to de grade over time . There is mounting evidence that high-fidelity simulation ( HFS ) is advantageous to teaching ACLS . The aspects of HFS that enhance learning are not entirely clear , but the anxiety generated by a scenario may enhance retention through well-established learning pathways . We sought to determine whether an HFS with added emotional stress could provoke anxiety and , if so , whether or not participants learning ACLS would demonstrate better written and applied knowledge retention 6 months after their initial course . METHODS Twenty-five student volunteers from Year 1 and 2 at Mount Sinai School of Medicine were r and omly assigned to a control group or an emotional content ( EC ) group for a sudden cardiac death management course . All subjects were monitored for heart rate and were assessed using the State-Trait Anxiety Inventory . Control group participants experienced an HFS in which actors were not scripted to add stress , whereas EC group participants were exposed to an emotionally charged environment using the same actors . RESULTS Participants across the two groups were well matched by resting heart rates , baseline anxiety and prior ACLS knowledge . The EC group participants experienced greater anxiety than controls ( mean state anxiety score : 35.0 versus 28.2 [ p<0.05 ] ; average heart rate [ HR ] : 94.6 bpm versus 72.9 bpm [ p<0.05 ] ; maximum HR : 120.8 bpm versus 95.3 bpm [ p<0.05 ] ) . Six months later , written test scores were similar , but the EC group participants achieved higher practical competency examination ( ' mega code ' ) scores than controls ( 32.5 versus 25.0 ; p<0.05 ) . Independent t-tests and Spearman rank coefficients were employed where applicable . CONCLUSIONS Simulation with added emotional stressors led to greater anxiety during ACLS instruction but correlated with enhanced performance of ACLS skills after this course . The quantitative and qualitative values of added stressors need further exploration , but these values represent important variables in simulation-based education Context No r and omised controlled trial has yet compared different video laryngoscopes in respect of the success rates and the time taken to achieve endotracheal intubation in trapped car accident victims . Objective The aim of the present study was to evaluate whether five video laryngoscopes facilitate tracheal intubation more quickly or more securely than conventional laryngoscopy . Design Prospect i ve , controlled , r and omised crossover trial . Setting An airway manikin was placed on the driver 's seat of a compact car . Access was possible only through the opened driver 's door . Participants Twenty-five experienced anaesthetists . Intervention Tracheal intubation in a simulated trapped patient using video laryngoscopes in a typical out-of-hospital setting . Main outcome measures Times to achievement of a view of the glottis , tracheal intubation , cuff inflation , first ventilation and tracheal tube position were compared using a st and ard Macintosh laryngoscope or Glidescope Ranger , Storz C-MAC , Ambu-Pentax AWS , Airtraq and McGrath Series 5 video laryngoscopes in a r and omised order . Wilcoxon signed-rank test and McNemar test were used for statistical analysis . A P value of less than 0.05 was considered statistically significant . Results Twenty-five anaesthetists ( 35.1 ± 7.3 years ; 16 male , nine female ) with an intubation experience of 374 ± 96 intubations per year and an experience of 9.1 ± 7.3 years participated . Glottic view , tracheal intubation , cuff inflation and first ventilation were achieved most rapidly with the Macintosh laryngoscope , although the Airtraq and Pentax AWS video laryngoscopes were not significantly slower . Times were significantly longer when the Glidescope Ranger , McGrath Series 5 or Storz C-MAC video laryngoscopes were used ( P < 0.05 ) , failure to place the endotracheal tube correctly was significantly commoner with the McGrath Series 5 than with the Macintosh ( P = 0.031 ) . Conclusion When attempting to intubate a trapped car accident victim , video laryngoscopes provide a better view of the glottis , but some delay tracheal intubation significantly . The devices with a tube guide ( Airtraq and Ambu Pentax AWS ) enable tracheal intubation to be achieved significantly faster and with a lower failure rate than devices without a tube guide . No video laryngoscope outperformed direct laryngoscopy with a Macintosh laryngoscope in this simulation study . Trial registration Clinical trials.gov NCT01182740 |
12,590 | 28,276,151 | We found similar results in the subgroup with previous PTB , but only a reduction of PTB < 34 weeks in women with a short cervix .
Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or < 34 weeks .
Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk , reducing PTB < 34 weeks , < 37 weeks , neonatal demise and other sequelae .
TWEETABLE ABSTRACT Progesterone was better than cerclage and pessary to prevent preterm birth , neonatal death and more in network meta- analysis | BACKGROUND Preterm birth ( PTB ) is the leading cause of infant death , but it is unclear which intervention is best to prevent it .
OBJECTIVES To compare progesterone , cerclage and pessary , determine their relative effects and rank them . | OBJECTIVE The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage . STUDY DESIGN From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks ' gestation were r and omly assigned to receive a McDonald cerclage or no cerclage . Before r and om assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics . After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation . RESULTS Of the 61 patients 31 were r and omly assigned to cerclage and 30 were r and omly assigned to no cerclage . There were no differences between groups with respect to maternal demographic characteristics , risk factors for preterm birth , cervical measurements , rescue procedures , readmission , chorioamnionitis , and abruptio placentae . The mean gestational age at delivery ( 33.5 + /- 6.3 weeks ) and the perinatal death rate ( 12 . 9 % ) in the cerclage group were similar to the mean gestational age at delivery ( 34.7 + /- 4.7 weeks ; P = .4 ) and the perinatal death rate ( 10.0 % ; P = .9 ) in the no-cerclage group . CONCLUSION Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes Objective . To assess efficacy and tolerability of vaginal compared with intramuscular progesterone in reducing the rate of recurrent preterm birth before 34 weeks of gestation . Design . Prospect i ve r and omized study . Setting . Obstetrics and Gynecology Department , Armed Forces Hospital Southern Region , Kingdom of Saudi Arabia . Sample . Five‐hundred and eighteen women with a prior history of preterm birth . Methods . Women were r and omized to receive either 90 mg of vaginal progesterone gel once daily or 250 mg of intramuscular progesterone weekly . Treatment began between 14 and 18 weeks of gestation and continued until 36 complete weeks of gestation , delivery or the occurrence of premature rupture of membranes . Main outcome measures . The primary outcome measure was delivery before 34 weeks of gestation . The secondary outcome measures were PTB between 34 and 37 weeks of gestation and neonatal outcomes including birthweight , neonatal death , and the need for admission to the neonatal intensive care unit . Results . The baseline characteristics of the study participants were similar . Two‐hundred and thirty‐eight ( 94.1 % ) patients in the vaginal group and 226 ( 90.8 % ) patients in the intramuscular group were compliant with their medications . Vaginal progesterone was associated with a lower percentage of deliveries before 34 weeks of gestation than the intramuscular preparation ( p= 0.02 ) . This association was also observed at 28 and 32 weeks of gestation ( p= 0.04 ) . Adverse effects were reported in 14.1 % of patients in the intramuscular group , but in only 7.5 % of patients in the vaginal group ( p= 0.017 ) . Conclusions . Vaginal progesterone was more effective than intramuscular progesterone for the prevention of preterm birth and had fewer adverse effects OBJECTIVE The purpose of this guideline is to provide a framework that clinicians can use to determine which women are at greatest risk of having cervical insufficiency and in which set of circumstances a cerclage is of potential value . EVIDENCE Published literature was retrieved through search es of PubMed or MEDLINE , CINAHL , and The Cochrane Library in 2012 using appropriate controlled vocabulary ( e.g. , uterine cervical incompetence ) and key words ( e.g. , cervical insufficiency , cerclage , Shirodkar , cerclage , MacDonald , cerclage , abdominal , cervical length , mid-trimester pregnancy loss ) . Results were restricted to systematic review s , r and omized control trials/controlled clinical trials , and observational studies . There were no date or language restrictions . Search es were up date d on a regular basis and incorporated in the guideline to January 2011 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology-related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies . VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care ( Table ) . Recommendations 1 . Women who are pregnant or planning pregnancy should be evaluated for risk factors for cervical insufficiency . A thorough medical history at initial evaluation may alert clinicians to risk factors in a first or index pregnancy . ( III-B ) 2 . Detailed evaluation of risk factors should be undertaken in women following a mid-trimester pregnancy loss or early premature delivery , or in cases where such complications have occurred in a preceding pregnancy . ( III-B ) 3 . In women with a history of cervical insufficiency , urinalysis for culture and sensitivity and vaginal cultures for bacterial vaginosis should be taken at the first obstetric visit and any infections so found should be treated . ( I-A ) 4 . Women with a history of three or more second-trimester pregnancy losses or extreme premature deliveries , in whom no specific cause other than potential cervical insufficiency is identified , should be offered elective cerclage at 12 to 14 weeks of gestation . ( I-A ) 5 . In women with a classic history of cervical insufficiency in whom prior vaginal cervical cerclage has been unsuccessful , abdominal cerclage can be considered in the absence of additional mitigating factors . ( II-3C ) 6 . Women who have undergone trachelectomy should have abdominal cerclage placement . ( II-3C ) 7 . Emergency cerclage may be considered in women in whom the cervix has dilated to < 4 cm without contractions before 24 weeks of gestation . ( II-3C ) 8 . Women in whom cerclage is not considered or justified , but whose history suggests a risk for cervical insufficiency ( 1 or 2 prior mid-trimester losses or extreme premature deliveries ) , should be offered serial cervical length assessment by ultrasound . ( II-2B ) 9 . Cerclage should be considered in singleton pregnancies in women with a history of spontaneous preterm birth or possible cervical insufficiency if the cervical length is ≤ 25 mm before 24 weeks of gestation . ( I-A ) 10 . There is no benefit to cerclage in a woman with an incidental finding of a short cervix by ultrasound examination but no prior risk factors for preterm birth . ( II-1D ) 11 . Present data do not support the use of elective cerclage in multiple gestations even when there is a history of preterm birth ; therefore , this should be avoided . ( I-D ) 12 . The literature does not support the insertion of cerclage in multiple gestations on the basis of cervical length . ( II-1D ) OBJECTIVE The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate ( 17OHP-C ) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery , such as previous preterm birth , cervical surgery , uterine anomalies , or prenatal diethylstilbestrol ( DES ) exposure . STUDY DESIGN This open-label , multicenter , r and omized controlled trial included asymptomatic singleton pregnancies from 20(+0 ) through 31(+6 ) weeks of gestation with a cervical length less than 25 mm and a history of preterm delivery or cervical surgery or uterine malformation or prenatal DES exposure . R and omization assigned them to receive ( or not ) 500 mg of intramuscular 17OHP-C weekly until 36 weeks . The primary outcome was time from r and omization to delivery . RESULTS After enrolling 105 patients , an interim analysis demonstrated the lack of efficacy of 17OHP-C in prolonging pregnancy . The study was discontinued because of futility . The groups were similar for maternal age , body mass index , parity , gestational age at inclusion , history of uterine anomalies , DES syndrome , previous preterm delivery or midtrimester abortion , and cervical length at r and omization . The enrollment-to-delivery interval did not differ between patients allocated to 17OHP-C ( n = 51 ) and those allocated to the control group ( n = 54 ) ( median [ interquartile range ] time to delivery : 77 [ 54 - 103 ] and 74 [ 52 - 99 ] days , respectively ) . The rate of preterm delivery less than 37 ( 45 % vs 44 % , P > .99 ) , less than 34 ( 24 % vs 30 % , P = .51 ) , or less than 32 ( 14 % vs 20 % , P = .44 ) weeks was similar in patients allocated to 17OHP-C and those in the control group . CONCLUSION 17OHP-C did not prolong pregnancy in women with singleton gestations , a sonographic short cervix , and other risk factors of preterm delivery ( prior history , uterine malformations , cervical surgery , or prenatal DES exposure ) OBJECTIVE To determine the effectiveness of cerclage pessary in the prevention of preterm birth in asymptomatic Chinese women with a short cervix at 20 to 24 weeks . METHODS Low-risk women carrying singleton pregnancies were screened with transvaginal ultrasound , and those with a cervical length < 25 mm at 20 to 24 weeks were recruited into a r and omized controlled trial , comparing the prophylactic use of cerclage pessary with expectant management . The analysis was by intent-to-treat . The primary outcome measure was preterm delivery before 34 weeks . RESULTS Among 4438 screened women , 203 women ( 4.6 % ) met the inclusion criteria and 108 ( 58 % ) consented for the study . A total of 53 and 55 women were allocated to pessary and control groups , respectively . There was no difference in background demographics , including the mean cervical length ( 19.6 mm versus 20.5 mm ) and the mean gestational age at r and omization ( both 21.9 weeks ) . Delivery before 34 weeks occurred in 9.4 % and 5.5 % ( p = 0.46 ) in the pessary and the control groups , respectively . No differences in major side effects were noted between the groups . CONCLUSION In our population , < 5 % had a cervical length of less than 25 mm at 20 to 24 weeks ' gestation . The prophylactic use of cerclage pessary did not reduce the rate of preterm delivery before 34 weeks Background Preterm birth is a worldwide health concern due to its various negative consequences . Therefore , the prevention of preterm birth is a top priority for healthcare systems in all countries . Objective To compare the effectiveness of vaginal versus intramuscular progesterone in the prevention of preterm delivery . Methods This r and omized clinical trial was conducted at Shahid Sadoughi Hospital in Yazd , Iran , from November 21 , 2012 to January 20 , 2015 . Seventy-eight pregnant women with singleton pregnancy and one risk factor of preterm delivery were included in the study . The subjects were assigned r and omly to two groups , with group one receiving Cyclogest and group two receiving 17-α hydroxyprogesterone caproate . Subsequently , we analyzed drug complications during pregnancy , delivery time , neonatal outcomes , and patients ’ satisfaction among the two groups . The data were analyzed using SPSS version 16 . We used descriptive statistics , chi-squared , t-test , and ANOVA for the analyses of primary and secondary outcomes . Results Among the 39 births in group one , 33.3 % occurred preterm , and , among the 39 births in group two , 30.7 % occurred preterm ( < 37 weeks ) . The mean gestational ages at delivery in groups 1 and 2 were 37.07 ± 2.23 and 36.81 ± 2.77 weeks , respectively ( p = 0.765 ) . Other variables were not significantly different between the two groups , including birth weight ( p = 0.745 ) , Apgar scores for the first and fifth minutes ( p = 0.574 , 0.630 ) , length of stay in the neonatal intensive care unit ( NICU ) when the newborns needed hospitalization ( p = 0.358 ) , and the patients ’ satisfaction with the drugs that were used ( p = 0.615 ) . Conclusions In this study , vaginal progesterone and intramuscular progesterone had the same levels of effectiveness , safety and acceptance by patients in the prevention of preterm delivery . Therefore , both can be used for this purpose in clinical practice s , but more studies are needed OBJECTIVE The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population . STUDY DESIGN A r and omized , double-blind , placebo-controlled study included 142 high-risk singleton pregnancies . Progesterone ( 100 mg ) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes , between 24 and 34 weeks of gestation . Progesterone ( n = 72 ) and placebo ( n = 70 ) groups were compared for epidemiologic characteristics , uterine contraction frequency , and incidence of preterm birth . Data were compared by chi(2 ) analysis and Fisher exact test . RESULTS The preterm birth rate was 21.1 % ( 30/142 ) . Differences in uterine activity were found between the progesterone and placebo groups ( 23.6 % vs 54.3 % , respectively ; P < .05 ) and in preterm birth between progesterone and placebo ( 13.8 % vs 28.5 % , respectively ; P < .05 ) . More women were delivered before 34 weeks in the placebo group ( 18.5 % ) than in the progesterone group ( 2.7 % ) ( P < .05 ) . CONCLUSION Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity We sought to evaluate the effectiveness of daily oral micronized progesterone ( MP ) in preventing recurrent spontaneous preterm birth ( RSPB ) and whether MP increases maternal serum progesterone . We performed a pilot , single-center , r and omized , double-blind , placebo-controlled trial in women with a prior preterm birth and current singleton gestation at 16 to 20 weeks ( N = 33 ) . The primary outcome was the rate of RSPB . Subjects were given either daily MP ( 400 mg ) or placebo from 16 to 34 weeks . Serum progesterone was obtained at enrollment and in the late second/early third trimester . Pregnancy outcome data were collected . RSPB occurred in 5/19 ( 26.3 % ) in the MP group versus 8/14 ( 57.1 % ) in placebo group ( P = 0.15 ) . The mean age at delivery was 37.0 ± 2.7 weeks for the MP group versus 35.9 ± 2.6 weeks for the placebo ( P = 0.3 ) . Mean serum progesterone at 28 weeks was 122.6 ± 61.8 pg/mL for MP group versus 90.1 ± 38.7 pg/mL for placebo ( P = 0.19 ) . MP was associated with a trend toward a reduction in RSPB and an increase in the maternal serum progesterone . Although the primary outcome in this pilot study did not reach statistical significance , the results suggest a favorable trend meriting further investigation We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients . Premature delivery did not occur in 18 patients receiving the progestational agent , whereas 41 per cent of the 22 receiving the palcebo had premature delivery ( P less than 0.01 ) . The mean duration of pregnancy and the mean birth weight in the former group ( 38.6 weeks + /- 1.6 S.D. , and 2836 g + /- 412 S.D. ) were both significantly greater ( P less than 0.025 ) than that in the latter ( 35.2 weeks + /- 6.7 S.D. ; 2361 g + /- 1085 S.D. ) . The perinatal mortality rate in the group given the progestational agent ( O per cent ) was significantly less than that observed in the placebo group ( 27 per cent ) ( P less than 0.05 ) . Although there were no complications attributable to the progestational drug , the study population was too small for assessment of immediate or long term safety . However , the results indicate a possible obstetric use for this drug OBJECTIVE To compare preterm delivery rates ( before 34 weeks of gestation ) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone . STUDY DESIGN Cervical length was measured in patients with risk factors or symptoms of cervical incompetence . Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence , previous preterm premature rupture of membranes before 32 weeks of gestation , history of cold knife conization , diethylstilbestrol exposure , and uterine anomaly . When a cervical length of < 25 mm was measured before a gestational age of 27 weeks , a r and omization for therapeutic cerclage and bed rest ( cerclage group ) or bed rest alone ( bed rest group ) was performed . The analysis is based on intention to treat . RESULTS Of the 35 women who met the inclusion criteria , 19 were allocated r and omly to the cerclage group and 16 to the bed rest group . Both groups were comparable for mean cervical length and mean gestational age at time of r and omization , mean overall 20 mm and 21 weeks . Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group ( 7 of 16 vs none , respectively ; P = .002 ) . There was no statistically significant difference in neonatal survival between the groups ( 13 neonates survived in the bed rest group vs all in the cerclage group ) . The compound neonatal morbidity , defined as admission to the neonatal intensive care unit or neonatal death , was significantly higher in the bed rest group than in the cerclage group ( 8 of 16 vs 1 of 19 , respectively ; P = .005 ; RR = 9.5 , 95 % CI , 1.3 - 68.1 ) . CONCLUSIONS Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and /or symptoms of cervical incompetence and a cervical length of < 25 mm before 27 weeks of gestation OBJECTIVE The purpose of this study was to determine the efficacy of cerclage and bed rest versus bed rest-only for the prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination . STUDY DESIGN Women with > or = 1 of high-risk factors for preterm birth ( > or = 1 preterm birth at < 35 weeks of gestation , > or = 2 curettages , diethylstilbestrol exposure , cone biopsy , Mullerian anomaly , or twin gestation ) were screened with transvaginal ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23 weeks 6 days of gestation . Enrollment was offered to both asymptomatic women who were at high risk and who were identified to have short cervix ( < 25 mm ) or significant funneling ( > 25 % ) and nonscreened women who were at low risk and who were identified incidentally . The women who gave written consent were assigned r and omly to receive either McDonald cerclage or bed rest-only . Both groups received similar counseling and treatment . Primary outcome was preterm birth at < 35 weeks of gestation . RESULTS Sixty-one women were assigned r and omly . Forty-seven pregnancies ( 77 % ) were high-risk singleton gestations . Thirty-one women ( 51 % ) were allocated to cerclage , and 30 women ( 49 % ) were allocated to bed rest . There were no differences between the groups in demographic characteristics , risk factors , and cervical variables . Preterm birth at < 35 weeks of gestation occurred in 14 women ( 45 % ) in the cerclage group and in 14 women ( 47 % ) in the bed rest group ( relative risk , 0.94 ; 95 % CI , 0.34 - 2.58 ) . There was no difference in any obstetric or neonatal outcomes . A sub analysis of singleton pregnancies with previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm ( n = 31 women ) also revealed no significant difference in recurrent preterm birth at < 35 weeks of gestation ( 40 % vs 56 % ; relative risk , 0.52 ; 95 % CI , 0.12 - 2.17 ) . CONCLUSION Cerclage did not prevent preterm birth in women with a short cervix . These results should be confirmed by larger trials AIM This is the first report of a r and omized trial of cerclage on pure cervical shortening without vaginosis or cervicitis . The objective of our multicenter r and omized controlled trial was to assess the benefits of ultrasound-indicated cervical cerclage in the mid-trimester to prevent preterm birth in women who have no signs of infection or inflammation of the lower genital tract . MATERIAL AND METHODS Women with a short cervical length < 25 mm between 16 and 26 weeks of gestation were r and omly assigned to receive a Shirodkar cerclage , McDonald cerclage , or bedrest ( no cerclage ) . Before being r and omly assigned to one of the three groups , all women were screened for infection/inflammation of the lower genital tract ; those with positive results were excluded from the study . The ratio of preterm delivery as a primary end-point was evaluated in the groups . RESULTS A total of 106 singleton patients with a short cervical length were assessed for study eligibility ; 106 patients were r and omized to the three treatment options . Ultimately , 98 patients ( in the Shirodkar [ n = 34 ] , McDonald [ n = 34 ] and bedrest [ n = 30 ] groups ) were analyzed . No differences in preterm delivery or perinatal outcomes were found between the three groups . Significantly fewer patients in the Shirodkar group required hospitalization for treatment of threatened preterm labor when compared to patients in the bedrest group . CONCLUSION For women with a short cervical length < 25 mm between 16 and 26 weeks of gestation , Shirodkar cerclage might be considered to reduce the occurrence of threatened preterm labor Purpose The purpose of this study was to evaluate whether the prophylactic administration of vaginal progesterone would reduce the preterm birth rate in high-risk population including singleton and twin pregnancies . Methods This was a r and omized , double blind , placebo-controlled study that included 150 high-risk pregnancies . Risk groups included prior spontaneous preterm birth , twin pregnancy , and uterine malformation . Micronized progesterone or placebo ( 100 mg ) was administered daily by vaginal suppository between 24 and 34 weeks of gestation . We compared progesterone and placebo groups for incidence of preterm labor and preterm delivery . Data were compared by χ² analysis and Fisher exact test . Results There was a statistically significant difference in the rate of preterm labor between placebo and progesterone groups ( 45.7 vs. 25 % , respectively ; p < 0.05 ) . More women delivered before 37 weeks in placebo group ( 57.2 % ) than in progesterone group ( 40 % ; p < 0.05 ) . Administering progesterone also reduced the preterm birth before 34 weeks of gestation . The difference between placebo and progesterone group was statistically significant ( 24.3 vs. 8.8 % ; p < 0.05 ) . However , there was no significant difference in neonatal death between placebo and progesterone groups . Conclusion Prophylactic vaginal progesterone reduced the rate of preterm labor and preterm delivery in high-risk pregnancies OBJECTIVES Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery . This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix ( 10 - 20 mm ) at 19 + 0 to 23 + 6 weeks of gestation . Women were allocated r and omly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks , rupture of membranes or delivery , whichever occurred first . R and omization sequence was stratified by center and history of a previous preterm birth . The primary endpoint was preterm birth before 33 weeks of gestation . Analysis was by intention to treat . RESULTS Of 465 women r and omized , seven were lost to follow-up and 458 ( vaginal progesterone gel , n=235 ; placebo , n=223 ) were included in the analysis . Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo ( 8.9 % ( n=21 ) vs 16.1 % ( n=36 ) ; relative risk ( RR ) , 0.55 ; 95 % CI , 0.33 - 0.92 ; P=0.02 ) . The effect remained significant after adjustment for covariables ( adjusted RR , 0.52 ; 95 % CI , 0.31 - 0.91 ; P=0.02 ) . Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks ( 5.1 % vs 10.3 % ; RR , 0.50 ; 95 % CI , 0.25 - 0.97 ; P=0.04 ) and 35 weeks ( 14.5 % vs 23.3 % ; RR , 0.62 ; 95 % CI , 0.42 - 0.92 ; P=0.02 ) , respiratory distress syndrome ( 3.0 % vs 7.6 % ; RR , 0.39 ; 95 % CI , 0.17 - 0.92 ; P=0.03 ) , any neonatal morbidity or mortality event ( 7.7 % vs 13.5 % ; RR , 0.57 ; 95 % CI , 0.33 - 0.99 ; P=0.04 ) and birth weight < 1500 g ( 6.4 % ( 15/234 ) vs 13.6 % ( 30/220 ) ; RR , 0.47 ; 95 % CI , 0.26 - 0.85 ; P=0.01 ) . There were no differences in the incidence of treatment-related adverse events between the groups . CONCLUSIONS The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45 % reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome OBJECTIVE The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester . STUDY DESIGN From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were r and omly assigned to McDonald cerclage or no cerclage : internal os dilation and either membrane prolapse into the endocervical canal at least 25 % of the total cervical length but not beyond the external os or a shortened distal cervix < 2.5 cm . Before r and omization , all patients were treated identically with an amniocentesis , multiple urogenital cultures , and therapy with indomethacin and clindamycin for 48 to 72 hours . Except for the cerclage , all patients were treated identically after r and omization . Multiple variables of perinatal outcome were analyzed . A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable . This model was applied to 3 population s : the cerclage group , the no cerclage group , and both groups combined . RESULTS Of the 135 patients , 20 patients declined r and omization , and 2 patients were diagnosed with acute chorioamnionitis . Of the 113 patients remaining , 55 patients were r and omly assigned to the cerclage group , and 58 patients were r and omly assigned to the no cerclage group . There were 8 rescue cerclage procedures ( 4 in each group ) . Regression analysis showed that readmission for preterm labor , chorioamnionitis , and abruption were consistently associated with early gestational age at delivery and increased morbidity . Cerclage did not affect perinatal outcome . CONCLUSION The sonographic findings of second trimester internal os dilation , membrane prolapse , and distal cervical shortening likely represent a common pathway of several pathophysiologic processes . Use of cerclage does not alter any perinatal outcome variables . Increased neonatal morbidity in these patients appears to be associated with sub clinical infection , preterm labor , and abruption AIM Preterm delivery is defined as a birth before 37 weeks ' gestation and is the cause of two-thirds of perinatal mortality and thus one of the major problems in obstetrics . Its etiology is unknown , but hormonal factors have been reported to play a part . Progesterone is a placental hormone and effective in maintaining pregnancy . The aim of this study is to evaluate the efficacy of 17α-hydroxyprogesterone caproate in the prevention of preterm delivery . METHODS This interventional study was performed with 100 pregnant women who had been referred to the Obstetrics Clinic of Ghaem Hospital ( related to Mashhad University of Medical Sciences ) during 2007 to 2008 . They were r and omly divided into two groups of 50 cases and 50 controls . The case group received 250 mg of intramuscular 17α-hydroxyprogesterone caproate weekly from 16 weeks ' gestation up to a maximum of 37 weeks ' gestation . In the control group , routine perinatal care was performed and the pregnancy outcomes were compared in both groups . RESULTS The mean gestational age was 36 weeks in the case group and 34 weeks in the control group . The mean birth weight was 2695 g in the case group and 2399 g in the control group . A significant difference was observed between the two groups in terms of gestational age and birth weight ( P < 0.05 ) . CONCLUSION Weekly administration of 17α-hydroxyprogesterone caproate to pregnant women with a history of preterm delivery was associated with a decrease in preterm delivery and improvement in birth weight OBJECTIVE Preterm birth is the leading cause of perinatal morbidity and mortality worldwide . Treatment of preterm labor with tocolysis has not been successful in improving infant outcome . The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth . The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth . METHODS This r and omized , double-blind , placebo- controlled , multinational trial enrolled and r and omized 659 pregnant women with a history of spontaneous preterm birth . Between 18 + 0 and 22 + 6 weeks of gestation , patients were assigned r and omly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery , 37 weeks ' gestation or development of preterm rupture of membranes . The primary outcome was preterm birth at < /= 32 weeks of gestation . The trial was analyzed using an intent-to-treat strategy . RESULTS Baseline characteristics were similar in the two treatment groups . Progesterone did not decrease the frequency of preterm birth at < /= 32 weeks . There was no difference between the groups with respect to the mean gestational age at delivery , infant morbidity or mortality or other maternal or neonatal outcome measures . Adverse events during the course of treatment were similar for the two groups . CONCLUSION Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth ( < /= 32 weeks ) in women with a history of spontaneous preterm birth . The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone ( e.g. sonographic cervical length ) requires further investigation OBJECTIVE The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth ( PTB ) in low-risk pregnant women with a short cervical length ( CL ) . STUDY DESIGN Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks . Women with a CL ≤ 30 mm received vaginal progesterone or placebo . Primary outcome was adverse neonatal outcome , defined as a composite of respiratory distress syndrome , bronchopulmonary dysplasia , intracerebral hemorrhage > grade II , necrotizing enterocolitis > stage 1 , proven sepsis , or death before discharge . Secondary outcomes included time to delivery , PTB before 32 , 34 , and 37 weeks of gestation . Analysis was by intention to treat . RESULTS Between 2009 and 2013 , 20,234 women were screened . A CL of 30 mm or less was seen in 375 women ( 1.8 % ) . In 151 women , a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial . We r and omly allocated 41 women to progesterone and 39 to placebo . Adverse neonatal outcomes occurred in two ( 5.0 % ) women in the progesterone and in four ( 11 % ) women in the control group ( relative risk [ RR ] , 0.47 ; 95 % confidence interval [ CI ] , 0.09 - 2.4 ) . The use of progesterone result ed in a nonsignificant reduction of PTB < 32 weeks ( 2.0 vs. 8.0 % ; RR , 0.33 ; 95 % CI , 0.04 - 3.0 ) and < 34 weeks ( 7.0 vs. 10 % ; RR , 0.73 ; 95 % CI , 0.18 - 3.1 ) but not on PTB < 37 weeks ( 15 vs. 13 % ; RR , 1.2 ; 95 % CI , 0.39 - 3.5 ) . CONCLUSION In women with a short cervix , who are otherwise low risk , we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB OBJECTIVE To evaluate oral micronized progesterone ( OMP ) to prevent preterm birth ( PTB ) . METHODS A r and omized , double-blind , placebo-controlled trial of 150 women with at least one PTB who received 100 mg of OMP or placebo twice a day from recruitment ( 18 - 24 weeks ) until 36 weeks or delivery . RESULTS PTB occurred in 29 ( 39.2 % ) women in the OMP group ( n=74 ) compared with 44 ( 59.5 % ) in the control group ( n=74 , P=0.002 ) . Mean gestational age at delivery was higher in the OMP group ( 36.1 vs 34.0 weeks , P<0.001 ) . Fewer preterm births occurred between 28 and 31 weeks plus 6 days in the OMP group ( RR 0.20 ; 95 % CI , 0.05 - 0.73 , P<0.001 ) . Neonatal age at delivery ( 34 vs 32 weeks , P<0.001 ) , birth weight ( 2400 vs 1890 g , P<0.001 ) , NICU stay ( > 24 h , P<0.001 ) , and Apgar scores ( P<0.001 ) were more favorable in the OMP group , and fewer neonatal deaths occurred ( 3 vs 7 , P=0.190 ) . CONCLUSION OMP reduced the risk of PTB between 28 and 31 weeks plus 6 days , NICU admissions , and neonatal morbidity and mortality in high risk patients Summary In a prospect i ve , r and omised trial , 100 pregnant women with ≥ one prior spontaneous pre-term birth were r and omised into two groups . Group 1 women received 100 mg natural micronised progesterone intravaginally once daily from 20–24 weeks ' gestation until 36 weeks . Group 2 women did not receive progesterone . Both groups were regularly supervised until delivery . Pre-term birth ( < 37 and < 34 weeks ) and other maternal , neonatal outcomes were primary and secondary outcomes , respectively . Chi-square test and Fisher exact test were used to compare categorical variables . Independent sample t-test and one-way ANOVA were used to compare continuous variables and multiple comparisons , respectively . Pre-term births < 37 weeks were significantly lower in Group 1 ( 12 % vs 38 % , p = 0.002 ) , but pre-term births < 34 weeks were similar . The mean birth weight of neonates born to women in Group 1 was significantly higher ( 2800 vs 2,500 g , p = 0.023 ) . We concluded intravaginal administration of 100 mg of natural micronised progesterone significantly reduced the incidence of pre-term birth < 37 weeks in women with ≥ one prior pre-term birth . Future research is warranted to assess the long-term safety and efficacy of progesterone Abstract Objective : To determine pregnancy outcome in patients with short cervix on transvaginal ultrasound between 16 and 24 weeks ' gestation treated with McDonald cerclage compared to weekly intramuscular injections of 17 α-hydroxyprogesterone caproate ( 17OHP-C ) . Methods : From November 2003 through December 2006 , asymptomatic , singleton pregnancies were screened with transvaginal ultrasound between 16–24 weeks ' gestation . Patients with a cervical length ( CL ) ≤25 mm were offered enrollment . Patients were r and omly assigned to treatment with McDonald cerclage or weekly intramuscular injections of 17OHP-C. The primary outcome was spontaneous preterm birth ( PTB ) prior to 35 weeks ' gestation . Results : Seventy-nine patients met inclusion criteria ; 42 were r and omly assigned to the cerclage and 37 to 17OHP-C. Spontaneous PTB prior to 35 weeks ' gestation occurred in 16/42 ( 38.1 % ) of the cerclage group and in 16/37 ( 43.2 % ) of the 17OHP-C group ( relative risk , 1.14 95 % CI , 0.67 , 1.93 ) . A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB < 35 weeks between groups . A similar analysis of patients with a CL≤15 mm showed a reduction in spontaneous PTB < 35 weeks in the cerclage group ( relative risk 0.48 , 0.24–0.97 ) . Conclusion : Women with CL ≤25 mm in the second-trimester appear to have similar risks of delivering prior to 35 weeks ' gestation when treated with 17OHP-C or McDonald cerclage . However , cerclage may be more effective in preventing spontaneous PTB in women with CL≤15 mm Abstract Objectives : To compare vaginal with intramuscular progesterone administration to prevent preterm labor in women with singleton pregnancies and at increased risk of preterm birth . Study design : Prospect i ve comparative clinical trial . Population : One hundred and sixty pregnant women at 20–24 weeks gestation at the risk of preterm labor were classified into : 80 women who received micronized progesterone tablets 200 mg vaginally daily ( Group A ) and 80 women who received 100 mg progesterone in the form of intramuscular every third day ( Group B ) . Methods : Estimation of gestational age , assessment of fetal growth and fetal biophysical profile by trans-abdominal ultrasonographic examination was done every 4 weeks till delivery . Measurement of cervical length was achieved by transvaginal ultrasonography , done every 4 weeks till delivery . Main outcome measures : Incidence of preterm delivery , mean gestational age and the incidence of adverse events of intramuscular versus vaginal route of progesterone administration . Results : The incidence of preterm delivery in Group A was 20 % and in Group B was 27.5 % . The difference between both groups was statistically insignificant . In addition , the rate of adverse events reported in women received injectable progesterone was significantly higher than the rate of adverse events reported in women who received vaginal progesterone therapy . Conclusion : Vaginally administrated progesterone was nearly as equally effective as intramuscular progesterone in the prevention of preterm labor in women at risk and in the meantime has less undesirable events Summary . A total of 506 women at moderate risk of preterm delivery were r and omly allocated to either cervical cerclage or a control group . Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral toco‐lytic drugs . There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant OBJECTIVE We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate ( 17-OHP ) reduces preterm birth ( PTB ) in nulliparous women with a midtrimester cervical length ( CL ) < 30 mm . STUDY DESIGN In this multicenter r and omized controlled trial , nulliparous women with a singleton gestation between 16 and 22 3/7 weeks with an endovaginal CL < 30 mm ( < 10th percentile in this population ) were r and omized to weekly intramuscular 17-OHP ( 250 mg ) or placebo through 36 weeks . The primary outcome was PTB < 37 weeks . RESULTS The frequency of PTB did not differ between the 17-OHP ( n = 327 ) and placebo ( n = 330 ) groups ( 25.1 % vs 24.2 % ; relative risk , 1.03 ; 95 % confidence interval , 0.79 - 1.35 ) . There also was no difference in the composite adverse neonatal outcome ( 7.0 % vs 9.1 % ; relative risk , 0.77 ; 95 % confidence interval , 0.46 - 1.30 ) . CONCLUSION Weekly 17-OHP does not reduce the frequency of PTB in nulliparous women with a midtrimester CL < 30 mm |
12,591 | 24,824,338 | CONCLUSIONS A variety of methods are available that research ers can use for specifying the target difference in an RCT sample size calculation . | BACKGROUND R and omised controlled trials ( RCTs ) are widely accepted as the preferred study design for evaluating healthcare interventions .
When the sample size is determined , a ( target ) difference is typically specified that the RCT is design ed to detect .
This provides reassurance that the study will be informative , i.e. , should such a difference exist , it is likely to be detected with the required statistical precision .
The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation . | Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format Abstract The assessment of clinical ly meaningful changes in patient‐reported pain has become increasingly important when interpreting results of clinical studies . However , proposed response criteria , such as the minimal clinical ly important difference , do not correspond with the growing need for information on truly meaningful , individual improvements . The aim of the present study was to investigate satisfactory improvements in pain from the patient ’s perspective . Data were collected in a 2‐week prospect i ve study of 181 arthritis patients treated with a local corticosteroid injection . Baseline and follow‐up pain were assessed on 100 mm visual analogue scales for pain intensity ( VAS‐PI ) . At baseline , patients also marked a hypothetical level on a VAS‐PI representing a satisfactory improvement in pain . Patient‐perceived satisfactory improvement ( PPSI ) was constructed using a 5‐point categorical rating of change scale at follow‐up as the anchor . PPSI was associated with a minimal reduction of 30 mm or 55 % on the VAS‐PI . Since absolute change in pain associated with satisfactory improvement proved highly dependent on baseline pain , percent change scores performed better in classifying improved patients . The 55 % threshold for satisfactory improvement was consistent over the course of treatment and reasonably consistent across groups of patients . Our data suggest that PPSI is a clinical ly relevant and stable concept for interpreting truly meaningful improvements in pain from the individual perspective In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background Acupuncture is increasingly being used for many conditions including chronic neck pain . However the evidence remains inconclusive , indicating the need for further well- design ed research . The aim of this study was to conduct a pilot r and omised controlled parallel arm trial , to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain . Methods Patients whose GPs had diagnosed neck pain were recruited from one general practice , and r and omised to receive usual GP care only , or acupuncture ( up to 10 treatments over 3 months ) as an adjunctive treatment to usual GP care . The primary outcome measure was the Northwick Park Neck Pain Question naire ( NPQ ) at 3 months . The primary analysis was to determine the sample size for the full scale study . Results Of the 227 patients with neck pain identified from the GP data base , 28 ( 12.3 % ) consenting patients were eligible to participate in the pilot and 24 ( 10.5 % ) were recruited to the trial . Ten patients were r and omised to acupuncture , receiving an average of eight treatments from one of four acupuncturists , and 14 were r and omised to usual GP care alone . The sample size for the full scale trial was calculated from a clinical ly meaningful difference of 5 % on the NPQ and , from this pilot , an adjusted st and ard deviation of 15.3 % . Assuming 90 % power at the 5 % significance level , a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14 % . In order to achieve this sample , one would need to identify patients from data bases of GP practice s with a total population of 230,000 patients , or approximately 15 GP practice s roughly equal in size to the one involved in this study ( i.e. 15,694 patients ) . Conclusion This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial , which in turn will help to clarify the existing evidence base on acupuncture for neck pain Context . The term “ sufficiently important difference ” ( SID ) refers to the overall amount of benefit that people consider sufficient to justify the costs and risks of treatment . Little is known about patient preferences regarding benefits and harms of common cold treatments . Objectives . To develop methods to assess SID and to estimate SID for common cold . Design : The authors conducted in-person and telephone interviews with people with colds , using benefit harm tradeoff methods . The hypothetical benefit of reduction in length of illness was traded off against best estimates of costs and risks . First , the authors briefly described costs , risks , and possible symptomatic benefits of 4 treatment scenarios , based on evidence regarding vitamin C , echinacea , zinc , and pleconaril , an antiviral . Hypothetical benefit ( reduction of illness duration ) was then varied until the cold sufferer indicated that the treatment was minimally desirable . Participants . Interviews were conducted in person with 149 community-recruited adult participants , once at the beginning of their colds , and then again within a few days after symptoms had resolved . Additionally , 162 adult callers with self-identified colds completed interviews via telephone . Results . A total of 460 benefit harm tradeoff interviews ( 1840 treatment scenarios ) estimated overall mean SID as 52.6 h ( 95 % CI , 50.6 to 54.6 ) . For the scenario based on vitamin C , mean SID was estimated as 26.1 h ( 95 % CI , 23.2 to 29.3 ) , with 142 of 460 ( 31 % ) saying they would take it regardless of duration benefit , and 22 of 460 ( 5 % ) saying they would not take it , regardless of duration benefit . For the echinacea-based scenario , mean SID was estimated at 36.8 h ( 33.4 to 40.2 ) , with 105 ( 23 % ) favoring and 41 ( 9 % ) rejecting treatment , regardless of duration benefit . For the zinc lozenge-based scenario , mean SID was estimated as 64.8 h ( 61.0 to 67.9 ) , with 42 ( 9 % ) favoring and 109 ( 24 % ) rejecting treatment . For the prescription antiviral-based scenario , mean SID was estimated as 82.6 h ( 78.7 to 86.7 ) , with 29 ( 6 % ) favoring and 223 ( 48 % ) rejecting . Severity of illness at the time of interview did not appear to significantly influence responses . Possible side effects , treatment type ( tablet v. lozenge v. liquid ) , monetary costs , and opportunity costs ( e.g. , getting to the doctor or pharmacy , dosing frequency ) did appear to be important in influencing these preference patterns . Conclusions . Our study suggests that , on average , people want the duration of their colds to be reduced by between 26 and 65 h to justify potential harms of popular cold treatments . A prescription antiviral would require a greater benefit ( 83 h ) to justify larger perceived risks This study applied a cost-effectiveness model to seven r and omized trials . The model demonstrates the effect of design choices made in the planning stages of a clinical trial on the costs and benefits derived from conducting the trial . The study focused on one parameter used to calculate sample size : the minimum clinical ly important difference in event rates between control and experimental therapies . The study shows that the model can be operationalized to these trials . A computerized software package and manual has been developed to simplify the calculations . While there was some variation in the incremental cost-effectiveness ratios across the seven trials in this study , all ratios may be below the funding threshold . This analytical technique can be used to demonstrate explicitly the re source consequences of the design of r and omized trials and perhaps to set funding priorities Background Central to the design of a r and omised controlled trial ( RCT ) is a calculation of the number of participants needed . This is typically achieved by specifying a target difference , which enables the trial to identify a difference of a particular magnitude should one exist . Seven methods have been proposed for formally determining what the target difference should be . However , in practice , it may be driven by convenience or some other informal basis . It is unclear how aware the trialist community is of these formal methods or whether they are used . Purpose To determine current practice regarding the specification of the target difference by surveying trialists . Methods Two surveys were conducted : ( 1 ) Members of the Society for Clinical Trials ( SCT ) : participants were invited to complete an online survey through the society ’s email distribution list . Respondents were asked about their awareness , use of , and willingness to recommend methods ; ( 2 ) Leading UK- and Irel and -based trialists : the survey was sent to UK Clinical Research Collaboration registered Clinical Trials Units , Medical Research Council UK Hubs for Trial Methodology Research , and the Research Design Services of the National Institute for Health Research . This survey also included questions about the most recent trial developed by the respondent ’s group . Results Survey 1 : Of the 1182 members on the SCT membership email distribution list , 180 responses were received ( 15 % ) . Awareness of methods ranged from 69 ( 38 % ) for health economic methods to 162 ( 90 % ) for pilot study . Willingness to recommend among those who had used a particular method ranged from 56 % for the opinion-seeking method to 89 % for the review of evidence -base method . Survey 2 : Of the 61 surveys sent out , 34 ( 56 % ) responses were received . Awareness of methods ranged from 33 ( 97 % ) for the review of evidence -base and pilot methods to 14 ( 41 % ) for the distribution method . The highest level of willingness to recommend among users was for the anchor method ( 87 % ) . Based upon the most recent trial , the target difference was usually one viewed as important by a stakeholder group , mostly also viewed as a realistic difference given the interventions under evaluation , and sometimes one that led to an achievable sample size . Limitations The response rates achieved were relatively low despite the surveys being short , well presented , and having utilised reminders . Conclusion Substantial variations in practice exist with awareness , use , and willingness to recommend methods varying substantially . The findings support the view that sample size calculation is a more complex process than would appear to be the case from trial reports and protocol s. Guidance on approaches for sample size estimation may increase both awareness and use of appropriate formal methods To test the impact of nasal dilator strips ( NDSs ) on insomnia severity , sleep-disordered breathing ( SDB ) symptoms , sleep quality , and quality of life . R and omized , controlled trial of 4 weeks ' duration . Community sample of nonobese , adults with a primary sleep complaint of chronic sleep-maintenance insomnia and mild to moderate SDB symptoms ( treatment , n=42 ; control , n=38 ) . Primary outcomes were four vali date d scales : Insomnia Severity Index ( ISI ) , Pittsburgh Sleep Quality Index ( PSQI ) , Functional Outcomes of Sleep Question naire ( FOSQ ) , and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . Secondary outcomes were sleep indices , nonrestorative sleep ratings , and SDB symptoms , assessed retrospectively and prospect ively . Both groups received nonspecific education about sleep disorders . Treatment group also received a brief SDB education and nasal strip instructions . At 4 weeks ' follow-up , the treatment group demonstrated significant ( p=.0001 ) , large improvements in ISI and PSQI ( mean Cohen 's d=1.18 ) and significant ( p<.02 ) , medium-sized improvements in FOSQ and QLESQ ( mean d=0.51 ) compared to small , nonsignificant changes in control group ( Cohen 's d range=0.36–0.09 ) . Treatment group change scores among all four primary variables were significantly correlated ( mean r=0.50 , p=0.01 ) . Secondary prospect i ve and retrospective outcomes showed medium to large improvements in treatment compared to controls for sleep indices ( mean d=0.52 vs 0.28 ) , nonrestorative sleep ratings ( mean d=0.69 vs 0.11 ) , and sleep breathing symptoms ( mean d=0.47 vs 0.09 ) . Significance was obtained for prospect i ve sleep indices ( p=0.01 ) , retrospective , and prospect i ve nonrestorative sleep ratings ( p=0.003 , < 0.05 ) , and retrospective sleep breathing symptoms ( p=0.03 ) . SDB education and NDSs demonstrated therapeutic efficacy in a select sample of insomnia patients with SDB symptoms . Replication of results requires placebo controls and objective ly confirmed SDB cases In the near future it is to be expected that many new inhaled corticosteroids or formulations of these drugs will be compared with older ones , to discover whether they are therapeutically equivalent or not . The statistical evaluation of these trials differs from the classic methods . When two averages are similar or differ only slightly , power is very low . The regulatory bodies dem and a power of at least 80 % . This problem was initially solved by using the so-called power approach . Research ers included enough volunteers to enable them to detect a predefined difference , considered to be without any clinical significance , with a power of 80 % . This approach , however , has been shown to be incorrect and has been replaced by the two one-sided tests procedure , where a new sample size equation is derived . Important elements of this new equation are the coefficient of variation of the parameter measured , the difference between the averages of the two groups and the equivalence limit ( the difference between the means still tolerable ) . This equation was used in the present study to estimate the number of volunteers needed in a parallel inhaled corticosteroids equivalence trial . The end points chosen were the changes in FEV1 and PC20 due to the corticosteroid effect . Calculations were performed by extracting data from published placebo-controlled trials , and defining a range of equivalence limits and differences between the group averages . It was shown that a huge number of volunteers ( 500–1000 ) will be needed , as a result of the small corticosteroid effect and the high variance . In the case of inhaled corticosteroids , the equivalence limit is not known and needs defining to avoid discussion s on the outcome . Due to the high number of patients who need to be included , the trial will most probably be multicentre and take place in several countries . Such a trial will suffer from several sources of bias . For instance , the definition of asthma can differ from country to country and from research er to research er , result ing in non-comparable groups of patients . The many sources of bias will make the outcome difficult to interpret . Therefore alternative methods to establish therapeutic equivalence are proposed and discussed Background This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t ™ , a question naire specifically design ed to measure patient-reported outcomes ( PRO ) associated with toenail onychomycosis . Methods 504 patients with toenail onychomycosis r and omized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD ® trial completed the OnyCOE-t ™ at baseline , weeks 6 , 12 , 24 , and 48 . The OnyCOE-t ™ is composed of 6 multi-item scales and 1 single-item scale . These include a 7-item Toenail Symptom assessment , which comprises both Symptom Frequency and Symptom Bothersomeness scales ; an 8-item Appearance Problems scale ; a 7-item Physical Activities Problems scale ; a 1-item Overall Problem scale ; a 7-item Stigma scale ; and a 3-item Treatment Satisfaction scale . In total , 33 toenail onychomycosis-specific items are included in the OnyCOE-t ™ . Clinical data , in particular the percent clearing of mycotic involvement in the target toenail , and OnyCOE-t ™ responses were used to evaluate the question naire 's reliability , validity , responsiveness , and the minimally clinical important difference ( MCID ) . Results The OnyCOE-t ™ was shown to be reliable and valid . Construct validity and known groups validity were acceptable . Internal consistency reliability of multi-item scales was demonstrated by Cronbach 's alpha > .84 . Responsiveness was good , with the Treatment Satisfaction , Symptom Frequency , Overall Problem , and Appearance Problem scales demonstrating the most responsiveness ( Guyatt 's statistic of 1.72 , 1.31 , 1.13 , and 1.11 , respectively ) . MCID was evaluated for three different clinical measures , and indicated that approximately an 8.5-point change ( on a 0 to 100 scale ) was clinical ly meaningful based on a 25 % improvement in target nail clearing . Conclusion The OnyCOE-t ™ question naire is a unique , toenail-specific PRO question naire that can be used with confidence in future studies of toenail onychomycosis . MCID was evaluated for three different clinical measures , and indicated that approximately a 7-point change ( on a 0 to 100 scale ) was clinical ly meaningful based on a 12.5 % improvement in target nail clearing PURPOSE To examine the responsiveness of the National Eye Institute Visual Function Question naire-25 ( NEI VFQ-25 ) by using data from the MARINA and ANCHOR trials in neovascular age-related macular degeneration ( AMD ) and to establish the change in the NEI VFQ-25 associated with a 15-letter change in best corrected visual acuity ( BCVA ) . METHODS In MARINA , 716 patients were r and omized to monthly intravitreal ranibizumab ( 0.3 or 0.5 mg ) or sham injections . In ANCHOR , 423 patients were r and omized to monthly ranibizumab ( 0.3 or 0.5 mg ) with sham photodynamic therapy ( PDT ) or sham ocular injections with verteporfin PDT . Patients had follow-up interviews and BCVA measurements over 24 months . Data were analyzed separately for MARINA and ANCHOR , and treatment groups were pooled within each trial . The clinical ly relevant difference in NEI VFQ-25 was estimated based on regression models of change from baseline to month 12 in BCVA . RESULTS Subgroups categorized by BCVA change ( > or=15 letters gained , < 15 letters lost or gained , or > or=15 letters lost ) differed substantially in mean change in NEI VFQ-25 composite scores and three pre-specified subscale scores ( near activities , distance activities , and vision-specific dependency ) over 12 months . According to the regression models , the difference associated with a 15-letter change was 4 to 6 points for the composite score and the three pre-specified subscales . CONCLUSIONS These data support the use of the NEI VFQ-25 as a responsive and sensitive measure of vision-related function in neovascular AMD population s. Based on MARINA and ANCHOR data , a 4- to 6-point change in NEI VFQ-25 scores represents a clinical ly meaningful change corresponding to a 15-letter change in BCVA UNLABELLED This study adopted a perspective of the individual to define domains of everyday life for the analysis of clinical ly meaningful change . The purpose was to compare the clinical significance of two interventions for patients with musculoskeletal pain , applying an idiographic outcome measure , The Patient Goal Priority Question naire , in combination with the Jacobson and Truax methodology [ ( 1991 ) . CLINICAL SIGNIFICANCE A statistical approach to defining meaningful change in psychotherapy research . Journal of Consulting and Clinical Psychology , 67 ( 3 ) , 300 - 307 ] for determination of clinical significance . The concurrent validity of the outcome variables behavioral performance , satisfaction with behavioral performance , and fulfilled pre-treatment expectations was also studied . Eighty-two patients , r and omized to either individually tailored behavioral medicine treatment ( experimental group ) or physical exercise therapy ( control group ) were evaluated at baseline and 3 months post-treatment regarding behavioral treatment goals . The experimental intervention had high impact on participants ' performance of their highest ranked everyday life activities , and result ed in larger proportions of clinical ly significant outcomes compared with controls . The concurrent validity of the outcomes was high for those reporting clinical ly significant changes , but more generally , there was a moderate agreement across outcome categories . The individual should be the unit for analyses of clinical significance to enhance the ecological validity of the construct . Further development of idiographic outcome measures is necessary , as is the inclusion in pain intervention research In this study , the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures , in order to identify the threshold where changes in clinical asthma measures are perceivable by patients . The study included 281 asthmatic patients , aged 18 - 63 yrs , in a r and omized , placebo-controlled clinical trial of a leukotriene antagonist . Changes were related in : 1 ) asthma symptom scores ; 2 ) inhaled beta-agonist use ; 3 ) forced expiratory volume in one second ( FEV1 ) ; and 4 ) peak expiratory flow ( PEF ) to a global question that queried overall change in asthma since starting the study drug . Additional analyses examined differences in the group reporting minimal improvement by treatment ( active treatment versus placebo ) , sex and age groups . The average minimal patient perceivable improvement for each measure was : 1 ) -0.31 points for the symptom score on a scale of 0 - 6 ; 2 ) -0.81 puffs x day(-1 ) for inhaled beta-agonist use ; 3 ) 0.23 L for FEV1 ; and 4 ) 18.79 L x min(-1 ) for PEF . In general placebo-treated patients and older patients , who reported minimal improvement , experienced less mean improvement from baseline than active-treated patients and younger patients , who reported minimal improvement . Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes . However , interpretation should be carried out cautiously when reporting a single value as a clinical ly important change Background Estimating a realistic effect size is an important issue in the planning of clinical studies of complementary and alternative medicine therapies . When a minimally important difference is not available , research ers may estimate effect size using the published literature . This evidence -based effect size estimation may be used to produce a range of empirically-informed effect size and consequent sample size estimates . We provide an illustration of deriving plausible effect size ranges for a study of acupuncture in the relief of post-chemotherapy fatigue in breast cancer patients . Methods A PubMed search identified three uncontrolled studies reporting the effect of acupuncture in relieving fatigue . A separate search identified five r and omized controlled trials ( RCTs ) with a wait-list control of breast cancer patients receiving st and ard care that reported data on fatigue . We use these published data to produce best , average , and worst-case effect size estimates and related sample size estimates for a trial of acupuncture in the relief of cancer-related fatigue relative to a wait-list control receiving st and ard care . Results Use of evidence -based effect size estimation to calculate sample size requirements for a study of acupuncture in relieving fatigue in breast cancer survivors relative to a wait-list control receiving st and ard care suggests that an adequately-powered phase III r and omized controlled trial comprised of two arms would require at least 101 subjects ( 52 per arm ) if a strong effect is assumed for acupuncture and 235 ( 118 per arm ) if a moderate effect is assumed . Conclusion Evidence -based effect size estimation helps justify assumptions in light of empirical evidence and can lead to more realistic sample size calculations , an outcome that would be of great benefit for the field of complementary and alternative medicine Objective . To evaluate patient opinions on acceptable risks in exchange for a given degree of weight loss and their implication s for sample size determination in obesity r and omized clinical trials ( RCTs ) . Design . Survey of patients entering RCTs for weight loss in a university-based clinical research setting and power calculations based on their responses . Participants . Men ( n = 8) and women ( n = 66 ) between 24 and 73 years of age with body mass indices ranging from 26.8 to 40.5 kg/m2 . Measurements . Survey responses to questions assessing the added risk of serious adverse events ( SAEs ) or death one is willing to assume for a given degree of weight loss . Results . For 5 % and 10 % weight loss against risk for death per se , the mean acceptable risk tended to be about 3.5 % , but the median ( 0.00 ) and mode ( 0.00 ) suggested that for most individuals , only a risk of ≤ 1 % would be acceptable . Figures , estimated dropout rates , and base rates of SAEs ( including deaths ) from recent obesity trials indicate that 1-year 2-group obesity RCTs would need tens of thous and s of participants per group to have 80 % power to detect risks that are meaningful to patients at the 2-tailed 0.05 α level . Conclusion . Patient education is needed to explain which risks are realistically detectable in RCTs so that patients may provide truly informed consent , or RCT st and ards should be modified to meet patients ’ implicit expectations OBJECTIVE To define the minimal clinical ly important difference ( MCID ) for the FIM instrument in patients poststroke . DESIGN Prospect i ve case series discharged over a 9-month period . SETTING Long-term acute care hospital . PARTICIPANTS Patients with stroke ( N=113 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Admission , discharge , and change scores were calculated for the total FIM , motor FIM , and cognitive FIM . Assessment s of clinical change were rated at discharge on a 15-point ( -7 to + 7 ) Likert scale by attending physicians , with MCID defined at a cutoff score of 3 . The FIM change scores associated with MCID were identified from receiver operating characteristic curves . Bayesian analysis was used to determine the probability of individual patients achieving MCID . RESULTS FIM change scores associated with MCID were 22 , 17 , and 3 for the total FIM , motor FIM , and cognitive FIM , respectively . The accuracy of the MCID was greater when subjects were categorized based on admission FIM scores than when considering the sample as a whole . Larger FIM change scores were related to MCID in subjects with lower admission FIM scores . CONCLUSIONS These findings will assist in the interpretation of FIM change scores relative to physicians ' assessment s of important clinical change PURPOSE We undertook a study to estimate the sufficiently important difference ( SID ) for the common cold . The SID is the smallest benefit that an intervention would require to justify costs and risks . METHODS Benefit-harm tradeoff interviews ( in-person and telephone ) assessed SID in terms of overall severity reduction using evidence -based simple- language scenarios for 4 common cold treatments : vitamin C , the herbal medicine echinacea , zinc lozenges , and the unlicensed antiviral pleconaril . RESULTS Response patterns to the 4 scenarios in the telephone and in-person sample s were not statistically distinguishable and were merged for most analyses . The scenario based on vitamin C led to a mean SID of 25 % ( 95 % confidence interval [ CI ] 0.23–0.27 ) . For the echinacea-based scenario , mean SID was 32 % ( 95 % CI , 0.30–0.34 ) . For the zinc-based scenario , mean SID was 47 % ( 95 % CI , 0.43–0.51 ) . The scenario based on preliminary antiviral trials provided a mean SID of 57 % ( 95 % CI , 0.53–0.61 ) . Multivariate analyses suggested that ( 1 ) between-scenario differences were substantive and reproducible in the 2 sample s , ( 2 ) presence or severity of illness did not predict SID , and ( 3 ) SID was not influenced by age , sex , tobacco use , ethnicity , income , or education . Despite consistencies supporting the model and methods , response patterns were diverse , with wide spreads of individual SID values within and among treatment scenarios . CONCLUSIONS Depending on treatment specifics , people want an on-average 25 % to 57 % reduction in overall illness severity to justify costs and risks of popular cold treatments . R and omized trial evidence does not support benefits this large . This model and these methods should be further developed for use in other disease entities PURPOSE The purpose of this analysis was to assess the impact of pretreatment factors on quality of life ( QOL ) in cancer patients . METHODS AND MATERIAL S Pretreatment QOL ( via Functional Assessment of Cancer Therapy [ FACT ] , version 2 ) was obtained in 1,428 patients in several prospect i ve Radiation Therapy Oncology Group ( RTOG ) trials including nonmetastatic head- and -neck ( n = 1139 ) , esophageal ( n = 174 ) , lung ( n = 51 ) , rectal ( n = 47 ) , and prostate ( n = 17 ) cancer patients . Clinical ly meaningful differences between groups were defined as a difference of 1 st and ard error of measurement ( SEM ) . RESULTS The mean FACT score for all patients was 86 ( 20.7 - 112 ) with SEM of 5.3 . Statistically significant differences in QOL were observed based on age , race , Karnofsky Performance Status , marital status , education level , income level , and employment status , but not by gender or primary site . Using the SEM , there were clinical ly meaningful differences between patients < /=50 years vs. > /=65 years . Hispanics had worse QOL than whites . FACT increased linearly with higher Karnofsky Performance Status and income levels . Married patients ( or live-in relationships ) had a better QOL than single , divorced , or widowed patients . College graduates had better QOL than those with less education . CONCLUSION Most pretreatment factors meaningfully influenced baseline QOL . The potentially devastating impact of a cancer diagnosis , particularly in young and minority patients , must be addressed OBJECTIVE To identify the minimal clinical ly important difference ( MCID ) for the Montgomery-Asberg Depression Rating Scale ( MADRS ) in r and omised studies of depression , and to cross-vali date the estimated MCID . DESIGN AND METHODS Placebo-treated patients from three similarly- design ed , 8-week , double-blind , r and omised depression trials with a stable health status between baseline and Week 1 ( ' no change ' rating on the Clinical Global Impression-Improvement scale ) were eligible . To calculate the MCID using the distribution-based approach , the st and ard deviation was estimated using baseline MADRS data while the reliability parameter was measured as the intraclass correlation coefficient between baseline and Week 1 . For cross-validation , patients from an observational study were matched to identify the ' MCID change ' ( MADRS change from baseline to endpoint score plus the estimated MCID ) and ' control ' groups . Comparisons of clinical and health-related quality of life measures were performed . RESULTS In total , 177 placebo-treated patients were identified . MCID estimates for MADRS ranged from 1.6 to 1.9 . A total of 105 matched pairs were identified for the cross-validation analyses . Mean change from baseline in MADRS scores ( 10.6 + /- 8.5 vs. 12.5 + /- 7.9 , p = 0.038 ) and remission rates ( 71.6 % vs. 57.1 % , p < 0.05 ) significantly differed between the ' MCID change ' and ' control ' groups at endpoint . Numerically higher response rates and greater improvements in HRQoL scores in the ' MCID change ' group were also found . CONCLUSION These preliminary findings support the value of the estimated MCID for the MADRS and may aid decision makers in evaluating antidepressant treatment effects and improving long-term patient outcomes BACKGROUND Vali date d health-related quality -of-life measures have become important st and ards in the evaluation of the outcomes of lumbar spine surgery . However , there are few well-defined criteria for clinical success based on these measures . The minimum clinical ly important difference is an important demarcation , but it could be considered a floor value rather than a goal in defining clinical success . Therefore , we sought to define thresholds of substantial clinical benefit for commonly used health-related quality -of-life measures following lumbar spine arthrodesis . METHODS Prospect ively collected preoperative and one-year postoperative health-related quality -of-life measures from 357 patients who were managed with lumbar spine arthrodesis for the treatment of degenerative conditions were identified . C and i date substantial clinical benefit thresholds for the Short Form-36 physical component score , Oswestry Disability Index , and back and leg pain numeric rating scales were identified with use of receiver operating characteristic curve analysis . Receiver operating characteristic curves were used to discriminate between patients who reported being " much better " or " about the same " with use of the vali date d Short Form-36 health transition item and between those who reported being " mostly satisfied " or " unsure " with use of a nonvali date d but more surgery-specific satisfaction-with- results survey . For each health-related quality -of-life measure , three response parameters were used : net change , percent change , and raw score at the time of the one-year follow-up . RESULTS Substantial clinical benefit thresholds for the Short Form-36 physical component score were a 6.2-point net improvement , a 19.4 % improvement , or a final raw score of > or = 35.1 points . Substantial clinical benefit thresholds for the Oswestry Disability Index were an 18.8-point net improvement , a 36.8 % improvement , or a final raw score of < 31.3 points . Substantial clinical benefit thresholds for the back pain and leg pain numeric rating scales were a 2.5-point net improvement or a final raw score of < 3.5 points . Substantial clinical benefit thresholds for percent change were 41.4 % for the back pain numeric rating scale and 38.8 % for the leg pain numeric rating scale . CONCLUSIONS We believe that thresholds of substantial clinical benefit for commonly used health-related quality -of-life measures following lumbar spine arthrodesis are important as they describe a magnitude of change that the patient recognizes as a major improvement Study Design . Prospect i ve , longitudinal cohort study Objective . To examine the validity of a threshold that has been used to define a successful outcome for patients with low back pain ( LBP ) , undergoing nonsurgical rehabilitation based on a 50 % improvement on the Modified Oswestry disability index ( ODI ) . Summary of Background Data . Making research findings interpretable is a goal of evidence -based practice . One attempt to improve interpretability is reporting treatment results as the percentage of patients achieving a threshold level of improvement within treatment groups along with mean between-group differences . The most recommended threshold is the minimum clinical ly important difference of the outcome tool . For clinical conditions with favorable natural histories such as LBP , thresholds requiring more than minimal improvement may be preferable for defining success . Methods . Patients with LBP receiving 4 weeks of physical therapy were examined . The ODI and measures of pain , fear-avoidance beliefs , and demographic characteristics were recorded at baseline and after treatment . A 15-point global rating of change was also completed after treatment . The percent ODI change with treatment was computed and compared between groups known to have different prognoses . The percent ODI change was compared to the global rating of change to determine the accuracy of various thresholds of success based on the percent ODI change . Results . A total of 243 subjects ( mean age 37.2 ± 11.4 years , 44.9 % female ) were included . Mean percent ODI change was 43.1 % ( ±40.5 ) , and 109 subjects ( 44.9 % ) had a successful outcome ( ≥50 % ODI improvement ) . As hypothesized , baseline factors with known prognostic importance were less likely to be present in subjects with a successful outcome . The 50 % ODI improvement threshold for success had high sensitivity ( 0.84 ; 95 % CI : 0.79 , 0.88 ) and specificity ( 0.89 ; 95 % CI : 0.85 , 0.93 ) when compared with success based on the global rating of change . No other percent improvement threshold for the ODI had a higher accuracy than the 50 % threshold when compared to the global rating of change . Conclusion . A threshold of 50 % improvement on the ODI may be a valid measure for defining a successful outcome for patients with LBP The original chronic respiratory question naire ( CRQ ) , one of the most widely used measures of health-related quality of life ( HRQL ) in chronic respiratory disease ( CRD ) , is traditionally interviewer administered ( IA ) and includes an individualised dyspnoea domain . The present authors studied the impact of self-administered ( SA ) and st and ardised dyspnoea questions on CRQ measurement properties . In a factorial design multicentre trial , 177 patients with CRD ( mean age 67.7 yrs ; mean forced expiratory volume in one second per cent predicted 44.6 % ) were r and omised to CRQ-IA ( n = 86 ) or CRQ-SA ( n = 91 ) , and to initially complete the st and ardised or individualised items before and after respiratory rehabilitation . While maintaining validity , the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains . Compared with the st and ardised dyspnoea domain , the individualised dyspnoea domain indicated greater responsiveness . The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA . In conclusion , self-administration and st and ardisation of the chronic respiratory question naire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory question naire . These results challenge the assumption that interviewer-administered question naires are superior to self-administered question naires in older patients with chronic respiratory disease Outcome scores are very useful tools in the field of spinal surgery as they allow us to assess a patient ’s progress and the effect of various treatments . The clinical importance of a score change is not so clear . Although previous studies have looked at the minimum clinical ly important score change , the degree of score change varies considerably . Our study is a prospect i ve cohort study of 193 patients undergoing discectomy , decompression and fusion procedures with minimum 2-year follow-up . We have used three st and ard outcome measures in common usage , the oswestry disability index ( ODI ) , the low back outcome score ( LBOS ) and the visual analogue score ( VAS ) . We have defined each of these scores according to a global measure of outcome grade d by the patient as excellent , good , fair or poor . We have also grade d patient perception and classified excellent and good as success and fair and poor as failure . Our results suggest that a median 24-point change in the ODI equates with a good outcome or is the minimum change needed for success . We have also found that different surgical disorders have very different minimal clinical ly important differences as perceived by patient perception . We found that for a discectomy a minimum 27-point change in the ODI would be classed as a success , for a decompression the change in ODI needed to class it as a success would be 16 points , whereas for a fusion the change in the ODI would be only 13 points . We believe that patient-rated global measures of outcome are of value and we have quantified them in terms of the st and ard outcome measures used in spinal surgery BACKGROUND Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes , whether or not a treatment has delivered a specified minimum clinical ly important difference ( MCID ) is also relevant to patients and their caregivers and doctors . Many dementia treatment r and omised controlled trials ( RCTs ) have not reported MCIDs and , where they have been done , observed differences have not reached these . METHODS As part of the development of the Statistical Analysis Plan for the DOMINO trial , investigators met to consider expert opinion- and distribution-based values for the MCID and triangulated these to provide appropriate values for three outcome measures , the St and ardised Mini-mental State Examination ( sMMSE ) , Bristol Activities of Daily Living Scale ( BADLS ) and Neuropsychiatric Inventory ( NPI ) . Only st and ard deviations ( SD ) were presented to investigators who remained blind to treatment allocation . RESULTS Adoption of values for MCIDs based upon 0.4 of the SD of the change in score from baseline on the sMMSE , BADLS and NPI in the first 127 participants to complete DOMINO yielded MCIDs of 1.4 points for sMMSE , 3.5 for BADLS and 8.0 for NPI . CONCLUSIONS Reference to MCIDs is important for the full interpretation of the results of dementia trials and those conducting such trials should be open about the way in which they have determined and chosen their values for the MCIDs OBJECTIVES To assess the feasibility , validity and responsiveness of an individualized measure-- goal attainment scaling-in long-term care . DESIGN Prospect i ve descriptive study . SETTING One academic and three community-based long-term care facilities . SUBJECTS 53 nursing-home patients seen in consultation between July 1996 and June 1997 . INTERVENTION Specialized geriatric medicine consultation . MAIN OUTCOME MEASURES Effect size and relative efficiency of the Barthel index , hierarchical assessment of balance and mobility , global deterioration scale , axis 8 ( behaviour ) of the brief cognitive rating scale , cumulative illness rating scale and the goal attainment scale . RESULTS Mean goal attainment scale at follow-up was 46+/-7 . The goal attainment scale was the most responsive measure , with an effect size of 1.29 and a relative efficiency of 53.7 . The goal attainment scale did not correlate well with the other measures ( -0.22 to 0.17 ) . CONCLUSION Goal attainment scaling is a feasible and responsive measure in long-term care . Although fewer problems in nursing-home patients than elderly in patients are susceptible to intervention , clinical ly important goals can be achieved in this population OBJECTIVE To evaluate reliability , validity and responsiveness of the Fear-Avoidance Beliefs Question naire ( FABQ ) for use in Norwegian patients with low back pain . DESIGN A prospect i ve cohort study with 2 groups . PATIENTS The question naire was tested in 123 patients with acute low back pain and 50 patients with chronic low back pain . METHODS A translation and cross-cultural adaptation was performed . Test-retest reliability was assessed in 28 patients with chronic low back pain . Responsiveness was assessed in acute low back pain . RESULTS Two factors for the FABQ were confirmed ; fear-avoidance beliefs about work ( FABQ-Work ) and physical activity ( FABQ-PA ) , accounting for 60 % and 54 % of the total variance in acute and chronic low back pain , respectively . For FABQ-Work and FABQ-PA internal consistency was 0.90 and 0.79 , intra-class correlation coefficients 0.82 and 0.66 , minimal detectable changes 12 and 9 points , and coefficients of variation were 16 % and 23 % . The FABQ correlated weakly to moderately with pain , disability , distress , and clinical variables . St and ardized response means were low for FABQ-Work ( 0.32 ) and moderate ( 0.56 ) for FABQ-PA . Both FABQ subscales showed initially floor and /or ceiling effects . CONCLUSION The Norwegian FABQ version had acceptable factor structure , internal consistency , test-retest reliability and construct validity . The responsiveness of the FABQ-Work was low , and for the FABQ-PA moderate , in the acute sample As the data for economic analyses are increasingly collected prospect ively alongside clinical trials , many commentators have highlighted that the sample sizes in such trials should be based on the requirements for the economic analysis as well as those for the clinical evaluation . However , issues associated with sample size calculations for economic analysis have yet to receive the rigorous attention given to sample size calculation for clinical evaluation . In particular , no sample size formula for cost-ef fectiveness analysis is available for analysts hoping either to calculate the required sample size at the design stage of a study or to calculate the power a given size of clinical trial will generate for cost-effectiveness analysis . Building on the recent liter ature for calculating confidence intervals for cost-effectiveness ratios , the authors ex plore possible techniques for deriving a sample size formula for cost-effectiveness analysis based on simple combination of the confidence limits on costs and effects . Key words : cost-effectiveness ; economic analysis ; sample size ; methodology . ( Med Decis Making 1998;18 suppl : S81-S92 Bloom LF , Lapierre NM , Wilson KG , Curran D , DeForge DA , Blackmer J : Concordance in goal setting between patients with multiple sclerosis and their rehabilitation team . Am J Med Phys Rehabil 2006;85:807–813 . Objective : To determine the concordance between patients with multiple sclerosis and their clinical team members on the identification of goals for an inpatient rehabilitation stay . Design : Prospect i ve cohort study of patients admitted for rehabilitation in an adult inpatient neurospinal unit at a Rehabilitation Centre in Ottawa , Canada . Twenty-seven patients ( 11 men and 16 women , mean age of 45.3 yrs ) with either a laboratory or a clinical ly supported diagnosis of multiple sclerosis . Patients rated 55 goals from a preexisting list , indicating the importance of each goal to be addressed during the inpatient stay . The goals fell into five broad domains of health/medical issues , daily activities , mobility , community life , and personal well-being . Patients also identified their five most important individual goals . In a separate session , the clinical team also rated the 55 goals in relation to each patient and identified an independent list of the five most important rehabilitation goals . Main outcome measures included concordance between patient and team ratings in the identification of goals , ratings of the likelihood of success of achieving each goal , and ratings of the amount of change required to realize a minimal clinical ly important difference . Results : The patients and the team agreed on an average of 1.7 of the patient 's five top-rated goals . Compared with the team , patients gave higher importance ratings to goals within the health/medical , mobility , and daily activities domains . They also considered that a greater average improvement would be required to achieve a meaningful benefit , and they gave higher ratings of the likelihood of success in achieving their selected goals . Conclusion : Patients with multiple sclerosis and clinical team members do not necessarily agree on specific goals for a rehabilitation stay . Patients may also have greater expectations than clinicians with respect to the amount of improvement and the likelihood of achieving their goals Background . It is generally agreed that r and omized controlled trials should be powered to detect small but clinical ly significant treatment effects . Toward these ends , minimal important difference ( MID ) was proposed as a benchmark for design ing trials and for interpreting health-related quality -of-life instrument scores . MID was defined in 1989 as “ the smallest difference in score in the domain of interest which patients perceive as beneficial and which would m and ate , in the absence of troubling side effects and excessive cost , a change in the patient ’s management . ” Objective . 1 ) To exp and the idea of minimal clinical ly important difference so as to take into account harms as well as benefits . 2 ) To propose concepts and methods with which to do so . Summary . The authors define sufficiently important difference ( SID ) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs , risks , and other harms . As a means toward estimation of SID , the authors propose benefit-harm tradeoff methods , in which domains of benefit and harm are systematic ally traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile . Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and /or public health policy . This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID Background : Comparative responsiveness data are needed to inform choices about pain outcome measures . Objectives : To compare responsiveness of pain intensity , pain-related function , and composite measures , using data from a r and omized trial and observational study . Research Design : Analysis of responsiveness . Subjects : A total of 427 adults with persistent back , hip , or knee pain were recruited from primary care . Methods : Participants completed Brief Pain Inventory , Chronic Pain Grade ( CPG ) , Rol and disability , SF-36 bodily pain , and pain global rating of change measures . We used the global rating as the anchor for st and ardized response mean and receiver operating characteristic curve analyses . We used the distribution-based st and ard error of measurement to estimate minimally important change . To assess responsiveness to the trial intervention , we evaluated st and ardized effect size statistics stratified by trial arm . Results : All measures were responsive to global improvement and all had fair-to-good accuracy in discriminating between participants with and without improvement . SF bodily pain was less responsive than other measures in several analyses . The 3-item PEG was similarly responsive to full Brief Pain Inventory scales . CPG and SF bodily pain were less responsive to the trial intervention and did not perform well among participants with hip/knee pain . Agreement between anchor and distribution-based methods was modest . Conclusions : If a brief measure is desired , the 3-item PEG is more responsive than the SF bodily pain scale . CPG and SF bodily pain scales may be relatively poor choices for trial outcome assessment . Both anchor and distribution-based methods should be considered when determining clinical ly important change Background Traditional sample size calculations for r and omized clinical trials depend on somewhat arbitrarily chosen factors , such as type I and II errors . As an alternative , taking a societal perspective , and using the expected value of information based on Bayesian decision theory , a number of authors have recently shown how to determine the sample size that maximizes the expected net gain , i.e. , the difference between the cost of the trial and the value of the information gained from the results . Other authors have proposed Bayesian methods to determine sample sizes from an industry perspective . Purpose The purpose of this article is to propose a Bayesian approach to sample size calculations from an industry perspective that attempts to determine the sample size that maximizes expected profit . Methods A model is proposed for expected total profit that includes consideration of per-patient profit , disease incidence , time horizon , trial duration , market share , discount rate , and the relationship between the results and the probability of regulatory approval . The expected value of information provided by trial data is related to the increase in expected profit from increasing the probability of regulatory approval . The methods are applied to an example , including an examination of robustness . The model is extended to consider market share as a function of observed treatment effect . Results The use of methods based on the expected value of information can provide , from an industry perspective , robust sample size solutions that maximize the difference between the expected cost of the trial and the expected value of information gained from the results . Limitations The method is only as good as the model for expected total profit . Although the model probably has all the right elements , it assumes that market share , per-patient profit , and incidence are insensitive to trial results . The method relies on the central limit theorem which assumes that the sample sizes involved ensure that the relevant test statistics are normally distributed . Conclusions Industry officials should consider the use of expected value of information methods for determining sample sizes for proposed trials . The method also can be used to select , from a number of proposed trials , those which maximize return from a fixed research budget |
12,592 | 12,900,095 | Some patterns emerged between level of anxiety and characteristics of the decision .
As raised levels of anxiety are associated with both more effective decision strategies and stressful health interventions , anxiety is an inappropriate measure to employ when evaluating decision aids . | Several trials have employed anxiety measures to assess decision aid effectiveness .
This study employed a systematic review method to integrate their findings .
The affective impact of decision aids and the appropriateness of anxiety as a measure of decision aid effectiveness are explored . | Abstrac Objective : To test the effect of extra non-directive information about prenatal testing , given individually or in a class . Setting : Antenatal clinics in a district general hospital and a university hospital . Design : R and omised controlled trial ; participants allocated to control group or offer of extra information individually or in class . Subjects : 1691 women booking antenatal care before 15 weeks ' gestation . Interventions : All participants received the usual information about prenatal tests from hospital staff . Individual participants were offered a separate session with a research midwife in which prenatal screening was described in detail . Class participants were offered the same extra information in an early prenatal class . Main outcome measures : Attendance at extra information sessions ; uptake rates of prenatal tests ; levels of anxiety , underst and ing , and satisfaction with decisions . Results : Attendance at classes was lower than at individual sessions ( adjusted odds ratio 0.45 ; 95 % confidence interval 0.35 to 0.58 ) . Ultrasonography was almost universally accepted ( 99 % ) and was not affected by either intervention . Uptake of cystic fibrosis testing , high in controls ( 79 % ) , was lowered in the individual group ( 0.44 ; 0.20 to 0.97 ) and classes ( 0.39 ; 0.18 to 0.86 ) . Uptake of screening for Down 's syndrome , already low ( 34 % ) in controls , was not further depressed by extra information in classes ( 0.99 ; 0.70 to 1.39 ) and was slightly higher in the individual group ( 1.45 ; 1.04 to 2.02 ) . Women offered extra information had improved underst and ing and were more satisfied with information received ; satisfaction with decisions about prenatal testing was unchanged . The offer of individual information reduced anxiety later in pregnancy . Conclusions : Ultrasonography is valued for non-medical reasons and chosen even by fully informed people who eschew prenatal diagnosis . The offer of extra information has no overall adverse effects on anxiety and reduces uptake of blood tests when background uptake rate is high ( but not when it is already low ) . High uptake of prenatal blood tests suggests compliant behaviour and need for more information The purpose of this study was to determine if providing men with information about screening for prostate cancer would enable them to assume a more active role in decision making with their family physician , and lower levels of anxiety and decisional conflict . Men were recruited from one family medical clinic in Winnipeg , Manitoba . One hundred men scheduled for a periodic health examination ( PHE ) were r and omly assigned to receive verbal and written information either prior to the PHE , or following the second interview . Men completed measures of preferred decisional role and anxiety prior to the PHE ; and assumed decisional role , decisional conflict , and anxiety post PHE . Results demonstrated that men who received the information prior to the PHE assumed a significantly more active role in making a screening decision , and had lower levels of decisional conflict post PHE . The two groups did not differ with regard to levels of state anxiety . Providing men with information enables them to make informed screening decisions with their family physicians Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with " decisional confidence , " and least with " desire to participate in health care de cisions " and " satisfaction with provider " The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64 A r and omised-controlled trial compared outcomes for women recently diagnosed with breast cancer who either received support and information from a multidisciplinary team or used a shared decision-making programme on an interactive video disk ( IVD ) system . Using the IVD did not have a significant effect on the decisions women made about treatment , yet it was evaluated positively by those who used it . The results suggest that the role of clinical staff is more significant than the form of information provided . Potential benefits for the IVD were apparent such as st and ardising the information received by patients , promoting evidence -based practice and providing a measure for quality assurance Abstract Objective : To determine whether a decision aid on benign prostatic hypertrophy influences decision making , health outcomes , and re source use . Design : R and omised controlled trial . Setting : 33 general practice s in the United Kingdom . Participants : 112 men with benign prostatic hypertrophy . Intervention : Patients ' decision aid consisting of an interactive multimedia programme with booklet and printed summary . Outcome measures : Patients ' and general practitioners ' perceptions of who made the decision , decisional conflict scores , treatment choice and prostatectomy rate , American Urological Association symptom scale , costs , anxiety , utility , and general health status . Results : Both patients and general practitioners found the decision aid acceptable . A higher proportion of patients ( 32 % v 4 % ; mean difference 28 % , 95 % confidence interval 14 % to 41 % ) and their general practitioners ( 46 % v 25 % ; 21 % , 3 % to 40 % ) perceived that treatment decisions had been made mainly or only by patients in the intervention group compared with the control group . Patients in the intervention group had significantly lower decisional conflict scores than those in the control group at three months ( 2.3 v 2.6 ; −0.3 , −0.5 to −0.1 , P<0.01 ) and this was maintained at nine months . No differences were found between the groups for anxiety , general health status , prostatic symptoms , utility , or costs ( excluding costs associated with the video disc equipment ) . Conclusions : The decision aid reduced decisional conflict in men with benign prostatic hypertrophy , and the patients played a more active part in decision making . Such programmes could be delivered cheaply by the internet , and there are good arguments for coordinated investment in them , particularly for conditions in which patient utilities are important . What is already known on this topic Patients want more information about their condition and treatment options , and many want to play an active part in decision making Decision aids improve patients ' knowledge of their conditions and treatment options What this study adds The decision aid was highly acceptable to both the patients and their general practitioners Decisional conflict was reduced in the intervention group Patients who viewed the programme played a more active part in the decision making process and were less anxious than control patients Such aids could be introduced throughout the NHS at relatively low cost by using the Abstract Objective : To determine whether a decision aid on hormone replacement therapy influences decision making and health outcomes . Design : R and omised controlled trial . Setting : 26 general practice s in the United Kingdom . Participants : 205 women considering hormone replacement therapy . Intervention : Patients ' decision aid consisting of an interactive multimedia programme with booklet and printed summary . Outcome measures : Patients ' and general practitioners ' perceptions of who made the decision , decisional conflict , treatment choice , menopausal symptoms , costs , anxiety , and general health status . Results : Both patients and general practitioners found the decision aid acceptable . At three months , mean scores for decisional conflict were significantly lower in the intervention group than in the control group ( 2.5 v 2.8 ; mean difference −0.3 , 95 % confidence interval −0.5 to −0.2 ) ; this difference was maintained during follow up . A higher proportion of general practitioners perceived that treatment decisions had been made “ mainly or only ” by the patient in the intervention group than in the control group ( 55 % v 31 % ; 24 % , 8 % to 40 % ) . At three months a lower proportion of women in the intervention group than in the control group were undecided about treatment ( 14 % v 26 % ; −12 % , −23 % to −0.4 % ) , and a higher proportion had decided against hormone replacement therapy ( 46 % v 32 % ; 14 % , 1 % to 28 % ) ; these differences were no longer apparent by nine months . No differences were found between the groups for anxiety , use of health service re sources , general health status , or utility . The higher costs of the intervention were largely due to the video disc technology used . Conclusions : An interactive multimedia decision aid in the NHS would be popular with patients , reduce decisional conflict , and let patients play a more active part in decision making without increasing anxiety . The use of web based technology would reduce the cost of the intervention . What is already known on this topic Patients want more information about their conditions and treatment options , and many want to play an active part in decision making Decision aids improve patients ' knowledge of their conditions and treatment options What this study adds The decision aid was acceptable to both the patients and their general practitioners Decisional conflict was reduced in the intervention group Patients who viewed the programme played a more active part in the decision making process and were no more anxious than control patients Such aids could be introduced throughout the NHS at relatively low cost by using the Decision aids help patients make treatment choices . There is little empirical evidence to explain how they work . The results from this r and omised controlled trial comparing routine with decision-aided consultations in the prenatal diagnosis for Down 's syndrome context are used to describe the strategies employed during decision making , to assess the impact of a decision aid on decision processes , and to investigate decision process and outcome associations . Data were elicited from two content analyses of consultation transcripts and question naires assessing knowledge , anxiety , decisional conflict , reasons , and information usefulness . 68/106 women completed measures at consultation and follow-up . Decision-aided women employed more cognitive and emotional strategies during decision making . More negative evaluations during decision making were associated with better outcomes . Decision-aided consultations facilitated the employment of strategies associated with more effective choices . These consultations take longer and elicit greater expressions of negative affect , so may be less rewarding encounters for health professionals A decision aid for the surgical treatment of early breast cancer was evaluated in a r and omized controlled trial . The decision aid , a tape and workbook , includes explicit presentation of probabilities , photographs and graphics , and a values clarification exercise . Community surgeons were r and omized to use the decision aid or a control pamphlet . Patients completed a question naire prior to using the decision aid , after review ing it but prior to surgery , and 6 months after enrollment . There was no difference in anxiety , knowledge , or decisional regret across the 2 groups . There was a nonsignificant trend toward lower decisional conflict in the decision aid group . A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict . Although the decision aid had minimal impact on the main study outcomes , a subgroup may have benefited . Such subgroups should be identified , and appropriate decision support interventions should be developed and evaluated The purpose of this study was to explore the hypothesis that assisting men with prostate cancer to obtain information would enable them to assume a more active role in treatment decision making and decrease their levels of anxiety and depression . Respondents were recruited from one community urology clinic in Winnipeg , Manitoba . Sixty newly diagnosed men were r and omly assigned to receive either a self-efficacy information intervention that consisted of a written information package with discussion , a list of questions they could ask their physician , and an audiotape of the medical consultation ( n = 30 ) , or a written information package alone ( n = 30 ) . Men completed measures of preferred decisional role as the pretest ; anxiety and depression before the intervention , and at 6 weeks post-intervention ; and assumed decisional role at 6 weeks post-intervention . Results demonstrated that men in the intervention group assumed a significantly more active role in treatment decision making , and had lower state anxiety levels at 6 weeks . Levels of depression were similar for both groups at 6 weeks . This group of older men do want to be informed and participate in medical decisions . Further efforts are required to evaluate the efficacy of such an intervention in other community urology clinics |
12,593 | 27,790,783 | No consistent reports were found for c and i date gene studies of LTMs .
In c and i date gene studies of ICS , the most consistent results were found for rs28364072 in FCER2 .
AND CLINICAL RELEVANCE There is a lack of replication of genetic variants associated with poor ICS or LTM response .
The most consistent results were found for the FCER2 gene [ encoding for a low-affinity IgE receptor ( CD23 ) ] and poor ICS response . | BACKGROUND Pharmacogenetics studies of anti-inflammatory medication of asthma have exp and ed rapidly in recent decades , but the clinical value of their findings remains limited .
OBJECTIVE To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids ( ICS ) and leukotriene modifiers ( LTMs ) in patients with asthma . | CysLT(1 ) antagonists are effective for a subset of patients with asthma ; however , there has been no good way to predict a given patient 's response . We examined the interaction between the clinical response to a cysLT(1 ) antagonist , pranlukast , and DNA sequence variant A(-444)C in leukotriene C(4 ) synthase ( LTC(4 ) S ) gene in Japanese patients with moderate asthma . The frequency of LTC(4 ) S C(-444 ) allele was 21.6 % in the Japanese general population ( n = 171 ) and 19.4 % in the asthmatic subjects ( n= 349 ) . A 4-week prospect i ve , open trial of pranlukast ( 225 mg twice daily ) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid ( beclomethasone 400 - 800 microg/day or fluticasone 200 - 400 microg/day ) . The C(-444 ) allele carriers ( n = 16 ) responded better to pranlukast compared to the A(-444 ) allele homozygotes ( n= 31 ) [ 14.3 5.3 % vs. 3.1 2.4 % improvement of forced expiratory volume in one second ( FEV(1 ) ) , 0.01 ] , while LTC(4 ) S genotype-stratified response to inhaled beta-agonist salbutamol ( 200 microg ) was not observed ( 17.5 2.1 % vs. 18.7 2.2 % improvement of FEV(1 ) ) . Univariate analysis demonstrated that the better response to pranlukast ( more than 10 % improvement of FEV(1 ) ) was correlated with LTC(4 ) S genotype ( P < 0.01 ) and pretreatment airway reversibility to salbutamol ( P < 0.01 ) , but not with sex , age , atopic status , urinary leukotriene E(4 ) excretion rate , or daily dose of inhaled corticosteroid . Furthermore , multivariate regression analysis suggested that LTC(4 ) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast ( P < 0.05 ) . We conclude that LTC(4 ) S genotype is predictive of the clinical response to a cysLT(1 ) antagonist , pranlukast , in Japanese patients with moderate asthma The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability . The goal of the present study was to identify novel variants that associate with response to common asthma controllers : fluticasone , combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms ( SNPs ) in β2-adrenergic receptor , corticosteroid and leukotriene pathway c and i date genes . Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study . A total of 169 SNPs in 26 c and i date genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone ( 100 μg bid ) , fluticasone propionate ( 100 μg ) + salmeterol ( 50 μg ) ( FP/Salm ) or montelukast ( 5 or 10 mg ) each night for 16 weeks . Primary outcomes were the slopes of plots of Asthma Control Question naire ( ACQ ) scores versus time following r and omization ; and the percent change in percent predicted FEV1 ( ΔFEV1%pred ) from enrollment to the end of the study . Associations between SNPs and outcomes were analyzed using general linear models . False discovery rate and Bonferroni corrections were used to correct for multiple comparisons . In all , 16 SNPs in seven genes were significantly associated with outcomes . For FP/Salm , three SNPs in CHRM2 associated with ACQ slope ( P=2.8 × 10−5 ) , and rs1461496 in HSPA8 associated with ΔFEV1%pred . For fluticasone , five SNPs in CRHR1 ( P=1.9 × 10−4 ) , and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred , respectively . For montelukast , four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone ( P=9 × 10−3 ) . The present study indentified several novel SNPs that associate with response to common asthma controllers , and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment Objective Interindividual clinical response to leukotriene modifiers is highly variable , and less efficacious than inhaled corticosteroids in treating asthma . Genetic variability in 5-lipoxygenase biosynthetic and receptor pathway gene loci may influence cysteinyl-leukotriene production and subsequent response to leukotriene modifiers . Methods Using data from two clinical trials of 12-week duration , post-hoc analyses were performed in 174 patients r and omized to montelukast . Associations between polymorphisms in 10 c and i date genes ( ALOX5 , ALOX5AP , LTC4S , CYSLTR1 , CYSLTR2 , PLA2G4A , CYP2C9 , CYP3A4 , ADRB2 , and NR3C1 ) and response to montelukast were modeled using change in morning peak expiratory flow and forced expiratory volume in 1 s ( FEV1 ) to define the response phenotype . Results In our sample , eight out of 25 markers in 10 c and i date genes were statistically associated with response to montelukast , with an estimated proportion of false discoveries of 16 % . The strongest statistical evidence of clinical ly relevant pharmacogenetic effects peak expiratory flow were identified in CYSLTR2 ( rs91227 and rs912278 ; P=0.02 and P=0.02 , respectively ) and ALOX5 ( rs4987105 and rs4986832 ; P=0.01 and P=0.01 , respectively ) . Patients with these variant genotypes , found in roughly 10–13 % of patients , had an 18–25 % improvement in peak expiratory flow . In contrast , the majority of patients with the wild-type alleles had only a marginal ( 8–10 % ) improvement . Conclusions The overall mean response to montelukast may be skewed towards a response phenotype by a small subset ( < 15 % ) of asthma patients . CYSLTR2 and ALOX5 polymorphisms may predispose a minority of individuals to excessive cysteinyl-leukotriene concentrations , yielding a distinct asthma phenotype most likely to respond to leukotriene modifier pharmacotherapy . These findings require replication to establish validity and clinical utility For patients with persistent asthma , the National Asthma Education and Prevention Program recommends the regular use of controller medications to provide long-term control , together with as-needed use of rescue medications ( 1 ) . Inhaled corticosteroids are currently the most commonly used controller medications ( 1 ) . Although inhalation into the airway has advantages in terms of both safety and efficacy , problems with compliance with inhaled agents may limit their real-world effectiveness , especially in elderly and pediatric patients ( 2 , 3 ) . Cysteinyl leukotrienes are important pro-inflammatory mediators of asthma ( 4 ) . Recent clinical studies of leukotriene receptor antagonists ( 5 - 7 ) and a 5-lipoxygenase inhibitor ( 8) have shown these agents to have clinical benefit in patients with chronic asthma , and treatment guidelines now consider these agents alternative , first-line controller medications ( 1 ) . Recent studies showed that montelukast , a potent and specific leukotriene receptor antagonist ( 9 ) , had efficacy in adult ( over a 12-week period ) and pediatric ( over an 8-week period ) patient with chronic asthma and had a tolerability profile similar to that of placebo ( 10 - 12 ) . To date , no comparisons of leukotriene receptor antagonists and inhaled corticosteroids have been published . Our placebo-controlled , parallel-group study , which was primarily design ed to compare the effect of montelukast with that of placebo in a phase III clinical development trial , also compared montelukast and inhaled beclomethasone in patients with chronic asthma who require the daily use of a controller medication . Methods Patients Healthy , nonsmoking , male and female patients 15 years of age and older were eligible to participate if they had had asthma for at least 1 year before the initial study evaluation . Each patient also had to have 1 ) an FEV1 between 50 % and 85 % of predicted value , 2 ) an increase of at least 15 % in absolute FEV1 after the use of inhaled -agonist on at least two of three visits during period 1 [ see below ] , 3 ) a daytime asthma symptom score of at least 64 [ of a possible 336 ] , and 4 ) average daily use of at least one puff of as-needed , short-acting , inhaled -agonist ( salbutamol ) . Patients were excluded from the study if they had used inhaled and oral corticosteroids , cromolyn , or nedocromil within 4 weeks before the initial evaluation ; had used long-acting -agonists , antimuscarinics , and newly instituted theophylline within 2 weeks before the initial evaluation ; or had used long-acting antihistamines ( for example , they could not have used astemizole within 3 months of the initial evaluation , and they could not have used terfenadine or loratadine within 2 weeks of the initial evaluation ) . Intermittent use of short-acting antihistamines was allowed , and immunotherapy was permitted if it had been started at least 6 months before the initial study evaluation and if the monthly dose remained constant . Protocol Our r and omized , double-dummy , placebo-controlled , parallel-group trial had a 2-week , single-blind placebo run-in period ( period 1 ) ; a 12-week , double-blind treatment period ( period 2 ) ; and a 3-week , double-blind placebo washout period [ period 3 ] . Eligible patients were r and omly assigned to one of three treatment regimens : 1 ) montelukast , 10 mg once daily in the evening ; 2 ) inhaled beclomethasone , 200 g twice daily ; or 3 ) placebo . The ratio of montelukast recipients to beclomethasone recipients to placebo recipients was 3:2:2 , with a blocking factor of 7 , according to a single , computer-generated allocation schedule . Patients , investigators , and coordinating center staff were blinded to the treatment schedule until all corrections to the data base were completed . During period 3 , a subset of patients originally assigned to receive active treatment ( approximately 40 , as determined by the allocation schedule ) was switched to placebo in a blinded manner . The other patients originally assigned to receive active treatment continued to receive that treatment . This allowed us to assess withdrawal from therapy . The study was done at 36 clinical centers in 19 countries in Europe , Africa , Australia , Central America , and South America . The study protocol and informed consent were approved by local ethics review committees . All participants gave written informed consent before participation ; consent of parents or guardians was obtained for patients younger than 18 years of age . Patients were recruited from the patient pool of each clinical study center and through local newspaper advertisements . Medication The study medication consisted of 10-mg montelukast film-coated tablets , placebo tablets that were identical in appearance to the montelukast tablets , beclomethasone ( 100 g/puff ) in inhalers ( Allen & Hanburys , Stockley Park , United Kingdom ) , and placebo in inhalers identical to those used for beclomethasone . Patients were instructed to take one tablet at bedtime and to take two puffs from the inhaler ( using the AeroChamber spacer device [ Clement Clark , Columbus , Ohio ] ) at bedtime and in the morning . Short-acting , inhaled -agonist ( salbutamol , 100 g/puff ) ( Allen & Hanburys ) was to be used as needed . Patients with worsening episodes of asthma that required additional therapy were treated with oral corticosteroids according to a st and ard protocol . Patients who had more than two worsening episodes of asthma requiring corticosteroid therapy were dropped from the study . Measurements Central ized spirometry training was done according to st and ard American Thoracic Society criteria before the start of the study . Spirometry was done at each visit after inhaled -agonist therapy had been withheld for at least 6 hours , theophylline therapy had been withheld for at least 24 hours , and antihistamine therapy had been withheld for at least 48 hours . At least three spirometry maneuvers were done , and the largest FEV1 was reported . Spirometry data were transmitted electronically to a central data base and monitored continuously for quality , and feedback was given to the study centers ( 13 ) . If quality was not maintained , sites were visited by coordinating center personnel . Answers to four questions on daytime asthma symptoms and one question on nocturnal awakenings were collected on a daily diary card , as were morning and evening peak expiratory flow rate and daily use of as-needed salbutamol . With respect to daytime asthma symptoms , patients used a 7-point scale ( on which 0 means best and 6 means worst ) to rate the severity of symptoms , their frequency , the degree to which they were bothersome , and their impact on daily activities . These ratings were combined into a mean daily score . Nocturnal awakenings were evaluated by the patient 's response ( on a four-point scale ) to a single question ( 14 ) . The validation of these questions has been published elsewhere ( 14 ) . Peak expiratory flow was measured in the morning and in the evening immediately before study medication was taken . The best of three measurements was recorded . Prespecified end points other than peak expiratory flow included peripheral blood eosinophil counts , global evaluations by physicians and patients ( on a 7-point scale , on which 6 means very much worse and 0 means very much better ) ( 7 ) , and asthma-specific quality of life ( 15 ) . Asthma outcome end points , including asthma attacks ( defined as worsening asthma requiring oral corticosteroid treatment or an unscheduled visit to a physician , emergency department , or hospital ) , percentage of days with asthma exacerbations , and percentage of asthma-control days ( as defined elsewhere [ 11 , 16 ] ) , were also evaluated . The diary card , the Asthma Quality -of-Life Question naire ( 15 ) , and the global evaluation questions were translated from English into appropriate local language s and were vali date d for linguistic equivalence and cultural differences ( 17 ) . Patient compliance with study therapy was determined by weighing inhalers and counting tablets . The weight of a full canister was determined by averaging the weights of at least 50 canisters of beclomethasone and placebo . A st and ard puff weight was determined by repeatedly actuating and weighing 10 canisters . Laboratory safety tests , including hematologic tests , serum biochemistry analysis , and urinalysis , were done at prespecified visits , and the results were analyzed by a central laboratory . The central laboratory also determined eosinophil counts with an automated cell counter . Statistical Analysis Our primary objective was to compare montelukast with placebo with respect to two prespecified primary end points : FEV1 and daytime symptom score . Other objectives were to compare beclomethasone with placebo and to compare montelukast with beclomethasone in a stepwise manner in accordance with the Dunnet-Tamhane approach , with the comparison of montelukast and beclomethasone prespecified as an estimation of the difference using 95 % CIs ( 18 ) . No multiplicity adjustments were made for each of the secondary end points , which were prespecified as supportive . The analysis for each efficacy end point included all patients who had a measurement taken at baseline and at least one measurement taken after r and omization . Treatment responses were calculated as the average change or percentage change from baseline to period 2 ; the baseline value was the average value for period 1 . With SAS software ( SAS Institute , Inc. , Cary , North Carolina ) , we used an analysis of variance ( ANOVA ) model to estimate treatment group means and between-group differences and to construct 95 % CIs by using the least-square means and the differences in least-square means . The model contained factors for treatment , study center , and stratum ( theophylline use ) . The consistency of the treatment effect across study centers , strata , and subgroups ( which were formed according to sex , age , ethnicity , history of allergic rhinitis , and history of exercise-induced asthma ) was assessed by interaction testing done using the ANOVA model with an The two classes of leukotriene modifiers work by inhibiting different portions of the same pathway . We hypothesized that single nucleotide polymorphisms ( SNPs ) in genes associated with response to montelukast ( a cys-leukotriene receptor antagonist ) would also be associated with response to zileuton ( a 5-lipoxygenase inhibitor ) . We genotyped 26 SNPs that had previously been interrogated for association with montelukast response in five c and i date genes ( ABCC1 , ALOX5 , CYSLTR1 , LTA4H , LTC4S ) in a population of 577 asthmatics who participated in a clinical trial comparing intermittent and continuous-release zileuton to placebo . After adjusting for age and sex , six SNPs in three genes were associated with longitudinal forced expiratory volume at 1 s in response to zileuton ( P values 0.005–0.05 ) . After adjusting for age and sex , six SNPs in three genes were associated with longitudinal forced expiratory volume at 1 s in response to zileuton ( P values 0.005–0.05 ) , including two SNPs ( ALOX5 rs2115819 and ABCC1 rs119774 ) that we had previously reported as associated with FEV1 response to montelukast . Thus , the lung function response to zileuton is modulated by several of the loci that also influence montelukast response TBX21 encodes for the transcription factor T-bet ( T-box expressed in T cells ) , which influences naïve T lymphocyte development and has been implicated in asthma pathogenesis . Specifically , the T-bet knockout mouse spontaneously develops airway hyperresponsiveness and other changes consistent with asthma . Because airway responsiveness is moderated by the use of inhaled corticosteroids in asthma , it is conceivable that genetic variation in TBX21 may alter asthma phenotypes in a treatment-specific fashion . Here we demonstrate that the nonsynonymous variation in TBX21 coding for replacement of histidine 33 with glutamine is associated with significant improvement in the PC20 ( a measure of airway responsiveness ) of asthmatic children in a large clinical trial spanning 4 years . We note that this increase occurs only in the children r and omized to inhaled corticosteroids and that it dramatically enhances the overall improvement in PC20 associated with inhaled corticosteroid usage . The average PC20 at trial end for subjects on inhaled corticosteroids possessing a variant allele was in the normal range for nonasthmatics . In cellular models , we show that the TBX21 variant increases T helper 1 and decreases T helper 2 cytokine expression comparably with wild type . TBX21 may thus be an important determinant pharmacogenetic response to the therapy of asthma with inhaled corticosteroids Background Glucocorticoid function is dependent on efficient translocation of the glucocorticoid receptor ( GR ) from the cytoplasm to the nucleus of cells . Importin-13 ( IPO13 ) is a nuclear transport receptor that mediates nuclear entry of GR . In airway epithelial cells , inhibition of IPO13 expression prevents nuclear entry of GR and abrogates anti-inflammatory effects of glucocorticoids . Impaired nuclear entry of GR has been documented in steroid-non-responsive asthmatics . We hypothesize that common IPO13 genetic variation influences the anti-inflammatory effects of inhaled corticosteroids for the treatment of asthma , as measured by change in methacholine airway hyperresponsiveness ( AHR-PC20 ) . Methods 10 polymorphisms were evaluated in 654 children with mild-to-moderate asthma participating in the Childhood Asthma Management Program ( CAMP ) , a clinical trial of inhaled anti-inflammatory medications ( budesonide and nedocromil ) . Population -based association tests with repeated measures of PC20 were performed using mixed models and confirmed using family-based tests of association . Results Among participants r and omized to placebo or nedocromil , IPO13 polymorphisms were associated with improved PC20 ( i.e. less AHR ) , with subjects harboring minor alleles demonstrating an average 1.51–2.17 fold increase in mean PC20 at 8-months post-r and omization that persisted over four years of observation ( p = 0.01–0.005 ) . This improvement was similar to that among children treated with long-term inhaled corticosteroids . There was no additional improvement in PC20 by IPO13 variants among children treated with inhaled corticosteroids . Conclusion IPO13 variation is associated with improved AHR in asthmatic children . The degree of this improvement is similar to that observed with long-term inhaled corticosteroid treatment , suggesting that IPO13 variation may improve nuclear bioavailability of endogenous glucocorticoids BACKGROUND AND OBJECTIVE Inhaled corticosteroids ( ICS ) are widely used as maintenance regimens for asthma patients . However , response to ICS shows marked inter-individual variability . Genetic factors have been shown to be potential predictors of responsiveness to ICS . We aim ed to evaluate those pharmacogenetic effects on asthma control in further detail . METHODS Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes : beta2-adrenergic receptor ( ADRB2 ) , adenylate cyclase 9 ( ADCY9 ) , neurokinin receptor 2 ( NK2R ) and T-box 21 ( TBX21 ) . The principal clinical outcome was the achievement of asthma control , as assessed using the Global Initiative for Asthma ( GINA ) guidelines . During treatment with ICS , the forced expiratory volume in 1 second ( FEV(1 ) ) , maximal mid-expiratory flow ( MMEF ) and peak expiratory flow rate ( PEFR ) were monitored every 4 weeks and twice daily . RESULTS Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS , whereas five asthmatics were in an uncontrolled state even after active treatment . Of the four genetic polymorphisms examined , NK2R G231E G > A and TBX21 H33Q C > G were significantly associated with asthma control status ( P = 0.041 and P = 0.006 ) . The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state , as compared to those with mutant alleles . At 5 - 12 weeks after ICS treatment , the NK2R G231E G > A was associated with therapeutic response to ICS , as reflected by improvement in predicted FEV(1)% . CONCLUSION Our results suggest that NK2R G231E G > A and TBX21 H33Q C > G are genetic predictors of response to ICS , at least with respect to asthma control status and changes in FEV(1)% , in Korean patients with asthma . Further prospect i ve validation of those associations is necessary Some case-control genome-wide association studies ( CCGWASs ) select promising single nucleotide polymorphisms ( SNPs ) by ranking corresponding p-values , rather than by applying the same p-value threshold to each SNP . For such a study , we define the detection probability ( DP ) for a specific disease-associated SNP as the probability that the SNP will be " T-selected , " namely have one of the top T largest chi-square values ( or smallest p-values ) for trend tests of association . The corresponding proportion positive ( PP ) is the fraction of selected SNPs that are true disease-associated SNPs . We study DP and PP analytically and via simulations , both for fixed and for r and om effects models of genetic risk , that allow for heterogeneity in genetic risk . DP increases with genetic effect size and case-control sample size and decreases with the number of nondisease-associated SNPs , mainly through the ratio of T to N , the total number of SNPs . We show that DP increases very slowly with T , and the increment in DP per unit increase in T declines rapidly with T. DP is also diminished if the number of true disease SNPs exceeds T. For a genetic odds ratio per minor disease allele of 1.2 or less , even a CCGWAS with 1000 cases and 1000 controls requires T to be impractically large to achieve an acceptable DP , leading to PP values so low as to make the study futile and misleading . We further calculate the sample size of the initial CCGWAS that is required to minimize the total cost of a research program that also includes follow-up studies to examine the T-selected SNPs . A large initial CCGWAS is desirable if genetic effects are small or if the cost of a follow-up study is large BACKGROUND Corticosteroids exert their anti-inflammatory action by binding and activating the intracellular glucocorticoid receptor heterocomplex . OBJECTIVE We sought to evaluate the genes HSPCB , HSPCA , STIP1 , HSPA8 , DNAJB1 , PTGES3 , FKBP5 , and FKBP4 on corticosteroid response . METHODS White asthmatic subjects ( n = 382 ) r and omized to once-daily flunisolide or conventional inhaled corticosteroid therapy were genotyped . Outcome measures were baseline FEV1 , percent predicted FEV1 , and percent change in FEV1 after corticosteroid treatment . Multivariable analyses adjusted for age , sex , and height were performed , fitting the most appropriate genetic model based on the quantitative mean derived from ANOVA models to determine whether there was an independent effect of polymorphisms on change in FEV1 independent of baseline level . RESULTS Positive recessive model correlations for STIP1 single nucleotide polymorphisms were observed for baseline FEV1 ( rs4980524 , P = .009 ; rs6591838 , P = .0045 ; rs2236647 , P = .002 ; and rs2236648 ; P = .013 ) , baseline percent predicted FEV1 ( rs4980524 , P = .002 ; rs6591838 , P = .017 ; rs2236647 , P = .003 ; and rs2236648 , P = .008 ) , and percent change in FEV1 at 4 weeks ( rs4980524 , P = .044 ; rs6591838 , P = .016 ; and rs2236647 , P = .01 ) and 8 weeks ( rs4980524 , P = .044 ; rs6591838 , P = .016 ; and rs2236647 ; P = .01 ) or therapy . Haplotypic associations were observed for baseline FEV1 and percent change in FEV1 at 4 weeks of therapy ( P = .05 and P = .01 , respectively ) . Significant trends toward association were observed for baseline percent predicted FEV1 and percent change in FEV1 at 8 weeks of therapy . Positive correlations between haplotypes and percent change in FEV1 were also observed . CONCLUSIONS STIP1 genetic variations might play a role in regulating corticosteroid response in asthmatic subjects with reduced lung function . Replication in a second asthmatic population is required to confirm these observations BACKGROUND Although inhaled corticosteroids ( ICSs ) generally protect against severe exacerbations in asthma , they may result in elevated IgE levels , which are associated with exacerbations . OBJECTIVE To determine whether variation in the low-affinity IgE receptor gene , FCER2 , is associated with severe exacerbations defined as emergency department visits and /or hospitalizations in patients with asthma on ICSs . METHODS We resequenced , then genotyped 10 FCER2 single nucleotide polymorphisms ( SNPs ) in 311 children r and omized to inhaled budesonide as part of the Childhood Asthma Management Program . We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial . We also evaluated differences in cellular expression of the novel FCER2 SNP , T2206C . RESULTS In white subjects , 3 FCER2 SNPs were significantly associated ( P < .05 ) with elevated 4-year IgE level ; each was also associated with increased severe exacerbations . Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children ( hazard ratio , 3.95 ; 95 % CI , 1.64 - 9.51 ; and hazard ratio , 3.08 ; 95 % CI , 1.00 - 9.47 ) , despite ICS use . Interaction models supported a true gene-environment effect in white subjects ( interaction P = .004 ) . T2206C was also associated with decreased FCER2 expression ( P = .02 ) . CONCLUSION FCER2 predicts the likelihood of treatment protocol success in asthma . The associations of T2206C with IgE level , severe exacerbations , and FCER2 expression may provide a mechanistic basis for the observed findings . CLINICAL IMPLICATION S Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma WHAT IS KNOWN AND OBJECTIVE Montelukast , a cysteinyl leukotriene receptor 1 antagonist , is safe and efficacious in patients with asthma . The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be , in part , because of genetic variability . METHODS To examine the associations between polymorphisms in c and i date genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4 - 8 weeks , we evaluated the changes in peak expiratory flow ( PEF ) , forced expiratory volume in 1 s ( FEV(1·0 ) ) and patients ' subjective symptom before and after montelukast treatment . DNA was collected from 252 Japanese participants . RESULTS AND DISCUSSION Two single-nucleotide polymorphisms ( SNPs ) in the ALOX5 ( rs2115819 ) and LTA4H ( rs2660845 ) genes were successfully typed . There was no difference between members of the general population ( n = 200 ) and patients ( n = 52 ) in each genotype frequency . Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0 ) . The PEF and FEV(1·0 ) responses to montelukast in the A/A genotypes ( n = 4 ) for the LTA4H SNP were significantly higher than those in the G allele carriers ( A/G+G/G ) ( n = 17 ) . WHAT IS NEW AND CONCLUSION Despite the small sample size , our results suggest that genetic variation in leukotriene pathway c and i date genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma Clinical ly similar asthma patients may develop airway obstruction by different mechanisms . Asthma treatments that specifically interfere with the 5-lipoxygenase ( ALOX5 ) pathway provide a method to identify those patients in whom the products of the ALOX5 pathway ( that is , the leukotrienes ) contribute to the expression of the asthma phenotype . Failure of an asthma patient to respond to treatment with ALOX5-pathway modifiers indicates that leukotrienes are not critical to the expression of the asthmatic phenotype in that patient . We previously defined a family of DNA sequence variants in the core promoter of the gene ALOX5 ( on chromosome 10q11.2 ) associated with diminished promoter-reporter activity in tissue culture . Because expression of ALOX5 is in part transcriptionally regulated , we reasoned that patients with these sequence variants may have diminished gene transcription , and therefore decreased ALOX5 product production and a diminished clinical response to treatment with a drug targeting this pathway . Such an effect indicates an interaction between gene promoter sequence variants and drug-treatment responses , that is , a pharmacogenetic effect of a promoter sequence on treatment responses AIMS To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma , based independently on lung function changes or asthma exacerbations . MATERIAL S & METHODS We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children ( aged 5 - 12 years ) r and omized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program ( CAMP ) . RESULTS Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response . A history of prior asthma exacerbations , younger age and a higher IgE level ( p < 0.05 ) are associated with recurrent exacerbations . By contrast , lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206C in FCER2 ( p < 0.05 ) are associated with poor lung function response . Poor lung function response does not increase the risk of exacerbations and vice versa ( p = 0.72 ) . CONCLUSION Genetic and phenotypic predictors of a poor long-term response to inhaled corticosteroids differ markedly depending on definition of outcome ( based on exacerbations vs lung function ) . These findings are important in comparing outcomes of clinical trials and in design ing future pharmacogenetic studies Background Thromboxane A2 receptor ( TBXA2R ) gene polymorphism has been associated with atopy and asthma , but few studies have reported the effect of this gene polymorphism on asthma‐related phenotype or responsiveness to leukotriene receptor antagonist ( LTRA ) in asthmatic children . This study investigated associations between asthma‐related phenotypes and TBXA2R polymorphism , and also analysed whether the TBXA2R polymorphism has an effect on the efficacy of the LTRA , montelukast , in asthmatic children with exercise‐induced bronchoconstriction ( EIB ) BACKGROUND Inhaled corticosteroids ( ICSs ) are considered first-line treatment for persistent asthma , yet there is significant variability in treatment response . Dual-specificity phosphatase 1 ( DUSP1 ) appears to mediate the anti-inflammatory action of corticosteroids . OBJECTIVE We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment . METHODS Study participants with asthma were drawn from the following multiethnic cohorts : the Genetics of Asthma in Latino Americans ( GALA ) study ; the Study of African Americans , Asthma , Genes & Environments ( SAGE ) ; and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity ( SAPPHIRE ) . We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response . We then replicated our findings in SAGE and SAPPHIRE participants . In a group of SAPPHIRE participants treated with ICSs for 6 weeks , we examined whether a DUSP1 polymorphism was associated with changes in FEV(1 ) and self-reported asthma control . RESULTS The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants . This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants . Among the group of SAPPHIRE participants prospect ively treated with ICSs for 6 weeks , rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV(1 ) . CONCLUSION DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment BACKGROUND Treatment with antileukotriene drugs results in clinical improvement in many , though not all , patients with asthma . It can be hypothesized that the sub population of asthmatic patients , characterized by aspirin intolerance and cysteinyl-leukotriene overproduction , might profit most from antileukotriene treatment . MATERIAL S AND METHODS We compared the clinical response to montelukast in two well-matched groups of patients with mild asthma : 26 aspirin-intolerant asthmatics ( AIAs ) and 33 aspirin-tolerant asthmatics ( ATAs ) . We also search ed for possible predictors of the clinical response among the parameters reflecting the expression and production of cysteinyl-leukotrienes ( cys-LTs ) . This was an 8-week , single-blind , placebo-controlled trial . RESULTS Following a 3-week montelukast 10 mg day-1 treatment compared with placebo , there was a statistically significant reduction in the mean daytime and nocturnal asthma symptoms and beta 2-agonist use , as well as a significant improvement in the morning and evening peak expiratory flows and quality of life . Both groups showed a similar significant improvement in the parameters studied . Clinical response did not correlate with the baseline urinary LTE4 excretion level . Improvement of asthma was observed mostly in patients with a low baseline and non-IL-5 inducible expression of LTC4 synthase ( LTC4S ) mRNA in eosinophils . There was a trend toward a better response in carriers of LTC4S allele C , but no relationship to the CC10 genetic polymorphism . CONCLUSIONS No difference in the clinical response to the montelukast treatment was observed between the AIAs and the ATAs Heterogeneous therapeutic responses to leukotriene modifiers ( LTMs ) are likely due to variation in patient genetics . Although prior c and i date gene studies implicated multiple pharmacogenetic loci , to date , no genome-wide association study ( GWAS ) of LTM response was reported . In this study , DNA and phenotypic information from two placebo-controlled trials ( total N=526 ) of zileuton response were interrogated . Using a gene – environment ( G × E ) GWAS model , we evaluated 12-week change in forced expiratory volume in 1 second ( ΔFEV1 ) following LTM treatment . The top 50 single-nucleotide polymorphism associations were replicated in an independent zileuton treatment cohort , and two additional cohorts of montelukast response . In a combined analysis ( discovery+replication ) , rs12436663 in MRPP3 achieved genome-wide significance ( P=6.28 × 10−08 ) ; homozygous rs12436663 carriers showed a significant reduction in mean ΔFEV1 following zileuton treatment . In addition , rs517020 in GLT1D1 was associated with worsening responses to both montelukast and zileuton ( combined P=1.25 × 10−07 ) . These findings implicate previously unreported loci in determining therapeutic responsiveness to LTMs BACKGROUND It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported . METHODS Sixty-one patients ( mean age 24.9 years , range 14 - 52 ) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast . T and em repeat polymorphisms were genotyped in the promoter ( -147 to -176 ) of 5-lipoxygenase gene ( ALOX5 ) . RESULTS Thirty-two patients ( 52.5 % ) were homozygous for the five repeats allele ; 17 ( 27.9 % ) were heterozygous ( 4/5 repeats ) and 12 ( 19.7 % ) were homozygous for 4/4 repeats . After the montelukast treatment decrease number of asthma exacerbations , improvement of FEV(1 ) and decreased use of beta(2 ) agonists was observed in patients with 5/5 or 4/5 repeats . Conversely , the patients with 4/4 repeats genotype did not modify these data after treatment . CONCLUSIONS It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients . The genetic study could identify those patients most likely to respond to montelukast Asthma is a common chronic condition that places substantial burden on patients and healthcare services . Despite the st and ards of asthma control that international guidelines recommend should be achieved , many patients continue to suffer sub-optimal control of symptoms and experience exacerbations ( acute asthma attacks ) . In addition to being associated with reduced quality of life , asthma exacerbations are a key cost driver in asthma management . Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems , so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations . This prospect i ve study , conducted in a total of 15 countries , assessed the local cost of asthma exacerbations managed in either primary or secondary care . Healthcare re sources used were costed using actual values appropriate to each country in local currency and in Euros . Results are presented for exacerbations managed in primary care in Brazil , Bulgaria , Croatia , Czech Republic , Hungary , Pol and , Russia , Slovakia , Slovenia , Spain and Ukraine , and in secondary care in Croatia , Denmark , Irel and , Latvia , Norway , Pol and , Russia , Slovakia , Slovenia and Spain . Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country ( P<0.0001 ) . Mean costs were significantly higher in secondary care ( euro 1349 ) than primary care ( euro 445 , P=0.0003 ) . Age was a significant variable ( P=0.0002 ) , though the effect showed an interaction with care type ( P<0.0001 ) . As severity of exacerbation increased , so did secondary care costs , though primary care costs remained essentially constant . In conclusion , the study showed that asthma exacerbations are costly to manage , suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic benefits , as well as improved quality of life Background IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness , and is known to influence leukotriene levels . Objective We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist ( LTRA ) in Korean asthmatic children with exercise-induced bronchoconstriction ( EIB ) . Methods We enrolled 242 normal controls and 374 patients with asthma . Of the asthmatic patients , 100 performed exercise challenge tests before and after receiving montelukast ( 5 mg/day ) for 8 weeks and included 80 subjects in drug responsiveness analysis . We assessed IL-13 polymorphisms ( −1512A/C , −1112C/T , + 2044G/A ) through PCR – restriction fragment length polymorphism analysis . Results Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s ( FEV1 ) ( % ) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 + 2044A versus those homozygous for + 2044 G ( P=0.011 and 0.040 , respectively ) . We further noted a correlation of total IgE with maximum percent fall in FEV1 ( % ) in asthmatic patients , as well as a reverse correlation with improvement of maximum percent fall in FEV1 ( % ) after exercise challenge tests . Finally , we observed a significant association between responsiveness to montelukast and IL-13 −1112C/T polymorphism and the haplotype of IL-13 polymorphisms . Conclusion The IL-13 + 2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB , and thus could potentially be considered as a disease-modifying gene . Moreover , the IL-13 −1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness , and thus might prove useful as a target for modulation of LTRA drug responsiveness Background Genetic polymorphisms may be responsible for the wide variation in response to inhaled corticosteroids in asthmatic patients . We had previously reported that one polymorphism rs7772821 , located on the 3′-UTR of trace amine-associated receptor 6 ( TAAR6 ) , is significantly associated with percentile changes in the forced expiratory volume in 1 s ( % [INCREMENT]FEV1 ) after inhaled corticosteroid treatment in asthmatics using a genome-wide association study . The aim of the present study was to vali date the association between 15 single-nucleotide polymorphisms ( SNPs ) on the TAAR6 and airway responsiveness to inhaled corticosteroids in the asthmatics . Methods The % [INCREMENT]FEV1 induced by 4 weeks ’ treatment with inhaled fluticasone propionate ( 1000 & mgr;g daily ) was measured in 246 asthmatics . The 15 SNPs of TAAR6 were genotyped using a TaqMan assay . An association analysis between % [INCREMENT]FEV1 and TAAR6 polymorphisms was carried out using a linear regression model controlling for age , sex , smoking status , presence of atopy , and baseline FEV1 as covariates . Results Among the 15 SNPs and seven haplotypes of TAAR6 , rs7772821 ( T > G ) on the 3′-UTR showed the strongest correlation with inhaled corticosteroid-induced % [INCREMENT]FEV1 ( Pcorr=0.002 in the codominant model , Pcorr=0.03 in the dominant model , Pcorr=0.01 in the recessive model ) . The % [INCREMENT]FEV1 of the rs7772821T > G minor homozygotes ( 60.77 % ) was higher than that of patients harboring either the rs7772821 T/G or T/T genotypes ( 21.32 and 31.60 % , respectively ) . Conclusion The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics The Childhood Asthma Management Program ( CAMP ) is a multicenter , r and omized , double-masked clinical trial design ed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma : budesonide ( a glucocorticoid used daily ) and albuterol ( a short-acting beta-agonist bronchodilator used as needed ) ; nedocromil ( a nonsteroid anti-inflammatory agent used daily ) and albuterol ; and placebo and albuterol . One thous and forty-one children ( 32 % from ethnic minority groups ) , aged 5 to 12 years at screening , are currently participating . The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second ( FEV1 ) percent of predicted , observed over 5- to 6-year period . The trial also assesses differences between treatment groups with respect to airway responsiveness , morbidity , physical growth and development , and psychological growth and development . This report describes the design of the trial , the rationale for the design choices made , and the methods used to carry out the trial BACKGROUND Maintaining asthma control is a major objective of therapy . Traditionally , the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control . OBJECTIVE An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects , as judged by days of asthma control . METHODS In a r and omized , multicenter , double-blind , placebo-controlled , parallel-group study , asthmatic patients ( n = 782 ) with FEV(1 ) percent predicted values of between 50 % and 85 % and a weekly average beta-agonist use of more than 2 puffs per day were r and omized to receive montelukast ( 10 mg daily ) , beclomethasone ( 200 microg twice daily ) , or placebo treatment for 6 weeks in a double-dummy fashion . We examined the distribution of the primary end point : percentage of days of asthma control . Secondary end points included FEV(1 ) , albuterol use , occurrence of an asthma attack , asthma flare-up , rescue corticosteroid use , sustained asthma control , and adverse experiences . RESULTS The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups ( 98 % overlap in the distribution ) . Montelukast was at least equal to beclomethasone , and both were greater than placebo on the basis of frequency of asthma attacks , asthma flare-ups , and rescue corticosteroid use . Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1 ) . CONCLUSIONS Montelukast was as effective as beclomethasone , as judged by indices of clinical control other than FEV(1 ) . When evaluating the outcome of montelukast therapy , FEV(1 ) might underestimate clinical effectiveness |
12,594 | 20,627,403 | In contrast , ADT as an adjuvant to radiation therapy in patients with high-risk localised disease or locally advanced disease was associated with substantial OS and CSS benefits .
A similar benefit was seen in patients with proven systemic disease ( node-positive patients after radical prostatectomy ) .
We conclude that an interaction between local treatment and ADT is suggested by this systematic review .
In patients with advanced and aggressive disease who are at a high risk to die from PCa and who are treated for their primary tumour with curative intent , immediate and sustained ADT improves OS and CSS significantly .
However , this intensive treatment is unnecessary in a substantial number of patients with T3 and /or N1 disease with a slow natural history or high competing death risk | CONTEXT And rogen-deprivation therapy ( ADT ) plays a pivotal role in the management of locally advanced and metastatic prostate cancer ( PCa ) .
When and for how long to apply ADT have remained controversial issues .
OBJECTIVE To review r and omised studies of ADT ( orchiectomy or luteinising hormone-releasing hormone analogues ) in PCa-both immediate and deferred/adjuvant studies -to eluci date a possible interaction between local treatment and ADT . | PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 CONTEXT Clinical ly localized prostate cancer is very prevalent among US men , but recurrence after treatment with conventional radiation therapy is common . OBJECTIVE To evaluate the hypothesis that increasing the radiation dose delivered to men with clinical ly localized prostate cancer improves disease outcome . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen ( PSA ) levels less than 15 ng/mL r and omized between January 1996 and December 1999 and treated at 2 US academic institutions . Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 ( range , 1.2 - 8.2 ) years . INTERVENTION Patients were r and omized to receive external beam radiation to a total dose of either 70.2 Gy ( conventional dose ) or 79.2 Gy ( high dose ) . This was delivered using a combination of conformal photon and proton beams . MAIN OUTCOME MEASURE Increasing PSA level ( ie , biochemical failure ) 5 years after treatment . RESULTS The proportions of men free from biochemical failure at 5 years were 78.8 % [ corrected ] ( 95 % confidence interval , 73.1%-84.6 % ) [ corrected ] for conventional-dose and 91.3 % [ corrected ] ( 95 % confidence interval , 87.2%-95.4 % ) [ corrected ] for high-dose therapy ( P<.001 ) , a 59 % [ corrected ] reduction in the risk of failure . The advantage to high-dose therapy was statistically significant [ corrected ] in both the low-risk subgroup [ corrected ] ( risk reduction , 84 % [ P<.001 ] ) [ corrected ] There has been no significant difference in overall survival rates between the treatment groups . Only 1 % of patients receiving conventional-dose and 2 % receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group ( RTOG ) grade 3 or greater . So far , only 2 % and 1 % , respectively , have experienced late morbidity of RTOG grade 3 or greater . CONCLUSIONS Men with clinical ly localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation . This advantage was achieved without any associated increase in RTOG grade 3 acute or 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 To determine if immediate hormonal therapy is advantageous compared with deferred treatment in newly diagnosed asymptomatic prostate cancer patients who , for any reason , were not c and i date s for curative local treatment . PATIENTS AND METHODS Between February 1988 and February 1992 , 197 patients with a median age of 76 years ( range , 56 to 86 years ) were r and omly assigned to receive either immediate or deferred orchiectomy on symptomatic progression . The two groups did not differ significantly in clinical or laboratory parameters ; 67 % had T3 - 4 tumors and 20 % had lymph node metastases . Patient accrual was stopped prematurely because of a similar competing trial . Therefore , observation time was prolonged to achieve the desired number of events and statistical power . RESULTS Deferred orchiectomy was necessary in 58 % of the patients . Median time to disease progression was 2.8 years less than for patients with immediate orchiectomy . However , overall pain-free time from r and om assignment to symptomatic progression after immediate or deferred orchiectomy , and performance status , were identical in both groups . Cancer-specific survival tended to be longer in the immediate group ( P = .09 ) but there was no difference in overall survival between the two groups ( P = .96 ) . The median hemoglobin value decreased significantly after immediate orchiectomy ( P < .001 ) . CONCLUSION For elderly , asymptomatic patients not undergoing curative local treatment , we were unable to show any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival in our limited number of patients . Disabling complications were prevented in the deferred-treatment arm by careful follow-up ; 42 % of these patients never required any tumor-specific treatment OBJECTIVE To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced , lymph node-negative prostate cancer . METHODS Men with locally advanced , lymph node-negative prostate cancer were r and omized after radical prostatectomy to receive either flutamide 750 mg daily or no adjuvant treatment . Recurrence-free and overall survival were the study end points . Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence . RESULTS 309 patients ( 157 in the control arm and 152 in the flutamide arm ) were eligible for efficacy analysis . The median follow-up was 6.1 years . Recurrence-free survival was better in the flutamide group ( P=0.0041 ) , there was , however , no detectable difference in overall survival ( p=0.92 ) . Moreover , there was a considerable toxicity reported in the flutamide group . CONCLUSION Although having some effect on disease recurrence , adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced , lymph node-negative prostate cancer 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 OBJECTIVE EORTC trial 30891 compared immediate versus deferred and rogen-deprivation therapy ( ADT ) in T0 - 4 N0 - 2 M0 prostate cancer ( PCa ) . Many patients r and omly assigned to deferred ADT did not require ADT because they died before becoming symptomatic . The question arises whether serum prostate-specific antigen ( PSA ) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment . METHODS PSA data at baseline , PSA doubling time ( PSADT ) in patients receiving no ADT , and time to PSA relapse ( > 2 ng/ml ) in patients whose PSA declined to < 2 ng/ml within the first year after immediate ADT were analyzed in 939 eligible patients r and omly assigned to immediate ( n=468 ) or deferred ADT ( n=471 ) . RESULTS In both arms , patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA < or=8 ng/ml . If baseline PSA was between 8 and 50 ng/ml , the risk of PCa death was approximately 7.5-fold higher in patients with PSADT<12 mo than in patients with PSADT>12 mo . Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA , suggesting that baseline PSA may also reflect disease aggressiveness . CONCLUSIONS Patients with a baseline PSA>50 ng/ml and /or a PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT , whereas patients with a baseline PSA<50 ng/ml and a slow PSADT ( > 12 mo ) were likely to die of causes unrelated to PCa , and thus could be spared the burden of immediate ADT PURPOSE This study ( EORTC 30891 ) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred and rogen ablation . PATIENTS AND METHODS We r and omly assigned 985 patients with newly diagnosed prostate cancer T0 - 4 N0 - 2 M0 to receive and rogen deprivation either immediately ( n = 493 ) or on symptomatic disease progression or occurrence of serious complications ( n = 492 ) . RESULTS Baseline characteristics were well balanced in the two groups . Median age was 73 years ( range , 52 to 81 ) . At a median follow-up of 7.8 years , 541 of 985 patients had died , mostly of prostate cancer ( n = 193 ) or cardiovascular disease ( n = 185 ) . The overall survival hazard ratio was 1.25 ( 95 % CI , 1.05 to 1.48 ; noninferiority P > .1 ) favoring immediate treatment , seemingly due to fewer deaths of nonprostatic cancer causes ( P = .06 ) . The time from r and omization to progression of hormone refractory disease did not differ significantly , nor did prostate-cancer specific survival . The median time to the start of deferred treatment after study entry was 7 years . In this group 126 patients ( 25.6 % ) died without ever needing treatment ( 44 % of the deaths in this arm ) . CONCLUSION Immediate and rogen deprivation result ed in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival . This must be weighed on an individual basis against the adverse effects of life-long and rogen deprivation , which may be avoided in a substantial number of patients with a deferred treatment policy BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p<0.0001 ) . Of 49 histopathology slides received ( 19 immediate ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups < or = 6 , 7 , and > or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p<0.0001 ) . INTERPRETATION Early ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments 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 PURPOSE The timing of endocrine treatment for prostate cancer remains controversial . The issue is addressed in protocol 30846 of the European Organisation for Research and Treatment of Cancer for patients with lymph node positive cancer without local treatment of the primary tumor . MATERIAL S AND METHODS A total of 302 patients with metastatic regional lymph nodes who had not received local treatment for the primary tumor were included in the trial , of whom 234 were r and omized to immediate vs delayed endocrine treatment . Endocrine treatment consisted of an luteinizing hormone-releasing hormone agonist and 1 month of anti and rogen treatment or surgical castration . The main end point of the trial was overall survival . Analysis followed the intent to treat principle . RESULTS At a median followup of 9.6 years ( 8.7 in the r and omized sample ) 190 patients ( 62.9 % ) had died , including 76 % of prostate cancer . In the r and omized sample the HR for survival on delayed vs immediate treatment was 1.23 ( 95 % CI 0.88 to 1.71 ) , indicating a 23 % nonsignificant trend in favor of early treatment . However , the wide CI showed that results remained compatible with true effects , ranging from a 12 % benefit in favor of delayed treatment to a 71 % detriment for the same treatment approach . CONCLUSIONS While this study suggests an advantage for early treatment , it is under powered to show equivalence or superiority for the early or delayed approach . When dealing with individual patients , the potential survival advantage on early treatment must be balanced against potential advantages in quality of life on delayed treatment 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 The results of a large r and omized prospect i ve clinical trial conducted by the Veterans Administration Co-operative Urological Research Group ( VACURG ) in 1968 are up date d and reevaluated . In this study , placebo , diethylstilbestrol ( DES , 5 mg/day ) , orchiectomy plus placebo , and orchiectomy plus DES were compared in patients whose conditions were initially diagnosed as stage III and IV carcinoma of the prostate . Results showed that orchiectomy alone or in combination with estrogen did not improve overall survival rates in stage III and IV carcinoma of the prostate . In the two treatment groups receiving estrogen , however , there were fewer deaths due to cancer of the prostate , but this effect tended to be offset by an increased number of deaths due to cardiovascular causes . Deaths from other causes showed no particular pattern with respect to treatment . These studies showed that estrogen is more effective than orchiectomy in preventing deaths from cancer and that the addition of orchiectomy to estrogen does not offer any clear-cut advantage over estrogen therapy alone . If cancer symptoms necessitate treatment , initial therapy with estrogen is preferred . Orchiectomy should be reserved for those circumstances in which a patient is not reliable , can not tolerate estrogens , or has severe cardiovascular disease 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 BACKGROUND And rogen deprivation is an established treatment regimen for disseminated prostate cancer ; however , its role in patients with localised cancer is less clear . We did a large r and omised controlled trial to determine whether 3 months or 6 months of and rogen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer . METHODS 818 men with locally advanced prostate cancer were r and omly assigned to : no and rogen deprivation ( ie , radiotherapy alone : 66 Gy in 33 fractions of 2 Gy per day over 6.5 - 7.0 weeks to the prostate and seminal vesicles ) ; 3 months ' and rogen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy ( same regimen as control group ) ; or 6 months ' and rogen deprivation , with the same regimen , starting 5 months before radiotherapy ( same regimen as control group ) . Primary endpoints were time to local failure and prostate-cancer-specific survival ; secondary endpoints were distant failure , disease-free survival , and freedom from salvage treatment . Analyses were done by intention to treat . FINDINGS 802 ( 98 % ) patients were eligible for analysis . Median follow-up was 5.9 years ( range 0.1 - 8.5 ) . Compared with patients assigned no and rogen deprivation , those assigned 3 months ' treatment had significantly improved local failure ( hazard ratio [ HR ] 0.56 [ 95 % CI 0.39 - 0.79 ] , p=0.001 ) , biochemical failure-free survival ( 0.70 [ 0.56 - 0.88 ] , p=0.002 ) , disease-free survival ( 0.65 [ 0.52 - 0.80 ] , p=0.0001 ) , and freedom from salvage treatment ( 0.73 [ 0.56 - 0.96 ] , p=0.025 ) . 6 months ' and rogen deprivation significantly improved local failure ( 0.42 [ 0.28 - 0.62 ] , p<0.0001 ) , biochemical failure-free survival ( 0.58 [ 0.46 - 0.74 ] , p<0.0001 ) , disease-free survival ( 0.56 [ 0.45 - 0.69 ] , p<0.0001 ) , freedom from salvage treatment ( 0.53 [ 0.40 - 0.71 ] , p<0.0001 ) , distant failure ( 0.67 [ 0.45 - 0.99 ] , p=0.046 ) and prostate-cancer-specific survival ( 0.56 [ 0.32 - 0.98 ] , p=0.04 ) compared with no and rogen deprivation . INTERPRETATION 6 months ' and rogen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer . Further follow-up is needed to estimate precisely the size of survival benefits . Increased radiation doses and additional periods of and rogen deprivation might lead to further benefit PURPOSE This trial was design ed to test the hypothesis that total and rogen suppression and whole pelvic radiotherapy ( WPRT ) followed by a prostate boost improves progression-free survival ( PFS ) by > or = 10 % compared with total and rogen suppression and prostate only RT ( PORT ) . This trial was also design ed to test the hypothesis that neoadjuvant hormonal therapy ( NHT ) followed by concurrent total and rogen suppression and RT improves PFS compared with RT followed by adjuvant hormonal therapy ( AHT ) by > or = 10 % . METHODS AND MATERIAL S Patients eligible for the study included those with clinical ly localized adenocarcinoma of the prostate and an elevated prostate-specific antigen level of < 100 ng/mL. Patients were stratified by T stage , prostate-specific antigen level , and Gleason score and were required to have an estimated risk of lymph node involvement of > 15 % . RESULTS The difference in overall survival for the four arms was statistically significant ( p = 0.027 ) . However , no statistically significant differences were found in PFS or overall survival between NHT vs. AHT and WPRT compared with PORT . A trend towards a difference was found in PFS ( p = 0.065 ) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT arms . CONCLUSIONS Unexpected interactions appear to exist between the timing of hormonal therapy and radiation field size for this patient population . Four Phase III trials have demonstrated better outcomes when NHT was combined with RT compared with RT alone . The Radiation Therapy Oncology Group 9413 trial results have demonstrated that when NHT is used in conjunction with RT , WPRT yields a better PFS than does PORT . It also showed that when NHT + WPRT results in better overall survival than does WPRT + short-term AHT . Additional studies are warranted to determine whether the failure to demonstrate an advantage for NHT + WPRT compared with PORT + AHT is chance or , more likely , reflects a previously unrecognized biologic phenomenon BACKGROUND The combination of radiotherapy plus long-term medical suppression of and rogens ( > or = 2 years ) improves overall survival in patients with locally advanced prostate cancer . We compared the use of radiotherapy plus short-term and rogen suppression with the use of radiotherapy plus long-term and rogen suppression in the treatment of locally advanced prostate cancer . METHODS We r and omly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of and rogen suppression to two groups , one to receive no further treatment ( short-term suppression ) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist ( long-term suppression ) . An outcome of noninferiority of short-term and rogen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival , with a one-sided alpha level of 0.05 . An interim analysis showed futility , and the results are presented with an adjusted one-sided alpha level of 0.0429 . RESULTS A total of 1113 men were registered , of whom 970 were r and omly assigned , 483 to short-term suppression and 487 to long-term suppression . After a median follow-up of 6.4 years , 132 patients in the short-term group and 98 in the long-term group had died ; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group . The 5-year overall mortality for short-term and long-term suppression was 19.0 % and 15.2 % , respectively ; the observed hazard ratio was 1.42 ( upper 95.71 % confidence limit , 1.79 ; P=0.65 for noninferiority ) . Adverse events in both groups included fatigue , diminished sexual function , and hot flushes . CONCLUSIONS The combination of radiotherapy plus 6 months of and rogen suppression provides inferior survival as compared with radiotherapy plus 3 years of and rogen suppression in the treatment of locally advanced prostate cancer . ( Clinical Trials.gov number , NCT00003026 . CONTEXT Comorbidities may increase the negative effects of specific anticancer treatments such as and rogen suppression therapy ( AST ) . OBJECTIVES To compare 6 months of AST and radiation therapy ( RT ) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality . DESIGN , SETTING , AND PATIENTS At academic and community-based medical centers in Massachusetts , between December 1 , 1995 , and April 15 , 2001 , 206 men with localized but unfavorable-risk prostate cancer were r and omized to receive RT alone or RT and AST combined . All-cause mortality estimates stratified by r and omized treatment group and further stratified in a postr and omization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test . MAIN OUTCOME MEASURE Time to all-cause mortality . RESULTS As of January 15 , 2007 , with a median follow-up of 7.6 ( range , 0.5 - 11.0 ) years , 74 deaths have occurred . A significant increase in the risk of all-cause mortality ( 44 vs 30 deaths ; hazard ratio [ HR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.1 - 2.9 ; P = .01 ) was observed in men r and omized to RT compared with RT and AST . However , the increased risk in all-cause mortality appeared to apply only to men r and omized to RT with no or minimal comorbidity ( 31 vs 11 deaths ; HR , 4.2 ; 95 % CI , 2.1 - 8.5 ; P < .001 ) . Among men with moderate or severe comorbidity , those r and omized to RT alone vs RT and AST did not have an increased risk of all-cause mortality ( 13 vs 19 deaths ; HR , 0.54 ; 95 % CI , 0.27 - 1.10 ; P = .08 ) . CONCLUSIONS The addition of 6 months of AST to RT result ed in increased overall survival in men with localized but unfavorable-risk prostate cancer . This result may pertain only to men without moderate or severe comorbidity , but this requires further assessment in a clinical trial specifically design ed to assess this interaction . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116220 |
12,595 | 26,749,516 | Upon the limitations of the studies included in this systematic review , the present outcomes suggested that there is insufficient evidence in favour or against the conservative therapies for TMD on changes in otologic signs and symptoms . | The most common temporom and ibular disorders ( TMD ) signs and symptoms are related to muscle sensitivity through palpation , restricted mouth opening , asymmetric m and ibular movements , joint sounds , pain and otologic signs and symptoms .
To date , counselling , occlusal splints , exercises , biofeedback and acupuncture are examples of conservative modalities proposed for TMD therapy .
The aim of this systematic review was to investigate the effect of these conservative therapies for TMD on otologic signs and symptoms . | BACKGROUND The authors compared the efficacy of bilateral balanced and canine guidance ( occlusal ) splints in the treatment of temporom and ibular joint ( TMJ ) pain in subjects who experienced joint clicking with a nonoccluding splint in a double-blind , controlled r and omized clinical trial . METHODS The authors r and omly assigned 57 people with signs of disk displacement and TMJ pain into three groups according to the type of splint : bilateral balanced , canine guidance and nonoccluding . The authors followed the groups for six months using analysis of a visual analog scale ( VAS ) , palpation of the TMJ and masticatory muscles , m and ibular movements and joint sounds . They used repeated analysis of variance and a chi(2 ) test to test the hypothesis . RESULTS The type of guidance used did not influence the pain reduction , yet both occlusal splints were superior to the nonoccluding splint , on the basis of the VAS . Despite similar outcomes in relation to opening , left lateral and protrusive movements , TMJ and muscle pain on palpation , subjects who used the occlusal splints had improved clinical outcomes . The frequency of joint noises decreased over time , with no significant differences among groups . Subjects in the groups using the occlusal splints reported more comfort . CONCLUSION The type of lateral guidance did not influence the subjects ' improvement . All of the subjects had a general improvement on the VAS , though subjects in the occlusal splint groups had better results that did subjects in the nonoccluding splint group Thirty-two patients with disabling tinnitus received stomatognathic treatment and biofeedback therapy according to a cross-over design . The evaluation of treatment outcomes showed some improvements at the group level : decrease of tinnitus intensity , mood improvement and reduction of clinical signs of dysfunction in the masticatory system . Qualitative observations indicated numerous positive changes in patients ' emotional and cognitive orientation vis à vis tinnitus . Some possible predictors of positive treatment outcome were observed : comparatively low severity of tinnitus , normal hearing or compensated hearing loss , occlusal interferences , jaw fatigue , diurnal bruxism and fluctuations in tinnitus intensity . Left-sided tinnitus seemed to be a negative predictor of stomatognathic and biofeedback treatment outcome . Consequently , stomatognathic and biofeedback treatment seem to have some positive effects on subgroups of tinnitus patients OBJECTIVE To measure the effect of occlusal splints as an additional treatment on psychological aspects in temporom and ibular disorder patients . DESIGN A r and omized controlled trial was performed comprising 60 adults diagnosed with masticatory myofascial pain according the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . The participants were divided equally into 2 treatment groups , which received only counselling ( Group 1 ) or occlusal splints in addition to counselling ( Group 2 ) . The assessment s occurred at baseline and at 2 and 5 months after treatment . The outcomes were symptoms of anxiety and depression , as well as pain catastrophizing . Two-way ANOVA , Friedman and Mann-Whitney tests were used to perform the statistical analysis , considering a significance level of 5 % . RESULTS In relation to the baseline assessment , 60 % of the subjects had at least mild anxiety and 25 % had at least mild depression , and the mean and st and ard deviation ( SD ) of pain catastrophizing was 2.41 ( 1.33 ) for Group 1 and 2.06 ( 1.04 ) for Group 2 . Comparisons between baseline and the fifth-month evaluation showed an improvement in anxiety and depression symptoms only in Group 2 ( p<0.05 ) . Otherwise , there was a significant reduction in pain catastrophizing in both groups ( p<0.05 ) , with a mean ( SD ) of 1.14 ( 1.28 ) for Group 1 and 0.76 ( 0.82 ) for Group 2 . CONCLUSION Minimally invasive strategies could provide an improvement in the psychological aspects of temporom and ibular disorder patients , and the use of an occlusal splint seems to hasten the manifestation of these effects The aim of this research was to test the hypothesis that treatment with intra-oral appliances with different occlusal design s was beneficial in the management of pain of masticatory muscles compared with a control group . A total of 51 patients were analysed according to the research diagnostic criteria for temporom and ibular disorders ( RDC/TMD ) to obtain the diagnosis of masticatory myofascial pain ( MMP ) . The sample was then r and omly divided into three groups : group I ( n = 21 ) wore a full coverage acrylic stabilisation occlusal splint ; group II ( n = 16 ) wore an anterior device nociceptive trigeminal inhibitory ( NTI ) system ; and group III ( n = 14 ) only received counselling for behavioural changes and self-care ( the control group ) . The first two groups also received counselling . Follow-ups were performed after 2 and 6 weeks and 3 months . In these sessions , patients were evaluated by means of a visual analogue scale ( VAS ) and pressure pain threshold ( PPT ) of the masticatory muscles . Possible adverse effects were also recorded , such as discomfort while using the appliance and occlusal changes . The results were analysed with Kruskal-Wallis , anova , Tukey 's and Friedman tests , with a significance level of 5 % . Group I showed improvement in the reported pain at the first follow-up ( 2 weeks ) , whereas for groups II and III , this progress was detected only after 6 weeks and 3 months , respectively . The PPT values did not change significantly . It was concluded that behavioural changes are effective in the management of pain in MMP patients . However , the simultaneous use of occlusal devices appears to produce an earlier improvement Objective . The aim of the study was to investigate the presence of symptoms and signs of temporom and ibular disorders ( TMD ) in patients with tinnitus and to evaluate the effect of TMD treatment on tinnitus in a long-term perspective in comparison with a control group of patients on a waiting list . Material and Methods . One-hundred- and -twenty patients with tinnitus were subjected to a clinical examination of the masticatory system and whether they had co-existing TMD to TMD treatment . Ninety-six patients had TMD , most frequently localized myalgia . Seventy-three of these completed the treatment and responded to a question naire 2 years later . Fifty patients with tinnitus who were on the waiting list served as a control group . Results . Eighty percent of the patients had signs of TMD , most commonly myofascial pain . Forty-three percent of the patients reported that their tinnitus was improved at the 2-year follow-up , 39 % that it was unchanged , and 17 % that it was impaired compared to before the treatment . Twelve percent of the subjects in the control group reported that their tinnitus was improved compared to 2 years previously , 32 % that it was unchanged , and 56 % that it was impaired . The difference between groups was significant ( χ2 : p<0.001 ) . Conclusion . The results of this study showed that TMD symptoms and signs are frequent in patients with tinnitus and that TMD treatment has a good effect on tinnitus in a long-term perspective , especially in patients with fluctuating tinnitus BACKGROUND Whether the co-occurrence of signs and symptoms of a craniom and ibular disorder ( CMD ) and chronic tinnitus are coincidental or causal is controversial . Therefore , the effects of splint therapy and self-therapy on perceived tinnitus were evaluated . PATIENTS AND METHODS Fifty-nine patients with chronic tinnitus were divided into three groups . In a cross-over design , two groups received the two different treatments and were compared with a control group . All patients received the initial basic tinnitus therapy . RESULTS No significant correlation was established between the groups receiving treatment and the control group that would vali date a link between tinnitus and CMD . CONCLUSION The results of this study suggest a coincidental relationship between the two complexes of symptoms The aim of this study was to investigate the frequency of otologic symptoms and their relationship to orofacial signs and symptoms of temporom and ibular disorder ( TMD ) , and the effect of orofacial myofunctional therapy . The study was conducted on eight asymptomatic subjects ( Group C ) and 20 subjects with articular TMD , r and omly distributed over two groups : one treated using orofacial myofunctional therapy ( OMT Group ) and a control group with TMD ( Group CTMD ) . Patient selection was based upon the Research Diagnostic Criteria for TMD ( RDC/TMD ) . All subjects su bmi tted to a clinical examination with self-reporting of symptom severity , and to orofacial myofunctional and electromyographic evaluation at diagnosis and again , at the end of the study . Correlations were calculated using the Pearson test and inter- and intragroup comparisons were made ( p < 0.05 ) . In the diagnosis phase , subjects with TMD reported earache ( 65 % ) , tinnitus ( 60 % ) , ear fullness ( 90 % ) , and 25 % of the asymptomatic subjects reported tinnitus . The otologic symptoms were correlated with tenderness to palpation of the temporom and ibular muscles and joints and with orofacial symptoms . Only the OMT group showed a reduction of otologic and orofacial symptoms , of tenderness to palpation and of the asymmetric index between muscles . OMT may help with muscle coordination and a remission of TMD symptoms In clinical practice , it is commonly assumed that occlusal splints have therapeutic value in the treatment of temporom and ibular disorders ( TMD ) , but the evidence based on r and omized controlled trials is scarce . This study evaluated the short-term ( 10-week ) efficacy of a stabilization splint in subjects with recurrent secondary otalgia and active TMD treatment need using a r and omized , controlled , double-blind design . Thirty-six subjects were r and omly allocated to the two treatment groups : the stabilization splint and the control splint group . After 10 weeks ' treatment , the intensity of secondary otalgia , measured on a VAS scale ( from 0 to 100 mm ) , decreased statistically significantly in the stabilization splint group ( t 2.12 ; P 0.006 ) , but not in the control group . Improvement in active TMD treatment need in subjects showing moderate or severe signs and symptoms of TMD was reported significantly more often in the stabilization splint group than in the control splint group ( χ2 5.71 ; P .017 ) . A statistically significant decrease in the Helkimo clinical dysfunction index was seen in the subjects with stabilization splint ( Z -2.63 ; P .009 ) , but not in the subjects with control splint . The results indicate that the use of a stabilization splint is beneficial with regard to secondary otalgia and active TMD treatment need STATEMENT OF PROBLEM The frequent concurrence of tinnitus and temporom and ibular joint and masticatory muscle disorders ( TMD ) has led to the assumption that a possible relationship exists between these 2 conditions . PURPOSE The present prospect i ve clinical study was conducted to assess the possible association between tinnitus and TMD and to investigate the effect of stomatognathic therapy on tinnitus distress . MATERIAL AND METHODS The prevalence of TMD and tinnitus was investigated in a consecutive series of 951 patients at the Department of Prosthetic Dentistry at the University Medical Center Regensburg , Germany . Patients with TMD and simultaneous tinnitus were included in the prospect i ve clinical trial ( n=25 ) . Baseline examination comprised a detailed functional analysis , diagnosis of temporom and ibular joint and masticatory muscle disorder , and a tinnitus question naire . All the participants received individual dental functional therapy ( oral splints , physiotherapy ) . The effects of functional therapy on TMD and tinnitus symptoms were examined 3 to 5 months after the initiation of dental functional therapy . Means ( st and ard deviations ) were calculated , and 1-way ANOVA was used to investigate statistical differences ( α=.05 ) . The differences of the 2 binary outcomes were compared with the Pearson χ(2 ) test , and the relative risk was calculated . RESULTS Prevalence of tinnitus was found to be 8 times higher in participants with TMD ( 30 of 82 [ 36.6 % ] ) than in participants without TMD ( 38 of 869 [ 4.4 % ] ) . All the participants with unilateral TMD and unilateral tinnitus showed these conditions on the same side . Stomatognathic therapy improved tinnitus symptoms in 11 of 25 participants ( 44 % ) . CONCLUSIONS The results of this study and the prospect i ve clinical trial showed a significant correlation between tinnitus and TMD . The observed treatment outcome suggests that dental functional therapy may have a positive effect on TMD-related tinnitus |
12,596 | 25,726,920 | Single-session treatments might increase the likelihood of quitting over multiple sessions , but both regimens produced positive outcomes .
Evidence is unclear at present on the optimal number of follow-up calls .
Motivational interviewing may assist people to quit smoking . | BACKGROUND Motivational Interviewing ( MI ) is a directive patient-centred style of counselling , design ed to help people to explore and resolve ambivalence about behaviour change .
It was developed as a treatment for alcohol abuse , but may help people to a make a successful attempt to quit smoking .
OBJECTIVES To determine whether or not motivational interviewing ( MI ) promotes smoking cessation . | Residential treatment for substance use disorders ( SUD ) provides opportunity for smoking intervention . A r and omized controlled trial compared : ( 1 ) motivational interviewing ( MI ) to brief advice ( BA ) , ( 2 ) in one session or with two booster sessions , for 165 alcoholics in SUD treatment . All received nicotine replacement ( NRT ) . MI and BA produced equivalent confirmed abstinence , averaging 10 % at 1 month , and 2 % at 3 , 6 and 12 months . However , patients with more drug use pretreatment ( > 22 days in 6 months ) given BA had more abstinence at 12 months ( 7 % ) than patients in MI or with less drug use ( all 0 % ) . Boosters produced 16 - 31 % fewer cigarettes per day after BA than MI . Substance use was unaffected by treatment condition or smoking cessation . Motivation to quit was higher after BA than MI . Thus , BA plus NRT may be a cost-effective way to reduce smoking for alcoholics with comorbid substance use who are not seeking smoking cessation BACKGROUND Motivational interviewing ( MI ) is widely used for adolescent smoking cessation but empirical support for this approach is mixed . METHODS Adolescent cigarette smokers 14 - 18 years old ( N=162 ) were recruited from medical , school , and community setting s and r and omly assigned to enhanced MI or brief advice ( BA ) for smoking cessation . MI comprised an in-person individual session , a telephone booster session one week later , and a brief telephone-based parent intervention . BA consisted of st and ardized brief advice to quit smoking . Assessment s occurred at baseline , post-treatment and at 1- , 3- , and 6-month follow ups . RESULTS Biochemically-confirmed 7-day point prevalence abstinence rates were low ( e.g. , 4.5 % for MI ; 1.4 % for BA at 1 month ) and did not differ significantly by group at any follow up . Only those in MI reported significant decreases in cigarettes smoked per day ( CPD ) from baseline to 1 month . At 3 and 6 months , smokers in both groups reported significantly reduced CPD with no differences between groups . MI reduced perceived norms regarding peer and adult smoking rates , while BA had no effect on normative perceptions . No group differences emerged for self-reported motivation or self-efficacy to quit smoking . CONCLUSIONS Findings support the efficacy of MI for addressing normative misperceptions regarding peer and adult smoking and for modestly reducing CPD in the short-term ; however , these effects did not translate to greater smoking abstinence . MI may have more promise as a prelude to more intensive smoking intervention with adolescents than as a st and -alone intervention INTRODUCTION The efficacy of contingency-management ( CM ) and motivational enhancement therapy ( MET ) for college student smoking cessation was examined . METHODS Nontreatment-seeking daily smokers ( N = 110 ) were r and omly assigned to 3 weeks of CM versus noncontingent reinforcement ( NR ) and to three individual sessions of MET versus a relaxation control in a 2 x 2 experimental design . Expired carbon monoxide ( CO ) sample s were collected twice daily for 3 weeks . Participants earned 5 US dollars for providing each sample ; additionally , those r and omized to CM earned escalating monetary rewards based on CO reductions ( Week 1 ) and smoking abstinence ( Weeks 2 - 3 ) . RESULTS Compared with NR , CM result ed in significantly lower CO levels and greater total and consecutive abstinence during the intervention . Those in the CM and MET groups reported greater interest in quitting smoking posttreatment , but rates of confirmed abstinence at follow-up were very low ( 4 % at 6-month follow-up ) and did not differ by group . DISCUSSION Findings support the short-term efficacy of CM for reducing smoking among college students . Future research should explore enhancements to CM in this population , including a longer intervention period and the recruitment of smokers who are motivated to quit ABSTRACT Background : Tobacco use is higher among homeless individuals than the general population . Homeless individuals are also more likely to have symptoms of depression . Depression symptoms may add to the burden of homelessness by increasing psychological distress and serve as a barrier to quitting smoking . Objectives : The primary goal of this study is to assess the impact of depression symptoms on psychological distress in homeless smokers . The effect of depression symptoms on abstinence and the effect of Motivational Interviewing ( MI ) on cessation among smokers is also explored . Methods : Homeless smokers ( N = 430 ) enrolled in a smoking cessation study were r and omized to Motivational Interviewing ( MI ) or st and ard care ( SC ) . Participants received nicotine replacement therapy and were followed for 26 weeks . Participants were categorized into a depression symptoms ( DS ) group or control group using the Patient Health Question naire-9 . Between group differences of perceived stress , hopelessness , confidence , craving and abstinence were assessed at weeks 8 and 26 . The interaction between depression symptoms ( levels : DS and control ) and the intervention ( levels : MI and SC ) was also assessed . Results : Homeless smokers in the DS group reported higher levels of hopelessness , perceived stress , and craving . There was no effect of DS status on abstinence at week 8 or week 26 . There was no significant interaction between depression symptoms ( DS vs. Control ) and the intervention ( MI vs. SC ) . Conclusion : Despite reporting greater psychological distress , homeless smokers with depression symptoms in this sample had abstinence levels similar to the control group . Future research should explore protective factors among depressed smokers OBJECTIVE To evaluate the effectiveness of a lifestyle intervention for male workers in the construction industry at risk of cardiovascular disease ( CVD ) . METHODS In a r and omized controlled trial performed in the Netherl and s between 2007 and 2009 , usual care was compared to 6 months of individual counseling using motivational interviewing techniques , delivered face to face and by telephone . Participants aim ed at improving energy balance-related behavior or smoking cessation . Linear regression analyses were performed to determine the effects . RESULTS Body weight had significantly decreased at 6 ( β=-1.9 , 95 % CI -2.6 ; -1.2 ) and 12 months ( β=-1.8 , 95%CI -2.8 ; -1.1 ) . The intervention effects were also significant for diastolic blood pressure at 6 months ( β=-1.7 , 95 % CI -3.3 ; -0.1 ) . Among participants who had aim ed at energy balance , the intervention had a significant favorable effect on body weight at 6 ( β=-2.1 , 95 % CI -2.9 ; -1.3 ) and 12 months ( β=-2.2 , 95 % CI -3.1 ; -1.3 ) and at HDL cholesterol ( β=0.05 , 95 % CI 0.01 ; 0.10 ) and HbA1c ( β=-0.06 , 95%CI -0.12 ; -0.001 ) at 12 months , although there was no intervention effect on these variables over time . CONCLUSION Individual-based counseling result ed in significant beneficial long-term effects on body weight . This is an important finding for occupational health , considering the rising prevalence of obesity and CVD INTRODUCTION Smokers with serious mental illness ( SMI ) have a high smoking prevalence and a low quit rate . Motivational interviewing ( MI ) is an empirically supported approach for addressing substance use disorders and may motivate smokers with SMI to quit . METHODS We r and omized smokers ( N = 98 ) with SMI to receive a single 45-minute session of ( 1 ) MI with personalized feedback or ( 2 ) interactive education . We hypothesized that participants receiving the MI intervention would be more likely to follow-up on a referral for tobacco dependence treatment , to make a quit attempt , and to quit smoking than those receiving the interactive educational intervention . RESULTS Smokers receiving an MI intervention were significantly more likely to make a quit attempt by the 1-month follow-up ( 34.7 % vs. 14.3 % ; OR = 4.39 [ 95 % CI = 1.44 to 13.34 ] , P = .009 ) ; however , these quit attempts did not translate into abstinence . In addition , 32.7 % of those receiving MI followed-up on a referral for tobacco dependence treatment ( vs. 20.4 % receiving interactive education ; OR = 2.02 [ 95 % CI = 0.76 to 3.55 ] , P = .157 ) . MI Treatment Integrity Code ratings indicated that the interventions were easily distinguishable from each other and that MI was delivered with proficiency . Despite the intervention 's brevity , participants reported high levels of therapeutic alliance with their therapist . CONCLUSIONS A brief adaptation of MI with personalized feedback appears to be a promising approach for increasing quit attempts in smokers with SMI , but future research is required to determine how to best help smokers with SMI to attain sustained abstinence Background Intensive lifestyle interventions in well-controlled setting s are effective in lowering the risk of chronic diseases such as type 2 diabetes ( T2DM ) and cardiovascular diseases ( CVD ) , but there are still no effective lifestyle interventions for everyday practice . In the Hoorn Prevention Study we aim ed to assess the effectiveness of a primary care based lifestyle intervention to reduce the estimated risk of developing T2DM and for CVD mortality , and to motivate changes in lifestyle behaviors . Methods The Hoorn Prevention Study is a parallel group r and omized controlled trial , implemented in the region of West-Friesl and , the Netherl and s. 622 adults with ≥10 % estimated risk of T2DM and /or CVD mortality were r and omly assigned and monitored over a period of 12 months . The intervention group ( n=314 ) received a theory-based lifestyle intervention based on an innovative combination of motivational interviewing and problem solving treatment , provided by trained practice nurses in 12 general practice s. The control group ( n=308 ) received existing health brochures . Primary outcomes was the estimated diabetes risk according to the formula of the Atherosclerosis Risk In Communities ( ARIC ) Study , and the estimated risk for CVD mortality according to the Systematic COronary Risk Evaluation ( SCORE ) formula . Secondary outcomes included lifestyle behavior ( diet , physical activity and smoking ) . The research assistants , the principal investigator and the general practitioners were blinded to group assignment . Linear and logistic regression analysis was applied to examine the between-group differences in each outcome measure , adjusted for baseline values . Results 536 ( 86.2 % ) of the 622 participants ( age 43.5 years ) completed the 6-month follow-up , and 502 ( 81.2 % ) completed the 12-month follow-up . The mean baseline T2DM risk was 18.9 % ( SD 8.2 ) and the mean CVD mortality risk was 3.8 % ( SD 3.0 ) . The intervention group participated in a median of 2 sessions . Intention-to-treat analyses showed no significant differences in outcomes between the two groups at 6 or 12-months follow-up . Conclusions The lifestyle intervention was not more effective than health brochures in reducing risk scores for T2DM and CVD or improving lifestyle behavior in an at-risk population .Trial registration Current Controlled Trials : IS RCT INTRODUCTION Concerns about retention are a major barrier to conducting studies enrolling homeless individuals . Since smoking is a major problem in homeless communities and research on effective methods of promoting smoking cessation is needed , we describe strategies used to increase retention and participant characteristics associated with retention in smoking cessation study enrolling homeless adults . METHODS The parent study was a 2-group r and omized controlled trial with 26-week follow-up enrolling 430 homeless smokers from emergency shelters and transitional housing units in Minneapolis/Saint Paul , MN , USA . Multiple strategies were used to increase retention , including conducting visits at convenient locations for participants , collecting several forms of contact information from participants , using a schedule that was flexible and included frequent low-intensity visits , and providing incentives . Participant demographics as well as characteristics related to tobacco and drug use and health status were analyzed for associations with retention using univariate and multivariate analysis . RESULTS Overall retention was 75 % at 26 weeks . Factors associated with increased retention included greater age ; having healthcare coverage ; history of multiple homeless episodes , lower stress level ; and higher PHQ-9 ( Patient Health Question naire-9 ) score . A history of excessive drinking and drug use were associated with decreased retention . CONCLUSIONS It is possible to successfully retain homeless individuals in a smoking cessation study if the study is design ed with participants ' needs in mind BACKGROUND Smoking reduction has been introduced as an alternative to smokers unable or unwilling to quit but has never been implemented in a population -based intervention . METHODS Two thous and four hundred eight daily smokers in all motivational stages were included in a r and omised population -based intervention study , in Copenhagen , Denmark . Smokers , unwilling or unable to quit , were encouraged to reduce their tobacco consumption . Furthermore , smokers in the high-intensity intervention were offered participation in smoking reduction groups . RESULTS Twenty-three percent of those who attended both baseline and 1 year visit reported reduction by at least 5 g and 8 % reported a halving or more . Halving of tobacco consumption was achieved significantly more often than in the background population , OR = 2.6 ( 1.6 - 4.4 ) , even when assuming that non- participants had not reduced , OR = 1.7 ( 1.0 - 2.8 ) . Reduction of at least 5 g doubled the probability of increased motivation to quit and a halving increased it more than four times . The reductions were not vali date d. Less than 2 % attended the smoking reduction groups . CONCLUSION The smoking reduction intervention was significant in self-reported reduction of tobacco consumption and subsequently increased motivation to quit . This may open new perspectives , with reduction as a first step towards cessation , a possible supplement to smoking cessation strategies Background Smoking is the world 's fourth most common risk factor for disease , the leading preventable cause of death , and it is associated with tremendous social costs . In the Netherl and s , the smoking prevalence rate is high . A total of 27.7 % of the population over age 15 years smokes . In addition to the direct advantages of smoking cessation for the smoker , parents who quit smoking may also decrease their children 's risk of smoking initiation . Methods / Design A r and omized controlled trial will be conducted to evaluate the effectiveness of proactive telephone counselling to increase smoking cessation rates among smoking parents . A total of 512 smoking parents will be proactively recruited through their children 's primary schools and r and omly assigned to either proactive telephone counselling or a control condition . Proactive telephone counselling will consist of up to seven counsellor-initiated telephone calls ( based on cognitive-behavioural skill building and Motivational Interviewing ) , distributed over a period of three months . Three supplementary brochures will also be provided . In the control condition , parents will receive a st and ard brochure to aid smoking cessation . Assessment s will take place at baseline , three months after start of the intervention ( post-measurement ) , and twelve months after start of the intervention ( follow-up measurement ) . Primary outcome measures will include sustained abstinence between post-measurement and follow-up measurement and 7-day point prevalence abstinence and 24-hours point prevalence abstinence at both post- and follow-up measurement . Several secondary outcome measures will also be included ( e.g. , smoking intensity , smoking policies at home ) . In addition , we will evaluate smoking-related cognitions ( e.g. , attitudes towards smoking , social norms , self-efficacy , intention to smoke ) in 9 - 12 year old children of smoking parents . Discussion This study protocol describes the design of a r and omized controlled trial to evaluate the effectiveness of proactive telephone counselling in smoking cessation . It is expected that , in the telephone counseling condition , parental smoking cessation rates will be higher and children 's cognitions will be less favorable about smoking compared to the control condition . Trial registration The protocol for this study is registered with the Netherl and s Trial Register NTR2707 Abstract Objective To determine whether motivational interviewing — a behavioural therapy for addictions — provided at home by specially trained midwives helps pregnant smokers to quit . Design R and omised controlled non-blinded trial analysed by intention to treat . Setting Clinics attached to two maternity hospitals in Glasgow . Participants 762/1684 pregnant women who were regular smokers at antenatal booking : 351 in intervention group and 411 in control group . Interventions All women received st and ard health promotion information . Women in the intervention group were offered motivational interviewing at home . All interviews were recorded . Main outcome measures Self reported smoking cessation verified by plasma or salivary cotinine concentration . Results 17/351 ( 4.8 % ) women in the intervention group stopped smoking ( according to self report and serum cotinine concentration < 13.7 ng/ml ) compared with 19/411(4.6 % ) in the control group . Fifteen ( 4.2 % ) women in the intervention group cut down ( self report and cotinine concentration less than half that at booking ) compared with 26 ( 6.3 % ) in the control group . Fewer women in the intervention group reported smoking more ( 18 ( 5.1 % ) v 44 ( 10.7 % ) ; relative risk 0.48 , 95 % confidence interval 0.28 to 0.81 ) . Birth weight did not differ significantly ( mean 3078 g v 3048 g ) . Conclusion Good quality motivational interviewing did not significantly increase smoking cessation among pregnant women OBJECTIVE To examine the efficacy of four individually-delivered Motivational Interviewing counseling sessions for smoking cessation versus a matched intensity comparison condition . METHOD From 2006 - 2009 , students attending college in the Midwest smoking at least 1 of 30 days were recruited regardless of their interest in quitting . 30 fraternities and sororities were r and omized , result ing in 452 participants . RESULTS No significant differences were found for 30-day cessation between treatment and comparison at end of treatment ( 31.4 % vs 28 % , OR=1.20 , 95 % CI 0.72,1.99 ) or at follow-up ( 20.4 % vs 24.6 % , OR=0.78 , 95 % CI 0.50,1.22 ) . Predictors of cessation at follow-up , regardless of condition , included more sessions attended ( OR 1.2 , 95 % CI 1.1,1.8 ) and more cigarettes smoked in 30 days at baseline ( OR 4.7 , 95 % CI 2.5,8.9 ) . The odds of making at least one quit attempt were significantly greater for those in the smoking group at end of treatment ( OR 1.75 , 95 % CI 1.11,2.74 ) and follow-up ( OR 1.66 , 95 % CI 1.11,2.47 ) . Modeling showed reduction in days smoked for both groups . At end of treatment , more frequent smokers in the treatment condition had greater reductions in days smoked . CONCLUSION Motivational Interviewing for smoking cessation is effective for increasing cessation attempts and reducing days smoked in the short run Objective . To evaluate an intervention programme on smoking cessation in patients with diabetes mellitus in primary healthcare . Design . Regional controlled intervention study . Setting . Seventeen primary healthcare centres in Sweden . Intervention . In the intervention centres , nurses with education in diabetes were given one half-day of training in motivational interviewing and smoking cessation . An invitation to participate in a smoking cessation group was mailed to patients from the intervention centres followed by a telephone call from the patient 's diabetes nurse . The nurses who intervened were specially educated in smoking cessation . The control group received a letter containing advice to stop smoking and information about a one-year follow-up . Patients . Daily smokers with diabetes mellitus , 30–75 years of age . In the intervention centres 241 patients fulfilled the criteria and in the control centres 171 patients . Main outcome measures . Self-reported smoking habits after one year . Results . In total , 21 % of the smokers accepted group treatment . After 12 months , 20 % ( 42/211 ) in the intervention centres reported that they had stopped smoking and 7 % ( 10/140 ) in the control centres ; 40 % ( 19/47 ) of the smokers who had participated in group treatment reported that they had stopped smoking . Conclusion . A computerized record system for patients in primary healthcare was used to identify diabetic patients who were smokers . The selected group was invited to a stop smoking programme . At a one-year follow-up significantly more patients in the intervention centres had stopped smoking compared with patients in the control centres Background Of all workers in Dutch construction industry , 20 % has an elevated risk of cardiovascular disease ( CVD ) . A major risk factor for CVD risk is an unhealthy lifestyle . The aim of our study is to design a lifestyle intervention for construction workers with an elevated CVD risk , and to evaluate its ( cost- ) effectiveness . Methods / Design In a RCT , 692 participants will be r and omised to either the control or the intervention group . The control group will receive usual care . For the intervention group , a lifestyle intervention has been design ed based on interviews and current literature . The intervention will last 6 months and will comprise 3 face-to-face and 4 telephone contacts , consisting of individual counselling aim ed at increasing daily physical activity ( PA ) and improving dietary behaviour , and /or smoking cessation . Counselling will take place at the Occupational Health Service ( OHS ) , and will be done according to motivational interviewing ( MI ) . Additional written information about healthy lifestyle will also be provided to those in the intervention group . At baseline , after 6 and after 12 months , measurements will take place . Primary outcome variables will be the lifestyle behaviours of concern , i.e. daily PA , dietary intake , and smoking status . Secondary outcome variables will be body mass index ( BMI ) , systolic and diastolic blood pressure , total and HDL blood cholesterol , Hba1c and cardio-respiratory fitness ( CRF ) . Sickness absenteeism and cost-effectiveness will be assessed as well . Multilevel analysis will be performed to compare all outcome measures between the intervention group and the control group . Discussion By improving lifestyle , CVD risk may be lowered , yielding benefits for both employee and employer . If proven effective , this lifestyle intervention will be implemented on a larger scale within the Occupational Health Services in construction industry . Trial registration Current Controlled Trials IS RCT Purpose . This study describes the design , recruitment , and baseline data of the first smoking-cessation clinical trial for African-American light smokers , Kick It at Swope II ( KIS-II ) . Design . KIS-II was a r and omized trial testing the efficacy of nicotine gum ( vs. placebo gum ) in combination with counseling ( motivational interviewing or health education ) . Setting . This study was conducted at an urban community-based clinic serving predominantly lower-income African-Americans . Subjects . African-Americans who smoked 1 to 10 cigarettes per day were eligible . Of 1933 individuals screened , 1012 ( 52 % ) were eligible and 755 ( 75 % ) were enrolled in the study . Measures . Baseline assessment included smoking history and psychometric measures . Analysis . The majority of participants were women ( 67 % ) with a mean age of 45.1 years ( SD = 10.7 ) . Participants smoked on average 7.6 cigarettes ( SD = 3.21 ) per day , had a mean exhaled carbon monoxide level of 13.9 ppm ( SD = 8.9 ) and a mean serum cotinine level of 244.2 ng/mL ( SD = 154.4 ) , and reported high levels of motivation and confidence to quit smoking . Conclusion . African-American light smokers were motivated to stop smoking and to enroll in a smoking-cessation program . Characteristics of our sample suggest African-American light smokers are an appropriate group for inclusion in smoking-cessation interventions OBJECTIVE To test the efficacy of a family-assisted smoking cessation intervention based on Motivational interviewing ( MI ) among low-motivated Chinese smokers . METHODS A two-armed r and omized controlled trial study design was utilized . 159 Smoker-supporter pairs were r and omly allocated to the intervention ( a family-assisted MI intervention-77 ) or control ( an intensity-matched health education-82 ) group ( IG & CG ) . Change in smoking characteristics , communication characteristics , Partner Intervention Question naire ( PIQ ) , Decisional Balance Scale ( DBL ) , and Situational Temptations Scale ( STP ) were measured at baseline , post-intervention , 3-month and 6-month follow-up . RESULTS Compared to CG , IG had more significant increase over time in self-report quitting attempts of at least 24h , biochemically verified 7-day smoking abstinence , the Positive dimension of PIQ and the Cons in DBL , whereas the daily cigarettes smoked , the Pros in DBL and STP were showed more significant decrease over time in IG ( P<0.05 ) . After intervention , the communication frequency and satisfactory were also improved by smokers ( P<0.01 ) . CONCLUSION The family-assisted MI intervention is more effective in changing the smoking behaviors and increasing the communication between smokers and family , than health education . PRACTICAL IMPLICATION S Using the family-assisted smoking cessation intervention based on MI , community health service providers can influence and empower low-motivated smokers positively for quit smoking AIMS To test whether , in comparison to usual care , brief motivational or reduction interventions increase quit attempts ( QA ) or abstinence among smokers who are not ready to quit . DESIGN A parallel-group r and omized controlled trial of brief motivational ( n = 185 ) , reduction ( n = 186 ) or usual care ( n = 189 ) telephone interventions delivered over the course of 4 weeks . Outcomes were assessed at 6- and 12-month follow-ups . No medication was provided . SETTING United States . PARTICIPANTS A total of 560 adult smokers of ≥ 10 cigarettes per day who were not ready to quit in the next 30 days . MEASUREMENTS The primary outcomes were whether participants made a QA that lasted ≥ 24 hours and whether they made a QA of any length between baseline and 6 months . Secondary outcomes included 7-day point-prevalence abstinence at 6 and 12 months . The 12-month follow-up was added after the study began . FINDINGS A priori-defined comparisons were between motivational versus usual care and reduction versus usual care conditions . The probability of making a QA that lasted ≥ 24 hours was not significantly different between the motivational ( 38 % ) or the reduction ( 31 % ) conditions and the usual care ( 34 % ) condition [ motivational versus usual care odds ratio ( OR ) = 1.19 , 95 % confidence interval ( CI ) = 0.78 - 1.82 ; reduction versus usual care OR = 0.89 , 95 % CI = 0.57 - 1.36 ] . Bayes factors ranged from 0.13 to 0.18 . Findings regarding a QA of any length were similar . At 6 months , the motivational condition had marginally more abstinence than usual care ( 11 versus 5 % , OR = 2.17 , 95 % CI = 0.99 - 4.77 ) , but the reduction condition was not significantly different from usual care ( 8 versus 5 % , OR = 1.57 , 95 % CI = 0.69 - 3.59 ) . At 12 months , the motivational condition had significantly more abstinence than usual care ( 10 versus 4 % , OR = 2.80 , 95 % CI = 1.14 - 6.88 ) and the reduction condition had marginally more abstinence than usual care ( 9 versus 4 % , OR = 2.45 , 95 % CI = 0.98 - 6.09 ) . CONCLUSIONS Among adult smokers who are not ready to quit , both logistic regression and Bayesian analysis indicate that neither motivational nor reduction-based telephone interventions increased the odds of making a quit attempt in comparison to usual care at 6 months . The motivational intervention appeared to increase abstinence at 6 months and did increase abstinence at 12 months . The reduction intervention did not increase abstinence at 6 months but appeared to increase abstinence at 12 months INTRODUCTION Hospitalization is a unique opportunity for smoking cessation , but prior interventions have measured efficacy with narrowly defined population s. The objective of this study was to enroll smokers admitted to two " safety net " hospitals and compare the effectiveness of two post-discharge cessation interventions . DESIGN A r and omized comparative effectiveness trial was conducted . SETTING / PARTICIPANTS At two New York City public hospitals , every hospitalized patient identified as a smoker ( based on admission records ) was approached . Inclusion criteria were : smoked cigarettes in the past 30 days ; spoke English , Spanish , or M and arin ; had a U.S. phone number ; not discharged to an institution where follow-up or smoking was limited ; and not pregnant/breastfeeding . Of 18,797 patients identified as current smokers between July 2011 and April 2014 , a total of 3,047 ( 16 % ) were discharged before being approached , 3,273 ( 17 % ) were not current smokers , 4,026 ( 21 % ) had no U.S. phone number , 2,831 ( 15 % ) were ineligible for other reasons , and 3,983 ( 21 % ) refused participation . In total , 1,618 ( 9 % ) participants enrolled in the study . During follow-up , 69 % of participants were reached at 2 months and 68 % at 6 months . INTERVENTION At discharge , participants were r and omized to multisession telephone counseling from study staff ( n=804 ) or referral to the state quitline for proactive outreach and counseling ( n=814 ) . MAIN OUTCOME MEASURES Self-reported abstinence at 6 months was measured . Analyses were conducted in late 2015 . RESULTS One quarter of participants were homeless or in unstable housing , 60 % had a history of substance abuse , 43 % reported current hazardous drinking , and half had a psychiatric diagnosis other than substance abuse . At follow-up , the rate of abstinence ( 30-day point prevalence ) was higher in the intensive counseling arm than the quitline arm at 2 months ( 29.0 % vs 20.7 % ; relative risk=1.40 ; 95 % CI=1.13 , 1.73 ) and 6 months ( 37.4 % vs 31.5 % ; relative risk=1.19 ; 95 % CI=1.01 , 1.40 ) . CONCLUSIONS Intensive counseling was more effective than referral to the state quitline . Long-term abstinence was excellent in both groups . Many patients were not eligible for enrollment despite minimal exclusion criteria . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT01363245 Background Although the current Clinical Practice Guideline recommend Motivational Interviewing for use with smokers not ready to quit , the strength of evidence for its use is rated as not optimal . The purpose of the present study is to address key method ological limitations of previous studies by ensuring fidelity in the delivery of the Motivational Interviewing intervention , using an attention-matched control condition , and focusing on unmotivated smokers whom meta-analyses have indicated may benefit most from Motivational Interviewing . It is hypothesized that MI will be more effective at inducing quit attempts and smoking cessation at 6-month follow-up than brief advice to quit and an intensity-matched health education condition . Methods / Design A sample of adult community resident smokers ( N = 255 ) who report low motivation and readiness to quit are being r and omized using a 2:2:1 treatment allocation to Motivational Interviewing , Health Education , or Brief Advice . Over 6 months , participants in Motivational Interviewing and Health Education receive 4 individual counseling sessions and participants in Brief Advice receive one brief in-person individual session at baseline . Rigorous monitoring and independent verification of fidelity will assure the counseling approaches are distinct and delivered as planned . Participants complete surveys at baseline , week 12 and 6-month follow-up to assess demographics , smoking characteristics , and smoking outcomes . Participants who decide to quit are provided with a self-help guide to quitting , help with a quit plan , and free pharmacotherapy . The primary outcome is self-report of one or more quit attempts lasting at least 24 hours between r and omization and 6-month follow-up . The secondary outcome is biochemically confirmed 7-day point prevalence cessation at 6-month follow-up . Hypothesized mediators of the presumed treatment effect on quit attempts are greater perceived autonomy support and autonomous motivation . Use of pharmacotherapy is a hypothesized mediator of Motivational Interviewing ’s effect on cessation . Discussion This trial will provide the most rigorous evaluation to date of Motivational Interviewing ’s efficacy for encouraging unmotivated smokers to make a quit attempt . It will also provide effect-size estimates of MI ’s impact on smoking cessation to inform future clinical trials and inform the Clinical Practice Guideline .Trial registration Clinical Trials.gov Purpose The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training ( DSMT ) . Methods A r and omized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center . A total of 114 subjects were r and omized to intervention ( n = 57 ; face-to-face motivational interviewing plus telephone counseling and offering of medication ) or st and ard care ( n = 57 ) . Outcome measures included tobacco cessation rates , mean number of cigarettes smoked , A1C , weight , blood pressure , and lipids . Results Intensive intervention using motivational interviewing integrated into a st and ard DSMT program result ed in a trend toward greater abstinence at 3 months of follow-up in those receiving the intervention . However , this same trend was not observed at 6 months . The addition of this structured smoking cessation intervention did not negatively affect either diabetes education or other measures of diabetes management , including A1C values Abstract Objective . To study the effectiveness of a comprehensive diabetes programme in general practice that integrates patient-centred lifestyle counselling into structured diabetes care . Design and setting . Cluster r and omised trial in general practice s. Intervention . Nurse-led structured diabetes care with a protocol , record keeping , reminders , and feedback , plus training in motivational interviewing and agenda setting . Subjects . Primary care nurses in 58 general practice s and their 940 type 2 diabetes patients with an HbA1c concentration above 7 % , and a body mass index ( BMI ) above 25 kg/m2 . Main outcome measures . HbA1c , diet , and physical activity ( medical records and patient question naires ) . Results . Multilevel linear and logistic regression analyses adjusted for baseline outcomes showed that despite active nurse participation in the intervention , the comprehensive programme was no more effective than usual care after 14 months , as shown by HbA1c levels ( difference between groups = 0.13 ; CI 20.8–0.35 ) and diet ( fat ( difference between groups = 0.19 ; CI 20.82–1.21 ) ; vegetables ( difference between groups = 0.10 ; CI-0.21–0.41 ) ; fruit ( difference between groups = 20.02 ; CI 20.26–0.22 ) ) , and physical activity ( difference between groups = 21.15 ; CI 212.26–9.97 ) , or any of the other measures of clinical parameters , patient 's readiness to change , or quality of life . Conclusion . A comprehensive programme that integrated lifestyle counselling based on motivational interviewing principles integrated into structured diabetes care did not alter HbA1c or the lifestyle related to diet and physical activity . We thus question the impact of motivational interviewing in terms of its ability to improve routine diabetes care in general practice Background Smoking rates , and associated negative health outcomes , are disproportionately high among people with mental illness compared to the general population . Smoke-free policies within mental health hospitals can positively impact on patients ’ motivation and self-efficacy to address their smoking . However , without post-discharge support , preadmission smoking behaviours typically resume . This protocol describes a r and omised controlled trial that aims to assess the efficacy of linking mental health in patients to community-based smoking cessation supports upon discharge as a means of reducing smoking prevalence . Methods / Design Eight hundred participants with acute mental illness will be recruited into the r and omised controlled trial whilst in patients at one of four psychiatric inpatient facilities in the state of New South Wales , Australia . After completing a baseline interview , participants will be r and omly allocated to receive either : ‘ Supported Care ’ , a multimodal smoking cessation intervention ; or ‘ Normal Care ’ , consisting of existing hospital care only . The ‘ Supported Care ’ intervention will consist of a brief motivational interview and a package of self-help material for abstaining from smoking whilst in hospital , and , following discharge , 16 weeks of motivational telephone-based counselling , 12 weeks of free nicotine replacement therapy , and a referral to the Quitline . Data will be collected at 1 , 6 and 12 months post-discharge via computer-assisted telephone interview . The primary outcomes are abstinence from smoking ( 7-day point prevalence and prolonged cessation ) , and secondary outcomes comprise daily cigarette consumption , nicotine dependence , quit attempts , and readiness to change smoking behaviour . Discussion If shown to be effective , the study will provide evidence in support of systemic changes in the provision of smoking cessation care to patients following discharge from psychiatric inpatient facilities . Trial registration Australian New Zeal and Clinical Trials Registry ANZTCN : ACTRN12612001042831 . Date registered : 28 September 2012 The purpose of this prospect i ve , r and omized controlled study was to determine the efficacy of an intensified , late pregnancy , smoking cessation intervention for resistant pregnant smokers ( n = 269 ) . Participants received 3 - 5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter ; at 28 weeks , all had been smoking in the past 28 days . The experimental group received a stage of change-based , personalized feedback letter and two telephone counseling calls using Motivational Interviewing ( MI ) strategies . The control group received care as usual . The 34th week cotinine data demonstrated no overall difference between groups . However , an implementation analysis suggested that 43 % of women who received the full intervention ( E2 ) were classified as not smoking compared to 34 % of the control group . At 6 weeks postpartum , 27.1 % of the E2 group reported being abstinent or light smokers vs. 14.6 % of the controls . No differences were detected at 3 and 6 months postpartum . Results lend preliminary but very modest support for this intervention with resistant pregnant smokers . Improvements in the intervention and implementation issues are discussed INTRODUCTION People with a mental health diagnosis have high rates of tobacco use and encounter limited availability of tobacco treatment targeted to their needs . This study compared the effectiveness of a specialized telephone smoking-cessation intervention developed for mental health patients with st and ard state quit-line counseling . DESIGN RCT . SETTING / PARTICIPANTS The study was conducted at six Veterans Health Administration facilities in the Northeast U.S. Participants were 577 mental health clinic patients referred by their providers for smoking-cessation treatment . INTERVENTION From 2010 to 2012 , the study implemented a telephone program that included patient referral from a mental health provider , mailed cessation medications , and telephone counseling . Participants were r and omized to receive a specialized multisession telephone counseling protocol ( n=270 ) or transfer to their state 's quit-line for counseling ( n=307 ) . MAIN OUTCOME MEASURES Participants completed telephone surveys at baseline , 2 months , and 6 months . The study 's primary outcome was self-reported 30-day abstinence at 6 months . Secondary outcomes were self-reported 30-day abstinence , counseling satisfaction and counseling content at 2 months , and self-reported use of cessation treatment and quit attempts at 6 months . Logistic regression was used to compare treatment groups on outcomes , controlling for baseline cigarettes per day and site . Inverse probability weighting and multiple imputation were used to h and le missing abstinence outcomes . Data were analyzed in 2014 - 2015 . RESULTS At 6 months , participants in the specialized counseling arm were more likely to report 30-day abstinence ( 26 % vs 18 % , OR=1.62 , 95 % CI=1.24 , 2.11 ) . There was no significant group difference in abstinence at 2 months ( 18 % vs 14 % , OR=1.31 , 95 % CI=0.49 , 3.49 ) . Participants in the specialized arm were more likely to be assisted with developing a quit plan ; receive follow-up calls after quitting ; and receive counseling on several domains , including motivation , confidence , smoking triggers , coping with urges , and mental health symptoms ( all p<0.05 ) . Specialized counseling participants were more satisfied with treatment and more likely to find the counseling useful ( p<0.05 ) . CONCLUSIONS The specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line . Patients were more satisfied with the specialized counseling program . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00724308 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 Background Mental health in patients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence . Despite the advent of smoke free policies within mental health hospitals , limited systems are in place to support a cessation attempt post hospitalisation , and international evidence suggests that most smokers return to pre-admission smoking levels following discharge . This protocol describes a r and omised controlled trial that will test the feasibility , acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness . Methods / Design This study will be conducted as a r and omised controlled trial . 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility . Participants will complete a baseline survey and will be r and omised to either a multimodal smoking cessation intervention or provided with hospital smoking care only . R and omisation will be stratified by diagnosis ( psychotic , non-psychotic ) . Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge : nicotine replacement therapy ( NRT ) ; referral to Quitline ; smoking cessation groups ; and fortnightly telephone support . Outcome data , including cigarettes smoked per day , quit attempts , and self-reported 7-day point prevalence abstinence ( vali date d by exhaled carbon monoxide ) , will be collected via blind interview at one week , two months , four months and six months post discharge . Process information will also be collected , including the use of cessation supports and cost of the intervention . Discussion This study will provide comprehensive data on the potential of an integrated , multimodal smoking cessation intervention for persons with an acute mental illness , linking inpatient with community cessation support . Trial Registration Australian and New Zeal and Clinical Trials Registry ANZTCN : This study reports on the evaluation of the feasibility , cost , and cost-effectiveness of a proactively provided telephone-based motivational smoking cessation intervention to an underserved population of pregnant smokers who may or may not receive ongoing prenatal care . As part of the New Engl and SCRIPT r and omized clinical trial comparing the efficacy of three types of smoking cessation interventions for pregnant smokers , one-third of the women ( n = 358 ) received a motivational telephone counseling intervention ( MI ) delivered by trained counselors using a semistructured protocol . Although this population was very mobile , the MI counselors were able to reach 86 % of the women with at least one call and 46 % received all three calls . The group receiving three MI calls had a cotinine-confirmed quit rate of 23 % . Cost-effectiveness analyses for those women receiving telephone counseling supported the net benefit in favor of the three phone calls compared with the women who did not receive any telephone calls , with an effectiveness to cost ratio of 1:US dollars 84 . Our results suggest that telephone-based motivational smoking cessation counseling may be a feasible and cost-effective method for low-income pregnant smokers enrolled in prenatal care 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 Background Smoking remains the leading cause of preventable illness and mortality in the United States . Individuals with Posttraumatic Stress Disorder ( PTSD ) have smoking rates higher than that of others and fewer individuals with PTSD have quit smoking . This r and omized controlled trial was design ed to test the effectiveness of integrating telehealth care management and smoking cessation with motivational interviewing for Veterans with PTSD . Methods / Design All smokers with PTSD , regardless of their desire to quit , were invited to participate . Enrollment occurred between November 2009 and April 2013 . Target enrollment was 120 participants . Enrolled participants were r and omized to either the control group , receiving usual care including a telehealth PTSD program , with a device that delivered PTSD information and in-home care management , or the intervention group , which included ( 1 ) a telehealth PTSD program , ( 2 ) motivational interviewing-based smoking cessation curricula via the telehealth device , and ( 3 ) weekly motivational interviewing counseling phone calls . Outcomes are self-reported 24-hour quit attempts , progression along the stages of change and 7-day point prevalence quit smoking rates for the intervention group compared to usual care alone . Secondary outcomes include participants ’ perception of care coordination , patient satisfaction with motivational interviewing , PTSD symptoms , pain , depression and quality of life . Discussion Motivational interviewing has been shown to increase readiness for change and smoking cessation care has been shown to be more successful when incorporated into in-person mental health care . Our study builds on previous studies . It integrates a written smoking cessation curriculum and phone-based motivational interviewing counseling into an established PTSD home telehealth care coordination program . This paper describes the design and methods of our r and omized control trial . Trial registration Clinical Trials.gov , NCT00908882 , May 22 , 2009 AIMS To test the effectiveness of tailored quitline ( telephone ) counselling among smoking parents recruited into cessation support through their children 's primary schools . DESIGN Two-arm r and omized controlled trial with 3- and 12-month follow-up . SETTING Proactive telephone counselling was administered by the Dutch national quitline . PARTICIPANTS Smoking parents were recruited through their children 's primary schools and received either intensive quitline support in combination with tailored supplementary material s ( n = 256 ) or a st and ard self-help brochure ( n = 256 ) . MEASUREMENTS The primary outcome was 7-day point-prevalence abstinence at 12-month follow-up . Also measured were baseline characteristics , use of and adherence to nicotine replacement therapy and pharmacotherapy , smoking characteristics and implementation of a home smoking ban . FINDINGS Parents who received quitline counselling were more likely to report 7-day point-prevalence abstinence at 12-month assessment [ 34.0 versus 18.0 % , odds ratio ( OR ) = 2.35 , confidence interval ( CI ) = 1.56 - 3.54 ] than those who received a st and ard self-help brochure . Parents who received quitline counselling were more likely to use nicotine replacement therapy ( P < 0.001 ) than those who received a st and ard self-help brochure . Among parents who did not achieve abstinence , those who received quitline counselling smoked fewer cigarettes at 3-month ( P < 0.001 ) and 12-month assessment ( P < 0.001 ) , were more likely to make a quit attempt ( P < 0.001 ) , to achieve 24 hours ' abstinence ( P < 0.001 ) and to implement a complete home smoking ban ( P < 0.01 ) . CONCLUSIONS Intensive quitline support tailored to smoking parents is an effective method for helping parents quit smoking and promoting parenting practice s that protect their children from adverse effects of smoking 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 The prevalence of overweight and elevated cardiovascular disease ( CVD ) risk among workers in the construction industry is relatively high . Improving lifestyle lowers CVD risk and may have work-related benefits . The purpose of the study was to evaluate the effects on physical activity ( PA ) , diet , and smoking of a lifestyle intervention consisting of individual counseling among male workers in the construction industry with an elevated risk of cardiovascular disease ( CVD ) . Methods In a r and omized controlled trial including 816 male blue- and white-collar workers in the construction industry with an elevated risk of CVD , usual care was compared to a 6-month lifestyle intervention . The intervention consisted of individual counseling using motivational interviewing techniques , and was delivered by an occupational physician or occupational nurse . In three face to face and four telephone contacts , the participant 's risk profile , personal determinants , and barriers for behavior change were discussed , and personal goals were set . Participants chose to aim at either diet and PA , or smoking . Data were collected at baseline and after six and 12 months , by means of a question naire . To analyse the data , linear and logistic regression analyses were performed . Results The intervention had a statistically significant beneficial effect on snack intake ( β-1.9 , 95%CI -3.7 ; -0.02 ) and fruit intake ( β 1.7 , 95%CI 0.6 ; 2.9 ) at 6 months . The effect on snack intake was sustained until 12 months ; 6 months after the intervention had ended ( β -1.9 , 95%CI -3.6 ; -0.2 ) . The intervention effects on leisure time PA and metabolic equivalent-minutes were not statistically significant . The beneficial effect on smoking was statistically significant at 6 ( OR smoking 0.3 , 95%CI 0.1;0.7 ) , but not at 12 months ( OR 0.8 , 95%CI 0.4 ; 1.6 ) . Conclusions Beneficial effects on smoking , fruit , and snack intake can be achieved by an individual-based lifestyle intervention among male construction workers with an elevated risk of CVD . Future research should be done on strategies to improve leisure time PA and on determinants of maintenance of changed behavior . Considering the rising prevalence of unhealthy lifestyle and CVD , especially in the aging population , implementation of this intervention in the occupational health care setting is recommended . Trial registration Current Controlled Trials IS RCT OBJECTIVE Schizophrenic patients have high rates of cigarette smoking . The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications . METHOD Forty-five subjects were r and omly assigned to 1 ) the group therapy program of the American Lung Association ( N=17 ) or 2 ) a specialized group therapy program for smokers with schizophrenia ( N=28 ) that emphasized motivational enhancement , relapse prevention , social skills training , and psychoeducation . All subjects participated in 10 weeks of treatment with the nicotine transdermal patch ( 21 mg/day ) and 10 weekly group therapy sessions and continued to receive their pre study atypical ( N=18 ) or typical ( N=27 ) antipsychotic medications . Outcome variables included treatment retention , rate of smoking abstinence , and expired-breath carbon monoxide level . RESULTS Smoking abstinence rates did not differ in the two group therapy programs . However , atypical antipsychotic agents , in combination with the nicotine transdermal patch , significantly enhanced the rate of smoking cessation ( 55.6 % in the atypical agent group versus 22.2 % in the typical group ) , which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels . Risperidone and olanzapine were associated with the highest quit rates . CONCLUSIONS The results suggest that 1 ) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia , 2 ) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation , and 3 ) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia Background Smoking , excessive alcohol consumption , lack of exercise and an unhealthy diet are the key modifiable factors contributing to premature morbidity and mortality in the developed world . Brief interventions in health care consultations can be effective in changing single health behaviours . General Practice holds considerable potential for primary prevention through modifying patients ' multiple risk behaviours , but feasible , acceptable and effective interventions are poorly developed , and uptake by practitioners is low . Through a process of theoretical development , modeling and exploratory trials , we have developed an intervention called Behaviour Change Counselling ( BCC ) derived from Motivational Interviewing ( MI ) . This paper describes the protocol for an evaluation of a training intervention ( the Talking Lifestyles Programme ) which will enable practitioners to routinely use BCC during consultations for the above four risk behaviours . Methods / Design This cluster r and omised controlled efficacy trial ( RCT ) will evaluate the outcomes and costs of this training intervention for General Practitioners ( GPs ) and nurses . Training methods will include : a practice -based seminar , online self-directed learning , and reflecting on video recorded and simulated consultations . The intervention will be evaluated in 29 practice s in Wales , UK ; two clinicians will take part ( one GP and one nurse ) from each practice . In intervention practice s both clinicians will receive training . The aim is to recruit 2000 patients into the study with an expected 30 % drop out . The primary outcome will be the proportion of patients making changes in one or more of the four behaviours at three months . Results will be compared for patients seeing clinicians trained in BCC with patients seeing non-BCC trained clinicians . Economic and process evaluations will also be conducted . Discussion Opportunistic engagement by health professionals potentially represents a cost effective medical intervention . This study integrates an existing , innovative intervention method with an innovative training model to enable clinicians to routinely use BCC , providing them with new tools to encourage and support people to make healthier choices . This trial will evaluate effectiveness in primary care and determine costs of the intervention . Trial Registration IS RCT BACKGROUND Many patients in primary care setting s present with multiple behavioral risk factors for cardiovascular disease . Research has provided little information on the most effective ways to approach multiple behavior change counseling in clinical setting s. METHODS We implemented a r and omized trial in a publicly funded primary care setting to test whether a sequential presentation of stage of change-based counseling to stop smoking , reduce dietary sodium level to less than 100 mEq/L per day , and increase physical activity by at least 10,000 pedometer steps per week would be more effective than simultaneous counseling . African Americans with hypertension , aged 45 to 64 years , initially nonadherent to the 3 behavioral goals , were r and omized to the following conditions : ( 1 ) 1 in-clinic counseling session on all 3 behaviors every 6 months , supplemented by motivational interviewing by telephone for 18 months ; ( 2 ) a similar protocol that addressed a new behavior every 6 months ; or ( 3 ) 1-time referral to existing group classes ( " usual care " ) . The primary end point was the proportion in each arm that met at least 2 behavioral criteria after 18 months . RESULTS A total of 289 individuals ( 67.3 % female ) were r and omized , and 230 ( 79.6 % ) completed the study . At 18 months , only 6.5 % in the simultaneous arm , 5.2 % in the sequential arm , and 6.5 % in the usual-care arm met the primary end point . However , results for single behavioral goals consistently favored the simultaneous group . At 6 months , 29.6 % in the simultaneous , 16.5 % in the sequential , and 13.4 % in the usual-care arms had reached the urine sodium goal ( P = .01 ) . At 18 months , 20.3 % in the simultaneous , 16.9 % in the sequential , and 10.1 % in the usual-care arms were urine cotinine negative ( P = .08 ) . CONCLUSIONS Long-term multiple behavior change is difficult in primary care . This study provides strong evidence that addressing multiple behaviors sequentially is not superior to , and may be inferior to , a simultaneous approach BACKGROUND A multicomponent motivational smoking cessation intervention was evaluated in 33 prenatal , family planning , and pediatric services in 12 public health clinics . Clinic-based intervention components were implemented by clinic personnel as part of routine medical visits . METHODS The evaluation design included pre- and postintervention measurements of multiple study outcomes in a baseline ( all clinics prior to the start of the intervention ) and an experimental period ( matchedpair r and om assignment of clinics to intervention or control conditions ) . Subjects were 683 ( baseline ) and 1,064 ( experimental ) smokers with measurements of smoking outcomes at both times . Mixed-effects regressions analyzed individual outcomes clustered within clinics and services . RESULTS Control and intervention clinics had similar outcomes in the baseline period . In the experiment , outcomes improved in the intervention but not in the control clinics . Compared to controls , smokers exposed to the intervention were more likely to have quit ( 14.5 versus 7.7 % ) or take actions toward quitting and had higher mean action , stage of readiness , and motivation to quit scores . These positive effects persisted when clustering within clinics and services was controlled . CONCLUSIONS This intervention , implemented by clinic personnel as part of routine medical visits , was effective under these natural conditions across different types of clinic service Background There is current controversy about the efficacy of smoking cessation interventions that are based on information obtained by spirometry . The objective of this study is to evaluate the effectiveness in the primary care setting of structured motivational intervention to achieve smoking cessation , compared with usual clinical practice . Methods Design Multicentre r and omized clinical trial with an intervention and a control group . Setting 12 primary care centres in the province of Tarragona (Spain).Subjects of study 600 current smokers aged between 35 and 70 years with a cumulative habit of more than 10 packs of cigarettes per year , attended in primary care for any reason and who did not meet any of the exclusion criteria for the study , r and omly assigned to structured intervention or st and ard clinical attention . InterventionUsual advice to quit smoking by a general practitioner as well as a 20-minute personalized visit to provide detailed information about spirometry results , during which FEV1 , FVC , FEF 25 - 75 % and PEF measurements were discussed and interpreted in terms of theoretical values . Additional information included the lung age index ( defined as the average age of a non-smoker with the same FEV1 as the study participant ) , comparing this with the chronological age to illustrate the pulmonary deterioration that results from smoking . Measurements Spirometry during the initial visit . Structured interview question naire administered at the primary care centre at the initial visit and at 12-month follow-up . Telephone follow-up interview at 6 months . At 12-month follow-up , expired CO was measured in patients who cl aim ed to have quit smoking . Main variablesSmoking cessation at 12 months . Analysis Data will be analyzed on the basis of " intention to treat " and the unit of analysis will be the individual smoker . Expected results Among active smokers treated in primary care we anticipate significantly higher smoking cessation in the intervention group than in the control group . Discussion Application of a motivational intervention based on structured information about spirometry results , improved abstinence rates among smokers seen in actual clinical practice conditions in primary care . Trial registration Clinical Trial.gov , number NCT01194596 BACKGROUND Smokers are more prone to develop postoperative complications . Smoking cessation intervention beginning 4 - 8 weeks prior to surgery improves the postoperative outcome . Cancer patients , however , often undergo surgery less than 4 weeks after diagnosis . The primary objective of this study was therefore to examine if a brief smoking cessation intervention shortly before breast cancer surgery would influence postoperative complications and smoking cessation . METHODS A r and omized controlled multicentre trial with blinded outcome assessment conducted at 3 hospitals in Denmark . One hundred and thirty patients were r and omly assigned to brief smoking intervention ( n = 65 ) or st and ard care ( n = 65 ) . The intervention followed the principles of motivational interviewing and included personalized nicotine replacement therapy aim ed at supporting smoking cessation from 2 days before to 10 days after surgery . RESULTS The overall postoperative complication rate ( including seroma requiring aspiration ) was 61 % in both groups risk ratio ( RR ) 1.00 ( 95 % CI 0.75 - 1.33 ) . The wound complication rate was 44 % versus 45 % . The effect on perioperative smoking cessation was modest , 28 % intervention versus 11 % control group patients , RR 2.49 ( 95 % CI 1.10 - 5.60 ) . There was no effect on smoking cessation at 12 months , 13 % versus 9 % . CONCLUSIONS Brief smoking intervention administered shortly before breast cancer surgery modestly increased self-reported perioperative smoking cessation without having any clinical impact on postoperative complications . The study adds to the body of evidence indicating that brief intervention has no clinical importance for surgical patients in regard to postoperative morbidity . Future studies should be design ed to determine the optimal time of smoking cessation before surgery PURPOSE In this study , the effectiveness of a motivational interviewing smoking cessation YOU-TURN program for adolescents was examined . The program was based on the self-determination theory . METHODS The study was carried out with a nonequivalent control group pretest-posttest design . Participants in the present study were 136 high school students living in D city . The students were assigned to the experimental group ( n=52 ) who participated in the motivational interviewing smoking cessation YOU-TURN program based on self-determination theory , or to the control group ( n=84 ) who participated in a general smoking cessation program . Data were collected from September 1 , 2013 through April 30 , 2014 . Collected data were analyzed using SPSS PC+ 21.0 with Chi-square test , Fisher 's exact test , t-test , Mann-Whitney U test , Repeated Measures ANOVA , and MANOVA-Wilk 's Lambda . RESULTS The experimental group had a significant increase in basic psychological needs , and duration of quitting-smoking in comparison with the control group . The experimental group had a significant decrease in cigarettes smoked per day and cotinine in urine in comparison with the control group . CONCLUSION The motivational interviewing YOU-TURN program , when delivered to adolescents who smoked , was effective in discouraging smoking , and can be utilized as an effective nursing intervention for adolescents who smoke PURPOSE Cancer survivors smoke at rates that are only slightly lower than the general population . This article reports on the final outcomes of Partnership for Health , a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study ( CCSS ) . METHODS This study is a r and omized control trial with follow-up at 8 and 12 months that involved smokers ( n = 796 ) enrolled onto the CCSS cohort . Participants were r and omly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor , tailored and targeted material s , and free nicotine replacement therapy . The intervention was delivered by telephone and postal service mail . RESULTS The quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month ( 16.8 % v 8.5 % ; P < .01 ) and 12-month follow-ups ( 15 % v 9 % ; P < or = .01 ) . Controlling for baseline self-efficacy and readiness to change , the intervention group was twice as likely to quit smoking , compared with the self-help group . Smoking cessation rate increased with an increase in the number of counseling calls . The cost of delivering the intervention was approximately 300 dollars per participant . The incremental cost-effectiveness of the intervention compared with controls was 5,371 dollars per additional quit . CONCLUSION Interventions to prevent future illnesses are of critical importance to childhood cancer survivors . The Partnership for Health intervention result ed in a doubling of smoking cessation quit rates . Because of the seriousness of smoking among childhood cancer survivors , this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke BACKGROUND Rates of smoking among adolescents with psychiatric comorbidity are high , despite the well-known health risks . The current longitudinal study examined patterns of quitting behavior in adolescent smokers with psychiatric comorbidity . METHODS The study evaluated 191 inpatient adolescents who had been enrolled in a r and omized controlled trial of motivational interviewing versus brief advice for smoking cessation , and assessed their intentions to quit smoking . RESULTS Rates of quit attempts at post-hospital , 1-month , and 6-month assessment s were 23 % , 17 % , and 17 % , respectively . Adolescents who reported an intention to quit smoking ( 43 % ) were significantly more likely to report a quit attempt , regardless of psychiatric symptoms , cognitive factors , or substance use . CONCLUSIONS Intention to quit smoking appears to translate to substantial quit behavior , even in a high-risk adolescent population that may otherwise be viewed as uninterested in quitting , suggesting the need to proactively connect this population with adequate services and follow-up support . ( Am J Addict 2013;XX:1 - 6 ) Background GEE and mixed models are powerful tools to compare treatment effects in longitudinal smoking cessation trials . However , they are not capable of assessing the relapse ( from abstinent back to smoking ) simultaneously with cessation , which can be studied by transition models . Methods We apply a first-order Markov chain model to analyze the transition of smoking status measured every 6 months in a 2-year r and omized smoking cessation trial , and to identify what factors are associated with the transition from smoking to abstinent and from abstinent to smoking . Missing values due to non-response are assumed non-ignorable and h and led by the selection modeling approach . Results Smokers receiving high-intensity disease management ( HDM ) , of male gender , lower daily cigarette consumption , higher motivation and confidence to quit , and having serious attempts to quit were more likely to become abstinent ( OR = 1.48 , 1.66 , 1.03 , 1.15 , 1.09 and 1.34 , respectively ) in the next 6 months . Among those who were abstinent , lower income and stronger nicotine dependence ( OR = 1.72 for ≤ vs. > 40 K and OR = 1.75 for first cigarette ≤ vs. > 5 min ) were more likely to have relapse in the next 6 months . Conclusions Markov chain models allow investigation of dynamic smoking-abstinence behavior and suggest that relapse is influenced by different factors than cessation . The knowledge of treatments and covariates in transitions in both directions may provide guidance for design ing more effective interventions on smoking cessation and relapse prevention . Trial Registration clinical trials.gov identifier : AIM To test whether beneficial effects of a single session of Motivational Interviewing ( MI ) on alcohol , tobacco and illicit drug use apparent after 3 months were maintained until 12 months . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either MI ( n = 105 ) or to an assessment -only control condition ( n = 95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people who were current users of illegal drugs ( age range 16 - 20 years ) with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from MI in the form of a topic-based 1-hour single-session discussion . MEASUREMENTS Changes in cigarette , alcohol , cannabis and other drug use and perceptions of risk and harm between the time of recruitment and follow-up interviews after 3 and 12 months . FINDINGS A satisfactory follow-up rate ( 81 % ) was achieved . After 12 months , 3-month differences between MI and assessment -only groups have disappeared almost entirely . Unexpected improvements by the assessment -only control group on a number of outcomes suggest the possibility of reactivity to the research assessment at 3-month follow-up . CONCLUSION In the terms of the original experiment , there is little evidence of enduring intervention effectiveness shown by between-group differences after 12 months . Deterioration of effect is the most probable explanation , although reactivity to 3-month assessment , a late Hawthorne effect , can not be ruled out Background Although smoking prevalence remains strikingly high in homeless population s ( ~70 % and three times the US national average ) , smoking cessation studies usually exclude homeless persons . Novel evidence -based interventions are needed for this high-risk sub population of smokers . Purpose To describe the aims and design of a first-ever smoking cessation clinical trial in the homeless population . The study was a two-group r and omized community-based trial that enrolled participants ( n = 430 ) residing across eight homeless shelters and transitional housing units in Minnesota . The study objective was to test the efficacy of motivational interviewing ( MI ) for enhancing adherence to nicotine replacement therapy ( NRT ; nicotine patch ) and smoking cessation outcomes . Methods Participants were r and omized to one of the two groups : active ( 8 weeks of NRT + 6 sessions of MI ) or control ( NRT + st and ard care ) . Participants attended six in-person assessment sessions and eight retention visits at a location of their choice over 6 months . Nicotine patch in 2-week doses was administered at four visits over the first 8 weeks of the 26-week trial . The primary outcome was cotinine-verified 7-day point-prevalence abstinence at 6 months . Secondary outcomes included adherence to nicotine patch assessed through direct observation and patch counts . Other outcomes included the mediating and /or moderating effects of comorbid psychiatric and substance abuse disorders . Results Lessons learned from the community-based cessation r and omized trial for improving recruitment and retention in a mobile and vulnerable population included : ( 1 ) the importance of engaging the perspectives of shelter leadership by forming and convening a Community Advisory Board ; ( 2 ) locating the study at the shelters for more visibility and easier access for participants ; ( 3 ) minimizing exclusion criteria to allow enrollment of participants with stable psychiatric comorbid conditions ; ( 4 ) delaying the baseline visit from the eligibility visit by a week to protect against attrition ; and ( 5 ) regular and persistent calls to remind participants of upcoming appointments using cell phones and shelter-specific channels of communication . Limitations The study ’s limitations include generalizability due to the sample drawn from a single Midwestern city in the United States . Since inclusion criteria encompassed willingness to use NRT patch , all participants were motivated and were ready to quit smoking at the time of enrollment in the study . Findings from the self-select group will be generalizable only to those motivated and ready to quit smoking . High incentives may limit the degree to which the intervention is replicable . Conclusions Lessons learned reflect the need to engage communities in the design and implementation of community-based clinical trials with vulnerable population Health risk perception in smoking behavior was prospect ively evaluated in a cluster-r and omized trial for smoking cessation in Greek college students . Perceived Vulnerability ( PV ) , Pre caution Effectiveness , Optimistic Bias , and smoking behavior measures ( quit attempts and cessation ) were assessed in college-aged Greek student smokers at baseline , end of treatment ( 3 months ) , and follow-up ( 6 months ) . Using generalized estimating equations , baseline risk perception variables and change in risk perception variables between baseline and end of treatment were examined as predictors of the dichotomous smoking outcome variables . Results revealed that higher baseline PV [ OR = 1.42 ( 1.21 , 1.68 ) ] predicted a greater likelihood of a quit attempt ( n = 267 ) . An increased likelihood of cessation [ OR = 1.41 ( 1.15 , 1.72 ) ] was also predicted by an increase in PV from baseline to end of treatment ( n = 243 ) . Overall results suggested that PV was the strongest predictor of smoking behavior change , supporting further examination of health risk perceptions in promoting smoking cessation among Greek college smokers Periodic health examinations are an excellent opportunity to counsel smokers to quit . The impact of a specialized smoking cessation counselor on the smoking behavior of patients having periodic health examinations was studied in a general internal medicine practice . One hundred fifty-five smokers having periodic health examinations were r and omly assigned to a control group who received usual physician advice or an intervention group who received usual physician advice and two counseling sessions with a smoking cessation counselor . The two groups were similar in all demographic variables , smoking-related baseline variables , and baseline levels of motivation and intention to quit smoking . The smoking status of 97 % of the subjects was assessed 6 months later . In the intervention group , 46 % made quit attempts and 19 % quit , compared with 34 % and 12 % , respectively , in the control group . Intervention-group smokers made more quit attempts ( mean + /- SD , 5.0 + /- 2.5 vs 1.8 + /- 0.2 ) and had a greater reduction in daily cigarette use ( 8.4 + /- 1.5 vs 3.5 + /- 1.3 ) . Of the 74 % of smokers with higher levels of motivation to quit smoking , more intervention-group smokers attempted to quit ( 70.8 % vs 45.5 % ) and succeeded in quitting at the 6-month follow-up ( 27.1 % vs 10.9 % ) . Periodic health examinations are an excellent opportunity to counsel smokers to quit , especially those smokers with higher levels of motivation to quit smoking OBJECTIVE To compare the results of 6-month follow-ups for hospitalized patients who were divided into two groups of low- and high-intensity treatments for smoking cessation and compared to the results of st and ard hospital treatment . METHODS A total of 2414 patients were screened . Two hundred thirty-seven current smokers were r and omly assigned to high-intensity intervention ( HII ; 30-min motivational interview plus seven routine telephone calls after hospital discharge ) or to low-intensity intervention ( LII ; 15-min counseling about the benefits of quitting ) and 80 comprised the usual care ( UC ) group . Six months after hospital discharge , all participants were contacted by phone . The main outcome measure was smoking cessation . RESULTS The smoking-cessation rates were 44.9 % , 41.7 % and 26.3 % for the HII , LII and UC groups , respectively ( P = .03 ) . The multivariable analysis identified the following variables which are associated with the failure to stop smoking : the absence of a tobacco-related disease ( TRD ) , younger age and a low motivation for cessation at the initial contact . CONCLUSIONS There was a great difference between intervention and nonintervention . The LII had an impact similar to the HII . The variables associated with no smoking cessation demonstrate the need for more personalized interventions for smokers who present lower indexes of motivation , are younger and do not have smoking-related diseases The purpose of this study was to compare substance involvement among psychiatrically hospitalized adolescent smokers who had received motivational interviewing ( MI ) versus brief advice ( BA ) for smoking cessation . One hundred and ninety-one ( 191 ) adolescent smokers ( 62.3 % female ; 15.4 years of age ) were r and omly assigned to MI ( n=116 ) or BA ( n=75 ) . All patients were assessed at baseline , immediately after hospitalization , and at 1- , 3- , 6- , 9- , and 12-month follow-ups . Rates of substance use in the MI condition during follow-up increased from a low of 8.2 % ( SD=18.5 ) to a high of 15.4 % ( SD=30.0 ) substance use days , whereas in BA , substance use days increased from a low of 8.4 % ( SD=20.8 ) to a high of 21.4 % ( SD=35.2 ) . The results of this study suggest that MI , relative to BA , for smoking cessation was associated with better substance use outcomes during the first 6 months following psychiatric hospitalization among adolescents . This finding is consistent with previous studies that have shown that smoking cessation does not have a detrimental effect on substance abuse treatment outcomes among youth INTRODUCTION Combining behavioural support and pharmacotherapy is most effective for smoking cessation and recommended in clinical guidelines . Despite that smoking cessation assistance from the general practitioner can be effective , dissemination of clinical practice guidelines and efforts on upskilling has not lead to the routine provision of smoking cessation advice among general practitioners . Intensive counselling from the practice nurse could contribute to better smoking cessation rates in primary care . However , the effectiveness of intensive counselling from a practice nurse versus usual care from a general practitioner in combination with varenicline is still unknown . MATERIAL S AND METHODS A pragmatic r and omized controlled trial was conducted comparing : ( a ) intensive individual counselling delivered by a practice nurse and ( b ) brief advice delivered by a general practitioner ; both groups received 12-weeks of open-label varenicline . A minimum of 272 adult daily smoking participants were recruited and treated in their routine primary care setting . The primary outcome was defined as prolonged abstinence from weeks 9 to 26 , biochemically vali date d by exhaled carbon monoxide . Data was analysed blinded according to the intention-to-treat principle and participants with missing data on their smoking status at follow-up were counted as smokers . Secondary outcomes included : one-year prolonged abstinence , short-term incremental cost-effectiveness , medication adherence , and baseline predictors of successful smoking cessation . DISCUSSION This trial is the first to provide scientific evidence on the effectiveness , cost-effectiveness , and potential mechanisms of action of intensive practice nurse counselling combined with varenicline under real-life conditions . This paper explains the methodology of the trial and discusses the pragmatic and /or explanatory design aspects . TRIAL REGISTRATION Dutch Trial Register NTR3067 Objectives : State and national tobacco quitlines have exp and ed rapidly and offer a range of services . We examined the effectiveness and cost effectiveness of offering callers single session versus multisession counselling , with or without free nicotine patches . Methods : This 3 × 2 r and omised trial included 4614 Oregon tobacco quitline callers and compared brief ( one 15-minute call ) , moderate ( one 30-minute call and a follow-up call ) and intensive ( five proactive calls ) intervention protocol s , with or without offers of free nicotine patches ( nicotine replacement therapy , NRT ) . Blinded staff assessed tobacco use by phone at 12 months . Results : Abstinence odds ratios were significant for moderate ( OR = 1.22 , CI = 1.01 to 1.48 ) and intensive ( OR = 1.29 , CI = 1.07 to 1.56 ) intervention , and for NRT ( OR = 1.58 , CI = 1.35 to 1.85 ) . Intent to treat quit rates were as follows : brief no NRT ( 12 % ) ; brief NRT ( 17 % ) ; moderate no NRT ( 14 % ) ; moderate NRT ( 20 % ) ; intensive no NRT ( 14 % ) ; and intensive NRT ( 21 % ) . Relative to brief no NRT , the added costs for each additional quit was $ 2467 for brief NRT , $ 1912 for moderate no NRT , $ 2109 for moderate NRT , $ 2641 for intensive no NRT , and $ 2112 for intensive NRT . Conclusion : Offering free NRT and multisession telephone support within a state tobacco quitline led to higher quit rates , and similar costs per incremental quit , than less intensive protocol Background Despite a significant decrease in smoking prevalence over the past ten years , cigarette smoking still represents the leading cause of preventable morbidity and mortality in the United States . Moreover , smoking prevalence is significantly higher among those with low levels of education and those living at , or below , the poverty level . These groups tend to be confronted with significant barriers to utilizing more traditional smoking cessation intervention approaches . The purpose of the study , Project ACTION ( Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods ) , is to utilize a mobile clinic model , a network of community sites ( i.e. , community centers and churches ) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved , low-income communities . Methods / Design We are using a group-r and omized design , with the community site as the sampling unit , to compare the efficacy of three smoking cessation interventions : 1 ) St and ard Care - brief advice to quit smoking , nicotine replacement therapy ( NRT ) , and self-help material s ; 2 ) Enhanced Care - st and ard care components plus a cell phone-delivered text/graphical messaging component ; and 3 ) Intensive Care - enhanced care components plus a series of 11 cell phone-delivered proactive counseling sessions . An economic evaluation will also be performed to evaluate the relative cost effectiveness of the three treatment approaches . We will recruit 756 participants ( 252 participants in each of the 3 intervention groups ) . At the time of r and omization , participants complete a baseline assessment , consisting of smoking history , socio-demographic , and psychosocial variables . Monthly cell phone assessment s are conducted for 6 months-post enrollment , and a final 12-month follow-up is conducted at the original neighborhood site of enrollment . We will perform mixed-model logistic regression to compare the efficacy of the three smoking cessation intervention treatment groups . Discussion It is hypothesized that the intensive care approach will most successfully address the needs of the target population and result in the highest smoking cessation rates . In addition to increasing cessation rates , the intervention offers several features ( including neighborhood outreach and use of mHealth technology ) that are likely to reduce treatment barriers while enhancing participant engagement and retention to treatment . Trial registration This r and omized controlled trial is registered with clinical trials.gov registration number NCT00948129 IMPORTANCE Widening socioeconomic disparities in mortality in the United States are largely explained by slower declines in tobacco use among smokers of low socioeconomic status ( SES ) than among those of higher SES , which points to the need for targeted tobacco cessation interventions . Documentation of smoking status in electronic health records ( EHRs ) provides the tools for health systems to proactively offer tobacco treatment to socioeconomically disadvantaged smokers . OBJECTIVE To evaluate a proactive tobacco cessation strategy that addresses socio context ual mediators of tobacco use for low-SES smokers . DESIGN , SETTING , AND PARTICIPANTS This prospect i ve , r and omized clinical trial included low-SES adult smokers who described their race and /or ethnicity as black , Hispanic , or white and received primary care at 1 of 13 practice s in the greater Boston area ( intervention group , n = 399 ; control group , n = 308 ) . INTERVENTIONS We analyzed EHRs to identify potentially eligible participants and then used interactive voice response ( IVR ) techniques to reach out to them . Consenting patients were r and omized to either receive usual care from their own health care team or enter an intervention program that included ( 1 ) telephone-based motivational counseling , ( 2 ) free nicotine replacement therapy ( NRT ) for 6 weeks , ( 3 ) access to community-based referrals to address socio context ual mediators of tobacco use , and ( 4 ) integration of all these components into their normal health care through the EHR system . MAIN OUTCOMES AND MEASURES Self-reported past-7-day tobacco abstinence 9 months after r and omization ( " quitting " ) , assessed by automated caller or blinded study staff . RESULTS The intervention group had a higher quit rate than the usual care group ( 17.8 % vs 8.1 % ; odds ratio , 2.5 ; 95 % CI , 1.5 - 4.0 ; number needed to treat , 10 ) . We examined whether use of intervention components was associated with quitting among individuals in the intervention group : individuals who participated in the telephone counseling were more likely to quit than those who did not ( 21.2 % vs 10.4 % ; P < .001 ) . There was no difference in quitting by use of NRT . Quitting did not differ by a request for a community referral , but individuals who used their referral were more likely to quit than those who did not ( 43.6 % vs 15.3 % ; P < .001 ) . CONCLUSIONS AND RELEVANCE Proactive , IVR-facilitated outreach enables engagement with low-SES smokers . Providing counseling , NRT , and access to community-based re sources to address socio context ual mediators among smokers reached in this setting is effective . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01156610 AIMS To screen promising intervention components design ed to reduce smoking and promote abstinence in smokers initially unwilling to quit . DESIGN A balanced , four-factor , r and omized factorial experiment . SETTING Eleven primary care clinics in southern Wisconsin , USA . PARTICIPANTS A total of 517 adult smokers ( 63.4 % women , 91.1 % white ) recruited during primary care visits who were willing to reduce their smoking but not quit . INTERVENTIONS Four factors contrasted intervention components design ed to reduce smoking and promote abstinence : ( 1 ) nicotine patch versus none ; ( 2 ) nicotine gum versus none ; ( 3 ) motivational interviewing ( MI ) versus none ; and ( 4 ) behavioral reduction counseling ( BR ) versus none . Participants could request cessation treatment at any point during the study . MEASUREMENTS The primary outcome was percentage change in cigarettes smoked per day at 26 weeks post- study enrollment ; the secondary outcomes were percentage change at 12 weeks and point-prevalence abstinence at 12 and 26 weeks post- study enrollment . FINDINGS There were few main effects , but a significant four-way interaction at 26 weeks post- study enrollment ( P = 0.01 , β = 0.12 ) revealed relatively large smoking reductions by two component combinations : nicotine gum combined with BR and BR combined with MI . Further , BR improved 12-week abstinence rates ( P = 0.04 ) , and nicotine gum , when used without MI , increased 26-week abstinence after a subsequent aided quit attempt ( P = 0.01 ) . CONCLUSIONS Motivation-phase nicotine gum and behavioral reduction counseling are promising intervention components for smokers who are initially unwilling to quit Background Hospitalization may be a particularly important time to promote smoking cessation , especially in the immediate post-discharge period . However , there are few studies to date that shed light on the most effective or cost-effective methods to provide post-discharge cessation treatment , especially among low-income population s and those with a heavy burden of mental illness and substance use disorders . Methods / design This r and omized trial will compare the effectiveness and cost-effectiveness of two approaches to smoking cessation treatment among patients discharged from two urban public hospitals in New York City . During hospitalization , staff will be prompted to ask about smoking and to offer nicotine replacement therapy ( NRT ) on admission and at discharge . Subjects will be r and omized on discharge to one of two arms : one arm will be proactive multi-session telephone counseling with motivational enhancement delivered by study staff , and the other will be a faxed or online referral to the New York State Quitline . The primary outcome is 30-day point-prevalence abstinence from smoking at 6-month follow-up post-discharge . We will also examine cost-effectiveness from a societal and a payer perspective , as well as explore subgroup analyses related to patient location of hospitalization , race/ethnicity , immigrant status , and inpatient diagnosis . Discussion This study will explore issues of implementation feasibility in a post-hospitalization patient population , as well as add information about the effectiveness and cost-effectiveness of different strategies for design ing smoking cessation programs for hospitalized patients .Trial registration Clinical trials.gov ID # BACKGROUND Continued high rates of smoking among socioeconomically disadvantaged women lead to increases in children 's health problems associated with exposure to tobacco smoke . The pediatric clinic is a " teachable setting " in which to provide advice and assistance to parents who smoke . OBJECTIVE To evaluate a smoking cessation intervention for women . DESIGN Two-arm ( usual care vs intervention ) r and omized trial . SETTING Pediatric clinics serving an ethnically diverse population of low-income families in the greater Seattle , Wash , area . INTERVENTION During the clinic visit , women received a motivational message from the child 's clinician , a guide to quitting smoking , and a 10-minute motivational interview with a nurse or study interventionist . Women received as many as 3 outreach telephone counseling calls from the clinic nurse or interventionist in the 3 months following the visit . PARTICIPANTS Self-identified women smokers ( n = 303 ) whose children received care at participating clinics . MAIN OUTCOME MEASURE Self-reported abstinence from smoking 12 months after enrollment in the study , defined as not smoking , even a puff , during the 7 days prior to assessment . RESULTS Response rates at 3 and 12 months were 80 % and 81 % . At both follow-ups , abstinence rates were twice as great in the intervention group as in the control group ( 7.7 % vs 3.4 % and 13.5 % vs 6.9 % , respectively ) . The 12-month difference was statistically significant . CONCLUSIONS A pediatric clinic smoking cessation intervention has long-term effects in a socioeconomically disadvantaged sample of women smokers . The results encourage implementation of evidence -based clinical guidelines for smoking cessation in pediatric practice Background The Swedish National Tobacco Quitline ( SNTQ ) , which has both a proactive and a reactive service , has successfully provided tobacco cessation support since 1998 . As there is a dem and for an increase in national cessation support , and because the quitline works under funding constraints , it is crucial to identify the most clinical ly effective and cost-effective service . A r and omized controlled trial was performed to compare the effectiveness of the high-intensity proactive service with the low-intensity reactive service at the SNTQ . Methods Those who called the SNTQ for smoking or tobacco cessation from February 2009 to September 2010 were r and omized to proactive service ( even date s ) and reactive service ( odd date s ) . Data were collected through postal question naires at baseline and after 12 months . Those who replied to the baseline question naire constituted the study base . Outcome measures were self-reported point prevalence and 6-month continuous abstinence at the 12-month follow-up . Intention-to-treat ( ITT ) and responder-only analyses were performed . Results The study base consisted of 586 persons , and 59 % completed the 12-month follow-up . Neither ITT- nor responder-only analyses showed any differences in outcome between proactive and reactive service . Point prevalence was 27 % and continuous abstinence was 21 % in analyses treating non-responders as smokers , and 47 % and 35 % , respectively , in responder-only analyses . Conclusion Reactive service may be used as the st and ard procedure to optimize re source utilization at the SNTQ . However , further research is needed to assess effectiveness in different subgroups of clients . Trial registration Clinical Trials.gov : The Parents of Asthmatics Quit Smoking ( PAQS ) project contrasts two theory-based smoking cessation interventions for parents of children with asthma , and compares mechanisms of behavior change within and across theoretical perspectives . We hypothesize that enhancing the perception of risk to self and child will motivate smoking cessation more than st and ard approaches that emphasize building self-efficacy and coping skills for quitting in a population that is largely not motivated to quit smoking . Smokers ( n = 288 ) and their asthmatic children who receive nurse-delivered in-home asthma education ( as part of the insurance carrier 's st and ard of care ) are r and omized into one of two treatment conditions : ( 1 ) the Behavioral Action Model ( BAM ) , in which nurses emphasize goal setting and skill building to enhance self-efficacy to quit smoking , or 2 ) the Pre caution Adoption Model ( PAM ) , in which nurses tailor the intervention to the smoker 's readiness to quit and incorporate biomarker feedback [ i.e. level of carbon monoxide exposure to the smoker and level of environmental tobacco smoke ( ETS ) exposure to the child ] in order to increase risk perception in smokers . In both conditions , smokers who are ready to quit receive the nicotine patch . Analyses will examine ( 1 ) quit rates , ETS level and motivation to quit as the primary dependent variables , ( 2 ) mediators of behavior change between and within conditions , and ( 3 ) relations between parent smoking outcomes and child asthma morbidity ( i.e. ER visits and asthma symptoms ) post-treatment . Results will help tailor interventions to this population , and identify mechanisms of behavior change that result in adaptive health outcomes for smokers and their children who have asthma OBJECTIVES To examine the impact of knowing quitters on cessation among homeless smokers . METHODS Secondary analysis of data derived from a community-based r and omized controlled trial of 430 homeless smokers . We conducted multivariable logistic regression analysis to determine whether knowing quitters impacted the likelihood of cessation ( salivary cotinine ≤ 20 ng/ml ) at 26-week follow-up . RESULTS Multivariable logistic regression showed cessation was more likely for smokers who knew ≥ 5 quitters compared with those who knew no quitters ( Odds Ratio = 3.79 , CI = 1.17 , 12.27 , p = .008 ) , adjusting for age , education , income , and time to first cigarette in morning . CONCLUSIONS Knowing former smokers was associated with increased likelihood of achieving smoking abstinence among homeless smokers INTRODUCTION Military personnel are twice as likely as civilians to use smokeless tobacco ( ST ) . This study evaluated the efficacy of a minimal-contact ST cessation program in military personnel . METHODS Participants were recruited from 24 military dental clinics across the United States during annual dental examinations . Participants were 785 active-duty military personnel who were r and omly assigned to receive a minimal-contact behavioral treatment ( n = 392 ) or usual care ( n = 393 ) . The behavioral treatment included an ST cessation manual , a videotape cessation guide tailored for military personnel , and three 15-min telephone counseling sessions using motivational interviewing methods . Usual care consisted of st and ard procedures that are part of the annual dental examination , including recommendations to quit using ST and referral to extant local tobacco cessation programs . Participants were assessed at 3 and 6 months after enrollment . RESULTS Participants in the ST cessation program were significantly more likely to be abstinent from all tobacco , as assessed by repeated point prevalence at both 3 and 6 months ( 25.0 % ) , and were significantly more likely to be abstinent from ST use for 6 months , as assessed by prolonged abstinence ( 16.8 % ) , compared with participants in usual care ( 7.6 % and 6.4 % , respectively ) . DISCUSSION These results indicate that a minimal-contact behavioral treatment can significantly reduce ST use in military personnel and has the potential for widespread dissemination . If ST users were identified in dental visits and routinely referred to telephone counseling , this could have a substantial benefit for the health and well-being of military personnel How can pregnant women be helped to stop smoking ? This was a pilot study of midwife home-based motivational interviewing . Clients were 100 consecutive self-reported smokers booking at clinics in Glasgow from March to May 1997 . Smoking guidance is routinely given at booking . In addition , intervention clients received a median of four home-based motivational interviewing sessions from one specially trained midwife . All sessions ( n = 171 ) were audio-taped and interviews ( n = 49 ) from 13 r and omly selected clients were transcribed for content analysis . Three ' experts ' assessed intervention quality using a recognized rating scale . Cotinine measurement on routine blood sample s confirmed self-reported smoking change from late pregnancy telephone interview . Postnatal telephone question naire measured client satisfaction . Focus groups of routine midwives explored acceptability , problems and disruption of normal care . Fisher exact , chi 2 and Mann-Whitney tests compared enrolment characteristics . Two- sample t-tests assessed outcome between groups . Motivational interviewing was satisfactory in more than 75 % of transcribed interviews . In this pilot study , self-reported smoking at booking ( 100 of 100 available ) corroborated by cotinine ( 93 of 100 ) compared with late pregnancy self-reports ( intervention 47 of 48 ; control 49 of 49 ) and cotinine ( intervention 46 of 48 ; control 47 of 49 ) showed no significant difference between groups . Tools have been developed to answer the question : ' Can proactive opportunistic home-based motivational interviewing help pregnant smokers reduce their habit ? ' BACKGROUND One fifth of Canadians are smokers despite the availability of community-based smoking cessation programs . It was hypothesized that offering a post-discharge smoking cessation program to cardiac patients would decrease smoking rates at six months . METHOD This pilot r and omized study explored the feasibility , acceptability and preliminary efficacy of a smoking cessation intervention delivered by a smoking cessation nurse specialist ( SCNS ) to cardiac patients after hospital discharge . SAMPLE Participants ( N=40 ) were r and omized to either a postdischarge telephone intervention delivered weekly for the first month and then monthly until the third month ( experimental group [ EG ] ) , or referral to usual community care ( control group [ CG ] ) . FINDINGS The research ers confirmed the feasibility of recruitment and acceptability of the intervention , but dfficulty with follow-up . The intention-to-treat analysis showed similar smoking cessation rates in both groups at six months ( 25 % EG versus 30 % CG ; p = 0.72 ) . CONCLUSION An intensifed follow-up protocol , or a more intensive , comprehensive and multidisciplinary intervention might be required , given the characteristics of the smokers 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 AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed AIM To test whether a single session of Motivational Interviewing ( MI ) focussing on drinking alcohol , and cigarette and cannabis smoking , would successfully lead to reductions in use or problems . METHODS Naturalistic quasi-experimental study , in 162 young people ( mean age 17 years ) who were daily cigarette smokers , weekly drinkers or weekly cannabis smokers , comparing 59 receiving MI with 103 non-intervention assessment -only controls . MI was delivered in a single session by youth workers or by the first author . Assessment was made of changes in self-reported cigarette , alcohol , cannabis use and related indicators of risk and problems between recruitment and after 3 months by self-completion question naire . RESULTS 87 % of subjects ( 141 of 162 ) were followed up . The most substantial evidence of benefit was achieved in relation to alcohol consumption , with those receiving MI drinking on average two days per month less than controls after 3 months . Weaker evidence s of impact on cigarette smoking , and no evidence of impact on cannabis use , were obtained . CONCLUSIONS Evidence of effectiveness for the delivery of MI by youth workers in routine conditions has been identified . However , the extent of benefit is much more modest than previously identified in efficacy studies INTRODUCTION Smoking prevalence in homeless population s is strikingly high ( ∼70 % ) ; yet , little is known about effective smoking cessation interventions for this population . We conducted a community-based clinical trial , Power To Quit ( PTQ ) , to assess the effects of motivational interviewing ( MI ) and nicotine patch ( nicotine replacement therapy [ NRT ] ) on smoking cessation among homeless smokers . This paper describes the smoking characteristics and comorbidities of smokers in the study . METHODS Four hundred and thirty homeless adult smokers were r and omized to either the intervention arm ( NRT + MI ) or the control arm ( NRT + Brief Advice ) . Baseline assessment included demographic information , shelter status , smoking history , motivation to quit smoking , alcohol/other substance abuse , and psychiatric comorbidities . RESULTS Of the 849 individuals who completed the eligibility survey , 578 ( 68.1 % ) were eligible and 430 ( 74.4 % of eligibles ) were enrolled . Participants were predominantly Black , male , and had mean age of 44.4 years ( S D = 9.9 ) , and the majority were unemployed ( 90.5 % ) . Most participants reported sleeping in emergency shelters ; nearly half had been homeless for more than a year . Nearly all the participants were daily smokers who smoked an average of 20 cigarettes/day . Nearly 40 % had patient health question naire-9 depression scores in the moderate or worse range , and more than 80 % screened positive for lifetime history of drug abuse or dependence . CONCLUSIONS This study demonstrates the feasibility of enrolling a diverse sample of homeless smokers into a smoking cessation clinical trial . The uniqueness of the study sample enables investigators to examine the influence of nicotine dependence as well as psychiatric and substance abuse comorbidities on smoking cessation outcomes Abstract OBJECTIVE : To examine the predictors of quitting among African American ( AA ) light smokers ( < 10 cigarettes per day ) enrolled in a smoking cessation trial . METHODS : Baseline variables were analyzed as potential predictors from a 2 × 2 cessation trial in which participants were r and omly assigned to 1 of 4 treatment groups : nicotine gum plus health education ( HE ) counseling , nicotine gum plus motivational interviewing ( MI ) counseling , placebo gum plus HE counseling , or placebo gum plus MI counseling . Chi-square tests , 2 sample t-tests , and multiple logistic regression analyses were used to identify predictors of cotinine ( COT ) verified abstinence at month 6 . RESULTS : In the final regression model , HE rather than MI counseling ( odds ratio [OR]=2.26 % , 95 % confidence interval [CI]=1.36 to 3.74 ) , older age ( OR=1.03 % , 95 % CI=1.01 to 1.06 ) , and higher body mass index ( OR=1.04 % , 95 % CI=1.01 to 1.07 ) significantly increased the likelihood of quitting , while female gender ( OR=0.46 % , 95 % CI=0.28 to 0.76 ) , ≤$1,800/month income ( OR=0.60 % , 95 % CI=0.37 to 0.97 ) , higher baseline COT ( OR=0.948 % , 95 % CI=0.946 to 0.950 ) , and not completing all counseling sessions ( OR=0.48 % , 95 % CI=0.27 to 0.84 ) reduced the odds of quitting . CONCLUSIONS : Individual characteristics may decrease the likelihood of quitting ; however , the provision of directive , advice-oriented counseling focused on the addictive nature of nicotine , health consequences of smoking , benefits of quitting , and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers OBJECTIVE To examine whether telephone counselling based on the stages of change component of Transtheoretical model of behaviour change together with educational material s could help non-motivated smoking parents of young children to cease . DESIGN R and omised controlled trial . SETTING Hong Kong Special Administrative Region , PR China . PARTICIPANTS 952 smoker fathers and mothers of Chinese children aged 5 years . INTERVENTION Participants were r and omly allocated into two groups : the intervention group received printed self-help material s and three-session telephone-based smoking cessation counselling delivered by trained counsellors ; the control group received printed self-help material s only . A structured question naire was used for data collection at baseline and at 1 , 3 and 6 month follow up . MAIN OUTCOME MEASURES The main outcome is 7 day point prevalence quit rate at 6 months ( defined as not smoking during the 7 days preceding the 6 month follow up ) determined by self reports . Other secondary outcomes were self reported 24 h point prevalence quit rate and self-reported continuous quit rate and bio-chemically vali date d quit rate at 6 months . RESULTS A total of 952 smoker fathers and mothers were r and omized to the intervention ( n = 467 ) and control ( n = 485 ) groups . Most were daily smokers ( 92.4 % ) and the mean number of cigarettes smoked per day was 14.5 ( SD = 8.9 ) . By using intention-to-treat analysis , the 7 day point prevalence quit rate at 6 month follow up was significantly greater in the intervention group ( 15.3 % ; 68/444 ) than the control group ( 7.4 % ; 34/459 ) ( P < 0.001 ) . The absolute risk reduction was 7.9 % ( 95 % confidence interval : 3.78 % to 12.01 % ) . The number needed to treat to get one additional smoker to quit was 13 ( 95 % CI : 8 - 26 ) . The crude odds ratio of quitting was 2.3(95 % CI : 1.5 - 3.5 ) . The adjusted odds ratio was 2.1 ( 95 % CI : 1.4 - 3.4 ) ( adjusted for age , number of years smoked , and alcohol dependency ) . CONCLUSION Proactive telephone counselling is an effective aid to promote smoking cessation among parents of young children Individuals with schizophrenia have a much higher prevalence of tobacco smoking , a lower cessation rate , and a higher incidence of tobacco-related diseases than the general population . The initial challenge has been to motivate these individuals to quit smoking . This study tested whether motivational interviewing is effective in motivating smokers with schizophrenia or schizoaffective disorder to seek tobacco dependence treatment . Participants ( N = 78 ) were r and omly assigned to receive a 1-session motivational interviewing ( MI ) intervention , st and ard psychoeducational counseling , or advice only . As hypothesized , a greater proportion of participants receiving the MI intervention contacted a tobacco dependence treatment provider ( 32 % , 11 % , and 0 % , respectively ) and attended the 1st session of counseling ( 28 % , 9 % . and 0 % ) by the 1-month follow-up as compared with those receiving comparison interventions BACKGROUND This study evaluated the effectiveness of three smoking cessation interventions for this population : ( 1 ) modified usual care ( UC ) ; ( 2 ) brief advice ( A ) ; and ( 3 ) brief advice plus more extended counseling during and after hospitalization ( A + C ) . METHODS Smokers ( 2,095 ) who were in- patients in four hospitals were r and omly assigned to condition . Smoking status was ascertained via phone interview 7 days and 12 months post-discharge . At 12 months , reports of abstinence were vali date d by analysis of saliva cotinine . Intent to treat analyses were performed . RESULTS At 7-day follow-up , 24.2 % of participants reported abstinence in the previous 7 days . There were no differences between conditions . At 12-month follow-up , self-reported abstinence was significantly higher in the A + C condition ( UC ( 15.0 % ) vs. A ( 15.2 % ) vs. A + C ( 19.8 % ) ) . There was no significant difference among conditions in cotinine-vali date d abstinence , however ( UC ( 8.8 % ) vs. A ( 10.0 % ) vs. A + C ( 9.9 % ) ) . CONCLUSIONS These interventions for hospital in- patients did not increase abstinence rates . Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria , the fact that pharmacological aids were not provided , and a stage-matching approach that result ed in less intensive counseling for participants unwilling to set a quit date BACKGROUND Parental smoking is associated with an increased risk of smoking among youth . Epidemiological research has shown that parental smoking cessation can attenuate this risk . This study examined whether telephone counselling for parents and subsequent parental smoking cessation affect smoking-related cognitions and smoking initiation among children of smoking parents . METHODS Data of a two-arm r and omized controlled trial were used in which 512 smoking parents were recruited into cessation support through their children 's primary schools . After the baseline assessment , smoking parents were r and omly assigned to tailored telephone counselling or a st and ard self-help brochure . Parental cessation was measured as 6-month prolonged abstinence at the 12-month follow-up . Children 's smoking-related cognitions and smoking initiation were examined at 3-month , 12-month , and 30-month follow-up . RESULTS No statistical evidence was found that children of parents who received telephone counselling tailored to smoking parents or children of parents who achieved prolonged abstinence differ in smoking-related cognitions ( i.e. , smoking outcome expectancies , perceived safety of smoking , self-efficacy to refrain from smoking , susceptibility to smoking ) or smoking initiation rate on any follow-up assessment . CONCLUSIONS This study is the first to examine the effects of an evidence -based smoking cessation treatment for parents and treatment-induced parental smoking cessation on cognitive and behavioural outcomes among children . Although descriptive statistics showed lower smoking initiation rates among children of parents who achieved prolonged abstinence , there was no statistical evidence that telephone counselling tailored to parents or treatment-induced parental smoking cessation affects precursors of smoking or smoking initiation among youth AIM Approximately 50 % of African American smokers are light smokers ( smoke < or = 10 cigarettes a day ) . The prevalence of light smoking in the United States is increasing , yet there has not been a single smoking cessation clinical trial targeting light smokers . The purpose of this 2 x 2 factorial , r and omized clinical trial was to evaluate the efficacy of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) for African American light smokers . DESIGN Participants were assigned r and omly to one of four study arms : 2 mg nicotine gum plus health education ( HE ) ; 2 mg nicotine gum plus motivational interviewing ( MI ) ; placebo gum plus HE ; and placebo gum plus MI . PARTICIPANTS AND SETTING A total of 755 African American light smokers ( 66 % female , mean age = 45 ) were enrolled at a community health center over a 16-month period . INTERVENTION AND MEASUREMENTS Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study . Biochemical measures included expired carbon monoxide ( CO ) and serum and salivary cotinine . FINDINGS Seven-day quit rates for nicotine gum were no better than for the placebo group ( 14.2 % versus 11.1 % , P = 0.232 ) at 6 months . However , a counseling effect emerged , with HE performing significantly better than MI ( 16.7 % versus 8.5 % , P < 0.001 ) . These results were consistent across outcome time-points ( weeks 1 , 8 , and 26 ) . CONCLUSIONS Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation . Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit RATIONALE Secondh and smoke exposure ( SHSe ) is a significant modifiable risk for respiratory health in children . Although SHSe is declining overall , it has increased for low-income and minority population s. Implementation of effective SHSe interventions within community organizations has the potential for significant public health impact . OBJECTIVES To evaluate the effectiveness of motivational interviewing ( MI ) delivered in the context of a SHS education reduction initiative within Head Start to reduce preschool children 's SHSe . METHODS A total of 350 children enrolled in Baltimore City Head Start whose caregivers reported a smoker living in the home were recruited . Caregivers were r and omized to MI + education or education alone . Assessment s were conducted at baseline , 3 , 6 , and 12 months . MEASUREMENTS AND MAIN RESULTS The primary outcome measure was household air nicotine levels measured by passive dosimeters . Secondary outcomes included child salivary cotinine , self-report of home smoking ban ( HSB ) , and smoking status . Participants in the MI + education group had significantly lower air nicotine levels ( 0.29 vs. 0.40 mg ) , 17 % increase in prevalence of caregiver-reported HSBs , and a 13 % decrease in caregiver smokers compared with education-alone group ( all P values < 0.05 ) . Although group differences in salivary cotinine were not significant , among all families who reported having an HSB , salivary cotinine and air nicotine levels declined in both groups ( P < 0.05 ) . CONCLUSIONS MI may be effective in community setting s to reduce child SHSe . More research is needed to identify ways to tailor interventions to directly impact child SHSe and to engage more families to make behavioral change . Clinical trial registered with www . clinical trials.gov ( NCT 00927264 ) OBJECTIVE We evaluated integrating a motivational interviewing (MI)-based smoking cessation curricula and MI counseling into a posttraumatic stress disorder ( PTSD ) home telehealth care management program to determine if smoking behaviors improved . METHOD We r and omized 178 Veterans with PTSD to a 90-session MI-based home telehealth program or to usual care . Outcome measures included self-reported 24-hour quit attempts , seven-day point prevalence abstinence , progression along the stages of change , and mental health symptoms . RESULTS Favorable smoking cessation rates were observed in both groups . There was no statistical difference in self-reported 24-hour quit attempts , seven-day point prevalence smoking abstinence or progression along the stages of change . The intervention group showed improved depression and PTSD symptoms . CONCLUSION Integrating MI-based smoking cessation treatment into PTSD home telehealth is an effective method to help Veterans with PTSD quit smoking . Further research is needed to underst and how to optimize MI integration into home telehealth to achieve sustained smoking cessation rates OBJECTIVE Smokers who are not ready to quit are a very difficult group to treat . Physicians , nurses , and nurse practitioners are in a unique position to encourage patients to quit smoking . However , the best approach to do so is not clear . METHODS A two-group r and omized controlled trial with 218 pack-a-day precontemplative and contemplative smokers recruited from the community . The laboratory-based study was design ed to simulate outpatient visits to general practitioners . Participants were r and omized to a 15-min intervention to compare the effectiveness of brief motivational or prescriptive counseling by a health professional . Thirteen outcome variables included intentions to quit and verbal reports at 1 and 6 months with biological verification . A composite outcome measure was constructed to provide greater power to detect study differences . RESULTS Approximately 33 % of the sample reported at least one 24-h quit period during the 6 months they were followed after the trial . Results suggest that while neither treatment was superior , there were subgroup differences . Participants in the motivational condition were also more likely to respond to follow-up calls . CONCLUSIONS AND PRACTICE IMPLICATION S Motivational interviewing and prescriptive advice were equally effective for precontemplative and contemplative smokers . Practitioners should use the method that appeals to them Abstract INTRODUCTION : Many smokers reduce their cigarette consumption during failed attempts to quit . We report the impact of changes in consumption on smoking-related respiratory symptom severity ( SRRSS ) . METHODS : Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a r and omized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation . Cigarette use in the 28 days prior to the interview , and severity of SRRSS using a 7-item respiratory index , were assessed at baseline and at 3-month follow-up . OUTCOME : Baseline minus 3-month assessment difference in SRRSS score . RESULTS : Follow-up of 319 participants ( 83.3 % ) , mean age 40.4 years , 51.4 % male , who smoked 26.4 cigarettes per day , demonstrated a mean reduction of 16.7 cigarettes per day . A reduction in cigarette use was positively and significantly ( b=0.29 , t=5.16 , P<.001 ) associated with a reduction in smoking-related symptom severity after adjusting for age , gender , race , years of regular smoking , baseline nicotine dependence , and history of treatment for asthma or emphysema . A 1 st and ard deviation reduction in average daily smoking ( about 14.1 cigarettes ) was associated with a 0.28 st and ard deviation decrease in smoking-related symptom severity . CONCLUSION : Reduction in symptom severity increases as absolute reduction in daily smoking increases . This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking Background : Preventive guidelines on cardiovascular risk management recommend lifestyle changes . Support for lifestyle changes may be a useful task for practice nurses , but the effect of such interventions in primary prevention is not clear . We examined the effect of involving patients in nurse-led cardiovascular risk management on lifestyle adherence and cardiovascular risk . Methods : We performed a cluster r and omized controlled trial in 25 practice s that included 615 patients . The intervention consisted of nurse-led cardiovascular risk management , including risk assessment , risk communication , a decision aid and adapted motivational interviewing . The control group received a minimal nurse-led intervention . The self-reported outcome measures at one year were smoking , alcohol use , diet and physical activity . Nurses assessed 10-year cardiovascular mortality risk after one year . Results : There were no significant differences between the intervention groups . The effect of the intervention on the consumption of vegetables and physical activity was small , and some differences were only significant for subgroups . The effects of the intervention on the intake of fat , fruit and alcohol and smoking were not significant . We found no effect between the groups for cardiovascular 10-year risk . Interpretation : Nurse-led risk communication , use of a decision aid and adapted motivational interviewing did not lead to relevant differences between the groups in terms of lifestyle changes or cardiovascular risk , despite significant within-group differences This study evaluates the performance of the Project EX tobacco use cessation program in Russian summer recreational camps . An eight-session clinic-based tobacco use cessation program for adolescents was tested during the summer of 2011 in an experimental pilot trial that involved different youth that rotated through camps . Conditions were nested within camps . Two rotations of unique subject groups of smokers ( program and st and ard care control ) through each of five camps provided the means of controlling for campsite by condition . Assignment of condition by rotation was r and om ( by a flip of a coin ) , achieving reasonable baseline comparability ( total n=164 smokers at baseline , 76 program group , 88 st and ard care control group ) . Evaluation involved an immediate pretest and posttest and a six-month telephone follow-up . At immediate posttest , Project EX was moderately well-received , significantly reduced future smoking expectation ( 46 % reduction in EX program condition versus 8 % in control , p<.0001 ) , decreased intention to not quit smoking ( -5.2 % in EX versus + 1.4 % in control , p<.05 ) , and increased motivation to quit smoking ( 0.72 versus -0.04 , p<.0001 ) . At the six-month follow-up , program subjects reported a higher intent-to-treat quit rate during the last 30days ( 7.5 % versus 0.1 % , p<.05 ) . For the subjects who remained monthly smokers at the six-month follow-up , Project EX reduced subjects ' level of nicotine dependence ( -0.53 versus + 0.15 , p<.001 ) . The results were quite promising for this program , which included motivation enhancement , coping skill , and alternative medicine material . However , further research on teen tobacco use cessation programming in Russia with larger sample sizes , involving other locations of the country , and with stronger research design s is needed AIM To test , in combination with the nicotine patch , the incremental efficacy of a maximal , tailored behavioral treatment over a minimal treatment for smoking cessation . DESIGN R and omized clinical trial with 6-month follow-up . SETTING Five methadone maintenance treatment centers in Rhode Isl and . PARTICIPANTS Three hundred and eighty-three methadone-maintained smokers . INTERVENTION Participants were assigned r and omly to nicotine patch ( 8 - 12 weeks ) plus either ( 1 ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session and a relapse prevention follow-up session ( Max ) or ( 2 ) brief advice using the National Cancer Institute 's 4 As model ( Min ) . An intent-to-treat analysis with those lost to follow-up assumed to smoke was used . MEASUREMENTS Carbon monoxide (CO)-confirmed 7-day point smoking cessation prevalence at 3 and 6 months , and self-reported numbers of cigarettes smoked per day . FINDINGS Participants had a mean age of 40 years , were 53 % male , 78 % Caucasian , smoked 26.7 ( + /- 12.2 ) cigarettes/day and had a mean methadone dose of 95.5 mg . At 3 months , 317 ( 83 % ) were re-interviewed ; at 6 months , 312 ( 82 % ) were re-interviewed . The intent-to-treat , 7-day point prevalence estimate of cessation was 5.2 % in the Max group and 4.7 % in the Min group ( P=0.81 ) at 6 months . In logistic models with treatment condition , age , gender , race , Fagerström Test for Nicotine Dependence and cigarettes per day as covariates , males were more likely to be abstinent at 3 months ( OR 4.67 ; P=0.003 ) and 6 months ( OR 4.01 ; P=0.015 ) . CONCLUSION A tailored behavioral intervention did not increase quit rates over patch and minimal treatment . Smoking cessation rates in methadone-maintained smokers are low , with men having greater success BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease BACKGROUND Several large and well-conducted community interventions have failed to detect an effect on prevalence of smoking . METHODS Two thous and four hundred eight daily smokers in all motivational stages were actively recruited and included in a r and omised population -based intervention study in Copenhagen , Denmark . All smokers completed a question naire and underwent a health examination and a lifestyle consultation . Daily smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS The vali date d abstinence rate at 1-year follow-up was 16.3 % in the high intensity group and 12.7 % in the low intensity group compared with a self-reported abstinence rate of 7.3 % in the background population . The adjusted odds ratio of abstinence in the high intervention group was significantly higher , OR = 2.2 ( 1.6 - 3.0 ) than in the background population , also in the ' intention-to-treat ' analyses , OR = 1.5 ( 1.1 - 2.0 ) . Higher socioeconomic status , higher age at onset of daily smoking , and a higher wish to quit were predictors of success . CONCLUSION In a population -based setting , using active recruitment and offering assistance to quit , it was possible to include many smokers and to achieve a significantly higher vali date d abstinence in the high intensity intervention than in the background population , even when using ' intention-to-treat ' analyses Despite high rates of smoking among people with psychotic disorders , and the associated health and financial burden , few studies have investigated the characteristics of this group of smokers . This paper reports data from 298 smokers with an ICD-10 psychotic disorder residing in the community ( 56.7 % with schizophrenia or schizoaffective disorder ) , including an examination of their demographic and clinical characteristics , smoking behaviours , severity of nicotine dependence , stage of change , and reasons for smoking and for quitting . St and ardized self-report instruments were used , in conjunction with structured interviews , as part of the first phase of a r and omized controlled trial . On average , participants smoked 30 cigarettes per day , commenced smoking daily at about 18 years of age ( 5 years before illness onset ) , and had made 2 - 3 quit attempts in their lifetime . Higher levels of nicotine dependence and concurrent hazardous use of alcohol or cannabis were associated with a younger age at smoking initiation . The present sample was also more likely to report stress reduction , stimulation and addiction as reasons for smoking , compared to a general sample of smokers . Males , precontemplators and participants with concurrent hazardous substance use cited fewer reasons for quitting smoking . These and other subgroup differences in smoking characteristics are used to illustrate potential implication s for the nature and timing of smoking interventions among people with a psychotic disorder INTRODUCTION Misreporting smoking behavior is common among younger smokers participating in clinical trials for smoking cessation . This study focused on the prevalence of and factors associated with adolescent misreporting of smoking behaviors within the context of a r and omized clinical trial for smoking cessation . METHODS Adolescent smokers ( N=129 ) participated in a r and omized clinical trial that compared two brief interventions for smoking cessation . Following the final ( 6-month ) follow-up , a confidential , self-administered exit question naire examined the extent to which participants admitted to having misreported smoking quantity , frequency and /or consequences during the study . Factors associated with under- and over-reporting were compared to accurate-reporting . RESULTS One in 4 adolescent smokers ( 25.6 % ) admitted to under-reporting during the study and 14.7 % admitted to over-reporting ; 10.9 % of the adolescents admitted to both under- and over-reporting . Rates of admitted misreporting did not differ between treatment conditions or recruitment site . Compared to accurate-reporting , under- and over-reporting were significantly associated with home smoking environment and the belief among adolescents that the baseline interviewer wanted them to report smoking more or less than they actually smoked . Compared to accurate reporters , over-reporters were more likely to be non-White and to report being concerned with the confidentiality of their responses . CONCLUSIONS A post- study confidential debriefing question naire can be a useful tool for estimating rates of misreporting and examining whether potential differences in misreporting might bias the interpretation of treatment effects . Future studies are needed to thoroughly examine potentially addressable reasons that adolescents misreport their smoking behavior and to develop methods for reducing misreporting Residential drug treatment provides an opportunity to intervene with smokers with substance use disorders ( SUD ) . A r and omized controlled clinical trial compared : ( 1 ) contingent vouchers ( CV ) for smoking abstinence to noncontingent vouchers ( NCV ) , crossed with ( 2 ) motivational interviewing ( MI ) or brief advice ( BA ) , for 184 smokers in SUD treatment . During the voucher period , 36 % of carbon monoxide readings indicated smoking abstinence for those receiving CV versus 13 % with NCV ( p < .001 ) . Post-treatment ( 3 - 9 months ) point-prevalence abstinence rates were low ( 3 - 4 % at each follow up ) , with more abstinence when CV was combined with MI ( 6.6 % on average ) than with BA ( 0 % on average ) . No differential effects on drug use or motivation to quit smoking occurred . Thus , CV had limited effects on long-term smoking abstinence in this population but effects were improved when CV was combined with MI . More effective methods are needed to increase motivation to quit smoking and quit rates in this high-risk population AIM To evaluate the effectiveness of repeated-contact proactive telephone counselling for smoking cessation in a UK setting . DESIGN R and omized controlled trial . SETTING The Quitline , an established national telephone counselling service available throughout the UK . PARTICIPANTS AND INTERVENTION A total of 1,457 callers to the Quitline in 2000 and 2001 were allocated r and omly to a Control group to receive usual care or to a Repeated Contact group to be offered five proactive calls in addition to usual care . MEASUREMENTS Prolonged abstinence and 24-hour point-prevalent abstinence 6 and 12 months after recruitment , quit attempts and 24-hour periods of abstinence in non-quitters . FINDINGS No significant differences were found between the Repeated Contact and Control groups on prolonged or point-prevalent abstinence . On an intention-to-treat basis , 9.5 % of the Control group were abstinent for longer than 6 months at the 12-month follow-up , compared with 9.3 % of the Repeated Contact group ; 18.9 % and 20.2 % , respectively , were point-prevalent abstinent at the 6-month follow-up . Significantly more non-quitters in the Control group made a quit attempt in the first 6 months following recruitment than in the Repeated Contact group ( 62.6%/56.1 % , P < 0.05 ) . CONCLUSIONS Proactive telephone counselling did not significantly increase abstinence rates , and appeared to decrease quit attempts , in callers to the Quitline . A non-structured , client-led counselling protocol and insufficient pre-quit motivational counselling could account for the lack of effect BACKGROUND Hospitalization may be an opportune time to change smoking behavior because it requires smokers to abstain from tobacco at the same time that illness can motivate them to quit . A hospital-based intervention may promote smoking cessation after discharge . METHODS We tested the efficacy of a brief bedside smoking counseling program in a r and omized controlled trial at Massachusetts General Hospital , Boston . The 650 adult smokers admitted to the medical and surgical services were r and omly assigned to receive usual care or a hospital-based smoking intervention consisting of ( 1 ) a 15-minute bedside counseling session , ( 2 ) written self-help material , ( 3 ) a chart prompt reminding physicians to advise smoking cessation , and ( 4 ) up to 3 weekly counseling telephone calls after discharge . Smoking status was assessed 1 and 6 months after hospital discharge by self-report and vali date d at 6 months by measurement of saliva cotinine levels . RESULTS One month after discharge , more intervention than control patients were not smoking ( 28.9 % vs 18.9 % ; P=.003 ) . The effect persisted after multiple logistic regression analyses adjusted for baseline group differences , length of stay , postdischarge smoking treatment , and hospital readmission ( adjusted odds ratio , 2.19 ; 95 % confidence interval , 1.34 - 3.57 ) . At 6 months , the intervention and control groups did not differ in smoking cessation rate by self-report ( 17.3 % vs 14.0 % ; P=.26 ) or biochemical validation ( 8.1 % vs 8.7 % ; P=.72 ) , although the program appeared to be effective among the 167 patients who had not previously tried to quit smoking ( 15.3 % vs 3.7 % ; P=.01 ) . CONCLUSIONS A low-intensity , hospital-based smoking cessation program increased smoking cessation rates for 1 month after discharge but did not lead to long-term tobacco abstinence . A longer period of telephone contact after discharge might build on this initial success to produce permanent smoking cessation among hospitalized smokers Background : Smoking cessation of patients with cancer can improve treatment efficacy and survival . Objective : To determine whether a motivational interviewing intervention increased successful smoking cessation attempts of patients with cancer attending a South Australian public hospital , as compared with usual care . Methods : A r and omized controlled trial was used to study 137 patients with mixed cancer sites , including 74 intervention patients and 63 control patients . The motivational interviewing intervention was delivered over a 3-month period . The intervention included a visit with a smoking cessation counselor , provision of smoking cessation booklets , nicotine replacement therapy , family advice to quit , and an in-person or telephone follow-up conversation . Results : At the 6-month follow-up visit , an intention-to-treat analysis found no difference in biochemically confirmed 3-month prevalence quit rates between the intervention ( 5 % ) and control ( 6 % ) groups . A sensitivity analysis using more lenient criteria indicated quit rates of 29 % for the intervention group and 18 % for the control group ( p = .32 ) . The predictors of smoking cessation at 6 months for all the patients included a smoking-related cancer site , more cessation attempts in the year before enrollment in the study , and no radiation therapy . Conclusions : Future efforts to improve smoking cessation in this patient group might focus on the delivery of more direct methods for encouraging spouse cessation and support to the patient in quitting , and the use of bupropion ( Zyban ) as an adjunct to cessation for this heavy smoking patient group This study aim ed to evaluate the effect of a motivational , minimal intervention approach to smoking cessation in an open , r and omized design conducted by nurses as routine work in a lung clinic . Subjects who smoked less than 10 cigarettes x day(-1 ) , and subjects who smoked > or = 10 cigarettes x day(-1 ) and who had refused to participate in a smoking cessation trial with nicotine replacement therapy , were r and omly allocated to a motivational approach to smoking cessation or to a control group . The motivational approach consisted of a nurse-conducted 5 min consultation concerning reasons to quit smoking , brochures about smoking cessation and advice about how to quit . After 4 - 6 weeks , subjects in the motivational group received a letter encouraging them to quit smoking . After 1 year , all subjects were contacted by phone and smoking status reported . Subjects cl aim ing to be abstinent attended the clinic for carbon monoxide verification . A total of 507 subjects were enrolled , 254 in the motivational group and 253 in the control group . The mean age of the motivational group was 51 yrs , 50 % were males and they smoked a mean of 13 cigarettes x day(-1 ) . The mean age of the control group was 53 yrs , 61 % were males and they smoked a mean of 12 cigarettes x day(-1 ) . At the 1 year follow-up , the success rate for point prevalence ( no smoking at 1 year and during the preceding month ) was 8 , 7 % in the motivational group versus 3.6 % in the control group ( p=0.025 ) . The 12 months sustained success rate ( no smoking at all during the year ) was 3.1 versus 1.2 % ( p=0.22 ) . The point prevalence for light smokers ( < 10 cigarettes x day(-1 ) ) was 13.9 % in the motivational group versus 6.3 % in control group ( p=0.12 ) , and for heavy smokers ( 10 or more cigarettes x day(-1 ) ) 5.2 % versus 1.9 % ( p=0.20 ) . In conclusion , the effect of this nurse-conducted , minimal intervention , motivational approach seems promising as the quit rate at 1 year follow-up had doubled BACKGROUND Motivational interviewing is a technique used to promote change in addictive behaviour , initially used to treat alcoholism . Despite this , its effectiveness has not been sufficiently demonstrated for giving up smoking . AIM The aim of the study was to establish whether motivational interviewing , compared with anti-smoking advice , is more effective for giving up the habit . DESIGN OF STUDY R and omised controlled trial . SETTING Primary care in Albecete , Spain . METHOD R and om experimental study of 200 smokers assigned to two types of interventions : anti-smoking advice ( n = 86 ) and motivational interviewing ( n = 114 ) . Subjects in both groups were offered bupropion when nicotine dependency was high ( Fagerström score > 7 ) . The success rate was evaluated by intention to treat ; point prevalence abstinence was measured 6 and 12 months post intervention by personal testimony , confirmed by means of CO-oximetry ( value < 6ppm ) . RESULTS The measure of effectiveness of the treatment for giving up smoking after both 6 and 12 months , showed that the motivational interviewing action was 5.2 times higher than anti-smoking advice ( 18.4 % compared to 3.4 % ; 95 % confidence interval = 1.63 to 17.13 ) . CONCLUSION The results of our study show that motivational interviewing is more effective than brief advice for giving up smoking The purpose of this study was to test two combination motivational plus pharmacological interventions for smoking cessation among HIV positive smokers . Participants were 40 adults receiving HIV care who smoked daily reporting interest in smoking reduction . Measures were administered at baseline , 1-month , and 3-month follow-ups . Participants were r and omly assigned to self-guided reading plus nicotine patch ( n = 18 ) or motivational interviewing plus nicotine patch ( n = 22 ) . Groups did not differ at 3 months on biochemically-verified abstinence . The sample reduced cigarettes per day by half a pack and the percent of smoking days by 41 % , and 22 % were abstinent at 3-month follow-up . Compliance with the nicotine patch was poor and declined over time , but patch use was unrelated to carbon monoxide level at 3-month follow-up . Smoking cessation interventions for people with HIV can be helpful and should include components that encourage some smoke-free days , increase self-efficacy , and attend to adherence to nicotine replacement treatment Smokeless tobacco ( ST ) use has been associated with numerous negative health consequences , yet the prevalence of ST has increased dramatically since the 1970s . Young males in the military are at an elevated risk for ST use relative to the general population . Sixty active-duty male participants were identified as ST users during their annual preventive health screening and r and omly assigned to minimal-contact intervention or usual care . Intervention participants were proactively contacted by phone and recruited , using a motivational interviewing style , for a cessation program consisting of a treatment manual , video , and two supportive phone calls from a cessation counselor . Sixty-five per cent ( 20/31 ) agreed to participate in the minimal-contact intervention . Three- and 6-month follow-up contacts found that the cessation rates reported by intervention participants were double those reported by participants receiving usual care ( 41 % vs. 17 % at 3 months , 37 % vs. 19 % at 6 months ) . These pilot study data suggest that proactive recruitment using a motivational interviewing approach to offer a treatment provides a good opportunity to reduce the use of ST in military setting OBJECTIVE Motivation plays an important role in a variety of behaviors , including smoking cessation , and is integral to theory and treatment of smoking . For many women , pregnancy offers a motivational shift that helps them stop smoking and maintain abstinence during pregnancy . However , women 's motivation to maintain smoking abstinence postpartum is not well-understood and may play a role in high postpartum relapse rates . The current study utilized multiple measures of prepartum motivation to maintain smoking abstinence to predict postpartum smoking abstinence . METHODS As part of a r and omized clinical trial on postpartum smoking relapse prevention , pregnant women who quit smoking during pregnancy reported their motivation to continue smoking abstinence at a prepartum baseline session . Biochemically verified continued smoking abstinence was assessed at 8 and 26 weeks postpartum . RESULTS Direct relationships among multiple measures of motivation were significant , and ranged in strength from weak to moderate . All motivation measures individually predicted continuous smoking abstinence , after controlling for treatment group , demographics , and prequit tobacco use . When tested simultaneously , a global motivation measure and parenthood motives for quitting remained significant predictors of abstinence . Backward selection modeling procedures result ed in a reduced model of prepartum predictors of postpartum abstinence including global motivation , parenthood motives , and stage of change . CONCLUSIONS Global motivation for smoking abstinence and parenthood motives for quitting are particularly important motivational constructs for pregnant women 's continued smoking abstinence INTRODUCTION Nearly 80 % of substance dependent individuals also use tobacco , and smoking cessation efforts during treatment for other substance use is associated with similar or even improved outcomes . However , smoking cessation is not routinely addressed during treatment for substance use disorders . The present study tested a computerized brief motivational intervention ( C- BMI ) for smoking cessation in an understudied population : a cohort recruited from a recovery community organization ( RCO ) center . METHODS Following baseline assessment , participants were r and omly assigned to either a 30-minute C- BMI plus access to free nicotine replacement therapy ( NRT ) , or an information-only control group plus NRT access . RESULTS Reductions in CO were observed for both groups . Quit rates in the C- BMI group ( 5%-7 % , vs. 0 % for the control group ) approximated those observed elsewhere for physician advice and minimal counseling . Participants in the C- BMI group were also more likely to express a desire to quit . CONCLUSIONS Computer-delivered smoking cessation interventions within RCOs appear feasible . These organizations treat a wide variety of individuals , and C- BMI s for smoking in this context have the potential to reduce smoking-related morbidity and mortality AIM To compare the effectiveness of proactive telephone counselling , reactive telephone counselling and an internet- and text-message-based intervention with a self-help booklet for smoking cessation . DESIGN A r and omized controlled trial with equal allocation to four conditions : ( 1 ) proactive telephone counselling ( n = 452 ) , ( 2 ) reactive telephone counselling ( n = 453 ) , ( 3 ) internet- and text-message-based intervention ( n = 453 ) and ( 4 ) self-help booklet ( control ) ( n = 452 ) . SETTING Denmark . PARTICIPANTS Smokers who had participated previously in two national health surveys were invited . Eligibility criteria were daily cigarette smoking , age ≥ 16 years , having a mobile phone and e-mail address . MEASUREMENTS Primary outcome was prolonged abstinence to 12 months from the end of the intervention period . FINDINGS At 12-month follow-up , higher prolonged abstinence was found in the proactive telephone counselling group compared with the booklet group [ 7.3 versus 3.6 % , odds ratio ( OR ) = 2.2 , 95 % confidence interval ( CI ) = 1.2 - 4.0 ] . There was no clear evidence of a difference in prolonged abstinence between the reactive telephone counselling group or the internet-based smoking cessation program and the booklet group : 1.8 versus 3.6 % , OR = 0.8 , 95 % CI = 0.6 - 1.2 and 5.3 versus 3.6 % , OR = 1.6 , 95 % CI = 0.8 - 3.0 , respectively . In the proactive telephone counselling group , the cost per additional 12-month quitter compared with the booklet group was £ 644 . CONCLUSIONS Proactive telephone counselling was more effective than a self-help booklet in achieving prolonged abstinence for 12 months . No clear evidence of an effect of reactive telephone counselling or the internet- and text-message-based intervention was found compared with the self-help booklet OBJECTIVE : Reducing tobacco use in pregnancy is a public health priority . Brief smoking counseling during prenatal care is effective but generates modest cessation rates . Telephone counseling is an effective smoking cessation method that could offer pregnant women convenient access to more intensive smoking cessation counseling . METHODS : The efficacy of proactive pregnancy-tailored telephone counseling for smoking cessation was compared with a “ best- practice ” brief-counseling control in a r and omized controlled trial of 442 pregnant smokers referred by prenatal providers and a managed care plan . Trained counselors using cognitive-behavioral and motivational interviewing methods called intervention subjects throughout pregnancy and for 2 months postpartum ( mean = 5 calls , mean total contact = 68 minutes ) . Controls received one 5-minute counseling call . RESULTS : Cotinine-vali date d 7-day tobacco abstinence rates in intervention and control groups were 10.0 % and 7.5 % at end of pregnancy ( odds ratio [ OR ] 1.37 , 95 % confidence interval [ CI ] 0.69–2.70 ; number needed to treat = 40 ) and 6.7 % versus 7.1 % at 3 months postpartum ( OR 0.93 , 95 % CI 0.44–1.99 ) . The intervention increased end-of-pregnancy cessation rates among 201 light smokers ( < 10 cigarettes/day at study enrollment ) ( intervention 19.1 % versus control 8.4 % ; OR 2.58 , 95 % CI 1.1–6.1 ; number needed to treat = 9.3 ) and among 193 smokers who attempted to quit in pregnancy before enrollment ( intervention 18.1 % versus control 6.8 % ; OR 3.02 , CI 1.15–7.94 ; number needed to treat = 8.8 ) ; 63 % of the sample ( n = 267 ) was in one of these subgroups . CONCLUSION : Proactive pregnancy-tailored telephone counseling did not outperform a brief “ best practice ” intervention among pregnant smokers . The intervention had efficacy in light smokers and in women who had attempted cessation earlier in pregnancy . Future studies should confirm whether telephone counseling benefits these groups of pregnant smokers . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , # NCT00181909 . LEVEL OF EVIDENCE : BACKGROUND AND AIMS Tuberculosis ( TB ) patients who smoke risk adverse TB outcomes and other long-term health effects of smoking . This study aim ed to determine the efficacy of brief motivational interviewing by lay health-care workers ( LHCWs ) in assisting TB patients to quit smoking . DESIGN Multi-centre two-group parallel individual r and omized controlled trial . SETTING Six primary care tuberculosis clinics in a South African township . PARTICIPANTS Newly diagnosed adult TB patients identified as current smokers were r and omized to brief motivational interviewing by a LHCW ( intervention group , n = 205 ) or brief smoking cessation advice from a TB nurse ( control group , n = 204 ) . MEASUREMENTS The primary outcome was self-reported sustained 6-month smoking abstinence . Exhaled carbon monoxide ( CO ) testing was offered to about half the participants . Secondary outcomes were sustained abstinence at 3 months ; 7-day point prevalence abstinence at 1 , 3 and 6 months ; and quit attempts . Allocation was concealed . Primary analysis relied on intention to treat . Multi-level analysis accounted for site heterogeneity of effect . FINDINGS Self-reported 6-month sustained abstinence was 21.5 % for the intervention group versus 9.3 % for the control group [ relative risk ( RR ) = 2.29 , 95 % confidence interval ( CI ) = 1.34 , 3.92 ] . Biochemically verified 6-month sustained abstinence was also higher in the intervention group ( RR 2.21 , 95 % CI = 1.08 , 4.51 ) for the 166 participants who were offered carbon monoxide testing . Self-reported 3-month sustained abstinence was 25.4 % for the intervention group and 12.8 % for the control group ( RR = 1.98 , 95 % CI = 1.24 , 3.18 ) . CONCLUSIONS Motivational interviewing by lay counsellors to promote smoking cessation in tuberculosis patients in South Africa approximately doubled sustained smoking abstinence for at least 6 months compared with brief advice alone 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 OBJECTIVE Passive smoke exposure among children is widespread in the United States ; estimates suggest that almost 40 % of children who are younger than 5 years live with a smoker . Few r and omized studies of passive smoke exposure reduction among children have been conducted , and the impact of interventions that have been evaluated has been limited . The objective of this study was to determine whether a motivational intervention for smoking parents of young children will lead to reduced household passive smoke exposure . METHODS Project KISS ( Keeping Infants Safe From Smoke ) , a theory-driven exposure reduction intervention targeting low-income families with young children , was a r and omized controlled study in which participants -smoking parents/caregivers ( N = 291 ) who had children who were younger than 3 years and who were recruited through primary care setting s-were r and omly assigned to either the motivational intervention ( MI ) or a self-help ( SH ) comparison condition was used . Follow-up assessment s were conducted at 3 and 6 months . The MI condition consisted of a 30- to 45-minute motivational interviewing session at the participant 's home with a trained health educator and 4 follow-up telephone counseling calls . Feedback from baseline household air nicotine assessment s and assessment of the participant 's carbon monoxide level was provided as part of the intervention . Participants in the SH group received a copy of the smoking cessation manual , the passive smoke reduction tip sheet , and the re source guide in the mail . Household nicotine levels were measured by a passive diffusion monitor . RESULTS The 6-month nicotine levels were significantly lower in MI households . Repeated measures analysis of variance across baseline , 3-month , and 6-month time points showed a significant time-by-treatment interaction , whereby nicotine levels for the MI group decreased significantly and nicotine levels for the SH group increased but were not significantly different from baseline . CONCLUSIONS This study targeted a large sample of racially and ethnically diverse low-income families , in whom both exposure and disease burden is likely to be significant . This is the first study to our knowledge that has been effective in reducing objective measures of passive smoke exposure in households with healthy children . These findings have important implication s for pediatric health care providers , who play an important role in working with parents to protect children 's health . Providers can help parents work toward reducing household passive smoke exposure using motivational strategies and providing a menu of approaches regardless of whether the parents are ready to quit 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 Many r and omized controlled trials in which motivational interviewing ( MI ) is a key intervention make no provision for the assessment of treatment fidelity . This method ological shortcoming makes it impossible to distinguish between high- and low- quality MI interventions , and , consequently , to know whether MI provision has contributed to any intervention effects . This article makes some practical recommendations for the collection , selection , coding and reporting of MI fidelity data , as measured using the Motivational Interviewing Treatment Integrity Code . We hope that research ers will consider these recommendations and include MI fidelity measures in future studies Although motivational interviewing ( MI ) has been shown to be effective in changing health behaviors , its effects on smoking cessation have been mixed . The purpose of the present study is to assess factors of motivation and self-efficacy as they mediate the relationship between MI and smoking cessation . This is a secondary analysis of an MI based smoking cessation r and omized trial . MI counseling was associated with change in smoking behaviors during a 12 months intervention but was not related to autonomous motivation , controlled motivation , or self-efficacy at baseline and 6 months , the hypothesized mediators . This study confirmed the pathway to quit smoking through increase in self-efficacy INTRODUCTION Despite decades of tobacco use decline among the general population in the United States , tobacco use among low-income population s continues to be a major public health concern . Smoking rates are higher among individuals with less than a high school education , those with no health insurance , and among individuals living below the federal poverty level . Despite these disparities , smoking cessation treatments for low-income population s have not been extensively tested . In the current study , the efficacy of 2 adjunctive smoking cessation interventions was evaluated among low-income smokers who were seen in a primary care setting . METHODS A total of 846 participants were r and omly assigned either to motivational enhancement treatment plus brief physician advice and 8 weeks of nicotine replacement therapy ( NRT ) or to st and ard care , which consisted of brief physician advice and 8 weeks of NRT . Tobacco smoking abstinence was at 1 , 2 , 6 , and 12 months following baseline . RESULTS The use of the nicotine patch , telephone counseling , and positive decisional balance were predictive of increased abstinence rates , and elevated stress levels and temptation to smoke in both social/habit and negative affect situations decreased abstinence rates across time . Analyses showed intervention effects on smoking temptations , length of patch use , and number of telephone contacts . Direct intervention effects on abstinence rates were not significant , after adjusting for model predictors and selection bias due to perir and omization attrition . CONCLUSIONS Integrating therapeutic approaches that promote use of and adherence to medications for quitting smoking and that target stress management and reducing negative affect may enhance smoking cessation among low-income smokers 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 Abstract This study examines predictors of smoking cessation in tuberculosis patients with high HIV co-infection rates in a South African primary care setting . Current smokers were r and omly allocated to brief motivational interviewing ( n = 205 ) or receipt of a brief message ( n = 204 ) . Multi-level logistic regression was performed to identify predictors of sustained 3- and 6-month abstinence and 7-day point prevalence abstinence ( PPA ) at 1 month , with the facility as a r and om effect . The intervention was ineffective among smokers with high nicotine-dependence at 1 month , but was effective for all smokers over longer periods . Higher baseline self-efficacy predicted the 1-month 7-day PPA , but not sustained abstinence . HIV-positive participants ’ odds of sustained abstinence were about three times higher than those of their HIV-negative counterparts . Results support a more intensive motivational intervention and /or coping skills ’ training to increase self-efficacy and abstinence rates . Tobacco cessation services can be introduced in tuberculosis services where high HIV co-infection rates occur To determine predictors of smoking cessation duration in a r and omized clinical trial , we assigned participants to nicotine patch ( 8 - 12 weeks ) plus either ( a ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session , and a relapse prevention follow-up session , or ( b ) brief advice using the National Cancer Institute 's 4A 's model . A total of 383 smokers from five methadone maintenance treatment centers in Rhode Isl and were enrolled , of whom 312 ( 82 % ) completed 6-month follow-up assessment s. The primary outcome was longest period of self-reported abstinence during follow-up . Participants were on average 40.5 years of age ; 51.9 % were male , and 77.6 % were White . In multivariate analysis controlling for demographics , nicotine dependence , depressive symptoms , and smoking-related symptoms , we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline ( OR = 1.97 , p = .003 ) , in those anticipating success in cessation ( OR = 1.33 , p = .024 ) , and in those with a greater percentage of nicotine patch use days ( OR = 2.78 , p<.001 ) . Past quit attempts , self-efficacy , and constant nicotine replacement were associated with duration of abstinence among methadone-maintained smokers . Attention to these domains in future intervention studies may improve treatment success Current treatment guidelines recommend that all smokers be given motivational or action-oriented counseling , as is appropriate to their readiness to quit smoking . The present study assessed the acceptability and impact of a proactively delivered , motivationally tailored phone counseling program targeted to women with elevated risk for cervical cancer . Female smokers with a recent abnormal pap exam or a colposcopy were contacted and invited to participate , regardless of their interest in quitting smoking . Participants were r and omly assigned to usual care ( UC ) or UC plus motivationally enhanced phone counseling ( MEC ) . The intervention was well received : 79 % of eligible women enrolled ( n = 275 ) , and 90 % completed at least three of four calls . Participation did not vary by baseline motivation to quit . Compared with control subjects , counseling participants were more likely to seek additional treatment services and had a higher 7-day point-prevalence abstinence rate at 6 months ( 20 % MEC vs. 12 % UC , p<.05 ) . MEC impact was sustained at 12 months , but abstinence increased among the UC group ( 18 % MEC vs. 20 % UC , p = ns ) . There was no difference in repeated point-prevalence abstinence at 6 and 12 months ( 11 % MEC vs. 10 % UC , p = ns ) . Outcomes were similar in a subgroup of 229 women who , at baseline , were interested in quitting in the next 6 months This is a pilot study of a r and omized controlled trial of an individualized motivational intervention ( IMI ) provided by nurses to help smoking parents of sick children quit smoking . Eighty parents who brought their sick children to the hospital were entered into the study . The intervention group received an IMI from a trained nurse counselor and telephone reminders were given 1 week after the intervention . The quit rate at 1 month was 7.5 % ( 95 % CI , 0 - 21 ) in the intervention group and 2.5 % ( 95 % CI , 0 - 7 ) in the control group . Preliminary results indicated that the IMI provided by nurses seemed to be effective in helping resistant parents of sick children stop smoking . They also suggested that it was acceptable and feasible to implement such intervention in a pediatric outpatient clinic/ward in Hong Kong BACKGROUND Clinical guidelines for smoking cessation may not be sufficient for helping some subgroups of smokers quit . Incorporating smoking cessation into home-based medical care can proactively reach high-risk smokers who may not have access to ( or spontaneously seek ) smoking cessation . METHOD Home health care nurses ( N = 98 ) were r and omly assigned to deliver either Motivational Enhancement ( ME ; Motivational Interviewing + Carbon Monoxide Feedback ) or St and ard Care ( AHCPR Guidelines for smoking cessation ) to their patients . Seventy percent of patients were eligible and willing to participate ( N = 273 ; 54 % female , mean age = 57 years , 83 % Caucasian , 41 % < high school education ) . The study was conducted in Providence , RI , USA from 1998 to 2003 . RESULTS Biochemically verified continuous abstinence rates at the 12-month follow-up were 4.2 % ( SC ) and 8.7 % ( ME ) for intent to treat analyses , and 5.2 % ( SC ) and 11.8 % ( ME ) using all available cases ( P > 0.05 ) . ME reported more quit attempts and significantly greater reductions in the number of cigarettes smoked per day at all follow-ups through 12 months of post-treatment ( all P values < 0.05 ) . CONCLUSIONS Use of an existing public health channel such as home health care to reach smokers who vary in their motivation to quit could have the potential for large public health impact PURPOSE Recruitment is often the rate-limiting step in conducting clinical trials among ethnic minorities . Little is known about participants who consent and enroll into a trial , but do not return for r and omization . Why participants fail to return for r and omization is largely unknown . METHODS We compared 287 enrolled African American smokers who did not return for r and omization , to the 500 who returned and were r and omized to participate in a clinical trial for smoking cessation in African Americans . Analyses were conducted to identify variables associated with not returning for r and omization . RESULTS Univariate comparisons found the nonr and omized group to be significantly different from those r and omized . Logistic regression showed younger age , less readiness to quit , having been proactively recruited , lacking a regular source of health care , believing that they will be smoking in 6 months , less church attendance , and a lower literacy level to be jointly related with not returning for r and omization . CONCLUSIONS African American participants who did not return for r and omization into a clinical trial were different from those who did . Better underst and ing of these factors may allow research ers to target recruitment efforts result ing in enhanced accrual in clinical trials and increased efficiency Purpose . When a patient is diagnosed with lung cancer , members of his/her social network may be more likely to engage in smoking cessation efforts . Proactive telephone counseling combined with a tailored self-directed intervention may be more effective at promoting smoking cessation than a tailored self-directed intervention alone . Design . R and omized controlled trial . Setting . Four clinical sites . Subjects . Current smokers who are family members and close friends of patients with lung cancer . Intervention . Six counselor-initiated counseling calls using motivational interviewing techniques and focusing on teaching adaptive coping skills based on the transactional model of stress and coping along with tailored self-directed material s ( including nicotine patches , if not contraindicated ) ( n = 245 ) vs. tailored self-directed material s ( including nicotine patches , if not contraindicated ) ( n = 251 ) . Measures . Participants were surveyed at baseline and at 2 weeks , 6 months , and 12 months postintervention . The outcome was 7-day point prevalent abstinence . Analysis . The objective of this study was to test for arm differences in smoking cessation rates at 2 weeks and 6 months postintervention ( primary ) and at 12 months postintervention ( secondary ) . Results . We found no overall effect of the proactive intervention on cessation rates . Among younger participants ( age < 50 ) , the cessation rate in the intervention group was higher than in the control group at 2 weeks postintervention ( 16 % vs. 4 % , p = .046 ) . For older participants ( age > 50 ) , there were no group differences . Conclusion . Proactive telephone counseling focusing on adaptive coping skills was difficult to implement among smokers in lung cancer patients ' social network . Although this study did not demonstrate any added benefit to cessation rates , this null finding may be a result of an intervention that was weaker than intended , owing to difficulties in completing the counseling phone calls . We discuss lessons learned and areas for future research in this special population We tested whether a 3-month beneficial effect of telephone counseling as an adjunct to the use of medications for smoking cessation was maintained through 12 months . Health plan members filling a prescription for cessation medications were r and omized either to a no-contact control group or to proactive recruitment into telephone counseling . An increased point-prevalence quit rate at 3 months ( 33.1 % vs. 27.4 % , p<.05 ) among smokers r and omized to proactive recruitment for telephone counseling was not maintained . Although at 12 months smokers in the proactive recruitment arm were more likely to report a 24-hr quit attempt , compared with control group smokers ( 86.7 % vs. 80.8 % , p = .027 ) , we found no differences between the groups in repeated ( 3-month and 12-month ) 7-day point-prevalence quit rates . In an analysis of predictors of quitting , age , marital status , making a lifestyle change , and the presence of household smokers were associated with repeated 3-month and 12-month point-prevalence abstinence . Offering telephone counseling to insured smokers who have filled prescriptions for cessation medications did not increase long-term quit rates . Although other variations of this approach might be tested , we suspect that it might be more useful to test innovative ways to influence the factors we identified as being most strongly predictive of lack of successful quitting OBJECTIVES The purpose of this study was to evaluate a brief smoking cessation intervention for women 15 to 35 years of age attending Planned Parenthood clinics . METHODS Female smokers ( n = 1154 ) were r and omly assigned either to advice only or to a brief intervention that involved a 9-minute video , 12 to 15 minutes of behavioral counseling , clinician advice to quit , and follow-up telephone calls . RESULTS Seventy-six percent of those eligible participated . Results revealed a clear , short-term intervention effect at the 6-week follow-up ( 7-day self-reported abstinence : 10.2 % vs 6.9 % for advice only , P < .05 ) and a more ambiguous effect at 6 months ( 30-day biochemically vali date d abstinence : 6.4 % vs 3.8 % , NS ) . CONCLUSIONS This brief , clinic-based intervention appears to be effective in reaching and enhancing cessation among female smokers , a traditionally underserved population OBJECTIVE To evaluate the effectiveness of a nurse led shared care programme to improve coronary heart disease risk factor levels and general health status and to reduce anxiety and depression in patients awaiting coronary artery bypass grafting ( CABG ) . DESIGN R and omised controlled trial . SETTING Community , January 1997 to March 1998 . STUDY GROUPS 98 ( 75 male ) consecutive patients were recruited to the study within one month of joining the waiting list for elective CABG at Glasgow Royal Infirmary University NHS Trust . Patients were r and omly assigned to usual care ( control ; n = 49 ) or a nurse led intervention programme ( n = 49 ) . INTERVENTION A shared care programme consisting of health education and motivational interviews , according to individual need , was carried out monthly . Care was provided in the patients ' own homes by the community based cardiac liaison nurse alternating with the general practice nurse at the practice clinic . OUTCOME MEASURES Smoking status , obesity , physical activity , anxiety and depression , general health status , and proportion of patients exceeding target values for blood pressure , plasma cholesterol , and alcohol intake . RESULTS Compared with patients who received usual care , those participating in the nurse led programme were more likely to stop smoking ( 25 % v 2 % , p = 0.001 ) and to reduce obesity ( body mass index > 30 kg/m2 ) ( 16.3 % v 8.1 % , p = 0.01 ) . Target systolic blood pressure improved by 19.8 % compared with a 10.7 % decrease in the control group ( p = 0.001 ) and target diastolic blood pressure improved by 21.5 % compared with 10.2 % in the control group ( p = 0.000 ) . However , there was no significant difference between groups in the proportion of patients with cholesterol concentrations exceeding target values . There was a significant improvement in general health status scores across all eight domains of the 36 item short form health survey with changes in difference in mean scores between the groups ranging from 8.1 ( p = 0.005 ) to 36.1 ( p < 0.000 ) . Levels of anxiety and depression improved ( p < 0.000 ) and there was improvement in time spent being physically active ( p < 0.000 ) . CONCLUSIONS This nurse led shared care intervention was shown to be effective for improving care for patients on the waiting list for CABG PURPOSE To determine which factors predict smoking cessation treatment completion and retention among adolescents . METHODS In a multisite , r and omized , controlled trial , the efficacy of motivational interviewing was compared with structured brief advice for smoking cessation and reduction in adolescents ( n = 355 ) aged 14 - 18 years ( 55 % female , 45 % black , 12 % Hispanic ) . Treatment spanned 12 weeks , with follow-up assessment s at 24 weeks . Treatment completion was defined as completion of all five counseling sessions . Study retention was defined as completing the 24-week assessment . Participant and study variables served as predictors of treatment completion and retention . RESULTS In all , 79 % of participants completed all five counseling sessions and the same percent completed the 24-week assessment . Black race , precontemplation stage to cut back , and shorter length of time between the baseline assessment and the first counseling session were significantly associated with treatment completion . For every 7.5-day delay in starting treatment after the baseline visit , there was a 50 % decrease in the odds of completing all five treatment sessions . Retention at 24 weeks was predicted by black race , younger age , greater maternal education , expectations of graduating college , and structured brief advice intervention . CONCLUSIONS High rates of treatment completion and study retention can be achieved in a multisession , behavioral intervention for adolescent smoking cessation . Findings suggest that treatment should begin soon after the intake session to maximize treatment completion . Enhanced efforts to retain older adolescents and youth with lower academic goals and lower family income will be important in future studies OBJECTIVES This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs . METHODS Twenty-four worksites were r and omized to 6 conditions that differed in cessation program format and the use of incentives . Programs were offered for 18 months in each worksite . A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation . RESULTS A total of 407 ( 16.9 % ) of the smoker cohort registered for programs ; on the 12- and 24-month surveys , 15.4 % and 19.4 % of the cohort , respectively , reported that they had not smoked in the previous 7 days . Registration for programs in incentive sites was almost double that of no-incentive sites ( 22.4 % vs 11.9 % ) , but increased registration did not translate into significantly greater cessation rates . Program type did not affect registration or cessation rates . CONCLUSIONS Although incentives increase rates of registration in worksite smoking cessation programs , they do not appear to increase cessation rates . Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites BACKGROUND Smoking cessation after myocardial infa rct ion ( MI ) has been associated with a 50 % reduction in mortality but in-hospital smoking cessation interventions are rarely part of routine clinical practice . METHODS One hundred cigarette smokers consecutively admitted during 1996 with MI were assigned to minimal care or to a hospital-based smoking cessation program . Intervention consisted of bedside cessation counseling followed by seven telephone calls over the 6 months following discharge . Primary outcomes were abstinence rates measured at 6 months and 1 year post-discharge . RESULTS At follow-up , 43 and 34 % of participants in minimal care and 67 and 55 % of participants in intervention were abstinent at 6 and 12 months . respectively ( P<0.05 ) . Abstinence rates were calculated assuming that participants lost to attrition were smokers at follow-up . Intervention and self-efficacy were independent predictors of smoking status at follow-up . Low self-efficacy combined with no intervention result ed in a 93 % relapse rate by 1 year ( P<0.01 ) . CONCLUSIONS A hospital-based smoking cessation program consisting of inpatient counseling and telephone follow-up substantially increases smoking abstinence 1 year after discharge in patients post-MI . Patients with low self-efficacy are almost certain to relapse without intervention . Such smoking cessation programs should be part of the management of patients with MI INTRODUCTION The present study aim ed to assess the effect of adding motivational interviewing ( MI ) to the first session of an effective smoking cessation treatment protocol in an ordinary clinical setting : the Swedish National Tobacco Quitline ( SNTQ ) . METHOD The study was design ed as a controlled clinical trial . Between September 2005 and October 2006 , 772 clients accepted the invitation to participate in the study and were semi-r and omised to either st and ard treatment ( ST ) or MI . The primary outcome measures were self-reported 7-day point prevalence abstinence and 6-month continuous abstinence . RESULTS At 12-month follow-up , the 772 clients were included in an intention to treat analysis . Of the clients allocated to MI , 57/296 ( 19 % ) reported 6-month continuous abstinence compared to 66/476 ( 14 % ) of the clients allocated to ST ( OR 1.48 , 95 % CI 1.00 - 2.19 ; P=.047 ) . CONCLUSIONS Integrating MI into a cognitive behavioural therapy-based smoking cessation counselling in an ordinary clinical setting at a tobacco quitline increased client 6-month continuous abstinence rates by 5 % INTRODUCTION Tobacco use is a serious public health problem among low-income Chinese Americans with limited English proficiency . Chinese men are at high risk for smoking-related morbidity and mortality . We tested the feasibility of a culturally and linguistically sensitive smoking intervention program with combined counseling and pharmacological components for Chinese smokers in New York City ; identified factors and techniques that enhance the administration and appropriateness of the intervention program ; and examined the overall impact of this program on quit attempts , quit rates , and overall smoking reduction . METHODS We were guided by the transtheoretical model and used an adapted motivational interviewing ( MI ) approach . The study involved a r and omized sample with pretreatment assessment and multiple follow-up measures . Eligible participants ( N = 122 ) were r and omly assigned to intervention ( 4 individualized counselor-led MI sessions and nicotine replacement therapy [ NRT ] ) or control groups ( 4 general health education sessions , self-help material s , and NRT ) . RESULTS Quit rate at 6 months in the intervention group was 67 % versus 32 % for the control group , indicating minimal relapse and a highly successful intervention program . Increase in self-efficacy and decease in pros of smoking from baseline to 6-month follow-up were positively associated with smoking cessation . The number of cigarette smoked at baseline was inversely related to smoking cessation . Results indicate that a combined intensive behavioral counseling and pharmacological intervention can reduce smoking substantially . CONCLUSION The results of this pilot will be used as a basis for a large-scale r and omized trial of an intervention with combined culturally and linguistically sensitive MI and NRT components for Chinese and other Asian ethnic groups OBJECTIVE Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs , few studies have investigated the efficacy of smoking cessation interventions among this group . The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone . METHOD The authors recruited 298 regular smokers with a psychotic disorder residing in the community and r and omly assigned them to a routine care comparison condition ( N=151 ) or an eight-session , individually administered smoking cessation intervention ( N=147 ) , which consisted of nicotine replacement therapy , motivational interviewing , and cognitive behavior therapy . Outcome variables included continuous and point-prevalence abstinence rates , smoking reduction status , and changes in symptoms and functioning . RESULTS While there were no overall differences between the treatment group and comparison group in abstinence rates , a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions ( point-prevalence rates : 3 months , 30.0 % versus 6.0 % ; 6 months , 18.6 % versus 4.0 % ; and 12 months , 18.6 % versus 6.6 % ) . Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months ( 21.4 % versus 4.0 % ) . There was a strong dose-response relationship between treatment session attendance and smoking reduction status , with one-half of those who completed the intervention program achieving a 50 % or greater reduction in daily cigarette consumption across the follow-ups , relative to less than one-fifth of the comparison subjects . There was no evidence of any associated deterioration in symptoms or functioning . CONCLUSIONS These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder . Further development of more efficacious interventions is required for those who do not respond to existing interventions Context Smoking cessation is difficult and may require repeated or intensive interventions . Contribution In this multicenter trial , 750 primary care patients who smoked at least 10 cigarettes per day were r and omly assigned to pharmacotherapy ( nicotine patch or bupropion ) , pharmacotherapy supplemented with up to 2 calls from trained counselors , or pharmacotherapy supplemented with up to 6 counseling calls . Utilization of the interventions , which were offered every 6 months for 2 years , declined over time . Smoking abstinence rates at 2 years were 23 % , 24 % , and 28 % in the 3 groups . Caution Pharmacotherapy was free . Smoking abstinence was self-reported . The Editors Cigarette smoking is a chronic illness characterized by repeated cycles of quit attempts and relapse . Most models for addressing smoking cessation are based on single , short-term interventions lasting only a few weeks or months ( 1 ) . Although most smokers will not quit after a single intervention , few studies have addressed the chronic nature of nicotine dependence by providing systematic , repetitive treatment opportunities ( 1 ) . Providing treatment only to smokers who are already prepared to quit further limits the reach of current smoking cessation interventions ( 2 ) . New models of chronic disease care might provide an alternative approach for exp and ing the reach and effectiveness of smoking cessation efforts ( 3 ) . Physicians are in direct contact with approximately 70 % of smokers each year ( 4 , 5 ) . Their potential role in promoting smoking cessation has been well delineated and incorporated into current clinical practice guidelines ( 1 ) . With the development of new , more effective prescription pharmacotherapy for smoking cessation , the role of primary care practice s in promoting smoking cessation is now more important than ever . Unfortunately , only half of the smokers who see their physicians are asked about their smoking ( 6 ) , and even fewer receive advice from their health care provider to quit or receive pharmacotherapy or follow-up ( 4 , 7 ) . Smoking cessation counseling competes with other pressing clinical tasks , and beyond brief advice , many physicians feel they are too busy to routinely and repeatedly counsel participants who smoke ( 810 ) . To assist primary care physicians in the treatment of rural smokers , we developed KanQuit , a smoking cessation program based on the chronic care model ( 4 ) , which integrates principles of disease management into the treatment of smokers seen in rural primary care . Our objective was to enroll smokers , regardless of their willingness to quit , into a disease registry and compare cessation rates among smokers who received pharmacotherapy alone or combined with either moderate-intensity or high-intensity disease management that includes counseling and provider feedback . Methods Design Overview We did a r and omized , single-blind trial of varying levels of disease management for smoking cessation . We recruited participants who smoked more than 10 cigarettes per day from rural primary care clinics across Kansas and r and omly assigned them to receive pharmacotherapy alone , pharmacotherapy supplemented by 1 to 2 counseling calls every 6 months ( moderate-intensity disease management ) , or pharmacotherapy supplemented by up to 6 counseling calls every 6 months ( high-intensity disease management ) . For recipients of moderate-intensity and high-intensity disease management , we faxed periodic progress reports to their physician . We offered all participants free pharmacotherapy ( either bupropion or transdermal nicotine patch ) every 6 months . We enrolled participants from June 2004 to October 2005 and followed them for 24 months , completing follow-up in December 2007 . All participants provided written informed consent . The University of Kansas Medical Center 's Human Subjects Committee approved the study . Setting and Participants We conducted our study in 50 rural primary care practice s in the Kansas Physicians Engaged in Prevention Research network ( 11 ) . As part of a rural primary care research experience , trained medical students systematic ally screened participants , identified smokers , and recruited them for this study , regardless of their interest in quitting ( 12 ) . We considered smokers eligible if they had a primary care physician who participated in this study ; were older than 18 years ; smoked more than 10 cigarettes per day for at least 1 year and for at least 25 of the past 30 days ; spoke English ; and had a telephone . We excluded smokers if they were pregnant or planned to become pregnant , planned to move out of the study area , had signs of dementia or mental illness that would preclude participation , or lived with a smoker already enrolled in the study . Of the 1827 smokers we screened , 61 % met criteria for study entry ( Figure 1 ) . Of these , we enrolled 67 % . Figure 1 . Study flow diagram . HDM = high-intensity disease management ; MDM = moderate-intensity disease management ; PM = pharmacotherapy management . R and omization and Interventions Participant R and omization R and omization occurred at the participant level . A computer-generated r and om-number table was used to generate allocation cards in blocks of 24 , with allocation equally distributed across treatment groups . To conceal allocation , we placed these cards in sequentially numbered , opaque , sealed envelopes . After research assistants verified participant eligibility and completed the baseline assessment , the project director opened the next sequential sealed envelope and determined the participant 's treatment allocation . One of 9 counselors trained in smoking cessation and motivational interviewing ( 12 ) conducted all interventions from a single central site . We assigned participants to counselors without regard to practice site . Pharmacotherapy At baseline , all smokers received a health education mailing that consisted of a welcome letter , information about the use of bupropion and the nicotine patch for smoking cessation , and copies of You Can Quit Smoking : Consumer Guide ( 13 ) and When Smokers QuitThe Health Benefits Over Time ( 14 ) . At baseline and at 6 , 12 , and 18 months , participants received a mailed offer for free pharmacotherapy that consisted of either a 6-week course of a nicotine patch ( 21 mg/d ) or a 7-week course of sustained-release bupropion ( 150 mg twice daily ) . Participants interested in using either medication could return a postage-paid postcard or call a toll-free number . We screened all participants who requested pharmacotherapy for potential contraindications ( 15 ) . Participants with absolute contraindications for a given drug were ineligible to receive that drug but were offered the option of receiving the other drug . Participants with contraindications to both drugs were not eligible to receive medication from the study but could participate in all other aspects of the intervention . For participants who requested bupropion and those with relative contraindications to the nicotine patch , research staff faxed a prescription request to their primary care physicians . This prescription request delineated any relative contraindications or potential drug interactions . For these participants , their physicians made the final assessment of the appropriateness of the bupropion or the patch . For participants without contraindications to the nicotine patch or on receipt of a faxed , signed prescription , the bupropion or patches were mailed to the participant along with instructions for use . Disease Management In addition to pharmacotherapy , the moderate-intensity and high-intensity disease management groups received educational support , telephone counseling , and periodic progress reports with counseling suggestions faxed to their physician . Every 6 months , they received a KanQuit newsletter that addressed tips on quitting smoking , talking with their physician about smoking , and using pharmacotherapy for cessation . The newsletters were personalized to include study up date s , counselor photographs , physician feature stories , and testimonials of participants who had quit smoking . We offered participants assigned to moderate-intensity disease management up to 2 telephone-based counseling sessions every 6 months ( 1 session to promote a quit attempt and 1 additional follow-up session for those who made a quit attempt ) . We offered participants assigned to high-intensity disease management up to 6 counseling calls every 6 months to either promote quitting or prevent relapse . We scheduled calls at the participant 's convenience , and they varied according to the participant 's quit plan but followed a rough schedule of calls at 1 , 3 , 6 , 9 , and 16 weeks after the onset of each 6-month treatment cycle . Counselors used motivational interviewing techniques and followed a semistructured protocol to promote a cessation attempt or , for abstinent smokers , to encourage relapse prevention . During counseling calls , case managers reminded participants about the availability of pharmacotherapy and , for interested participants , provided immediate support for acquiring either the nicotine patch or bupropion , as described previously . We faxed personalized progress reports with suggestions for interventions to the participant 's physician after the first counseling call ( both moderate-intensity and high-intensity disease management participants ) and after the last counseling call ( high-intensity disease management participants only ) during each 6-month cycle . We faxed additional progress reports to the participant 's physician whenever the moderate-intensity or high-intensity disease management participant set a quit date . Outcomes , Measurements , and Follow-up Research assistants who were blinded to treatment group assignment conducted assessment s by telephone at baseline and at 6 , 12 , 18 , and 24 months . Primary Outcome The primary outcome measure was self-reported 7-day abstinence at 24 months , defined as not having smoked a cigarette during the previous 7 days . Although self-reported abstinence has been Smokers not currently interested in quitting ( N = 616 ) were r and omized to receive telephone-based ( a ) reduction counseling plus nicotine replacement therapy ( NRT ) plus brief advice to quit , ( b ) motivational advice plus brief advice , or ( c ) no treatment . More smokers in the reduction ( 43 % ) and motivational ( 51 % ) conditions made a 24-hr quit attempt over 6 months than smokers in the no-treatment condition ( 16 % ; p < or = .01 ) , but the 2 active conditions did not differ ( p > or = .05 ) . Similarly , 18 % , 23 % , and 4 % of each condition were abstinent ( 7-day point prevalence ) at 6 months ( p < or = .01 ) . Results indicate smoking reduction using NRT does not undermine cessation but rather increases the likelihood of quitting to a degree similar to motivational advice AIM To evaluate the effectiveness of a nurse intervention aim ed at helping college student smokers quit smoking . DESIGN Single-blind , pragmatic r and omized controlled trial which compares a multi-component intervention , tailored specifically to college students , with a brief advice session with a 6-month follow-up . SETTING S This study was conducted at the University of Navarra , Spain . PARTICIPANTS A total of 255 college student smokers ( age range = 18 - 24 years ) were r and omized to an intervention group ( n = 133 ) or to a control group ( n = 122 ) . INTERVENTION A multi-component intervention based on the Theory of Triadic Influence of Flay was developed . The intervention consisted of a 50-minute motivational interview conducted by a nurse and online self-help material . The follow-up included a reinforcing e-mail and group therapy . MEASUREMENTS The primary outcome was self-reported abstinence , with biochemical verification at 6 months . The secondary outcomes consisted of the mean number of cigarettes smoked per day , self-reported attempts to quit smoking and stage of change at 6 months . FINDINGS At the 6-month follow-up , the smoking cessation incidence was 21.1 % in the intervention group compared with 6.6 % in the control group ( difference = 14.5 confidence interval = 6.1 - 22.8 ; relative risk = 3.41 , 95 % confidence interval = 1.62 - 7.20 ) . The difference in the mean number of cigarettes at 6 months was significantly different ( difference = -2.2 , confidence interval = -3.6 to -0.9 ) . CONCLUSIONS A multi-component intervention tailored to college students and managed by a nurse is effective in increasing smoking cessation among college students INTRODUCTION Postpartum relapse rates are high among women who spontaneously quit smoking during pregnancy . This r and omized clinical trial tested a Motivation and Problem-Solving ( MAPS ) treatment for reducing postpartum relapse among diverse low-income women who quit smoking during pregnancy ( N = 251 ; 32 % Black , 30 % Latino , and 36 % White ; 55 % < $ 30,000/year household income ) . METHODS Pregnant women were r and omly assigned to MAPS/MAPS+ or Usual Care ( UC ) . Continuation ratio logit models were used to examine differences in biochemically confirmed continuous abstinence at Weeks 8 and 26 postpartum by treatment group and moderators of the treatment effect . Analyses controlled for age , race/ethnicity , partner status , education , smoking rate , and the number of smokers in the participant 's environment . RESULTS MAPS/MAPS+ was more efficacious than UC in the prevention of postpartum relapse ( p = .05 ) . An interaction between treatment and the number of cigarettes smoked per day before quitting approached significance ( p = .09 ) , suggesting that the MAPS/MAPS+ treatment effect was stronger among women who smoked more cigarettes per day . DISCUSSION MAPS , a holistic and dynamic approach to changing behavior using a combined motivational enhancement and social cognitive approach , is a promising intervention for postpartum smoking relapse prevention among low-income women , which may have particular relevance for women with higher prequit smoking rates Despite high smoking rates among those living in poverty , few cessation studies are conducted in these population s. This cluster-r and omized trial tested nicotine gum plus motivational interviewing ( MI ) for smoking cessation in 20 low-income housing developments ( HDs ) . Intervention participants ( 10 HDs , n = 66 ) received educational material s , 8 weeks of 4 mg nicotine gum , and 5 MI sessions on quitting smoking . Comparison participants ( 10 HDs , n = 107 ) received 5 MI sessions and educational material s addressing fruit and vegetable consumption . Participants had a mean age of 46.3 years and were predominantly female ( 70 % ) and African American ( 83 % ) . Biochemically-verified 7-day abstinence rates at 8 weeks were 6.1 % and 5.6 % in the intervention and comparison arms , respectively ( p = ns ) ; and at 26 weeks were 7.6 % and 9.3 % , respectively ( p = ns ) . Results suggest that nicotine gum plus MI were not effective for smoking cessation in low-income housing . Programs are needed to enhance the effectiveness of pharmacotherapy and counseling in underserved population INTRODUCTION Maximizing smoking abstinence in lung cancer screening participants is important to reduce individual risk of disease and improve screening cost-effectiveness ; however , the optimal strategy remains undefined . We hypothesized that a single session of tailored face-to-face counseling on the day of screening CT scan , coupled with audio and printed cessation information would be feasible to deliver in a CT screening trial . METHODS We r and omized volunteer smokers in the Queensl and Lung Cancer Screening Study to intervention ( counseling session , audio quit material s , printed quit material s , Quitline contact details ) or control group ( printed quit material s , Quitline contact details ) . Participants self-reported point prevalence quit rates at 1 year . RESULTS Fifty-five smokers were enrolled ; 28 r and omized to intervention and 27 controls . Median cigarette consumption was 25/day ; 54/55 smoked at least 15 cigarettes per day . Median smoking duration was 46 years . Median Fagerström dependence score was 6 . In total 58 % did not report any quit attempt in the prior 12 months . Mean duration of counseling was 26.5 minutes . After 1 year , four participants ( 14.3 % ) in the intervention group and five participants ( 18.5 % ) in the control group had quit ( P = .74 ) . Combined annual point prevalence quit rate was 16.4 % . CONCLUSIONS Although feasible to deliver a single session of tailored counseling on the day of screening this intervention had no discernible impact on cessation over and above printed material s and Quitline access . As participants exhibited hardcore smoking characteristics , more intensive strategies , in larger cohorts , should be explored . IMPLICATION S The optimal smoking cessation strategy within a lung cancer screening program is not known . This study demonstrates that a single session of counseling can be feasibly delivered on the day of screening but may not have been intensive enough for long-term , hard-core smokers OBJECTIVE To determine knowledge about smoking , reasons for smoking , and reasons for wishing to quit and the association of these variables with abstinence at ten weeks and six months . DESIGN Descriptive study and longitudinal intervention . SETTING Inner-city public hospital clinics . PARTICIPANTS 410 African-American cigarette smokers interested in quitting were surveyed at baseline and subsequently enrolled into a double-blind , placebo-controlled , r and omized trial of the transdermal nicotine patch . MAIN OUTCOME MEASURES Descriptive information about smoking knowledge , reasons for smoking , and reasons for wishing to quit , and association of these variables with abstinence at 10 weeks and 6 months . RESULTS Among the 410 patients r and omized , mean age was 48 years , 61 % were female , 41 % had less than a high school education , 51 % had an annual household income less than $ 8,000 , and the average number of cigarettes smoked a day was twenty . The average number of questions answered correctly was nine out of eleven ( 84 % ) . The most cited reason for smoking was relaxation/tension reduction and the least cited were stimulation and h and ling of the cigarette . Ninety-nine percent of patients stated they wished to quit for health reasons . Knowledge , reasons for smoking , and reasons for wishing to quit were not significantly associated with 10-week or 6-month abstinence . CONCLUSIONS In this group of inner-city African-American smokers , knowledge about cigarette smoking was high . Reasons for smoking were related to relaxation , craving , and pleasure , and reasons for wishing to quit were largely health-related . Knowledge , reasons for smoking , and reasons for wishing to quit were not associated with 10 week or 6 month abstinence . Since knowledge about smoking is already high , future efforts should be directed at promoting cessation through proven behavioral and pharmacological approaches , rather than didactic patient education INTRODUCTION The effectiveness of low-cost smoking interventions targeted to pregnant women has been demonstrated , although few gains in absolute cessation rates have been reported in the past decade . Under conditions of typical clinical practice , this study examined whether outcomes achieved with brief counseling from prenatal care providers and a self-help booklet could be improved by adding more re source -intensive cognitive-behavioral programs . DESIGN R and omized Clinical Trial . SETTING A large-group-model managed care organization . PARTICIPANTS 390 English-speaking women 18 years of age or older who self-reported to be active smokers at their initial prenatal appointment . INTERVENTION Participants were r and omized to one of three groups : ( 1 ) a self-help booklet tailored to smoking patterns , stage of change , and lifestyle of pregnant smokers ; ( 2 ) the booklet plus access to a computerized telephone cessation program based on interactive voice response technology ; or ( 3 ) the booklet plus proactive telephone counseling from nurse educators using motivational interviewing techniques and strategies . No attempt was made to change smoking-related usual care advice from prenatal providers . MAIN OUTCOME MEASURE Biochemically confirmed abstinence measured by level of cotinine in urine sample s obtained during a routine prenatal visit at approximately the 34th week of pregnancy . RESULTS Twenty percent of participants were confirmed as abstinent with no significant differences found between intervention groups . Multivariate baseline predictors of cessation included number of cigarettes smoked per day , confidence in ability to quit , exposure to passive smoke , and educational level . No differential intervention effects were found within strata of these predictors or by baseline stage of readiness to change . Cessation rates among heavier smokers were strikingly low in all intervention groups . CONCLUSION Neither a computerized telephone cessation program nor systematic provision of motivational counseling improved cessation rates over a tailored self-help booklet delivered within the context of brief advice from prenatal providers . Innovative strategies need to be developed to increase the effectiveness of existing prenatal smoking interventions . Special attention should be paid to the needs of heavier smokers AIMS To test the efficacy of two smoking cessation interventions in a HIV positive ( HIV+ ) sample : st and ard care ( SC ) treatment plus nicotine replacement therapy ( NRT ) versus more intensive motivationally enhanced ( ME ) treatment plus NRT . DESIGN R and omized controlled trial . SETTING HIV+ smoker referrals from eight immunology clinics in the northeastern United States . PARTICIPANTS A total of 444 participants enrolled in the study ( mean age = 42.07 years ; 63.28 % male ; 51.80 % European American ; mean cigarettes/day = 18.27 ) . INTERVENTIONS SC participants received two brief sessions with a health educator . Those setting a quit date received self-help quitting material s and NRT . ME participants received four sessions of motivational counseling and a quit-day counseling call . All ME intervention material s were tailored to the needs of HIV+ individuals . MEASUREMENTS Biochemically verified 7-day abstinence rates at 2-month , 4-month and 6-month follow-ups . FINDINGS Intent-to-treat ( ITT ) abstinence rates at 2-month , 4-month and 6-month follow-ups were 12 % , 9 % and 9 % , respectively , in the ME condition , and 13 % , 10 % and 10 % , respectively , in the SC condition , indicating no between-group differences . Among 412 participants with treatment utilization data , 6-month ITT abstinence rates were associated positively with low nicotine dependence ( P = 0.02 ) , high motivation to quit ( P = 0.04 ) and Hispanic American race/ethnicity ( P = 0.02 ) . Adjusting for these variables , each additional NRT contact improved the odds of smoking abstinence by a third ( odds ratio = 1.32 , 95 % confidence interval = 0.99 - 1.75 ) . CONCLUSIONS Motivationally enhanced treatment plus NRT did not improve cessation rates over and above st and ard care treatment plus NRT in this HIV+ sample of smokers . Providers offering brief support and encouraging use of nicotine replacement may be able to help HIV+ patients to quit smoking INTRODUCTION Cigarette smoking during pregnancy is associated with poor maternal and child health outcomes . Effective interventions to increase smoking cessation rates are needed particularly for pregnant women unable to quit in their first trimester . Real-time ultrasound feedback focused on potential effects of smoking on the fetus may be an effective treatment adjunct , improving smoking outcomes . METHODS A prospect i ve r and omized trial was conducted to evaluate the efficacy of a smoking cessation intervention consisting of personalized feedback during ultrasound plus motivational interviewing-based counseling sessions . Pregnant smokers ( N = 360 ) between 16 and 26 weeks of gestation were r and omly assigned to one of three groups : Best Practice ( BP ) only , Best Practice plus ultrasound feedback ( BP+US ) , or Motivational Interviewing-based counseling plus ultrasound feedback ( MI+US ) . Assessment s were conducted at baseline and end of pregnancy ( EOP ) . RESULTS Analyses of cotinine-verified self-reported smoking status at EOP indicated that 10.8 % of the BP group was not smoking at EOP ; 14.2 % in the BP+US condition and 18.3 % who received MI+US were abstinent , but differences were not statistically significant . Intervention effects were found conditional upon level of baseline smoking , however . Nearly 34 % of light smokers ( < or = 10 cigarettes/day ) in the MI+US condition were abstinent at EOP , followed by 25.8 % and 15.6 % in the BP+US and BP conditions , respectively . Heavy smokers ( > 10 cigarettes/day ) were notably unaffected by the intervention . DISCUSSION Future research should confirm benefit of motivational interviewing plus ultrasound feedback for pregnant light smokers and explore mechanisms of action . Innovative interventions for pregnant women smoking at high levels are sorely needed INTRODUCTION One in 5 young adults in the United States currently smoke , and young adults are less likely than other smokers to make aided quit attempts . Telephone quitlines may be a useful tool for treating this population . This study tested a quitline-based smoking cessation intervention versus mailed self-help material s in smokers 18 - 24 years old . METHODS This was a 2-group r and omized clinical trial . The quitline-based counseling intervention ( CI ) included up to 4 proactive telephone counseling sessions ; participants in the self-help ( SH ) group received only mailed cessation material s. Participants included 410 young adults who had smoked at least 1 cigarette in the past 30 days and who called the Wisconsin Tobacco Quit Line ( WTQL ) for help with quitting . Primary study outcomes included whether or not a quit date was set , whether or not a serious quit attempt was undertaken , and self-reported 7-day point-prevalence abstinence at 1- , 3- , and 6-month postenrollment . RESULTS The CI and SH groups did not differ in the intent-to-treat abstinence analyses at any of the follow-ups . However , the CI group was significantly more likely to set a quit date at 1-month postenrollment . Follow-up response rates were low ( 67.8 % at 1 month ; 53.4 % at 3 months ; and 48.3 % at 6 months ) reflecting lower motivation to participate in this kind of research . CONCLUSIONS Relative to self-help , quitline counseling motivated young adults to set a quit date but abstinence rates were not improved . Research is needed on how to motivate young adult smokers to seek cessation treatment including quitline services INTRODUCTION Although homeless individuals smoke at an alarmingly high rate , few smoking cessation clinical trials have focused on this vulnerable population . Little is known about recruitment efforts and suitable eligibility criteria for tobacco control research in homeless population s. METHODS The aim of this article is to describe the recruitment , eligibility , and enrollment of homeless smokers who participated in the Power to Quit smoking study , a r and omized smoking cessation clinical trial funded by the National Institutes of Health . The study compared motivational interviewing and st and ard counseling while participants received an 8-week treatment of the nicotine patch . RESULTS Working with local emergency shelters , a total of 839 adult smokers were screened for study eligibility , 580 of whom ( 69.1 % ) met eligibility criteria . Of those eligible , 430 ( 74.1 % ) returned for r and omization . Those who returned for r and omization were older and more likely to have a phone number compared with eligible participants not enrolled . The most common reasons for exclusion included exhaled carbon monoxide levels less than or equal to 5 parts per million ( indicating nonsmoking status ) , use of smoking cessation aid during the past 30 days , and not meeting the study definition of homelessness . CONCLUSION Knowledge of these factors may help research ers tailor criteria that accurately identify and include homeless smokers in future research INTRODUCTION Despite limitations in evidence , the current Clinical Practice Guideline advocates Motivational Interviewing for smokers not ready to quit . This study evaluated the efficacy of Motivational Interviewing for inducing cessation-related behaviors among smokers with low motivation to quit . DESIGN R and omized clinical trial . SETTING / PARTICIPANTS Two-hundred fifty-five daily smokers reporting low desire to quit smoking were recruited from an urban community during 2010 - 2011 and r and omly assigned to Motivational Interviewing , health education , or brief advice using a 2:2:1 allocation . Data were analyzed from 2012 to 2014 . INTERVENTION Four sessions of Motivational Interviewing utilized a patient-centered communication style that explored patients ' own reasons for change . Four sessions of health education provided education related to smoking cessation while excluding elements characteristic of Motivational Interviewing . A single session of brief advice consisted of brief , personalized advice to quit . MAIN OUTCOMES MEASURES Self-reported quit attempts ; smoking abstinence ( biochemically verified ) ; use of cessation pharmacotherapies ; motivation ; and confidence to quit were assessed at baseline and 3- and 6-month follow-ups . RESULTS Unexpectedly , no significant differences emerged between groups in the proportion who made a quit attempt by 6-month follow-up ( Motivational Interviewing , 52.0 % ; health education , 60.8 % ; brief advice , 45.1 % ; p=0.157 ) . Health education had significantly higher biochemically verified abstinence rates at 6 months ( 7.8 % ) than brief advice ( 0.0 % ) ( 8 % risk difference , 95 % CI=3 % , 13 % , p=0.003 ) , with the Motivational Interviewing group falling in between ( 2.9 % abstinent , 3 % risk difference , 95 % CI=0 % , 6 % , p=0.079 ) . Both Motivational Interviewing and health education groups showed greater increases in cessation medication use , motivation , and confidence to quit relative to brief advice ( all p<0.05 ) , and health education showed greater increases in motivation relative to Motivational Interviewing ( Cohen 's d=0.36 , 95 % CI=0.12 , 0.60 ) . CONCLUSIONS Although Motivational Interviewing was generally more efficacious than brief advice in inducing cessation behaviors , health education appeared the most efficacious . These results highlight the need to identify the context s in which Motivational Interviewing may be most efficacious and question recommendations to use Motivational Interviewing rather than other less complex cessation induction interventions . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT01188018 OBJECTIVE Several cessation treatments effectively enhance cessation , but it is not always clear which treatment may be most suitable for a particular client . We examined predictors of treatment outcome and treatment moderators among smoking parents in the Netherl and s. METHOD We conducted secondary analyses of a r and omized controlled trial in which smoking parents received either quitline counselling ( n=256 ) or a self-help brochure ( n=256 ) . Data collection was completed in October 2012 . Endpoints were 7-day point prevalence abstinence and 6-month prolonged abstinence at 12-month follow-up . Potential predictors and moderators included socio-demographic characteristics , smoking-related variables , and child-related variables . RESULTS Male gender , higher employment status , lower daily cigarette consumption , higher levels of confidence in quitting , presence of a child with a chronic respiratory illness , and wanting to quit for the health of one 's child predicted abstinence at 12months . Significant treatment moderators were intention to quit and educational level . Quitline counselling was effective regardless of intention to quit and educational level , but self-help material was less effective among less motivated and lower educated parents . CONCLUSION Certain subgroups of smokers , such as parents who are concerned about the health of their child , are particularly receptive to cessation support . Individual characteristics should be considered in treatment selection Objectives To evaluate the effect of training primary care health professionals in behaviour change counselling on the proportion of patients self reporting change in four risk behaviours ( smoking , alcohol use , exercise , and healthy eating ) . Design Cluster r and omised trial with general practice s as the unit of r and omisation . Setting General practice s in Wales . Participants 53 general practitioners and practice nurses from 27 general practice s ( one each at all but one practice ) recruited 1827 patients who screened positive for at least one risky behaviour . Intervention Behaviour change counselling was developed from motivational interviewing to enable clinicians to enhance patients ’ motivation to change health related behaviour . Clinicians were trained using a blended learning programme called Talking Lifestyles . Main outcome measures Proportion of patients who reported making beneficial changes in at least one of the four risky behaviours at three months . Results 1308 patients from 13 intervention and 1496 from 14 control practice s were approached : 76 % and 72 % respectively agreed to participate , with 831 ( 84 % ) and 996 ( 92 % ) respectively screening eligible for an intervention . There was no effect on the primary outcome ( beneficial change in behaviour ) at three months ( 362 ( 44 % ) v 404 ( 41 % ) , odds ratio 1.12 ( 95 % CI 0.90 to 1.39 ) ) or on biochemical or biometric measures at 12 months . More patients who had consulted with trained clinicians recalled consultation discussion about a health behaviour ( 724/795 ( 91 % ) v 531/966 ( 55 % ) , odds ratio 12.44 ( 5.85 to 26.46 ) ) and intended to change ( 599/831 ( 72 % ) v 491/996 ( 49 % ) , odds ratio 2.88 ( 2.05 to 4.05 ) ) . More intervention practice patients reported making an attempt to change ( 328 ( 39 % ) v 317 ( 32 % ) , odds ratio 1.40 ( 1.15 to 1.70 ) ) , a sustained behaviour change at three months ( 288 ( 35 % ) v 280 ( 28 % ) , odds ratio 1.36 ( 1.11 to 1.65 ) ) , and reported slightly greater improvements in healthy eating at three and 12 months , plus improved activity at 12 months . Training cost £ 1597 per practice . Discussion Training primary care clinicians in behaviour change counselling using a brief blended learning programme did not increase patients reported beneficial behaviour change at three months or improve biometric and a biochemical measure at 12 months , but it did increase patients ’ re collection of discussing behaviour change with their clinicians , intentions to change , attempts to change , and perceptions of having made a lasting change at three months . Enduring behaviour change and improvements in biometric measures are unlikely after a single routine consultation with a clinician trained in behaviour change counselling without additional intervention . Trial registration IS RCT N AIMS To assess the effects of adding motivational interviewing ( MI ) counseling to nicotine patch for smoking cessation among homeless smokers . DESIGN Two-group r and omized controlled trial with 26-week follow-up . PARTICIPANTS AND SETTING A total of 430 homeless smokers from emergency shelters and transitional housing units in Minneapolis/St Paul , Minnesota , USA . INTERVENTION AND MEASUREMENTS All participants received 8-week treatment of 21-mg nicotine patch . In addition , participants in the intervention group received six individual sessions of MI counseling which aim ed to increase adherence to nicotine patches and to motivate cessation . Participants in the st and ard care control group received one session of brief advice to quit smoking . Primary outcome was 7-day abstinence from cigarette smoking at 26 weeks , as vali date d by exhaled carbon monoxide and salivary cotinine . FINDINGS Using intention-to-treat analysis , verified 7-day abstinence rate at week 26 for the intervention group was non-significantly higher than for the control group ( 9.3 % versus 5.6 % , P = 0.15 ) . Among participants who did not quit smoking , reduction in number of cigarettes from baseline to week 26 was equally high in both study groups ( -13.7 ± 11.9 for MI versus -13.5 ± 16.2 for st and ard care ) . CONCLUSIONS Adding motivational interviewing counseling to nicotine patch did not increase smoking rate significantly at 26-week follow-up for homeless smokers AIMS We tested two aims : ( 1 ) the teachable moment ( TM ) : whether second-h and smoke exposure ( SHSe ) feedback motivates cessation in parents of children with asthma versus parents of healthy children ( HC ) ; and ( 2 ) whether greater intervention intensity [ enhanced-pre caution adoption model ( PAM ) ] produces greater cessation than a previously tested intervention ( PAM ) . DESIGN AND INTERVENTIONS Aim 1 : two home visits ( asthma education or child wellness ) , and cessation induction using motivational interviewing and SHSe feedback . Aim 2 : post-home-visits , parents with asthmatic children were r and omized to PAM ( n = 171 ; six asthma education calls ) or enhanced-PAM ( n = 170 ; six asthma education/smoking cessation calls + repeat SHSe feedback ) . SETTING Rhode Isl and , USA . PARTICIPANTS Parents of asthmatic ( n = 341 ) or healthy ( n = 219 ) children who did not have to want to quit smoking to enroll . MEASUREMENTS Measurements were given at baseline , 2 , 4 , 6 and 12 months . Abstinence was bioverified . Outcomes were 7-day and 30-day point prevalence abstinence ( ppa ) and SHSe ( primary ) and asthma morbidity ( secondary ) . FINDINGS Aim 1 : the TM was supported : parents of asthmatic children were more than twice as likely to achieve 30-day [ odds ratio ( OR ) = 2.60 , 95 % confidence interval ( CI ) = 1.22 - 5.54 ] and 7-day ppa ( OR = 2.26 , 95 % CI = 1.13 - 4.51 ) at 2 months ( primary end-point ) and have non-detectable levels of SHSe than HCs . Greater treatment intensity yielded stronger TM effects ( OR = 3.60 ; 95 % CI = 1.72 - 7.55 ) . Aim 2 : enhanced-PAM was more likely to achieve 30-day ppa at the primary end-point , 4 months ( OR = 2.12 , 95 % CI 1.09 - 4.12 ) and improved asthma outcomes versus PAM . CONCLUSIONS Smoking cessation intervention ( Motivational Interviewing plus biomarker feedback ) appear to motivate smoking cessation more strongly among parents of asthmatic children than among parents of healthy children . Increased intervention intensity yields greater smoking cessation among parents of asthmatic children and better asthma outcomes Cigarette smoking is highly prevalent among people living with HIV/AIDS and poses unique health risks . Smoking cessation programs tailored to this population have documented improved smoking outcomes with nicotine replacement therapy ( NRT ) . The current study examined 6-month abstinence rates from a r and omized clinical trial targeting 412 HIV-positive adult current smokers ( 51 % European American , 19 % African American , and 17 % Hispanic American ) and tested whether psychosocial variables , such as self-efficacy and decisional balance , mediated the relationship between NRT and long-term abstinence . Meeting criteria for complete mediation , 6-month smoking abstinence rates improved significantly with increases in these mediators , and the association of NRT and smoking abstinence was no longer significant once changes in self-efficacy and decisional balance were taken into account . Failure to translate gains in self-efficacy among African Americans into improved abstinence rates accounted for racial/ethnic differences among participants . Specific psychosocial factors , such as self-efficacy , may be particularly amenable to change in cessation interventions and should be addressed with greater awareness of how cultural and social context ual factors impact treatment response among people living with HIV/AIDS Background The diabetes of many patients is managed in general practice ; healthcare providers aim to promote healthful behaviors , such as healthful diet , adequate physical activity , and smoking cessation . These measures may decrease insulin resistance , improve glycemic control , lipid abnormalities , and hypertension . They may also prevent cardiovascular disease and complications of diabetes . However , professionals do not adhere optimally to guidelines for lifestyle counseling . Motivational interviewing to change the lifestyle of patients with type 2 diabetes is intended to improve diabetes care in accordance with the national guidelines for lifestyle counseling . Primary care nurses will be trained in motivational interviewing embedded in structured care in general practice . The aim of this paper is to describe the design and methods of a study evaluating the effects of the nurses ' training on patient outcomes . Methods / Design A cluster , r and omized , controlled trial involving 70 general practice s ( 35 practice s in the intervention arm and 35 in the control arm ) starting in March 2007 . A total of 700 patients with type 2 diabetes will be recruited . The patients in the intervention arm will receive care from the primary care nurse , who will receive training in an implementation strategy with motivational interviewing as the core component . Other components of this strategy will be adaptation of the diabetes protocol to local circumstances , introduction of a social map for lifestyle support , and educational and supportive tools for sustaining motivational interviewing . The control arm will be encouraged to maintain usual care . The effect measures will be the care process , metabolic parameters ( glycosylated hemoglobin , blood pressure and lipids ) , lifestyle ( diet , physical activity , smoking , and alcohol ) , health-related quality of life , and patients ' willingness to change behaviors . The measurements will take place at baseline and after 14 months . Discussion Applying motivational interviewing for patients with diabetes in primary care has been studied , but to our knowledge , no other study has yet evaluated the implementation and sustainability of motivating and involving patients in day-to-day diabetes care in general practice . If this intervention proves to be effective and cost-effective , large-scale implementation of this nurse-oriented intervention will be considered and anticipated . Trial registration Current Controlled Trials IS RCT N68707773 |
12,597 | 27,898,998 | Nasogastric feeding was poorly tolerated .
There is very low- quality evidence from one trial ( 57 participants , mainly men ) of no evidence for an effect of tube feeding followed by oral supplementation on mortality or complications .
Tube feeding , however , was poorly tolerated .
There is very low- quality evidence from one trial ( 80 participants ) that a combination of intravenous feeding and oral supplements may not affect mortality but could reduce complications .
There is low- quality evidence that oral multinutrient supplements started before or soon after surgery may prevent complications within the first 12 months after hip fracture , but that they have no clear effect on mortality .
There is very low- quality evidence that oral supplements may reduce ' unfavourable outcome ' ( death or complications ) and that they do not result in an increased incidence of vomiting and diarrhoea . | BACKGROUND Older people with hip fractures are often malnourished at the time of fracture , and subsequently have poor food intake .
This is an up date of a Cochrane review first published in 2000 , and previously up date d in 2010 .
OBJECTIVES To review the effects ( benefits and harms ) of nutritional interventions in older people recovering from hip fracture .
However , this expensive intervention is usually reserved for people with non-functioning gastrointestinal tracts , which is unlikely in this trial . | BACKGROUND Undernutrition and weight loss are important determinants of clinical outcome in older patients after hip fracture but the effectiveness of nutritional support programs in routine clinical practice remains controversial . AIMS OF THE PROJECT : To determine if oral nutritional supplements given daily for 28 days after hip fracture surgery could prevent weight loss and /or lead to improved clinical outcomes ( mortality rates , discharge destination , activities of daily living or length of hospital stay ) in non-malnourished community-dwelling older women with hip fracture . METHODS One hundred and nine women with BMI range 20 - 30 kg/m(2 ) were allocated to either nutritional supplements ( 352 kcal/day ) or usual hospital nutrition using a quasi-r and omisation technique . Body weight changes were monitored at 4 and 8 weeks and clinical outcomes were recorded at discharge and at 6 months . RESULTS No significant differences in weight change or clinical outcomes were seen between the two groups . Compliance with consuming the nutritional supplements was quite variable and there was a significant negative correlation between the amount of supplement consumed and subsequent weight change ( r=-0.36 , P=0.019 ) . CONCLUSIONS Poor compliance with oral nutritional supplements is an important determinant of the effectiveness of oral nutritional interventions in preventing weight loss after hip fracture . Whilst this may explain the lack of clinical improvements seen , our data do not support the routine use of oral nutritional supplements in non-malnourished hip fracture patients 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 This study aim ed to evaluate whether food fortification and snacks could increase the energy and protein intakes of hospital patients . The control group of 82 consecutive admissions on medical , elderly care and orthopaedic wards ate freely from the hospital menu . Subsequently , an intervention group of 62 patients were offered fortified food and snacks , providing an extra 22.2|g protein/day and 966 kcal/day in addition to the st and ard menu . Fortification significantly increased energy intake in the intervention group ( P = 0.007 , independent sample s t-test ) , having the greatest effect on groups with the lowest energy intake , that is male and female orthopaedic , female medical and female elderly patients ( 84 cent of total ) . The increases in energy intake were 21.3 cent , 21.4 cent , 23 cent and 19.6 cent respectively . Although the increased energy and protein intake represented 25.6 cent and 22.5 cent respectively , of the supplements given , and suggested that wastage was high , it was nevertheless sufficient to remove energy deficit . We therefore propose that provision of fortified food and snacks is a convenient method of improving the nutritional intakes of hospital patients 59 elderly patients ( mean age 82 ) with femoral neck fractures were r and omised into two groups . 27 patients received daily an oral nutrition supplement ( 250 ml , 20 g protein , 254 kcal ) for a mean of 32 days ; 32 patients acted as controls . On admission most patients had nutritional deficiencies . Despite being offered adequate quantities , nutritional requirements were not met during the hospital stay . Clinical outcome was significantly better in the supplemented group ( 56 % favourable course vs 13 % in controls ) during the stay in the convalescent hospital . The rates of complications and deaths were also significantly lower in supplemented patients ( 44 % vs 87 % ) . 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients ( 40 % vs 74 % ) . The median duration of hospital stay was significantly shorter in the supplemented group ( 24 vs 40 days ) . Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation A total of 744 elderly women with fractured neck of femur were classified into three groups according to anthropometric measurements on admission : group 1 , well nourished ; group 2 , thin ; group 3 , very thin . Group 1 ate well and had a low mortality and a short rehabilitation time . The thinner the patients the lower their voluntary food intake , the higher their mortality and the longer their rehabilitation time . A series of 122 patients from groups 2 and 3 were entered postoperatively into a r and omised controlled trial of overnight supplementary nasogastric tube feeding ( 4.2 MJ ( 1000 kcal ) , including 28 g protein ) in addition to their normal ward diet . This treatment was associated with improvements not only in anthropometric and plasma protein measurements but also in clinical outcome , especially in the very thin group 3 patients . Rehabilitation time and hospital stay were shortened . Mortality in group 3 was less in the tube fed patients ( 8 % ) than in the controls ( 22 % ) but this difference did not reach statistical significance . One in five patients could not tolerate the nasogastric tube , but in the remainder the treatment caused no side effects and did not seriously diminish voluntary oral food intake by day OBJECTIVE To examine how improved attention to nutritional status and dietary intake , achieved through the employment of dietetic assistants ( DAs ) , will affect postoperative clinical outcome among elderly women with hip fracture . DESIGN Open prospect i ve r and omised controlled trial , comparing conventional nursing care with the additional nutritional support provided by DA . SETTING Thirty-eight bedded acute trauma ward in a teaching hospital . PARTICIPANTS All but 11 of 344 consecutive admissions with acute nonpathological hip fracture were approached . Three hundred and eighteen ( 93 % ) agreed to inclusion . Sixteen were ineligible as they were immediately transferred to another acute ward , were managed conservatively or died preoperatively . PRIMARY OUTCOME MEASURE Postoperative mortality in the acute trauma unit . SECONDARY OUTCOME MEASURES Postoperative mortality at 4 months after fracture , length of stay , energy intake and nutritional status . RESULTS DA-supported participants were less likely to die in the acute ward ( 4.1 versus 10.1 % , P = 0.048 ) . This effect was still apparent at 4 month follow-up ( 13.1 versus 22.9 % , P = 0.036 ) . DA-supported subjects had significantly better mean daily energy intake ( 1,105 kcal versus 756 kcal/24 h , 95 % CI 259 - 440 kcal/24 h , P<0.001 ) , significantly smaller reduction in mid-arm circumference during their inpatient stay ( 0.39 cm , P = 0.002 ) and nonsignificantly favourable results for other anthropometric and laboratory measurements . CONCLUSION Dietetic or nutrition assistants are being introduced in units across the UK . This , the largest ever study of nutritional support after hip fracture , shows that their employment significantly reduced patients ' risk of dying in the acute trauma unit ; an effect that persisted at 4 month follow-up BACKGROUND & AIMS Malnutrition is common in hip fracture elderly patients . The purpose of this study was to examine the relationship between the Mini Nutrition Assessment Short Form ( MNA-SF ) and cognitive , functional status , comorbidity and outcome of operated patients . METHODS Clinical data , MNA , functioning , cognition were prospect ively determined . Retrospectively , the Charlson Comorbidity Index ( CCI ) and Cumulative Illness Rating Scale for Geriatrics ( CIRS-G ) were applied . RESULTS The study consisted of 95 well-nourished ( WN ) , 95 at risk of malnutrition ( ARM ) and 25 malnourished ( MN ) patients . More WN patients were independent vs. partially or fully dependent ; more WN patients were cognitively normal vs. cognitively impaired ( p < 0.001 ) . CIRS-G was higher in MN vs. WN patients and CCI was higher in MN and ARM vs. WN patients ( p < 0.001 ) . During a 6 month period , 100 patients were readmitted , with less readmissions in the WN group ( p = 0.024 ) . During a 36 month follow-up , 79 patients died . The mortality rate was lower in the WN group ( p = 0.01 ) . Stepwise regression analysis found that the only independent variables for mortality were CCI and functioning ( p < 0.01 ) . CONCLUSIONS Patients with higher cognitive and functional status were in superior nutritional condition . Poor nutritional status was associated with higher comorbidity indices , mortality and readmissions . However , we found that only comorbidity and low functioning can predict long-term mortality A group of 40 consecutive patients with hip fractures were studied and confirmed to have a high incidence of protein-calorie malnutrition . The prospect i ve nutritional assessment performed for this study included : serum albumin , serum transferrin , anthropometric measurements , skin testing for delayed hypersensitivity , total lymphocyte count , and a 24-h urine collection for metabolic and nitrogen balance determinations . At 3 months after their hip fracture , 37.5 % returned to their premorbid ambulatory status ; 42.5 % sustained a decrement in their ambulatory status or independence ; 12.5 % died ; 7.5 % were lost to follow-up . Of the nutritional parameters studied , albumin was significantly associated with mortality ( p = 0.004 ) . Considering those patients with an albumin less than 3.0 , a mortality rate of 70 % was observed in follow-up ( maximum of 11 months ) , compared with a mortality rate of 18 % in patients with an albumin greater than or equal to 3.0 . It is concluded that the serum albumin has value as a nutritional index without specialized nutritional parameters , and that a more aggressive approach to nutritional support is needed for the hypoalbuminemic patient with a hip fracture , particularly for those with a serum albumin below 3.0 OBJECTIVE Hip fractures are a major cause of morbidity for older women , which result in impaired health related quality of life ( HRQOL ) . Few studies have prospect ively evaluated the effect of hip fractures in women on HRQOL with different health state preference measures . We compared how 4 different preference measures change in women post-hip fracture and evaluated the responsiveness of the preference measures . We also compared HRQOL in women with recent hip fractures to a control sample at baseline and to normative Canadian data at followup . METHODS Health status measures [ the Medical Outcomes Study Short Form-36 ( SF-36 ) ] and preferences ( direct and indirect ) of women over age 50 years with hip fractures were measured at baseline and at 3 and 9 months . Baseline preferences [ Health Utilities Index ( HUI ) , Feeling Thermometer , St and ard Gamble , and SF-36 ] were obtained from women without hip fractures for comparison . Independent sample t tests were used to compare baseline scores of fracture and nonfracture controls . Correlations between preference and health status measures were assessed and repeated measures ANOVA was used to assess change in health status and preferences over time . RESULTS Health status and preference measures were lower in women with hip fractures in comparison to nonfracture controls . After 9 months , the SF-36 , HUI , Feeling Thermometer , and SF-6D scores improved significantly . Values for the SF-36 remained lower than an age-matched normative sample . The HUI and SF-6D were sensitive to change over time , but the St and ard Gamble was not . CONCLUSION HRQOL and preference measures improve over time in women with recent hip fractures , with the majority of the change occurring in the initial 3 months . Our results suggest that the HUI and SF-6D are valid measures to assess change over time post-hip fracture BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients . This has been shown to be effective even in normally nourished or mildly undernourished geriatric patients . Whether perioperative administration of these products is also effective and suitable is not known . METHODS R and omized , controlled , open , paralleled two-arms clinical trial , comparing energy-protein supplements ( 40 g of protein and 400 kcal per day ) , with no intervention in normally nourished or mildly undernourished patients . Outcomes were serum proteins , body mass index , postoperative complications among others . RESULTS 60 Elderly patients were included . Patients in the intervention group ( n = 30 ) ingested 52.2 ± 12.1 % of the prescribed supplements per day for 5.8 ± 1.8 days before surgery and until hospital discharge . There was a significant change in serum albumin at follow-up ( F = 22.536 , P < 0.001 ) , and between the two groups ( F = 5.763 , P = 0.002 ) , favouring the intervention . The same was observed for serum prealbumin ( F = 6.654 , P = 0.001 within subjects , F = 2.865 , P = 0.045 for interaction ) . Logistic regression showed that only supplemented proteins per day ( OR[95%CI ] = 0.925[0.869 - 0.985 ] ) were associated with less postoperative complications ( R(2 ) = 0.323 , χ(2 ) = 11.541 , P = 0.003 ) . CONCLUSION Perioperative supplements in geriatric patients with hip fracture su bmi tted to surgery showed better recovery of plasma proteins . Higher daily protein intakes were associated with less postoperative complications Several studies have reported the rate of post-operative mortality after the surgical treatment of a fracture of the hip , but few data are available regarding the delayed morbidity . In this prospect i ve study , we identified 568 patients who underwent surgery for a fracture of the hip and who were followed for one year . Multivariate analysis was carried out to identify possible predictors of mortality and morbidity . The 30-day , four-month and one-year rates of mortality were 4.3 % , 11.4 % , and 18.8 % , respectively . General complications and pre-operative comorbidities represented the basic predictors of mortality at any time interval ( p < 0.01 ) . In-hospital , four-month and one-year general complications occurred in 29.4 % , 18.6 % and 6.7 % of patients , respectively . After adjusting for confounding variables , comorbidities and poor cognitive status determined the likelihood of early and delayed general complications , respectively ( p < 0.001 ) . Operative delay was the main predictor of the length of hospital stay ( p < 0.001 ) and was directly related to in-hospital ( p = 0.017 ) and four-month complications ( p = 0.008 ) The authors prospect ively explored the consequences of hip fracture with regard to discharge placement , functional status , and mortality using the Survey on Assets and Health Dynamics Among the Oldest Old ( AHEAD ) . Data from baseline ( 1993 ) AHEAD interviews and biennial follow-up interviews were linked to Medicare cl aims data from 1993 - 2005 . There were 495 postbaseline hip fractures among 5,511 respondents aged > or=69 years . Mean age at hip fracture was 85 years ; 73 % of fracture patients were white women , 45 % had pertrochanteric fractures , and 55 % underwent surgical pinning . Most patients ( 58 % ) were discharged to a nursing facility , with 14 % being discharged to their homes . In-hospital , 6-month , and 1-year mortality were 2.7 % , 19 % , and 26 % , respectively . Declines in functional-status-scale scores ranged from 29 % on the fine motor skills scale to 56 % on the mobility index . Mean scale score declines were 1.9 for activities of daily living , 1.7 for instrumental activities of daily living , and 2.2 for depressive symptoms ; scores on mobility , large muscle , gross motor , and cognitive status scales worsened by 2.3 , 1.6 , 2.2 , and 2.5 points , respectively . Hip fracture characteristics , socioeconomic status , and year of fracture were significantly associated with discharge placement . Sex , age , dementia , and frailty were significantly associated with mortality . This is one of the few studies to prospect ively capture these declines in functional status after hip fracture BACKGROUND & AIMS In patients with recent hip fracture , reduced serum IGF-I in relation to protein undernutrition is frequent . Elevation of circulating IGF-I in response to a daily oral supplement of 20 g of casein was observed after 6 months . This study determined if the response to casein as compared to whey protein can be observed as early as after one week . METHODS 45 women were r and omized after recent hip fracture in 3 groups receiving a preparation of 20 g of casein , an isocaloric supplement of 20 g of whey protein or an isocaloric supplement of 15 g of whey protein combined with 5 g of essential amino acids ( a.a . ) . RESULTS A similar significant elevation of serum IGF-I was already observed after 7 days for casein ( + 37.3 microg/L ) , whey ( + 29.4 ) and for whey+a.a . ( + 34.3 ) . From day 7 - 28 , no further significant rise in IGF-I was recorded . CONCLUSION After one week of protein supplementation , the percent increase of IGF-I was of similar magnitude to that previously observed after 6 months of protein supplementation . It suggests that in hip fracture patients , long-term effects of various protein preparations on IGF-I could be predicted from changes observed as early as 7 days after the onset of supplementation In a prospect i ve , r and omized , controlled study an intravenous vitamin B complex and vitamin C preparation was administered pre- and post-operatively to 28 elderly patients with a fractured proximal femur and compared with 32 nonsupplemented postoperative controls . Vitamin supplementation significantly , though only transiently , improved postoperative thiamine status ( P less than 0.001 ) , but had no influence on mental state or outcome during the postsurgical period . Therefore , the use of parenteral vitamins for postoperative confusion can not be justified on a routine basis Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs ) Fracture of the proximal femur is the most dramatic clinical sequela of osteoporosis [ 1 , 2 ] . It is associated with a high mortality rate , need for long-term medical care , and prolonged disability [ 3 - 5 ] . Protein malnutrition is often seen in elderly persons and is more severe in patients with hip fracture [ 6 - 11 ] . Protein deficiency may contribute to the occurrence of hip fracture by reducing muscle strength , impairing movement coordination , and diminishing the protective layer of soft tissue padding [ 9 , 10 , 12 - 14 ] It may also be associated with lower bone mineral density at the proximal femur [ 15 ] . Furthermore , malnutrition in general and protein deficiency in particular at admission and during recovery may adversely influence clinical outcome after hip fracture [ 7 , 9 , 10 , 16 - 18 ] . Protein restriction has been shown to reduce plasma levels of insulin-like growth factor-I ( IGF-I ) by inducing resistance to the action of growth hormone in the liver and increasing the metabolic clearance rate of the growth factor [ 19 - 23 ] . Furthermore , evidence shows that protein depletion may blunt the effect of IGF-I on target organs [ 20 ] . Thus , low protein intake in elderly persons may be detrimental to skeletal integrity , muscle strength , and immune response [ 11 , 24 - 27 ] because of decreased production and action of IGF-I , which favorably influences these systems [ 28 - 33 ] . Previous studies [ 16 , 17 ] have shown that a 5-week course of protein supplements can reduce the medical complication rate and duration of hospital stay in patients with recent hip fracture . These findings were independent of energy , calcium , and vitamin D intake [ 17 ] . Whether these observations were related to the restoration of decreased IGF-I levels and whether bone may benefit from long-term protein supplementation are not known . We investigated whether protein supplements in vitamin D-replete patients with a recent hip fracture who were receiving calcium supplements could increase circulating IGF-I levels and favorably influence bone mineral density . Methods Patients Patients were recruited in the orthopedic ward of Geneva University Hospital , the referral center that receives 94.6 % of all patients with hip fracture from an area with a population of approximately 400 000 persons [ 5 ] . The protocol was approved by the ethical committee of the Geneva University Hospital Department of Surgery . Inclusion criteria were age greater than 60 years ; recent hip fracture ( within 2 weeks ) attributable to osteoporosis ( that is , a fracture after a minor trauma , such as a fall from st and ing height ) ; and the ability to give written , informed consent . Exclusion criteria were pathologic fracture ; fracture caused by severe trauma ; history of contralateral hip fracture ; severe mental impairment ; active metabolic bone disease ; renal failure ( plasma creatinine concentration 200 mol/L ) ; acute illness that could interfere with the study protocol ; severe malnutrition ( serum albumin level < 15 g/L ) ; consumption of drugs known to alter bone metabolism , such as calcitonin , fluoride , sex hormones , corticosteroids , or bisphosphonates ; and life expectancy of less than 1 year . Using a r and om number table , we assigned patients to receive an oral protein supplement composed of 90 % milk proteins or a placebo made isocaloric by the addition of maltodextrins . Patients took the assigned intervention 5 days a week for 6 months in addition to their regular diet . All patients received one oral dose of vitamin D3 , 200 000 IU ( vitamine D3B.O.N. , Doms-Adrian , Courbevoie , France ) , to correct any possible vitamin D deficiency [ 34 ] . The daily protein supplement ( Meritene , S and oz Nutrition Ltd. , Berne , Switzerl and ) provided 1050 kJ ( 250 kcal ) of energy in the form of 20 g of proteins , 3.1 g of lipids , and 35.7 g of carbohydrates ( 54.4 g in placebo ) . The other constituents of the 65 g powder supplement were vitamin A ( 1000 IU ) , vitamin K1 ( 30 g ) , vitamin C ( 20 mg ) , calcium ( 550 mg ) , magnesium ( 91 mg ) , phosphorus ( 429 mg ) , and sodium ( 228 mg ) . The supplement is design ed to normalize but not overcompensate for the insufficient dietary intake of protein of elderly persons with a recent fracture of the proximal femur [ 16 ] . Compliance was verified by weekly phone calls and by counting the remaining nutritional supplement bags , which were forwarded monthly by mail . Clinical Data Medical history , clinical characteristics , anthropometric data , and performance status according to an Activities of Daily Living score [ 35 ] were evaluated . Dietary intakes were recorded by using a food-frequency question naire [ 36 ] about the week before the fracture . Food intakes were analyzed by using a nutrient software system ( Fruitdor , Astra-Calve , Paris , France ) . Dietary intake of calcium , phosphorus , and protein was calculated from intake of dairy products , meat , fish , and vegetables . Because many patients were unable to st and a few days after hip fracture , their height was determined with a fathom measure while they were recumbent . Body weight was determined with a scale that correlated highly with that provided by measurement of whole body bone , fat , and lean mass as assessed by dual x-ray absorptiometry [ 37 ] . Mid-arm circumference was measured with a tape measure ( coefficient of variation , 2 % ) . Isometric muscle strength of the biceps of the dominant arm was evaluated with a dynamometer ( Lido , Lidoactive Isokinetic System , Loredan Biomedical Inc. , West Sacramento , California ) , which measures the peak torque ( coefficient of variation < 5 % ) . The grip strength of the same arm was measured with a dynamometer ( Vigorimeter , Martin Medizin-Technik , Tuttlingen , Germany ) [ 38 ] . The mean of three measurements was used for calculation . Biochemical Data Within 120 hours after surgery , we used st and ard methods to analyze venous blood sample s for protein-corrected plasma levels of calcium , phosphate , creatinine , total proteins , albumin , and prealbumin . We also measured levels of IGF-I ( Nichols Institute , San Juan Capistrano , California ) after acid-ethanol extraction and cryoprecipitation [ 39 ] , intact parathyroid hormone ( Immulite , Diagnostic Products , Los Angeles , California ) , calcitriol , calcidiol ( Incstar , Stillwater , Minnesota ) , and osteocalcin ( CIS-BIO International , Gif-sur-Yvette , France ) . Biochemical measurements were repeated 6 and 12 months after the fracture . Serum IGF-I binding proteins were measured by Western lig and blot analysis [ 40 ] . Briefly , 3 L of serum was boiled and separated onto 15 % sodium dodecylsulfate polyacrilamide gel electrophoresis under nonreducing conditions . Proteins were electrically blotted onto a nitrocellulose membrane , and IGF-I binding proteins were detected after incubating the membranes with radioiodinated IGF-I at 4C for 24 hours . Insulin-like growth factor binding proteins were quantified by phosphorimaging ( Molecular Dynamics , Sunnyvale , California ) . The intensity of the b and s corresponding to the appropriate molecular weights [ 40 ] was expressed as the percentage of total bound radioactive IGF-I. Measurements of calcium , phosphate , and creatinine were obtained from the second fasting morning urine . The ratio of hydroxyproline to creatinine in the same sample was taken as a reflection of bone resorption . Markers of bone resorption ( pyridinoline and deoxypyridinoline ) in the first morning spot urine were measured by detecting fluorescence emission after acid hydrolysis and separation with isocratic reverse-phase high-performance liquid chromatography ( BioRad System , Munich , Germany ) , and the values were adjusted to the creatinine concentration . Immunologic Data Concentrations of IgA , IgG , IgM , and isohemagglutinins were measured by using st and ard methods . Cell-mediated immunity was assessed by using a skin-test antigens for cellular hypersensitivity system ( STACH , Institut Merieux , Lyon , France ) , which evaluates the size of the skin reaction to various antigens injected intradermally [ 41 ] . Bone Mass Assessment We measured areal bone mineral density at the lumbar spine ( anteroposterior and lateral views ) , the contralateral proximal femur ( femoral neck and trochanter ) , and the contralateral mid-femoral shaft . We also measured whole-body bone mineral content , fat , and lean mass by using dual x-ray absorptiometry ( Hologic QDR-2000 , Waltham , Massachusetts ) . The coefficients of variation of these measurements are reported elsewhere [ 37 , 42 ] . Vertebral Deformity Two series of lateral radiography of the thoracic and lumbar spine were taken at the start of the study and at 12 months . The films were examined by a single investigator ( who was unaware of treatment group assignment ) according to a 6-point analysis procedure for each vertebral body from T4 to L4 [ 43 , 44 ] ( intra-observer coefficient of variation , 1.8 % to 3.1 % ) . At baseline , fracture was defined by a decrease of 20 % in the ratio of anterior or middle height to posterior height . Patients were considered to have a new vertebral deformity if the anterior , middle , or posterior height decreased by more than 20 % between the two examinations . Statistical Analysis All values are given as the mean SD for baseline measurement and the mean SE for comparisons of outcome results . All analyses were performed by using the SAS procedure ( Cary , North Carolina ) . One-way analysis of variance was used . A two-tailed P value less than 0.05 was considered significant . Role of the Funding Sources This study was supported by grants from S and oz Nutrition Ltd. , Berne , Switzerl and , and the Swiss National Research Science Foundation . The skin-test antigens for cellular hypersensitivity system was supplied by Rhone-Poulenc , Thalwil , Switzerl and . No organization influenced the design , conduct , or reporting of the study . Results Of 842 patients evaluated from April 1992 to February 1994 , 82 were recruited into the r and omized , double-blind , placebo-controlled trial . This low enrollment rate was due to patients ' poor medical or cognitive conditions and reluctance to give informed consent . R and omised controlled trials , when appropriately design ed , conducted , and reported , represent the gold st and ard in evaluating healthcare interventions . However , r and omised trials can yield biased results if they lack method ological rigour [ 1 ] . To assess a trial accurately , readers of a published report need complete , clear , and transparent information on its methodology and findings . Unfortunately , attempted assessment s frequently fail because authors of many trial reports neglect to provide lucid and complete descriptions of that critical information [ 2,3,4 ] . That lack of adequate reporting fuelled the development of the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement in 1996 [ 5 ] and its revision five years later [ 6,7,8 ] . While those statements improved the reporting quality for some r and omised controlled trials [ 9,10 ] , many trial reports still remain inadequate [ 2 ] . Furthermore , new method ological evidence and additional experience has accumulated since the last revision in 2001 . Consequently , we organised a CONSORT Group meeting to up date the 2001 statement [ 6,7,8 ] . We introduce here the result of that process , CONSORT 2010 . BACKGROUND & AIMS The aim of this study of women with hip fracture was to describe nutritional status with biochemical markers and anthropometric variables , and to evaluate the effect of nutritional intervention with the intention of increasing protein and energy intake . METHODS The first consecutive 44 women were included , and used as controls . The next 44 were matched for age , fracture and mental state . Anthropometric variables , IGF-I , hormones and serum albumin were collected 4 - -6 days ( baseline ) , 1 and 3 months after surgery . Twenty-four women filled out a 7-day food record . RESULTS At baseline , one fourth had BMI < 20 kg/m(2 ) and subnormal triceps skinfold thickness . Baseline serum albumin , IGF-I and growth hormone levels were low , probably as an acute response to trauma . Women with BMI < 20 kg/m(2)had lower IGF-I levels compared to those with higher BMI . At 3 months , one-third of both groups were protein and energy malnourished . The intervention group obtained higher daily energy percentage from fat but none of the groups reached their calculated energy need . CONCLUSIONS Using biochemical markers in the acute postoperative situation to assess nutritional status is not recommended . The intervention had no impact on anthropometric or biochemical variables BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients to reduce postoperative complications . However , tolerability of supplements could be a limitation , and their universal use is not supported by the heterogeneity of previous studies , especially in patients without malnutrition . METHODS This study is a r and omized , controlled , open , parallel , 3-arm clinical trial comparing supplementation with protein powder dissolved in liquids to aim at 36 g of protein per day , energy and protein supplements to aim at 37.6 g of protein and 500 kcal per day , or no intervention in normally nourished or mildly undernourished patients . Outcomes were serum albumin , prealbumin , retinol-binding globulin , and body mass index , among others . Postoperative complications were also recorded . RESULTS Ninety patients aged 83.8 + /- 6.6 years were included . The mean ingested amount of supplements was 41.1 % + /- 20.6 % in the protein powder supplement group and 51.4 % + /- 13.2 % in the energy protein supplement group ( t = 2.278 , P = .027 ) . Postoperative supplements had no effect on the nutrition status during in-hospital follow-up , as assessed by serum albumin ( P = .251 ) , prealbumin ( P = .530 ) , retinol-binding globulin ( P = .552 ) , or body mass index ( P = .582 ) . Multivariate analysis showed that length of hospital stay with an established complication until its resolution ( beta = .230 , P = .031 ) , total hospital stay ( beta = .450 , P < .001 ) , baseline body mass index ( beta = .204 , P = .045 ) , and total daily ingested proteins per body weight ( beta = .252 , P = .018 ) were predictive variables on the change in serum albumin ( R2 = 0.409 , F = 11.246 , P < .001 ) . CONCLUSIONS Oral nutritional supplements in normally nourished or only mildly undernourished geriatric patients with hip fracture su bmi tted to surgery may be of interest for patients with postoperative complications and long hospital stays BACKGROUND & AIMS Optimizing nutritional intake has been recommended for geriatric patients undergoing hip-fracture surgery . Whether nutritional support guided by repeated measurements of resting energy requirements ( REE ) improves outcomes in these patients is not known . METHODS A r and omized , controlled , unblinded , prospect i ve , cohort study comparing provision of energy with a goal determined by repeated REE measurements using indirect calorimetry , with no intervention . Oral nutritional supplements were started 24 h after surgery and the amount adjusted to make up the difference between energy received from hospital food and measured energy expenditure . RESULTS 50 Geriatric patients were included in the study . Patients in the intervention group ( n = 22 ) received significantly higher daily energy intake than the control group ( n = 28 ) ( 1121.3 ± 299.0 vs. 777.1 ± 301.2 kcal , p = 0.001 ) . This was associated with a significantly less negative cumulative energy balance ( -1229.9 ± 1763 vs. -4975.5 ± 4368 kcal , p = 0.001 ) . A significant negative correlation was found between the cumulative energy balance and total complication rate ( r = -0.417 , p = 0.003 ) as well as for length of hospital stay ( r = -0.282 , p = 0.049 ) . CONCLUSION We have demonstrated that nutritional support actively supervised by a dietician and guided by repeated measurements of REE was achievable and improved outcomes in geriatric patients following surgery for hip fractures . Clinical trials.gov Identifier : NCT017354435 |
12,598 | 28,770,973 | The trials were carried out in countries across the world , and in both high- and low-re source setting s. In low-re source setting s women receiving usual care may have received no additional postnatal care after early hospital discharge .
There was no evidence that home visits were associated with improvements in maternal and neonatal mortality , and no consistent evidence that more postnatal visits at home were associated with improvements in maternal health .
There was some evidence that postnatal care at home may reduce infant health service utilisation in the weeks following the birth , and that more home visits may encourage more women to exclusively breastfeed their babies .
There was some evidence that home visits are associated with increased maternal satisfaction with postnatal care .
Increasing the number of postnatal home visits may promote infant health and maternal satisfaction and more individualised care may improve outcomes for women , although overall findings in different studies were not consistent . | BACKGROUND Maternal complications including psychological and mental health problems and neonatal morbidity have been commonly observed in the postpartum period .
Home visits by health professionals or lay supporters in the weeks following the birth may prevent health problems from becoming chronic with long-term effects on women , their babies , and their families .
OBJECTIVES To assess outcomes for women and babies of different home-visiting schedules during the early postpartum period .
The review focuses on the frequency of home visits , the duration ( when visits ended ) and intensity , and on different types of home-visiting interventions . | Abstract Objectives : To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives . Design : R and omised controlled trial with six month follow up . Setting : Recruitment in a university teaching hospital and care provided in women 's homes . Participants : 623 postnatal women allocated at r and om to intervention ( 311 ) or control ( 312 ) group . Intervention : Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker . Main outcome measure : General health status as measured by the SF-36 and risk of postnatal depression . Breast feeding rates , satisfaction with care , use of services , and personal costs . Results : At six weeks there was no significant improvement in health status among the women in the intervention group . At six weeks the mean total NHS costs were £ 635 for the intervention group and £ 456 for the control group ( P=0.001 ) . At six months figures were £ 815 and £ 639 ( P=0.001 ) . There were no differences between the groups in use of social services or personal costs . The women in the intervention group were very satisfied with the support worker visits . Conclusions : There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36 . There were no savings to the NHS over six months after the introduction of the community postnatal support worker service CONTEXT Home-visitation services have been promoted as a means of improving maternal and child health and functioning . However , long-term effects have not been examined . OBJECTIVE To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on women 's life course and child abuse and neglect . DESIGN R and omized trial . SETTING Semirural community in New York . PARTICIPANTS Of 400 consecutive pregnant women with no previous live births enrolled , 324 participated in a follow-up study when their children were 15 years old . INTERVENTION Families received a mean of 9 home visits during pregnancy and 23 home visits from the child 's birth through the second birthday . DATA SOURCES AND MEASURES : Women 's use of welfare and number of subsequent children were based on self-report ; their arrests and convictions were based on self-report and archived data from New York State . Verified reports of child abuse and neglect were abstract ed from state records . MAIN RESULTS During the 15-year period after the birth of their first child , in contrast to women in the comparison group , women who were visited by nurses during pregnancy and infancy were identified as perpetrators of child abuse and neglect in 0.29 vs 0.54 verified reports ( P<.001 ) . Among women who were unmarried and from households of low socioeconomic status at initial enrollment , in contrast to those in the comparison group , nurse-visited women had 1.3 vs 1.6 subsequent births ( P=.02 ) , 65 vs 37 months between the birth of the first and a second child ( P=.001 ) , 60 vs 90 months ' receiving Aid to Families With Dependent Children ( P=.005 ) , 0.41 vs 0.73 behavioral impairments due to use of alcohol and other drugs ( P=.03 ) , 0.18 vs 0.58 arrests by self-report ( P<.001 ) , and 0.16 vs 0.90 arrests disclosed by New York State records ( P<.001 ) . CONCLUSIONS This program of prenatal and early childhood home visitation by nurses can reduce the number of subsequent pregnancies , the use of welfare , child abuse and neglect , and criminal behavior on the part of low-income , unmarried mothers for up to 15 years after the birth of the first child STUDY OBJECTIVES : The main aim of the study was to discover if a midwife home visiting programme has a significant effect on the prevalence of health problems and breast feeding behaviour of mothers who delivered normally and their healthy fullterm newborn babies , during a period of 42 days after delivery . Another aim was to compare the mothers ' , the midwife 's , and the doctor 's findings of prevalence of health problems at the end of the puerperium period . DESIGN : A r and omised controlled trial was carried out . One group of mothers and their infants were r and omly allocated to a home visiting group ( Group A ) ; the other group ( Group B ) was only visited at day 42 . SETTING : The study was carried out at the University Teaching Hospital ( UTH ) in Lusaka , the capital city of Zambia . PARTICIPANTS : A total of 408 mothers who had a normal delivery and gave birth to a healthy fullterm infant , as assessed by the attending midwife , were r and omised to two groups . Group A consisted of 208 mother/infant dyads who were visited by a midwife in their homes at days 3 , 7 , 28 , and 42 after delivery and Group B consisted of 200 mother/infant dyads who were only visited at day 42 . MAIN RESULTS : At day 42 an equal proportion ( 30 % ) of mothers in both groups perceived that they had health problems . The prevalence of infant health problems in Group B was significantly higher ( p < 0.01 ) as perceived by mothers . There were more mothers in Group B ( p < 0.01 ) perceiving insufficient milk production and giving supplementary feeding . At day 42 , mothers in Group A ( 56 % ) took more actions than mothers in Group B ( 41 % ) to solve infant health problems ( p < 0.03 ) . In both groups the mothers ' perceived own health problems , were significantly higher ( p < 0.01 ) than those observed by the obstetrician and those observed by the midwife . The midwife found more infant health problems in Group B ( p < 0.01 ) than in Group A and more infants with health problems in both groups compared with the paediatrician 's findings ( p < 0.01 ) . CONCLUSIONS : There was a significant difference between the mothers ' reported health problems and the health problems identified by the midwife and the doctors . The study shows that a midwife home visit and individual health education to mothers , reduce the prevalence of infant health problems , and enables the mother to more often take action when an infant health problem is identified . There is a need to re-evaluate the midwifery training curriculums with the intention to include more infant management care OBJECTIVES This study examined differences between nurses and paraprofessionals in implementation of a home visiting program for low-income , first-time parents during pregnancy and the first 2 years of the child 's life . METHODS Mothers were r and omly assigned to either a nurse-visited ( n = 236 ) or a paraprofessional-visited ( n = 244 ) condition . Nurse- and paraprofessional-visited families were compared on number and length of visits , topics covered , number of program dropouts , and relationship with home visitor . RESULTS On average , nurses completed more visits than paraprofessionals ( 28 vs 23 ; P < .001 ) and spent a greater proportion of time on physical health issues during pregnancy ( 38 % vs 27 % ; P < .001 ) and on parenting issues during infancy ( 46 % vs 32 % ; P < .001 ) . Paraprofessionals conducted visits that lasted longer and spent a greater proportion of time on environmental health and safety issues ( 15 % vs 7 % pregnancy ; 15 % vs 8 % infancy ; P < .001 ) . While home visitors were viewed equally positively by mothers , nurses had fewer dropouts than did paraprofessionals ( 38 % vs 48 % ; P = .04 ) . More paraprofessional-visited families than nurse-visited families experienced staff turnover . CONCLUSIONS Nurses and paraprofessionals , even when using the same model , provide home visiting services in different ways Background In the year after birth one in six women has a depressive illness , and 30 % are still depressed , or depressed again , when their child is 2 years old , 94 % experience at least one major health problem ( e.g. back pain , perineal pain , mastitis , urinary or faecal incontinence ) , 26 % experience sexual problems and almost 20 % have relationship problems with partners . Women with depression report less practical and emotional support from partners , less social support overall , more negative life events , and poorer physical health . Their perceptions of factors contributing to depression are lack of support , isolation , exhaustion and physical health problems . Fewer than one in three affected women seek help in primary care despite frequent contacts . Methods / Design PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners ' response to these issues , and through community-based strategies to develop broader family and community supports for recent mothers . Eligible local governments will be recruited and r and omised to intervention or comparison arms , after stratification ( urban/rural , size , birth numbers , extent of community activity ) , avoiding contiguous boundaries . Maternal depression and physical health will be measured six months after birth , in a one year cohort of mothers , in intervention and comparison communities . The sample size to detect a 20 % relative reduction in depression , adjusting for cluster sampling , and estimating a population response fraction of 67 % is 5740 × 2 . Analysis of the physical and mental health outcomes , by intention to treat , will adjust for the correlated structure of the data OBJECTIVE To examine the effectiveness of home visiting by paraprofessionals and by nurses as separate means of improving maternal and child health when both types of visitors are trained in a program model that has demonstrated effectiveness when delivered by nurses . METHODS A r and omized , controlled trial was conducted in public- and private-care setting s in Denver , Colorado . One thous and one hundred seventy-eight consecutive pregnant women with no previous live births who were eligible for Medicaid or who had no private health insurance were invited to participate . Seven hundred thirty-five women were r and omized to control , paraprofessional , or nurse conditions . Nurses completed an average of 6.5 home visits during pregnancy and 21 visits from birth to the children 's second birthdays . Paraprofessionals completed an average of 6.3 home visits during pregnancy and 16 visits from birth to the children 's second birthdays . The main outcomes consisted of changes in women 's urine cotinine over the course of pregnancy ; women 's use of ancillary services during pregnancy ; subsequent pregnancies and births , educational achievement , workforce participation , and use of welfare ; mother-infant responsive interaction ; families ' home environments ; infants ' emotional vulnerability in response to fear stimuli and low emotional vitality in response to joy and anger stimuli ; and children 's language and mental development , temperament , and behavioral problems . RESULTS Paraprofessional-visited mother-child pairs in which the mother had low psychological re sources interacted with one another more responsively than their control-group counterparts ( 99.45 vs 97.54 st and ard score points ) . There were no other statistically significant paraprofessional effects . In contrast to their control-group counterparts , nurse-visited smokers had greater reductions in cotinine levels from intake to the end of pregnancy ( 259.0 vs 12.32 ng/mL ) ; by the study child 's second birthday , women visited by nurses had fewer subsequent pregnancies ( 29 % vs 41 % ) and births ( 12 % vs 19 % ) ; they delayed subsequent pregnancies for longer intervals ; and during the second year after the birth of their first child , they worked more than women in the control group ( 6.83 vs 5.65 months ) . Nurse-visited mother-child pairs interacted with one another more responsively than those in the control group ( 100.31 vs 98.99 st and ard score points ) . At 6 months of age , nurse-visited infants , in contrast to their control-group counterparts , were less likely to exhibit emotional vulnerability in response to fear stimuli ( 16 % vs 25 % ) and nurse-visited infants born to women with low psychological re sources were less likely to exhibit low emotional vitality in response to joy and anger stimuli ( 24 % vs 40 % and 13 % vs 33 % ) . At 21 months , nurse-visited children born to women with low psychological re sources were less likely to exhibit language delays ( 7 % vs 18 % ) ; and at 24 months , they exhibited superior mental development ( 90.18 vs 86.20 Mental Development Index scores ) than their control-group counterparts . There were no statistically significant program effects for the nurses on women 's use of ancillary prenatal services , educational achievement , use of welfare , or their children 's temperament or behavior problems . For most outcomes on which either visitor produced significant effects , the paraprofessionals typically had effects that were about half the size of those produced by nurses . CONCLUSIONS When trained in a model program of prenatal and infancy home visiting , paraprofessionals produced small effects that rarely achieved statistical or clinical significance ; the absence of statistical significance for some outcomes is probably attributable to limited statistical power to detect small effects . Nurses produced significant effects on a wide range of maternal and child outcomes OBJECTIVE To compare office-based care ( OBC ) with a care model using a home nursing visit ( HNV ) as the initial postdischarge encounter for " well " breastfeeding newborns and mothers . DESIGN R and omized controlled trial . SETTING A single academic hospital . PARTICIPANTS A total of 1154 postpartum mothers intending to breastfeed and their 1169 newborns of at least 34 weeks ' gestation . INTERVENTIONS Home nursing visits were scheduled no later than 2 days after discharge ; OBC timing was physician determined . OUTCOME MEASURES Mothers completed telephone surveys at 2 weeks , 2 months , and 6 months . The primary outcome was unplanned health care utilization for mothers and newborns within 2 weeks of delivery . Other newborn outcomes were proportion seen within 2 days after discharge and breastfeeding duration . Maternal mental health , parenting competence , and satisfaction with care outcomes were assessed . Analyses followed an intent-to-treat paradigm . RESULTS At 2 weeks , hospital readmissions and emergency department visits were uncommon , and there were no study group differences in these outcomes or with unplanned outpatient visit frequency . Newborns in the HNV group were seen no more than 2 days after discharge more commonly than those in the OBC group ( 85.9 % vs 78.8 % ) ( P = .002 ) and were more likely to be breastfeeding at 2 weeks ( 92.3 % vs 88.6 % ) ( P = .04 ) and 2 months ( 72.1 % vs 66.4 % ) ( P = .05 ) but not 6 months . No group differences were detected for maternal mental health or satisfaction with care , but HNV group mothers had a greater parenting sense of competence ( P < .01 at 2 weeks and 2 months ) . CONCLUSIONS Home nursing visits are a safe and effective alternative to OBC for the initial outpatient encounter after maternity/nursery discharge with similar patterns of unplanned health care utilization and modest breastfeeding and parenting benefits OBJECTIVES To determine whether the outcomes of routine home visiting by public health nurses ( PHN ) after early obstetrical discharge differ from those of a screening telephone call design ed to identify mothers who need further intervention . METHODS Primiparas delivering a singleton infant and eligible for postpartum follow-up were r and omized to a home visit or screening telephone call . Data were collected by telephone from 733 participants located at two tertiary care centres in Ontario . Outcomes included maternal confidence at two weeks , health problems of the infants between discharge and four weeks postpartum , breastfeeding rates at six months and costs of the two models . RESULTS Differences between the sample s at the two sites necessitated stratified analyses . No differences were detected between the groups in maternal confidence ( p = 0.96 ) , health problems of infants ( p = 0.87 ) , or rates of breastfeeding at six months ( p = 0.22 ) . However , at both sites the cost of routine home visits was found to be higher than that of screening by telephone . CONCLUSION Although universal access to postpartum support is important , the results suggest that a routine home visit is not always necessary to identify the women who need it . These results can be generalized only to low-risk women and infants Background In the year after birth one in six women has a depressive illness , 94 % experience at least one major health problem ( e.g. back pain , perineal pain , mastitis , urinary or faecal incontinence ) , 26 % experience sexual problems and almost 20 % have relationship problems with partners . Women with depression report less practical and emotional support from partners , less social support , more negative life events , and poorer physical health and see factors contributing to depression as lack of support , isolation , exhaustion and physical health problems . Fewer than one in three seek help in primary care despite frequent health care contacts . Methods Primary care and community-based strategies embedded in existing services were implemented in a cluster-r and omised trial involving 16 rural and metropolitan communities , pair-matched , within the State of Victoria , Australia . Intervention areas were also provided with a community development officer for two years . The primary aim was to reduce the relative risk of depression by 20 % in mothers six months after birth and to improve their physical health . Primary outcomes were obtained by postal question naires . The analysis was by intention-to-treat , unmatched , adjusting for the correlated nature of the data . Results 6,248 of 10,144 women ( 61.6 % ) in the intervention arm and 5057/ 8,411 ( 60.1 % ) in the comparison arm responded at six months , and there was no imbalance in major covariates between the two arms . Women 's mental health scores were not significantly different in the intervention arm and the comparison arm ( MCS mean score 45.98 and 46.30 , mean EPDS score 6.91 and 6.82 , EPDS ≥ 13 ( ' probable depression ' ) 15.7 % vs. 14.9 % , Odds ratioadj 1.06 ( 95%CI 0.91–1.24 ) . Women 's physical health scores were not significantly different in intervention and comparison arms ( PCS mean scores 52.86 and 52.88 ) . Conclusion The combined community and primary care interventions were not effective in reducing depression , or in improving the physical health of mothers six months after birth BACKGROUND Stresses imposed by parenthood can provoke or intensify relationship problems between parents . These problems , which are often associated with postnatal depression , can have serious consequences for family well-being but are often not revealed to primary health care personnel . AIM To evaluate a means of extending the primary health care team 's ability to identify and respond to relationship problems of mothers and their partners in the postnatal period . DESIGN OF STUDY Cluster r and omised controlled trial . SETTING Specially trained health visitors in nine ' intervention ' clinics -- each matched with a ' control ' clinic ' in an outer London borough . METHOD Health visitors in intervention clinics invited mothers attending for the six-to-eight-week developmental check to complete a screening scale for relationship problems , and offered help ( supportive listening , advice , or referral ) if needed . When visiting the clinic for the 12-week immunizations , mothers from all clinics were asked to complete a follow-up self-report question naire . After the completion of the trial , 25 women who had attended the intervention clinics and had been offered support with a relationship problem were interviewed to elicit their views on the acceptability and value of the intervention . All 25 of the health visitors engaged in the intervention were asked to complete a question naire on their experience . RESULTS Screening led to striking differences between intervention and control clinics in the percentage of women identified at the six-to-eight-week check as potentially in need of help with a relationship problem ( 21 % versus 5 % , P = 0.007 ) and in the percentage actually offered help ( 18 % versus 3 % , P = 0.014 ) . About one-half of the mothers so identified were also identified as having postnatal depression . At the 12-week visit for immunizations , the intervention group was twice as likely ( P = 0.006 ) as the control group to report having discussed relationship problems with the health visitor and 75 % more likely ( P = 0.046 ) to report having received help with a problem . CONCLUSION The intervention offers a useful way of extending the primary health care team 's ability to respond to problems that often have serious consequences for family well-being Objectives : To evaluate the effectiveness and cost effectiveness of an intensive home visiting programme in improving outcomes for vulnerable families . Design : Multicentre r and omised controlled trial in which eligible women were allocated to receive home visiting ( n = 67 ) or st and ard services ( n = 64 ) . Incremental cost analysis . Setting : 40 general practitioner practice s across 2 counties in the UK . Participants : 131 vulnerable pregnant women . Intervention : Selected health visitors were trained in the Family Partnership Model to provide a weekly home visiting service from 6 months antenatally to 12 months postnatally . Main outcome measures : Mother – child interaction , maternal psychological health attitudes and behaviour , infant functioning and development , and risk of neglect or abuse . Results : At 12 months , differences favouring the home-visited group were observed on an independent assessment of maternal sensitivity ( p<0.04 ) and infant cooperativeness ( p<0.02 ) . No differences were identified on any other measures . A non-significant increase in the likelihood of intervention group infants being the subject of child protection proceedings , or being removed from the home , and one death in the control group were found . The mean incremental cost per infant of the home visiting intervention was £ 3246 ( bootstrapped 95 % CI for the difference £ 1645–4803 ) . Conclusion : This intervention may have the potential to improve parenting and increase the identification of infants at risk of abuse and neglect in vulnerable families . Further investigation is needed , along with long-term follow-up to assess possible sleeper effects BACKGROUND Postpartum home visiting by nurses can benefit higher-risk families . Yet , little is known about the effects of universal services which provide care for all families including those at lowest risk ( e.g. , provision by health visitors-United Kingdom specialist community public health nurses ) . OBJECTIVE It was to determine the effect of frequency of health visitors ' home visits on ' low-risk ' first-time families ' outcomes to 8 weeks postpartum and 7 months follow-up . DESIGN A cluster r and omised controlled trial . SETTING Within one health and social care managerial area in Northern Irel and . PARTICIPANTS First-time ' low risk ' mothers who had given birth during 2002 - 2004 and were visited by a health visitor who had agreed to take part in the study , were invited to participate . In total , n=39 health visitors were allocated to ' intervention ' and n=41 to ' control ' . Of n=295 ' low-risk ' first-time mothers who agreed to take part , n=136 with intervention health visitors were offered six home visits 2 - 8 weeks postpartum and n=159 within the control group were offered one planned visit . METHODS Self-completed measures of parenting , maternal wellbeing and service use were gathered pre-intervention , 8 weeks and 7 months postpartum . The main outcome was the Edinburgh Postnatal Depression Scale ( EPDS ) . At 8 weeks and 7 months postpartum , n=129 and n=115 intervention mothers , also n=151 and n=141 control mothers completed outcome measures . RESULTS An intention to treat analysis was performed using multilevel modelling analysis which statistically controlled for pre-home visit outcomes , clinic attendance and antenatal contact . The intervention had no impact on most outcomes , however , it was associated with an increased EPDS score ( after adjustment : 0.16 , 2.36 95 % CI ) at 8 weeks ( before accounting for outliers ) but not at 7 months ( -0.62 , 1.65 95 % CI ) . Intervention mothers had higher service satisfaction ( 7.7 , 21.28 , 95 % CI 8 weeks ; 4.69 , 22.71 , 7 months ) and were less likely to have used emergency medical services for their infants to 8 weeks ( OR : 0.15 , 0.85 , 95 % CI ) . CONCLUSION Weekly postpartum visits to ' low-risk ' mothers had variable effects , therefore , practitioners and research ers should consider further development and application of effective , evidence based home visiting content OBJECTIVE Harmful effects of short postpartum hospital stays include dehydration and malnutrition of breastfed infants . These may be prevented by adequate breastfeeding frequency ; however , rigorous research to determine the relative effectiveness of various follow-up strategies in supporting breastfeeding frequency is absent . This study addressed the question , " Is there a difference in breastfeeding frequency or infant weight gain for singleton infants discharged within 36 hours ' postpartum who received either community nurse ( home visit ) or hospital nurse ( clinic ) follow-up ? " METHODS A r and omized , controlled trial was conducted at a university teaching hospital ( 3700 births/y ) and affiliated community health centers . A consecutive sample of 586 healthy mother-infant pairs were recruited from January 1997 to September 1998 before discharge ; 513 ( 87.5 % ) contributed data on 1 or more outcomes . Forty-eight-hour postpartum telephone contact and day 3 nurse contact in the home ( experimental ) or at the hospital ( control ) were provided . The main outcomes measured were breastfeeding frequency and infant weight gain assessed at 2 weeks ' postpartum by maternal diary and weight at home by research assistants , masked to group allocation . RESULTS No clinical ly important or statistically significant group differences were found in daily breastfeeding frequency ( mean difference experimental minus control = 0.1 feeds [ 95 % confidence interval : -0.1 - 0.3 ] ) or daily rate of infant weight gain ( -1.1 g [ -2.5 - 0.3 ] ) based on intention-to-treat analyses . CONCLUSIONS Follow-up by nurses after short postpartum hospital stays , in either the home or a hospital-based clinic , of healthy infants discharged at < 36 hours seems associated with satisfactory infant breastfeeding outcomes BACKGROUND Recently enacted federal legislation m and ates insurance coverage of at least 48 hours of postpartum hospitalization , but most mothers and newborns in the United States will continue to go home before the third postpartum day . National guidelines recommend a follow-up visit on the third or fourth postpartum day , but scant evidence exists about whether home or clinic visits are more effective . METHODS We enrolled 1163 medically and socially low-risk mother-newborn pairs with uncomplicated delivery and r and omly assigned them to receive home visits by nurses or pediatric clinic visits by nurse practitioners or physicians on the third or fourth postpartum day . In contrast with the 20-minute pediatric clinic visits , the home visits were longer ( median : 70 minutes ) , included preventive counseling about the home environment , and included a physical examination of the mother . Clinical utilization and costs were studied using computerized data bases . Breastfeeding continuation , maternal depressive symptoms , and maternal satisfaction were assessed by means of telephone interviews at 2 weeks ' postpartum . RESULTS Comparing the 580 pairs in the home visit group and the 583 pairs in the pediatric clinic visit group , no significant differences occurred in clinical outcomes as measured by maternal or newborn rehospitalization within 10 days postpartum , maternal or newborn urgent clinic visits within 10 days postpartum , or breastfeeding discontinuation or maternal depressive symptoms at the 2-week interview . The same was true for a combined clinical outcome measure indicating whether a mother-newborn pair had any of the above outcomes . In contrast , higher proportions of mothers in the home visit group rated as excellent or very good the preventive advice delivered ( 80 % vs 44 % ) , the provider 's skills and abilities ( 87 % vs 63 % ) , the newborn 's posthospital care ( 87 % vs 59 % ) , and their own posthospital care ( 75 % vs 47 % ) . On average , a home visit cost $ 255 and a pediatric clinic visit cost $ 120 . CONCLUSIONS For low-risk mothers and newborns in this integrated health maintenance organization , home visits compared with pediatric clinic visits on the third or fourth postpartum hospital day were more costly , but were associated with equivalent clinical outcomes and markedly higher maternal satisfaction . This study had limited power to identify group differences in rehospitalization , and may not be generalizable to higher-risk population s without comparable access to integrated hospital and outpatient care The current study examined whether the Nurse Family Partnership ( NFP ) , an intervention in which mothers received home visitation by registered nurses pre- and postnatally , reduced mothers ' vulnerability to the effects of stressful life events several years after the program was completed . Data from a r and omized trial of the NFP were examined for mothers ( N = 324 ) who were generally low-income , young , and unmarried at the time of the birth of their first child . Structured interviews were done with mothers about 15 years after the program began . Results showed that experiencing uncontrollable stressful life events , such as the death of a loved one , led to fewer negative outcomes ( fewer mental health problems , less binge drinking , and better parenting practice s ) among nurse-visited mothers than among mothers receiving no visitation . Furthermore , the program 's effect on reducing vulnerability to the negative impact of life events was particularly evident among parents who were younger or had a lower sense of personal control at intake . These findings suggest that , in addition to preventing the occurrence of negative outcomes that were direct targets of the intervention , the NFP more generally enhanced mothers ' ability to cope with future stressful life events The increasing imperative to find what works in health services has meant a rise in research trialing interventions deemed ' complex ' . While the strength of these interventions comes from taking a ' whole of problem ' approach using multiple and inter-linking strategies , ways of examining implementation are under-explored . Building sustainability is an important part of implementing complex intervention research , but this too has received little exploration in the implementation literature . This paper explores issues of implementation and sustainability by examining the case of PRISM ( Program of Re sources , Information and Support for Mothers ) , a community r and omised trial in Victoria , Australia aim ed at improving maternal health and wellbeing . It examines documents placed on the project website . Three groups of documents relating to implementation of the intervention were examined - implementation reports , media reports and community newsletters . Analysing these documents allowed a focus on the ' work ' of the intervention - who does the work and what activities comprise the work - in order to examine implementation as it relates to sustainability . Document analysis provides a useful way of considering implementation and sustainability of complex intervention research . It can ' value add ' to findings from process evaluation and extend our underst and ing of an intervention beyond outcome measures . Analysis of the documents in this case provides insights into why sustainability of an intervention may be difficult to achieve during implementation Objective To compare a shortened hospital stay with midwife visits at home to usual hospital care after delivery Objectives To investigate whether a visit to a general practitioner one week after discharge results in less depression , increased breastfeeding rates , improved patient wellbeing , fewer physical problems and greater satisfaction with general practice care than the traditional six week postnatal check‐up BACKGROUND Much postpartum physical and psychological morbidity is not addressed by present care , which tends to focus on routine examinations . We undertook a cluster r and omised controlled trial to assess community postnatal care that has been re design ed to identify and manage individual needs . METHODS We r and omly allocated 36 general practice clusters from the West Midl and s health region of the UK to intervention ( n=17 ) or control ( 19 ) care . Midwives from the practice s recruited women and provided care . 1087 ( 53 % ) of 2064 women were in practice s r and omly assigned to the intervention group , with 977 ( 47 % ) women in practice s assigned to the control group . Care was led by midwives , with no routine contact with general practitioners , and was extended to 3 months . Midwives used symptom checklists and the Edinburgh postnatal depression scale ( EPDS ) to identify health needs and guidelines for the management of these needs . Primary outcomes at 4 months were obtained by postal question naire and included the women 's short form 36 physical ( PCS ) and mental ( MCS ) component summary scores and the EPDS . Secondary outcomes were women 's views about care . Multilevel analysis accounted for possible cluster effects . FINDINGS 801 ( 77 % ) of 1087 women in the intervention group and 702 ( 76 % ) of 977 controls responded at 4 months . Women 's mental health measures were significantly better in the intervention group ( MCS , 3.03 [ 95 % CI 1.53 - 4.52 ] ; EPDS -1.92 [ -2.55 to -1.29 ] ; EPDS 13 + odds ratio 0.57 [ 0.43 - 0.76 ] ) than in controls , but the physical health score did not differ . INTERPRETATION Re design of care so that it is midwife-led , flexible , and tailored to needs , could help to improve women 's mental health and reduce probable depression at 4 months ' postpartum OBJECTIVE Short postpartum stays are common . Current guidelines provide scant guidance on how routine follow-up of newly discharged mother-infant pairs should be performed . We aim ed to compare 2 short-term ( within 72 hours of discharge ) follow-up strategies for low-risk mother-infant pairs with postpartum length of stay ( LOS ) of < 48 hours : home visits by a nurse and hospital-based follow-up anchored in group visits . METHODS We used a r and omized clinical trial design with intention-to-treat analysis in an integrated managed care setting that serves a largely middle class population . Mother-infant pairs that met LOS and risk criteria were r and omized to the control arm ( hospital-based follow-up ) or to the intervention arm ( home nurse visit ) . Clinical utilization and costs were studied using computerized data bases and chart review . Breastfeeding continuation , maternal depressive symptoms , and maternal satisfaction were assessed by means of telephone interviews at 2 weeks postpartum . RESULTS During a 17-month period in 1998 to 1999 , we enrolled and r and omized 1014 mother-infant pairs ( 506 to the control group and 508 to the intervention group ) . There were no significant differences between the study groups with respect to maternal age , race , education , household income , parity , previous breastfeeding experience , early initiation of prenatal care , or postpartum LOS . There were no differences with respect to neonatal LOS or Apgar scores . In the control group , 264 mother-infant pairs had an individual visit only , 157 had a group visit only , 64 had both a group and an individual visit , 4 had a home health and a hospital-based follow-up , 13 had no follow-up within 72 hours , and 4 were lost to follow-up . With respect to outcomes within 2 weeks after discharge , there were no significant differences in newborn or maternal hospitalizations or urgent care visits , breastfeeding discontinuation , maternal depressive symptoms , or a combined clinical outcome measure indicating whether a mother-infant pair had any of the above outcomes . However , mothers in the home visit group were more likely than those in the control group to rate multiple aspects of their care as excellent or very good . These included the preventive advice delivered ( 76 % vs 59 % ) and the skills and abilities of the provider ( 84 % vs 73 % ) . Mothers in the home visit group also gave higher ratings on overall satisfaction with the newborn 's posthospital care ( 71 % vs 59 % ) , as well as with their own posthospital care ( 63 % vs 55 % ) . The estimated cost of a postpartum home visit to the mother and the newborn was $ 265 . In contrast , the cost of the hospital-based group visit was $ 22 per mother-infant pair ; the cost of an individual 15-minute visit with a registered nurse was $ 52 ; the cost of a 15-minute individual pediatrician visit was $ 92 ; and the cost of a 10-minute visit with an obstetrician was $ 92 . CONCLUSIONS For low-risk mothers and newborns in an integrated managed care organization , home visits compared with hospital-based follow-up and group visits were more costly but achieved comparable clinical outcomes and were associated with higher maternal satisfaction . Neither strategy is associated with significantly greater success at increasing continuation of breastfeeding . This study had limited power to identify group differences in rehospitalization and may not be generalizable to higher-risk population s without comparable access to integrated hospital and outpatient care BACKGROUND Recent review s have shown that home visiting programmes that address parenting have the potential to improve long term health and social outcomes for children . However there are few studies exploring the cost-effectiveness of such interventions . The objective of this study was to evaluate the cost-effectiveness of an intensive home visiting programme directed at vulnerable families during the antenatal and postnatal periods . METHODS The design was an economic evaluation alongside a multicentre r and omized controlled trial , in which 131 eligible women were r and omly allocated to receive 18 months of intensive home visiting ( n=67 ) or st and ard services ( n=64 ) . Due to the public health nature of the intervention a cost-effectiveness analysis was undertaken from a societal perspective . RESULTS The mean ' societal costs ' in the control and intervention arms were 3874 pounds and 7120 pounds , respectively , a difference of 3246 pounds ( p<0.000 ) . The mean ' health service only ' costs were 3324 pounds and 5685 pounds respectively , a difference of 2361 pounds ( p<0.000 ) . As well as significant improvements in maternal sensitivity and infant cooperativeness there was also a non-significant increase in the likelihood of the intervention group infants being removed from the home due to abuse and neglect . These incremental benefits were delivered at an incremental societal cost of 3246 pounds per woman . CONCLUSIONS The results of the study provide evidence to suggest that , within the context of regular home visits , specially trained home visitors can increase maternal sensitivity and infant cooperativeness and are better able to identify infants in need of removal from the home for child protection . The extent to which these benefits are ' worth ' the societal cost of 3246 pounds per woman however is a matter of judgment OBJECTIVE Early postpartum home visiting is universal in many Western countries . Studies from developing countries on the effects of home visits are rare . In Syria , where the postpartum period is rather ignored , this study aim ed to assess whether a community-based intervention of postnatal home visits has an effect on maternal postpartum morbidities ; infant morbidity ; uptake of postpartum care ; use of contraceptive methods ; and on selected neonatal health practice s. DESIGN A r and omized controlled trial was carried out in Damascus . Three groups of new mothers were r and omly allocated to receive either 4 postnatal home visits ( A ) , one visit ( B ) , or no visit ( C ) . SAMPLE A total of 876 women were allocated and followed up . INTERVENTION Registered midwives with special training made a one or a series of home visits providing information , educating , and supporting women . RESULTS A significantly higher proportion of mothers in Groups A and B reported exclusively breastfeeding their infants ( 28.5 % and 30 % , respectively ) as compared with Group C ( 20 % ) , who received no visits . There were no reported differences between groups in other outcomes . CONCLUSIONS While postpartum home visits significantly increased exclusive breastfeeding , other outcomes did not change . Further studies framed in a nonbiomedical context are needed . Other innovative approaches to improve postnatal care in Syria are needed At approximately 37 weeks ' gestation , 131 women were r and omly assigned to one of three postpartum hospital discharge times : 12 to 24 hours , 25 to 48 hours , and 4 days . Depending on group assignment , the women received from one to five home visits by a maternity nurse clinician during the first 10 days postpartum . The results indicated the maternal and infant morbidity were low regardless of discharge time , although sample sizes were too small to detect significant differences in the outcomes . More early discharge mothers were breastfeeding without supplement at 1 month than were mothers in the long stay group . Mothers in the two early discharge groups were significantly more satisfied with their care than were those who remained longer . Those hospitalized longer scored higher on measures of depression and lower on scores of confidence at selected time periods BACKGROUND Teenage pregnancies are associated with negative socioeconomic effects . Our aim was to ascertain whether a postnatal home-visiting service for teenage mothers younger than age 18 years could reduce the frequency of adverse neonatal outcomes and improve knowledge of contraception , breastfeeding , and infant vaccination schedules in this parent group . METHODS We enrolled 139 adolescents , attending a teenage pregnancy clinic , in a r and omised controlled trial . After completing an antenatal question naire design ed to assess their knowledge of contraception , infant vaccination , and breastfeeding , we assigned participants to either receive five structured postnatal home visits by nurse-midwives ( n=65 ) or not ( n=71 ) . Assessment interviews were done 6 months postpartum . Our primary endpoint was unadjusted difference in knowledge between groups , and incidence of predefined adverse neonatal outcomes . Analysis was by intention to treat . FINDINGS Three women withdrew before r and omisation because of late fetal loss , 11 mothers withdrew because of adverse neonatal outcomes ( adverse neonatal outcome was a primary endpoint , but result ed in withdrawal from the study for knowledge outcomes ) , and one left voluntarily . Follow-up data were , therefore , available for 124 teenagers . Postnatal home visits were associated with a reduction in adverse neonatal outcomes ( intervention : 2 ; control : 9 ; relative risk 0.24 , 95 % CI 0.05 - 1.08 ) , and a significant increase in contraception knowledge ( mean difference 0.92 , 95 % CI 0.32 - 1.52 ) . However , there was no significant increase in knowledge with respect to breastfeeding or infant vaccination schedules associated with the home visits . INTERPRETATION Postnatal home-visiting services by nurse-midwives reduce adverse neonatal events and improve contraception outcomes , but do not affect breastfeeding or infant vaccination knowledge or compliance |
12,599 | 26,558,953 | AUTHORS ' CONCLUSIONS There is insufficient evidence for using OIT or SLIT to treat allergy to fruit , specifically related to peach and apple .
Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT .
However , these reactions could be treated successfully with medications | BACKGROUND Food allergy is an abnormal immunological response following exposure ( usually ingestion ) to a food .
Elimination of the allergen is the principle treatment for food allergy , including allergy to fruit .
Accidental ingestion of allergenic foods can result in severe anaphylactic reactions .
Allergen-specific immunotherapy ( SIT ) is a specific treatment , when the avoidance of allergenic foods is problematic .
Recently , studies have been conducted on different types of immunotherapy for the treatment of food allergy , including oral ( OIT ) and sublingual immunotherapy ( SLIT ) .
OBJECTIVES To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits , when compared with placebo or an elimination strategy . | BACKGROUND Food allergy may be life-threatening , and patients affected need to receive accurate diagnoses and treatment . Hazelnut has often been implicated as responsible for allergic reactions , and trace quantities can induce systemic reactions . OBJECTIVE The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a st and ardized hazelnut extract in patients allergic to hazelnut . METHODS This was a r and omized , double-blind , placebo-controlled study . Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results . Patients were then r and omly assigned into 2 treatment groups ( hazelnut immunotherapy or placebo ) . Efficacy was assessed by double-blind , placebo-controlled food challenge after 8 to 12 weeks of treatment . Blood sample s were drawn for measurement of specific IgE , IgG(4 ) , and serum cytokines before and after treatment . RESULTS Twenty-three patients were enrolled and divided into 2 treatment groups . Twenty-two patients reached the planned maximum dose at 4 days . Systemic reactions were observed in only 0.2 % of the total doses administered . Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g ( P = .02 ; active group ) versus 3.49 g to 4.14 g ( placebo ; NS ) . Moreover , almost 50 % of patients who underwent active treatment reached the highest dose ( 20 g ) , but only 9 % in the placebo . Laboratory data showed an increase in IgG(4 ) and IL-10 levels after immunotherapy in only the active group . CONCLUSION Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind , placebo-controlled food challenge , and good tolerance to this treatment BACKGROUND There are presently no available therapeutic options for patients with peanut allergy . OBJECTIVE We sought to investigate the safety , efficacy , and immunologic effects of peanut sublingual immunotherapy ( SLIT ) . METHODS After a baseline oral food challenge ( OFC ) of up to 2 g of peanut powder ( approximately 50 % protein ; median successfully consumed dose [ SCD ] , 46 mg ) , 40 subjects , aged 12 to 37 years ( median , 15 years ) , were r and omized 1:1 across 5 sites to daily peanut or placebo SLIT . A 5-g OFC was performed after 44 weeks , followed by unblinding ; placebo-treated subjects then crossed over to higher dose peanut SLIT , followed by a subsequent crossover Week 44 5-g OFC . Week 44 OFCs from both groups were compared with baseline OFCs ; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders . RESULTS After 44 weeks of SLIT , 14 ( 70 % ) of 20 subjects receiving peanut SLIT were responders compared with 3 ( 15 % ) of 20 subjects receiving placebo ( P < .001 ) . In peanut SLIT responders , median SCD increased from 3.5 to 496 mg . After 68 weeks of SLIT , median SCD significantly increased to 996 mg ( compared with Week 44 , P = .05 ) . The median SCD at the Week 44 Crossover OFC was significantly higher than baseline ( 603 vs 71 mg , P = .02 ) . Seven ( 44 % ) of 16 crossover subjects were responders ; median SCD increased from 21 to 496 mg among responders . Of 10,855 peanut doses through the Week 44 OFCs , 63.1 % were symptom free ; excluding oral-pharyngeal symptoms , 95.2 % were symptom free . CONCLUSIONS Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo . Longer duration of therapy showed statistically significant increases in the SCD BACKGROUND Cross-reactivity between the major birch pollen allergen , Bet v 1 , and the apple protein , Mal d 1 , frequently causes food allergy . OBJECTIVE To investigate the effects of successful sublingual immunotherapy ( SLIT ) with birch pollen extract on apple allergy and the immune response to Bet v 1 and Mal d 1 . METHODS Before and after 1 year of SLIT , Bet v 1-sensitized patients with oral allergy syndrome to apple underwent nasal challenges with birch pollen and double-blind placebo-controlled food challenges with apple . Bet v 1-specific and Mal d 1-specific serum antibody levels and proliferation in P BMC s and allergen-specific T-cell lines ( TCLs ) were determined . Bet v 1-specific TCLs were mapped for T-cell epitopes . RESULTS In 9 patients with improved nasal provocation scores to birch pollen , apple-induced oral allergy syndrome was not significantly reduced . Bet v 1-specific IgE and IgG(4 ) levels significantly increased . Bet v 1-specific T-cell responses to all epitopes and those cross-reactive with Mal d 1 significantly decreased . However , neither Mal d 1-specific IgE and IgG(4 ) levels nor Mal d 1-induced T-cell proliferation changed significantly . In contrast , Mal d 1-specific TCLs showed increased responses to Mal d 1 after 1 year of SLIT . CONCLUSION This longitudinal study indicates that pollen SLIT does not efficiently alter the immune response to pollen-related food allergens , which may explain why pollen-associated food allergy is frequently not ameliorated by pollen immunotherapy even if respiratory symptoms significantly improve . CLINICAL IMPLICATION S SLIT with birch pollen may have no clinical effect on associated apple allergy INTRODUCTION Treatment of food allergy essentially consists of food avoidance , but immunotherapy with food is emerging as a new therapeutic option . OBJECTIVE To evaluate clinical improvement and immunological changes in patients with peach allergy following sublingual immunotherapy ( SLIT ) with a Prup3 quantified peach extract . METHODS A r and omized , double-blind , placebo-controlled clinical trial with peach SLIT was conducted . We assessed clinical efficacy after 6 months of treatment by means of double-blind , placebo-controlled oral challenges with peach and also evaluated immunological changes ( basophil activation test [ BAT ] and determination of sulphidoleukotriene production ) following stimulation with peach peel and pulp , rPrup3 , rMald 1 , and rMal d 4 stimulation . We also measured specific IgE and IgG4 to Pru p3 . RESULTS After 6 months of SLIT ( T6 ) , the active group showed a 3-fold improvement in tolerance to Prup3 and a significant increase in IgE to rPrup3 and in sLT production following stimulation with peach peel and rPrup3 . There was also a significant increase in BAT results after stimulation with rPrup3 at 1 month of SLIT ( T1 ) . Statistically significant between-group differences were only observed for BAT with peach peel and pulp at T1 and T6 and for BAT with rPru p3 at T6 . No changes were observed in BAT with rMal d 1 or rMal d 4 or in IgG4 levels to nPrup3 . CONCLUSIONS SLIT with a Pru p 3 quantified peach extract is clinical ly effective and leads to an increase in basophil activation and sulphidoleukotriene production following stimulation with rPru p3 and peach peel in the first months of treatment BACKGROUND Open-label oral immunotherapy ( OIT ) protocol s have been used to treat small numbers of patients with peanut allergy . Peanut OIT has not been evaluated in double-blind , placebo-controlled trials . OBJECTIVE To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind , placebo-controlled study . METHODS In this multicenter study , children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo . Initial escalation , build-up , and maintenance phases were followed by an oral food challenge ( OFC ) at approximately 1 year . Titrated skin prick tests ( SPTs ) and laboratory studies were performed at regular intervals . RESULTS Twenty-eight subjects were enrolled in the study . Three peanut OIT subjects withdrew early in the study because of allergic side effects . During the double-blind , placebo-controlled food challenge , all remaining peanut OIT subjects ( n = 16 ) ingested the maximum cumulative dose of 5000 mg ( approximately 20 peanuts ) , whereas placebo subjects ( n = 9 ) ingested a median cumulative dose of 280 mg ( range , 0 - 1900 mg ; P < .001 ) . In contrast with the placebo group , the peanut OIT group showed reductions in SPT size ( P < .001 ) , IL-5 ( P = .01 ) , and IL-13 ( P = .02 ) and increases in peanut-specific IgG(4 ) ( P < .001 ) . Peanut OIT subjects had initial increases in peanut-specific IgE ( P < .01 ) but did not show significant change from baseline by the time of OFC . The ratio of forkhead box protein 3 (FoxP3)(hi ) : FoxP3(intermediate ) CD4 + CD25 + T cells increased at the time of OFC ( P = .04 ) in peanut OIT subjects . CONCLUSION These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation . The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance BACKGROUND There are no treatments currently available for peanut allergy . Sublingual immunotherapy ( SLIT ) is a novel approach to the treatment of peanut allergy . OBJECTIVE We sought to investigate the safety , clinical effectiveness , and immunologic changes with SLIT in children with peanut allergy . METHODS In this double-blind , placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind , placebo-controlled food challenge . RESULTS Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge . Dosing side effects were primarily oropharyngeal and uncommonly required treatment . During the double-blind , placebo-controlled food challenge , the treatment group safely ingested 20 times more peanut protein than the placebo group ( median , 1,710 vs 85 mg ; P = .011 ) . Mechanistic studies demonstrated a decrease in skin prick test wheal size ( P = .020 ) and decreased basophil responsiveness after stimulation with 10(-2 ) μg/mL ( P = .009 ) and 10(-3 ) μg/mL ( P = .009 ) of peanut . Peanut-specific IgE levels increased over the initial 4 months ( P = .002 ) and then steadily decreased over the remaining 8 months ( P = .003 ) , whereas peanut-specific IgG4 levels increased during the 12 months ( P = .014 ) . Lastly , IL-5 levels decreased after 12 months ( P = .015 ) . No statistically significant changes were found in IL-13 levels , the percentage of regulatory T cells , or IL-10 and IFN-γ production . CONCLUSION Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy , with evidence of immunologic changes suggesting a significant change in the allergic response . Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance Most patients with birch pollen allergy report oral allergy symptoms after eating fresh apples and other vegetable foods . Major birch pollen and apple allergens , Bet v 1 and Mal d 1 , are highly homologous ; as a consequence , pollen‐specific immunotherapy ( SIT ) might be expected to improve apple hypersensitivity Background : Peanut allergy is common , potentially severe and rarely resolves causing impaired quality of life . No disease‐modifying treatment exists and there is therefore a need to develop a therapeutic intervention Between 1973 and 1985 , 114 children , aged 2 to 14 years , underwent double-blind , placebo-controlled , food challenge ( DBPCFC ) to peanut . Thirty-two of 46 children with symptoms produced by DBPCFC to peanut were included in this longitudinal evaluation . Contact was made with the 32 subjects 2 to 14 years after their positive DBPCFC to peanut . All 32 subjects had exhibited a positive puncture skin test to peanut at the time of the original evaluation . Sixteen subjects had experienced symptoms caused by accidental peanut ingestion in the year before contact . Eight subjects had reacted to accidental ingestion in more than 1 year but less than 5 years before contact . Eight subjects had completely avoided peanut since the original evaluation and positive DBPCFC . No subjects could be demonstrated to have " outgrown " their peanut reactivity . All subjects tested continued to have skin reactivity to a puncture skin test with peanut extract . It appears uncommon for peanut-sensitive patients to lose their clinical reactivity , even after many years have elapsed . In addition , data were collected concerning reactions to other legumes and other ( nonlegume ) nuts . Only two patients with DBPCFC to peanut reacted on DBPCFC to soy or pea ( one each ) . None of the subjects with a positive DBPCFC to peanut reacted to nonlegume nuts OBJECTIVE : The goal of this study was to better estimate the prevalence and severity of childhood food allergy in the United States . METHODS : A r and omized , cross-sectional survey was administered electronically to a representative sample of US households with children from June 2009 to February 2010 . Eligible participants included adults ( aged 18 years or older ) able to complete the survey in Spanish or English who resided in a household with at least 1 child younger than 18 years . Data were adjusted using both base and poststratification weights to account for potential biases from sampling design and nonresponse . Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy . Multiple logistic regression models were constructed to identify characteristics significantly associated with outcomes . RESULTS : Data were collected for 40 104 children ; incomplete responses for 1624 children were excluded , which yielded a final sample of 38 480 . Food allergy prevalence was 8.0 % ( 95 % confidence interval [ CI ] : 7.6–8.3 ) . Among children with food allergy , 38.7 % had a history of severe reactions , and 30.4 % had multiple food allergies . Prevalence according to allergen among food-allergic children was highest for peanut ( 25.2 % [ 95 % CI : 23.3–27.1 ] ) , followed by milk ( 21.1 % [ 95 % CI : 19.4–22.8 ] ) and shellfish ( 17.2 % [ 95 % CI : 15.6–18.9 ] ) . Odds of food allergy were significantly associated with race , age , income , and geographic region . Disparities in food allergy diagnosis according to race and income were observed . CONCLUSIONS : Findings suggest that the prevalence and severity of childhood food allergy is greater than previously reported . Data suggest that disparities exist in the clinical diagnosis of disease Conflicting results concerning the effect of specific pollen immunotherapy ( SIT ) on allergy to plant foods have been reported . The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple . Seventy-four birch pollen-allergic patients were included in a double-blind , double-dummy , and placebo-controlled comparison of sublingual-swallow ( SLIT ) and subcutaneous ( SCIT ) administration of a birch pollen extract . Sixty-nine percent of these patients reported allergy to apple . The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a question naire . The immunoglobulin E (IgE)-reactivity was assessed by skin prick test ( SPT ) , specific IgE , and leukocyte histamine release ( HR ) . Forty patients were included in the final evaluation of the effect of SIT . The challenges were positive in 9 ( SCIT ) , 6 ( SLIT ) , and 8 ( placebo ) patients after treatment compared to 10 , 4 , and 10 patients , respectively , before SIT . The symptom scores to apple during challenges decreased in all groups , but only significantly in the placebo group ( p = 0.03 ) . As evaluated by the question naire , the severity of food allergy in general did not change and there were no differences between the groups . In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity , SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo . Therefore , oral allergy syndrome ( OAS ) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present Background : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no st and ardized programmes are yet available To cite this article : Kopac P , Rudin M , Gentinetta T , Gerber R , Pichler C , Hausmann O , Schnyder B , Pichler WJ . Continuous apple consumption induces oral tolerance in birch‐pollen‐associated apple allergy . Allergy 2012 ; 67 : 280–285 BACKGROUND Oral immunotherapy ( OIT ) has been thought to induce clinical desensitization to allergenic foods , but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported . OBJECTIVE The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT . METHODS Children with peanut allergy underwent an OIT protocol including initial day escalation , buildup , and maintenance phases , and then oral food challenge . Clinical response and immunologic changes were evaluated . RESULTS Of 29 subjects who completed the protocol , 27 ingested 3.9 g peanut protein during food challenge . Most symptoms noted during OIT resolved spontaneously or with antihistamines . By 6 months , titrated skin prick tests and activation of basophils significantly declined . Peanut-specific IgE decreased by 12 to 18 months , whereas IgG(4 ) increased significantly . Serum factors inhibited IgE-peanut complex formation in an IgE-facilitated allergen binding assay . Secretion of IL-10 , IL-5 , IFN-gamma , and TNF-alpha from P BMC s increased over a period of 6 to 12 months . Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter . In addition , T-cell microarrays showed downregulation of genes in apoptotic pathways . CONCLUSION Oral immunotherapy induces clinical desensitization to peanut , with significant longer-term humoral and cellular changes . Microarray data suggest a novel role for apoptosis in OIT Background The FAST project ( Food Allergy Specific ImmunoTherapy ) aims at the development of safe and effective treatment of food allergies . Classical allergen-specific immunotherapy ( SIT ) for treatment of food allergy using subcutaneous injections with food extracts has proven to be effective but too dangerous due to anaphylactic side-effects . FAST aims at developing a safe alternative by replacing food extracts with hypo-allergenic recombinant major allergens , the active ingredients of SIT . Fish allergy is caused by a single major allergen , parvalbumin . In phase I and II of the study r and omized double-blind placebo-controlled trials will be performed . A recipe for fishblinding does not exist and is needed to determine the clinical reactivity when including patients in the trial and to assess efficacy in the Phase II trial BACKGROUND Oral immunotherapy ( OIT ) and sublingual immunotherapy ( SLIT ) are potential therapies for food allergy , but the optimal method of administration , mechanism of action , and duration of response remain unknown . OBJECTIVE We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow 's milk ( CM ) allergy . METHODS We r and omized children with CM allergy to SLIT alone or SLIT followed by OIT . After screening double-blind , placebo-controlled food challenges and initial SLIT escalation , subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg ( the OITB group ) or 2000 mg ( the OITA group ) of milk protein . They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance . If they passed the 60-week challenge , therapy was withdrawn , with challenges repeated 1 and 6 weeks later . Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4 ) levels , basophil histamine release , constitutive CD63 expression , CD203c expression , and intracellular spleen tyrosine kinase levels . RESULTS Thirty subjects with CM allergy aged 6 to 17 years were enrolled . After therapy , 1 of 10 subjects in the SLIT group , 6 of 10 subjects in the SLIT/OITB group , and 8 of 10 subjects in the OITA group passed the 8-g challenge ( P = .002 , SLIT vs OIT ) . After avoidance , 6 of 15 subjects ( 3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group ) regained reactivity , 2 after only 1 week . Although the overall reaction rate was similar , systemic reactions were more common during OIT than during SLIT . By the end of therapy , titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4 ) levels increased in all groups , whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group . CONCLUSION OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects . Clinical desensitization was lost in some cases within 1 week off therapy |
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